Books by Subject

all 392 titles

Biomedical Engineering

  • 2015From: Springer
    Narayan Yoganandan, Alan M. Nahum, John W. Melvin, The Medical College of Wisconsin Inc on behalf of Narayan Yoganandan, editors.
    This book provides a state-of-the-art look at the applied biomechanics of accidental injury and prevention. The editors, Drs. Narayan Yoganandan, Alan M. Nahum and John W. Melvin are recognized international leaders and researchers in injury biomechanics, prevention and trauma medicine. They have assembled renowned researchers as authors for 29 chapters to cover individual aspects of human injury assessment and prevention. This third edition is thoroughly revised and expanded with new chapters in different fields. Topics covered address automotive, aviation, military and other environments. Field data collection; injury coding/scaling; injury epidemiology; mechanisms of injury; human tolerance to injury; simulations using experimental, complex computational models (finite element modeling) and statistical processes; anthropomorphic test device design, development and validation for crashworthiness applications in topics cited above; and current regulations are covered. Risk functions and injury criteria for various body regions are included. Adult and pediatric populations are addressed. The exhaustive list of references in many areas along with the latest developments is valuable to all those involved or intend to pursue this important topic on human injury biomechanics and prevention. The expanded edition will interest a variety of scholars and professionals including physicians, biomedical researchers in many disciplines, basic scientists, attorneys and jurists involved in accidental injury cases, and governmental bodies. It is hoped that this book will foster multidisciplinary collaborations by medical and engineering researchers, and academicians and practicing physicians for injury assessment and prevention and stimulate more applied research, education and training in the field of accidental-injury causation and prevention.
  • 2014From: Wiley
    edited by Ashutosh Tiwari and Anis N. Nordin.
    1. Frotiers for bulk nanostructured metals in biomedical applications -- 2. Stimuli-responsive materials used as medical devices in loading and releasing of drugs -- 3. Recent advances with liposomes as drug carriers -- 4. Fabrication, properties of nanoshells with controllable surface charge and its applications -- 5. Chitosan as an advanced healthcare material -- 6. Chitosan and low molecular weight chitosan: biological and biomedical applications -- 7. Anticipating behaviour of advanced materials in healthcare -- 8. Label-free biochips -- 9. Polymer MEMS sensors -- 10. Assembly of polymers/metal nanoparticles and their applications as medical devices -- 11. Combination of molecular imprinting and nanotechnology: beginning of a new horizon -- 12. Prussian blue and analogues: biosensing applications in health care -- 13. Efficiency of biosensors as new generation of analytical approaches at the biochemical diagnostics of diseases -- 14. Nanoparticles: scope in drug delivery -- 14. Smart polypeptide nanocarriers for malignancy therapeutics -- Index.
  • 2010From: CRCnetBASE
    edited by Andrei G. Pakhomov, Damijan Miklavčič, Marko S. Markov.
    "A reflection of the intense study of the effects of electromagnetic fields on living tissues that has taken place during the last several decades, this book discusses the theoretical and experimental evidence and considerations the effects of strong electromagnetic fields and/or electric pulses and their importance in medicine and biology. The authors present the basic techniques applied in electroporation and the advanced methods for creation of nanopores, highlighting their basic science and clinical applications. Topics include nano electroporation, classic electroporation, experimental evidence for electroporation of living cells, and electroporation for cancer and wound healing"--Provided by publisher.
  • 2014From: Wiley
    edited by Ashutosh Tiwari, Biosensors and Bioelectronics Centre, Linkping University, Sweden.
    "Advanced Healthcare Nanomaterials summarises the current status of knowledge in the fields of advanced materials for functional therapeutics, point-of-care diagnostics, translational materials, up and coming bio-engineering devices"-- Provided by publisher.
  • 2013From: Wiley
    edited by Roger Narayan, Paolo Colombo ; volume editors Michael Halbig, Sanjay Mathur.
  • 2007From: Springer
    Thorsten M. Buzug (ed.).
  • 2010From: Springer
    edited by Venkatram Prasad Shastri, George Altankov, Andreas Lendlein.
    Cell Adhesions and Signaling: A Tool for Biocompatibility Assessment / Roumen Pankov and Albena Momchilova -- Development of Provisional Extracellular Matrix on Biomaterials Interface: Lessons from In Vitro Cell Culture / George Altankov, Thomas Groth, Elisabeth Engel, Jonas Gustavsson and Marta Pegueroles, et al. -- Endothelial Progenitor Cells for Tissue Engineering and Tissue Regeneration Endothelial Progenitor Cells / Joyce Bischoff -- Dermal Precursors and the Origins of the Wound Fibroblast / Jeffrey M. Davidson -- Cell Based Therapies: What Do We Learn from Periosteal Osteochondrogenesis? / Peter J. Emans, Tim J. M. Welting and Venkatram Prasad Shastri -- Bioreactor Systems in Regenerative Medicine / Ivan Martin, Stefania A. Riboldi and David Wendt -- Biomimetic Approaches to Design of Tissue Engineering Bioreactors / Bojana Obradovic, Milica Radisic and Gordana Vunjak-Novakovic -- The Nature of the Thermal Transition Influences the Shape-Memory Behavior of Polymer Networks / Andreas Lendlein, Marc Behl and Stefan Kamlage -- Nanoengineered Systems for Regenerative Medicine Surface Engineered Polymeric Biomaterials with Improved Bio-Contact Properties / Todorka Vladkova and Natalia Krasteva -- Nanocomposites for Regenerative Medicine / Ryan Hoshi, Antonio R. Webb, Hongjin Qiu and Guillermo A. Ameer -- Role of Spatial Distribution of Matricellular Cues in Controlling Cell Functions / Daniela Guarnieri and Paolo A. Netti -- Materials Surface Effects on Biological Interactions / Josep A. Planell, Melba Navarro, George Altankov, Conrado Aparicio and Elisabeth Engel, et al. -- Chemical and Physical Modifications of Biomaterial Surfaces to Control Adhesion of Cells / Thomas Groth, Zhen-Mei Liu, Marcus Niepel, Dieter Peschel and Kristin Kirchhof, et al. -- Results of Biocompatibility Testing of Novel, Multifunctional Polymeric Implant Materials In-Vitro and In-Vivo / Dorothee Rickert, Rosemarie Fuhrmann, Bernhard Hiebl, Andreas Lendlein and Ralf-Peter Franke -- UFOs, Worms, and Surfboards: What Shapes Teach Us About Cell-Material Interactions / Julie A. Champion and Samir Mitragotri -- Nano-engineered Thin Films for Cell and Tissue-Contacting Applications / Richard F. Haglund -- Injectable Hydrogels: From Basics to Nanotechnological Features and Potential Advances / Biancamaria Baroli -- Polyelectrolyte Complexes as Smart Nanoengineered Systems for Biotechnology and Gene Delivery / Vladimir A. Izumrudov.
  • Raymond Albert Ryckman.
    In this work we present a series of scientific contributions made to the study of the impact of projectiles into tissue-like materials, specifically the synthetic artificial tissue simulant Perma-Gel. These contributions consist of a combination of experimental observations, algorithmic ideas and numerical tools which demonstrate a series of problems and solutions to trying to simulate nearly incompressible soft tissues using finite elements. A number of experiments were performed by taking high-speed footage of the firing of spherical steel bullets at different speeds into Perma-Gel, a new thermoplastic material used as a proxy to human muscle tissue. This work appears to be the first publicly released experimental work using Perma-Gel and is part of the small amount of non-classified work looking at ballistic gelatin behavior. A number of experimental observations were made regarding the material behavior, elastic and plastic deformation around the projectile, and the possibility of cavitation. This work introduces an explicit dynamic contact algorithm that takes advantage of the asynchronous time stepping nature of Asynchronous Variational Integrators (AVI) to improve performance when simulating elastic-body rigid-wall contact. We demonstrate a number of desirable properties over traditional one-time-step methods for the simulation of solid dynamics and provide a number of examples highlighting the advantages of this method. The explicit contact algorithm and AVI was used to simulate the impact of a projectile into a simulated block of gelatin, but was hindered by difficulties using the realistic material parameters. Using a parallelized version of the algorithm, large-scale simulations were performed for progressively smaller shear moduli. As the simulations approached realistic values for the shear modulus, unstable element configurations formed which required infeasibly small time steps to successfully resolve. The behavior observed for the shear moduli we could numerically simulate with did not resemble the experimental results. To simulate with smaller values, we had to go to an axisymmetric setting. The axisymmetric setting increased the range of shear moduli which could be simulated and demonstrated the same dynamic behavior, though the issue of unstable element configurations continued to occur in extreme cases. To deal with the issue of unstable elements, we created an axisymmetric remeshing strategy to compensate for the unstable element configurations and insufficient spatial resolution. This strategy consists of periodically applying a remeshing and transfer algorithm that updates highly deformed finite element meshes with configurations formed with elements having uniform aspect ratios and local refinement in important areas. The axisymmetric setting with remeshing increased the range of potential shear modulus values that could be simulated. This allowed for the identification of qualitative similarities in the transient behavior between the numerical results and the experimental footage.
  • 2010From: Atypon
    Fábio J. Ayres, Rangaraj M. Rangayyan, and J.E. Leo Desautels.
    The presence of oriented features in images often conveys important information about the scene or the objects contained; the analysis of oriented patterns is an important task in the general framework of image understanding. As in many other applications of computer vision, the general framework for the understanding of oriented features in images can be divided into low- and high-level analysis. In the context of the study of oriented features, low-level analysis includes the detection of oriented features in images; a measure of the local magnitude and orientation of oriented features over the entire region of analysis in the image is called the orientation field. High-level analysis relates to the discovery of patterns in the orientation field, usually by associating the structure perceived in the orientation field with a geometrical model. This book presents an analysis of several important methods for the detection of oriented features in images, and a discussion of the phase portrait method for high-level analysis of orientation fields. In order to illustrate the concepts developed throughout the book, an application is presented of the phase portrait method to computer-aided detection of architectural distortion in mammograms.
  • 2014From: ScienceDirect
    edited by Ashish S. Verma, Anchal Singh.
    Animal Biotechnology introduces applications of animal biotechnology and implications for human health and welfare. It begins with an introduction to animal cell cultures and genome sequencing analysis and provides readers with a review of available cell and molecular tools. Topics here include the use of transgenic animal models, tissue engineering, nanobiotechnology, and proteomics. The book then delivers in-depth examples of applications in human health and prospects for the future, including cytogenetics and molecular genetics, xenografts, and treatment of HIV and cancers. All this is complemented by a discussion of the ethical and safety considerations in the field. Animal biotechnology is a broad field encompassing the polarities of fundamental and applied research, including molecular modeling, gene manipulation, development of diagnostics and vaccines, and manipulation of tissue. Given the tools that are currently available and the translational potential for these studies, animal biotechnology has become one of the most essential subjects for those studying life sciences. Highlights the latest biomedical applications of genetically modified and cloned animals with a focus on cancer and infectious diseases. Provides firsthand accounts of the use of biotechnology tools, including molecular markers, stem cells, and tissue engineering.
  • Nam Keun Kim.
    Of the two pathways through which we hear, air conduction (AC) and bone conduction (BC), the fundamental mechanisms of the BC pathway remains to be poorly understood, despite its clinical significance. In the first study, a finite-element (FE) model of a human middle ear and cochlea was developed to gain insight into the mechanisms of BC hearing. BC excitations were simulated in the form of rigid-body vibrations of the surrounding bony structures in the x, y, and z orthogonal directions. The results show that the BM vibration characteristics are essentially invariant regardless of whether the excitation is BC, independent of excitation directions, or for AC. Analysis reveals that this is because the BM vibration apparently responds only to the anti-symmetric slow wave cochlea fluid pressure component and not the symmetric fast wave pressure component. In the second study, an improved three-dimensional FE model of a human middle ear coupled to a cochlea was formulated. The geometry of both the middle ear and cochlea, including semicircular canals, was obtained from micro-computed tomography ([mu]CT) images. In the study, BC and AC excitations were simulated as the same way as the previous simulation in the first study. After testing a range of vibrational directions, it was found that the vibrational direction normal to the BM surface at the base of the cochlea caused the highest BM velocity response across all tested frequencies--higher even than an excitation direction normal to the BM surface at the (non-basal) best-frequency locations corresponding to the other stimulus frequencies. The basal part of the human cochlea features a well-developed hook region, in which the BM undergoes a sudden curvature that produces the largest difference in fluid volume between the scala vestibuli (SV) and scala tympani (ST) found throughout the whole cochlea, and due to the sudden curvature of the hook region, the normal direction to the BM surface in this region differs significantly from the normal directions to the BM along the rest of the length of the cochlea. In the third study, the effects of otosclerosis and superior semicircular canal (SSC) dehiscence (SSCD) on hearing sensitivity were investigated via AC and BC pathways, using the FE model developed in the second study. Otosclerosis conditions were simulated by stiffing stapes annular ligament and removing the middle-ear inertia through removing stapedius tendon and incudostapedial joint. Dehiscences were modeled by removing a section of the outer bony wall of the SSC and applying a zero-pressure condition to the fluid surface thus exposed. In the results, otosclerosis condition caused the biggest bone-conduction hearing loss around 1.5 kHz, which is called 'Carhart notch'. In addition, dehiscence caused decreasing of the basilar membrane velocity, VBM(x), and fluid pressure in the cochlea in air conduction whereas increasing in bone conduction at low frequencies. Furthermore, the location and size of dehiscence affected the BC hearing threshold. Not previously shown is that the initial width (defined as the edge of dehiscence at which the flowing energy from the oval window meets for the first time) on the vestibular side of the dehiscence has more effect than the area of the dehiscence. The analyses of the FE model further predict that the ABG due to a dehiscence should converge to 0 dB at 10 kHz.
  • 2009From: CRCnetBASE
    Dhanjoo N. Ghista.
    Analysis for internal fixation of a fractured bone by means of bone-fixator plate -- Human lumbar vertebral body : analysis of its functionally optimal design -- Human spinal intervertebral disc : optimal structural design characteristics -- Biomechanics of fitness index : optimal walking and jogging modes, and hip joint assessment -- Analysis of spinning ball trajectories of soccer kicks and basketball throws -- Mechanics of baseball pitching and batting -- Biodynamics analysis of women's gymnastics : Yurchenko layout vault. Biomechanics in medical diagnosis in the form of nondimensional physiological indices -- Left ventricular mechanics -- Left ventricular contractility indices -- Vascular biomechanics -- Lung ventilation modeling for lung disease diagnosis -- Lung gas-transfer performance analysis -- Indicators for extubation of mechanically ventilated COPD patients using lung ventilation modeling -- Glucose-insulin dynamics modeling -- Glucose tolerance tests modeling -- Modeling of OGTT blood glucose and insulin responses and diagnostic indices --
  • 2007From: CRCnetBASE
    Mohsen Shahinpoor, Kwang J. Kim, Mehran Mojarrad.
  • 2009From: Springer
    Nadey Hakim (ed.).
  • Gerald E. Miller.
    Artificial heart valves -- Artificial heart and cardiac assist devices -- Cardiac pacemakers -- Dialysis.
  • 2007From: Springer
    Mark S. Humayun ... [et al.] (eds.).
  • Jae Mo Park.
    Unlike normal tissues, solid tumors have a metabolic phenotype that favors energy-inefficient glycolysis rather than more efficient, but oxygen consuming, oxidative phosphorylation, even when oxygen levels are adequate. This metabolic shift towards glycolysis, discovered by Warburg in 1924, has been studied for more than 80 years, but the mechanism of the phenomena is still unclear due to lack of tools for in vivo investigation. Dynamic nuclear polarization in combination with the recent development of a dissolution process that retains the increased polarization into the liquid state opened new possibilities for the real-time investigation of in vivo metabolism using C13 magnetic resonance spectroscopy. In particular, hyperpolarized [1-13C]pyruvate, a substrate occupying a key nodal point in the glucose metabolic pathway, has been successfully demonstrated as a neoplasm biomarker via elevated lactate labeling in tumors. However, additional downstream products of pyruvate metabolism, such as that occur in mitochondria of brain tumor, have been veiled due to low signal-to-noise ratios. The first part of the thesis is on the quantitative assessment of mitochondrial function in normal rat brain and glioma by detecting 13C-bicarbonate following the bolus injection of [1-13C]pyruvate. The feasibility of quantitatively detecting 13C-bicarbonate in tumor-bearing rat brain is demonstrated for the first time. The optimized protocol for chemical shift imaging and high concentration of hyperpolarized [1-13C]pyruvate were used to improve measurements of lactate and bicarbonate in C6 glioma-transplanted rat brains. Moreover, the immediate response to dichloroacetate treatment, which upregulates pyruvate flux to acetyl-CoA, is also presented. It is demonstrated that the simultaneous detection of lactate and bicarbonate provides a tool for a more comprehensive analysis of glioma metabolism and the assessment of metabolic agents as anti-cancer drugs. In the second part of the thesis, further investigation on mitochondrial metabolism, including tricarboxylic acid cycle, is presented by acquiring single-time point chemical shift imaging data from rat brain in vivo after administration of highly concentrated [2-13C]pyruvate. A C13 surface coil optimized for rat brain was built to increase sensitivity of signal detection. [5-13C]glutamate, [1-13C]acetyl carnitine, and [1-13C]citrate were detected besides [2-13C]pyruvate and [2-13C]lactate, for the first time in brain. Change of the tricarboxylic acid cycle activity in brain was also investigated by infusing dichloroacetate. The increase of [5-13C]glutamate was detected primarily from brain, whereas [1-13C]acetyl carnitine was increased in peripheral tissues after the infusion of dichloroacetate. The third part focuses on dynamic measurements of hyperpolarized substrates to obtain exchange rates in addition to concentrations, and proposes the apparent conversion rate as a new metric to detect glioma by comparing the conversion rates in glioma, normal appearing brain, and basilar vasculature in female Sprague-Dawley rats with C6 glioma cells implanted. Whereas single-time point measurements give a snapshot image of tissue metabolism, the estimated apparent rate constant yielded a better differentiation between the tissue types than the lactate-to-pyruvate ratio, which has been the most common metric used to date. This study demonstrates the feasibility of quantitatively detecting C13-labeled bicarbonate and glutamate in vivo, permitting the assessment of dichloroacetate-modulate changes in pyruvate dehydrogenase flux in both normal rat brain and glioma. The simultaneous detection of both lactate dehydrogenase and pyruvate dehydrogenase activities will likely improve our ability to both assess and monitor metabolic therapies of brain and other cancers by providing non-invasive in vivo measures of glycolysis and oxidative phosphorylation.
  • Elizabeth Ann Hager-Barnard.
    Recent successes in the pharmaceutical industry have yielded a variety of new drugs based on proteins and nucleic acids. While these drugs are very promising, they are only effective once they are inside cells. Unfortunately, transporting drugs into cells tends to be challenging because cell membranes provide a protective barrier. However, there is hope for these drugs since researchers have identified many drug delivery agents that can shuttle drugs past this barrier. Cell penetrating peptides (CPPs) are particularly promising delivery agents due to their low toxicity and ability to deliver a wide number of therapeutic agents. However there are challenges to using CPPs, because their delivery mechanisms cannot yet be controlled. Engineering new CPPs that use specific, known translocation mechanisms would be a key achievement that could increase delivery efficiency and prevent unwanted side effects. Accomplishing this goal requires new experimental methods for determining the factors that control a CPP's translocation mechanisms. In this thesis I present new atomic force microscopy (AFM) methods for studying CPPs and other cell membrane active species. I first present a theoretical model that shows how results from AFM can indicate whether CPPs change the energy barrier to bilayer penetration. I then describe new experimental AFM methods we developed for examining CPP transduction mechanisms.
  • 2011From: Springer
    Fan-Gang Zeng, Arthur N. Popper, Richard R. Fay, editors.
    1. Advances in Auditory Prostheses / Fan-Gang Zeng -- 2. Bilateral Cochlear Implants / Richard van Hoesel -- 3. Combining Acoustic and Electric Hearing / Christopher W. Turner and Bruce J. Gantz -- 4. Implantable Hearing Devices for Conductive and Sensorineural Hearing Impairment / Ad Snik -- 5. Vestibular Implants / Justin S. Golub, James O. Phillips, and Jay T. Rubinstein -- 6. Optical Stimulation of the Auditory Nerve / Claus-Peter Richter and Agnella Izzo Matic -- 7. A Penetrating Auditory Nerve Array for Auditory Prosthesis / John C. Middlebrooks and Russell L. Snyder -- 8. Cochlear Nucleus Auditory Prostheses / Douglas B. McCreery and Steven R. Otto -- 9. Midbrain Auditory Prostheses / Hubert H. Lim, Minoo Lenarz, and Thomas Lenarz -- 10. Central Auditory System Development and Plasticity After Cochlear Implantation / Anu Sharma and Michael Dorman -- 11. Auditory Training for Cochlear Implant Patients / Qian-Jie Fu and John J. Galvin III -- 12. Spoken and Written Communication Development Following Pediatric Cochlear Implantation / Sophie E. Ambrose, Dianne Hammes-Ganguly, and Laurie S. Eisenberg -- 13. Music Perception / Hugh McDermott -- 14. Tonal Languages and Cochlear Implants / Li Xu and Ning Zhou -- 15. Multisensory Processing in Cochlear Implant Listeners / Pascal Barone and Olivier Deguine.
  • Eric Tatt Wei Ho.
    The fruit fly, Drosophila melanogaster, is a key model species for biological research. Trained humans can manipulate, inspect and dissect individual flies, but these operations are often rate-limiting bottlenecks for screening and experimentation. Here I present a high-speed, economical robot for handling non-anesthetized adult flies. Using machine vision the robot tracks a fly's thorax and gently grabs it ~400 ms after targeting. The robot can then translate and rotate the picked fly, inspect its phenotype, dissect or release it, and thereby rapidly prepare multiple flies sequentially for a wide range of experimental formats. In one illustration, the robot restrained flies and dissected the cuticle to permit two-photon imaging of neural dynamics. In another, the robot sorted flies by sex. The robot's tireless capacity for accurate, repeatable manipulations will enable experiments and biotechnology applications that would otherwise be totally infeasible, especially those requiring high-throughput capture, testing and assessment of individual fly attributes.
  • Charles S. Lessard.
  • John D. Enderle, David C. Farden, Daniel J. Krause.
  • 2012From: Wiley
    [edited by] Julian Jones and Alexis G. Clare.
    The unique nature of glass / Alexis G. Clare -- Melt derived bioactive glass / Matthew D. O'Donnell -- Sol-gel derived glasses for medicine / Julian R. Jones -- Phosphate glasses / Delia S. Brauer -- The structure of bioactive glasses and their surfaces / Alastair N. Cormack -- Bioactive borate glasses / Steven B. Jung -- Glass-ceramics / Wolfram H'land -- Bioactive glass- and glass-ceramic coatings / Enrica Vern -- Composites containing bioactive glass / Aldo R. Boccaccini and Qi-Zhi Chen -- Inorganic-organic sol-gel hybrids / Yuki Shirosaki [and others] -- Dental applications of glasses / Leena Hupa and Antti Yli-Urpo -- Bioactive glass as synthetic bone grafts and scaffolds for tissue engineering / Julian R. Jones -- Glasses for radiotherapy / Delbert E. Day.
  • Salomon Joseph Trujillo.
    The priorities of a climbing legged robot are to maintain a grasp on its climbing surface and to climb efficiently against the force of gravity. Climbing robots are especially susceptible to thermal overload during normal operation, due to the need to oppose gravity and to frequently apply internal forces for clinging. These priorities guided us to develop optimal climbing behaviors under thermal constraints. These behaviors in turn profoundly constrain the choice of gait regulation methods. We propose a novel algorithm: "travel-based" gait regulation that varies foot detachment timing, effectively modifying stride length and frequency in order to maintain gait phasing, subject to kinematic and stability constraints. A core feature of the algorithm is "travel, " a new metric that plays a similar role to relative phasing. The method results in linear equations in terms of travel, leading to straightforward tests for local and global convergence when, for example, disturbances such as foot slippage cause departures from the nominal phasing. We form recurrence maps and use eigenvalue and singular value decomposition to examine local convergence of gaits. To examine global convergence, we implemented a computational geometry technique in high-order spaces. Our travel-based algorithm benefits from a compact code size and ease of implementation. We implemented the algorithm on the RiSE and Stickybot III robots as well as a virtual hexapod in a physics simulator. We demonstrated quickly converging gaits on all platforms as well as gait transitions on Stickybot III and the virtual hexapod.
  • 2014From: Wiley
    edited by Anthony B. Brennan, Chelsea M. Kirschner.
    ECM-inspired chemical cues : biomimetic molecules and techniques of immobilization / Roger Y. Tam, Shawn C. Owen and Molly S. Shoichet -- Dynamic materials mimic developmental and disease changes in tissues / Matthew G. Ondeck and Adam J. Engler -- The role of mechanical cues in regulating cellular activities and guiding tissue development / Liming Bian -- Contribution of physical forces to the design of biomimetic tissue substitutes / M. Ermis, E.T. Baran, T. Dursun, E. Antmen and V. Hasirci -- Cellular responses to engineered bio-inspired topographic cues / Chelsea M. Kirschner, James F. Schumacher and Anthony B. Brennan -- Engineering the mechanical and growth factor signaling roles of fibronectin fibrils / Christopher A. Lemmon -- Biologic scaffolds composed of extracellular matrix as a natural material for wound healing / Stephen Badylak -- Bio-inspired integration of natural materials / Albino Martins, Marta Alves da Silva, Ana Costa-Pinto, Rui L. Reis and Nuno M. Neves -- Bio-inspired design of skin replacement therapies / Dennis P. Orgill -- Epithelial engineering: from sheets to branched tubes / Hye Young Kim and Celeste M. Nelson -- A biomimetic approach toward the fabrication of epithelial-like tissue / Meng Xu and Hongjun Wang -- Nano- and micro-structured ECM and biomimetic scaffolds for cardiac tissue engineering / Quentin Jallerat, John M. Szymanski and Adam W. Feinberg -- Cardiovascular biomaterials / Elaine L. Lee and Joyce Y. Wong -- Evaluation of bio-inspired materials for mineralized tissue regeneration using type I collagen reporter cells / Lisa T. Kuhn, Emily Jacobs, and A. Jon Goldberg -- Learning from tissue equivalents : biomechanics and mechanobiology / David D. Simon and Jay D. Humphrey -- Mimicking the hematopoietic stem cell niche by biomaterials approaches / Eike Müller, Michael Ansorge, Carsten Werner and Tilo Pompe -- Engineering immune responses to allografts / Anthony W. Frei and Cherie L. Stabler -- Immunomimetic materials / Jamal S. Lewis and Benjamin G. Keselowsky.
  • 2007From: CRCnetBASE
    edited by Wanjun Wang, Steven A. Soper.
  • 2015From: Wiley
    Robert B. Heimann and Hans D. Lehmann.
  • Oscar John Abilez.
    Cardiovascular disease affects more than 70 million Americans and is the number one cause of mortality in the United States. Because the regenerative capacity of cardiac tissue is limited, human pluripotent stem cells (hPSC) have emerged as a potential source for cellular-based therapies. However, for these therapies to be effective, sufficient amounts of differentiated cells must be produced, these cells must be identified and sorted, and, upon implantation, arrhythmias must be avoided. In this dissertation, I describe the biochemical control of hPSC for their directed differentiation into cardiomyocytes, electrical control for electrophysiology-based cell sorting, and optogenetic control for temporal synchronization. For future therapy, the in vivo application of optical stimulation could allow immediate, precise, and specific synchronization of efficiently derived and purified hPSC-CM with patient cardiac rates and rhythms. This, in turn, would significantly reduce the chance of arrhythmias arising from implanted hPSC-CM, and, therefore, contribute towards establishing a safe and effective cell-based therapy.
  • editors, Paul G. Yock, Stefanos Zenios, Joshua Makower, Todd J. Brinton, Uday N. Kumar, F.T. Jay Watkins ; principal writer, Lyn Denend ; specialy editor, Thomas M. Krummel ; web editor, Christina Kurihara.
    Status: Not Checked OutLane Catalog Record
    "This step-by-step guide to medical technology innovation, now in full color, has been rewritten to reflect recent trends of industry globalization and value-conscious healthcare. Written by a team of medical, engineering, and business experts, the authors provide a comprehensive resource that leads students, researchers, and entrepreneurs through a proven process for the identification, invention, and implementation of new solutions. Case studies on innovative products from around the world, successes and failures, practical advice, and end-of-chapter 'Getting Started' sections encourage readers to learn from real projects and apply important lessons to their own work. A wealth of additional material supports the book, including a collection of nearly 100 videos created for the second edition, active links to external websites, supplementary appendices, and timely updates on the companion website at Readers can access this material quickly, easily, and at the most relevant point in the text from within the ebook"--Provided by publisher.
  • 2010From: ProQuest Safari
    Stefanos Zenios, Josh Makower, Paul Yock.
    Stage 1. Needs finding -- 1.1. Strategic focus -- 1.2. Observation and problem identification -- 1.3. Need statement development -- Stage 2. Needs screening -- 2.1. Disease state fundamentals -- 2.2. Treatment options -- 2.3. Stakeholder analysis -- 2.4. Market analysis -- 2.5. Needs filtering -- Stage 3. Concept generation -- 3.1. Ideation and brainstorming -- 3.2. Concept screening -- Stage 4. Concept selection -- 4.1. Intellectual property basics -- 4.2. Regulatory basics -- 4.3. Reimbursement basics -- 4.4. Business models -- 4.5. Prototyping -- 4.6. Final concept selection -- Stage 5. Development strategy and planning -- 5.1. Intellectual property strategy -- 5.2. Research and development strategy -- 5.3. Clinical strategy -- 5.4. Regulatory strategy -- 5.5. Quality and process management -- 5.6. Reimbursement strategy -- 5.7. Marketing and stakeholder strategy -- 5.8. Sales and distribution strategy -- 5.9. Competitive advantage and business strategy -- Stage 6. Integration -- 6.1. Operating plan and financial model -- 6.2. Business plan development -- 6.3. Funding sources -- 6.4. Licensing and alternate pathways.
    Also available: Print – 2010
  • 2016From: Cambridge
    Minoru Taya, Makoto Mizunami, Shûhei Nomura, Elizabeth Van Volkenburgh.
    From experts in engineering and biology, this is the first book to integrate sensor and actuator technology with bioinspired design.
  • John D. Enderle.
  • 2006Click fulltext button, Click guest acess (upper right) and Search for standard number 10993-2From: ANSI
  • 2009Click fulltext button, Click guest acess (upper right) and Search for standard number 10993-1From: ANSI
  • 2010Click fulltext button, Click guest acess (upper right) and Search for standard number 10993-13From: ANSI
  • 2003Click fulltext button, Click guest acess (upper right) and Search for standard number 10993-3From: ANSI
  • 2009Click fulltext button, Click guest acess (upper right) and Search for standard number 10993-5From: ANSI
  • 2007From: Springer
    Heide Schatten, James Pawley, editors.
  • 2007From: CRCnetBASE
    edited by Joyce Y. Wong, Joseph D. Bronzino.
    Metallic biomaterials / Joon B. Park and Young Kon Kim -- Ceramic biomaterials / W.C. Billotte -- Polymeric biomaterials / Hai Bang Lee, Gilson Khang, and Jin Ho Lee -- Composite biomaterials / Roderic S. Lakes -- Biodegradable hydrogels : tailoring properties and function through chemistry and structure / Andrew T. Metters and Chien-Chi Lin -- Biodegradable polymeric biomaterials : an updated overview / Chih-Chang Chu -- Biologic biomaterials : tissue-derived biomaterials (collagen) / Shu-Tung Li -- Soft tissue replacements / K.B. Chandran, K.J.L. Burg, and S.W. Shalaby -- Hard tissue replacements / Sang-Hyun Park ... [et al.] -- Controlling and assessing cell-biomaterial interactions at the micro- and nanoscale : applications in tissue engineering / Jessica Kaufman, Joyce Y. Wong, and Catherine Klapperich.
  • 2014From: Wiley
    edited by Véronique Migonney.
    History of biomaterials / Véronique Migonney -- Definitions / Véronique Migonney -- Materials used in biomaterial applications / Géraldine Rohman -- Biocompatibility and norms / Véronique Migonney -- Bioactive polymers and surfaces: a solution for implant devices / Véronique Migonney -- Functionalization of biomaterials and applications / Céline Falentin-Daudre -- Biomaterial structures for anterior cruciate ligament replacement / Cédryck Vaquette -- Animal models for orthopedic applications of tissue engineering / Véronique Viateau, Adeline Decambron, Mathieu Manassero -- Ceramic materials for dental prostheses / Amélie Mainjot -- Dental adhesives / Mathieu Derbanne, Stéphane Le Goff, Jean-Pierre Attal -- Glass ionomer cements: application in pediatric dentistry / Elisabeth Dursun, Stéphane Le Goff, Jean-Pierre Attal -- List of authors.
  • 2007From: Springer
    Joon Park, R.S. Lakes.
  • 2014From: Cambridge
    2014From: Knovel
    edited by Peter X. Ma, University of Michigan.
    "Written by world-leading experts, this book focusses on the role of biomaterials in stem cell research and regenerative medicine. Emphasising basic principles and methodology, it covers stem cell interactions, fabrication technologies, design principles, physical characterisation and biological evaluation, across a broad variety of systems and biomaterials. Topics include: stem cell biology, including embryonic stem cells, IPS, HSC and progenitor cells; modern scaffold structures, including biopolymer, bioceramic, micro- and nanofiber, ECM and biohydrogel; advanced fabrication technologies, including computer-aided tissue engineering and organ printing; cutting-edge drug delivery systems and gene therapy techniques; medical applications spanning hard and soft tissues, the cardiovascular system and organ regeneration. With a contribution by Nobel laureate Shinya Yamanaka, this is a must-have reference for anyone in the field of biomaterials, stem cell biology and engineering, tissue engineering and regenerative medicine"--Provided by publisher.
  • 2008From: CRCnetBASE
    edited by Paul K. Chu and Xuanyong Liu.
    Electrohydrodynamic processing of micro- and nanometer biological materials / Yiquan Wu and Robert Lewis Clark -- Fabrication and function of biohybrid nanomaterials prepared via supramolecular approaches / Katsuhiko Ariga -- Polypyrrole nano- and microsensors and actuators for biomedical applications / Yevgeny Berdichevsky and Yu-Hwa Lo -- Processing of biosensing materials and biosensors / Yingchun Zhu, Yu Yang, and Yanyan Liu -- Synthetic and natural degradable polymeric biomaterials / Sanjukta Deb -- Electroactive polymers as smart materials with intrinsic actuation properties: new functionalities for biomaterials / Federico Carpi and Danilo De Rossi -- Blood contacting surfaces / Menno L.W. Knetsch -- Improving blood compatibility of biomaterials using a novel antithrombin-heparin covalent complex / Leslie Roy Berry and Anthony Kam Chuen Chan -- Surface modification of biomaterials using plasma immersion ion implantation and deposition / Xuanyong Liu, Ricky K.Y. Fu, Paul K. Chu -- Biomaterials for gastrointestinal medicine, repair and reconstruction / Richard M. Day -- Biomaterials for cartilage reconstruction and repair / Wojciech Swieszkowski ... [et al.]. Inorganic and composite bioactive scaffolds for bone tissue engineering / Q.Z. Chen, Oana Bretcanu, Aldo R. Boccaccini -- Design, fabrication and characterization of scaffolds via solid free-form fabrication techniques / Dietmar W. Hutmacher and Maria Ann Woodruff -- Control and monitoring of scaffold architecture for tissue engineering / Ying Yang ... [et al.] -- Rapid prototyping methods for tissue engineering applications / Giovanni Vozzi and Arti Ahluwalia -- Design and fabrication principles of electrospinning of scaffolds / Dietmar W. Hutmacher and Andrew K. Ekaputra -- Nanoparticles in cancer drug delivery systems / So Yeon Kim and Young Moo Lee -- Polymeric nano/microparticles for oral delivery of proteins and peptides / S. Sajeesh and Chandra P. Sharma -- Nanostructured porous biomaterials for controlled drug release systems / Yang Yang Li, Jifan Li, and Bunichiro Nakajima -- Inorganic nanostructures for drug delivery / Ying-Jie Zhu -- Self-assembly of nanostructures as biomaterials / Hua Ai, Yujiang Fan, and Zhongwei Gu --
  • 2012From: Cambridge
    editors S. Rodil, A. Almaguer, K. Anselme, J. Castro.
  • 2015From: Karger
    volume editor, Sanjukta Deb.
    Biomaterials in relation to dentistry / Deb, S. -- Polymer therapeutics in relation to dentistry / Rojo, L., Deb, S . -- Biological impact of bioactive glasses and their dissolution products / Hoppe, A., Boccaccini, A.R. -- Organic-inorganic composites toward biomaterial application / Miyazaki, T., Sugawara-Narutaki, A., Ohtsuki, C. -- New advanced materials for high performance at the resin-dentine interface / Toledano, M., Osorio, R. -- Nanobiomaterial coatings in dentistry / Choi, A.H., Cazalbou, S., Ben-Nissan, B. -- The effect of titanium surface modifications on dental implant osseointegration / Annunziata, M., Guida, L. -- Global gene expression analysis for the assessment of nanobiomaterials / Hanagata, N. -- Membranes for periodontal regeneration -- a material perspective / Bottino, M.C., Thomas, V. -- Biomaterials in the reconstruction of the oral and maxillofacial region / Ayoub, A., Al-Fotawei, R.
  • 2009From: Springer
    Antonio Merolli, Thomas J. Joyce, (eds.) ; foreword by Frédéric Schuind.
  • 2013From: Wiley
    edited by Susmita Bose, Amit Bandyopadhyay, Roger Narayan.
    This volume is a collection of 15 research papers from the Next Generation Biomaterials and Surface Properties of Biomaterials symposia which took place during the Materials Science & Technology 2012 Conference & Exhibition (MS & T'12) in Pittsburgh, Pennsylvania.
  • 2014From: Wiley
    edited by Susmitya Bose, Amit Bandyopadhyay Roger Narayan.
    This volume is a collection of research papers from the Next Generation Biomaterials and Surface Properties of Biomaterials symposia which took place during the Materials Science & Technology 2013 Conference & Exhibition (MS&T'13) in Montréal, Quebec, Canada.
  • KwonSoo Chun.
    While coronary heart diseases are considered the most deadly medical conditions in terms of overall deaths per year, orthopedic maladies are the costliest. One of the most prevalent orthopedic conditions is low back pain, which stems from degenerative tissue changes within the spinal column and associated spinal cord and peripheral nerve injuries. Treatment successes in conservative and surgical treatment are mixed, although the rates of spine surgery have dramatically increased over the past decade. Surgical treatment is considered a last resort, and of all the surgical approaches, spinal fusion is the most common for the treatment of low back pain. Since spinal fusion has been in use in the clinic for several decades now, results of long-term retrospective clinical reviews are now becoming available. Some of these studies have shown that spinal fusion may induce secondary injuries such as adjacent tissue regeneration, which may require additional surgical treatment. To overcome some of these complications, posterior dynamic stabilization has been introduced as an alternative to fusion surgery. Posterior dynamic stabilization is still considered mostly experimental and the majority of spine companies with ambitions in this field have not yet settled on particular design goals and implant concepts. A significant hurdle for entry to the market for such devices is the lack of understanding of what the ideal function of the device is, and how the implants should interact with the spinal column. The objective of this thesis was to evaluate the functionality of posterior dynamic stabilization depending on patient conditions such as mobility and body mass and to suggest efficient rigidities of the dynamic device when considering patients' characteristics. This study is divided into three specific aims. The purpose of the first aim was to investigate the significant influence of a patient's spinal kinematics on dynamic stabilization. The patients were divided by segmental range of motion (L3-L4) into two groups (hyper-mobility and hypo-mobility) and finite element (FE) models were generated for these respective groups. This study showed that patient characteristics such as mobility produced different spinal kinematics after dynamic stabilization and demonstrated that the effectiveness of dynamic stabilization was increased when the mechanical properties of the device were changed in response to patient characteristics. The purpose of the second aim was to evaluate the stabilization devices in relation to patients' body mass and spinal mobility, testing the effects of dynamic stabilization devices of varying levels of rigidity. Based on analyzed results of the spinal mobility at the diseased level (L4-L5), the hyper-mobility patients were divided into three groups, based on severity. Depending on the body mass in the hyper-mobility patients, the patients were divided into three groups. The findings of the study demonstrated the significant influence of patients' body mass and mobility on spinal kinematics after dynamic stabilization. The purpose of the third aim was to investigate the effect of implant rigidity on spinal kinematics utilizing a cadaveric tissue model. This in-vitro study was designed to validate the biomechanical influence of physiological loading after dynamic stabilization. The results of this in-vitro study showed that patients' characteristics change spinal segmental motion and different implant rigidities of the dynamic stabilization device also produce varying spinal kinematics depending on patients' conditions. Through these in-vitro tests, this thesis readdresses the importance of considering patient characteristics in the design of appropriate devices for spinal stabilization, and to select the right implants for the right patient population.
  • 2017From: Wiley
    Ghias Kharmanda, Abdelkhalak El Hami.
  • 2016From: Springer
    Dominique G. Poitout, editor.
    I. Introduction -- II. Biocompatible Materials -- III. Tissue Biomechanics and Histomorphology -- IV. Biomechanics of Bone Growth -- V. Applications of Biomechanical Principles to Orthopedics and Traumatology -- VI. Applications of Biomechanics Principles to Oncology -- VII. Articular Biomechanics.
  • 2011From: Springer
    Mark R. Pitkin.
    Floating Skeleton Concept -- Sanomechanics -- Biomechanics for Life -- SanomechanicsTM Exercises -- About Forces and Moments in Locomotion -- Sanomechanics for Respiration.
  • Jennifer Tryggvi Blundo.
    This dissertation investigated the role of biomechanics in two physiological systems, the heart and bone. Biomechanics motivates the study and characterization of how cells sense external forces and convert these signals into an intracellular response in a process called mechanotransduction. Three independent studies were designed with the goal of applying mechanical forces that mimic the in vivo microenvironment of either the heart or bone. The aim of these studies was to better under the mechanisms driving cellular processes, including cardiac myocyte differentiation and osteoblast mechanotransduction. The first study presents the design and implementation of tissue engineering approach to stem cell-based myocardial therapy. Three dimensional engineered heart tissue was formed by suspending human embryonic stem cell-derived cardiac myocytes isolated from beating embryoid bodies in a soluble extracellular matrix, and an in vitro mechanical conditioning regimen was applied at physiological levels of myocardial strain. The viability of the engineered stem cell tissue was monitored in vitro and in vivo for up to 8 weeks using molecular imaging of reporter gene activity. The application of cyclic mechanical strain in vitro resulted in cellular alignment along the axis of strain and an elongated cellular morphology with a high nuclear to cytoplasmic ratio, typical of neonatal cardiac myocytes, as well as increased expression of cardiac troponin I, in comparison to static controls. Analysis of the in vitro and in vivo bioluminescence imaging data demonstrated the viability of engineered heart tissue constructs; however, histology results showed immature cells within the implanted constructs, suggesting an inability of the stem cell-derived cardiac precursors to maintain a cardiac phenotype in vivo, as well the inherent inefficiency of the beating embryoid body method to identify and isolate cardiac myocyte precursors. The functional shortcomings exhibited by the embryoid body-based differentiation of embryonic stem cell-derived cardiac myocytes in the first study motivated further refinement of cardiac myocyte differentiation techniques. Therefore, the second study executed the design and fabrication of a microelectromechanical platform to study the role of electrical and mechanical stimulation in cardiac myocyte differentiation. The fabrication process used a combination of soft lithography and traditional microfabrication techniques to pattern thin film metal electrodes on an elastomeric polymer membrane. The completed device enabled coupled characterization and imaging of cardiac myocytes precursors, and the ability to assess the range of mechanical forces, up to 10% equibiaxial strain, that may induce or maintain a cardiac fate. Electrical continuity was demonstrated under static conditions but not under strain, and improvements in metal deposition and adhesion could address this performance defect. Beating clusters containing human embryonic stem cell-derived cardiac myocytes were plated on fabricated membranes, uncoated and coated with Matrigel, and cell viability was monitored using contrast microscopy. The third study transitioned to a different mechanical model of physiological forces, which was the application of oscillatory fluid flow-mediated fluid shear stress generated by the loading and unloading of bone. Specifically, the role of focal adhesion kinase, a protein tyrosine kinase recruited at focal adhesions and a major mediator of integrin signaling pathways, was studied in osteoblast mechanotransduction. The biochemical and transcriptional response of focal adhesion kinase mutant osteoblasts to physiological levels of shear stress induced by oscillatory fluid flow was impaired as measured by prostaglandin E2 release and cyclooxygenase-2 gene expression. Restoration of focal adhesion kinase expression with site-specific mutations at two tyrosine phosphorylation sites demonstrated that phosphorylation events play a role in prostaglandin release following oscillatory fluid flow. In conclusion, the role of mechanical forces, including the effect of cyclic mechanical strain in human embryonic stem cell-derived cardiac myocyte tissue engineering and the fluid shear stress-induced response of focal adhesion kinase mutant osteoblasts, was successfully demonstrated and quantified in this dissertation.
  • 2014From: CRCnetBASE
    Megh R. Goyal, PhD, PE, and Vijay K. Goyal, PhD.
    1. Biofluid dynamics of cardiopulmonary bypass surgery -- 2. Biomechanics of artificial heart -- 3. Biomaterials for an artificial pacemaker -- 4. Biomaterials for carotid stenting -- 5. Biomechanics of angioplasty : ballooning and stenting -- 6. Biomechanics of artificial lung -- 7. Biomechanics of artificial kidney -- 8. Biomechanics of arthritis and human body pain -- 9. Biomechanics of orthopaedic fixations -- 10. Biomechanics of total knee replacement -- 11. Biomechanics of dental prostheses.
  • Kemal Levi.
    The outermost layer of human skin, the stratum corneum (SC), is subject daily to variable ambient moisture and temperature conditions as well as application of potentially damaging cleansing agents. The inevitable results of these exposures are "tightness" of the skin which is directly related to the buildup of tensile residual drying stresses in the SC layer. In this work, we first describe the application of the substrate curvature technique to quantitatively measure the magnitude of these stresses and their relationship to selected drying environments and times. The SC drying stresses were observed to be very sensitive to the relative humidity and temperature of the drying environment as well as harshness of the chemical treatment. There was a strong correlation with the SC drying stresses and the chemical potential of water in the drying environment. The evolution of drying stresses in SC is discussed in relation to the effects of hydration and damage caused by chemical treatments on the underlying SC structure. We also describe the application of the substrate curvature technique to characterize stresses in occlusive topical coatings. We then extend the substrate curvature technique to measure the combined effects of the coating applied to human stratum corneum (SC) where the overall drying stresses may have contributions from the coating, the SC and the interaction of the coating with the SC. We show how these separate contributions in the coating and SC layers can be differentiated. Using this methodology, we characterize the effect of a range of moisturizing treatments on the drying stresses in human stratum corneum. Following moisturizer treatment, the SC was observed to have distinctive stress profiles with drying time depending on the effectiveness of the treatment. The stress values of specimens treated with the humectant moisturizers were observed to increase and stabilize after a few hours in the drying environment where they remained relatively constant until the end of exposure to the drying environment whereas the stress values of specimens treated with the emollient treatments were observed to rise rapidly to a peak stress value and relax to a final stress value. The effect of moisturizing treatments on the SC drying stresses was rationalized in terms of SC water loss and the chemical state of the SC components. Finally, we employ a fracture mechanics approach to understand the implications of the drying stresses in SC as a mechanical driving force for damage propagation (e.g. cracking and chapping) in the tissue. The crack driving force G was found for several cracking configurations and compared with the intercellular delamination energy, Gc, which is a property of the tissue that provides a measure of the resistance to cracking. Using this approach, we demonstrate how damaging treatments enhance and moisturizing treatments alleviate the propensity for dry skin damage.
  • 2011From: CRCnetBASE
    [edited by] Raymond Tong.
  • 2012From: Springer
    Jaroslav Šebestík, Milan Reiniš, Jan Ježek.
    Introduction -- Chemistry and structure of dendrimers. Definition of terms and nomenclature ; Sugar code (glyc code) ; Classes of peptide-, glyco, and glycopeptide dendrimers ; The dendritic state and dendritic effects ; Synthesis of dendrimers : convergent and divergent approaches ; Purification and characterization of dendrimers ; Dendrimeric libraries ; Dendrimers in catalysis -- Dendrimers and their biological and therapeutic applications. Dendrimers and solubility ; Biocompability and toxicity of dendrimers ; Dendrimers in nanoscience and nanotechnology ; Dendrimers in drug delivery ; Dendrimers in gene delivery ; Dendrimers and bacteria ; Dendrimers and viruses ; Dendrimers and parasites ; Cancer ; Diagnostics, lectin detection and cell-cell interactions ; Dendrimers as biosensors and imaging tools ; Dendrimers regulating in intracellular signaling pathways ; Vaccines and immunomodulation ; Dendrimers in neurodegenerative diseases ; Conclusions and perspectives. .
  • 2006From: CRCnetBASE
    edited by Joseph D. Bronzino.
    Sect. I. Physiologic systems. An outline of cardiovascular structure and function -- Endocrine system -- Nervous system -- Vision system -- Auditory system -- Gastrointestinal system -- Respiratory system -- sect. II. Physiological modeling, simulation, and control. Modeling strategies and cardiovascular dynamics -- Compartmental models of physiologic systems -- Cardiovascular models and control -- Respiratory models and control -- Neural networks for physiological control -- Methods and tools for identification of physiologic systems -- Autoregulating windkessel dynamics may cause low frequency oscillations -- External control of movements -- The fast eye movement control system -- A comparative approach to analysis and modeling of cardiovascular function -- Cardiopulmonary resuscitation: biomedical and biophysical analyses -- sect. III. Bioelectric phenomena. Basic electrophysiology -- Volume conductor theory -- The electrical conductivity of tissues -- Membrane models -- Computaitonal methods and software for bioelectric field problems -- Principles of electrocardiography -- Principles of electromyography -- Principles of electroencephalography -- Biomagnetism -- Electrical stimulation of excitable systems -- sect. IV. Neuroengineering. History and overview of neural engineering -- Electrical stimulation of the central nervous system -- Transcutaneous FES for ambulation: the parastep system -- Comparing electrodes for use as cortical control signals: tiny tines, tiny wires, or tiny cones on wires: which is best? -- Development of a multi-functional 22-channel functional electrical stimulator for paraplegia -- An implantable bionic network of injectable neural prosthetic devices: the future platform for functional electrical stimulation and sensing to restore movement and sensation -- Visual prostheses -- Interfering with the genesis and propagation of epileptic seizures by neuromodulation -- Transcranial magnetic stimulation of deep brain regions -- sect. V. Biomaterials. Metallic biomaterials -- Ceramic biomaterials -- Polymeric biomaterials -- Composite biomaterials -- Biodegradable polymeric biomaterials: an updated overview -- Biologic biomaterials: tissue-derived biomaterials (collagen) -- Soft tissue replacements -- Hard tissue replacements -- Controlling and assessing cell-biomaterial interactions at the micro- and nanoscale: applications in tissue engineering -- sect. VI. Biomechanics. Mechanics of hard tissue -- Musculoskeletal soft tissue mechanics -- Joint-articulating surface motion -- Joint lubrication -- Analysis of gait -- Mechanics of head/neck -- Biomechanics of chest and abdomen impact -- Cardiac biomechanics -- Heart valve dynamics -- Arterial macrocirculatory hemodynamics -- Mechanics of blood vessels -- The venous system -- Mechanics, molecular transport, and regulation in the microcirculation -- Mechanics and deformability of hematocytes -- Mechanics of tissue/lymphatic transport -- Modeling in cellular biomechanics -- Cochlear mechanics -- Vestibular mechanics -- Exercise physiology -- Factors affecting mechanical work in humans -- sect. VII. Rehabilitation engineering. Rehabilitation engineering, science, and technology -- Orthopedic prosthetics and orthotics in rehabilitation -- Wheeled mobility: wheelchairs and personal transportation -- Externally powered and controlled orthoses and prostheses -- Sensory augmentation and substitution -- Augmentative and alternative communication -- Measurement tools and processes in rehabilitation engineering -- Rehabilitation engineering technologies: principles of application -- sect. VIII. Human performance engineering. The elemental resource model for human performance -- Measurement of neuromuscular performance capacities -- Measurement of sensory-motor control performance capacities: tracking tasks -- Measurement of information-processing subsystem performance capacities -- High-level task analysis: cognitive components -- Task analysis and decomposition: physical components -- Human-computer interaction design -- Applications of human performance measurements to clinical trials to determine therapy effectiveness and safety -- Applications of quantitative assessment of human performance in occupational medicine -- Human performance engineering design and analysis tools -- Human performance engineering: challenges and prospects for the future -- sect. IX. Ethics. Beneficence, nonmaleficence, and medical technology -- Ethical issues related to clinical research.
  • Jules J. Berman.
    Status: Not Checked OutLane Catalog Record
  • 2012From: Wiley
    edited by Ashutosh Tiwari, Murugan Ramalingam, Hisatoshi Kobayashi, Anthony P.F. Turner.
    Application of the collagen as biomaterials / Kwangwoo Nam and Akio Kishida -- Biological and medical significance of nanodimensional and nanocrystalline calcium orthophosphates / Sergey V. Dorozhkin -- Layer-by-layer (LbL) thin film : from conventional to advanced biomedical and bioanalytical applications / Wing Cheung -- Polycaprolactone based nanobiomaterials / Narendra K. Singh and Pralay Maiti -- Bone substitute materials in trauma and orthopedic surgery properties and use in clinic / Esther M.M. Van Lieshout -- Surface functionalized hydrogel nanoparticles / Mehrdad Hamidi, Hajar Ashrafi, and Amir Azadi -- Utility and potential application of nanomaterials in medicine / Ravindra P. Singh [and others] -- Gold nanoparticle-based electrochemical biosensors for medical applications / Ulku Anik -- Impedimetric DNA sensing employing nanomaterials / Manel del Valle and Alessandra Bonanni -- Bionanocomposite matrices in electrochemical biosensors / Ashutosh Tiwari, Atul Tiwari -- Biosilica-nonocomposites-nanobiomaterials for biomedical engineering and sensing applications / Nikos Chaniotakis, Raluca Buiculescu -- Molecularly imprinted nanomaterial-based highly sensitive and selective medical devices / Bhim Bali Prasad and Mahavir Prasad Tiwari -- Immunosensors for diagnosis of cardiac injury / Swapneel R. Deshpande [and others] -- Ground-breaking changes in mimetic and novel nanostructured composites for intelligent-, adaptive-, and in vivo-responsive drug delivery therapies / Dipak K. Sarker -- Progress of nanobiomaterials for theranostic systems / Dipendra Gyawali [and others] -- Intelligent drug delivery systems for cancer therapy / Mousa Jafari [and others] -- The evolution of abdominal wall reconstruction and the role of nonobiotecnology in the development of intelligent abdominal wall mesh / Cherif Boutros, Hany F. Sobhi, and Nader Hanna -- Poly(polyol sebacate)-based elastomeric nanobiomaterials for soft tissue engineering / Qizhi Chen -- Electrospun nanomatrix for tissue regeneration / Debasish Mondal and Ashutosh Tiwari -- Conducting polymer composites for tissue engineering scaffolds / Yashpal Sharma, Ashutosh Tiwari, and Hisatoshi Kobayashi -- Cell patterning technologies for tissue engineering / Azadeh Seidi and Murugan Ramalingam.
  • 2005From: CRCnetBASE
    edited by Neelina H. Malsch.
    Converging technologies : nanotechnology and biomedicine / Mihail C. Roco -- Trends in biomedical nanotechnology programs worldwide / Mark Morrison and Ineke Malsch -- Nanotechnology and trends in drug delivery systems with self-assembled carriers / Kenji Yamamoto -- Implants and prostheses / Jeroen J.J.P. van den Beucken, X. Frank Walboomers, and John A. Jansen -- Diagnostics and high throughput screening / Aránzazu del Campo and Ian J. Bruce -- Nano-enabled components and systems for biodefense / Calvin Shipbaugh ... [et al.] -- Social and economic contexts : making choices in the development of biomedical nanotechnology / Ineke Malsch -- Potential risks and remedies / Emmanuelle Schuler.
    Also available: Print – 2005
  • 2011From: Springer Protocols
    edited by Sarah J. Hurst.
    Biomedical nanotechnology / Sarah J. Hurst -- Multiplexed detection of oligonucleotides with biobarcoded gold nanoparticle probes / Jae-Seung Lee -- Molecular detection of biomarkers and cells using magnetic nanoparticles and diagnostic magnetic resonance / Jered B. Haun ... [et al.] -- Real-time quantum dot tracking of single proteins / Jerry C. Chang and Sandra J. Rosenthal -- Titanium dioxide nanoparticles in advanced imaging and nanotherapeutics / Tijana Rajh, Nada M. Dimitrijevic, and Elena A. Rozhkova -- Surface modification and biomolecule immobilization on polymer spheres or biosensing applications / Chris R. Taitt ... [et al.] -- Multivalent conjugation of peptides, proteins, and DNA to semiconductor quantum dots / Duane E. Prasuhn, Kimihiro Susumu, and Igor L. Medintz -- Single snO2 nanowire-based microelectrode / Jun Zhou ... [et al.] -- Biosensing using nanoelectromechanical systems / Ashish Yeri and Di Gao -- Nano "Fly Paper" technology for the capture of circulating tumor cells / Shutao Wang, Gwen E. Owens, and Hsian-Rong Tseng -- Polymeric nanoparticles for photodynamic therapy / Young-Eun Koo Lee and Raoul Kopelman -- Hydrogel templates for the fabrication of homogeneous polymer microparticles / Ghanashyam Acharya ... [et al.] -- Antibacterial application of engineered bacteriophage nanomedicines : antibody-targeted, chloramphenicol prodrug loaded bacteriophages for inhibiting the growth of staphylococcus aureus bacteria / Lilach Vaks and Itai Benhar -- Viruses as nanomaterials for drug delivery / Dustin Lockney, Stefan Franzen, and Steven Lommel -- Applications of carbon nanotubes in biomedical studies / Hongwei Liao ... [et al.] -- Electrospun nanofibrous scaffolds for engineering soft connective tissues / Roshan James ... [et al.] -- Peptide amphiphiles and porous biodegradable scaffolds for tissue regeneration in the brain and spinal cord / Rutledge G. Ellis-Behnke and Gerald E. Schneider -- Computational simulations of the interaction of lipid membranes with DNA-functionalized gold nanoparticles / One-Sun Lee and George C. Schatz -- Cytotoxic assessment of carbon nanotube interaction with cell cultures / Hanene Ali-Boucetta, Khuloud T. Al-Jamal, and Kostas Kostarelos -- Nanoparticle toxicology : measurements of pulmonary hazard effects following exposures to nanoparticles / Christie M. Sayes, Kenneth L. Reed, and David B. Warheit -- Nanoparticle therapeutics : FDA approval, clinical trials, regulatory pathways, and case study / Aaron C. Eifler and C. Shad Thaxton -- Legislating the laboratory? Promotion and precaution in a nanomaterials company / Robin Phelps and Erik Fisher -- Navigating the patent landscapes for nanotechnology : english gardens or tangled grounds / Douglas J. Sylvester and Diana M. Bowman -- Scientific entrepreneurship in the materials and life science industries / Jose Amado Dinglasan, Darren J. Anderson, and Keith Thomas -- Applying the marketing mix (5 Ps) to bionanotechnology / Michael S. Tomczyk -- Managing the "Known Unknowns" : theranostic cancer nanomedicine and informed consent / Fabrice Jotterand and Archie A. Alexander.
  • 2007From: CRCnetBASE
    edited by Mike Jenkins.
  • 2014From: Atypon
    Joseph V. Tranquillo.
    Biomedical Signals and Systems is meant to accompany a one-semester undergraduate signals and systems course. It may also serve as a quick-start for graduate students or faculty interested in how signals and systems techniques can be applied to living systems. The biological nature of the examples allows for systems thinking to be applied to electrical, mechanical, fluid, chemical, thermal and even optical systems. Each chapter focuses on a topic from classic signals and systems theory: System block diagrams, mathematical models, transforms, stability, feedback, system response, control, time and frequency analysis and filters. Embedded within each chapter are examples from the biological world, ranging from medical devices to cell and molecular biology. While the focus of the book is on the theory of analog signals and systems, many chapters also introduce the corresponding topics in the digital realm. Although some derivations appear, the focus is on the concepts and how to apply them. Throughout the text, systems vocabulary is introduced which will allow the reader to read more advanced literature and communicate with scientist and engineers. Homework and Matlab simulation exercises are presented at the end of each chapter and challenge readers to not only perform calculations and simulations but also to recognize the real-world signals and systems around them.
  • 2010From: Atypon
    Phillip Weinfurt.
    Evaluating biomedical technology poses a significant challenge in light of the complexity and rate of introduction in today's healthcare delivery system. Successful evaluation requires an integration of clinical medicine, science, finance, and market analysis. Little guidance, however, exists for those who must conduct comprehensive technology evaluations. The 3Q Method meets these present day needs. The 3Q Method is organized around 3 key questions dealing with 1) clinical and scientific basis, 2) financial fit and 3) strategic and expertise fit. Both healthcare providers (e.g., hospitals) and medical industry providers can use the Method to evaluate medical devices, information systems and work processes from their own perspectives. The book describes the 3Q Method in detail and provides additional suggestions for optimal presentation and report preparation.
  • 2012From: Wiley
    edited by João F. Mano.
    Examples of natural and nature-inspired materials. Biomaterials from marine-origin biopolymers / Tiago H Silva, Ana R C Duarte, Joana Moreira-Silva, João F Mano, Rui L Reis -- Hydrogels from protein engineering / Midori Greenwood-Goodwin, Sarah C Heilshorn -- Collagen-based biomaterials for regenerative medicine / Christophe Helary, Abhay Pandit -- Silk-based biomaterials / Silvia Gomes, Isabel B Leonor, João F Mano, Rui L Reis, David L Kaplan -- Elastin-like macromolecules / Rui R Costa, Laura Martin, João F Mano, Jose C Rodriguez-Cabello -- Biomimetic molecular recognition elements for chemical sensing / Justyn Jaworski -- Surface aspects. Biology lessons for engineering surfaces for controlling cell-material adhesion / Ted T Lee, Andres J Garcia -- Fibronectin fibrillogenesis at the cell-material interface / Marco Cantini, Patricia Rico, Manuel Salmeron-Sanchez -- Nanoscale control of cell behavior on biointerfaces / E Ada Cavalcanti-Adam, Dimitris Missirlis -- Surfaces with extreme wettability ranges for biomedical applications / Wenlong Song, Natalia M Alves, João F Mano -- Bio-inspired reversible adhesives for dry and wet conditions / Aranzazu del Campo, Juan Pedro Fernandez-Blazquez -- Lessons from sea organisms to produce new biomedical adhesives / Elise Hennebert, Pierre Becker, Patrick Flammang -- Hard and mineralized systems. Interfacial forces and interfaces in hard biomaterial mechanics / Devendra K Dubey, Vikas Tomar -- Nacre-inspired biomaterials / Gisela M Luz, João F Mano -- Surfaces inducing biomineralization / Natalia M Alves, Isabel B Leonor, Helena S Azevedo, Rui L Reis, João F Mano -- Bioactive nanocomposites containing silicate phases for bone replacement and regeneration / Melek Erol, Jasmin Hum, Aldo R Boccaccini -- Systems for the delivery of bioactive agents. Biomimetic nanostructured apatitic matrices for drug delivery / Norberto Roveri, Michele Iafisco -- Nanostructures and nanostructured networks for smart drug delivery / Carmen Alvarez-Lorenzo, Ana M Puga, Angel Concheiro -- Progress in dendrimer-based nanocarriers / Joaquim M Oliveira, João F Mano, Rui L Reis -- Lessons from nature in regenerative medicine. Tissue analogs by the assembly of engineered hydrogel blocks / Shilpa Sant, Daniela F Coutinho, Nasser Sadr, Rui L Reis, Ali Khademhosseini -- Injectable -forming scaffolds for tissue engineering / Da Yeon Kim, Jae Ho Kim, Byoung Hyun Min, Moon Suk Kim -- Biomimetic hydrogels for regenerative medicine / Iris Mironi-Harpaz, Olga Kossover, Eran Ivanir, Dror Seliktar -- Bio-inspired 3d environments for cartilage engineering / Jose Luis Gomez Ribelles -- Soft constructs for skin tissue engineering / Simone S Silva, João F Mano, Rui L Reis.
  • 2014From: Springer Protocols
    edited by Gordana Vunjak-Novakovic, Department of Biomedical Engineering and Department of Medicine, Columbia University, New York, NY, USA, Kursad Turksen, Sprott Centre for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
    Derivation and network formation of vascular cells from human pluripotent stem cells -- High-throughput cell aggregate culture for stem cell chondrogenesis -- Microfluidic device to culture 3D in vitro human capillary networks -- Multifunction co-culture model for evaluating cell-cell interactions -- Multiwell plate tools for controlling cellular alignment with grooved topography -- Bioreactor cultivation of anatomically shaped human bone grafts -- Determining the role of matrix compliance in the differentiation of mammary stem cells -- Conjugation of proteins to polymer chains to create multivalent molecules -- An assay to quantify chemotactic properties of degradation products from extracellular matrix -- Biomimetic strategies incorporating enzymes into CaP coatings mimicking the in vivo environment -- Fabrication of biofunctionalized, cell-laden macroporous 3D PEG hydrogels as bone marrow analogs for the cultivation of human hematopoietic stem and progenitor cells -- Extracellular matrix mimetic peptide scaffolds for neural stem cell culture and differentiation -- The delivery and evaluation of RNAi therapeutics for heterotopic ossification pathologies -- Mimicking bone microenvironment for directing adipose tissue-derived mesenchymal stem cells into osteogenic differentiation -- Cultivation of human bone-like tissue from pluripotent stem cell-derived osteogenic progenitors in perfusion bioreactors.
  • Wei Huang.
    Nature has been evolving unparalleled molecular designs with extraordinary activity, simplicity, efficiency, and durability. The process of biomimicry takes inspiration from Nature. In this dissertation, I focused on the development of functional analogues of natural peptides and protein polymers for several applications that continue to challenge the biomedical field. Five applications were discussed: The first three sections focus on bioactive peptides that are generally shorter than 50 amino acids. The goal was to preserve the bioactivity of the natural peptides while reducing their natural sensitivity to proteases and fast in vivo clearance. The last two sections focus on developing protein polymer-based hydrogels. The goal was to generate biomimicking scaffolds for tissue regenerations. (i) Poly-N-substituted glycines, or peptoids, provide a biostable scaffold that can display a great diversity of side chains in highly tunable sequences via facile solid-phase synthesis. Current chemotherapeutics in oncology are often limited by side effect profiles and selection for drug resistance. Herein, I present a library of anticancer peptoids that mimic the cationic, amphipathic structural features of host defense peptides and explore their structure-activity relationship, and killing mechanisms. Several peptoids were found with broad cytotoxicity against cancer cells as well as the ability to overcome multidrug resistance. An initial in vivo study with a primary, orthotopic human breast cancer xenotransplantation model demonstrated anticancer efficacy of one of the studied peptoids. (ii) Cell-penetrating peptides have found numerous applications in biology and medicine as molecular transporters. We developed a library of cationic, amphipathic peptoids as a novel class of transporters and investigated the relationships between their structures, cellular uptake efficiency, and the associated cytotoxicity. Both guanidinium heads and bulky, aromatic hydrophobic residues were found to render the cationic, amphipathic constructs more permeable. Moreover, different internalization mechanisms were observed for peptoid transporters with distinct structures. One peptoid was identified as a promising transporter with excellent cellular uptake efficiency and low cytotoxicity. (iii) Bombesin (BBN) peptide can bind with high affinity and specificity to the GRP receptors (GRPR) which are upregulated invasive prostate cancer. BBN(7-14) provides a promising basis for developing radiometallated diagnostic or therapeutic radiopharmaceuticals to target GRPR positive prostate cancer. I report a design of a 4-arm PEG-based platform with multivalent BBN(7-14) for targeted delivery to the GRPR positive prostate cancer. The PEG-BBN conjugates displayed comparable tumor uptake as the free BBN while having both a lower liver uptake and higher tumor-to-blood ratio in a biodistribution study. (iv) Regenerative medicine is in need of bioactive extracellular matrix-like scaffolds that can interact with cells and allow tissue regeneration in a well-controlled manner. Via "controlled cloning", matrix metalloproteases (MMP) degradation sites were built into multiple sites along a protein polymer that can be enzymatically crosslinked into a previously established non-bioactive hydrogel systems. The incorporation of MMP degradation sites greatly improved cell infiltration into the hydrogel. (v) Lastly, a novel in situ forming hybrid, biomimetic hydrogel comprising bioactive recombinant protein polymers, hyaluronic acid (HA) and polyethylene glycol (PEG) was developed. In a preliminary study, this hydrogel was found to be biocompatible and bioactive, which opens up future studies with this hydrogel system.
  • 2007From: Springer
    Jos A.E. Spaan ... [et al.], (eds.).
  • Sean Damien Gates.
    The work presented herein is concerned with the development of biophysical methodology designed to address pertinent questions regarding the behavior and structure of select pathogenic agents. Two distinct studies are documented: a shock tube analysis of endospore-laden bio-aerosols and a correlated AFM/NanoSIMS study of the structure of vaccinia virus. An experimental method was formulated to analyze the biological and morphological response of endospores to gas dynamic shock waves. A novel laser diagnostic system was implemented to provide time resolved data concerning the structural decomposition of endospores in shock-heated flows. In addition, an ex situ methodology combining viability analysis, flow cytometry and scanning electron microscopy was employed to both assess the biological response of the endospore to the shock event, as well as to provide complementary data regarding the structural state of the treated endospore. This methodology was implemented to model the shock wave induced response of a variety of Bacillus endospores. The results are subsequently synthesized into a theoretical framework to be employed in modeling the interaction of endospore-laden bio-aerosols with blast waves. An analytical method combining atomic force microscopy (AFM) and nanometer-scale secondary ion mass spectrometry (NanoSIMS) was developed to examine the spatial localization and depth distribution of specific biological elements in viral systems. This methodology was implemented to analyze the distribution of 13C labeled fatty acids as well as 15N labeled thymidine in individual nanometer sized vaccinia viral particles. Based upon the 13C and 15N signals, three-dimensional depth-resolved data regarding the architecture and localization of the virion lipid membrane and the nucleoprotein complex was generated. In addition, this methodology was employed to provide direct correlation of architectural and chemical data for isolated sub-viral structures. The technique and results presented herein represent a novel tool for the structural and chemical study of both intact viral particles as well as specifically targeted sub-viral elements.
  • v. 1-2, 2009From: Springer Protocols
    v. 2, 2009From: Springer Protocols
    edited by Avraham Rasooly and Keith E. Herold.
    V. 1. Optical-based detectors. Pt. I. Optical-based detectors. Surface plasmon resonance and surface plasmon field-enhanced fluorescence spectroscopy for sensitive detection of tumor markers / Yusuke Arima ... [et al.] -- Surface plasmon resonance biosensor for biomolecular interaction analysis based on spatial modulation phase detection / Xiang Ding, Fangfang Liu, and Xinglong Yu -- Array-based spectral SPR biosensor: analysis of mumps virus infection / Jong Seol Yuk and Kwon-Soo Ha -- Optical biosensors based on photonic crystal surface waves / Valery N. Konopsky and Elena V. Alieva -- Surface plasmon resonance biosensing / Marek Piliarik, Hana Vaisocherová, and Jiří Homola -- Label-free detection with the resonant mirror biosensor / Mohammed Zourob ... [et al.] -- Label-free detection with the liquid core optical ring resonator sensing platform / Ian M. White ... [et al.] -- Reflectometric interference spectroscopy / Guenther Proll ... [et al.] -- Phase sensitive interferometry for biosensing applications / Digant P. Davé -- Label-free serodiagnosis on a grating coupler / Thomas Nagel, Eva Ehrentreich-Förster, and Frank F. Bier -- Pt. II. Indirect detectors. CCD camera detection of HIV infection / John R. Day -- Integrating waveguide biosensor / Shuhong Li ... [et al.] -- Detection of fluorescence generated in microfluidic channel using in-fiber grooves and in-fiber microchannel sensors / Rudi Irawan and Swee Chuan Tjin -- Multiplex integrating waveguide sensor: SignalyteTM-II / Shuhong Li ... [et al.] -- CCD based fiber-optic spectrometer detection / Rakesh Kapoor -- V. 2. Electrochemical and mechanical detectors, lateral flow and ligands for biosensors. Pt. I. Mechanical detectors. A set of piezoelectric biosensors using cholinesterases / Carsten Teller ... [et al.] -- Piezoelectric biosensors for aptomer-protein interaction / Sara Tombelli ... [et al.] -- Piezoelectric quartz crystal resonators applied for immunosensing and affinity interaction studies / Petr Skládal -- Biosensors based on cantilevers / Mar Alvarez ... [et al.] -- Piezoelectric-excited millimeter-sized cantilever biosensors / Raj Mutharasan -- Pt. II. Electrochemical detectors. Preparation of screen-printed electrochemical immunosensors for estradiol, and their application in biological fluids / Roy M. Pemberton and John P. Hart -- Electrochemical DNA biosensors: protocols for intercalator-based detection of hybridization in solution and at the surface / Kagan Kerman, Mun'delanji Vestergaard, and Eiichi Tamiya -- Electrochemical biosensor technology: application to pesticide detection / Ilaria Palchetti, Serena Laschi, and Marco Mascini -- Electrochemical detection of DNA hybridization using micro and nanoparticles / María Teresa Castañeda, Salvador Alegret, and Arben Merkuçi -- Electrochemical immunosensing using micro and nanoparticles / Alfredo de la Escosura-Muñiz ... [et al.] -- Methods for the preparation of electrochemical composite biosensors based on gold nanparticles / A. González-Cortés, P. Yáñez-Sedeño, and J.M. Pingarrón -- Pt. III. Lateral flow. Immunochromatographic lateral flow strip tests / Gaiping Zhang, Junqing Guo, Xuannian Wang -- Liposome-enhanced lateral-flow assays for the sandwich-hybridization detection of RNA / Katie A. Edwards and Antje J. Baeumner -- Rapid prototyping of lateral flow assays / Alexander Volkov ... [et al.] -- Lateral flow colloidal gold-based immunoassay for pesticide / Shuo Wang, Can Zhang, and Yan Zhang -- Pt. IV. Ligands. Synthesis of a virus electrode for measurement of prostate specific membrane antigen / Juan E. Diaz ... [et al.] -- Simple luminescence detector for capillary electrophoresis / Antonio Segura-Carretero, Jorge F. Fernández-Sánchez, and Alberto Fernández-Gutiérrez -- Optical system design for biosensors based on CCD detection / Douglas A. Christensen and James N. Herron --A simple portable electroluminescence illumination-based CCD detector / Yordan Kostov ... [et al.] -- Fluoroimmunoassays using the NRL array biosensor / Joel P. Golden and Kim E. Sapsford -- Biosensors technologies: acousto-optic tunable filter-based hyperspectral and polarization images for fluorescence and spectroscopic imaging / Neelam Gupta -- Photodiode-based detection system for biosensors / Yordan Kostov -- Photodiode array on-chip biosensor for the detection of E. coli O157:H7 pathogenic bacteria / Joon Myong Song and Ho Taik Kwon -- DNA analysis with a photo-diode array sensor / Hideki Kambara and Guohua Zhou -- Miniaturized and integrated fluorescence detectors for microfluidic capillary electrophoresis devices / Toshihiro Kamei -- Photomultiplier tubes in biosensors / Yafeng Guan -- In vivo bacteriophage display for the discovery of novel peptide-based tumor-targeting agents / Jessica R. Newton and Susan L. Deutscher -- Biopanning of phage displayed peptide libraries for the isolation of cell-specific ligands / Michael J. McGuire, Shunzi Li, and Kathlynn C. Brown -- Biosensor detection systems: engineering stable, high-affinity bioreceptors by yeast surface display / Sarah A. Richman, David M. Kranz, and Jennifer D. Stone -- Antibody affinity optimization using yeast cell surface display / Robert W. Siegel -- Using RNA aptamers and the proximity ligation assay for the detection of cell surface antigens / Supriya S. Pai and Andrew D. Ellington -- In vitro selection of protein-binding DNA aptamers as ligands for biosensing applications / Naveen K. Navani, Wing Ki Mok, and Yingfu Li -- Pt. V. Protein and DNA preparation. Immobilization of biomolecules onto silica and silica-based surfaces for use in planar array biosensors / Lisa C. Shriver-Lake, Paul T. Charles, and Chris R. Taitt -- Rapid DNA amplification using a battery-powered thin-film resistive thermocycler / Keith E. Herold ... [et al.].
  • 2012From: Springer
    Erik Mosekilde, Olga Sosnovtseva, Amin Rostami-Hodjegan, editors.
  • Fong Tian Wong.
    Polyketide synthases (PKSs) are multi-functional enzymes, which synthesize natural products known as polyketides. These complex molecules have a diverse range of medicinal properties. Biosynthetic engineering of the multi-modular PKSs is attractive due to their modularity and colinearity, which, if understood at the molecular level, could allow for the efficient and predictable regioselective chemical manipulation of polyketides. A minimum combination of a [beta]-ketosynthase (KS), an acyltransferase (AT), and an acyl carrier protein (ACP) is required for the assembly of acyl-CoA precursors into complex polyketide products. This work will focus on AT domains, which are the primary gatekeepers for stepwise incorporation of acyl-CoA building blocks into a growing polyketide chain. In our initial investigations, protein interactions between AT, ACP and flanking AT linkers from a prototypical multimodular 6-deoxyerythronolide B synthase (DEBS) were systematically explored, guided by recent high-resolution structures. Our results indicate that N/C terminal linkers of the modular DEBS AT domain contributed to both efficiency and specificity of transacylation. Representative DEBS AT3 and AT6 domains were also observed to have greater than 10-fold AT specificities for their cognate ACP substrates as compared to other ACPs in the DEBS PKS. In comparison, there is only modest discrimination for its native ACP by the standalone AT from the "AT-less" disorazole synthase (DSZS). These "AT-less" multimodular PKS lack AT domains in their modular assembly, and instead, transacylation is supplied by a trans-acting discrete AT. With its higher transacylation activity for DEBS ACPs compared to their natural ATs (> 40-fold), DSZS AT presents new opportunities for regioselective modification of a polyketide backbone and thus prompting further structural and biochemical investigations. Towards the analysis of DSZS AT, we report crystal structures of trans-acting AT resolved at 1.51 Å, and that of its acetate complex at 1.35 Å resolution. Comprehensive alanine-scanning mutagenesis of its native ACP1 substrate also identified a conserved Asp45 residue on the ACP for AT interactions. This conserved residue is proposed to contribute to the observed AT promiscuity. Supplementing in silico protein docking with these results, a model for DSZS AT and ACP interactions was derived. Working towards high-resolution structural characterization of this interface, we developed a novel strategy for covalently cross-linking and purifying a catalytically relevant DSZS AT-ACP complex. Finally, trans complementation of methylmalonyl CoA specific DEBS modules was also accomplished in vitro with DSZS AT for malonyl CoA incorporation. From our investigations, we have gained new insights into the protein-protein interactions that play a major role in the efficient biosynthesis of structurally complex polyketides. These results also reveal important considerations and opportunities for biosynthetic engineering within the multi-functional assembly lines.
  • Gail Baura.
  • v. 27-, 2003-From: CRCnetBase
    v. 29, 2005From: CRCnetBase
  • 2014From: CRCnetBASE
    Firdos Alam Khan.
    "This book is a comprehensive overview of all the important aspects of medical biotechnology intended for interested, scientifically oriented laypersons, along, who want a relatively low level presentation of important biotechnology medical specialties such as bacteriology, immunology, recombinant DNA, molecular diagnostics, gene therapy, synthetic biology, tissue engineering, bioethics, IP issues, vaccines, and more"-- Provided by publisher.
  • 2011From: Springer
    Robert J. Roselli, Kenneth R. Diller.
    Part I. Fundamentals of How People Learn (HPL) -- Introduction to HPL Methodology -- Part II. Fundamental Concepts in Biotransport -- Fundamental Concepts in Biotransport -- Modeling and Solving Biotransport Problems -- Part III. Biofluid Transport -- Rheology of Biological Fluids -- Macroscopic Approach for Biofluid Transport -- Shell Balance Approach for One Dimensional Biofluid Transport -- General Microscopic Approach for Biofluid Transport -- Part IV. Bioheat Transport -- Heat Transfer Fundamentals -- Macroscopic Approach to Bioheat Transport -- Shell Balance Approach for 1-D Bioheat Transport -- General Microscopic Approach for Bioheat Transport -- Section V. Biological Mass Transport -- Mass Transfer Fundamentals -- Macroscopic Approach to Biomass Transport -- Shell Balance Approach for 1-D Biomass Transport -- General Microscopic Approach for Biomass Transport.
  • 2006From: Springer
    Ulrich Meyer, Hans Peter Wiesmann ; with a contribution by Thomas Meyer.
    Also available: Print – 2006
  • 2005From: CRCnetBASE
    edited by Jeffrey O. Hollinger ... [et al.].
    Also available: Print – 2005
  • Andreina Parisi-Amon.
    Our bones are complex and beautiful structures that highlight that Nature is a masterful materials scientist. These composite structures of minerals, proteins, and cells are capable of maintaining a remarkable, ever-changing balance based on an individual's biomechanical needs. Growing, running, jumping, sitting, sleeping -- all of our actions and inactions are chronicled and inform the processes of new bone formation and old bone resorption. The hierarchical microstructure, building from calcium phosphate nanocrystals embedded in collagen fibers, underscores the importance of mineral and organic components that synergistically contribute to the toughness of bone needed daily. Unfortunately, due to trauma or disease, at times our bones fail and are unable to heal themselves. It is for these instances that the field of Regenerative Medicine works to develop therapies built on expertise from materials science, engineering, and medical fields. Using protein engineering and bone biology as the starting foundation, my thesis work has focused on the development of two protein-engineered biomaterials for the improvement of regenerative medicine therapies focused on osseointegration of implants and bone regeneration. Engineered protein biomaterials harness the extensive toolkit provided to us by Nature, which includes the machinery to synthesize protein materials and myriad functional pieces to mix and match in our novel designs. With these tools I've helped develop an engineered elastin-like protein to be a photocrosslinkable, cell-adhesive, thin-film coating to improve the osseointegration of implants used to stabilize fractures. The material demonstrates increased speed and extent of cell attachment to coated surfaces, serving as proof of principle for use of this material in stimulating integration of coated implants through improved implant-cell interactions. Focusing my attention on non-healing skeletal defects, I worked with MITCH, our Mixing-Induced, Two-Component Hydrogel, to develop it for stem cell delivery and bone regeneration applications. MITCH employs molecular recognition of a peptide domain binding pair for gentle, on-demand, 3D cell encapsulation at constant physiological conditions. Further using this binding strategy to emulate the intimate interface between organic and mineral phases in native bone by crosslinking mineral nanoparticles into the hydrogel network via specific molecular interactions, I created a material capable of delivering adipose-derived stem cells and stimulating fast bone regeneration in critical-size calvarial defects. Regenerative medicine brings together the renewing power of stem cells and the rational design of biomimetic niches to help the body heal when it is incapable of doing so without assistance. Taken together, this body of work validates the strategy of designing protein-engineered biomaterials by taking cues from Nature to further the development of regenerative medicine therapies, improving their success and widespread adoption.
  • Justin C. Sanchez and José C. Principe.
  • Erin Girard.
    Cardiac C-arm CT is a valuable imaging modality that can provide three-dimensional images of the heart during an interventional procedure. As the technology advances to provide better image quality and faster acquisition times, the potential clinical uses increase. Visualization of myocardial defects could directly impact the guidance, procedure time, and outcome of various interventional procedures. In this work, I developed protocols to optimize low-contrast detectability for cardiac C-arm CT and performed in vivo studies to validate using C-arm CT for imaging myocardial necrosis during a cardiac interventional procedure. Initial in vivo investigations were used to evaluate the contrast injection protocol for ideal timing, dilution, catheter type, and injection location. Additionally, x-ray parameters including filtration, kVp, dose, and collimation were optimized for low-contrast detectability and minimization of artifacts. A 4 sweep x 5 s, ECG-gated imaging protocol using low energy (70-90 kVp) and high dose (1.2 [mu]Gy/projection) optimizes low contrast detectability, while collimation around the heart improves SNR by reducing scatter. Images acquired both in vivo and in a slab phantom show that tight collimation and beam filtration result in improved SNR and a reduction of shading artifacts. Visualization of radiofrequency ablation lesions using contrast enhanced C-arm CT during the procedure provides a direct assessment of adequate lesion formation and may circumvent complications associated with cardiac ablation procedures. An in vivo validation study was completed in 9 swine by comparing lesion dimensions measured in C-arm CT images and pathology specimens. All ablation lesions were visualized and lesion dimensions, as measured on C-arm CT, correlated well with postmortem tissue measurements using triphenyltetrazolium chloride (TTC) staining (mean difference 1D dimensions: 0.09 ± 1.04 mm, area: -0.71 ± 5.86 mm2). C-arm CT visualization of myocardial infarction (MI) in the catheterization lab could furnish early prognostic information for risk stratification as well as provide 3D images for guidance of stem cell or ablation therapies. A porcine model using balloon occlusion in the coronary artery was used to study visualization of acute and subacute MI in 12 swine. Contrast enhanced C-arm CT imaging was performed the day of infarct creation or 4 weeks after infarct creation and the volume of the infarct was compared against pathology to validate the visualization of infarction. Acute MI is best visualized at 1 minute post contrast injection as a region of combined hyper- and hypoenhancement whereas subacute MI appears as a region of hyperenhancement with peak contrast enhancement at 5 minutes post contrast injection. C-arm CT infarct volumes compared well with TTC staining (mean difference acute: -0.5 cm3, subacute: -0.7cm3). In conclusion, cardiac C-arm CT with contrast and imaging protocols optimized for low-contrast detectability has been established as a consistent and reliable technique for imaging myocardial necrotic tissue in the interventional suite.
  • 2012From: CRCnetBASE
    Sergey Dorozhkin.
    Due to a great chemical similarity with the biological calcified tissues, many calcium orthophosphates possess remarkable biocompatibility and bioactivity. Materials scientists use this property extensively to construct artificial bone grafts that are either entirely made of or only surface-coated with the biologically relevant calcium orthophosphates. Porous scaffolds made of calcium orthophosphates are very promising tools for tissue engineering applications. A comprehensive overview of calcium orthophosphates, this book highlights their importance and biomedical uses.
  • Jay R. Goldberg.
  • 2012From: Atypon
    Jay R. Goldberg.
    The biomedical engineering senior capstone design course is probably the most important course taken by undergraduate biomedical engineering students. It provides them with the opportunity to apply what they have learned in previous years, develop their communication, teamwork, project management,and design skills,and learn about the product development process. It prepares students for professional practice and serves as a preview of what it will be like to work as a biomedical engineer.
  • 2008From: CRCnetBASE
    Silvana Fiorito.
  • 2008From: Springer
    2008Limited to 1 simultaneous usersFrom: ProQuest Ebook Central
    edited by Guruprasad Madhavan, Barbara Oakley, Luis Kun ; editorial by Joachim Nagel ; foreword by Robert Langer ; introduction by Bruce Alberts ; afterword by Shu Chien.
    What makes a bioengineer and a biotechnologist? / Robert A. Linsenmeier, David W. Gatchell -- Bioengineering and biotechnology: a European perspective / Joachim H. Nagel -- Bioengineering and biotechnology: an Asia-Pacific perspective / Makoto Kikuchi, James C.H. Goh -- Employment outlook and motivation for career preparation / John D. Enderle -- Academic research and teaching / Nitish V. Thakor -- Teaching colleges and universities / Maria E. Squire -- Industry research and management / Mark W. Kroll -- Independent research laboratories / David J. Schlyer -- Public sector research, development, and regulation / Jove Graham -- Clinical medicine and healthcare / Leann M. Lesperance -- Intellectual property law / Kenneth H. Sonnenfeld -- Clinical engineering / Jennifer McGill -- Entrepreneurship in medical device technologies / Dany Bérubé -- Entrepreneurship in pharmaceutical and biological drug discovery and development / Robert G.L. Shorr -- Human implantable technologies / Joseph H. Schulman -- Specialized careers in healthcare / Charles H. Kachmarik, Jr. -- Finance and investment industry / Kristi A. Tange -- Regulatory affairs / Ronald A. Guido, Alan V. McEmber -- Clinical research careers / Kathi G. Durdon -- Science and technology policy / Luis G. Kun -- Forensic psychology / Diana M. Falkenbach -- Energy / Mary E. Reidy -- Technology transfer / Eugene B. Krentsel -- Politics and legislation / David R. Koon -- Social entrepreneurship / Robert A. Malkin -- Technology and management consulting / Guruprasad Madhavan -- Expert witness and litigation consulting / John G. Webster -- Public relations / Cynthia Isaac -- Sales and marketing / Jason M. Alter -- Sports engineering / Celeste Baine -- Writing non-fiction books / Barbara A. Oakley -- Emerging innovative careers / Guruprasad Madhavan, Jennifer A. Flexman, Aimee L. Betker -- Holistic engineering: the dawn of a new era for the profession / Domenico Grasso, David Martinelli -- On searching for new genes: a 21st century DNA for higher education and lifelong learning / Rick L. Smyre -- Protean professionalism and career development / Steven Kerno, Jr. -- Leadership through social artistry / Jean Houston -- Career and life management skills for success / Bala S. Prasanna -- Perspectives on ethical development: reflections from life and profession / Jerry C. Collins -- Technology development and citizen engagement / Joseph O. Malo -- In defense of science and technology / Elizabeth M. Whelan -- Science, ethics, and human destiny / John c. Polanyi -- Motives, ethics, and responsibility in research and technology development / Subrata Saha, Pamela Saha -- Science and technology policy for social development / Semahat S. Demir -- Medicine and health safety / Richard A. Baird, Roderic I. Pettigrew -- Patient safety: building a triangle of importance / T.K. Partha Sarathy -- Design of appropriate medical technologies: engineering social responsibility and awareness / Nigel H. Lovell -- Ubiquitous healthcare: a fundamental right in the civilized world / Pradeep Ray, Dhanjoo Ghista -- Towards affordable and accessible healthcare systems / Xiaofei F. Teng, Yuan-Ting Zhang -- From war to law via science / John C. Polanyi -- Science and technology for sustainable well-being / Rajendra K. Pachauri -- Nonviolence for technocrats / Arun M. Gandhi -- Humanistic science and technology for a hunger-free world / M.S. Swaminathan -- Feeding the hungry / Norman E. Borlaug -- Environmental consciousness and sustainable engineering design / Raghav Narayanan, Ashbindu Singh -- Improving public health quality and equity through effective use of technology / Andrei Issakov, S. Yunkap Kwankam -- Information sharing in the 21st century / Vinton G. Cerf -- Energy and sustainability in the 21st century / John P. Holdren -- Health and human rights: a global mandate / Sarah Hall Gueldner -- Gender equality: progress and challenges / Yunfeng Wu, Yachao Zhou, Metin Akay -- Complexity: mastering the interdependence of biology, engineering and health / Yaneer Bar-Yam -- Enhancing humanity / Raymond C. Tallis -- Translational research / Gail D. Baura -- Research paving the way for therapeutics and diagnostics / Dieter Falkenhagen -- Interdisciplinary collaboration and competency development / Joaquin Azpiroz Leehan -- The 21st century mind: the roles of a futures institute / Rick L. Smyre -- Accelerating innovation in the 21st century / Ralph W. Wyndrum, Jr. -- Benign application of knowledge through evolutionary theory / David Sloan Wilson -- Honor thy profession / Max E. Valentinuzzi -- Technical leadership: an international imperative / Barry L. Shoop -- The art of achieving the menschhood / Guy Kawasaki -- Ten questions for individual leadership development / John C. Maxwell.
  • 2009From: Springer
    edited by Mohamed Al-Rubeai.
    Mammalian cell lines command an effective monopoly for the production of therapeutic proteins that require post-translational modifications. This book deals with the methodology involved in the development of cell lines and the cell engineering approach that can be employed to enhance productivity and improve cell function.
  • 2012From: CRCnetBASE
    edited by Kangde Yao, Junjie Li, Fanglian Yao, Yuji Yin.
    Due to their unique properties, chitosan-based materials have emerged as useful resources in a variety of medicines, drug controlled-release carriers, tissue engineering scaffolds, and immobilized enzymes. But many of these materials have yet to reach the commercial market. Therefore, more work must be completed to fill the gap between research and production. Exploring the state of the field, Chitosan-Based Hydrogels: Functions and Applications details the latest progress in the research and development of chitosan-based biomaterials. The book introduces the formation and chemical structure of chitosan-based hydrogels. It also discusses the relationship between their structure and functions, which provides a theoretical basis for the design of biomaterials. In addition, many real-world examples illustrate the potential application of chitosan-based hydrogels in various areas, including materials science, biotechnology, pharmaceuticals, regenerative medicine, and cell engineering. By examining the structure and functions of chitosan-based hydrogels in living systems, this book provides the foundation for future research. It encourages readers to contribute to further research and development of these unique biomaterials.
  • 2012From: Atypon
    Donald McEachron.
    This book represents the first in a two-volume set on biological rhythms. This volume focuses on supporting the claim that biological rhythms are universal and essential characteristics of living organisms, critical for proper functioning of any living system. The author begins by examining the potential reasons for the evolution of biological rhythms: (1) the need for complex, goal-oriented devices to control the timing of their activities; (2) the inherent tendency of feedback control systems to oscillate; and (3) the existence of stable and powerful geophysical cycles to which all organisms must adapt. To investigate the second reason, the author enlists the help of biomedical engineering students to develop mathematical models of various biological systems. One such model involves a typical endocrine feedback system. By adjusting various model parameters, it was found that creating a oscillation in any component of the model generated a rhythmic cascade that made the entire system oscillate. This same approach was used to show how daily light/dark cycles could cascade rhythmic patterns throughout ecosystems and within organisms.
  • 2015From: Springer
    Keith R. Pine, Brian H. Sloan, Robert J. Jacobs.
    This is the first textbook to offer a comprehensive account of ocular prosthetics and the evidence used to underpin and support this field of healthcare. It does so by bringing together information from ophthalmology, prosthetic eye and contact lens literature, and from experts actively engaged in these fields. The book describes the psychological, anatomical and physiological aspects of eye loss as well as surgical procedures for removing the eye, patient evaluation, constructing prosthetic eyes (including prosthetic and surgical techniques for dealing with socket complications), the socket's response to prosthetic eyes, prosthetic eye maintenance and the history of prosthetic eyes. Though primarily intended for prosthetists, ophthalmologists, ophthalmic nurses, optometrists and students in the fields of ocular medicine, maxillofacial medicine and anaplastology, the book also offers a useful resource for other health workers and family members who care for prosthetic eye patients, and for those patients seeking a deeper understanding of the issues affecting them than they can find elsewhere.
  • 2010From: CRCnetBASE
    edited by Monzer Fanun.
    Surfactants and block copolymers in drug delivery / Ambikanandan Misra ... [et al.] -- Application of colloidal properties in drug delivery / Swarnlata Saraf -- Polymeric nanocapsules for drug delivery : an overview / Sílvia S. Guterres ... [et al.] -- Poly(alkyl cyanoacrylate) nanoparticles for drug delivery and vaccine development / Anja Graf, Karen Krauel-Göllner, Thomas Rades -- Stimuli-sensitive polymer gels for dermal and transdermal drug delivery and their application in the development of smart textile materials / Witold Musial and Vanja Kokol -- Micelles : the multifunctional nanocarrier for colloidal drug delivery / Chandana Mohanty, Sarbari Acharya, and Sanjeeb K. Sahoo -- Multiple emulsions : an overview and pharmaceutical applications / Jatin Khurana, Somnath Singh, and Alekha K. Dash -- Pharmaceutical and biotechnological applications of multiple emulsions / Rita Cortesi and Elisabetta Esposito -- Nanoemulsions as drug delivery systems / Figen Tirnaksiz, Seyda Akkus, and Nevin Celebi -- Microemulsion systems : application in delivery of poorly soluble drugs / Ljiljana Djekic and Marija Primorac -- Diclofenac solubilization in mixed nonionic surfactants microemulsions / Monzer Fanun -- Self-emulsifying drug delivery systems / D. P. Maurya, Yasmin Sultana, and M. Abul Kalam -- Liquid crystals and their application in the field of drug delivery / Rakesh Patel and Tanmay N. Patel -- Liquid crystalline nanoparticles as drug nanocarriers / Anan Yaghmur and Michael Rappolt -- Niosomal delivery system for macromolecular drugs / Yongzhuo Huang, Faquan Yu, and Wenquan Liang -- A new class of mesoscopic aggregates as a novel drug delivery system / Federico Bordi, Cesare Cametti, and Simona Sennato -- Liposomes and biomacromolecules : effects of preparation protocol on in vitro activity / Paola Luciani, Debora Berti, and Piero Baglioni -- Colloidal nanocarrier systems as a tool for improving antimycobacterial and antitumor activities and reducing the toxicity of usnic acid / N. S. Santos-Magalhães ... [et al.] -- Dendrimers in drug delivery / Hu Yang -- Microsphere : a novel drug delivery system / Abdus Samad ... [et al.] -- Colloids in aerosol drug delivery system / Nazrul Islam -- Respiratory aerosol dynamics with applications to pharmaceutical drug delivery / Jinxiang Xi, P. Worth Longest, and Paula J. Anderson -- Colloidal carriers for drug delivery in dental tissue engineering / Nader Kalaji, Nida Sheibat-Othman, and Hatem Fessi -- Classification and application of colloidal drug delivery systems : passive or active tumor targeting / H. Yesim Karasulu, Burcak Karaca, and Ercüment Karasulu -- Nanocarriers for imaging applications / Vandana Patravale and Medha Joshi.
  • 2008From: CRCnetBASE
    Smita Gopalaswamy, Venky Gopalaswamy.
    Overview of combination products -- Ensuring successful combination product development -- Overview of FDA and other regulatory agency expectations -- Resource requirements -- Manufacturing of combination products -- Challenges and pitfalls to avoid with combination products -- Postlaunch compliance requirements -- Agency audits and challenges.
  • Mihalis S. Kariolis.
    Ligand-receptor interactions and the specific molecular recognition events that define them govern many important physiological processes. When these interactions become dysregulated, normal physiology quickly degenerates into disease states. Nowhere is this more evident than in metastatic cancer, where aberrant signaling drives uncontrolled cell growth and systemic dissemination of disease. In spite of much effort, the management of metastatic disease has largely remained an intractable clinical challenge as effective treatment options are limited. Protein-based biologics, which leverage the inherent affinity and specificity of protein-protein interactions, offer an effective strategy for targeting and modulating dysregulated disease pathways in order to bring them under control. In this dissertation, we use combinatorial and rational protein engineering methods to develop receptor-based therapeutics that target Axl, a receptor tyrosine kinase shown to be involved in driving metastasis and disease progression in a wide range of human cancers. Using yeast-surface display and directed evolution, Axl variants were engineered for improved binding to Gas6, Axl's activating ligand. To gain an understanding of the molecular basis of the increased binding, detailed biochemical and structural studies were performed, including solving the structure of a high affinity Axl variant in complex with Gas6. When reformatted for in vivo applications, the engineered Axl decoy receptors were found to have apparent affinities to Gas6 as low as 93 fM, which are among some of the strongest protein-protein interactions ever reported. Importantly, when tested in a panel of aggressive mouse models of metastatic disease, the engineered decoy receptors showed significant efficacy, reducing metastatic disease by up to 95%. Collectively, these results validate Axl as a therapeutic target in metastatic disease and highlight the potential clinical value of the engineered Axl decoy receptors as novel anti-metastatic therapies.
  • Heiko Schmiedeskamp.
    Dynamic susceptibility-contrast perfusion-weighted imaging (DSC PWI) is a magnetic resonance imaging (MRI) technique that measures the delivery of arterial blood to the tissue capillary bed using a contrast agent. DSC PWI can reveal important information in stroke patients by assessing hypoperfused brain tissue, while in tumor patients it is used to evaluate the tumor vasculature. For clinical applications, DSC PWI relies on both accurate and rapid image formation. Gradient-echo echo-planar imaging (EPI) is the most commonly used MRI pulse sequence for DSC PWI, mainly due to its fast image acquisition capability, a relatively high contrast-to-noise ratio, and its availability on most clinical MRI systems. However, quantification of perfusion parameters with gradient-echo EPI remains challenging. Gradient-echo EPI is most sensitive to larger vessels, including arteries and veins. These measurements do not provide specific information about true perfusion within the microvasculature, the site of oxygen and nutrient extraction to brain tissue. To acquire perfusion measurements that are more confined to the microvasculature, spin-echo EPI acquisition techniques have been proposed. Spin-echo EPI is most sensitive to smaller vessels, providing a clear advantage over gradient-echo EPI. Unfortunately, spin-echo EPI suffers from lower sensitivity to the contrast agent passage, and the determination of arterial contrast agent concentrations required for quantitative perfusion MRI remains an unsolved problem when using spin-echo EPI data. In the first part of this dissertation, a combined approach for simultaneous spin- and gradient-echo (SAGE) perfusion MRI is presented. The proposed imaging technique combines the advantages of higher overall sensitivity to contrast agent passage of gradient-echo EPI with superior microvascular selectivity of spin-echo EPI, resulting in complementary perfusion information. The combined method enabled improved detection of abnormal brain perfusion compared to conventionally processed DSC PWI data, as illustrated in cases of stroke and brain tumors. Specifically, reduced sensitivity to larger blood vessels of spin-echo data generated from SAGE perfusion MRI measurements improved the visibility of hypoperfused tissue. In the second part, the gradient-echo and spin-echo signal contributions to the proposed SAGE perfusion MRI acquisition technique are analyzed in detail. The development of an optimized pair of MRI excitation and refocusing pulses enhanced the contrast-to-noise ratio of the spin-echo signal. Moreover, augmented perfusion parameter estimation improved the accuracy of both gradient-echo and spin-echo signals to reduce perfusion quantification errors. In the last part, implications of contrast agent leakage from the brain vasculature are discussed. Considerable contrast agent extravasation, caused by blood-brain barrier leakage commonly observed in brain tumors and subacute strokes, results in additional quantification errors of brain perfusion parameters. To mitigate these errors, pharmacokinetic modeling of contrast agent distribution was applied to SAGE perfusion MRI data. Intravascular contrast agent concentrations could then be separated from extravascular concentrations, resulting in leakage-corrected perfusion data. Moreover, the applied pharmacokinetic modeling approach facilitated the extraction of permeability parameters. The combined evaluation of perfusion and permeability parameters, derived from SAGE perfusion MRI data, showed potential utility in brain tumor imaging with the goal of improving the diagnostic value of perfusion MRI in the assessment of brain tumor progression.
  • 2007From: Springer
    [edited by] J.L. Wu ... [et al.].
    Biomedical robotics and biomechatronics -- Complex virtual technology in medicine -- Information and communication technology in medicine -- Complex technology in rehabilitation -- Cognitive neuroscience and technology -- Complex bioinformatics.
  • 2006From: Springer
    A. Quarteroni (editor), L. Formaggia (editor), A. Veneziani (editor).
  • 2006.From: Springer
    edited by Thomas S. Deisboeck and J. Yasha Kresh.
  • Jessica Shih Coogan.
    Coarctation of the aorta is a congenital heart defect where a narrowing occurs in the thoracic aorta. Aortic coarctation accounts for approximately 5-10% of all congenital heart defects, affecting approximately 1 in 3000 newborns. While the condition has been recognized for over 70 years, many clinical questions still remain about the management of patients with aortic coarctation. There exists a need to investigate the complex hemodynamics associated with this disease using computational fluid dynamics to improve the diagnosis, treatment, and long-term management of these patients. First, computational simulations were used to determine the hemodynamic significance of various aortic arch obstructions, specifically to determine the significance of aortic hypoplasia, defined as long segment aortic narrowing, compared with aortic coarctation, defined as discrete narrowing. Ventricular workload was used as a metric for the degree of significance imposed by the narrowing. Results indicated that aortic hypoplasia was more significant that aortic coarctation when the same percent narrowing was considered. In addition, the simulations revealed that aortic hypoplasia consisting of 25-50% narrowing is not likely to be hemodynamically significant under resting conditions. Next, various treatment options were investigated by using simulations to compare surgical and stent-based treatment. In particular, stents placed in the aorta create a compliance mismatch because the stent is rigid and the aorta is deformable, so computational simulations were used to determine the significance of the mismatch. The results showed that the compliance mismatch associated with a rigid stent did not produce a clinically significant change in the required ventricular workload. This study refuted the claim that the compliance mismatch associated with stenting in aortic coarctation patients negatively impacts patient hemodynamics. Finally, patients with corrected aortic coarctation often suffer from hypertension and associated cardiovascular problems in the coronary and cerebral vessels. Computational simulations were used to determine the hemodynamics in the aorta, coronary, and cerebral vessels associated with hypertension and subsequent vascular remodeling. The results showed that hypertension induced with aortic coarctation is associated with nearly equal increases in mean pressure but different increases in pulse pressure throughout the model. This study revealed interesting and important information related to the hemodynamics in a large vascular model under the effects of hypertension and vascular wall remodeling. These studies showed the power of computational simulations to aid in the investigation of clinical questions regarding aortic coarctation.
  • 2011From: Atypon
    Ozkan Ufuk Nalbantoglu and Khalid Sayood.
    Recent advances in development of sequencing technology has resulted in a deluge of genomic data. In order to make sense of this data, there is an urgent need for algorithms for data processing and quantitative reasoning. An emerging in silico approach, called computational genomic signatures, addresses this need by representing global species-specific features of genomes using simple mathematical models. This text introduces the general concept of computational genomic signatures, and it reviews some of the DNA sequence models which can be used as computational genomic signatures. The text takes the position that a practical computational genomic signature consists of both a model and a measure for computing the distance or similarity between models. Therefore, a discussion of sequence similarity/distance measurement in the context of computational genomic signatures is presented. The remainder of the text covers various applications of computational genomic signatures in the areas of metagenomics, phylogenetics and the detection of horizontal gene transfer.
  • 2008From: CRCnetBASE
    Rezaul Begg, Daniel T.H. Lai, Marimuthu Palaniswami.
  • 2014From: ScienceDirect
    edited by Zhongmin Jin.
    1. Fundamentals of computational modelling of biomechanics in the musculoskeletal system -- 2. Finite element modeling in the musculoskeletal system: generic overview -- 3. Joint wear simulation -- 4. Computational modeling of cell mechanics -- 5. Computational modeling of soft tissues and ligaments -- 6. Computatonal modeling of muscle biomechanics -- 7. Computational modelling of articular cartilage -- 8. Computational modeling of bone and bone remodeling -- 9. Modelling fracture processes in bones -- 10. Modelling fatigue of bone cement -- 11. Modelling fracture processes in orthopaedic implants -- 12. Modelling cementless cup fixation in total hip arthroplasty (THA) -- 13. Computational modeling of hip implants -- 14. Computational modelling of knee implants -- 15. Computational modelling of spinal implants -- 16. Finite element modelling of bone tissue scaffolds -- Index.
  • Rashmi Raghu.
    It is well known that blood vessels exhibit viscoelastic properties. Vessel wall viscoelasticity is an important source of physical damping and dissipation in the cardiovascular system. There is a growing need to incorporate viscoelasticity of arteries in computational models of blood flow which are utilized for applications such as disease research, treatment planning and medical device evaluation. However, thus far the use of viscoelastic wall properties in blood flow modeling has been limited. As part of the present work, arterial wall viscoelasticity was incorporated into two computational models of blood flow: (1) a nonlinear one-dimensional (1-D) model and (2) a three-dimensional (3-D) fluid-solid interaction (FSI) model of blood flow. 1-D blood flow model: In blood flow simulations different viscoelastic wall models may produce significantly different flow, pressure and wall deformation solutions. To highlight these differences a novel comparative study of two viscoelastic wall models and an elastic model is presented in this work. The wall models were incorporated in a nonlinear 1-D model of blood flow, which was solved using a space-time finite element method. The comparative study involved the following applications: (i) Wave propagation in an idealized vessel with reflection-free outflow boundary condition; (ii) Carotid artery model with non-periodic boundary conditions; (iii) Subject-specific abdominal aorta model under rest and exercise conditions. 3-D FSI blood flow model: 3-D blood flow models enable physiologic simulations in complex, subject-specific anatomies. In the present work, a viscoelastic constitutive relationship for the arterial wall was incorporated in the 3-D Coupled Momentum Method for Fluid-Solid Interaction problems (CMM-FSI). Results in an idealized carotid artery stenosis geometry show that higher frequency components of flow rate, pressure and vessel wall motion are damped in the viscoelastic case. These results indicate that the dissipative nature of viscoelastic wall properties has an important impact in 3-D simulations of blood flow. Future work will include simulations of blood flow in patient-specific geometries such as aortic coarctation (a congenital disease) to assess the impact of wall viscoelasticity in clinically relevant scenarios. In the present work, arterial viscoelasticity has been incorporated in 1-D and 3-D computational models of blood flow. The biomechanical effects of wall viscoelasticity have been investigated through idealized and subject-specific blood flow simulations. These contributions are significant and suggest the potential importance of wall viscoelasticity in blood flow simulations for clinically relevant applications.
  • Joanna Lankester.
    The rapid rise in obesity in the US over the last several decades parallels a decrease in infectious disease incidence and a rise in antimicrobial usage. The role of the microbiome--which is influenced by both disease and by biocidal chemicals--on body weight is of increasing interest. We desired to quantify effects of changes in disease patterns and microbiome shifts on body weight of the population; however, no population-level model of body weight existed. Drawing from a collection of literature describing models of individual body weight, a model was built to quantify weight changes across the population using publicly available data from the National Health and Nutrition Examination Survey (NHANES). The model used an energy balance perspective, quantifying energy intake and expenditure. First, dietary data was obtained to describe energy intake. Dietary data comes primarily from self-report and is notoriously inaccurate as individuals tend to under-estimate their food consumption. A dataset was obtained from a study where participants had completed dietary recall surveys and had had energy expenditure measured. Using this as a "training dataset", Chapter 3 describes two predictive models developed which adjust dietary intake to a more biologically plausible range. The models were validated, with a simulation of NHANES data, for their ability to produce estimates within bounds established a priori. They produced substantially more realistic estimates than those derived from the raw data. With better estimates of energy intake, a simulation model of body weight in a population was built (Chapter 4). A population was drawn from NHANES which represented a realistic cross-section of the U.S. population based on age, sex, and survey sampling weights. Energy intake and expenditure were tracked for each individual in the model, and an excess or deficiency of energy was converted to a gain or loss of body weight. The effect of ageing on the weight distribution of the population was calculated. The excess energy necessary to produce the shift in the body weight distribution of the US population over a 20-year period was estimated. The effect of an infectious agent's alteration of energy intake and expenditure and associated body weight was also calculated. Finally, the relationship between NHANES data on triclosan and body mass index (BMI) was studied (Chapter 5). Triclosan is a biocide that likely affects the gut microbiome. The effect of triclosan on BMI in a linear regression was studied with triclosan expressed in two ways: (1). as a binary variable (present vs. absent) and (2). in quartiles (in order to assess whether increased quantity of triclosan led to a trend in BMI). Triclosan presence was found to be associated with an increase in BMI. By quartile, BMI was higher in lower levels of triclosan compared to higher levels, suggesting the possibility of multiple mechanisms of action.
  • Lampros C. Kourtis.
    A new method to evaluate bone rigidity and strength using tomographic bone images obtained via QCT (Quantitative Computed Tomography) is introduced. A newly developed computer program named VA-BATTS is used for image processing, bone segmentation, mesh creation, material assignment and calculation of far field normal and shear stresses as well as other cross sectional properties. In order to calculate torsional and transverse shear stresses in prismatic bodies having inhomogenous material properties, a new two-dimensional finite element formulation to estimate is presented. The formulation combines the torsional and transverse shear problem solutions and adds terms to account for the material inhomogeneity into one Weak Form of the problem, further discretized to yield a numerical approximation of the shear stresses problem. Results were validated using analytical models as well as three dimensional commercial code test cases yielding mean errors over the entire domain of less than 1%. This semi-automated application is publicly distributed and can be downloaded from VA-BATTS implements an elliptical stress failure criterion to predict bone strength. To validate, fifty-two fresh frozen femurs were tested under combined three-point bending and torsion to failure. VA-BATTS was able to predict bone failure under combined bending and torsion (R2=0.68) as well as bone torsional (R2=0.80) and bending (R2=0.50) rigidity. Using multivariate analysis that combined the elliptical stress failure and the torsional and bending rigidities, the prediction confidence level was raised (R2=0.87), comparable to existing more complex three dimensional finite element studies. The elliptical stress criterion suggests that the distal femur is weaker, in absolute terms, than the midshaft femur suggesting an explanation of the increased rate of distal femur fractures in patients with Spinal Cord Injury. In general, the newly introduced method proved to yield more accurate predictions compared to DXA derived Bone Mineral Density measurements (R2=0.56). Fracture patterns were analyzed to show mostly spiral patterns where torsional loads were applied. In addition, the accuracy of three point bending experiments was examined. Three parameters that may introduce errors in the predictions - transverse shear, local deformation (indentation) as well as cross sectional deformation effect -- were studied using a parametric finite element model. The model shows that depending on the geometric properties of the bone, errors as high as 75% may be introduced in the estimation of the bone elastic modulus. Bone rigidity estimates may now be corrected using the correction factors supplied in this study.
  • pt. A-B, C, 2009, 2011.From: ScienceDirect
    pt. B, 2009From: ScienceDirect
    pt. C, 2011From: ScienceDirect
    edited by Michael L. Johnson, Ludwig Brand.
  • Edith Merle Arnold.
    Walking and running rely on the complex coordination of the neurological, muscular, and skeletal systems. The role of muscles in this system is to produce force, a task that is dramatically affected by the dynamics of muscle fibers. In walking and running, we do not know how fiber dynamics affect force generation because experimental tools are ill suited to these measurements. Computer models can be powerful tools for estimating muscle dynamics that cannot be measured experimentally. During my doctoral research I created a model based on state-of-the-art muscle architecture data that estimates fiber lengths and velocities during movement. I used this model to create simulations of muscle fiber dynamics for five subjects walking and running at multiple speeds. Analysis of my simulations revealed how walking or running speed affects force generation, explained how running enables some muscles to produce more force than they do in walking, and yielded normative muscle fiber lengths and velocities of eleven muscles during walking and running. The results support the hypothesis that the walk-to-run transition in human gait is related to the force generation ability of the plantarflexors, offer insights into dynamic properties of muscles that have not yet been measured during walking and running, and permit comparisons among muscles with diverse architecture. The model and simulations created as part of this work can be applied to many other research areas in biomechanics and have been made freely available at
  • 2014From: Springer
    Eisei Noiri, Norio Hanafusa, editors.
    This pocket-sized manual serves as a concise and ideal reference work for therapeutic approaches using apheresis. Covering both basic theory and clinical details to facilitate improved treatment and patient outcomes, the text considers a variety of diseases, including myasthenia gravis, multiple sclerosis, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, nephrotic syndrome, TTP/TMA, dilated cardiomyopathy, and many other conditions. The book also reviews the growing trend toward adopting this unique therapy for a wide range of health management issues such as morbid obesity and/or type 2 diabetes, and for lowering LDL-cholesterol (cholesterol apheresis) in patients unresponsive to medication or lifestyle modification.
  • 2007From: CRCnetBASE
    edited by Terje A. Skotheim, John R. Reynolds.
    Conductive polymers as organic nanometals -- Conducting polymer fibre for smart fabric and interactive textile applications -- Inkjet printing and patterning of PEDOT-PSS -- Printing organic electronics on flexible substrates -- Light emitting polymers -- Organic electro-optic materials -- Conjugated polymer electronics -- Electrical bistable polymer films and their applications in memory devices -- Electroactive polymers for batteries and supercapacitors -- Conjugated polymer based photovoltaic devices -- Biomedical applications of ICPs -- Biosensors based on conducting electroactive polymers -- Optical biosensors based on conjugated polymers -- Conducting polymers for MEMS and other micro-devices -- Corrosion protection using conducting polymers -- Artificial muscles.
  • Jayodita Chetan Sanghvi.
    Significant progress has been made in experimentally discovering and understanding the molecular mechanisms of various cellular processes, from metabolism to cell division. However, integrating this knowledge into a comprehensive understanding of cellular physiology remains a challenge. We have attempted to synthesize the scientific community's knowledge of cell biology into one system by building the first computational model of the life cycle of a single cell. Our model describes Mycoplasma genitalium, the simplest known self-replicating organism. The model accounts for all known gene functions and molecular interactions. This "whole-cell" model provides a better understanding of basic cellular physiology and cell-to-cell variation. Furthermore, this model can be used to make systems level predictions and biological discoveries that would not have been possible without this integrated view of a cell. In order to represent all of the known gene functions of M. genitalium, we divided the genes into 28 functional groups describing cellular processes such as replication, transcription, translation, metabolism, supercoiling, and cytokinesis. We developed independent computational models for each of these cellular processes using the mathematical representation best fit for the given process, such as linear optimization, ordinary differential equations, and probabilistic and stochastic methods. To integrate the system, information was passed between these sub-modules at each second of the simulated cell cycle. Data and parameters for the model were acquired from hundreds of publications in the literature. The model was fit, benchmarked, and tested such that the cell grows and divides according to our understanding of cell physiology. The whole-cell model outputs the counts, actions, and interactions of every molecule at every time point of the cell cycle. It has made novel predictions about various aspects of cellular biology including protein occupation of the chromosomes, energy usage, and non-transcriptional forms of cell-cycle regulation. We performed an experimental study, measuring the growth rates of single-gene disruption M. genitalium strains, and found that 84% of the model predicted growth rates matched the experimental results, thus validating the predictive power of the model. The remaining 16% of growth rates indicated misrepresentations in the model--opportunities for biological discovery. We were able to predict biological behavior that would reconcile most of these discrepancies, and in three cases the model was able to predict refined kinetic parameters of compensatory metabolic reactions in the system. We performed kinetic assays to validate the accuracy of all three self-refining model predictions. This thesis presents the first gene-complete model of an organism that has been experimentally validated. Using the model to guide and support future experimentation, we hope to continue to discover previously unknown cellular physiology. Overall, the whole cell model enables a view of the entire inner workings of a cell, an integrated understanding that is difficult to achieve by experimentation alone. We hope that expansions of this model will continue to enable discovery of cellular biology, will increase our understanding of prokaryotes and higher organisms, will elucidate multifaceted behaviors like complex disease states, and will serve as predictive tools to guide synthetic biology.
  • Joshua Dale Webb.
    The shoulder bones provide few constraints on motion. Therefore, stability must be maintained by muscles and ligaments. Shoulder mobility allows versatility of function, but makes the shoulder prone to injury. A better understanding of the role of muscle in shoulder mechanics is needed to improve the treatment of shoulder injuries and pathologies. Computational models provide a valuable framework for characterizing joint mechanics. Previous shoulder models have used simple representations of muscle architecture and geometry that may not capture the details needed to fully understand muscle function. The purpose of this dissertation was to create a detailed 3D finite element model of the deltoid and the four rotator cuff muscles. This model was then used to characterize the muscle contributions to joint motion and stability. The model was constructed from magnetic resonance images of a healthy shoulder. From the images, the 3D geometry of the muscles, tendons and bones was acquired. A finite element mesh was constructed and the 3D trajectories of the muscle fibers were mapped onto the finite element mesh. A hyperelastic, transversely-isotropic material model was used to represent the nonlinear stress-strain relationship of muscle. Bone motions were prescribed and the resulting muscle deformations were simulated using an implicit finite element solver. To characterize muscle contributions to joint motion, we calculated moment arms for each modeled muscle fiber. We found that 3D models predicted substantial variability in moment arms across fibers within each muscle, which is not generally represented in line segment models. We also discovered that for muscles with large attachment regions, such as deltoid, the line segment models under constrained the muscle paths in some cases. As a result, line segment based moment arms changed more with joint rotation than moment arms predicted by the 3D models. Glenohumeral instability is common, and difficult to treat. To better understand the mechanics of instability we used the 3D model to investigate the role of the muscles in stabilizing the glenohumeral joint by simulating joint translations. We found that at the neutral position, anterior deltoid provides the largest potential to resist anterior translation which counters the conclusions of conventional line segment models. This is the result of compression generated by muscle contact, which must be considered when characterizing the ability of muscle to resist joint translation. This dissertation provides a new computational method for analyzing shoulder mechanics, and demonstrates the importance of 3D analysis when investigating the complex function of shoulder muscles.
  • 2015From: Springer
    edited by Fabio A. Guarnieri.
    This book presents a unique approach not found in any other text for those looking to improve the clinical results of refractive surgery by gaining a better understanding of corneal biomechanics and the instrumentation related to it. Written by leading experts in the field, this book provides authoritative coverage of the interactions of the cornea and the bioinstrumentation, such as corneal topography, pachymetry, aberrometers, tonometry and optical coherence tomography. Organized in an easy-to-read manner, Corneal Biomechanics and Refractive Surgery is designed for refractive surgeons and general ophthalmologists alike and describes the biomechanical role of the corneal tissue and how each part is affected in refractive surgery. Additionally, showing what the bioinstrumentation can measure, how models can improve understanding of the interaction between biomechanics, bioinstrumentation, and refractive surgery, and how these models and bioinstrumentation together can improve the refractive results, are also discussed.
  • editor, Barry N. Feinberg.
    Status: Not Checked OutLane Catalog Record
    v. 1. General principles.
  • Rostam Dinyari.
    In age-related macular degeneration (AMD) and retinitis pigmentosa (RP), two leading causes of blindness, the photoreceptor layer of the retina is degenerated while the rest of the retina is well preserved. The function of the photoreceptors is very similar to that of solar cells. Upon receiving light, they activate the inner layers of the retina by producing electrical and chemical signals. These signals are then processed and compressed by a complex circuit of retinal neurons (horizontal cells, bipolar cells, amacrine cells, and ganglion cells) and sent to the brain. The brain perceives these data as sight. Electronic retinal implant systems seek to restore sight in AMD and RP by electrical stimulation of the surviving retinal neurons. Currently the more dominant systems consist of a microelectrode array, which is placed directly on the ganglion cells (epiretinal). In this approach, a camera mounted on goggles captures video which is then processed by a pocket computer. The power and data are then transmitted wirelessly to an extraocular receiver unit. Through an intraocular cable, the receiver unit sends appropriate electrical stimuli to the array of microelectrodes. The electrodes then stimulate the ganglion cells by passing current pulses through the tissue. These stimulations are perceived by the brain as spots of light. The epiretinal approach has some disadvantages. Because the electrodes directly stimulate the ganglion cells, the image processing and data compression capabilities of the retina are not utilized. Placing the extraocular receiver unit and connecting it via a cable to the microelectrode array significantly complicates the surgical procedure and increases the chance of post surgical complications. Additionally, the perceived images are independent of the eye movements. We have developed an integrated photovoltaic monolithic silicon retinal implant that requires no electrical power or data connection. In our design, a miniature camera captures video that is processed by a pocket computer before being projected into the eye at a near-infrared wavelength ([Lambda] = 905 nm) onto the silicon implant located in the subretinal space (area in the back of the retina). The implant consists of a two-dimensional array of photovoltaic pixels. The projected image is provided in pulsed fashion and each pixel element consists of up to three series-connected photovoltaic cells such that the pixels deliver current pulses that are sufficiently strong to stimulate the remaining functional neural cells. The current pulses are interpreted as visual images by the brain. Placing the implant in the subretinal space allows for utilization of the existing image processing and data compression functions of the retina. Each pixel receives both power and data directly through laser radiation. This eliminates the need for a separate wireless receiver unit and simplifies the surgical procedures and reduces the post-surgical risks. Additionally, in this approach, eye movements change the perceived images. The novelty of the work reported here is the integration of photovoltaic devices in a MEMS process that allows the implant to deform to the natural curvature of the eye, while also providing isolation between the bodies of the three series-connected subpixels that make up each pixel. This was achieved by patterning the implants into an array of pixels connected together by deformable silicon flexures. In addition, the trenches also provide electrical isolation between the three series-connected photovoltaic subpixels. Curving the implant is advantageous since the complete implant is in focus, resulting in optimum quality of vision perceived. Curved implants can also be substantially larger than planar implants and can hence cover a larger part of the field of view. A curvable implant also causes no mechanical strain or abnormality in the eye. Usage of three series-connected subpixels per pixel improves the impedance matching to the surrounding tissue and enhances the injected current per pixel allowing for higher resolution implants. Fabricated implant with a resolution of 64 pixels/mm2 can inject sufficient current for neural activation at safe optical intensities. Additionally, the exchange of nutrients and waste, which is necessary for the survival of the retinal cells, is provided by diffusion through the trenches that define the silicon devices.
  • 2010From: CRCnetBASE
    William S. Kisaalita.
    "This book is based upon cutting-edge research conducted in the authors lab (Cellular Bioengineering), which over the past decade has developed a number of sophisticated techniques to facilitate use of 3D cell based assays or biosensors. This book uses data from peer-reviewed publications to conclusively justify use of 3D cell cultures in cell-based biosensors (assays) for (HTS). The majority of assays performed in accelerated drug discovery processes are biochemical in nature, but there is a growing demand for live cell-based assays. Unlike biochemical ones, cellular assays are functional approximations of in vivo biological conditions and can provide more biologically relevant information"--Provided by publisher.
  • Min-Sun Son.
    Meniscal degeneration often precedes cartilage degeneration, and effective detection and treatment can be critical in preventing osteoarthritis. The meniscus is a heterogeneous tissue, and obtaining information on the varying characteristics of meniscal regions is important in investigating such strategies. However, no current method exists that can detect such meniscal heterogeneity in the tissue matrix. In addition, the lack of quantitative information on meniscal heterogeneity hinders the development an effective, long-term solution that can treat degeneration in the meniscus. The purpose of this dissertation was thus 1) to find quantitative characteristics that defined meniscal heterogeneity and 2) to evaluate non-invasive diagnostic methods that could reflect the matrix tissue properties and detect meniscal heterogeneity. To accomplish the first goal, gene expression profiles of meniscal cells were statistically analyzed to identify quantitative markers that could distinguish between different regions of the meniscus, describing its heterogeneous properties. This information was then used to evaluate cell sources for meniscal tissue engineering, demonstrating the potential application of these quantitative markers in developing an effective treatment for meniscal degeneration. Secondly, in order to detect meniscal heterogeneity, which is reflected in the changing tissue properties within the tissue, magnetic resonance imaging was used. The potential of the imaging parameters T1[rho] and T2 relaxation times in detecting various meniscal tissue properties, including the matrix composition and mechanical properties, was examined. Ultimately, such information would be useful in identifying internal degenerative changes that take place in the matrix of the tissue prior to macroscopic injuries. In this study, both T1[rho] and T2 relaxation times showed variation with tissue properties but were highly correlated with one another, indicating that only one imaging parameter might be necessary as a diagnostic tool in a clinical setting. In addition, an exploratory aim visualized the internal secondary collagen network in the meniscus and examined its deformation in different mechanical loading positions. This work significantly adds to the understanding of the heterogeneous properties of the meniscus and the potential of magnetic resonance imaging parameters as detection markers. It contributes to the advancement of diagnosis and treatment strategies for meniscal degeneration, which has further implications for preventing osteoarthritis progression.
  • 2015From: Springer
    Dagmar Kainmueller.
    Segmentation of anatomical structures in medical image data is an essential task in clinical practice. Dagmar Kainmueller introduces methods for accurate fully automatic segmentation of anatomical structures in 3D medical image data. The author's core methodological contribution is a novel deformation model that overcomes limitations of state-of-the-art Deformable Surface approaches, hence allowing for accurate segmentation of tip- and ridge-shaped features of anatomical structures. As for practical contributions, she proposes application-specific segmentation pipelines for a range of anatomical structures, together with thorough evaluations of segmentation accuracy on clinical image data. As compared to related work, these fully automatic pipelines allow for highly accurate segmentation of benchmark image data. Contents Deformable Meshes for Accurate Automatic Segmentation Omnidirectional Displacements for Deformable Surfaces (ODDS) Coupled Deformable Surfaces for Multi-object Segmentation From Surface Mesh Deformations to Volume Deformations Segmentation of Anatomical Structures in Medical Image Data Target Groups Academics and practitioners in the fields of computer science, medical imaging, and automatic segmentation. The Author Dagmar Kainmueller works as a research scientist at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, with a focus on bio image analysis. The Editor The series Aktuelle Forschung Medizintechnik - Latest Research in Medical Engineering is edited by Thorsten M. Buzug.
  • 2007From: Springer
    Jasjit S. Suri, Aly A. Farag [editors].
  • James Francis Nishimuta.
    Osteoarthritis is a debilitating disease that affects 27 million Americans. Major risk factors for osteoarthritis include mechanical injury and obesity. Prolonged exposure to mechanical overload in the knee joint, either by injury, malalignment, or obesity, is associated with early onset of osteoarthritis. Recent evidence demonstrates that adipose tissue is a metabolically active and produces systemic biofactors known as adipokines associated with numerous diseases including cardiovascular disease, hypertension, insulin resistance, rheumatoid arthritis, and osteoarthritis. Interestingly, obesity is a significant risk factor for hand osteoarthritis, suggesting a biologic link between obesity and osteoarthritis that is perhaps mediated through adipokines. While many studies investigating in vitro osteoarthritic degradation have focused on cartilage tissue, the menisci has received relatively little attention despite it's important functional role in joint stability and load transfer in the knee. The purpose of this thesis was to explore the relative susceptibility of cartilage and meniscal tissue degradation to in vitro mechanical overload and adipokine exposure using an immature bovine tissue explant model. To explore the injury response, explants of cartilage and meniscal tissues were compressed at various strain rates to create a spectrum of peak injury forces and cultured for up to nine days post-injury. To investigate whether adipose tissue and adipokines can biochemically induce changes in cartilage and meniscal tissues, explants of cartilage and meniscal tissue were incubated with infrapatellar fat pad or individual adipokines and assessed for altered matrix metabolism. Overall, results indicate that, while mechanically robust, meniscal tissue is vulnerable to biologic damage induced by mechanical overload and adipokines. We also demonstrate for the first time that meniscal tissue is more catabolically sensitive to adipokines than cartilage tissue. These results provide evidence that obesity-driven degradation of knee joint could be biochemically mediated and suggest meniscal degradation as a possible early event in osteoarthritis development.
  • 2013From: Springer
    Sibel Yildirim.
    Dental Evolution -- Tooth development -- Dental Pulp is a Connective Tissue -- Dental Pulp Stem Cells (DPSC) -- Isolation methods of DPSC -- Characterization of DPSC -- Reprogramming of DPSC to induced pluripotent stem cells (iPSC) -- Immunomodulatory effects of DPSC -- Dental Pulp is a Complex Adaptive System.
  • Daniel McConnell Aukes.
    A balance between complexity and functional capabilities has been explored since the first years of multi-fingered robotic hands. In an age where DC motors are the de facto standard for actuation in robotics, the problem of needing to operate in a human-sized world puts severe constraints and limits on actuator size and placement in hands. While many successful examples of fully-actuated designs exist, these designs generally reflect the trade-offs and sacrifices imposed by such constraints. In that light, underactuation, employing fewer actuators than degrees of freedom, has gained attention as a method to achieve many of the functional capabilities of fully-actuated hands with fewer constraints on actuators and transmissions. Underactuated hands also have distinct advantages over fully actuated hands, especially when used on mobile robots, due to their reduced weight and control complexity, and the potential for increased robustness. However there is typically a trade-off in terms of reduced controllability or manipulability when handling grasped objects. When designing underactuated hands, extra care must be taken during the design process to ensure that such hands will grasp a wide range of object sizes and shapes robustly, particularly when friction is low and uncertain. Despite these concerns, underactuated hands have become increasingly popular in robotic and prosthetic applications. Robotic hands are also a venue in which novel, secondary mechanisms are often found. Devices such as differentials, valves, clutches, and low-power, shape-changing actuators have been used to improve grasp robustness on a wider range of objects and allow users more grasping and manipulation options. However, the location and placement of secondary actuators has not been studied in a comprehensive way with respect to the types of actuation methods possible. This is due in part to the lack of general analytic tools which enable designers to rapidly investigate their designs prior to the prototyping stage. Additionally, much of the analysis in the field of robotic hands is done once basic design choices have already been made, making subsequent analyses specific only to a set of design parameters specific to those choices. The same point can be made regarding quality metrics, which suffer from fragmented utilization due to the many different emphases placed on different design requirements. The primary goal of this thesis is to provide a framework for the analysis and evaluation of underactuated robotic hands. The first chapter discusses both the broad motivations for studying robotic hands and the specific contributions of this thesis. The next chapter reviews relevant designs from literature, analyses that have accompanied them, uses of secondary devices in underactuated hands, and the progress that dynamics simulators have made towards representing reality. In the next chapters, the issues related to modeling abstract, generic hand designs is discussed, and a kinematic framework is introduced to derive the force relationships between actuator and grasped object for many mechanisms commonly encountered in underactuated hands. Chapter 6 discusses difficulties associated with solving static force equations, and several methods are introduced to accomplish this. The last of these options relies on three-dimensional rigid-body dynamic simulations to evaluate the performance of compliant, underactuated mechanisms which may encounter conditions such as coulomb friction in contact and and damping at the joints. In the next chapters, these force relationships are derived and discussed for specific hand designs in the context of a force-field representation, and several performance metrics are derived which measure a hand's ability both to acquire and retain objects. The benefits of secondary actuation mechanisms are then discussed with two specific examples. First is the SRI/Stanford/Meka hand, a tendon-driven, compliant, underactuated hand capable of locking individual joints. Second is a mechanism implemented on the Seabed Hand, which increases the range of graspable objects and allows users to selectively change grasp properties based on their specific control needs. Finally, the impacts of friction are discussed, and the trends from simulations are compared with experimental data. From these experiments the benefits of secondary mechanisms can be demonstrated in a frictional world as well.
  • Prasheel Vashdev Lillaney.
    Using hybrid x-ray/MR (XMR) systems for image guidance during interventional procedures can enhance the diagnosis and treatment of neurologic, oncologic, cardiovascular, and other disorders. XMR suites have become more available, with various vendors offering dual-modality solutions. These systems combine the three-dimensional imaging capabilities and excellent soft tissue contrast provided by MR with the high spatial/temporal resolution and accurate device tracking provided by x-ray. To eliminate system compatibility concerns, the suites typically have long travel distances between MR and x-ray components. As a result, switching between modalities requires shuttling the patient several meters from one system to the other. Because patients typically have critically placed monitoring systems and intravenous lines for drug delivery and anesthesia, the cumbersome shuttling process impedes repeated switching between the modalities. To circumvent the hurdles associated with alternating between modalities, we proposed a close proximity hybrid system design in which a c-arm fluoroscopy unit is placed immediately adjacent to a closed bore MR system with a minimum distance of 1.2 meters between the x-ray and MR imaging field of views. Placing the x-ray system so close to the MR bore requires an x-ray tube capable of operating in a relatively strong MR fringe field environment. Existing rotating anode x-ray tube designs fail within MR fringe field environments because the magnetic fields alter the electron trajectories in the x-ray tube and act as a brake on the induction motor, reducing the rotation speed of the anode. In my work, I have developed (1) techniques to correct for the altered electron trajectories and (2) a novel motor design that eliminates the reduced rotation speed of the anode. Altering electron trajectories between the cathode and anode affects the location, size, and shape of the x-ray tube focal spot on the anode. I proposed a combination of approaches to control the trajectories. First, I derived an active magnetic shielding design using constrained optimization techniques that minimizes power consumption and heat deposition in the external deflection coils. I then adapted my shielding design to include rare earth permanent magnets, to further reduce the power and size requirements of the coils. Finally, I designed a split-focusing cup that controls the electron trajectories via electrostatic mechanisms, providing an alternative that is more space efficient and MR-compatible. High rotation speed of the anode is needed for sufficient instantaneous heat loading on the target area, to achieve the needed x-ray tube output. There is currently no available motor design to rotate the anode in the expected magnetic environment. To solve this problem, I designed a new motor that operates efficiently within the fringe field. The design is analogous to a modified three-pole brushed DC motor, with the radial component of the MR fringe field replacing the permanent magnet stator field used in conventional brushed DC motors. The motor support bearings provide rotating electrical contacts, while feedback signals from a position sensor control electrical commutation. A vacuum compatible prototype of the proposed motor design was assembled, and its performance was evaluated at various field strengths and orientations. Combining the control mechanisms for the electron trajectories with the new motor design yields a robust x-ray tube capable of operating in fringe fields with magnitudes on the order of 0.1 to 0.2 T.
  • Jae-Woong Jeong.
    Optical MEMS (Micro-Electro-Mechanical Systems) is an enabling technology that realizes miniaturized optical systems with high functionality and excellent performance. In this dissertation, two novel miniaturized optical systems are presented for applications in optical communication and biomedical imaging. In Part I, a multi-functional MEMS tunable optical filter are described, which is a key element for dynamic wavelength provisioning in reconfigurable optical networks and communication systems. This filter is built based on MEMS platform technology that allows large vertical mirrors (311 [mu]m x 450 [mu]m x 40 [mu]m) to be micro-assembled on actuated platforms to enable compact tunable optical filters with large apertures and high-quality optical mirrors with very low scattering losses. Besides, electrostatic combdrive actuators connected to the MEMS platforms provide independent and continuous control of the center wavelength and the optical bandwidth. The filter has been tested by integrating it in a 10Gb/s communication system. The performance of the MEMS tunable filter is demonstrated for amplified spontaneous emission (ASE) rejection and wavelength selection. In PART II, a 3-D MEMS scanning system utilizing 2-D lateral and 1-D vertical MEMS scanners is introduced for use in miniature in vivo dual-axis confocal (DAC) microendoscopes, which is an emerging biomedical-imaging technology with high resolution, good tissue penetration, large field of view, and ability to provide both reflectance and fluorescence contrast images. Both MEMS scanners are fabricated exclusively by front-side processing to enable compact and robust structures that facilitate handling and packaging for miniaturized optical instrumentation. Co-operation of a 2-D lateral scanner and a 1-D vertical scanner enables fast 3-D microscopy over a volume that measures 340[mu]m by 236[mu]m by 286[mu]m. This part describes the principle of the all-MEMS-based 3-D scanning DAC microscopy that gives the functionality of OCT (real-time vertical cross-section imaging) to a confocal microscope.
  • Paul J. Csonka.
    Over the last several years advances and miniaturization of technology have allowed legged robots to move from the research laboratory to the real world, as evidenced by the large number of flexible platforms only recently available. These platforms are successful, but fall short of capitalizing on the biggest advantage of legs: the ability for high speed locomotion over unstructured terrain. Additionally, no current articulated legged robot is able to perform both static and truly dynamic locomotion, as the actuation technology is not conducive to these two very different regimes of operation. Currently, machines that are dynamic are unable to walk or position themselves accurately, and machines that function very well with static motions are unable to move dynamically. The bipedal robot TRIP (Tendonized Running Inspired Platform) was built to study dynamic maneuvering and control of an articulated legged robot with high-inertia legs. Each leg includes an inelastic tendon which couples ankle joint rotations to knee joint rotations, resulting in simplified effective dynamics and control, and a high degree of passive stabilization with dynamic maneuvers. A hybrid pneumatic-electric actuator was built and tested while driving a knee joint; this actuator is capable of precise positioning, as well as highly energetic thrusting. It will be shown that static and dynamic maneuvers are attainable with a tendon-coupled ankle, and that a tendon allows simpler dynamic control through the concept of impulse compensation, and through the use of passive stabilization from the kinematics resulting from the tendon. Second, it will be shown that the hybrid actuator is superior in some respects to current available technology, both by specification, and by experimental results of static and dynamic maneuvers achieved through its use. And third, using a general heuristic-based control algorithm developed for various sized bipedal machines, dynamic maneuvers are possible with a high leg-to-body moment of inertia ratio, which would show that the control strategy takes into account the dynamics of the legs during high speed locomotion.
  • Lewis A. Marshall.
    Purified DNA serves as a template for a wide array of analysis techniques, ranging from sequencing to PCR and hybridization assays. DNA analysis can be used for clinical diagnosis, for forensic investigation, and for a range of research purposes. These analysis techniques improve each year, but they are all constrained by the availability of purified DNA. DNA is typically derived from raw biological samples that contain a host of other molecular species, including proteins, lipids and metal ions. These species can inhibit analysis of the DNA, so purification of DNA from complex sample matrices is a necessary precursor to analysis. Typically, DNA purification is performed using either liquid-liquid extraction or solid-phase extraction, both of which require manual labor, involve toxic chemicals, and are difficult to miniaturize. Isotachophoresis (ITP) is an alternative method for DNA purification that does not rely on specialized surface chemistry or toxic chemical species. Instead, ITP uses electric fields to selectively pre-concentrate DNA from a raw sample, and simultaneously separate it from inhibiting species. ITP purification of DNA has been demonstrated from human serum, plasma, and whole blood, and the same technique has been used to purify RNA from bacteria in human blood and urine. Until recently, the parameters governing extraction efficiency, throughput, and separation quality in ITP purification were not well established. This thesis is focused on rational analysis for designing and optimizing ITP systems for rapid, high quality DNA purification.
  • 2008From: Springer
    Patrick Langdon, John Clarkson, Peter Robinson editors.
  • Kathryn Elizabeth Keenan.
    Human articular cartilage can degrade, losing functional quality and eventually exposing bone surfaces; when significantly advanced, this cartilage degradation can be diagnosed as osteoarthritis (OA). Currently, knee OA can be diagnosed only when the disease is advanced and the patient is suffering from pain. There is no cure for knee OA, nor are there prevent preventative therapies; current treatment strategies relieve the pain of OA or completely replace the knee joint. To evaluate potential therapies and treatments, we need a method that can identify and measure changes to cartilage prior to the onset of degradation. Magnetic resonance imaging (MRI) is a potentially powerful tool to non-invasively evaluate the progression of knee OA by mapping MR image parameters to molecular and material properties that are known to change with disease. The goal of this dissertation was to determine MR image parameters that can be used to evaluate the progression of OA. We examined the biphasic and viscoelastic models of cartilage to determine cartilage material properties from indentation creep tests. We compared initial elastic modulus and cartilage macromolecules to MRI parameters, specifically T2 and T1rho relaxation times and T1rho dispersion. We determined that a predictive model based on T1rho relaxation time maps, which accounts for T2 relaxation time and the effects of age, may estimate longitudinal trends in GAG content in the same person. In addition, a simple T1rho dispersion estimate has the potential for substantial clinical impact by measuring changes in cartilage initial elastic modulus and macromolecules non-invasively. This work is an important step toward developing clinical methods for evaluating cartilage functional condition, and in turn, to advance work towards preventing and treating knee OA.
  • Minsub Chung.
    Many cellular processes including cell-cell communications and regulated membrane transport are mediated by membrane proteins and depend upon the ability of lipid membranes to be a differentially permeable barrier. However, the roles and function of membrane proteins are often difficult to study due to the complexity of the native membranes and lack of reliable and flexible artificial model lipid membranes. Supported lipid bilayers (SLB) have been used as a model system to study biological membrane behavior and the structure and function of membrane proteins and receptors in a simpler context apart from the complex cellular environment. Although SLBs have the advantages of simple formation, easy handling and are well-suited for investigation by a suite of surface sensitive methods due to their planar geometry, the close proximity of the lower leaflet to the solid support often leads to unfavorable interactions with integral membrane proteins. This causes distortion of the protein conformation and possible loss of its reactivity and function. Moreover, this interaction with the substrate often traps proteins and reduces their mobility in the membranes. Recognizing this limitation, we have developed a new model membrane architecture in which the DNA-tethered lipid bilayer is either to fixed DNA on a surface or to laterally mobile DNA displayed on a supported bilayer. This separates the lipid membranes from surface interactions and provides a more favorable environment for integral membrane protein with large globular domains. With mobile DNA hybrid tethers, stable tethered bilayers were made with specific lipid composition, while those with fixed tethers are stable regardless of membrane composition. The mobile tethers between a tethered and a supported lipid bilayer offer a particularly interesting architecture for studying the dynamics of membrane-membrane interactions. By careful choice of composition, improved stability was obtained and we can investigate the lateral segregation of DNA hybrids when different lengths are present. Based on a theoretical model, the effects of population, length and affinity of DNA complexes are simulated and described. This model system captures some of the essential physics of synapse formation and is a step toward understanding lipid membrane behavior in a cell-to-cell junction. To demonstrate the excellent environment provided by DNA-tethered membranes for studying transmembrane proteins free from any surface interactions, the behavior of a transmembrane protein, the photosynthetic reaction center, reconstituted in the DNA-tethered membranes is investigated. Inspired by DNA-mediated membrane fusion studies of our group, we applied the DNA-machinery to achieve fusion of small (~ 100 nm) proteoliposomes for delivery of membrane proteins to either giant vesicles or DNA-tethered planar lipid membrane patches. The diffusion behavior of delivered proteins is measured and compared with those in supported bilayers. Also, the protein activity and orientation before and after fusion is analyzed. This will offer a feasible method to incorporate intact membrane proteins to already formed model membranes. In addition, the behavior of proteins during the fusion event will provide insight into the mechanism of DNA-mediated lipid membrane fusion. The geometry of our model membrane system directly mimics that of a neuronal synapse. We expect that this architecture will be readily transferable to other model membrane fusion systems, including systems using reconstituted SNARE proteins. Consequently, it will be of considerable interest to a wide range of researchers.
  • Tracy Curtis Holmes, II.
    Developing novel therapies for gram-negative bacterial infections and glioblastoma multiforme I. cloning and characterization of the guadinomine biosynthetic gene cluster II. developing a novel chemo-sensitizing agent to treat glioblastoma. This thesis explores the development of novel therapies for the treatment of two complicated problems: Gram-negative bacterial infections and glioblastoma multiforme, the most aggressive form of brain cancer. Part I of the thesis summarizes the current body of knowledge regarding guadinomines, their biosynthesis and implications for developing novel anti-infective agents. Part II of the thesis summarizes the development of the small molecule, ERW1227B, and its ability to sensitize glioblastoma cells to standard therapies. Part I. Guadinomines are a recently discovered family of anti-infective compounds produced by Streptomyces sp. K01-0509. They are the first microbial metabolites shown to inhibit the Type III Secretion System (TTSS) of Gram-negative bacteria. The TTSS is required for the virulence of many pathogenic Gram-negative bacteria including Escherichia coli, Salmonella spp., Yersinia spp., Chlamydia spp., Vibrio spp., and Pseudomonas spp. Inhibition of the TTSS can mitigate virulence which is important considering that Gram-negative bacteria infect millions each year, leading to considerable morbidity and mortality. The guadinomine (gdn) biosynthetic gene cluster has been sequenced, and encodes a chimeric multimodular polyketide synthase -- nonribosomal peptide synthetase spanning 26 open reading frames and 51.2 kb. It also encodes enzymes responsible for the biosynthesis of the unusual aminomalonyl-ACP extender unit and the signature carbamoylated cyclic guanidine. Its identity was established by genetic inactivation of the cluster, as well as heterologous expression and analysis of enzymes in the biosynthetic pathway. Identifying the guadinomine gene cluster provides critical insight into the biosynthesis of these biologically important compounds. Part II. Glioblastomas display variable phenotypes that include increased drug-resistance associated with enhanced migratory and anti-apoptotic characteristics. These shared characteristics contribute to failure of clinical treatment regimens. Identification of novel compounds that both promote cell death and impair cellular motility is a logical strategy to develop more effective clinical protocols. Previously, we described the ability of the small molecule, KCC009, a tissue transglutaminase inhibitor, to sensitize glioblastoma cells to chemotherapy. In the current study, we synthesized a series of related compounds that show variable ability to promote cell death and impair motility in glioblastomas, irrespective of their ability to inhibit TG2. Each compound has a 3-bromo-4,5-dihydroisoxazole component that presumably reacts with a nucleophilic cysteine thiol residue in one (or more) target protein(s) that have affinity for the small molecule. Our studies focused on the effects of the compound, ERW1227B. Treatment of glioblastoma cells with ERW1227B was associated with both down-regulation of the PI-3 kinase/Akt pathway, which enhanced cell death; as well as disruption of focal adhesions and intracellular actin fibers, which impaired cellular mobility. Bioassays as well as time-lapse photography of glioblastoma cells treated with ERW1227B showed cell death and rapid loss of cellular motility. Mice studies with in vivo glioblastoma models demonstrated the ability of ERW1227B to sensitize tumor cells to cell death after treatment with either chemotherapy or radiation. The above findings identify ERW1227B as a potential novel therapeutic agent in the treatment of glioblastomas.
  • Aaron Sheng-Chieh Wang.
    Trauma patients require rapid diagnosis and treatment of hemorrhage. In the hospital, experienced sonographers can reliably diagnose vascular injury using duplex ultrasound. In trauma settings, such as the battlefield, a portable ultrasound device with an automated algorithm to detect bleeding would be useful for medics. Thus, an increasing interest in computer-aided bleed detection led to efforts in quantifying sonographic signatures of abnormalities at the site of vascular injury. However, since trauma patients often present with large areas of injury, there is a need to develop and evaluate bleed detection strategies for ultrasound that more efficiently assess a large vascular tree. The goal of this Ph.D. research dissertation is to address this need. The studies primarily focused on the upper extremity vasculature, specifically the brachial bifurcation, because the leading cause of preventable deaths due to vascular trauma has been exsanguinations from extremity injuries. The overall approach was to characterize normal blood flow with a well-established power law model and identify flows that deviate from the model. The power law states that blood flow is proportional to the vessel diameter raised to a power index k, where k is defined by the bifurcation geometry. A bleed detection metric, called the "flow split deviation" (FSD), was defined to quantify the flow deviations from the power law. Validation of this approach was undertaken in four steps. The first involved demonstrating that the power law model appropriately describes the normal brachial bifurcation and flows in man. The utility of the bleed metric was then evaluated with 3D computational models of bleeds. Finally, the proposed detection algorithm was applied on the early proof of concept humans in arteriovenous fistulas (AVF) of dialysis patients and in in vivo rabbit bleed models. A study with normal human subjects was used to determine that the best-fit k for the brachial bifurcation was 2.75, which is in agreement with other vasculatures previously studied. A k=2.75 power law was then shown to adequately predict forearm blood flows for both resting and exercise physiological states. The correlation coefficient R between predicted and measured normal flows was 0.98. Computational models suggested that FSD was a good indicator of the severity of bleed downstream from the bifurcation. In the patient case study, the bleed metric easily distinguished between normal arms and those with newly placed wrist AVFs, which caused on average an order of magnitude increase in flow deviations. Introduction of different femoral bleed rates in rabbits demonstrated good sensitivity and specificity of the bleed metric when applied to moderate lower extremity bleeds. Bifurcation FSDs can serve as a quantitative signature of bleeding and, moreover, as a strategic way to survey large vascular trees by following abnormal branch points to the likely source of hemorrhage. This approach can complement other quantitative sonographic methods to create a comprehensive, automated, ultrasound-based algorithm for vascular trauma detection.
  • Eric Cocker.
    A central goal in neuroscience is to explain animal behavior in terms of causal cellular processes. It has been a longstanding challenge, however, to simultaneously track behavior and the cellular dynamics driving it. In this thesis, I discuss how a series of one- and two-photon fluorescence microscopes, based on gradient refractive index (GRIN) lenses, were developed to meet this challenge. The predominant difficulty in the design of these microscopes was how to take a traditional bench top microscope and shrink it to a size small enough for a mouse to easily carry on its head, a limit of 3 grams. We chose mice as our design target due to the wide availability of genetically modified mouse models for the study of cognitive functions, animal behaviors, and disorders of the nervous system. The earlier devices, relying on fiber optics to bring light to and from the animal, met with limited success but still provided useful insight in the development of the surgical techniques and analytical tools necessary for later successful experiments. In contrast, our latest system fully integrates the entire light pathway onto the head of mouse, eliminating many of the remaining roadblocks to truly freely-moving imaging. This device has enabled novel observations of both microcirculatory and neuronal calcium dynamics in the cerebellum of freely-moving mice at frame rates up to 100 Hz. As the genetic toolbox for mice continues to mature, these miniaturized microscopes will facilitate a wide set of future studies of how cellular function in the brain varies across different behavioral and physiological states.
  • 2011From: Atypon
    Xiaolu Zhu, Rangaraj M. Rangayyan, Anna L. Ells.
    Fundus images of the retina are color images of the eye taken by specially designed digital cameras. Ophthalmologists rely on fundus images to diagnose various diseases that affect the eye, such as diabetic retinopathy and retinopathy of prematurity. A crucial preliminary step in the analysis of retinal images is the identification and localization of important anatomical structures, such as the optic nerve head (ONH), the macula, and the major vascular arcades. Identification of the ONH is an important initial step in the detection and analysis of the anatomical structures and pathological features in the retina. Different types of retinal pathology may be detected and analyzed via the application of appropriately designed techniques of digital image processing and pattern recognition. Computer-aided analysis of retinal images has the potential to facilitate quantitative and objective analysis of retinal lesions and abnormalities. Accurate identification and localization of retinal features and lesions could contribute to improved diagnosis, treatment, and management of retinopathy.
  • Limor Freifeld.
    Visual inputs are high-dimensional, dynamic, and may consist of significant levels of noise. Nevertheless, visual processing systems in many animals are capable of efficiently extracting information out of these signals to guide behavior. Flies, in particular, use visual information to guide behavior in challenging conditions such as during rapid flight maneuvers. In this dissertation we examine how early visual processing cells in the visual system of the Fruit Fly, Drosophila, achieve this feat. In particular, we focus on cells that provide inputs to motion detecting circuits and assess how these cells balance the goal of facilitating computational specializations with the goal of efficiently capturing all visual information. In these studies, we used two-photon calcium imaging in vivo to monitor the responses of specific cells in the fly visual system to visual stimuli. Using this system, we found that two first order interneurons providing inputs to pathways specialized for the detection of moving bright and dark edges nevertheless similarly encode information about both brightening and darkening. However, an in depth study of the functional properties of one of these interneurons revealed that it responds differently to bright and dark moving objects of different sizes in a manner that could facilitate the downstream specialization. Furthermore, via genetic and pharmacological manipulations it was found that GABAergic circuits providing lateral and feedback inputs to this cell enhance its responses to dark stimuli and thus enable it to relay critical information for the downstream pathway. These circuits were found to give rise to a center-surround antagonistic, anisotropic and spatiotemporally coupled RF structure in this cell. Interestingly, our studies uncovered deep similarities between the function of early visual processing cells in the fly and in vertebrate retinas. This suggests that different systems have converged on a similar set of solutions for addressing the challenge of efficiently using the resources available to the nervous system to process visual signals.
  • Katherine Muterspaugh Steele.
    This dissertation presents the first three-dimensional musculoskeletal simulations of individuals with cerebral palsy and has contributed to our understanding of how muscle contributions, joint loads, and the effects of muscle weakness change in individuals with cerebral palsy and crouch gait. The simulations created for these analyses have been made freely-available for researchers and clinicians to download, use, and evaluate at This work has provided insight into the underlying dynamics of crouch gait and created pathways to improve treatment. The first objective of this dissertation was to examine how individual muscles contribute to motion during crouch gait. We evaluated how muscles contribute to joint and mass center accelerations to support and propel the body during crouch gait and how these contributions change with crouch severity. The results of these analyses indicated that crouch gait uses similar muscles to support and propel the body as unimpaired gait; however, larger and more sustained muscle activity is required during crouch gait, which contributes to the inefficiencies of this gait pattern. The second objective of this dissertation was to examine how the compressive tibiofemoral force changes in individuals with cerebral palsy and crouch gait. Knee pain is common among individuals with crouch gait and the results of this study demonstrated that tibiofemoral load increases quadratically with crouch severity. Individuals who walk in a severe crouch gait experience three-times the tibiofemoral load than during unimpaired gait. The elevated tibiofemoral forces during crouch gait could contribute to cartilage degeneration and knee pain. The final objective of this dissertation was to examine how muscle weakness may contribute to crouch gait. We used musculoskeletal simulations to determine how much muscle groups can be weakened and still reproduce mild and moderate crouch gait. The results of this analysis demonstrated that crouch gait requires greater quadriceps strength but less hip abductor and ankle plantarflexor strength than unimpaired gait; suggesting that these latter muscles may be better targets for strength training programs. We also performed a meta-analysis of individuals with crouch gait who had participated in strength training programs. This analysis demonstrated that outcomes after strength training are inconsistent, even among individuals with cerebral palsy and crouch gait. Hamstring spasticity was associated with poor outcomes after strength training and may be a contraindication for strength training. The long term goal of the work presented in this dissertation is to improve quality of life for individuals with cerebral palsy. The freedom to walk, explore, and interact with the world is a skill that many of us take for granted every day. Through the combination of musculoskeletal modeling and simulation, experimental studies, and clinical outcomes we can help individuals with gait pathologies achieve this freedom throughout their life.
  • Michael Zabala.
    Rupture of the anterior cruciate ligament (ACL) is one of the most common injuries to the knee. Unfortunately, individuals who experience this injury are likely to develop osteoarthritis of the knee much earlier than would be expected due to the normal ageing process, and this remains true even after surgical reconstruction of the ligament. Research has suggested that a major contributing factor to the development of premature osteoarthritis is altered knee mechanics which change the loading conditions of the cartilage in the joint. Furthermore, it has been shown that altered knee mechanics are present following rupture of the ACL and persist after reconstruction surgery. Despite initial reports, there still remains a need for a comprehensive understanding of both altered knee mechanics in both ACL deficient and ACL reconstructed knees as well as changes in cartilage morphology following ACL injury. Therefore, the goal of this dissertation is to address the question of the relationship between certain changes in knee mechanics and cartilage morphology as they relate to the development of osteoarthritis following both ACL injury and reconstruction. The first study presented involves an analysis of the knee mechanics in individuals with unilateral ACL deficiencies. This group was important in that they were free of knee pain and had no sign of osteoarthritis on MRI over a time frame that ranged up to three decades from injury. This provided a unique opportunity to explore the potential for a protective functional adaption. The results of this study suggest that alteration in knee mechanics may act as a protective mechanism against osteoarthritis development since when subjects were separated into "Short Term" and "Long Term", based upon the time from injury, only those in the "Long Term" group demonstrated a relationship between the external knee flexion moment, which is representative of the interaction between quadriceps and hamstrings muscle to control rotation and translation during walking. This is indicative of an adaptive control mechanism present in some subjects who were able to last many years after the injury without reconstruction surgery. These results suggest the potential for new methods for rehabilitation following ACL injury. The second study presented involves an analysis of the knee mechanics of individuals with unilateral ACL reconstructions during gait, stair ascent, and stair descent at two years from surgery. The results demonstrate a reduction in the external joint moments of ACL reconstructed knees and an increase in the joint moments of uninjured contralateral knees during each activity compared to healthy controls. This suggests two things: 1.) compensation for residual muscle weakness in the affected limb is needed by the contralateral knee during ambulation and 2.) a decrease in daily joint loading in ACL reconstructed knees and an increase in joint loading in contralateral knees. Decreased loading of the ACL reconstructed knee may seem counterintuitive to what was expected in patients who will likely develop premature osteoarthritis in this knee. However, this finding is consistent with the suggestion that changes in joint kinematics and even decreased joint loading following the injury may contribute to the initial cartilage breakdown. Note: Taken together the results of study 1 and 2 suggest that the interaction between muscle function and kinematics should be further considered in the development of knee OA in this population. The third and final study involves articular cartilage morphology analysis of individuals with unilateral ACL reconstructions at two and four years from surgery. The results illustrate differences between cartilage thickness of ACL reconstructed and healthy contralateral knees at both times of testing. The findings show significantly thinner cartilage in the lateral tibial compartment of ACL reconstructed knees at two years from surgery. These differences became more pronounced at four years from surgery and include the addition of a significantly thicker medial region of the tibia of ACL reconstructed knees compared to healthy contralateral knees. The results indicate that patterns of cartilage thickness change are detectable as early two years following ACL reconstruction, and these patterns become more pronounced at 4 years which suggests cartilage begins a degenerative pathway substantially in advance of clinically detectable OA. This finding is important since it provides a basis for assessing early interventions to reduce the risk of knee OA following ACL injury. This dissertation helps to further the understanding of altered knee mechanics following both ACL rupture and reconstruction. In addition, a possible pattern of OA initiation has been reported. Each of these studies will benefit future studies with the ultimate goal of a complete understanding of OA initiation and development in ACL ruptured and reconstructed knees.
  • Thais Russomano, Gustavo Dalmarco, and Felipe Prehn Falcão.
  • Edwina S. Lai.
    The development of atherosclerosis, a chronic inflammatory disease of the arteries, can usually be attributed to specific regions of the blood vessel. In the straight segments of an artery, endothelial cells (ECs) align with the unidirectional blood flow which commonly occurs in these simple geometries. The elongated and aligned ECs are generally found to have a healthy, athero-resistant phenotype. In contrast, branches or curved vessel geometries have regions of disturbed flow, characterized by low shear stress and high shear stress gradients. In these regions of complicated flow patterns, ECs are non-aligned and have a cobblestone cellular morphology. The non-aligned ECs elicit biological properties that promote atherosclerosis, as the location of atherosclerotic fatty plaque is often found at these bends, branches, or bifurcations. Therefore, this correlation highly suggests that the morphology and biological function are inextricably linked in ECs. The ability to regulate both EC morphology and motility, with the aim to influence EC biology, might be highly beneficial in the prevention or treatment of vascular disease. In this dissertation, anisotropic matrices of collagen nanofibrils were fabricated with a simple flow processing technique and used to investigate fundamental cell-matrix interactions with ECs. The aligned fibrils were able to regulate both the morphology and biology of ECs, thereby suggesting the nanofibrillar collagen can be a useful tool to maintain vascular homeostasis. The ECs elongated and organized their actin cytoskeleton along the direction of the aligned collagen fibrils, as demonstrated by organized actin, microtubule networks, and focal adhesions. The nanofibrillar collagen also promoted increased cellular migration along the direction of the nanofibrils. The quantification of monocyte adhesion and expression level of adhesion molecules, known testing indicators of atherosclerosis development, suggested the aligned nanofibrils also promoted an athero-resistant phenotype in the ECs. ECs are subject to biophysical cues in vivo, either in the form of surface topography (provided by the basement membrane of the ECM) or the hemodynamic effects of blood flow. The combination of these cues regulate the organization and immunogenicity of ECs and is representative of the in vivo environment. Therefore, we also investigated the endothelial behavior when both types of cues (topography and flow) were simultaneously present. At physiological levels of high shear stress (14-17 dynes/cm2), the matrix-aligned ECs were able to resist reorientation despite shear flow perpendicular to the matrix direction. The anisotropic collagen matrix could preserve the alignment and elongation of ECs as well as promote an athero-resistant phenotype after exposure to antagonistic perpendicular flow. The ability of the anisotropic nanofibrillar collagen to regulate cell morphology and especially EC immunogenicity highlights its potential in the treatment of vascular diseases. Therefore, an aligned conduit of collagen nanofibrils was fabricated to address the need for a small-diameter vascular graft capable of regulating cellular function. The vascular graft was designed to have a mechanical integrity comparable to that of native vessels and was able to regulate EC attachment, morphology, and phenotype. In addition, the aligned collagen grafts could support an anti-thrombogenic surface modification, providing short-term patency in the carotid artery model of Sprague-Dawley rats.
  • Jonathan Joi-Mun Wong.
    The heart is an essential heterogeneous organ that depends on strong coupling between electrical, chemical, and mechanical dynamics to properly function as a pump that supplies blood to the rest of the body. Cardiac arrhythmias are common disorders characterized by irregular beating of the heart that lead to serious clinical conditions. It is estimated that approximately 2.2 million adults in the United States are affected by atrial fibrillation, a prevalent arrhythmia. Unfortunately, a clinician often does not have enough information to diagnose a patient's heart condition to determine the optimal treatment procedure. This is an area that computational mechanics can address. While development of mechanical and electrophysiological models of cardiac tissue primarily started in the 1950s, fully-coupled models have only more recently been developed due to factors regarding computational cost, difficulty in quantifying material properties, and difficulty in integrating complex models in a cohesive and efficient manner. Therefore, in order for simulation tools to have impact in the clinical or experimental setting, these tools must be efficient, fast, robust, and accessible. The focus of this thesis is to develop methods of addressing the aforementioned issues and then illustrate how efficient electromechanical finite element models can be developed for the heart such that their use in the clinical and experimental setting can be realized in several examples. In this thesis, a global-local variable splitting formulation borrowed from the field of plasticity is used to address the issues of complex model integration, and to maintain numerical stability at low costs. Through careful examination of classical phenomenological models and detailed biophysical ionic models of the electrophysiology of the heart, almost all models can be reformulated into this global-local splitting framework. The numerical properties of cost-expensive ionic models are briefly analyzed within the context of this framework. Use of implicit-time stepping in tandem with a simple iteration and error tolerance based adaptive time-stepping algorithm allows for reduction of computation time from hours to minutes. Flexibility and modularity of the framework are illustrated through the development of electrical, electro-chemical, electro-chemical-mechanical, and opto-electro-mechanical models of cardiac tissue. The heart is modeled efficiently using custom finite element ventricular cell models for physiological electrical simulations and large deformation excitation-contraction dry-pumping simulations of the heart. The results accurately model the physiological condition of the heart. The flexibility and multiscale nature of the framework is also leveraged in developing novel optical-induced cardiac cell excitation models of new genetically engineered Channelrhodpsin-2 (ChR2) cardiac myocytes. An ionic model was developed for these particular bio-engineered stem cells, calibrated with experimental data from collaborators, and was able to predict the electrical excitation behavior of the cells to a reasonable degree of accuracy. This model was then combined with ionic pacemaker cell models and also with ventricular cell models into respective finite elements to simulate experiments and predict future therapies using ChR2 genetically modified cardiac tissue. The thesis also addresses difficulties relating to identification and characterization of material parameter identification in inhomogeneous cardiac tissue. Metrics for determining smoothness in electrical conduction in tissue cultures were validated with stochastic finite element models of microelectrode array cell conduction experiments. The results indicate that these metrics are useful in characterizing different conduction patterns based on two metrics borrowed from texture analysis. Difficulties in obtaining structural fiber data from clinical images were addressed by developing an algorithmic method for designating approximate physiologically accurate fiber distributions for the heart using only geometrical information obtained from MRI scans of the surfaces of the heart. Poisson interpolation is used and results in a smooth continuous rotating fiber description that matches experimentally obtained fiber directions from MRI scans. The main benefits of this algorithm are its simplicity of implementation, physiologically accuracy, and generality in interpolating fiber distributions. Lastly, the thesis demonstrates possible benefits of GPU computing in order to achieve near-real-time electrical simulations of arrhythmias in the heart. The assembly and solver routines from the finite element code, FEAP from Berkeley, were ported to the GPU using CUDA. Even with a minimally optimized proof-of-concept, the GPU-only finite element code achieves performance comparable to twelve cores using only one GPU. To increase the overall efficiency of the method, current sparse matrix vector multiplication GPU algorithms are analyzed, and possible alternative algorithms are developed specifically with unstructured finite element meshes in mind. Altogether, the different methods developed in this thesis have been shown to be effective in addressing issues related to efficiency, numerical stability, modularity, and flexibility in real computational applications of the heart. Special consideration was taken in designing the different methods to be compatible with one another, such that a majority of the methods could be integrated and the benefits of each method could be leveraged with each other to gain maximum efficiency. While these developed methods can still be improved, the thesis work as a whole serves to demonstrate and highlight future uses for computational models within experimental and clinical settings.
  • Hesaam Esfandyarpour.
    The Human Genome Project was accomplished by a reduction in the cost of DNA sequencing by three orders of magnitude. Further cost reductions are required for sequencing to become a standard tool in clinical medicine and to enable personalized medicine via individual genome sequencing. The current cost varies between $50k to $100k over a period of months; depend on the technology, accuracy and read-length. It is desired to reduce the cost to $1000 per genome to enable profiling of individuals genome. To achieve this goal, a highly integrated platform with simplified chemistry is required. In this dissertation, we introduce a novel method for DNA sequencing based on electrical detection of polymerization reaction, called "Thermo/pH sequencing". Our proposed method is based on the direct measurement of the heat release or the pH modulation (change of H+ ion concentration in the solution) during DNA extension. For high throughput DNA sequencing, DNA strands are immobilized to small micron-size beads in a microfluidic platform. The DNA-beads are in a reaction mixture in contact with an array of sensitive micro-machined heat or pH sensors, which detect the electrical signature from incorporation of a complementary base (dNTP) in the presence of appropriate reagents (DNA polymerase, and polymerase reaction buffer). This results to a label-free, long-read and fast chemistry; 10x reduction in reagent cost with 10x increase in throughput can potentially yield to significant improvement in the cost of genome sequencing to less than $1000. In addition, substituting optical detection set-up with microelectronic sensor reduces the capital cost of sequencing instruments from $500k to less than $50k. We demonstrate the proof of concept for this technology at large scale. Then we describe the development of an appropriate microfluidic platform and two micromachined electrical biosensors that employ electrical detection for heat or pH detection. Both versatile platforms can be multiplexed and have the potential of providing rapid and inexpensive measurements without any compromise in the sensitivity, making them good potential candidates for use in the clinical setting. We report a chip-based integrated differential microfluidic nanocalimeters with on-chip injection and multiplexing unit, capable of characterizing the heat of reaction with unprecedented 2-nW resolution in 1 Hz bandwidth for nanoliter scale samples. We successfully demonstrate DNA Thermosequencing with sequential injection of different nucleotides into the integrated microfluidic calorimeter device. In addition, the device can serve as a powerful tool to characterize a variety of the biomedical processes, such as metabolic activities of microorganisms, living cells and catalyzed reactions. We also present a microfabricated device in microfluidics for pH sequencing, called nanoneedle biosensor. The key element for this device is a 10nm wide gap on the end of the needle of total diameter about 100nm. Any change in the population of molecules in this gap results in a change of impedance across the gap; single molecule detection should be possible. In addition, DNA-beads can be allocated iv near the sensors to measure the pH change during DNA extension. The design, fabrication, testing, optimization and a modified structure of the device for higher signal to noise ratio are presented. Toward an integrated sequencer platform, automation and reduced labor cost, higher throughput, accuracy and efficiency for genomics and proteomics analysis; further integration and optimization of the presented systems are required. We envision the integration of our CMOS-compatible devices with a CMOS integrated circuitry into a high throughput gene sequencer or proteomics system. The proteomics system enables multiplex analysis using an array of micro-channels for probing clinically relevant samples such as the human serum for various protein and nucleic acid biomarkers for cancer detection, and also the detection of pathogenic bacteria in solution.
  • John G. Webster, editor in chief.
  • Monica Elise Ortiz.
    Evolution has selected for organisms that benefit from genetically encoded cell-cell communication. We observe cell-cell communication throughout every scale in nature, from simple single-celled bacteria to complex multicellular mammals. Engineers have begun to repurpose elements of natural communication systems to coordinate their own population-level behaviors, including oscillations and programmed pattern formation. Existing engineered systems, however, rely on small, system-specific biomolecules to send messages among cells. However, such molecules are capable of sending only a single message, typically "regulate transcription.'' Thus, the information transmission capacity of such biological communication systems is fundamentally limited. Through this thesis, I demonstrated the decoupling of messages from a common communication channel via the autonomous transmission of numerous arbitrary genetic messages. To do so, I engineered a cell-cell communication platform using bacteriophage M13 gene products to autonomously package and deliver heterologous DNA messages of varying lengths and encoded functions. Further, I increased the range of engineered DNA messaging across semisolid media by coupling message transmission or receipt to active cellular chemotaxis. Through this coupling, I demonstrated that our system is adaptable to different contexts by creating simple patterns. Finally, using recombinase-mediated logic gates developed within the Endy laboratory, I demonstrated the ability to program bacteria by transmitting logic gates to surrounding cells. Overall, this work significantly enhances the suite of cell-cell communication tools available to engineers. I have shown that a variety of DNA messages can be transmitted among cells and have moved the field of synthetic biology closer to designing synthetic ecologies with more complex communication schemes and varied behaviors.
  • Sarah Jean Moore.
    Proteins and peptides are an incredibly versatile class of biological molecules, with a vast array of naturally occurring functions. In cancer, the natural roles of proteins become incorrectly regulated, and the presence of cancer-related proteins on tumor cells can be detected and targeted for diagnosis and treatment. This thesis decribes novel engineered peptides for molecular recognition of cell surface receptors expressed in cancers, and application of these engineered peptides as diagnostic agents to identify solid tumors in mouse models. For this work. three different cystine-knot peptides were used for development and engineering: Agatoxin (AgTx), Agouti-related protein (AgRP), and Ecballium elaterium trypsin inhibitor-II (EETI). In addition, two protein receptors were employed as model tumor targets relevant for molecular imaging of cancer: carbonic anhydrase IX (CA IX) and tumor associated integrin receptors. New methods were developed towards engineering AgTx and AgRP to bind CA IX, and work to produce these peptides for further study and their limitations are described. In a parallel line of research, to further understand the promise of using knottin peptides in cancer imaging, the influence of amino acid loops on tissue biodistribution was examined using engineered AgTx, AgRP, and EETI peptides that bind tumor target integrins in mouse xenograft models. Finally, an engineered EETI knottin peptide that binds tumor-associated integrins was shown to specifically target and illuminate brain tumors in mouse models of medulloblastoma. Importantly, the protein engineering methods and molecular imaging applications described here have promise for influencing the clinical outcome of cancer patients through image-guided surgical resection, disease staging and management, and monitoring the effectiveness of therapeutic treatments.
  • 2015From: Springer
    Luiz E. Bertassoni, Paulo G. Coelho, editors.
    This book offers a comprehensive overview of current challenges and strategies to regenerate load-bearing and calcified human tissues, including bone, cartilage,tendon, ligaments and dental structures (dentin, enamel, cementum and periodontal ligament). Tissue engineering has long held great promises as an improved treatment option for conditions affecting mineralized and load-bearing structures in the body. Although significant progress has been achieved in recent years, a number of challenges still exist. Scaffold vascularization, new biofabrication methods (3D printing, lithography, microfabrication), peptide conjugation methods, interface engineering, scaffold mechanical properties, iPS cells, organs-on-a-chip, are some of the topics discussed in this book. More specially, in the first section readers will find an overview of emerging biofabrication methods. In section 2, applied strategies for regeneration of (2.1) bone, cartilage and ligament, as well as (2.2) dentin, cementum, enamel and periodontal ligament are discussed across 14 chapters. While other volumes have addressed the regeneration of individual tissues, or exclusively focused on different regenerative strategies, the focus of this work is to bring together researchers integrating backgrounds in materials sciences, engineering, biology, mechanics, fluidics, etc, to address specific challenges common to regeneration of several load-bearing and calcified tissues. Therefore, this book provides a unique platform to stimulate progress in the regeneration of functional tissue substitutes. We envision that this book will represent a valuable reference source for university and college faculties, post-doctoral research fellows, senior graduate students, and researchers from R&D laboratories in their endeavors to fabricate biomimetic load bearing tissues.
    Also available: Print – 2015
  • Sheng Ding.
    Recombinant proteins have been used widely in both basic research and biomedical applications including protein therapeutics and biomaterials. Many efforts have been devoted to the investigation of novel synthetic strategies for producing recombinant proteins for various applications, which is the focus of this dissertation. In the first section, a biosynthetic strategy was developed to produce collagenous proteins with post-translational modifications in E. coli. Collagen is the most abundant protein in human, and plays a dominant role in maintaining the biological and structural integrity. Recombinant expression of collagens and fragments of collagens is often difficult as their stability requires appropriate proline hydroxylation. Prolyl 4-hydroxylases (P4H) are ascorbate-dependent oxygenases that play key roles in collagen folding by catalyzing the post-translational hydroxylation of specific proline residues on target proteins to form (2S, 4R)-4-hydroxyproline. Thus far, the study of these post-translational modifications has been limited by the lack of a prokaryotic recombinant expression system for producing hydroxylated proteins. Unlike eukaryotic cells such as yeast and insect cells, bacterial cytoplasm cannot activate P4H, which requires an ascorbate co-factor that bacteria do not produce. By introducing a biosynthetic shunt to produce ascorbate-like molecules in E. coli cells that heterologously express human P4H, we have created a strain of E. coli that produces collagenous proteins with (2S, 4R)-4-hydroxyproline. Different levels of proline hydroxylation can be obtained by tuning culture conditions. We have verified that hydroxylation of collagenous materials produced in the new system leads to an increase in thermostability. Using this new system, we have observed hydroxylation patterns indicative of a processive catalytic mode for P4H that is active even in the absence of ascorbate. Our results provide insights into P4H enzymology, and create a foundation for better understanding how post-translational hydroxylation affects proteins. Further, we applied the novel E. coli expression system to produce a collagenous protein, adiponectin, which has many beneficial effects on obesity-related metabolic and cardiovascular disorders, and reverses insulin insensitivity. By introducing key post-translational modification enzymes to E. coli, we have endowed the expression system with capabilities of making necessary modifications on adiponectin for its correct assembly, and thus obtained biomimetic adiponectins. High-molecular weight (HMW) multimers of adiponectin have been obtained, and their biological activities of suppressing endothelial cell apoptosis have been confirmed with in vitro cell assays. In section 2, modular protein polymers have been created through genetic engineering and enzymatically crosslinked into hydrogels with tunable properties. The many challenges currently faced in regenerative medicine research require the development of new, modular biomaterial systems that can serve as scaffolds for cellular maintenance, expansion and growth, and which can be tuned by the user to mimic any necessary aspects of natural ECM to an optimal degree. Toward this goal, we have created a family of block co-polypeptides comprising amino acid sequence elements that allow mild enzymatic crosslinking into gels. These new families of protein polymers were designed to be linear, random coil, and contain either lysine or glutamine, which have the recognition substrates for transglutaminase (TG) crosslinking, evenly spaced along the protein backbone. Crosslinking occurred within two minutes upon the addition of TG under physiological conditions, as determined by particle tracking microrheology. The material properties of the gel can be tuned with the hydrogel composition to mimic cellular microenvironment of different tissues. Furthermore, in order to introduce biofunctionalities into the hydrogels, a versatile expression vector has been engineered that allows the insertion of bioactive protein domains into these block co-polypeptide. For example, a cell adhesion signal based on the RGD sequence from human fibronectin was incorporated. The RGD-containing hydrogel was successful in enhancing cell adhesion, and were also proven to be compatible with the culture of mesenchymal stem cells. The specific nature of these protein polymer precursors of the modular hydrogel composition allows tailoring of mechanical and biochemical properties, rendering these gels valuable for various tissue engineering applications.
  • 2007From: Springer
    Felix Bronner, Mary C. Farach-Carson and Antonios G. Mikos (eds.).
  • 2014From: Wiley
    edited by Rebecca A. Bader, David A. Putnam.
    Polymers have played a critical role in the rational design and application of drug delivery systems that increase the efficacy and reduce the toxicity of new and conventional therapeutics. Beginning with an introduction to the fundamentals of drug delivery, Engineering Polymer Systems for Improved Drug Delivery explores traditional drug delivery techniques as well as emerging advanced drug delivery techniques. By reviewing many types of polymeric drug delivery systems, and including key points, worked examples and homework problems, this book will serve as a guide to for specialists and non-
  • 2010From: Springer Protocols
    edited by Kursad Turksen.
    Isolation of adult mouse stem keratinocytes using magnetic cell sorting (MACS) / Corina Lorz [and others] -- Functional investigations of keratinocyte stem cells and progenitors at a single-cell level using multiparallel clonal microcultures / Nicolas O. Furtunel [and others] -- Growth and stratification of epithelial cells in minimal culture conditions / Federica Riva [and others] -- Matched cultures of keratinocytes and fibroblasts derived from normal and NER-deficient mouse models / Alex Pines and Claude Backendorf -- Establishment of spontaneously immortalized keratinocyte lines from wild-type and mutant mice / Julia Reichelt and Ingo Haase -- Study of epidermal differentiation in human kertinocytes cultured in autocrine conditions / Frédéric Minner, Franc̦oise Herphelin, and Yves Poumay -- Directed differentiation of human embryonic stem cells to epidermal progenitors / Christian M. Metallo [and others] -- Expression and analysis of exogenous proteins in epidermal cells / Lina Dagnino, Ernest Ho, and Wing Y. Change -- Using siRNA knockdown in HaCaT cells to study transcriptional control of epidermal proliferation potential / Julie Wells and Xing Dai -- RNA interference in keratinocytes and an organotypic model of human epidermis / Cory L. Simpson, Shin-ichiro Kojima, and Spiro Getsios -- Scanning for transcription factor binding by a variant EMSA / Igor Gurevich, Carmen Zhang, and Brian J. Aneskievich -- Chromatin immunoprecipitation for identifying transcription factor targets in kertinocytes / Kori Ortt and Satrajit Sinha -- Gene expression profiling of mouse epidermal keratinocytes / Ramón García-Escudero and Jesús M. Paramio -- Analysis of tissue-specific gene expression using laser capture microdissection / Martin Ruetze [and others] --Comprehensive transcriptional profiling of human epidermis, reconstituted epidermal equivalents, and cultured keratinocytes using DNA microarray chips / Din-Dar Lee [and others] -- Molecular profiling of the epidermis : a proteomics approach / Jianjun Shen and Susan M. Fischer -- Detection of gene expression in embryonic tissues and stratified epidermis by in situ hybridization / Maria I. Morasso -- Embryonic mammary anlagen analysis using immunolabelling of whole mounts / Heena Panchal, Olivia Wansbury, and Beatrice A. Howard -- Whole-mount assays for gene induction and barrier formation in the developing epidermis / Carolyn Byrne [and others] -- Tetracycline-regulated gene expession in transgenic mouse epidermis / Rose-Anne Romano and Satrajit Sinha -- A versatile murine 3D organotypic model to evaluate aspects of wound healing and epidermal organization / Eve Kandyba, Malcolm Hodgins, and Patricia Martin -- Optical and biochemical dissection of connexin and disease-linked connexin mutants in 3D organotypic epidermis / Stéphanie Langlois, Jared M. Churko, and Dale W. Laird -- Cytokine release in tissue-engineered epidermal equivalents after prolonged mechanical loading / Lisette H. Cornelissen [and others] -- Three-dimensional human tissue models of wounded skin / Christophe Egles, Jonathan A. Garlick, and Yulia Shamis -- In vivo transplantation of genetically modified mouse embryonic epidermis / Ana Belén Martínez-Cruz [and others] -- A transplant model for human epidermal skin regeneration / Sophie Paquet-Fifield [and others] -- Identification of epithelial stem cells in vivo and in vitro using keratin 19 and brdU / Danielle Larouche [and others] -- Isolation and culture of hair follicle pluripotent stem (hfPS) cells and their use for nerve and spinal cord regeneration / Yasuyuki Amoh and Robert M. Hoffman -- Limiting dilution analysis of murine epidermal stem cells using an in vivo regeneration assay / Lauren R. Strachan and Ruby Ghadially.
  • 2014From: Springer Protocols
    edited by Kursad Turksen, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
    Differentiation of Human Induced Pluripotent Stem Cells into a Keratinocyte Lineage / Igor Kogut, Dennis R. Roop, and Ganna Bilousova -- Differentiation of Epidermal Keratinocytes from Human Embryonic Stem Cells / Fahad K. Kidwai, Tong Cao, and Kai Lu -- Protocol for Serial Cultivation of Epithelial Cells Without Enzymes or Chemical Compounds / Dongxia Ye and Antonio Peramo -- Growth and Differentiation of HaCaT Keratinocytes / Van G. Wilson -- Transgene Delivery to Cultured Keratinocytes Via Replication-Deficient Adenovirus Vectors / Vincent P. Ramirez and Brian J. Aneskievich -- Analyzing the Global Chromatin Structure of Keratinocytes by MNase-Seq / Jason M. Rizzo and Satrajit Sinha -- Analysis and Meta-Analysis of Transcriptional Profiling in Human Epidermis / Claudia Mimoso, Ding-Dar Lee, Jiri Zavadil, Marjana Tomic-Canic, and Miroslav Blumenberg -- Compound Screening and Transcriptional Profiling in Human Primary Keratinocytes: A Brief Guideline / Raphaela Rid, Harald Hundsberger, and Kamil Önder -- Preparation of Primary Cultures of Mouse Epidermal Keratinocytes and the Measurement of Phospholipase D Activity / Lakiea J. Bailey, Vivek Choudhary, Purnima Merai, and Wendy B. Bollag -- Lipid Rafts and Detergent-Resistant Membranes in Epithelial Keratinocytes / Kathleen P. McGuinn and Mỹ G. Mahoney -- MMP-2, 9 and TIMP-1, 2 Assays in Keratinocyte Cultures / Takashi Kobayashi -- Reactive Oxygen Species (ROS) Protection Via Cysteine Oxidation in the Epidermal Cornified Cell Envelope / Wilbert P. Vermeij and Claude Backendorf -- Modified Methods for Growing 3-D Skin Equivalents: An Update / Rebecca Lamb and Carrie A. Ambler -- A Novel Three-Dimensional Cell Culture Method to Analyze Epidermal Cell Differentiation In Vitro / Yoji Okugawa and Yohei Hirai -- Reconstruction of Normal and Pathological Human Epidermis on Polycarbonate Filter / Evelyne De Vuyst, Céline Charlier, Séverine Giltaire, Valérie De Glas, Catherine Lambert de Rouvroit, and Yves Poumay -- Methods for the Preparation of an Autologous Serum-Free Cultured Epidermis and for Autografting Applications / John J. Wille, Jeremy J. Burdge, and Jong Y. Park -- Human Keratinocyte Cultures in the Investigation of Early Steps of Human Papillomavirus Infection / Laura M. Griffin, Louis Cicchini, Tao Xu, and Dohun Pyeon -- Preparation and Delivery of 4-Hydroxy-Tamoxifen for Clonal and Polyclonal Labeling of Cells of the Surface Ectoderm, Skin, and Hair Follicle / Christine Chevalier, Jean-François Nicolas, and Anne-Cécile Petit -- Microdissection and Visualization of Individual Hair Follicles for Lineage Tracing Studies / Inês Sequeira, Emilie Legué, Suzanne Capgras, and Jean-François Nicolas -- Isolation and Characterization of a Stem Cell Side-Population from Mouse Hair Follicles / Paula L. Miliani de Marval, Sun Hye Kim, and Marcelo L. Rodriguez Puebla -- Multi-Scale Mathematical Modeling and Simulation of Cellular Dynamical Process / Shinji Nakaoka -- Erratum.
  • 2008From: CRCnetBASE
    editors, Alexiy Ya. Chebykin, Gregory Z. Bedny, and Waldemar Karwowski.
    Ecological ergonomics / Marvin J. Dainoff -- Integrating cognitive and digital human models for virtual product design / Daniel W. Carruth and Vincent G. Duffy -- Time study during vocational training / Gregory Z. Bedny and Waldemar Karwowski -- The laws of ergonomics applied to design and testing of workstations / V.F. Venda, V.K. Kalin, and A.Y. Trofimov -- Day-to-day monitoring of an operator's functional state and fitness-for-work : a psychophysiological and engineering approach / Oleksandr Burov -- Identification of mental modules ; Identification of neural modules / Saul Sternberg -- The new interface of brain, mind, and machine : will the emergent whole be greater than the sum of the parts? / Chris Berka ... [et al.] -- The interaction of sleep and memory / Jeffrey M. Ellenbogen -- Attention, selection for action, error processing, and safety / Magdalena Fafrowicz and Tadeusz Marek -- Activity theory : comparative analysis of Eastern and Western approaches / Waldemar Karwowski, Gregory Z. Bedney, and Olexiy Y. Chebykin -- Discourse in activity / Harry Daniels -- Movements of the cane prior to locomotion judgments : the informer fallacy and the training fallacy versus the role of exploration / Gregory Burton and Jennifer Cyr -- Emotional intelligence : a novel approach to operationalizing the construct / E.L. Nosenko -- Emotional regulation of the learning process / Olexiy Y. Chebykin and S.D. Maksymenko -- Emotional resources of the professional trainer / G.V. Lozhkin -- Good judgment : the intersection of intelligence and personality / Robert Hogan, Joyce Hogan and Paul Barrett -- Relational self in action : relationships and behavior / Susan E. Cross and Kari A. Terzino.
  • 2008From: CRCnetBASE
    Jan Dul, Bernard Weerdmeester.
    Posture and movement -- Information and operation -- Environmental factors -- Work organization jobs and tasks -- The ergonomic approach -- Sources of additional information.
  • 2009From: ScienceDirect
    editors, Robert Lanza ... [et al.].
    Introduction to stem cells -- Basic biology/mechanisms -- Tissue and organ development -- Methods -- Applications -- Regulation and ethics.
  • Laura Astolfi and Fabio Babiloni.
  • 2011From: Atypon
    Monique Frize.
    Increasingly, biomedical scientists and engineers are involved in projects, design, or research and development that involve humans or animals. The book presents general concepts on professionalism and the regulation of the profession of engineering, including a discussion on what is ethics and moral conduct, ethical theories and the codes of ethics that are most relevant for engineers. An ethical decision-making process is suggested. Other issues such as conflicts of interest, plagiarism, intellectual property, confidentiality, privacy, fraud, and corruption are presented. General guidelines, the process for obtaining ethics approval from ethics Review Boards,and the importance of obtaining informed consent from volunteers recruited for studies are presented. A discussion on research with animals is included. Ethical dilemmas focus on reproductive technologies, stem cells, cloning, genetic testing, and designer babies. The book includes a discussion on ethics and the technologies of body enhancement and of regeneration. The importance of assessing the impact of technology on people, society, and on our planet is stressed. Particular attention is given to nanotechnologies, the environment, and issues that pertain to developing countries. Ideas on gender, culture, and ethics focus on how research and access to medical services have, at times, been discriminatory towards women. The cultural aspects focus on organ transplantation in Japan, and a case study of an Aboriginal child in Canada; both examples show the impact that culture can have on how care is provided or accepted. The final section of the book discusses data collection and analysis and offers a guideline for honest reporting of results, avoiding fraud, or unethical approaches. The appendix presents a few case studies where fraud and/or unethical research have occurred.
  • Polina A. Segalova.
    Abdominal aortic aneurysms (AAA's) are characterized by a permanent and irreversible enlargement of the abdominal aorta to at least 150 percent its expected normal size. Endovascular treatment of AAA's with endografts has gained tremendous popularity in the last decade, largely due to decreased perioperative mortality and faster recovery times, when compared to open surgical repair. Although endografts are an appealing treatment option for many patients, some device design and safety issues have yet to be addressed. One of the biggest problems with endografts is their tendency to shift their position in the patient anatomy over time. The forces that cause this shift and their relation to endograft design are not well understood. In addition, the degree of blood damage due to the insertion of an endograft into the abdominal aorta has not been quantified. The following studies were completed in order to investigate the issues described above. 1. Calculation of endograft displacement force in patient-specific device models. This study used electron-beam computed tomography (CT) image data to generate patient-specific anatomical models using novel segmentation techniques. The patient models were then virtually modeled to represent three different endograft designs, based on aortic stent-graft devices already available in the U.S. or currently in clinical trials. Computational Fluid Dynamics (CFD) simulations were run to characterize the hemodynamic factors for each patient and a total displacement force was calculated for each model. Results show that the location of the device bifurcation impacts the overall displacement force, with proximal bifurcation endograft designs generating a lesser force than distal bifurcation designs. 2. Characterization of blood damage due to endograft placement. Patient-specific computational models were created to represent endograft features that partially obstruct blood flow to the renal arteries, which is sometimes necessary to attain complete exclusion of the aneurysm after deploying the device. Findings show that the insertion of an endograft causes a two-fold increase in blood damage. However, the magnitude of blood damage is within acceptable safety standards. 3. Benchtop testing of red blood cell damage. A benchtop experimental setup was created to measure the damage to red blood cells under various flow conditions and flow obstructions. Samples were characterized at different time points using light scatter methods to determine cell volume and hemoglobin concentration. Results indicate that significant damage to red blood cells occurs only after prolonged exposure (> 103 seconds) to high shear (> 4000 dynes/cm2) conditions. In addition, the presence of flow obstructions creates red blood cell fragments, instead of destroying the cells entirely. Future directions for this work include additional CFD modeling of devices in more patients treated with different aortic stent graft designs to derive statistical significance relative to various design and anatomical features and extend the analysis to the evaluation of devices used for the treatment of thoracic aortic aneurysms (TAA's). Follow-up studies on device migration studies can also be completed in the cohort of patients where the endograft displacement forces were calculated. Further, blood damage models that incorporate the fragmentation of red blood cells can be developed.
  • Erica M. Cherry.
    Magnetic drug targeting (MDT) is a noninvasive medical technique that has been proposed for treating diseases that are localized in the body. Currently, drugs meant to treat such conditions are inefficient and often damage healthy tissue because they spread throughout the blood stream. MDT combats this problem by steering the majority of the medicine to the right location in the body. An ideal MDT treatment would involve chemically binding the drug to magnetic particles, injecting the particles into the bloodstream, magnetically steering them through the arterial network, and trapping them near the diseased area so the drug they carry has time to diffuse into the surrounding tissue. There is still much to learn about how to manufacture drug-coated magnetic particles, image these particles in vivo, and control them using magnetic fields. This thesis focuses on understanding the dynamics of magnetic particles moving through the blood stream. A preliminary simulation and experiment were performed to determine realistic ranges of particle, flow, and magnetic field parameters within which MDT could work. Based on the results, an expanded simulation was performed and used to predict optimal conditions for successful magnetic drug targeting. The preliminary simulation and experiment evaluated the feasibility of stopping magnetic particles in a straight tube flow with conditions similar to those in a large artery. It was found that unrealistically high magnetic field gradients were needed to control particles small enough to safely inject into the circulatory system because the fluid drag force on the particles was too large to overcome with magnetic force. Composite spheres, made of micron-sized magnetic particles embedded in agarose (which could potentially be broken up in vivo), were much easier to control magnetically in the same setup. In order to develop an understanding of the dynamics of a cluster of small magnetic particles moving through the circulatory system, an expanded simulation was developed to track the motion of such a cluster in an artery-like flow. The hope was that the presence of an extended cloud of particles would reduce the average drag force per particle and thus small particles would be easier to control magnetically. Three unclosed forces needed to be modeled for this simulation. First, the viscous force on the particles was computed by formulating a non-Newtonian model for blood. Extensive simulations showed that non-Newtonian arterial flows differed significantly from Newtonian ones even in large arteries. Second, the interparticle magnetic force was calculated by developing a numerical method that summed magnetic interactions between grid cells instead of individual particle pairs. This approach is much more efficient than summing the forces for all particle pairs and is accurate as long as the grid is well-resolved and the local gradients of magnetic particle concentration are nonzero. Finally, the dispersion coefficient of the particles caused by their interactions with blood cells was computed by performing a separate Monte Carlo simulation of particles moving through a field of red blood cells with variable shear rate, hematocrit, and particle terminal velocity. The results of the expanded simulation showed that it was possible, but not easy, to slow down a particle cluster moving through a straight artery and somewhat easier to steer a particle cluster down one branch of an arterial bifurcation. In both cases, diffusion prevented successful control of the particle cluster long-term.
  • 2006From: Springer
    Hans-Joachim Bungartz, Michael Schäfer (eds.)
  • Timothy Ryan Julian.
    This dissertation examines the factors that influence fomite-mediated (e.g., indirect contact) transmission of viral gastrointestinal and respiratory illness. Specifically, the dissertation investigates virus transfer between surfaces and virus recovery from surfaces, models human-fomites interactions to estimate exposure and infection risk, and elucidates causal links between microbial contamination and illness in child care centers. Indirect contact transmission refers to person-to-person transmission of disease via an intermediate fomite (e.g., inanimate object acting as a carrier of infectious disease). The role of indirect contact in disease spread is poorly understood in part because the transmission route of viral pathogens is often difficult to determine. Transmission of respiratory and gastrointestinal viruses can occur through multiple routes (e.g., direct contact, indirect contact, airborne, and common vehicle), and the relative contribution of each route to total disease burden is unclear. The first study in this dissertation examines virus transfer between skin and surfaces, a necessary step in fomite-mediated transmission of viral disease. In the study, transfer of virus between fingerpads and fomites is explored in a laboratory setting. Bacteriophage (fr, MS2, and PHIX174) are used as proxies for pathogenic virus, and over 650 unique transfer events are collected from 20 different volunteers. The study concludes that approximately one quarter (23%) of recoverable virus is readily transferred from a contaminated surface (e.g., a fomite) to an uncontaminated surface (e.g., a finger) on contact. Using the large data set, the direction of transfer (from fingerpads-to-fomite or fomite-to-fingerpad) and virus species are demonstrated to both significantly influence the fraction of virus transferred by approximately 2-5%. To investigate the relative importance of factors contributing to fomite-mediated transmission, a child's risk of illness from exposure to a contaminated fomite is modeled. Specifically, the model estimates a child's exposure to rotavirus using a stochastic-mechanistic framework. Simulations of a child's contacts with the fomite include intermittent fomite-mouth, hand-mouth, and hand-fomite contacts based on activities of a typical child under six years of age. In addition to frequency of contact data, parameters estimated for use in the model include virus concentration on surface; virus inactivation rates on hands and the fomite; virus transfer between hands, fomite, and the child's mouth; and the surface area of objects and hands in contact. From the model, we conclude that a child's median ingested dose from interacting with a rotavirus-contaminated ball ranges from 2 to 1,000 virus over a period of one hour, with a median value of 42 virus. These results were heavily influenced by selected values of model parameters, most notably, the concentration of rotavirus on fomite, frequency of fomite-mouth contacts, frequency of hand-mouth contacts, and virus transferred from fomite to mouth. The model demonstrated that mouthing of fomite is the primary exposure route, with hand mouthing contributions accounting for less than one-fifth of the child's dose over the first 10 minutes of interaction. Based on the findings from the model that concentration of virus on a fomite influences a child's risk of illness, we investigate methods to recover virus from fomites. In a literature review and subsequent meta analysis, we demonstrate that the outcome currently used to describe virus contamination, positivity rate, is biased by the authors' selected sampling methods. We follow up, in the laboratory, with a comparison of the identified methods and demonstrate that polyester-tipped swabs prewetted in 1/4-strength Ringer's solution or saline solution is the most efficient sampling method for virus recovery tested. The recommended method is compatible with plaque assay and quantitative reverse-transcription polymerase chain reaction, two techniques used to quantify virus. The link between hand / fomite contamination and infection risk was explored in a field study at two child care centers over four months. Both respiratory and gastrointestinal disease incidence were tracked daily, while hand and environmental surface contamination were monitored weekly between February 2009 and June 2009. Microbial contamination was determined using quantitative densities of fecal indicator bacteria (e.g. Escherichia coli, enterococci, and fecal coliform) on hands and fomites as well as presence/absence of viral pathogens (e.g. enterovirus and norovirus). Health was monitored daily by childcare staff, who tracked absences, illness-related absences, and symptomatic respiratory and gastrointestinal illness. The resultant data suggests that increases in microbial contamination led to increases in symptomatic respiratory illness four to six days later, in agreement with typical incubation periods for respiratory illness. Similarly, respiratory illness led to increases in microbial contamination on hands during presentation of symptoms, and on fomites in the following three days.
  • 2008From: CRCnetBASE
    edited by Gerald F. Harris, Peter A. Smith, Richard M. Marks.
  • 2012From: Atypon
    Thanh M. Cabral and Rangaraj M. Rangayyan.
    Fractal analysis is useful in digital image processing for the characterization of shape roughness and gray-scale texture or complexity. Breast masses present shape and gray-scale characteristics in mammograms that vary between benign masses and malignant tumors. This book demonstrates the use of fractal analysis to classify breast masses as benign masses or malignant tumors based on the irregularity exhibited in their contours and the gray-scale variability exhibited in their mammographic images. A few different approaches are described to estimate the fractal dimension (FD) of the contour of a mass, including the ruler method, box-counting method, and the power spectral analysis (PSA) method. Procedures are also described for the estimation of the FD of the gray-scale image of a mass using the blanket method and the PSA method.
  • 2011From: Springer
    Carlos Hernández ... [et al.], editors.
    Introduction: From Brains to the Machines of the Future / Ricardo Sanz, Carlos Hernández and Jaime Gómez-Ramirez -- Emergent Feature Sensitivity in a Model of the Auditory Thalamocortical System / Martin Coath, Robert Mill, Susan L. Denham and Thomas Wennekers -- STDP Pattern Onset Learning Depends on Background Activity / James Humble, Steve Furber, Susan L. Denham and Thomas Wennekers -- Emergence of Small-World Structure in Networks of Spiking Neurons Through STDP Plasticity / Gleb Basalyga, Pablo M. Gleiser and Thomas Wennekers -- Coupling BCM and Neural Fields for the Emergence of Self-organization Consensus / Mathieu Lefort, Yann Boniface and Bernard Girau -- Alpha and Theta Rhythm Abnormality in Alzheimer's Disease: A Study Using a Computational Model / Basabdatta Sen Bhattacharya, Damien Coyle and Liam P. Maguire -- Oscillatory Neural Network for Image Segmentation with Biased Competition for Attention / Tapani Raiko and Harri Valpola -- Internal Simulation of Perceptions and Actions / Magnus Johnsson and David Gil -- Building Neurocognitive Networks with a Distributed Functional Architecture / Marmaduke Woodman, Dionysios Perdikis, Ajay S. Pillai, Silke Dodel and Raoul Huys, et al. -- Reverse Engineering for Biologically Inspired Cognitive Architectures: A Critical Analysis / Andreas Schierwagen -- Competition in High Dimensional Spaces Using a Sparse Approximation of Neural Fields / Jean-Charles Quinton, Bernard Girau and Mathieu Lefort -- Informational Theories of Consciousness: A Review and Extension / Igor Aleksander and David Gamez -- Hippocampal Categories: A Mathematical Foundation for Navigation and Memory / Jaime Gómez-Ramirez and Ricardo Sanz -- The Role of Feedback in a Hierarchical Model of Object Perception / Salvador Dura-Bernal, Thomas Wennekers and Susan L. Denham -- Machine Free Will: Is Free Will a Necessary Ingredient of Machine Consciousness? / Riccardo Manzotti -- Natural Evolution of Neural Support Vector Machines / Magnus Jändel -- Self-conscious Robotic System Design Process - From Analysis to Implementation / Antonio Chella, Massimo Cossentino and Valeria Seidita -- Simulating Visual Qualia in the CERA-CRANIUM Cognitive Architecture / Raúl Arrabales, Agapito Ledezma and Araceli Sanchis -- The Ouroboros Model, Selected Facets / Knud Thomsen.
    Also available: Print – 2011
  • 2012From: Springer
    Natasha Maurits.
    1. Introduction -- 2. Carpal Tunnel Syndrome, Electroneurography, Electromyography, and Statistics -- 3. Tremor, Polymyography, and Spectral Analysis -- 4. Epilepsia, Electroencephalography, Filtering, and Feature Extraction -- 5. Multiple Sclerosis, Evoked Potentials, and Enhancing Signal-to-Noise Ratio -- 6. Cortical Myoclonus, EEG-EMG, Back-Averaging, and Coherence Analysis -- 7. Psychogenic Movement Disorders, Bereitschaftspotential, and Event-Related Potentials -- 8. Brain Tumor, Preoperative Function Localization, and Source Localization -- 9. Neuromuscular Diseases, Ultrasound, and Image Analysis -- 10. Cerebrovascular Disease, Ultrasound, and Hemodynamical Flow Parameters -- 11. Spinal Dysfunction, Transcranial Magnetic Stimulation, and Motor Evoked Potentials.
  • Gary Shambat.
    Photonic nanocavities are wavelength-scale dielectric structures that possess remarkable properties due to their intrinsic small sizes and high quality factors. Simply by modifying the device materials and optical properties, one can realize nanocavities for diverse applications ranging from lasers to quantum optics and even biosensing. In this dissertation work, two drastically different functions of nanocavities are presented, both of which make them more practical for real-world adoption. The first part of this dissertation will focus on engineered optical devices for interconnect applications in computing and communications. We have shown that heavily doped germanium on silicon can be used as a CMOS-compatible light source with peak emission at 1.5 microns. Microdisk resonators were fabricated and shown to sustain cavity resonances through both photoluminescence (PL) and electroluminescence (EL) measurements. To access these microresonators, we developed a coupling process using a tapered optical fiber and further showed the versatility of these fibers by using them to tune the cavity wavelength. High performance optical sources were then demonstrated in a gallium arsenide platform containing embedded quantum dots (QDs). We have developed a new platform for efficiently driving photonic crystal (PC) cavities using a lithographically defined, lateral p-i-n junction. With our lateral junction we have demonstrated a world record low threshold laser with a threshold power of only 208 nW at 50K. At room temperature we find that these same devices behave as ultra-fast light-emitting diodes which can be directly modulated at up to 10 GHz with operational energies below 1 fJ/bit. Additional active photonic devices incorporating a lateral junction such as electro-optic modulators and photodetectors were also created using this same platform. The second part of this dissertation describes the demonstration of a whole new class of tools geared towards biomedical photonics that marry PC cavities to the tips of optical fibers. The form factor of the optical fiber lends itself to operation of the tool in exotic environments never before accessible to a nanocavity. Fiber-cavity hybrid devices were constructed using a custom epoxy-based assembly procedure which successfully relocates the small semiconductor templates containing nanocavities. The completed device, called a fiberPC, was then used as a sensor to detect gold nanoparticles through optical readout. We have used our probes to interrogate single human prostate cells with internalized PC cavities showing, for the first time, resonant photonic modes inside biological cells. The beams can be loaded in cells and tracked for days at a time, with cells undergoing regular division and migration. Furthermore, we present in vitro label-free protein sensing with our probes as a path towards quantitative, real-time biomarker detection in single cells. The developed tool may find future applications in drug screening, cancer detection, and fundamental cell biology.
  • Remy Durand.
    Functional brain imaging techniques such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) have emerged over the last several decades as powerful methods for understanding brain function and neuropsychiatric disorders. However, due to an inability to precisely and distinctly control the heterogeneous population of circuit elements in the brain, understanding the fundamental physiological mechanisms of these imaging modalities and realizing their potential for functional brain mapping has been limited. Optogenetics is a novel technique that allows for cell-type specific, reversible focal control within the mammalian brain with millisecond-timescale precision. In this thesis, I have utilized the unique cell-type specific neuromodulatory capacity of optogenetics to demonstrate and characterize, for the first time, the effect of direct stimulation of a subclass of excitatory neurons on the in vivo functional hemodynamic response of a rodent brain as measured with functional magnetic resonance imaging (fMRI). I have then used this technique, which we have called ofMRI, to perform large-scale functional mapping of distinct neural circuits that are specified by cell-type, cell-body location, and projection topology. To complement ofMRI studies, I have also developed the use of PET imaging and the radiotracer [18F]-fluorodeoxyglucose (FDG) to further characterize the metabolic and hemodynamic response resulting from activation of genetically-specified neurons in the mammalian brain. Additionally, I have constructed an automated, parallelized all-optical ex vivo system for modulation and recording of distinct neural circuits relevant to neuropsychiatric disorders using voltage sensitive dye imaging (VSDI). Combining the highly specific and rapid control of optogenetics with the biological process sensitivity of PET, the spatial and temporal resolution of BOLD fMRI, and the neural circuit analysis capabilities of optical imaging has the potential to vastly increase our understanding of the roles of neural circuits in both normal and diseased brain states.
  • 2007From: Springer
    Duane Knudson.
  • 2010From: Atypon
    Gerald E. Miller.
    Transport processes represents important life sustaining elements in all humans. These include mass transfer processes, including gas exchange in the lungs, transport across capillaries and alveoli, transport across the kidneys, and transport across cell membranes. These mass transfer processes affect how oxygen and carbon dioxide are exchanged in your bloodstream, how metabolic waste products are removed from your blood, how nutrients are transported to tissues, and how all cells function throughout the body. A discussion of kidney dialysis and gas exchange mechanisms is included. Another element in biomedical transport processes is that of momentum transport and fluid flow. This describes how blood is propelled from the heart and throughout the cardiovascular system, how blood elements affect the body, including gas exchange, infection control, clotting of blood, and blood flow resistance, which affects cardiac work. A discussion of the measurement of the blood resistance to flow (viscosity), blood flow, and pressure is also included. A third element in transport processes in the human body is that of heat transfer, including heat transfer inside the body towards the periphery as well as heat transfer from the body to the environment. A discussion of temperature measurements and body protection in extreme heat conditions is also included.
  • 2009From: Springer
    Ulrich Meyer, Thomas Meyer, Jörg Handschel, Hans Peter Wiesmann, (eds.).
  • 2006From: Springer
    edited by Jan A. Nolta.
    Also available: Print – 2006
  • 2014From: Springer
    György Marko-Varga, editor.
    This book offers a valuable resource that allows students, researchers, educators and the general public to learn about proteomics and genomics. Chromosomes form the basis for our genetic heritage and are the code for protein synthesis. The Human Genome Map was presented in 2002, and the Proteome Sequence Map is currently being created by a global consortia initiative. Proteome and genome building blocks already form the basis of scientific research areas and shape major areas of the pharmaceutical and biomedical industries. The book provides background information on and our current understanding of these gene and protein areas, and explains in detail how cutting-edge science is using these resources to develop new medicines and new diagnostics for patient treatment and care. The book will benefit all students and researchers who need a good understanding of genomics and proteomics within the clinical field. Its content is also suitable for a broad readership, including those not specialized in this field. Dr. Marko-Varga is head of Div. Clinical Protein Science & Imaging at the Biomedical Center, Dept. of Measurement Technology and Industrial Electrical Engineering, Lund University. He's also Professor at the 1st Department of Surgery, Tokyo Medical University, Tokyo, Japan.
  • Richard S. Gaster.
    Nanotechnology has the unique capability of manipulating and sensing matter at the molecular scale with unprecedented speed, sensitivity, and throughput. The medical application of nanotechnology, nanomedicine, has leveraged nanoscience tools for the advancement of medical diagnostics, therapy, and basic science research. In this work, arrays of magnetically responsive nanosensors, originally developed for use as read heads in computer hard disk drives, have been utilized to achieve in-depth proteomic studies for the advancement of medical diagnostics and therapy. In particular, this dissertation will focus on the following four topics of applying magnetic nanotechnology to science and medicine. First, the application of magnetic nanosensor arrays to early cancer diagnostics and monitoring response to chemotherapy. The utility of magnetic nanosensors as a molecular diagnostics tool capable of profiling a patient's disease state and leveraging a patient's unique molecular signature will be demonstrated. Second, this report will discuss a novel mathematical model expressly developed to describe the kinetic interactions of magnetically labeled biomolecules binding to capture agents immobilized on a surface. Third, a novel autoassembly immunoassay capable of screening for antibody cross-reactivity in a high-density, high-fidelity, and rapid manner will be described. Finally, this report will address the utility of the autoassembly immunoassay in conjunction with a miniaturized magnetic nanosensor platform for point-of-care diagnostics in a cost-effective and easy-to-use (e.g. wash-free) process that can make a significant contribution to global health.
  • Drew Alexander Hall.
    Nanotechnology has had a transformative effect on medical diagnostics due to the influx of new sensing modalities and transducers. Magnetic nanotechnologies, in particular, have shown significant potential in several areas of nanomedicine such as imaging, therapeutics, and early disease detection. Giant magnetoresistive spin-valve (GMR SV) sensors, commonly used in hard disk drives, coupled with magnetic nanotags have shown great promise as biosensors. In this work, we present several custom designed circuit interface and readout systems tailored to specific application spaces and their unique needs. Taken together, we have demonstrated that innovative electronic circuits play an indispensable role in unlocking the tremendous potential of nanosensors in the biomedical arena. The first system was designed for ultrasensitive early cancer diagnostics and built using off-the-shelf components for an 8x8 array of GMR SV sensors. At the core of this design, we demonstrate a new circuit architecture based on a transimpedance amplifier (TIA) with a carrier suppression technique to reduce the dynamic range requirement and a multiplexing scheme to reduce the readout time. This system is capable of real-time, multiplex detection with a detection limit of 5 femtomolar (fM) and over 6 orders of linear dynamic range. The second system is a miniaturized, portable platform called the nanoLAB. Although there is a growing need for point-of-care (POC) testing for global health, the current options are bulky, slow, expensive, and often not sensitive. The nanoLAB addresses these needs and pushes the state of the art with sensitive 8-plex detection using a wash-free assay that can be run by anyone, anywhere. This platform was tested and validated using human immunodeficiency virus (HIV) biomarkers with detection down to 50 fM in as little as 15 minutes. We also show how a GMR SV biosensor can be integrated into a continuous time sigma delta modulator. This proof-of-concept hybrid sigma delta modulator has a peak SNR of 99.3 dB and a dynamic range of over 92 dB in a 1 kHz bandwidth using the sensor as part of the first integrator. The carrier suppression and multiplexing concepts were also incorporated into the hybrid sigma delta modulator. Lastly, we conclude by describing an integrated platform for a large 16x16 array of GMR SV sensors implemented in a 0.18 [mu]m CMOS technology. Arranged like an imager chip, each of the 16 column level readout channels contains an analog front-end and an analog-to-digital converter. Each readout channel occupies less than 0.2 mm^2 of chip area and consumes 3.4 mW of power. This system is designed as a replacement for optical protein microarrays while being fully quantitative and providing real-time readout.
  • 2010From: Atypon
    Fabrizio De Vico Fallani and Fabio Babiloni.
  • 2017From: Thieme-Connect
    Bernhard Hirt, Harun Seyhan, Michael Wagner, Rainer Zumhasch ; translator: Karen Leube.
    Anatomy and functional anatomy of the hand -- Surface anatomy of the forearm, wrist, and hand structures.
  • 2015From: Cambridge
    [edited by] Sandro Carrara, EPFL, Lausanne, Switzerland, Krzysztof Iniewski, CMOS Emerging Technologies Research, Inc.
  • 2007From: CRCnetBASE
    edited by Frank S. Barnes, Ben Greenebaum.
    Introduction -- 1. Environmental and Occupationally Encountered Electromagnetic Fields / Kjell Hansson Mild and Ben Greenebaum -- 2. Endogenous Electric Fields in Animals / Richard Nuccitelli -- 3. Dielectric Properties of Biological Materials / Camelia Gabriel -- 4. Magnetic Properties of Biological Material / Jon Dobson -- 5. Interaction of Direct Current and Extremely Low-Frequency / Electric Fields with Biological Materials and Systems / Frank S. Barnes -- 6. Magnetic Field Effects on Free Radical Reactions in Biology / Stefan Engström -- 7. Signals, Noise, and Thresholds / James C. Weaver and Martin Bier -- 8. Biological Effects of Static Magnetic Fields / Shoogo Ueno and Tsukasa Shigemitsu -- 9. The Ion Cyclotron Resonance Hypothesis / A.R. Liboff -- 10. Computational Methods for Predicting Field Intensity and Temperature Change / James C. Lin and Paolo Bernardi -- 11. Experimental EMF Exposure Assessment / Sven Kühn and Niels Kuster -- 12. Electromagnetic Imaging of Biological Systems / William T. Joines, Qing H. Liu, and Gary Ybarra.
  • 2014From: Wiley
    edited by Konstantina S. Nikita.
  • 2008From: Springer
    edited by Anil K. Jain, Patrick Flynn, Arun A. Ross.
  • 2012From: CRCnetBASE
    edited by Gilson Khang.
    Pt. 1. Introduction -- pt. 2. Ceramic and metal scaffold -- pt. 3. Intelligent hydrogel -- pt. 4. Electrospinning nanofiber -- pt. 5. Novel biomaterials for scaffold -- pt. 6. Novel fabrication methods for scaffold -- pt. 7. Scaffold for target organ.
  • 2012From: Springer
    Kewal K. Jain.
    Nanotechnologies -- Nanotechnologies for Basic Research Relevant to Medicine -- Nanomolecular Diagnostics -- Nanopharmaceuticals -- Role of Nanotechnology in Biological Therapies -- Nanodevices and Techniques for Clinical Applications -- Nanooncology -- Nanoneurology -- Nanocardiology -- Nanopulmonology -- Nanoorthopedics -- Nano-ophthalmology -- Nanomicrobiology -- Miscellaneous Healthcare Applications of Nanobiotechnology -- Nanobiotechnology and Personalized Medicine -- Nanotoxicology -- Ethical and Regulatory Aspects of Nanomedicine -- Research and Future of Nanomedicine.
  • by Kewal K. Jain.
    Status: Not Checked OutLane Catalog Record
  • 2009From: CRCnetBASE
    edited by Valery V. Tuchin.
    "This handbook presents methods that improve the accuracy in glucose prediction based on infrared absorption spectroscopy, recent studies on the influence of acute hyperglycemia on cerebral blood flow, and the correlation between diabetes and the thermo-optical response of human skin. It examines skin glucose monitoring by near-infrared spectroscopy (NIR), fluorescence-based glucose biosensors, and a photonic crystal contact lens sensor. The contributors also explore problems of polarimetric glucose sensing in transparent and turbid tissues as well as offer a high-resolution optical technique for noninvasive, continuous, and accurate blood glucose monitoring and glucose diffusion measurement."--BOOK JACKET.
  • 2010From: CRCnetBASE
    edited by Valery V. Tuchin.
  • 2010From: CRCnetBASE
    edited by Robert Splinter.
  • 2013From: Atypon
    Monique Frize.
    The first chapter describes the health care delivery systems in Canada and in the U.S. This is followed by examples of various approaches used to measure physiological variables in humans, either for the purpose of diagnosis or monitoring potential disease conditions; a brief description of sensor technologies is included. The function and role of the clinical engineer in managing medical technologies in industrialized and in developing countries are presented. This is followed by a chapter on patient safety (mainly electrical safety and electromagnetic interference); it includes a section on how to minimize liability and how develop a quality assurance program for technology management. The next chapter discusses applications of telemedicine, including technical, social, and ethical issues. The last chapter presents a discussion on the impact of technology on health care and the technology assessment process.
  • 2013From: Atypon
    Monique Frize.
    Chapter 7 presents some statistics on the occurrence of medical errors and adverse events, and includes some technological solutions. A chapter on electronic medical records follows. The knowledge management process divided into four steps is described; this includes a discussion on data acquisition, storage, and retrieval. The next two chapters discuss the other three steps of the knowledge management process (knowledge discovery, knowledge translation, knowledge integration and sharing). The last chapter briefly discusses usability studies and clinical trials. The two parts consolidate material that supports courses on technology development and management issues in health care institutions. It can be useful for anyone involved in design, development, or research, whether in industry, hospitals, or government.
  • 2013From: Springer
    Paul A. Iaizzo, Richard W. Bianco, Alexander J. Hill, James D. St. Louis, editors.
    Anatomy, Physiology, Congenital Defects, and Disease -- The Anatomy and Function of the Atrioventricular Valves / Michael G. Bateman, Jason L. Quill, Alexander J. Hill, Paul A. Iaizzo -- The Anatomy and Function of the Semilunar Valves / Michael G. Bateman, Jason L. Quill, Alexander J. Hill, Paul A. Iaizzo -- Congenital Heart Defects That Include Cardiac Valve Abnormalities / Roosevelt Bryant III -- Acquired Valve Disease and Processes / Cindy M. Martin -- Valve Repair and Replacement -- History of Heart Valve Repair / Lauren B. Kwasny, Richard W. Bianco, Luis H. Toledo-Pereyra, -- Heart Valve Disease / Ranjit John, Kenneth Liao -- Advanced 3D Imaging and Transcatheter Valve Repair/Implantation / Paul Schoenhagen, Andrew C. Y. To -- Transcatheter Mitral Repair and Replacement / Jason L. Quill, Ana R. Menk, Gilbert H. L. Tang -- Percutaneous Pulmonary Valve Implantation: The First Transcatheter Valve / Silvia Schievano, Andrew M. Taylor, Philipp Bonhoeffer -- Transcatheter Aortic Valve Implantation / Nicolo Piazza, Darren Mylotte -- Tissue-Engineered Heart Valves / Jillian B. Schmidt, Robert T. Tranquillo -- Testing and Regulatory Issues -- In Vitro Testing of Heart Valve Substitutes / Timothy A. Kelley, Sal Marquez, Carl F. Popelar -- Numerical Methods for Design and Evaluation of Prosthetic Heart Valves / Michael J. Schendel, Carl F. Popelar -- Animal Models for Cardiac Valve Research / Sarah E. Ahlberg, Michael G. Bateman, Michael D. Eggen, Jason L. Quill -- The Use of Isolated Heart Models and Anatomic Specimens as Means to Enhance the Design and Testing of Cardiac Valve Therapies / Michael G. Bateman, Alexander J. Hill, Jason L. Quill, Michael D. Eggen -- Successful Development and Regulatory Approval of Replacement Cardiac Valves / Stephen A. Howard, Michael G. Bateman, Timothy G. Laske, Paul A. Iaizzo -- Clinical Trial Requirements for Cardiac Valves / Jenna C. Iaizzo, Anna T. F. Lovas.
  • Ga-Young Suh.
    Hemodynamic conditions are hypothesized to affect the initiation, growth, and rupture of abdominal aortic aneurysms (AAAs), a vascular disease characterized by progressive wall degradation and enlargement of the abdominal aorta. We hypothesized that the progression of AAA may be slowed by altering the hemodynamics in the abdominal aorta through exercise. The aim of the first study in this thesis was to use magnetic resonance imaging (MRI) and computational fluid dynamics (CFD) to quantify flow stagnation and recirculation in AAAs by computing particle residence time (PRT). Specifically, we used gadolinium-enhanced MR angiography (MRA) to obtain images of the vessel lumens, which were used to generate subject-specific models. Phase-contrast MRI was used to measure blood flow at supraceliac and infrarenal locations to prescribe physiologic boundary conditions. CFD was used to simulate pulsatile flow, and PRT, particle residence index, and particle half-life of PRT in the aneurysms were computed. We observed significant regional differences of PRT in the aneurysms with localized patterns that differed depending on aneurysm geometry and infrarenal flow. A saccular aneurysm with the lowest mean infrarenal flow demonstrated the slowest particle clearance. In addition, improvements in particle clearance were observed with increase of mean infrarenal flow. This result motivated the next study to quantify the effect of augmentation of mean infrarenal flow during exercise on reducing chronic flow stasis that may promote increased mural thrombus burden, degradation of the vessel wall, and aneurysm growth. In the second study, we investigated three levels of activity, rest, mild and moderate intensities of lower-limb exercise to quantify the effect of exercise on hemodynamic conditions in AAA subjects. We measured the abdominal aortic blood flow at rest and during dynamic exercise, and quantified mean wall shear stress (MWSS), oscillatory shear index (OSI), and PRT. We observed that an increase in the level of activity correlated with an increase of MWSS and a decrease of OSI at three locations in the abdominal aorta, and these changes were most significant below the renal arteries. As the level of activity increased, PRT in the aneurysm was significantly decreased: 50% of particles were cleared out of AAAs within 1.36 ± 0.43, 0.34 ± 0.10, and 0.22 ± 0.06 s at rest, mild exercise and moderate exercise levels, respectively. Most of the reduction of PRT occurred from rest to the mild exercise level suggesting that mild exercise may be sufficient to reduce flow stasis in AAAs. The third study aimed to correlate hemodynamic characteristics of AAA with its progression, and quantify morphologic changes of aneurysm from study intake to 1.5-3.5-year follow-up of subjects randomized to usual activity or exercise training cohort. We acquired MRA of 16 subjects, and mid-aneurysm wall content data of 12 subjects at each intake and follow-up visit. 3D lumen models were built based on each intake and follow-up MRAs of six subjects. We observed morphologic changes of aneurysm lumen from intake to follow-up MRA of 11 subjects which exhibited local smoothing, shrinkage or expansion. We observed thickening of thrombus burden from follow-up wall content image of seven subjects whose aneurysm lumen was eventually narrowed. Based on 3D model comparison between intake and follow-up, and the correlation of morphologic changes with wall content changes and PRT contour plots computed in the previous study, we suggest that the region of narrowed lumen induced by thrombus buildup may be consistent with the region of long PRT. As a future work, we will extend our research in conjunction with CT data to quantify the changes of aneurysm wall, and increase the number of subjects to find more conclusive results.
  • Anderson N. Nnewihe.
    Breast cancer is the second leading cause of female cancer death in the United States with an average lifetime risk of 1 in 8. Early detection of the disease and subsequent treatment increase the chance of survival. X-ray mammography is the standard imaging technique for breast cancer screening, but it is difficult to identify malignant lesions in women with dense breasts using x-ray mammography. Dynamic-contrast-enhanced (DCE) magnetic resonance imaging (MRI) has provided high sensitivity for breast cancer diagnosis due to its excellent soft tissue contrast, but there have been varied reports on its specificity. A recent study with a small surface coil has shown that high spatial and temporal resolution breast DCE MRI can improve sensitivity and specificity of ductal carcinoma in situ diagnosis by visualizing smaller scale features such as ductal and periductal enhancement. However, a small surface coil is not suitable for screening or bilateral staging exams where volumetric coverage of both breasts is necessary. Conversely, many commercially-available breast coils offer volumetric coverage of the breasts, but the large coil elements limit the signal-to- noise ratio (SNR) and thus the ability to increase spatial and temporal resolution with high parallel imaging acceleration factors. To address these concerns, we have designed and developed a custom-fitted 18-channel, bilateral breast radiofrequency (RF) coil array for providing high-resolution images in clinically-feasible scan times. The purpose of this work was three-fold: outline the construction process of a high- SNR custom-fitted array, benchmark its performance compared to a commercial design, and evaluate its utility for high-resolution clinical breast MRI. By placing a chain of overlapping small coil elements close to the tissue, we were able to obtain high SNR over the entire breast volume for medium-sized women. To reduce the overall exam time, we laid the coil elements in a geometry that facilitated bidirectional parallel imaging. Comparing the custom-fitted array to a commercially-available 8-channel breast array, the results show 3.6 times higher average SNR and superior parallel imaging quality for the custom-fitted array in volunteers. Using parallel imaging and taking advantage of the SNR benefits from the 18-channel coil array, we clinically demonstrated a 10-fold improvement in spatial resolution over the current Stanford Hospital protocol. We have conducted a clinical study comparing the diagnostic quality of high-resolution scans with the 18-channel array versus lower resolution scans in patients with suspicious lesions on mammography. The initial findings show that the improved resolution enables better depiction of overall lesion morphology and tissue interfaces. In summary, we have presented a method for constructing an 18-channel custom-fitted breast RF array and demonstrated its SNR and parallel imaging benefits. In a clinical setting, our initial findings show improved morphology characterization in high-resolution exams with the 18-channel array.
  • 2010From: Springer
    Vassilis Cutsuridis, Bruce Graham, Stuart Cobb, Imre Vida, editors.
  • 2014From: Springer
    Dierck Hillmann ; with a foreword by Gereon Hüttmann.
    Holoscopy is a new tomographic imaging modality that combines techniques of digital holography with Fourier-domain optical coherence tomography (FD-OCT). Dierck Hillmann gives a theoretical introduction to the mathematics and physics of holoscopy and develops an efficient numerical reconstruction procedure. Compared to FD-OCT, holoscopy provides unique advantages by enabling tomographic imaging without a limited depth of focus, but results in an increased numerical cost for reconstruction. In further chapters, the author introduces techniques for FD-OCT that are relevant to holoscopy as well. He demonstrates and compares numerical reconstruction methods for FD-OCT and shows how motion and dispersion artifacts in FD-OCT can be numerically compensated. Contents Theoretical Introduction to Optical Coherence Tomography and Digital Holography FD-OCT Signal Processing Using the Non-Equispaced Fast Fourier Transform Motion and Dispersion Correction in FD-OCT Holoscopy Target Groups Academics and practitioners in the fields of computer science, optical coherence tomography, digital holography, and medical imaging. The Author Dierck Hillmann received his doctoral degree in the group of Gereon Hüttmann at the Institute of Biomedical Optics in Lübeck and is currently working for a leading company in the fields of science and photonics. The Editor The series Aktuelle Forschung Medizintechnik is edited by Thorsten M. Buzug.
  • Katerina Blazek.
    Obesity, a condition characterized by excess adipose tissue, is becoming an important public health problem. Not only has the prevalence rate in adults risen steadily since the 1980's, obesity is a strong risk factor for the development of knee osteoarthritis (OA) and general mobility disability. There are currently no disease-modifying treatments for OA, so it is important to develop preventive strategies. However, we must first understand the mechanism of increased risk in the obese population. Knee cartilage and other joint structures respond both to mechanical loads during activities of daily living and to the biological environment within the joint, so the pathway to OA in the obese population therefore likely involves changes in both. The primary goal of this dissertation was to test the hypothesis that aging and obesity are linked to changes in gait mechanics and changes in the relationship between cartilage morphology and joint loads, and that these changes are consistent with increased knee OA risk. We also analyzed whether these changes are also observed in individuals with early asymptomatic knee joint degeneration. Finally, we tested the hypothesis that stair climbing requires adaptive changes that reflect a reduction in muscle strength in the aging obese population and indicate increased mobility disability risk. The results indicate that in obese, but not normal-weight individuals, age was associated with an increased adduction moment, which reflects increased loads on the medial compartment of the knee. Furthermore, the positive relationship between cartilage thickness and ambulatory load in young subjects was significantly weaker in middle-aged obese individuals. The increased OA risk in older obese individuals is therefore likely due to both an increase in ambulatory loads and to a change in the relationship between those ambulatory loads and cartilage properties due to the elevated pro-inflammatory cytokine levels characteristic of obesity. During stair climbing, middle-aged obese individuals also had lower peak knee flexion moments, indicative of quadriceps weakness due to aging and relative to their weight. Finally, the gait and stair climbing mechanics of individuals with early OA were not different from their age- and BMI-matched healthy counterparts, indicating that the gait alterations seen in healthy middle-aged obese individuals are the same as those in obese individuals who have already developed the disease, and are likely risk factors or early functional markers of OA.
  • 2009From: Springer
    edited by John R. Masters and Bernhard Ø. Palsson.
    1. Neural progenitors / Dustin R. Wakeman ... [et al.] -- 2. Multipotent stromal cells (hMSCs) / Margaret Wolfe ... [et al.] -- 3. Endothelium / Sangmo Kwon, Takayuki Asahara -- 4. Lung / Rabindra Tirouvanziam, Megha Makam, Bruno Péault -- 5. Eye / Maria Notara ... [et al.] -- 6. Colon / F. Iovino ... [et al.] -- 7. Spermatogonia / Makoto C. Nagano, Jonathan R. Yeh, Khaled Zohni -- 8. Hair follicle pluripotent stem (hfPS) cells / Robert M. Hoffman -- 9. Pancreas / Fang-Xu Jiang, Grant Morahan -- 10. Prostate / C. Foley ... [et al.].
  • 2012From: Springer
    Jan Schildmann...[et al.], editors.
    Part 1. Historical and Socio-Cultural Contexts in Medical Research / British Responses to Nazi Medical War Crimes / Fiona McClenaghan -- History and its Relevance in the Development and Teaching of Research Ethics / Rael D. Strous -- Human Embryo Research and Islamic Bioethics: A View from Iran / Mansooreh Saniei -- From Farming to Pharming: Transcending of Bodily Existence as a Question of Medical Ethics in an Intercultural Context / Axel Siegemund -- Introduction / Jan Schildmann, Verena Sandow, Oliver Rauprich and Jochen Vollmann -- Part 2. Considerations on Ethical and Legal Regulations for Medical Research / Rethinking the Therapeutic Obligation in Clinical Research / Nunziata Comoretto -- Biomedical Research in Developing Countries and International Human Rights Law / Ilja R. Pavone -- Research Involving Human Subjects and Human Biological Material from a European Patent Law Perspective. Autonomy, Commodification, Patentability / Tomasz Zimny -- The Development and Validation of a Guide for Peruvian Research Ethics Committees to Assist in the Review of Ethical-Scientific Aspects of Clinical Trials / Susy Olave Quispe, Duilio Fuentes Delgado, Gabriela Minaya Martínez, Rosa Surco Ibarra and Martín Yagui Moscoso, et al. -- Part 3. Conflicts in Medical Research / Conflicts of Interest in Medical Research: What can Ethics Contribute? / Verena Sandow, Jan Schildmann and Jochen Vollmann -- Research Ethics in Genomics Research: Feedback of Individual Genetic Data to Research Participants / Annelien L. Bredenoord and Johannes J. M. van Delden -- Regulating "Higher Risk, No Direct Benefit" Studies with Children: Challenging the US Federal Regulations / Anna E. Westra, Jan M. Wit, Rám N. Sukhai and Inez D. de Beaufort -- Part 4. New Developments in Medical Research and Ethical Implications / A Paradigm Change in Research Ethics / Rieke van der Graaf and Johannes J. M. van Delden -- Translation of Cancer Molecular Biomarkers: Ethical and Epistemological Issues / Flavio D'Abramo and Cecilia Guastadisegni -- Rethinking the Ethics of Human Biomedical Non-Interventional Research / Kristi L{tilde}ouk.
  • 2013From: CRCnetBASE
    edited by Hanry Yu, Nur Aida Abdul Rahim.
    "This book covers the full range of available imaging modalities and optical methods used to help evaluate material and biological behavior. It also highlights a wide range of optical and biological applications. Each chapter in the text describes a specific application and discusses relevant instrumentation, governing physical principles, data processing procedures, as well as advantages and disadvantages of each modality. Following a broad introduction to key topics, the main chapters are divided between in vitro and in vivo applications. The final section focuses on methods for data processing and analysis"--Provided by publisher.
  • 2015From: Springer
    John D. Lambris, Kristina N. Ekdahl, Daniel Ricklin, Bo Nilsson, editors.
    1. Thromboinflammation in therapeutic medicine -- 2. Complement interactions with blood cells, endothelial cells and microvesicles in thrombotic and inflammatory conditions -- 3. Role of complement on broken surfaces after trauma -- 4. Complement involvement in periodontitis: molecular mechanisms and rational therapeutic approaches -- 5. The lectin pathway of complement and biocompatibility -- 6. Foreign body reaction to subcutaneous implants -- 7. Molecular characterization of macrophage-biomaterial interactions -- 8. Heparan sulfate proteoglycan metabolism and the fate of grafted tissues -- 9. Xenotransplantation of cells, tissues, organs and the Greman research foundation Transregio Collaborative Research Centre 127 -- 10. Macroencapsulated pig islets correct induced diabetes in primates up to 6 months -- 11. Regulation of instant blood mediated inflammatory reaction (IBMIR) in pancreatic islet xeno-transplantation: points for therapeutic interventions -- 12. Cell surface engineering for reguation of immune reactions in cell therapy -- 13. Complement interception across humoral incompatibility in solid organ transplantation: a clinical perspective -- Index.
    Also available: Print – 2015
  • 2014From: Wiley
    edited by Evgeny Katz.
  • 2013From: Springer
    David Korpas.
    History and development of pacing -- Basic principles of cardiac pacemaker technology -- Heart anatomy and physiology -- Pharmacological treatment of cardiac rhythm disorders -- Pacing modes -- Indications for implantable system treatment -- Leads -- Pacing systems -- Pacemaker timing -- Implantable cardioverter-defibrillators -- Cardiac resynchronization therapy -- Implantation, explantation, and replacement of devices and leads -- Patient follow-up -- Electromagnetic compatibility and technical requirements.
  • Thomas Daniel O'Sullivan.
    Molecular imaging is an established technique used to visualize and quantify functional information about biological processes in living systems. In vivo fluorescence imaging, in particular, is a molecular imaging technique capable of quantitatively imaging one or more fluorophores at high spatial and temporal resolution with high sensitivity, either at microscopic or macroscopic (whole-body) scales. While current fluorescent imaging technologies have led to key advances in the understanding of biology and biochemistry, there are limitations. Modern in vivo fluorescence imagers are bulky, and typically take snapshots, and only sample discrete points of continuous, dynamic processes. In order to overcome these obstacles and enable long-term, continuous fluorescence imaging in live animals, we have miniaturized the components of the optical imaging system, allowing for direct implantation. Miniature fluorescence sensors have been fabricated to match a particular fluorescent probe utilizing semiconductor processing technology and appropriate materials. We present the design and fabrication of a monolithically integrated semiconductor (GaAs-based) sensor for far-red to near infrared (NIR) in vivo fluorescence sensing. The sensor incorporates three basic components of a fluorescence system, including: a 675nm vertical-cavity surface-emitting laser (VCSEL) excitation source, a GaAs PIN photodiode, and a fluorescence emission filter. We have packaged the sensors in several integrated configurations, and developed readout mechanisms that include a system that can be implanted in small rodents. We have utilized this device to demonstrate that in vivo fluorescence imaging is possible with miniaturized, un-cooled semiconductor devices, including a demonstration of sensing in a freely-moving rodent. Such miniaturized, implantable biomedical devices have the potential to accelerate pre-clinical research and revolutionize clinical care by providing an inexpensive means for diagnosis, monitoring disease progression, and evaluating long-term treatment efficacy. By integrating this implantable sensor with the appropriate read-out electronics and wireless telemetry, un-tethered operation can ultimately be achieved.
  • 2014From: Springer
    Gauri Mankekar, editor.
    Hearing loss can vary in type ranging from conductive, mixed to sensorineural, as well as in degree from mild, moderate, severe to profound. There could also be multiple permutations and combinations like moderate mixed hearing loss or severe conductive hearing loss. In addition, the hearing loss could be unilateral or bilateral. While cochlear implants were devised for bilateral profound sensorineural hearing loss, various other devices have been invented for other types of hearing losses. Research continues to design a suitable implant which would amplify sound for patients who cannot be candidates for cochlear implants.
  • Michael Quay Chen.
    The limited ability of the human heart to regenerate has made myocardial infarction and heart failure debilitating conditions. Recently, an approach using pluri- or multi-potent stem cells to repair damaged heart tissue is being explored for its potential to regenerate tissue as a tailored, patient-specific treatment. However, the mechanisms of integration remain unclear, and many cardiac grafting procedures utilizing both embryonic and adult stem cells have been met with limited success. While current evidence suggests that grafts are likely viable in host myocardium, clinical studies have reported pro arrhythmic side-effects following transplantation, which arise from disrupted propagation patterns. These issues may be attributed to grafts lacking cardiac differentiation, or possessing conduction properties inconsistent with the host tissue. Consequently, understanding the role of the electrical environment throughout the engraftment process is necessary, but infeasible due to a lack of proper tools. Elucidating the electrical aspects of stem cell transplantation aims to ensure proper integration of the transplanted cells to prevent aberrant electrical pathways in the heart. In this work, a set of in vitro tools were developed to study the potential mechanisms underlying the risk of arrhythmia following stem cell transplantation. A planar microelectrode array was first used to investigate the possibility of conduction block if undifferentiated or non cardiomyocyte stem cells, such as mesenchymal stem cells, are used as grafts. Conduction in murine cardiomyocytes was purposely blocked by co-culture with non-conducting murine fibroblasts, and a novel mathematical transform known as a co occurrence matrix was developed to quantitatively analyze the uniformity of conduction. The observed sensitivity of cardiomyocyte conduction illustrated the risk of grafting non-cardiomyocyte cell types despite any potential of differentiating into muscle-like cells. Unlike non-conducting fibroblasts, stem cell grafts are expected to electrically conduct if proper cardiac differentiation takes place. However, possible differences in the conduction properties of these grafts may still lead to arrhythmia. To perform a controlled study of such conduction mismatch, an in vitro co-culture system coupled to microelectrode arrays was developed. Spatially separated cultures representing the host and the graft were allowed to gradually merge above the microelectrode array, allowing the measurement of conduction throughout the integration process. Modeled host and graft cell populations were evaluated by analyzing the co occurrence matrix and conduction velocity for the quality and speed of conduction over time. Co cultures between murine cardiomyocytes (host) and murine skeletal myoblasts (graft) exhibited significant differences in conduction despite synchronous electrical activity. In contrast, conduction was well matched when the same host cells were co cultured with murine embryonic stem cells (mESC). A model using murine cardiomyocytes (host) and differentiating human embryonic stem cells (graft) allowed the characterization of conduction properties relevant to current trans-species animal models, and demonstrate the co-culture device as a screening platform for candidate graft cells. The limited region of the graft that supported conduction exhibited differences in the co-occurrence matrix as well as conduction velocity when compared to the host region. In an effort to improve the effects of conduction mismatch, both host and graft cell populations were electrically paced over the length of time the cultures remained viable (4-5 days). Although a difference between conduction velocities between host and graft was still observed, the overall uniformity of conduction improved in paced co-cultures, implying increased cardiac differentiation. A preliminary study of genomic changes due to paced mESCs resulted in a significant upregulation of several important cardiac genes and a significant downregulation of many embryonic genes. Further efforts are currently underway to examine gene expression with paced hESCs to optimize integration in the host-graft model, and ultimately to understand how the electrical environment influences stem cell transplantation.
  • 2012From: Springer
    Rihard Trebše, editor.
    Part 1 -- Introduction / Rihard Trebše -- Joint Replacement: Historical Overview / Rihard Trebše, Anže Mihelič -- Biomaterials in Artificial Joint Replacements / Rihard Trebše -- The Definition of Prosthetic Joint Infections (PJI) / Rihard Trebše, Andrej Trampuž -- Classification of Prosthetic Joint Infections / Rihard Trebše, Anže Mihelič -- The Epidemiology of Total Joint Arthroplasty Infections / David J. Jaekel, Kevin L. Ong, Edmund C. Lau -- Septic Complications in Arthroplasty / Gerold Labek -- Perioperative Antibiotic Prophylaxis in Total Joint Arthroplasty / Nataša Faganeli -- Risk Factors for Prosthetic Joint Infections / René Mihalič, Matevž Topolovec -- Pathogenesis of Prosthetic Joint Infections / Rihard Trebše, Jurij Štalc -- Bacteria-Biomaterial Interactions / Antti Soininen, Emilia Kaivosoja, Jaime Esteban -- Biomaterial-Host Interactions in Aseptic and Septic Conditions / Jukka Pajarinen, Yuya Takakubo, Zygmunt Mackiewicz -- Influence of Wear Particles on Local and Systemic Immune System / Emmanuel Gibon, Stuart B. Goodman -- Diagnostic Evaluations / Rihard Trebše -- Synovial Fluid Cytology / René Mihalič, Dunja Terčič -- Histological Analysis of Periprosthetic Tissue for Detecting Prosthetic Joint Infection / Andrej Cör -- Microbiological Diagnosis of Prosthetic Joint Infection / Jaime Esteban, Concepción Pérez-Jorge, Ramón Pérez-Tanoira -- Microbiological Processing of Samples in the Investigation of Suspected Prosthetic Joint Infection / David G. Partridge, Rob Towsend -- Part 2 -- Molecular Diagnosis of Prosthetic Joint Infection / Jaime Esteban, Diana Molina-Manso, Gema del-Prado -- Current Treatment Strategies in Prosthetic Joint Infections / Rihard Trebše Total Ankle Replacement Infections / Michaela Maria Schneiderbauer -- Periprosthetic Infection Issues with Osseointegrated (OI) Implant Technology in Amputees / Catherine Loc-Carrillo, Alec C. Runyon, James Peter Beck -- The Algorithm for Diagnostic Evaluation and Treatment / Rihard Trebše, Andrej Trampuž -- Bone Grafts and Bone Graft Substitutes in Infected Arthroplasty / Martin Clauss, Thomas Ilchmann.
  • Lauren Marie Aquino Shluzas.
    Through an inductive, multi-case analysis, this dissertation examines how design and development practices, involving physicians and medical device developers, influence the clinical and financial outcomes of early stage medical device companies. This research was motivated by an interest in understanding the role of physicians in the device development process, specifically in terms of how physician interaction influences the acceptance or rejection of new medical products. An analytic framework for case-based research was first developed based on exploratory interviews with leaders in the medical device field. Retrospective case studies were then conducted on eight entrepreneurial firms (four rival pairs) in the areas of pulse oximetry, robotic surgery, cardiac bypass surgery, and minimally invasive spine surgery. Primary data sources included interviews with engineers, physicians, and business executives from each company; product development data including device prototypes, regulatory clearance data, and intellectual property (IP); and clinical and financial outcomes data. Following the period of data collection, within-case and across-case analyses were performed. The interview data for each case was coded for design and development practices involving physician-developer interaction, using NVivo qualitative analysis software (QSR International, Version 8). Development practices were analyzed using logic models to examine causal relationships between practices, and product and company outcomes. Design and development practices were further examined and supported using a combination of qualitative and quantitative evidence. Based on the multi-case analysis, this dissertation provides an overview of physician-developer interaction characteristics throughout each phase of the medical device development process. This includes a description of the roles and responsibilities of physicians engaged in development efforts, and their corresponding team affiliations. The research also illustrates four key factors that contributed to medical device adoption for the cases studied. First, the data highlight that designing products under variable use conditions (i.e. with variable patient populations and physicians of varying skill levels), enabled firms to optimize products for widespread clinical use and to increase the predictability of product outcomes. Second, the study shows that product adoption relied on maximizing benefits for multiple product stakeholders, while minimizing required changes in physician behavior. The data further illustrate that total benefit to product stakeholders was influenced to the greatest degree by benefits afforded to hospitals and physicians, assuming patient benefit was greater than or equal to the standard of care. Third, the study highlights that managing perceptions toward product use through performance data positively influenced product adoption to a greater degree than did market demand or regulatory clearance. Fourth, rival explanations for outcomes, involving limited physician interaction, indicate that competitive advantages were achieved through maintaining dominant financial and intellectual property positions. From these findings, the Insight-Value-Perception (iVP) Model for user-centered medical device design was constructed. The model links design and development practices to outcomes, from a combination of consumer-oriented, technical, and financial perspectives. This research provides theoretical contributions to product development and user-centered design literature, and provides practical contributions for developers in the medical device field. A contribution to product development literature is made through documenting the combined benefits of maximizing product value for stakeholders while managing data-driven perceptions toward product use. For the field of user-centered design, this research captures the benefits of designing medical technology with and for a broad consortium of product end-users, as opposed to industry leaders alone. The research also documents the importance of identifying the often-conflicting needs of product stakeholders, and then optimizing devices to satisfy the needs of those with the greatest influence over product use and adoption. For medical device practitioners, this dissertation provides design, regulatory, and product-testing strategies shown to increase technology adoption across the eight cases studied. From this thesis, the author proposes future studies to inform policies and strategies for device manufacturers and the FDA, and to advance knowledge in the fields of user-centered design and product development.
  • 2012From: Wiley
    edited by Murugan Ramalingam [and others].
  • Jonathan S. Daniels.
    Affinity biosensors are important tools for detecting DNA, proteins, cells, and other biomedical analytes. Although optical readout is prevalent, impedance readout is promising for many applications due to lower cost, reduced system size, and label-free operation. Impedance biosensors detect the binding of a target biomolecule to an immobilized probe by quantifying changes in the the electrode-electrolyte interface impedance. Impedance biosensors traditionally use bulky and expensive instruments to monitor the impedance of a single electrode. We describe miniaturized and inexpensive readout circuitry for an array of such sensors. By using a sensor array, multiple analytes can be simultaneously detected and limitations inherent to individual sensors can be mitigated. Reducing the size and cost of the measurement system enables new applications. We present a measurement system for a 6x6 array of impedance biosensors built from off-the-shelf components. Experimental results with DNA probe-target pairs confirm others' reports that changes in the interface impedance can signify binding. Other experiments with proteins demonstrate that changes in the nonlinearity of the I-V relationship can also indicate probe-target binding. We show that the impedance and the nonlinearity can be quantified simultaneously by superimposing a large-amplitude tone on the impedance-measurement tone and analyzing the resulting intermodulation tones. We conclude by describing an integrated array of measurement circuits implemented in 0.18 um CMOS. Each of the 36 measurement pixels contains an impedance-measuring circuit plus tone cancellation circuitry, which enables simultaneous nonlinearity measurement. To prevent the large-amplitude excitation from saturating the amplifier output, a per-pixel digital feedback loop injects an appropriate cancelling current at the amplifier input. Impedance changes of 0.2% can be detected using the integrated measurement circuit. Each pixel occupies 0.14 mm2 and consumes 1.9 mW.
  • 2012From: Cambridge
    editors, C.J. Bettinger, J. Rogers, M. Irimia-Vladu, L. Torsi.
    Progress towards Melanin Integration in Bio-Inspired Devices. -- Bio Organic-Based Gate Dielectric Materials for Thin Film Transistors.
  • 2012From: Wiley
    edited by Marcus Textor, H. Michelle Grandin.
    Frontmatter -- Color Plates -- Stimulus-Responsive Polymers as Intelligent Coatings for Biosensors: Architectures, Response Mechanisms, and Applications / Vinalia Tjong, Jianming Zhang, Ashutosh Chilkoti, Stefan Zauscher -- Smart Surfaces for Point-of-Care Diagnostics / Michael A Nash, Allison L Golden, John M Hoffman, James J Lai, Patrick S Stayton -- Design of Intelligent Surface Modifications and Optimal Liquid Handling for Nanoscale Bioanalytical Sensors / Laurent Feuz, Fredrik H̲̲k, Erik Reimhult -- Intelligent Surfaces for Field-Effect Transistor-Based Nanobiosensing / Akira Matsumoto, Yuji Miyahara, Kazunori Kataoka -- Supported Lipid Bilayers: Intelligent Surfaces for Ion Channel Recordings / Andreas Janshoff, Claudia Steinem -- Antimicrobial and Anti-Inflammatory Intelligent Surfaces / Hans J Griesser, Heike Hall, Toby A Jenkins, Stefani S Griesser, Krasimir Vasilev -- Intelligent Polymer Thin Films and Coatings for Drug Delivery / Alexander N Zelikin, Brigitte St̃dler -- Micro- and Nanopatterning of Active Biomolecules and Cells / Daniel Aydin, Vera C Hirschfeld-Warneken, Ilia Louban, Joachim P Spatz -- Responsive Polymer Coatings for Smart Applications in Chromatography, Drug Delivery Systems, and Cell Sheet Engineering / Roǧrio P Pirraco, Masayuki Yamato, Yoshikatsu Akiyama, Kenichi Nagase, Masamichi Nakayama, Alexandra P Marques, Rui L Reis, Teruo Okano -- Index.
  • Der-Song Lin.
    Capacitive micromachined ultrasonic transducers (CMUTs), have been widely studied in academia and industry over the last decade. CMUTs provide many benefits over traditional piezoelectric transducers including improvement in performance through wide bandwidth, and ease of electronics integration, with the potential to batch fabricate very large 2D arrays with low-cost and high-yield. Though many aspects of CMUT technology have been studied over the years, packaging the CMUT into a fully practical system has not been thoroughly explored. Two important interfaces of packaging that this thesis explores are device encapsulation (the interface between CMUTs and patients) and full electronic integration of large scale 2D arrays (the interface between CMUTs and electronics). In the first part of the work, I investigate the requirements for the CMUT encapsulation. For medical usage, encapsulation is needed to electrically insulate the device, mechanically protect the device, and maintain transducer performance, especially the access of the ultrasound energy. While hermetic sealing can protect many other MEMS devices, CMUTs require mechanical interaction to a fluid, which makes fulfilling the previous criterion very challenging. The proposed solution is to use a viscoelastic material with the glass-transition-temperature lower than room temperature, such as Polydimethylsiloxane (PDMS), to preserve the CMUT static and dynamic performance. Experimental implementation of the encapsulated imaging CMUT arrays shows the device performance was maintained; 95 % of efficiency, 85% of the maximum output pressure, and 91% of the fractional bandwidth (FBW) can be preserved. A viscoelastic finite element model was also developed and shows the performance effects of the coating can be accurately predicted. Four designs, providing acoustic crosstalk suppression, flexible substrate, lens focusing, and blood flow monitoring using PDMS layer were also demonstrated. The second part of the work, presents contributions towards the electronic integration and packaging of large-area 2-D arrays. A very large 2D array is appealing for it can enable advanced novel imaging applications, such as a reconfigurable array, and a compression plate for breast cancer screening. With these goals in mind, I developed the first large-scale fully populated and integrated 2D CMUTs array with 32 by 192 elements. In this study, I demonstrate a flexible and reliable integration approach by successfully combining a simple UBM preparation technique and a CMUTs-interposer-ASICs sandwich design. The results show high shear strength of the UBM (26.5 g), 100% yield of the interconnections, and excellent CMUT resonance uniformity ([lowercase Sigma] = 0.02 MHz). As demonstrated, this allows for a large-scale assembly of a tile-able array by using an interposer. Interface engineering is crucial towards the development of CMUTs into a practical ultrasound system. With the advances in encapsulation technique with a viscoelastic polymer and the combination of the UBM technique to the TSV fabrication for electronics integration, a fully integrated CMUT system can be realized.
  • John D. Enderle, David C. Farden, Daniel J. Krause.
  • v. 1, 2006From: CRCnetBASE
    edited by Waldemar Karwowski.
  • Jules J. VanDersarl.
    Cells communicate through direct contact and soluble chemical signals. Mimicking an extracellular environment requires controlling these signals at micron length scales. Integrated circuits make electronic control at these scales trivial, but fluidic control at these length scales requires very different principles. Standard microfluidic devices can finely control flowing fluids, but fluid flow affects cells in a myriad of ways. Alternatively, diffusion based chemical delivery methods tend to be crude, ill defined systems that offer very limited control. This thesis describes three distinctive platforms that combine the active spatial and temporal control of microfluidic systems with a delivery system that relies purely on diffusion. First, we detail a silicon based array of nanoreservoirs underneath the cell culture surface which are used to store and release bioactive molecules. These reservoirs are opened and closed with electrochemical dissolution and deposition at a narrow reservoir opening. Next, we describe an adaptation of traditional, elastomer based microfluidics. In these devices the cell culture area is separated from a microfluidic channel located directly underneath the chamber by a nanoporous membrane. The desirable microfluidic properties, including temporal and spatial control, are preserved, while fluidic flow over the cells is eliminated. Finally, we demonstrate a novel "nanostraw" culture surface, which is combined with the previous device to offer fluidic access directly to the cell cytosol, creating a powerful tool with implications for cell delivery and sampling. Additional work on probing the assembly of protein structures is also detailed. Clathrin 2-dimensional lattice assembly on lipid monolayers, serving as cell membrane mimics, was monitored and studied through surface rheological techniques. Rheological measurements elucidated important network properties, and the formation process was compared to various models for clathrin network assembly.
  • Amin Nikoozadeh.
    Atrial fibrillation, the most common type of cardiac arrhythmia, now affects more than 2.2 million adults in the United States alone. Currently, electrophysiological interventions are performed under fluoroscopic guidance, which does not provide adequate soft-tissue resolution and exposes the patient and the operator to harmful ionizing radiation. Intracardiac echocardiography (ICE) provides real-time anatomical information that has proven valuable in reducing the fluoroscopy time and enhancing procedural success. This dissertation describes the design and implementation of two types of multi-functional, forward-looking ICE catheters developed using capacitive micromachined ultrasonic transducer (CMUT) technology: MicroLinear (ML) and Ring catheters. The ML catheter enables real-time, forward-looking 2D imaging using a 24-element, fine-pitch 1D CMUT phased array. The Ring catheter uses a 64-element, ring-shaped 2D CMUT array that enables real-time, forward-looking, volumetric imaging. Both of these catheters are equipped with custom-designed, front-end electronic circuits that are integrated with each transducer array at the catheter tip. The close integration of custom electronic circuits with the ML and Ring CMUT arrays improves the signal-to-noise ratio (SNR) in each case by 18 dB and 20dB, respectively. The integration process of the CMUT arrays with the electronics dice in the tight space available for full catheter construction shows 100% yield. The characterization of the fully-integrated CMUT arrays demonstrates excellent pulse-echo response with over 100% fractional bandwidth as well as surface transmit pressure levels in excess of 1 MPa (peak-to-peak). The first fully-functional 9F ML CMUT ICE catheter shows remarkable in vivo imaging performance using porcine animal models. A similar in vivo imaging experiment with the first fully-functional 12F Ring CMUT ICE catheter proves very promising. The volumetric imaging capability of the Ring ICE catheter and the versatility offered by its inner lumen make it an attractive interventional device. This dissertation also introduces a novel CMUT structure, called PCMUT. The preliminary simulation and experimental verification of the PCMUT structure show that it is possible to fabricate CMUTs that exhibit non-flexural piston-like plate motion with a significantly improved volume displacement and fill-factor.
  • 2011From: Springer
    Aleš Prokop, editor.
  • 2014From: Springer
    Ferenc A. Jolesz, editor.
    Image-guided therapy (IGT) uses imaging to improve the localization and targeting of diseased tissue and to monitor and control treatments. During the past decade, image-guided surgeries and image-guided minimally invasive interventions have emerged as advances that can be used in place of traditional invasive approaches. Advanced imaging technologies such as magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) entered into operating rooms and interventional suites to complement already-available routine imaging devices like X-ray and ultrasound. At the same time, navigational tools, computer-assisted surgery devices, and image-guided robots also became part of the revolution in interventional radiology suites and the operating room. Intraoperative Imaging and Image-Guided Therapy explores the fundamental, technical, and clinical aspects of state-of the-art image-guided therapies. It presents the basic concepts of image guidance, the technologies involved in therapy delivery, and the special requirements for the design and construction of image-guided operating rooms and interventional suites. It also covers future developments such as molecular imaging-guided surgeries and novel innovative therapies like MRI-guided focused ultrasound surgery. IGT is a multidisciplinary and multimodality field in which teams of physicians, nurses, and other professionals, such as physicists, engineers, and computer scientists, collaborate in performing these interventions, an approach that is reflected in the organization of the book. Contributing authors include members of the National Center of Image-Guided Therapy program at Brigham and Womens Hospital and international leaders in the field of IGT.
  • Douglas A. Christensen.
  • Kyriacos A. Athanasiou and Roman M. Natoli.
  • 2013From: Wiley
    edited by Dario Farina, Winnie Jensen, Metin Akay.
    pt. I. Injuries of the nervous system -- pt. II. Signal detection and conditioning -- pt. III. Function replacement (prostheses and orthosis) -- pt. IV. Function restoration -- pt. V. Rehabilitation through neuromodulation.
  • Kristina M. Ropella.
  • 2014From: Wiley
    Ravi Birla.
    Introduction to Tissue Engineering -- Cells for Tissue Engineering -- Biomaterials for Tissue Engineering -- Tissue Fabrication Technology -- Vascularization of Artificial Tissue.
  • Rodrigo Alvarez-Icaza Rivera.
    In this dissertation, I revisit Kawato's proposal, that the cerebellum predictively modulates descending motor commands, to achieve smooth and coordinated motion, by acquiring an inverse model of the biomechanical plant, and extend it by describing a novel and precise mapping between a cerebellar multizonal microcomplex and a joint's inverse model. This mapping renders two novel predictions: First, inferior olive's oscillations mirror the biomechanical joint's oscillations. Second, deep cerebellar neurons implement a gain factor, set by Purkinje cell inhibition, on inferior olive's signals to mirror the spinal cord's gain. I use biophysical modeling to show that oscillations within the inferior olive match the range of natural frequencies and damping ratios of biophysical joints, and that deep cerebellar neurons enable a multiplicative interaction between the Purkinje and the olivary pathways. Furthermore, I determine the effects of current injection into the inferior olive and the deep cerebellar nuclei and use these results within a control theory model to predict that experimentally disturbing the inferior olive will introduce motor output ringing, while disturbing the deep nuclei will also scale motor output. In both cases, manipulating the inverse model implemented by microzonal microcomplex will unmask the joint's natural dynamics as observed by motor ringing at the joint's natural frequency.
  • Widya Mulyasasmita.
    The repair of damaged tissues through cell and growth factor administration is a promising strategy in regenerative medicine. However, clinical success has been limited due to the lack of effective delivery methods. While deemed minimally invasive, the conventional approach of direct injection in saline compromises the efficacy of the biological payloads. Post-injection cell survival is often dismally low, owing to the combination of shear forces during injection and hostile environments at the injury site. Growth factors delivered by bolus injections face rapid clearance and distribution to off-target sites, leading to suboptimal concentrations at the sites of therapy and potential side effects in normal tissues. These are major therapeutic hurdles because symptomatic relief following cell therapy is often correlated with the number of surviving donor cells. In the case of growth factor therapy, spatiotemporal control over growth factor distribution is critical for normal recovery, as tissue regeneration is a tightly coordinated process. This thesis presents a biomaterials approach to overcome these hurdles by harnessing polymer and protein engineering strategies to design injectable hydrogel carries for optimal cell and drug delivery. A broad survey of protein-engineered biomaterials is first given in Chapter 1 to provide a foundation for the design principles, synthesis, and characterization methods employed in subsequent chapters. Chapter 2 describes a mechanistic investigation into the physical forces imposed on cells during injection, using alginate polysaccharides as model carriers. This study reveals extensional stresses to be the dominant cause of cell death, and that cell viability can be restored by pre-encapsulation in hydrogel carriers that exhibit thixotropy, or the ability to shear-thin and self-heal. Subsequent chapters describe the design and characterization of a thixotropic protein-engineered hydrogel system called MITCH, or Mixing-Induced Two-Component Hydrogels, and their applications as cell and drug delivery vehicles in regenerative medicine. The crosslinking of the MITCH network relies on the reversible binding between complementary peptide domains, enabling gelation and cell encapsulation by simple mixing at physiological conditions. The design rationale and demonstration of thixotropy, cyto-compatibility, and three-dimensional cell encapsulation are discussed in Chapter 3. In Chapter 4, the specificity and stoichiometric precision of the peptide-peptide crosslinking interactions are highlighted as a distinguishing feature of MITCH. Polymer physics considerations are combined with protein science methodologies to enable the predictable tuning of macroscopic-level gel mechanics through molecular-level variations of component concentration and stoichiometric ratio. The remainder of the thesis focuses on the utility of the MITCH material as a delivery carrier for cell and drug regenerative therapy. Cell protection is demonstrated in Chapter 5, where adipose-derived stem cells injected subcutaneously in mice exhibit improved retention when encapsulated and delivered in MITCH, relative to saline and control biomatrices. Moreover, histological analyses of explants show endogenous cell invasion and signs of native extracellular matrix remodeling at day 3. The simple mixing protocol allows the encapsulation and release of peptide drugs and growth factors in their bioactive state. Chapter 6 describes the engineering of an affinity- and avidity-based peptide drug delivery system, developed by using the molecular recognition domains in MITCH. Fusion of angiogenic peptides to MITCH-specific affinity tags enables drug immobilization, sustained release, and prolonged local drug availability. This controlled release strategy induces higher levels of endothelial cell migration and matrix invasion compared to delivery from saline alone. Chapter 7 presents a therapeutic angiogenesis strategy by dual delivery of human induced stem cell-derived endothelial cells (hiPSC-ECs) and vascular endothelial growth factor (VEGF). This chapter also introduces MITCH 2.0, a new class of protein polymer/synthetic polymer hybrid hydrogel system created to improve tunability and ease of synthesis. Similar to the original version, MITCH 2.0 protects cells during injection and delivers drugs with tunable kinetics. In a murine hindlimb ischemia model, hiPSC-ECs co-delivered with VEGF in MITCH show improved post-transplantation viability and restore blood perfusion to the ischemic limb. All in all, by improving the delivery of cells and biochemical factors, the biomaterials work completed here provides enabling tools to advance other biological research endeavors, to ultimately realize the clinical translation and success of regenerative medicine.
  • 2015From: Springer
    M. Soledad Cortina, Jose de la Cruz, editors.
    This book covers the field of keratoprosthesis in detail and focuses specifically on the Boston type 1 keratoprosthesis (KPro), which is the device most widely used today. Extensive information is provided on all aspects of KPro surgery, from history and preoperative evaluation to surgical techniques and postoperative management of complications. Surgical videos are included that will aid both beginning and advanced corneal surgeons in mastering these procedures. In addition, essential basic science concepts relevant to keratoprosthesis surgery are explained, and other keratoprostheses in use around the world are considered. A brief overview of integrating artificial corneas is provided, and the future of keratoprosthesis is also discussed. The book is written by some of the most distinguished and renowned experts in the field.
  • Shantanu Banik, Rangaraj M. Rangayyan, Graham S. Boag.
  • 2015From: Wiley
    edited by Catherine Picart, Frank Caruso, and Jean-Claude Voegel.
  • Yusuf Ozuysal.
    Neurons have a limited dynamic range. To more efficiently encode the large range of natural inputs, neural circuits adapt by dynamically changing their output range as a function of the input statistics. Variance adaptation provides an informative example of this process, whereby neurons change their response characteristics as a function of variance of their input. When their input distribution changes, sensory systems shift and scale their response curves to efficiently cover the new range of input values and they focus on different segments of the frequency spectrum, for example by choosing to average out the noise in a low signal-to-noise ratio environment by low-pass filtering their input and sacrificing resolution. In multiple sensory systems, adaptation to the variance of a sensory input changes the sensitivity, kinetics and average response over timescales ranging from < 100 ms to tens of seconds. Here we present a simple biophysically relevant model of retinal contrast adaptation that accurately captures both the membrane potential response and all adaptive properties. The adaptive component of this model is a first-order kinetic process of the type used to describe ion channel gating and synaptic transmission. We conclude that all adaptive dynamics can be accounted for by depletion of a signaling mechanism, and that contrast adaptation can be explained as adaptation to the mean of a thresholded signal. A diverse set of adaptive properties that implement theoretical principles of efficient coding can be generated by a single type of molecule or synapse with just a few microscopic states. The LNK model helps to highlight important aspects of adaptation by letting us focus on individual computational blocks separately. By using the LNK model, we investigate the source of the adaptive process in On-Off retinal ganglion cells, which show strong changes in their kinetics as a function of contrast. By analyzing properties of the LNK model, we conclude that most of the adaptive effect is due to differences in the threshold of the two pathways, with a smaller contribution from different adaptive kinetics. Adaptive temporal decorrelation in the retina arises due to differential thresholding in two parallel neural pathways.
  • Zuley Rivera Alvidrez.
    Any time we move, our brains solve the difficult problem of translating our motor intentions to muscle commands. Understanding how this computation takes place, and in particular, what role the motor cortex plays in movement generation, has been a central issue in systems neuroscience that remains unresolved. In this thesis, we took an unconventional approach to the analysis of cortical neural activity and its relationship to executed movements. We used dimensionality reduction to extract the salient patterns of neural population activity, and related those to the muscle activity patterns generated during arm reaches to a grid of targets. We found that salient neural activity patterns appeared to tightly reflect muscle activity patterns with a biologically-plausible lag. We also applied our analyses to movements that were planned before being executed, and found that a muscle-framework view of the cortical activity was consistent with previously-described predictions of movement kinematics based on the state of the cortical population activity. Overall, our results elucidate remarkable simplicity of the motor-cortical activity at the population level, despite the complexity and heterogeneity of individual cell's activities.
  • Henrique do Carmo Miranda.
    Neural recording systems are fundamental to the advancement of brain-machine interfaces that can significantly improve the quality of lives of patients with neurological diseases, such as spinal cord injuries or quadriplegia. This thesis presents two newly developed wireless neural recording systems that are able to provide a high degree of usability and neural decoding accuracy. They are capable of simultaneously transmitting 32 to 96 channels of neural signals detected by an implanted neural sensor array. This work was carried out within the framework of the Hermes project and its technical design challenges will be addressed. The Hermes project is aimed at primarily developing hardware and software tools that extract neural information from the motor cortex. Those tools can enable practical prosthetic devices used to significantly ameliorate the life of patients with neurological impairments that directly affect motor functions. The first developed system, HermesD, is a 32-channel broadband transmission system using an FSK modulated carrier at 24 Mbit/s in the 3.7-4.1 GHz band. The link range extends beyond 20 m and the total power consumption is 142 mW. The HermesD system uses only COTS components and can be easily replicated. HermesD is fully operational and is currently used to transmit broadband neural data for neuroscience research in the Neural Prosthetic Systems Laboratory (NPSL) at Stanford University. HermesD is also planned as the base platform for future human trials to take place in the same laboratory. The second system that represents the next Hermes generation, HermesE, uses a novel UWB transmitter architecture implemented in a custom IC in the 65-nm CMOS technology. The transmitted signal bandwidth covers the 3.6 to 7.5 GHz frequency range. The time domain waveform is digitally programmable, allowing a very flexible control of the output spectrum to avoid interference and to allow multi-band operation. The UWB transmitter chip is part of a 96-channel broadband recording system delivering 40 Mbit/s. Its power consumption is 230 uW for a communication range of about 5 m. The antenna subsystems for these wireless recording devices presented a design challenge given the requirements for small size, large bandwidth and high efficiency. While HermesD has an operating FBW of 10%, HermesE is much more demanding in this respect, with 70% FBW, requiring unconventional antenna structures. The design techniques and performance of the antennas required to meet the specifications of both systems are also addressed in this work.
  • Dokyoon Kim.
    This dissertation presents the basic principles of the magnetic protein chip immunoassay and applications of the magnetic protein chip for the detection of protein biomarkers. The magnetic protein chip is based on the giant magnetoresistive (GMR) spin-valve sensors, and electrical resistance changes of the sensors are measured as signals. Immunoassays were developed using the magnetic protein chips to quantitate protein biomarkers with high sensitivity. The magnetic protein chip immunoassay has several advantages over conventional non-magnetic techniques, such as multiplex capability, smaller sample volume requirement, enhanced signal-to-noise ratio, and facile integration with electronics. Ionizing radiation is high energy radiation that can remove electrons from atoms, and it causes various cellular damages some of which are lethal. Using an in vivo mouse radiation model, we developed protocols for measuring fms-related tyrosine kinase 3 ligand (Flt3lg) and serum amyloid A1 (Saa1) in small amounts of blood collected during the first week after X-ray exposures of sham, 0.1, 1, 2, 3, or 6 Gy. Flt3lg concentrations showed excellent dose discrimination at >= 1 Gy in the time window of 1 to 7 days after exposure except 1 Gy at day 7. Saa1 dose response was limited to the first two days after exposure. A discriminant analysis using both proteins could show improved dose classification accuracy. Our magnetic protein chip immunoassay demonstrated the dose and time responses and low-dose sensitivity that have important advantages in radiation triage biodosimetry. Necrotizing enterocolitis (NEC) is an inflammatory bowel disease often observed in pre-term babies and has high mortality rate. However, timely diagnosis of NEC has been hampered due to its unspecific symptoms and ineffective clinical tests currently available. We developed a magnetic protein chip immunoassay for the validation of NEC biomarkers. Three biomarkers, C-reactive protein (CRP), matrix metalloproteinase-7 (MMP7), and epithelial cell adhesion molecule (EpCAM) were quantitated using a small amount of blood samples. Receiver operating characteristic (ROC) curve analysis combined with bootstrapping technique showed excellent discrimination of NEC from healthy control and NEC from sepsis. Given the generality of the detection scheme used in the magnetic protein chip immunoassay, the magnetic protein chips are expected to hold great potential for medical diagnosis and clinical research.
  • Ernesto Staroswiecki.
    Osteoarthritis (OA) is a degenerative joint disease that affects over 80% of the population of the U.S. by age 65. However, there is currently no disease-modifying treatment for OA. In order to develop and evaluate potential treatments, it is necessary to assess cartilage health over the course of the disease. Here, an MRI method is presented to obtain sodium images of tissue that pushes the current state of the art of sodium MRI and can provide new information about cartilage. The method presented here enables sodium imaging at high resolution and with lower noise levels than previously reported. This technique uses custom-made radio-frequency (RF) coils and a 3D-cones k-space trajectory and is well suited to imaging at high field strengths like 3 T and 7 T. A second novel method is presented for generating high-resolution, 3D T2 and ADC maps of the human knee in vivo. The maps are derived from diagnostic-quality morphological MR images. This method is based on a new variation of the 3D double echo steady-state (DESS) sequence and solves many of the current challenges of traditional imaging techniques. Finally, a third method is presented allowing independent excitation of two or more volumes with a short RF pulse for MRI. This method enables different volumes to be excited with different RF pulse parameters, including flip angle, slice profile or thickness, phase modulation, etc., increasing the flexibility of the excitation. In summary, the techniques presented here generate measurements of sodium, T2, and ADC in cartilage, all biomarkers of interest for this tissue. These measurements are either less noisy or more efficiently obtained than with previous methods. The methods presented in this dissertation also improve the efficiency of diagnostic image acquisition for the knee.
  • Gaurav Krishnamurthy.
    The mitral valve (MV) is a bicuspid valve that allows the unidirectional flow of blood from the left atrium (LA) into the left ventricle (LV). MV disease afflicts millions each year worldwide and if sufficiently severe, surgical therapy is indicated. Surgical repair is currently preferred but valve replacement is often required. Current replacement therapy involves implantation of a mechanical valve, associated with anticoagulation/ thromboembolic complications, or a tissue valve, associated with less than ideal durability. To overcome these limitations, a currently important research goal is to create bioengineered autologous tissue valves. A key component of this thrust is to understand more completely the structure and function of native valves which reliably cycle 100,000 times per day, more than 3 billion times in an average lifetime. Toward this end, this thesis presents, for the first time, the material properties of the anterior mitral leaflet in the beating heart. The methodology used in this research is as follows: Surgical preparation and radiopaque marker data acquisition: 16 miniature radiopaque markers were sewn to the MV annulus, 16 to the anterior MV leaflet, and one on each papillary muscle tip in male sheep. 4-D coordinates were obtained from biplane videofluoroscopic marker images (60f/s) during three complete cardiac cycles. Data were acquired sequentially with repeat control runs between saddlehorn electrical pulse stimulation and intravenous administration of esmolol to study the effect of pharmacological agents on mitral leaflet contractility, and vagal nerve stimulation to assess the potential for central neural control. Inverse finite element analysis: A finite element model of the anterior MV leaflet was developed using marker coordinates at the end of isovolumic relaxation (IVR, when pressure difference across the valve is approximately zero), as the stress-free reference state. Leaflet displacements were simulated during IVR using measured left ventricular and atrial pressures. The elastic moduli in both the commisure-commisure (Ecirc) and radial (Erad) directions were optimized using the Method of Feasible Directions to minimize the difference between simulated and measured displacements. The derived material properties were found to be orders of magnitude greater than previously determined ex vivo material properties. Histologic studies have shown that the mitral leaflets, rather than being simple collagen flaps (as once thought), contain complex networks of contractile elements (smooth and striated muscle; valvular interstitial cells), blood vessels, and both afferent & efferent nerves. The finding of higher stiffness in vivo than ex vivo suggests a mechanistic role for these elements; to modulate the stiffness of the active mitral valve in vivo -- a property necessarily missing in excised, flaccid valves ex vivo. Using the derived material properties, a forward analysis was performed to determine the stress-strain behavior of the anterior leaflet at various trans-mitral pressure gradients during IVR. This analysis showed that the leaflet material behaved linearly over a physiologic range of pressures. It is also shown in this thesis that these leaflet material properties vary over the cardiac cycle; leaflet stiffness is higher during early systole (Isovolumic Contraction, IVC) most likely due to force development in cardiac muscle cells in the annular third of the anterior leaflet, and as this force development wanes during systole, the stiffness of the leaflet drops. Stimulation of the neutrally-rich annular saddlehorn region adjacent to the anterior leaflet was shown to almost double leaflet stiffness, whereas administration of a beta-blocker (Esmolol) eliminated the early systolic increase in anterior leaflet stiffness. The initial homogeneous finite element model of the anterior leaflet was further developed to incorporate regionally varying material properties. This heterogeneous finite element model confirmed that Esmolol selectively reduced leaflet stiffness in the annular region (which contains the slip of cardiac muscle) during IVC and did not affect edge stiffness (which is devoid of cardiac muscle). Saddlehorn stimulation caused an increase in leaflet stiffness values for all regions (edge, belly and annular regions) during both IVC and IVR. Loss of atrial contraction had a similar effect on the anterior leaflet as administration of Esmolol, i.e. without atrial depolarization the leaflet stiffness during IVC in the annular region dropped to baseline IVR values. Finally, the functional role of autonomic nerves in the anterior leaflet was investigated by remote stimulation of the vagus nerve. This study showed that vagal nerve stimulation can result in a decrease in anterior leaflet stiffness during both IVR and IVC. In summary, the findings of this thesis suggest a permanent paradigm shift from one viewing the mitral valve leaflets as passive flaps to one viewing the leaflets as active, potentially adaptive, neurally-controlled tissues whose complex function and dysfunction must be taken into account when considering not only therapeutic approaches to mitral valve disease, but even the definitions of mitral valve disease itself. The improved understanding of the structure-function relationships in these native, active valves could uncover new targets for pharmacologic intervention, as well as provide important insights to improve the future design and durability of tissue-engineered mitral valves.
  • 2013From: Cambridge
    [edited by] Jan de Boer, Clemens A. van Blitterswijk.
    "This complete, yet concise, guide introduces you to the rapidly developing field of high throughput screening of biomaterials: materiomics. Bringing together the key concepts and methodologies used to determine biomaterial properties, you will understand the adaptation and application of materomics in areas such as rapid prototyping, lithography and combinatorial chemistry. Each chapter is written by internationally renowned experts, and includes tutorial paragraphs on topics such as biomaterial-banking, imaging, assay development, translational aspects, and informatics. Case studies of state-of-the-art experiments provide illustrative examples, whilst lists of key publications allow you to easily read up on the most relevant background material. Whether you are a professional scientist in industry, a student, or a researcher, this book is not to be missed if you are interested in the latest developments in biomaterials research"--Provided by publisher.
  • Adam Shar Wang.
    Computed tomography (CT) has become an essential tool in modern medicine since its introduction in the early 1970s. It generates cross-sectional images of the body's x-ray attenuation by measuring the transmission of x-rays in many directions. Because CT uses ionizing radiation, a governing principle is to use the least amount of radiation dose that still provides diagnostic-quality images. One approach to ensure that dose is appropriately used is to explore the information content of CT scans. This work examines efficient methods for encoding, storing, and extracting information from CT scans, especially as they pertain to spectral x-ray imaging. CT systems that can take advantage of the different attenuation properties of x-rays at different energies can provide additional diagnostic information, known as dual energy imaging. A new technique called Synthetic CT is introduced that enables images from CT protocols other than what was acquired to be retrospectively synthesized. With this tool, the information contained within a dual energy scan can be used to demonstrate the effect of protocol selection on image quality and dose distribution. In addition to experimentally validating the developed synthetic CT theory, further efforts have led to image-based synthetic CT, incorporation of electronic noise models for ultra low dose simulation, and a simple graphical user interface that demonstrates the flexibility of synthetic CT. We also explore an important spectral imaging technology -- photon counting detectors with energy discrimination capabilities. In principle, these detectors capture all the spectral information of transmitted x-rays by counting the number of photons at each energy. Optimal configurations of ideal photon counting detectors are first investigated, leading to the elegant discovery that two energy-dependent weighted counts can form a sufficient statistic for dual energy imaging. In practice, photon counting detectors have count rate limitations and imperfect spectral responses. The performance of realistic photon counting detectors is modeled and compared to conventional dual kV techniques. We find that both optimized photon counting and dual kV systems can significantly increase the dose efficiency of dual energy imaging.
  • 2006From: Springer
    Scott A. Lipson.
  • 2016From: Springer
    Peter J. Fabri.
    Introduction to Measurement and Analysis -- Data and Types of Data -- Software for Analytics -- Measurement and Uncertainty -- Mathematical and Statistical Concepts in Data Analysis -- Analysis by Modeling Data -- Principles of Supervised Learning -- Unsupervised Machine Learning -- Datasets Without Outcomes -- Survival Analysis -- Interpreting Outcomes: Cause and Effect and p-values -- Useful Tools.
  • Melinda Joy Cromie.
    This dissertation addressed two challenges in musculoskeletal biomechanics. The first challenge was to understand the function of total knee prostheses after implantation in patients. Motions of the knee following total knee replacement affect a patient's ability to perform daily activities, such as walking and rising from a chair, and affect the longevity of the prosthesis. The millimeter-scale translations of the joint are difficult to measure with noninvasive methods such as analysis of skin mounted markers. We addressed this challenge by measuring passive knee kinematics using a surgical navigation system. The specific goal was to isolate the effects of posterior cruciate ligament removal on knee motion after total knee arthroplasty. We measured knee kinematics intraoperatively while the surgeon passively flexed and extended the knee at four surgical time points: after initial exposure, after removing the anterior cruciate ligament, after removing the posterior cruciate ligament, and after implanting the prosthesis. We calculated anterior femoral translation and the flexion angle at which femoral rollback began. We found that removing the posterior cruciate ligament introduced abnormal anterior translation, doubling the anterior translation from the initial exposure (from 5.1 +/- 4.3 mm to 10.4 +/- 5.1 mm) and increasing the flexion angle at which femoral rollback began (from 31.2 +/- 9.6 degrees to 49.3 +/- 7.3 degrees). Implanting the prosthesis did not restore the motion measured at initial exposure. Relative to the cruciate-deficient case, prosthesis implantation increased the amount of anterior translation (to 16.1 +/- 4.4 mm) and did not change the flexion angle at which femoral rollback began. Abnormal anterior translation was observed in low and mid flexion (0-60 degrees) after removing the posterior cruciate ligament, and normal motion was not restored by the posterior stabilized prosthesis. These findings can be used to interpret further motion analysis during functional tasks and to guide improvements in prosthesis design. The second challenge was to understand how the motions of sarcomeres, the contractile units of muscle, affect the force-generating capacity of muscles in humans. Sarcomere length over a muscle's range of motion in the body is an important factor that affects muscle excursions and force-generating capacity. The relationship between sarcomere length and joint angle can be altered in disease, and measurement of this relationship is important for guiding treatments. Second-harmonic generation (SHG) microendoscopy has recently been developed in our laboratories to image sarcomeres and measure their lengths in humans. However, technical challenges such as motion artifacts and low signal have thus far prevented this novel technique from being used to quantify sarcomere lengths in humans. We discovered that an excitation wavelength of 960 nm maximized image signal; this enabled an image acquisition rate of 3 frames-per-second, which decreased motion artifact. We then used microendoscopy to directly image sarcomeres in the extensor carpi radialis brevis (ECRB) in seven healthy adults with the wrist in 45 degrees extension and 45 degrees flexion. We determined the average sarcomere lengths and the length variability of in-series sarcomeres from the SHG images. Sarcomere lengths in 45 degrees wrist extension were 2.93 +/- 0.29 microns (mean +/- standard deviation) and increased to 3.58 +/- 0.19 microns in 45 degrees flexion. Within local regions of the fibers the standard deviation of sarcomere lengths in series was 0.20 +/- 0.07 microns. These measurements agree with measurements in the same muscle using laser diffraction. The lengths of sarcomeres in series within a small region of an individual fiber can vary substantially. This study demonstrates the suitability of SHG microendoscopy for imaging muscle microstructure and illustrates the potential of this technology to address a new class of questions about muscle architecture and remodeling in humans. The ability to measure sarcomere operating lengths in humans without surgery enables us to diagnose the involvement of specific muscles in neuromuscular disorders, and to design surgeries that will optimize an individual patient's outcome. Measurement of sarcomere operating length will also enable a new class of research questions to be addressed about the adaptations of muscles over time in response to surgeries or pharmacologic treatments.
  • Cynthia Anne Chestek.
    Cortical brain-machine interfaces, or BMIs, is a relatively new field with the potential to provide many different clinical treatments, particularly for fully paralyzed patients. In these applications, multichannel electrode arrays are implanted into motor cortical areas in order to extract useful control signals. My research focuses on taking proof-of-concept academic BMI systems, and solving the engineering challenges that currently prevent them from being used in a clinical setting. These challenges include running a BMI for more than a few hours or a single day, and finding ways to minimize the size, cost, and operational complexity of the complete system. This dissertation includes an analysis of neuron stability over long timescales. I will show that the relationship between neurons in motor cortices and behavior remains stationary over time despite substantial noise, which could mitigate some concerns about long-term BMI performance. I will also discuss the development of HermesC, a wireless system for recording multichannel neural data from freely moving primates. This device dramatically reduces the size and cost of current recording technology for real-time neural prosthetic systems, and could be useful for human clinical trials. It may also enable neural prosthetic studies with animals in a less constrained setting. Combining traditional neural recordings with overnight wireless neural recordings, I will also show that there are substantial changes in neural waveforms from single neurons across days. However, the quality of neural decodes (the extraction of useful control signals) is only slightly improved by sorting individual units rather than using simple threshold crossings. This may enable long term BMI operation because multiunit neural "hash" on electrode arrays tends to persist for a long time, perhaps years, after single neuron signals have declined due to various tissue responses. In fact, other recent work from this project has demonstrated high performance neural decodes using only threshold crossings on arrays ~2.5 years after implantation.
  • Julia Chinghua Chen.
    Our bones constantly adapt to their mechanical environment through a biological response from the womb to the tomb. Mechanobiology, the biological response to mechanical loading, is important for determining various properties of bone such as size and shape. During embryonic development, rapid growth generates significant tension in the periosteum, and tension has previously been shown to lead to bone apposition. In adults, intracortical stresses dominate and increased loading leads to elevated rates in bone apposition. Periosteal tension and intracortical stresses, then, are both experienced by bones, but their influences on bone apposition rates vary over time. This dissertation analyzes how embryonic bone growth rates and adult bone adaptation rates in long bones are related to their respective mechanical environments. The hypothesis that bones grow and adapt at rates corresponding to changes in the mechanical environment is investigated. In the first study, I investigated the mechanical environment of the periosteum during embryonic growth and its relationship to bone growth rates. The specific growth rate, or percent growth per day, was calculated using microCT images taken over embryonic days 11-20. Bones grew faster in length than in circumference during this time. Finite element techniques were then used to analyze the opening dimensions of incisions through the periosteum. Longitudinal and circumferential residual strains decreased from 46.2% to 29.3%, and 10.6% to 3.9%, respectively, during embryonic days 14-20. Residual strains were positively correlated to specific growth rates (p< 0.05). Many studies have investigated bone adaptation in adult mice and rats by applying loads to the long bones, and measuring changes in periosteal cortical bone apposition rates. However, results are difficult to compare because the loading schemes are generally different. The second study presents a theoretical framework for evaluating the mechanical stimulus based on the bone daily strain stimulus, which is a function of loading cycles and bone strains. The daily strain stimulus may act as a single unifying parameter for directly comparing data from existing in vivo experiments. Two approaches were used to determine the periosteal daily strain stimulus necessary for bone maintenance (xi_peri_0) and the strain-cycle weighting exponent (m), which are required to calculate the daily strain stimulus. In the first approach, data from bone maintenance studies were used to calculate xi_peri_0 to be 2793 microstrain/day, and m to be 4.5. In the second approach, strain gage recordings were used to calculate xi_peri_0 to be 1496 microstrain/day, and human bone compressive fatigue properties were used to assign m to be 11.88. Bone apposition rates generally increased with increasing daily strain stimulus, which was consistent with previous theoretical models. The third study provides examples of how the daily strain stimulus may be used to examine the effects of specific loading parameters on bone apposition rates. The effects of inserting periods of rest and frequency were examined. Inserting periods of rest during loading appeared to increase bone apposition rates by approximately 64% compared to continuously loaded bones. Frequency has been previously suggested to be most osteogenic at 5-10 Hz. Using this analysis, an increase in bone apposition rate was also observed at 10 Hz. The results of these studies provide insight into the effects of periosteal tension during embryonic development and intracortical strains during adulthood on bone apposition rates. These findings illustrate how important the mechanical loads experienced by bones and their surrounding tissues are in determining the sizes and shapes of bones.
  • Chelsey Savannah Simmons.
    The heart is a complex integrated system that leverages mechanoelectrical signals to synchronize cardiomyocyte contraction and push blood throughout the body. Due to the heart's limited regenerative capacity and the wide variety of cardiovascular pathologies, heart disease is often studied in vitro. However, it is difficult to accurately replicate the cardiac environment outside of the body. In this dissertation, I describe an integrated strain array for cell culture that mimics the mechanical movement of the heart and enables high-throughput mechanotransduction studies. Along with mechanical strain, substrate stiffness is an important mechanical stimulus. The heart and vasculature, along with other organs, remodel in both development and disease, changing their mechanical properties. I successfully implement a method that can simultaneously tune both substrate stiffness and mechanical strain in normal and pathological ranges. Polyacrylamide gels, attached to stretchable silicone platforms by interpenetrating networks, can be stretched up to 50% without delaminating. To fully harness the potential of studying heart disease in vitro, better techniques for studying heart cell contractions are required in addition to biomimetic dynamic culture. In this dissertation, I also describe two successful new approaches to quantifying cardiomyocyte contractility using simple phase contrast videos: one for single cells plated on soft gels and one for cell monolayers attached to glass or plastic. Together, these innovations provide a suite of tools to stimulate and assess cardiovascular cells and advance our collective knowledge of cardiovascular health and disease.
  • 2015From: Atypon
    Marnie M. Saunders, The University of Akron, Akron, Ohio.
    Mechanical testing is a useful tool in the field of biomechanics. Classic biomechanics employs mechanical testing for a variety of purposes. For instance, testing may be used to determine the mechanical properties of bone under a variety of loading modes and various conditions including age and disease state. In addition, testing may be used to assess fracture fixation procedures to justify clinical approaches. Mechanical testing may also be used to test implants and biomaterials to determine mechanical strength and appropriateness for clinical purposes. While the information from a mechanical test will vary, there are basics that need to be understood to properly conduct mechanical testing. This book will attempt to provide the reader not only with the basic theory of conducting mechanical testing, but will also focus on providing practical insights and examples.
  • 2013From: CRCnetBASE
    Qing-Hua Qin.
    Introduction to bone materials -- Basic bone remodeling theory -- Multifield internal bone remodeling -- Multifield surface bone remodeling -- Theoretical models of bone modeling and remodeling -- Effect of parathyroid hormone on bone metabolism -- Cortical bone remodeling under mechanical stimulus -- Bone remodelling under pulsed electromagnetic fields and clinical applications -- Experiments.
  • Manuel K. Rausch.
    The mitral valve is one of four heart valves that ensure unidirectional blood flow through the heart. Due to mitral valve failure approximately 44,000 people in the US alone undergo open heart surgery every year. Current treatment options include mitral valve replacement and mitral valve repair, neither of which have shown satisfying long-term success. A deepened understanding of mitral valve mechanics may help in improving current medical device designs and treatment options for mitral valve regurgitation. Here I provide an in depth analysis of the in vivo mechanics of the mitral valve using the theory of finite kinematics and based on this data develop non-linear in silico models of the mitral valve employing the finite element method. Using mechanical metrics such as strain and curvature I reveal the in vivo deformation of the mitral annulus and the mitral leaflet in the healthy, diseased, and repaired mitral valve. Furthermore, in silico I explore the effects of prestrain as well as growth and remodeling on the mechanics of the mitral valve. The results of my in vivo studies extend our current understanding of the healthy mitral valve, reveal new insight into disease characteristics and progressions, and evaluate the efficacy of current device designs. Furthermore, results from the in silico studies provide improved means to simulate mitral valve mechanics and predict long term adaptation for basic science research and medical device design. In conclusion, with the current work I take a large step toward a deepened understanding of mitral valve mechanics that may help to optimize medical device designs and treatment options.
  • 2017From: Wiley
    edited by Simon C. F. Rawlinson.
    Extracellular Matrix Structure and Stem Cell Mechanosensing / Nicholas D Evans, Camelia G Tusan -- Molecular Pathways of Mechanotransduction / Hamish T J Gilbert, Joe Swift -- Sugar-Coating the Cell / Stefania Marcotti, Gwendolen C Reilly -- The Role of the Primary Cilium in Cellular Mechanotransduction / Kian F Eichholz, David A Hoey -- Mechanosensory and Chemosensory Primary Cilia in Ciliopathy and Ciliotherapy / Surya M Nauli, Rinzhin T Sherpa, Caretta J Reese, Andromeda M Nauli -- Mechanobiology of Embryonic Skeletal Development / Andrea S Pollard, Andrew A Pitsillides -- Modulating Skeletal Responses to Mechanical Loading by Targeting Estrogen Receptor Signaling / Gabriel L Galea, Lee B Meakin -- Mechanical Responsiveness of Distinct Skeletal Elements / Simon C F Rawlinson -- Pulmonary Vascular Mechanics in Pulmonary Hypertension / Zhijie Wang, Lian Tian, Naomi C Chesler -- Mechanobiology and the Kidney Glomerulus / Franziska Lausecker, Christoph Ballestrem, Rachel Lennon -- Dynamic Remodeling of the Heart and Blood Vessels / Ken Takahashi, Hulin Piao, Keiji Naruse -- Aortic Valve Mechanobiology / K Jane Grande-Allen, Daniel Puperi, Prashanth Ravishankar, Kartik Balachandran -- Testing the Perimenopause Ageprint using Skin Visoelasticity under Progressive Suction / Gérald E Piérard, Claudine Piérard-Franchimont, Ulysse Gaspard, Philippe Humbert, Sébastien L Piérard -- Mechanobiology and Mechanotherapy for Skin Disorders / Chao-Kai Hsu, Rei Ogawa -- Mechanobiology and Mechanotherapy for Cutaneous Wound-Healing / Chenyu Huang, Yanan Du, Rei Ogawa -- Mechanobiology and Mechanotherapy for Cutaneous Scarring / Rei Ogawa, Chenyu Huang -- Mechanobiology and Mechanotherapy for the Nail / Hitomi Sano, Rei Ogawa -- Bioreactors / James R Henstock, Alicia J El Haj -- Cell Sensing of the Physical Properties of the Microenvironment at Multiple Scales / Julien E Gautrot -- Predictive Modeling in Musculoskeletal Mechanobiology / Hanifeh Khayyeri, Hanna Isaksson, Patrick J Prendergast -- Porous Bone Graft Substitutes / Charlie Campion, Karin A Hing -- Exploitation of Mechanobiology for Cardiovascular Therapy / Winston Elliott, Amir Keshmiri, Wei Tan.
  • Craig J. Goergen.
    The aorta is the largest blood vessel in the body, responsible for carrying blood from the heart directly to most major organs and ending at the iliac arteries which feed the lower extremities. This elastic vessel provides much of the vascular system's compliance and is composed of a heterogeneous mixture of smooth muscle cells, collagen, and elastin. The general purpose of our work has been to use in vivo imaging to determine abdominal aortic dynamics in a variety of healthy and diseased cases. First, a cross-species analysis in mice, rats, rabbits, pigs and humans showed with M-mode ultrasound that infrarenal abdominal aortic motion was similar in animals and humans, regardless of aortic size. Greater anterior than posterior wall motion was observed and aortic wall displacement increased linearly with diameter. Next, cardiovascular abnormalities in a recently developed mouse model for Williams-Beuren Syndrome (WBS) were investigated. WBS is a rare genetic disorder caused by a heterozygous 1.5-megabase deletion, which typically includes the elastin gene. In this study, we showed that Wbs mice have hypertension, reduced in vivo cyclic strain, and fragmented medial elastin sheets - all characteristics similar to human WBS. These data provide insight into the genotype-phenotype relationship between elastin levels, aortic stiffness, and the cardiovascular abnormalities associated with WBS and other microdeletion syndromes. Finally, the biomechanical influences on murine models of abdominal aortic aneurysms (AAA), a pathological dilation of the abdominal aorta, were investigated using magnetic resonance imaging. From this work, we showed that the location of aneurysm development may be correlated with the location of maximum abdominal aortic curvature in angiotensin II-induced murine AAAs. This model consistently forms abdominal aneurysms with repeatable leftward vessel expansion above the renal arteries. Our work has shown that this leftward saccular shape is likely influenced by leftward suprarenal aortic curvature and motion. Histological analysis provided evidence for degradation of medial elastin at one focal location on the left side of the vessel, with a majority of animals also developing an adventitial hematoma at a similar circumferential location. Conversely, elastase-induced infrarenal murine AAAs do not form in a location of high vessel curvature and do not expand in one general direction. This work will help to further our understanding of the role mechanics may play in AAA formation, progression, and eventual rupture.
  • 2003Click fulltext button, Click guest acess (upper right) and Search for standard number 13485From: ANSI
    Also available: Print – 2003
  • 2006.From: CRCnetBASE
    edited by Joseph D. Bronzino.
    Infrared imaging applied to dentistry -- Use of infrared imaging in veterinary medicine -- Standard procedures for infrared imaging in medicine -- Infrared detectors and detector arrays -- Infrared camera characterization -- Infrared camera and optics for medical applications -- sect. IV. Medical informatics. Hospital information systems: their function and state -- Computer-based patient records -- Overview of standards related to the emerging health care information infrastructure -- Introduction to informatics and nursing -- Non-AI decision making -- Medical informatics and biomedical emergencies: new training and simulation technologies for first responders -- sect. V. Biomedical sensors. Physical measurements -- Biopotential electrodes -- Electrochemical sensors -- Optical sensors -- Bioanalytic sensors -- Biological sensors for diagnostics -- sect. VI. Medical instruments and devices. Biopotential amplifiers -- Bioelectric impedance measurements -- Implantable cardiac pacemakers -- Medical instruments and devices used in the home -- Virtual instrumentation: applications in biomedical engineering -- sect. VII. Clinical engineering. Clinical engineering: evolution of a discipline -- Management and assessment of medical technology -- Risk factors, safety, and management of medical equipment -- Clinical engineering program indicators -- Quality of improvement and team building -- A standards primer for clinical engineers -- Regulatory and assessment agencies -- Applications of virtual instruments in health care -- sect. VIII. Ethical issues associated with the use of medical technology. Beneficence, nonmaleficence, and medical technology -- Ethical issues related to clinical research. Noninvasive arterial blood pressure and mechanics -- Cardiac output measurement -- External defibrillators -- Implantable defibrillators -- Implantable stimulators for neuromuscular control -- Respiration -- Mechanical ventilation -- Essentials of anesthesia delivery -- Electrosurgical devices -- Biomedical lasers -- Instrumentation for cell mechanics -- Blood glucose monitoring -- Atomic force microscopy: probing biomolecular interactions -- Parenteral infusion devices -- Clinical laboratory: separation and spectral methods -- Clinical laboratory: nonspectral methods and automation -- Noninvasive optical monitoring -- Sect. I. Biomedical signal analysis. Biomedical signals: origin and dynamic characteristics, frequency-domain analysis -- Digital biomedical signal acquisition and processing -- Compression of digital biomedical signals -- Time-frequency signal representations for biomedical signals -- Wavelet (time-scale) analysis in biomedical signal processing -- Higher-order spectral analysis -- Neural networks in biomedical signal processing -- complexity, scaling, and fractals in biomedical signals -- Future directions: biomedical signal processing and networked multimedia communications -- sect. II. Imaging. X-ray -- Computed tomography -- Magnetic resonance imaging -- Nuclear medicine -- Ultrasound -- Magnetic resonance microscopy -- Positron-emission tomography (PET) -- Electrical impedance tomography -- Medical applications of virtual reality technology -- Sect. III. Infrared imaging. Advances in medical infrared imaging -- The historical development of thermometry and thermal imaging in medicine -- Physiology of thermal signals -- Quantitative active dynamic thermal IR-imaging and thermal tomography in medical diagnostics -- Thermal texture maps (TTM): concept, theory, and applications -- IR imagers as fever monitoring devices: physics, physiology, and clinical accuracy -- Infrared imaging of the breast - an overview -- Functional infrared imaging of the breast: historical perspectives, current applications, and future considerations -- Detecting breast cancer from thermal infrared images by asymmetry analysis -- Advanced thermal image processing -- Biometrics: face recognition in thermal infrared -- Infrared imaging for tissue characterization and function -- Thermal imaging in diseases of the skeletal and neuromuscular systems -- Functional infrared imaging in clinical applications -- Thermal imaging in surgery --
  • 2010From: WHO
    Also available: Print – 2010
  • 2012From: Atypon
    Binseng Wang.
    In addition to being essential for safe and effective patient care, medical equipment also has significant impact on the income and, thus, vitality of healthcare organizations. For this reason, its maintenance and management requires careful supervision by healthcare administrators, many of whom may not have the technical background to understand all of the relevant factors. This book presents the basic elements of medical equipment maintenance and management required of healthcare leaders responsible for managing or overseeing this function. It will enable these individuals to understand their professional responsibilities, as well as what they should expect from their supervised staff and how to measure and benchmark staff performance against equivalent performance levels at similar organizations. The book opens with a foundational summary of the laws, regulations, codes, and standards that are applicable to the maintenance and management of medical equipment in healthcare organizations. Next, the core functions of the team responsible for maintenance and management are described in sufficient detail for managers and overseers. Then the methods and measures for determining the effectiveness and efficiency of equipment maintenance and management are presented to allow performance management and benchmarking comparisons. The challenges and opportunities of managing healthcare organizations of different sizes, acuity levels, and geographical locations are discussed. Extensive bibliographic sources and material for further study are provided to assist students and healthcare leaders interested in acquiring more detailed knowledge.
  • 2007From: CRCnetBASE
    edited by Jack M. Winters, Molly Follette Story.
  • John G. Webster, editor ; contributing authors, John W. Clark, Jr. ... [et al.].
    Basic concepts of medical instrumentation / Walter H. Olson -- Basic sensors and principles / Robert A. Peura and John G. Webster -- Amplifiers and signal processing / John G. Webster -- The origin of biopotentials / John W. Clark, Jr. -- Biopotential electrodes / Michael R. Neuman -- Biopotential amplifiers / Michael R. Neuman -- Blood pressure and sound / Robert A. Peura -- Measurement of flow and volume of blood / John G. Webster -- Measurements of the respiratory system / Frank P. Primiano, Jr. -- Chemical biosensors / Robert A. Peura -- Clinical laboratory instrumentation / Lawrence A. Wheeler -- Medical imaging systems / Melvin P. Siedband -- Therapeutic and prosthetic devices / Michael R. Neuman -- Electrical safety / Walter H. Olson.
  • Desmond J. Sheridan.
    Status: Not Checked OutLane Catalog Record
  • 2008From: CRCnetBASE
    A.R. Jha.
  • v. 1-3, 2006.From: CRCnetBASE
    v. 2, 2006From: CRCnetBASE
    v. 3, 2006From: CRCnetBASE
    2006Click LINK above for Print location/circulation status.
    edited by Mohamed Gad-el-Hak.
    [v. 1]. MEMS, introduction and fundamentals -- [v. 2]. MEMS, design and fabrication -- [v. 3]. MEMS, applications.
  • v. 1-2, 2010.From: CRCnetBASE
    v. 2From: CRCnetBASE
    edited by Christina D. Smolke.
    [v. 1.] Fundamentals -- [v. 2.] Tools and applications.
  • Angela Ruohao Wu.
    Protein--DNA interactions are responsible for numerous critical cellular events: for example, gene expression and silencing are mediated by transcription factor protein binding and histone protein modifications, and DNA replication and repair rely on site specific protein binding. Chromatin immunoprecipitation (ChIP) is the only molecular assay that directly determines, in a living cell, the binding association between a protein of interest and specific genomic loci. It is an indispensible tool in the biologists' toolbox, but the many limitations of this technique prevent broad adoption of ChIP in biological studies. The typical ChIP assay can take up to one week to complete, and the process is technically tricky, yet tedious. ChIP assay yields are also low, thus requiring on the order of millions to billions of cells as starting material, which makes the assay unfeasible for studies on rare or precious samples. Cancer stem cells (CSCs), for instance, are obtained from primary tumors, and FACS sorting of the dissociated tumor cells rarely yields more than ~100,000 CSCs per tumor. This thesis describes the microfluidics-based strategies for performing ChIP. The first design for a microfluidic ChIP design utilizes the automation and scalability aspects of microfluidics to reduce both total and hands-on assay time, and improve throughput. It can take chromatin prepared using any existing ChIP protocol as input, and generate ChIP-qPCR results in just 1 day. The device is shown to be comparable to existing ChIP protocols, and can detect cellular epigenetic changes induced by external cytokine stimulants. It was used to investigate transcription factor binding dynamics in an aging-related pathway, and was able to link transcription factor binding to local changes in histone modifications. The second design of the microfluidic ChIP platform focuses on addressing the cell number requirements of ChIP. In addition to reducing assay time through automation, this design incorporates microfluidic designs that allow whole fixed cells as input, and enables automated ChIP from as few as 2,000 cells. Finally, using this high-sensitivity ChIP device in conjunction with next-generation sequencing technology, a protocol for determining genome-wide epigenetic landscapes from as few as 2,000 cells is developed, with the ultimate goal of performing protein-DNA association studies on CSCs.
  • 2014From: Wiley
    edited by Dr. Mahmoud Torabinejad.
    Pulp and periradicular pathways, pathosis, and closure / Mahmoud Torabinejad -- Chemical properties of mineral trioxide aggregate / David W. Berzins -- Physical properties of mineral trioxide aggregate / Lawrence Gettleman and Ricardo Caicedo -- Use of MTA in vital pulp therapy / Till Dammaschke, Joe Camp, and George Bogen -- Use of MTA in teeth with necrotic pulps and open apices / Shahrokh Shabahang and David Witherspoon -- Use of MTA in regenerative endodontics / Mahmoud Torabinejad, Robert P. Corr, and George T.J. Huang -- Use of MTA as root perforation repair / Mahmoud Torabinejad and Ron Lemon -- Root canal obturation with MTA / George Bogen, Ingrid Lawaty, and Nicholas Chandler -- Use of MTA as root end filling / Seung-Ho Baek and Su-Jong Shin -- Calcium silicate-based cements / Masoud Parirokh and Mahmoud Torabinejad.
  • Kunal Kumar Ghosh.
    Fluorescence microscopy has emerged as a workhorse of modern biology and medicine. Fluorescence microscopes are indispensable as tools for basic research in the biological sciences, enable platforms for drug discovery in the biotechnology and pharmaceutical industries, and are increasingly aiding in several clinical diagnostic applications. However, state-of-the-art fluorescence microscopes remain bulky and expensive benchtop instruments with an architecture that impedes usage in certain applications and a cost that precludes adoption in large numbers. For example existing benchtop fluorescence microscopes are not amenable for in vivo imaging in animals, with the mouse being a common animal subject, especially during awake, active behavior. For the field of neuroscience in particular, such an experimental capability permits correlating causal cellular processes with animal behavior -- a longstanding goal. Inspired by this need, we have designed a miniature fluorescence microscope that can be borne by a mouse during active behavior. We have fabricated several such microscopes, each less than 2 g in mass, perhaps heralding a transformation in fluorescence microscopy from today's bulky and expensive benchtop paradigm towards miniature and mass-producible devices. Our fabricated microscopes achieve 2.5 μm spatial resolution imaging fields-of-view up to 800 μm x 600 μm at 36 Hz, suitable for cellular-level imaging at high temporal resolution. To facilitate design of our microscopes, we have adopted a modeling-based microscope design methodology, akin to that used in the design of integrated circuits, and have developed a set of tools to model the microscope as an integrated device from the specimen to final digital image. We have experimentally validated fabricated microscopes for in vivo brain imaging in freely behaving mice, specifically using them for: 1) Imaging cerebellar vasculature and hemodynamics during activity; and 2) Imaging cerebellar Purkinje cell Calcium dynamics, analyzing spiking activity of populations of neurons with single neuron specificity during different motor behaviors. We also show how several of these microscopes imaging in parallel can enable new high-throughput imaging solutions with the potential to achieve broad impact, specifically demonstrating high-throughput image-based assays for: 1) Mutant phenotype screening in genetic model species such as the zebrafish; and 2) Multiple well plate cell analyses. Finally, we use a Bayesian iterative image restoration algorithm to enhance acquired microscope images, and show how spatial resolution can be further scaled into the sub-micron regime by leveraging advances in digital image sensing technology in conjunction with our post-acquisition image restoration algorithm.
  • 2015From: Atypon
    Ghahari, Alireza; Enderle, John D.
  • 2014From: Atypon
    Alireza Ghahari, John D. Enderle.
    There are five different types of eye movements: saccades, smooth pursuit, vestibular ocular eye movements, optokinetic eye movements, and vergence eye movements. The purpose of this book series is focused primarily on mathematical models of the horizontal saccadic eye movement system and the smooth pursuit system, rather than on how visual information is processed. A saccade is a fast eye movement used to acquire a target by placing the image of the target on the fovea. Smooth pursuit is a slow eye movement used to track a target as it moves by keeping the target on the fovea. The vestibular ocular movement is used to keep the eyes on a target during brief head movements. The optokinetic eye movement is a combination of saccadic and slow eye movements that keeps a full-field image stable on the retina during sustained head rotation. Each of these movements is a conjugate eye movement, that is, movements of both eyes together driven by a common neural source. A vergence movement is a non-conjugate eye movement allowing the eyes to track targets as they come closer or farther away. In Part 1, early models of saccades and smooth pursuit are presented. A number of oculomotor plant models are described therein beginning with the Westheimer model published in 1954, and up through our 1995 model involving a 4th-order oculomotor plant model. In Part 2, a 2009 version of a state-of-the-art model is presented for horizontal saccades that is 3rd-order and linear, and controlled by a physiologically based time-optimal neural network. In this book, a multiscale model of the saccade system is presented, focusing on the neural network. Chapter 1 summarizes a whole muscle model of the oculomotor plant based on the 2009 3rd-order and linear, and controlled by a physiologically based time-optimal neural network. Chapter 2 presents a neural network model of biophysical neurons in the midbrain for controlling oculomotor muscles during horizontal human saccades. To investigate horizontal saccade dynamics, a neural circuitry, including omnipause neuron, premotor excitatory and inhibitory burst neurons, long lead burst neuron, tonic neuron, interneuron, abducens nucleus, and oculomotor nucleus, is developed. A generic neuron model serves as the basis to match the characteristics of each type of neuron in the neural network. We wish to express our thanks to William Pruehsner for drawing many of the illustrations in this book.
  • 2010From: Atypon
    John D. Enderle, Wei Zhou.
    There are five different types of eye movements: saccades, smooth pursuit, vestibular ocular eye movements, optokinetic eye movements, and vergence eye movements. The purpose of this book is focused primarily on mathematical models of the horizontal saccadic eye movement system and the smooth pursuit system, rather than on how visual information is processed. A saccade is a fast eye movement used to acquire a target by placing the image of the target on the fovea. Smooth pursuit is a slow eye movement used to track a target as it moves by keeping the target on the fovea. The vestibular ocular movement is used to keep the eyes on a target during brief head movements. The optokinetic eye movement is a combination of saccadic and slow eye movements that keeps a full-field image stable on the retina during sustained head rotation. Each of these movements is a conjugate eye movement, that is, movements of both eyes together driven by a common neural source. A vergence movement is a non-conjugate eye movement allowing the eyes to track targets as they come closer or farther away. In this book, a 2009 version of a state-of-the-art model is presented for horizontal saccades that is 3rd-order and linear, and controlled by a physiologically based time-optimal neural network. The oculomotor plant and saccade generator are the basic elements of the saccadic system. The control of saccades is initiated by the superior colliculus and terminated by the cerebellar fastigial nucleus, and involves a complex neural circuit in the mid brain. This book is the second part of a book series on models of horizontal eye movements.
  • Samuel Richard Hamner.
    Human running is a bouncing gait during which the body mass center slows and lowers during the first half of the stance phase; muscle forces then accelerate the mass center forward and upward in the second half of stance. Muscle-driven simulations of running allow us to determine how muscle forces give rise to the accelerations of the body mass center. Before this dissertation, it remained unclear how muscle forces modulate accelerations of the mass center at various running speeds as three-dimensional, muscle-driven simulations of running had yet been created or analyzed. Thus the goal of this dissertation was to better understand the functional role of muscles by generating the first three-dimensional, muscle-driven simulation of the running gait cycle and quantifying how muscles contribute to vertical and fore-aft accelerations of the body mass center over a range of running speeds. Initially, I created a three-dimensional, muscle-driven simulation of a single subject running at a single speed and quantitatively described how individual muscles accelerated the subject's body mass center. The simulation was generated with a musculoskeletal model driven by 92 musculotendon actuators of the lower extremities and torso. The model also included torque-driven arms, which allowed me to investigate the contributions of arm motion to running dynamics. This single simulation revealed that during the first half of the stance phase, quadriceps was the largest contributor to backward and upward accelerations of the mass center. During the second half of stance, the soleus and gastrocnemius muscles were the greatest contributors to forward and upward accelerations of the mass center. To determine how individual muscle forces in these simulations acted to generate the ground reaction force, and the resulting accelerations of the body mass center, it is necessary to model ground contact. The accelerations computed in such simulation analyses are sensitive to the model used to represent contact between the foot and ground. To have confidence in our ability to interpret muscle function, a ground contact model should be able to reproduce experimentally measured ground reaction forces and moments. I show that a rolling constraint accurately reproduces the measured ground reaction forces and moments in an induced acceleration analysis of muscle-driven simulations for walking, running, and crouch gait. I also evaluated other contact models used in previous studies (e.g., point and weld constraints) to illustrate that these models can produce inaccurate reaction moments and lead to contradictory interpretations of muscle function, including the contribution of major muscles, like the vasti and soleus, to fore-aft and upward mass center accelerations. To determine how muscles modulate ground reaction forces and mass center accelerations over a range of running speeds, I created muscle-driven simulations of ten subjects running at four speeds: 2 m/s, 3 m/s, 4 m/s, and 5 m/s. An induced acceleration analysis was used to determine the contribution of each muscle to body mass center accelerations. Analysis of the simulations revealed that soleus provides the greatest upward mass center acceleration at all running speeds, with a peak upward acceleration of 19.8 m/s/s (i.e., the equivalent of approximately 2.0 body weights of ground reaction force) at 5.0 m/s. Soleus also provided the greatest contribution to forward mass center acceleration, with contributions increasing from 2.5 m/s/s to 4.0 m/s/s as running speed increased from at 2.0 m/s to 5.0 m/s. Quadriceps produced the largest backward mass center acceleration; at 5.0 m/s peak contribution from quadriceps was 80% of total peak backward acceleration. At higher running speeds, greater velocity of the legs produced larger vertical angular momentum about the mass center, while vertical angular momentum from arm swing simultaneously increased to counterbalance that of the legs. The ability to reproduce the results of a study is an essential principle of the scientific method. However, reproducing results of simulation studies remains challenging because the software, models, and data used to create and analyze the simulations are generally not freely available. Thus, to promote the utilization and acceptance of simulations in movement science, I have provided open-access to the models, data, and subject-specific simulations developed for this dissertation at and The data and simulations can be visualized and results can be reproduced in OpenSim (, a freely-available biomechanics simulation package.
  • 2005From: NCBI Bookshelf
    [prepared by NCBI].
    "This book contains information on how to use My NCBI, a tool developed by the National Center for Biotechnology Information (NCBI) that replaces a previous feature called Cubby. This documentation is part of a growing collection of searchable help documents being produced for several resources available at NCBI."
  • 2012From: Springer
    Eran Zahavy ... [et al.], editors.
    Biomolecule/nanomaterial hybrid systems for nanobiotechnology -- Superresolution optical fluctuation imaging (SOFI) -- Application of nanoparticles for the detection and sorting of pathogenic bacteria by flow-cytometry -- Advancing nanostructured porous si-based optical transducers for label free bacteria detection -- Gold fibers as a platform for biosensing -- Surface-enhanced raman spectroscopy of organic molecules adsorbed on metallic nanoparticles -- Quantum dots and fluorescent protein FRET-based biosensors -- Semiconductor quantum dots as FRET acceptors for multiplexed diagnostics and molecular ruler application -- Assembly and microscopic characterization of DNA origami structures -- DNA nanotechnology -- Role of carbohydrate receptors in the macrophage uptake of dextran-coated iron oxide nanoparticles -- Toxicity of gold nanoparticles on somatic and reproductive cells -- Ultrasound activated nano-encapsulated targeted drug delivery and tumour cell poration -- Ultrasound mediated localized drug delivery -- Sonochemical proteinaceous microspheres for wound healing -- Alendronate liposomes for antitumor therapy: activation of [gamma] [delta] T cells and inhibition of tumor growth.
    Also available: Print – 2012
  • Kosar Baghbani Parizi.
    Biosensors are used for detecting biological molecules such as proteins and nucleic acids. Traditional techniques, such as Enzyme-linked Immuno-sorbent Assay (ELISA) are sensitive but require several hours to yield results and usually require attaching a fluorophore molecule to the target molecule. The creation of label-free, fast, more accurate and integrated detection devices is imperative and we are increasingly looking to the nano-world for such technology. Micro-machined biosensors that employ electrical detection are now being developed. Impedance biosensor is a class of electrical biosensors that shows promise for point-of-care and other applications due to low cost, ease of miniaturization and label-free operation. Critically important component of any bio-detection system is the core biosensor device. Here we have designed, developed, tested and optimized a nano-biosensor that is configured and fabricated using silicon process technology. Electrical nano-sensors rely on label free detection of biochemical reactions in real time. These electrical sensors can measure impedance change as an electrical 'signature' of the nucleic acid or proteins interactions via a number of different mechanisms that are determined by their specific design and geometry. These nano-sensor designs will lead to an improvement in sensitivity by increasing the signal to noise ratio which results in more accurate readings through a reduction of spurious signal generation. We have developed a nano-bridge biosensor with a depletion-mode silicon 'nano-resistor' for the detection of DNA and protein at very low concentrations. In order to achieve higher sensitivity the sensing surface area is significantly increased as well as doping profile of impurities in silicon nano-resistor is optimized.. In contrast to a conventional Si enhancement mode MOSFET, this device behaves similar to depletion mode MOSFET, thereby it is always in the "ON" state, and no threshold voltage is needed to turn it into the active sensing mode. In addition signal calibration is not required due to a linear I-Vg characteristic at low Vg. The nano-bridge design has been optimized for maximal [Delta]I/I. The linearity of the response shows that the design will allow measurement of charge induced changes over a wide range with no threshold and high signal to noise ratios. To increase sensing throughput we will flow the solution containing the target molecules over an array of such sensing structures each of which has its own integrated readout circuitry that will offer 'real-time' detection (i.e. several minutes) of un-labeled molecules without sacrificing sensitivity. These electrical nano-biosensors are much more suited for the development of affordable bio-detection platforms, because they do not require expensive labeling reagents, rely on fabrication processes well established in the semiconductor IC industry, do not need bulky, expensive optical readout systems, and more importantly, can generate data on real time. One of the most important issues in the design of these sensor devices is to achieve high signal to noise ratio in order to make them amenable to sensitive detection of biological events, molecular interactions or chemical reactions. In order to improve the sensitivity and signal to noise ratio and to address the need for high density array construction we have designed and partially tested a nano-scale sensor with spatial structure, type and signal detection principles. The nano-bridge sensor is a double-gated depletion-mode semiconductor nano-resistive sensor. The structure and fabrication of these sensors will lead to improved sensitivity and greater accuracy of DNA hybridization detection up to 10 fM.
  • Robert A. Freitas.
    Status: Not Checked OutLane Catalog Record
    v. 1. Basic capabilities
  • Chong Xie.
    Abstract: The small scale of nano-materials makes them one of the best man-made candidates to interact with biological systems at subcellular or even molecular level. It has been the focal point of the research interests to interfacing live cells with one dimensional nanostructures, such as nanowires and nanopillars. In my Phd research, I have utilized nanopillar based structures and devices to interface biological cells electrically, optically and mechanically. 1. We achieve improved electric interface between biological cells and solid state device by using arrays of vertically aligned nanopillar electrodes. Their tight attachment to the cell membrane allows us to acquire intracellular-like action potential signals non-destructively from cultured cardiomyocytes, which is responsible for various important cellular functions. 2. We demonstrate below-the-diffraction-limit observation volume in vitro and inside live cells by using vertically aligned silicon dioxide nanopillars. With a diameter much smaller than the wavelength of visible light, a transparent silicon dioxide nanopillar embedded in a nontransparent substrate restricts the propagation of light and affords evanescence wave excitation along its vertical surface. This effect creates highly-confined illumination volume that selectively excites fluorescence molecules in the vicinity of the nanopillar. We show that this nanopillar illumination can be used for in vitro single molecule detection with high fluorescence background. In addition, we demonstrate that vertical nanopillars interface tightly with live cells and function as highly localized light sources inside the cell. Furthermore, chemical modification of the nanopillar surface provides a unique way to locally recruit proteins of interest and simultaneously observe their behavior within the complex, crowded environment of the cell. 3. We engineer and fabricate vertically nanopillar arrays, and culture various types of cells atop. We study the cell growth pattern in presence of nanopillar arrays, including attachment, migration, etc. We also design patterned nanopillar arrays and utilized them to guide and control cell growth via cell-nanopillar interaction.
  • 2009From: Springer
    [edited by] Donglu Shi.
    Stem Cells and Nanostructured Materials / Vince Beachley and Xuejun Wen -- Biomedical Polymer Nanofibers for Emerging Technology / Kwideok Park, Won Ho Park, Jun Sik Son and Dong Keun Han -- Nanoscale Mechanisms for Assembly of Biomaterials / Zhijie Sui and William L. Murphy -- Fabrication and Assembly of Nanomaterials and Nanostructures for Biological Detections / Qingkai Yu and Jie Lian -- Nanostructured Materials Constructed from Polypeptides / Peng Jing, Jangwook P. Jung and Joel H. Collier -- Photoluminescent Carbon Nanomaterials: Properties and Potential Applications / Yaping Sun, Fushen Lu, Xin Wang, Li Cao and Yi Lin, et al. -- Microwave-assisted Synthesis and Processing of Biomaterials / Yingjie Zhu and Jiang Chang -- Characterizing Biointerfaces and Biosurfaces in Biomaterials Design / Kalpana S. Katti, Devendra Verma and Dinesh R. Katti -- Carbon Nanotubes for Electrochemical and Electronic Biosensing Applications / Ningyi Liu, Qing Zhang, Mary B Chan-Park, Changming Li and Peng Chen -- Heparin-Conjugated Nanointerfaces for Biomedical Applications / Ki Dong Park, Yoon Ki Joung, Jin Woo Bae and Dong Hyun Go -- Inorganic Nanoparticles for Biomedical Applications / Mei Chee Tan, Gan Moog Chow, Lei Ren and Qiqing Zhang -- Nano Metal Particles for Biomedical Applications / Kyung A. Kang, Bin Hong and Hanzhu Jin -- Micro- and Nanoscale Technologies in High-Throughput Biomedical Experimentation / Vikramaditya G. Yadav, Mark D. Brigham, Ling Yibo, Christopher Rivest and Utkan Demirci, et al. -- Delivery System of Bioactive Molecules for Regenerative Medicine / Gilson Khang, Yoon Sun Jung, Soon Hee Kim, Moon Suk Kim and Hai Bang Lee -- Modification of Nano-sized Materials for Drug Delivery / Tao Xu, Heather L. Nichols, Ning Zhang and Xuejun Wen -- Polymeric Nano Micelles as a Drug Carrier / Moon Suk Kim, Hyun Hoon, Gilson Khang and Hai Bang Lee -- DNA Nanotechnology / Junping Zhang and Roger J. Narayan -- Nanoscale Bioactive Surfaces and Endosseous Implantology / Yunzhi Yang, Yongxing Liu, Sangwon Park, Hyunseung Kim and Kwangmin Lee, et al. -- Carbon Nanotube Smart Materials for Biology and Medicine / Yeo Heung Yun, Vesselin N. Shanov, Adam Bange, William R. Heineman and H. Brian Halsall, et al. -- Microscopic Modeling of Phonon Modes in Semiconductor Nanocrystals / Wei Cheng, Shangfen Ren and David T. Marx -- Fracture Processes in Advanced Nanocrystalline and Nanocomposite Materials / I. A. Ovid'ko -- Synthesis, Properties and Application of Conducting PPY Nanoparticles / Xingui Li, Meirong Huang and Yunbin Xie -- Field Emission of Carbon Nanotubes / Baoqing Zeng and Zhifeng Ren -- Flexible Dye-Sensitized Nano-Porous Films Solar Cells / Dongshe Zhang, Tony Pereira, Torsten Oekermann, Katrin Wessels and Changyong Qin, et al. -- Magnetic Nanofluids: Synthesis and Structure / L. Vékás, M. V. Avdeev and Doina Bica.
  • 2008From: Springer Protocols
    edited by Ehud Gazit, Ruth Nussinov.
    Molecular design of performance proteins with repetitive sequences, recombinant flagelliform spider silk as basis for biomaterials / Charlotte Vendrely, ... [et al.] -- Creation of hybrid nanorods from sequences of natural trimeric fibrous proteins by use of the fibritin trimerization motif / Katerina Papanikolopoulou, Mark J. van Raaij, Anna Mitraki -- Leucine zipper as a building block for self-assembled protein fibers / Maxim G Ryadnov, David Papapostolou, Derek N Woolfson -- Bioimimetic synthesis of bimorphic nanostructures / Joseph M. Slocik, Rajesh R. Naik -- Synthesis and primary characterization of self-assembled peptide-based hydrogels / Radhika P. Nagarkar and Joel P. Schneider -- Periodic assembly of nanospecies on repetitive DNA sequences generated on gold nanoparticles by rolling circle amplification / Weian Zhao, Michael A. Brook, Yingfu Li -- Protocols for the In Silico design of RNA nanostructures / Bruce A. Shapiro, ... [et al.] -- Self-assembly of fused homo-oligomers to create nanotubes / Idit Buch, ... [et al.] -- Computational methods in nanostructure design, replica exchange simulations of self-assembling peptides / Giovanni Bellesia, Sotiria Lampoudi, Joan-Emma Shea -- Modeling amyloid fibril formation / Maarten G. Wolf, Jeroen van Gestel, Simon W. de Leeuw -- Computer modeling in biotechnology / Aleksei Aksimentiev, ... [et al.] -- What can we learn from highly-connected 7-rich structures for structural interface design / Ugur Emekli, ... [et al.].
  • 2007From: CRCnetBASE
    edited by Tuan Vo-Dinh.
  • Thomas D. Coates Jr., Ph.D.
  • 2016From: Wiley
    edited by Robert K. Shepherd.
    The historical foundation of bionics / Nick Donaldson and Giles S. Brindley -- Development of stable long-term electrode tissue interfaces for recording and stimulation / Jens Schouenborg -- Electrochemical principles of safe charge injection / Stuart F. Cogan, David J. Garrett and Rylie A. Green -- Principles of recording from an electrical stimulation of neural tissue / James B. Fallon and Paul M. Carter -- Wireless neurotechnology for neural prostheses / Arto Nurmikko, David Borton and Ming Yin -- Preclinical testing of neural prostheses / Douglas McCreery -- Auditory and visual neural prostheses / Robert K. Shepherd, Peter M. Seligman, Mohit N. Shivdasani -- Neurobionics : treatments for disorders of the central nervous system / Hugh McDermott -- Brain computer interfaces / David M. Brandman and Leigh R. Hochberg.
  • 2008From: CRCnetBASE
    edited by Daniel J. DiLorenzo, Joseph D. Bronzino.
    Comparing electrodes for use as cortical control signals : tiny tines, tiny wires, or tiny cones on wires : which is best? / Philip R. Kennedy -- Neuromotor prosthetics : design and future directions / Mijail D. Serruya, Sung-Phil Kim, and John P. Donoghue -- Transcutaneous FES for ambulation : the parastep system / Daniel Graupe -- Development of a multifunctional 22-channel functional electrical stimulator for paraplegia / Ross Davis ... [et al.] -- An implantable bionic network of injectable neural prosthetic devices : the future platform for functional electrical stimulation and sensing to restore movement and sensation / Joseph Schulman ... [et al.] -- History and overview of neural engineering / Daniel DiLorenzo and Robert E. Gross -- Cellular mechanisms of action of therapeutic brain stimulation / Zelma Kiss and Trent Anderson -- Neuromodulation : current trends in interfering with epileptic seizures / Ana Luisa Velasco ... [et al.] -- Responsive neurostimulation for epilepsy--neurosurgical experience : patient selection and implantation technique / Kostas N. Fountas and Joseph R. Smith -- Responsive neurostimulation for epilepsy : RNS technology and clinical studies / Thomas K. Tcheng and Martha Morrell -- Deep brain stimulation for pain management / Donald E. Richardson -- Spinal cord stimulation for pain management / Allen W. Burton and Phillip C. Phan -- Motor cortex stimulation for pain management / Shivanand P. Lad, Kevin Chao, and Jaimie M. Henderson -- Deep brain stimulation for obsessive compulsive disorder / Wael F. Asaad and Emad N. Eskandar -- Cochlear prostheses : an introduction / Donald K. Eddington -- Visual prostheses / Robert J. Greenberg -- General clinical issues relevant to brain-computer interfaces / Eric C. Leuthardt ... [et al.] -- Implantable brain-computer interfaces : neurosurgical experience and perspective / Roy A.E. Bakay -- Tapping into the spinal cord for restoring function after spinal cord injury / Lisa Guevremont and Vivian K. Mushahwar -- Theory and physiology of electrical stimulation of the central nervous system / Warren M. Grill -- Transient optical nerve stimulation : concepts and methodology of pulsed infrared laser stimulation of the peripheral nerve in vivo / Jonathan D. Wells ... [et al.] -- Transcranial magnetic stimulation of deep brain regions / Yiftach Roth and Abraham Zangen -- Application of neural plasticity for vision restoration after brain damage / Imelda Pasley ... [et al.].
  • v. 1-2, 2009.From: ScienceDirect
    2009From: ClinicalKey
    edited by Elliot S. Krames, P. Hunter Peckham, Ali R. Rezai.
    v. 1. Section I. An introduction to neuromodulation -- Section II. Fundamentals of neuromodulation -- Section IIA. Fundamentals of neuromodulation: mechanisms -- Section III. Biomedical engineering considerations -- Section IV. Neuromodulation for chronic pain -- Section IVA. Periphery and spinal cord electrical stimulation for non-visceral pain -- Section IVB. Infusional therapies for pain -- Section IVC. Brain stimulation for pain v. 2. Section V. Neuomodulation for movement disorders -- Section VI. Neurostimulation for epilepsy -- Section VII. Neuromodulation for psychiatric disorders -- Section VIII. Neuromodulation for functional restoration -- Section IX. Neuromodulation of body organs -- Section IXA. Neuromodulation for cardiovascular disorders -- Section IXB. Neuromodulation for gastrointestinal disorders -- Section IXC. Neuromodulation for urogenital disorders -- Section X. Neuromodulation for emerging applications -- Section XI. Neuromodulation device implant techniques.
  • 2016From: Springer
    David J. Reinkensmeyer, Volker Dietz, editors.
    Part I. Basic framework: motor recovery, learning, and neural impairment -- Part II. Human-machine interaction in rehabilitation practice -- Part III. Robots for upper extremity recovery -- Epilogue: what lies ahead? -- Index.
  • 2012From: CRCnetBASE
    edited by James Giordano.
  • Dongjun Shin.
    The increasing demand for physical interaction between humans and robots has led to an interest in robots whose behavior is guaranteed to be safe when they are in close proximity with humans. However, attaining sufficiently high levels of performance while ensuring safety creates formidable challenges in mechanical design, actuation, sensing, and control. To promote safety without compromising performance, a new actuation concept, referred to as hybrid actuation, has been developed. Since low impedance output at high frequencies is essential for robot safety, while optimal passive stiffness is needed for robot performance, the new actuation approach employs a pneumatic artificial muscle as a macro actuator to provide low-frequency torques. Artificial pneumatic muscles provide high force-to-weight ratio and inherent compliance, both of which allow for low impedance actuation. To compensate for the slow and non-linear dynamics of pneumatic actuation, a small electromagnetic actuator collocated at the robot's joint is employed as a mini actuator, which provides high mechanical bandwidth for high performance without increasing the inertia and size of the manipulator. To achieve the appropriate balance between safety and performance, design methodologies were developed that optimally determine key design parameters such as the required mini motor torque capacity, the joint stiffness introduced by an antagonistic pair of muscles, and the pulley radius. Using a testbed, referred to as the Stanford Safety Robot (S2rho), the hybrid actuation was evaluated for position tracking performance, force tracking performance, and impact behavior. The experimental results demonstrate that by significantly improving control performance with the hybrid actuation over performance with pneumatic muscles alone, while reducing the effective inertia significantly, the competing design objectives of safety and performance can be successfully integrated into a single robotic manipulator. As an extension of the hybrid actuation concept, the new design of dual four-degree-of-freedom robotic arms with torso is presented and detailed descriptions of the design are included.
  • 2013From: Springer
    Nikki P. Lee, C.Y. Cheng, John M. Luk, editors.
    Rising occurrences of various diseases and epidemics have pressurized the already-burdened health system across the globe, and this imposes an unprecedented challenge on our current research in identifying disease-specific biomarkers and molecular targets, in particular for cancers, neurological disorders and unexplained infertility. Despite decades of efforts in deciphering the fundamental biology underlying various diseases at discrete levels using an array of advanced technologies, attempts to identify reliable and disease-indicating markers for detection and biomolecules or cellular structures for targeting are still in vain. This monograph describes and discusses the updated findings in this field with a specific aim to compile prior and recent literature and from there to acquire some insights to facilitate future research to expand our options of understanding, detecting and treating diseases. Among the many possible areas of biomedical research, this content comprises two themes: disease biomarkers and molecular targets. We also cover topics that are more advanced in development to emerging scientific discoveries. In particular, we have included in this monograph concepts on the renovated use of oncofetal molecules in cancer prediction and treatment, the evolving development in cancer biology at the cellular and molecular levels and the recent involvement on new classes of molecules in diseases. We hope that this book can renew established concepts in the field, and at the same time lead to important insights for research and development of drugs, diagnostics, and interventions for managing diseases of unmet medical needs.
  • Cem Albayrak.
    Proteins in all living systems are composed predominantly of 20 natural amino acids, each of which is incorporated by a processive mechanism involving dedicated transfer RNAs and enzymes called aminoacyl-tRNA synthetases. Despite the diversity in protein structure and function, these natural amino acids provide side chains with only limited reactivity. Site-specific incorporation of non-natural amino acids (nnAAs) expands the chemical reactivity of proteins and enables their precise post-translational modification. These nnAAs are incorporated in a manner analogous to natural amino acids. An orthogonal synthetase specific to the nnAA first couples the nnAA to an orthogonal amber suppressor tRNA (o-tRNA). The aminoacylated o-tRNA then forms a three-molecule complex with Ef-Tu and GTP, enters the ribosome, and at an amber stop codon (UAG) in the mRNA, adds the nnAA to the nascent polypeptide chain. Of the more than 30 nnAAs that have been site-specifically incorporated using Escherichia coli-based protein synthesis systems, the Swartz laboratory has been particularly interested in the nnAAs p-azido-L-phenylalanine (pAzF) and p-propargyloxy-L-phenylalanine (pPaF), since proteins containing these nnAAs can be directly coupled using the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. In our laboratory, this technology is used to design unique and effective vaccines and diagnostic agents. Despite the improvements in the versatility and productivity of the cell-free protein synthesis (CFPS) platform, the yields of proteins containing nnAAs (i.e. modified proteins) have been substantially lower than their natural counterparts. The first part of this dissertation summarizes our efforts in improving the current methods for site-specific nnAA incorporation. Supplementing the initial CFPS system with additional o-tRNA doubled the modified protein yields. Titration experiments and turnover calculations suggested that, despite the apparent o-tRNA limitation, the synthetase is the more inefficient orthogonal component. Nonetheless, a convenient and modular method for adequate o-tRNA supply was demonstrated to further improve the efficiency of nnAA incorporation. Using this new method, in which the o-tRNA and the modified protein are produced simultaneously during the CFPS reaction, as much as 1.67 mg/ml full-length and soluble modified super-folder GFP (sfGFP) was obtained. This represents a 6-fold improvement over previous cell-free yields of modified sfGFP. This new method was used then to study nnAA incorporation at twelve different sites in sfGFP using two different o-tRNA sequences. Our results did not confirm the previous trends for the position effect (i.e. variation of modified protein yield with nnAA incorporation position). The use of the o-tRNA that was developed to better recognize the endogenous Ef-Tu decreased the size of the position effect. In addition, the method employing in situ o-tRNA synthesis was extended to the incorporation of the nnAAs into sfGFP at 2 or 3 positions. These proteins were subsequently purified and coupled to synthesize linear and branched protein polymers. After polymerization and removal of the catalyst, the specific activity of the proteins was fully retained. The second part of this dissertation describes our efforts towards developing a new set of orthogonal components from the endogenous tyrosyl tRNA/synthetase pair. A cell-free method was first developed to screen for an orthogonal variant of the E. coli tyrosyl tRNA. 201 potential orthogonal tRNAs were identified out of a library containing 384 tRNA mutants. Eight were more carefully analyzed for orthogonality (i.e. absence of cross-reactivity with E. coli synthetases) and one was identified to be both sufficiently orthogonal and not inhibitory to CFPS. Finally, the in vitro compartmentalization (IVC) method was adapted for the production of sfGFP in emulsion CFPS reactions. A method was also developed to quantify the number of adsorbed genes on a bead by fluorescence using FACS. This protocol promises to be a powerful high-throughput method for screening orthogonal synthetases.
  • 2007From: Springer
    M. Kusano, S. Shioda (eds.).
  • Chuba Benson Oyolu.
    The fate of a cell is largely determined by the unique patterns of gene expression found within it. Complex biological machinery exists within each cell to manipulate chromatin state, and ultimately control gene expression. Developmental processes such as cellular differentiation require very specific chemical signals and environmental conditions. These serve as triggers to put the chromatin modification schemes that produce the resultant patterns of differential gene expression into action, leading to the formation of the cell type of interest. My thesis work is an in depth study of the link between chromatin modification, gene expression, and the unique genetic signatures that characterize distinct cells on unicellular and multi-cellular levels. On the multi-cellular level, I have examined histone modification patterns for their effects on gene activation and repression during human embryonic stem cell differentiation. On the unicellular level, I have worked with a variety of cell types to ascertain the degree of individuality that exists between single members of relatively homogenous cell groups while simultaneously looking for housekeeping gene expression signatures that can be used to classify each cell type into a unique group. To further elucidate the patterns of gene expression found within cell groups and the single cells that comprise them, I have worked to develop new computational methods that produce visual aids to elucidate gene expression signatures of single cells and cell groups.
  • Elena Kaye.
    Magnetic resonance imaging (MRI) guided focused ultrasound (MRgFUS) is a promising non-invasive and non-ionizing therapy in which the acoustic energy penetrates to the target through the intact surrounding tissue without causing any significant bioeffects and without any incisions. At the target, ultrasound energy is converted to heat, causing tissue coagulation and necrosis. MRI guidance is used with FUS to provide high quality tumor margin definition as well as the ability to monitor the temperature of the tissue and assess the treatment. Among the MRgFUS applications are treatments of tumors in the prostate, breast, uterine fibroids, liver and brain. To make these applications widely acceptable and available to patients, improvement of image guidance is essential. The goal of this work was to develop novel MRI tools for visualization of the focal spot and for adaptive focusing of ultrasound. Visualization of the ultrasound focus is performed to con rm that the beam's focus is placed on the target anatomy. Currently, it is achieved by producing a small temperature rise in a test spot, which is detected using MRI temperature monitoring techniques. Focus localization often relies on multiple applications of ultrasound, the cumulative effects of which can lead to potentially irreversible changes in healthy tissue. In addition, visualization of the temperature rise with MRI is problematic in tissue with high fat content such as breast. The thesis addresses the challenges of focus visualization by introducing novel imaging methods, that image displacement of tissue due to acoustic radiation force: 2D Fourier Transform (2DFT) spin-echo and single-shot echo planar imaging (EPI) MR guided acoustic radiation force imaging (MR-ARFI). The new pulse sequences are demonstrated ex vivo and optimized for in vivo brain applications. One of the challenges of using FUS to treat brain pathology is overcoming the phase aberrations of ultrasound caused by heterogeneous acoustic properties of the skull bone. These aberrations result in partial or complete destruction of the focal spot, and therefore prevent the delivery of sufficient energy to the targeted volume, and cause heating where it was not intended. The current correction method estimates the aberrations from the thickness and density of the skull bone obtained from pre-operative computerized tomography (CT) images of the patient's head. Recently introduced alternative methods use adaptive focusing approach combined with MR-ARFI. The transducer elements' emissions are manipulated until the acoustic intensity, which is proportional to tissue displacement, is maximized. Promising, but very time consuming, these methods do not o er a practical solution. In this work, it is shown how using Zernike polynomials, actively utilized in optics, can increase the efficiency of MR-ARFI-based adaptive focusing, making it a more suitable technique for clinical applications.
  • 2006From: Springer
    V.V. Tuchin, L.V. Wang, D.A. Zimnyakov.
  • 2014From: CRCnetBASE
    edited by Stephen P. Morgan, Felicity R.A.J. Rose, Stephen J. Matcher.
    "This book is focused on the optical techniques that can be applied to regenerative medicine, including optical coherence tomography, acousto-optic imaging, Raman spectroscopy, machine vision, polarized light imaging, fibre optic sensors, second harmonic generation, multi-photon microscopy, coherent anti-Stokes Raman scattering, and polarized light imaging. It covers applications both in fundamental research and in the regenerative medicine industry for tissue engineering products. Each chapter gives an overview of a particular technique, its advantages and limitations in terms of structural and functional information provided, and examples of applications in regenerative medicine. The book provides a practical guide to the most appropriate techniques for a given application. It also offers a summary of major recent advances, such as use of machine vision for tracking growth of three-dimensional constructs in bioreactors and polarization sensitive optical coherence tomography for monitoring collagen alignment in cartilage growth"--Provided by publisher.
  • Geoffrey S. Nelson.
    Biopsy methods used in lung cancer typically have either significant complication rates or high rates of false negatives. The safest biopsy method (transbronchial biopsy) has high false negative rates. This thesis takes the initial steps towards adding real-time 3-dimensional imaging to this process via tomosynthesis. Currently transbroncial biopsies are guided by an Electromagnetic Navigation Bronchoscopy (ENB) system. This guidance assumes little physiological change between the CT scan and the procedure and also assumes that there is no movement of the catheter while removing the ENB probe from the working channel and inserting the needle or cytobrush for the biopsy. Thus the pulmonologist is 'blind' during the actual biopsy. The scanning-beam digital x-ray (SBDX) system (an inverse geometry fluoroscopic system) can add tomosynthesis imaging to the biopsy process. The SBDX system has a 2D array of small beams incident from multiple angles onto a small detector. The multiple angles allows 3-dimensional information to be reconstructed in the images via tomosynthesis. To maximize the tomographic angle of the SBDX system, the tomosynthetic angle as a function of tumor-to-detector distance (TDD) was calculated. Monte Carlo Software (PCXMC) was used to calculate organ doses and effective dose for source-to-detector distances (SDDs) for multiple system geometries. These calculations were performed for both the SBDX system and for standard fluoroscopy. The effect of system geometry on patient dose, both in absolute terms and in terms of image quality were investigated. The tomographic angle had more significant changes with SDD in the region near the detector, at a source to tumor distance that is 69.7% of the SDD assuming constant source and detector size. Changing the patient location in order to increase tomographic angle has a significant effect on organ dose distribution due to geometrical considerations. When tumor signal to noise ratio (SNR) is held constant (ie. x-ray fluence is scaled appropriately), SBDX gives 2-10 times less dose than fluoroscopy for the same conditions within the typical range of patient locations. These models suggested an ideal SDD of 100 cm because of practical considerations of varying patient size, and adequate room between the patient and the bracing securing the detector. To show that the SBDX could improve targeting of tumor lesions, realistic phantoms were needed. Pig lungs and hearts were preserved, the vasculature was filled, and lesions were created in them. The lungs were capable of breathing motion when placed in a custom vaccum chamber. A chest phantom with a rib cage was cut to fit in the vacuum chamber. This provided a very lifelike phantom model for the lungs including the capacity to mimic breathing motion. The prepared lungs were scanned by CT and the scans were used for ENB planning. The pulmonologist placed fiducials which represented the tissue sample site using the ENB system. During this process, the lungs were deformed to simulate the real clinical condition of breathing. After all the fiducials were placed, the lungs were scanned on the SBDX system. The shortest distance from the distal tip of the fiducial to the center of the lesion was measured using the SBDX images. The lungs were again scanned by CT and the fiducial-to-lesion distances were measured. The SBDX system fiducial-to-lesion distances had significant (p< 0.0001) agreement with the CT fiducial-to-lesion distances, indicating that SBDX images can accurately provide image guidance for ENB procedures. The ENB tip-to-target distances were not accurate. When auto-registered lungs were compared with manually registered lungs, it was found that the auto-registered lungs, which had less CT-to-body divergence, had more agreement with the CT fiducial-to-lesion measurements. This indicates that CT-to-body divergence both from rigid registration of primary bronchial passages and non-rigid breathing motion is responsible for the ENB inaccuracy in the distal regions of the lungs. Additional steps to bring this method to the clinic include testing with both guidance systems concurrently, continued development of the reconstruction algorithm, and testing the system in an in vivo model.
  • Murtaza Mogri.
    Optogenetic neuromodulation is giving scientists an unprecedented ability to modulate neural circuits, providing specificity with regards to location, cell type, as well as neuromodulatory effect. On the other hand, electrical stimulation and lesions, methods commonly used to study neural circuits, are lacking in specificity, often affecting both local cells and passing axons, as well as multiple cell types. Our laboratory has been at the forefront of the field of optogenetics, having developed, for use in mammalian systems, Channelrhodopsin-2 (ChR2), an algal light-activated cation channel that depolarizes neurons in response to blue light, and Natronomonas pharaonis halorhodopsin (eNpHR), a chloride pump that hyperpolarizes neurons in response to amber light. These proteins can control neuronal activity with millisecond timescale precision, and through promoters, they can be targeted to specific cell-types in heterogeneous tissue. Along with its specificity, light stimulation with optogenetic tools often allows the recording of neural activity without the artifact that obfuscates recordings with electrical stimulation. The advantages provided by optogenetics allowed us to make a breakthrough in determining the therapeutic mechanism of deep brain stimulation, a robust treatment for Parkinson's disease in which stimulating electrodes are implanted deep in the brain. Using optogenetics, we replicated the effect of deep brain stimulation by modulating cortical inputs into the region where the stimulating electrode is normally placed. Combined with other corroborating publications, a hypothesis is emerging that electrical stimulation deep in the brain actually produces its effect by modulating cortical projections to the deep brain region. Based on this concept, several clinical studies are being done to better understand the cortical role in Parkinson's disease and determine whether cortical stimulation (potentially non-invasive), could be an alternative to the invasive implants currently used. In order to perform these experiments, we studied the transmission of visible light in brain tissue to estimate the volume of activation produced by optogenetic stimulation and developed a device to measure fluorescence in awake, behaving animals, allowing the quantification of virally transfected gene expression over time, as well as the localization of expression along axon bundles. The knowledge gained from these experiments will have a significant impact on future experiments in the broader field of optogenetics.
  • Lisa Gunaydin.
    Social interaction is an essential and highly integrative behavioral task that is impaired in major psychiatric disorders such as autism, schizophrenia, social anxiety disorder, and depression. Current treatments for many of these disorders are based on pharmacological approaches that have been used for decades even though their mechanisms of action are poorly understood and carry many side effects. In particular, treatment of the asocial symptoms of these disorders has remained elusive due to a generally poor understanding of the neural circuitry underlying normal social behavior. In order to move toward a deeper circuit-level understanding of these complex neural processes, our lab has pioneered the use of two light-activated microbial opsins, Channelrhodopsin-2 (ChR2) and Halorhodopsin (NpHR), to achieve precise bidirectional optogenetic control of specific cell types in behaving animals. However, it has become clear that the complexity of the circuitry involved in psychiatric behaviors will require new classes of optogenetic tools to modulate cells in a more refined manner based on characteristics such as projection profile, receptor expression, and endogenous firing patterns. The purpose of this study was thus two-fold: 1) to develop novel optogenetic tools for more physiologically relevant stimulation of different cell types on different timescales, and 2) to apply these tools to define in socializing animals the real-time causal role not only of a specific brain region and cell type, but also of distinct subpopulations defined by projections to different downstream brain regions and distinct downstream cell types. The engineered opsins we develop here will be generalizable to dissect other neural circuits in health and disease, enabling new domains of optogenetic investigation that have thus far been inaccessible, and enhancing the precision of optical neural control in a broad variety of settings.
  • 2013From: Springer
    Hugh Devlin, Ichiro Nishimura, editors.
    Dentists are routinely faced with a huge choice of implant systems from different manufacturers, each of whom claims that its own particular system has advantages over the others. There is consequently a need for an evidence-based review of the field that offers authoritative practical guidance for dental practitioners. Oral and Cranial Implants: Recent Research Developments has been written with this in mind. It brings together all the recent key developments in implant research and discusses the underlying science relating to implant procedures and failures.
  • 2014From: CRCnetBASE
    Kevin L. Ong, Jonathan Black, Scott Lovald.
    Forces and equilibrium -- Deformation -- Mechanical properties -- Viscoelasticity -- Properties of natural materials -- Polymers -- Metals -- Ceramics and composites -- Tissue engineering -- Hybrid, combination, and replant materials -- Friction and wear -- Corrosion and degradation -- Fixation -- Host response -- Testing and introduction of new materials -- Materials retrieval and analysis -- Self-test.
  • 2013From: ClinicalKey
    [edited by] Michelle M. Lusardi, Milagros "Millee" Jorge, Caroline Nielsen.
    The most comprehensive physical therapy text available on the topic, Orthotics & Prosthetics in Rehabilitation, 3rd Edition, is your one-stop resource for clinically relevant rehabilitation information. Evidence-based coverage offers essential guidelines on orthotic/prosthetic prescription, pre- and post-intervention gait assessment and outcome measurement, and working with special populations. Whether you are a student or a clinician, this text provides the strong foundation in and appreciation for the field of orthotics and prosthetics that will give you the critical skills needed when working with this unique client population. Inside you'll find: comprehensive coverage of rehabilitation in a variety of environments, including acute care, long-term care, home health care, and outpatient settings; authoritative information from the Guide to Physical Therapist Practice, 2nd edition is incorporated throughout to keep you up to date with the recognized standard in the field; WHO International Classification of Function model provides consistent language and an international standard to describe and measure health and disability from a biopsychosocial perspective; case studies present real-life scenarios that demonstrate how key concepts apply to clinical decision making and evidence-based practice; and a visually appealing 2-color design and a wealth of tables and boxes highlight vital information for quick reference and ease of use. New to this edition: NEW! Chapter on athletics after amputation exploring advanced training and athletics, including running and athletic competition, to enhance the quality of life for persons with amputation; NEW! Chapter on the high risk foot and wound healing helps you recognize, treat, and manage wounds for the proper fit and managemnt of the patient; NEW! Chatper on advanced prosthetic rehabilitation provides more thorough rehabilitation methods beyond the early care of persons learning to use thier prostheses; updated photos and illustration reflect current clinical practice; and updated chapters covering assessment of gait with a focus on clinically useful outcome measures, motor control and motor learning incorporating new insights into neuroplasticity and functional recovery, and a NEW integrated chapter on lower extremity orthoses that assist in clincial decision making about the best options for your patients.
  • Blake Byers.
    Studies of Parkinson's disease (PD) have been greatly hindered by lack of access to affected human dopaminergic (DA) neurons. Here, we report generation of induced pluripotent stem cells that carry the p.G2019S mutation (LRRK2-G2019S-iPSCs) in the Leucine-Rich Repeat Kinase-2 (LRRK2) gene, the most common PD-related mutation; pluripotent lines that cells that carry a full SNCA gene triplication on one allele; and control pluripotent lines. We demonstrate that these PD autosomal dominant mutant LRRK2-G2019S-iPSCs, SNCA-triplication-iPSCs and Control-iPSCs were able to differentiate into dopaminergic neurons and showed increased expression of key oxidative stress response genes and alpha-synuclein protein. Moreover, LRRK2-G2019S iPSC derived dopaminergic neurons, specifically, were more sensitive to caspase-3 activation caused by exposure to hydrogen peroxide, MG-132, and 6-hydroxydopamine, compared to control dopaminergic neurons. While, SNCA-triplication iPSC derived dopaminergic neurons formed early ubiquitin positive puncta and were more sensitive to peak toxicity hydrogen peroxide induced cell stress. These findings suggest that LRRK2-G2019S and SNCA-triplication iPSC derived dopaminergic neurons exhibit early phenotypes linked to PD. Due to the high penetrance of the LRRK2 mutation, the expression of wild type protein in the SNCA-triplication line, and the clinical resemblance of patients afflicted with these disorders to sporadic PD patients, these neurons may provide a valuable platform for identification of novel pharmacological agents and diagnostics for modeling and alleviation of a subset of disease phenotypes.
  • 2013From: Cambridge
    2013From: Knovel
    William E. Schiesser.
    Gives graduate students and researchers an introductory overview of partial differential equation analysis of biomedical engineering systems through detailed examples.
  • 2014From: Springer
    Bryan D. Springer, Javad Parvizi, editors.
    Periprosthetic Joint Infection of the Hip and Knee is a practical reference for the diagnosis and treatment of total joint infections following hip and knee arthroplasty. In addition to useful chapters presenting common tests and algorithms used for diagnosis, the book gives background on the epidemiology, risk factors, and prevention strategies of periprosthetic joint infection. Additionally, practical clinical information is given, including antibiotic treatment strategies and delivery methods and medical optimization techniques for physicians to follow for patient care and follow-up. Covering a topic that is currently underrepresented in the medical literature, Periprosthetic Joint Infection of the Hip and Knee will be useful to orthopedic surgeons, rheumatologists, and other physicians involved in the care of patients with hip and knee prosthetic implants.
  • Adam David Grossman.
    Personalized medicine has arisen from the long-recognized fact that drug efficacy and safety vary from person to person. Genetics and genomics have been the main tools of "traditional" personalized medicine, yet the daily practice of physicians revolves around physiology. In this dissertation, I approached personalized medicine using clinical-level physiology and demonstrated this approach in two ways. First I showed how individualized understanding of pathophysiology could improve treatment of a patient with dystonia. Then I demonstrated using multivariate clinical physiology in the intensive care unit (ICU) to develop an understanding of the factors associated with poor outcome and the effects of drugs. Childhood dystonia is a movement disorder often caused by cerebral palsy. Its severity varies from barely noticeable to deeply profound, affecting every aspect of daily life. One application of personalized physiology modeling included the creation of an algorithm to estimate the user's intent when using a computer interface. Aside from doubling the patient's typing rate compared to his normal interface, we were also able to discern individual patterns reflective of his specific pathophysiological movements. Similarly, studying his reaching movement patterns enabled us to test a biofeedback protocol to train him to make better movements, resulting in straighter movements more resembling normal reaching. Thus, leveraging knowledge of individual patients led to speedy improvements over conventional treatments and improved outcome. Having demonstrated the applicability of these methods to two specific problems, I then approached the more general problem of modeling critical care patients in the intensive care unit. Physiology monitoring in the ICU has been common, but simplistic, in most cases using only single variables to define alarms to prevent catastrophic consequences. Using temporally dense multivariate data from the ICU, I discussed the definition of complex physiological states and associated them with the likelihood of poor outcomes. Furthermore, examining pairwise relationships between variables in the complex states most and least associated with survival suggested that mitochondrial dysfunction could be involved in the poor outcomes. Further examination of the relationships between variable pairs led to the construction of physiological correlation networks associated with the presence of infection and the administration of drugs. In both of these comparisons, clear differences were evident between the two cases. This demonstrated that physiological relationships depend on patient state and suggest further study to clarify them for implementation in patient monitoring routines. In this dissertation I demonstrated, using both a pilot study of critical care pathophysiology models and a concrete application of personalized modeling to pediatric dystonia patients, that personalized medicine could benefit by incorporating pathophysiology into its modeling efforts. Further developing an understanding of how patients transition between states predictive of good and poor outcomes will enable improvements in critical care treatment and beyond.
  • Keekok Lee.
    An exploration of the philosophical foundation of modern medicine which explains why such a medicine possesses the characteristics it does and where precisely its strengths as well as its weaknesses lie. Written in plain English, it should be accessible to anyone who is intellectually curious, lay-persons, and medical professionals alike. --From publisher description.
  • Adam de la Zerda.
    Biomedical imaging has seen a tremendous shift over the past decades, moving to non-invasive and high spatial-resolution imaging, spanning multiple imaging modalities and applications. However, one common limitation of traditional medical imaging is its intrinsic inability to provide information on the molecular levels of various biomarkers. Molecular Imaging solves this limitation by introducing an exogenous imaging agent that upon administration to the subject, binds to or interacts with the molecular target(s) and produces an imaging signal. The agent can be designed to produce the imaging signal in the form of visible fluorescent light, gamma rays, ultrasound waves and other forms of energy. In this thesis, we summarize our work on Photoacoustic Molecular Imaging, a technique where short laser light pulses are converted into ultrasound waves by a nanoparticle that was molecularly targeted to a diseased site. We summarize the physical basis for the technique and its first demonstration -- highlighting angiogenesis markers in living subjects (Chapter 2). We then summarize the development of second generation photoacoustic imaging agents and demonstrate their utility in ultrahigh sensitivity molecular imaging of tumors (Chapter 3) as well as in multiplexing studies (Chapter 4). Next, we describe a novel application for Photoacoustic Imaging in visualizing the retina and the posterior eye segment with unprecedented depth of penetration, giving hope for early diagnosis of age-related macular degeneration and other retinal diseases (Chapter 5). We then describe a novel molecular imaging technology called Optical Coherence Contrast Imaging, and demonstrate it provides ultrahigh resolution and sensitivity images of gold nanoparticles in living mice eyes (Chapter 6). Finally, we conclude with various therapeutic and theranostic (therapy and diagnostic combined) concepts and highlight the synergy between them and the imaging methods presented in earlier chapters (Chapter 7).
  • Lele Wang.
    Degenerative retinal diseases are among the leading causes of vision loss in the developed world. In these diseases, the "image capturing" photoreceptor layer slowly dies while the "image processing" inner retinal layers are preserved to large extent. One approach to restore vision of patients suffering from the selective photoreceptor loss is to deliver information to the visual system by patterned electrical stimulation of the remaining retinal circuitry. Several retinal prosthetic systems have achieved promising results in clinical studies, with the most successful prostheses allowing blind people to read large letters. However, the current retinal prosthetic designs require a trans-scleral cable to deliver power or data to the retinal stimulating array. We designed a photovoltaic prosthetic system with a silicon photodiode array placed behind the retina, in which each pixel of the array photovoltaically converts patterned pulsed near-infrared light projected from video goggles into pulses of bi-phasic electric current to stimulate the nearby retinal neurons. The light-powered 30-[micro]m thick photodiode array does not require any wired power connections, which greatly simplifies the surgical procedure and reduces chances of infection. Several arrays could be juxtaposed to tile a larger area on the retina and thereby expand the visual field. The local return electrodes in each pixel help to reduce the spatial spread of electric current, thereby reducing the cross-talk between pixels and improving the spatial resolution of the implant. Each pixel contains three photodiodes connected in series to increase charge injection levels. Deep reactive-ion etched trenches are used to isolate the three photodiodes in each pixel. Trenches between the pixels are open to allow perfusion of nutrient, which is essential for in-vitro electrophysiological experiments, and may also help with the in-vivo integration of the implant with the retina. We fabricated 1 and 2 mm wide arrays of photodiode for implantation in small and large animals. Three sizes of pixels (280 [micro]m, 140 [micro]m and 70 [micro]m) were fabricated to explore the resolution that could be achieved by the implant. The development of the fabrication process for the silicon photodiode array is presented, which involves eight mask layers, including deep isolation trench etch, n+ region predeposition, p+ region ion implantation, first via etching, first metal deposition and liftoff, second via etching, polysilicon etching in selected trenches, second metal deposition and liftoff. A detailed optoelectronic characterization of the fabricated photodiode array is also presented. The initial electrophysiological results of retinal stimulation in-vitro and in-vivo show that the fabricated devices are able to reliably elicit retinal responses at safe near-infrared light irradiances, with good acceptance of the photodiode array in the subretinal space.
  • Mario Alfonso Díaz de la Rosa.
    Protein-DNA interactions within the confines of the crowded cellular space control critical biological processes such as genome regulation, replication, and compaction. In turn, protein activity on the genome is susceptible to the structure and dynamics of the DNA itself, a complex relationship whose study falls within the realm of polymer physics. Using analytical theory and numerical simulations, we present a systematic study of the relationship between DNA structure and dynamics and cellular processes mediated by DNA-binding proteins, in particular those involving a search for a target-site on the chromosome. We build a theoretical description of the transport of DNA-binding proteins along linear DNA modeled as a wormlike chain and delineate the resulting dynamic strategies employed by the cell in order to maximize translocation speed and efficiency. We extend this model to address the otherwise imperceptible molecular events present during effective protein diffusion along a stretched DNA strand during single-molecule experiments. In an effort to address the genome's higher-order structural effects, we explore the structure and dynamics of supercoiled DNA both as a free molecule in solution and under confinement in the cell, as in the case of Caulobacter crescentus. Our investigation of supercoiled DNA in confinement highlights dynamic consequences of vital importance to the cell's genome regulatory strategies. Finally, we synthesize our study of DNA-binding protein transport with our investigation of supercoiling dynamics to address the effect of DNA superstructure on the target-site search process, and we identify the search enhancement wrought by supercoiling of the chromosome.
  • Andrew W. Wood ; with contributions by Anthony Bartel ... [et al.].
    Status: Not Checked OutLane Catalog Record
    "Preface The aim of this book is to show that many aspects of human physiology lend themselves to numerical analysis. Many ways of monitoring physiological function also rely on an understanding of physics and engineering to appreciate fully how they operate. The book arises out of an undergraduate course in medical biophysics and a postgraduate course in biomedical instrumentation the authors were involved in for many years. Although the emphasis is on numerical analysis only, a basic knowledge of mathematics is assumed and every effort is made to supplement mathematical formulae with qualitative explanations and illustrations to encourage an intuitive grasp on the processes involved. Most of the chapters have a range of numerical tutorial problems with, in most cases, worked solutions. These are based on examination questions at the middle and senior undergraduate level. For some of the material, the computational package MATLABʼ offers a convenient way to gain insight into some of the more advanced mathematical analysis of physiological or of clinical monitoring systems. Suitable MATLAB code is provided where this might aid understanding. I acknowledge the help of colleagues in the preparation of this book. Particular chapters have been authored as follows: Anthony Bartel, Per Line, Peter Cadusch, Joseph Ciorciari, David and Sheila Crewther, John Patterson , Mark Schier, Bruce Thompson. In addition, others have been associated with teaching the course over many years. These include: Peter Alabaster, David Liley, Ric Roberts and David Simpson"--Provided by publisher.
  • 2013From: Wiley
    Alexander Fridman and Gary Friedman.
    Introduction to fundamental and applied aspects of plasma medicine -- Fundamentals of plasma physics and plasma chemistry relevant to biological and medical applications -- Selected concepts in biology and medicine for physical scientists -- Major plasma disharges and their applicability for plasma medicine -- Mechanisms of plasma interactions with cells -- Plasma sterilization of different surfaces and living tissues -- Plasma decontamination of water and air streams -- Plasma treatment of blood : non-thermal plasma-assisted blood coagulation and plasma control of blood properties -- Plasma assisted healing and treatment of diseases -- Plasma pharmacology -- Fundamentals of plasma-assisted tissue engineering and plasma processing of polymers.
  • 2014From: ScienceDirect
    Vinny R. Sastri.
    1. Introduction -- 2. Regulations for medical devices and application to plastics suppliers : history and overview -- 3. Materials used in medical devices -- 4. Material requirements for plastics used in medical devices -- 5. Polymer additives used to enhance material properties for medical device applications -- 6. Commodity thermoplastics : polyvinyl chloride, polyolefins, and polystyrene -- 7. Engineering thermoplastics : acrylics, polycarbonates, polyurethanes, polyacetals, polyesters, and polyamides -- 8. High-temperature engineering thermoplastics : polysulfones, polyimides, polysulfides, polyketones, liquid crystalline polymers, and fluoropolymers -- 9. Other polymers : styrenics, silicones, thermoplastic elastomers, biopolymers, and thermosets -- 10. Purchasing controls and supplier quality for medical device manufacturers and their suppliers -- 11. Process validation for medical device manufacturers and their suppliers.
  • 2013From: Springer
    Ahsan Habib Khandoker, Chandan Karmakar, Michael Brennan, Andreas Voss, Marimuthu Palaniswami.
    The Poincaré plot (named after Henri Poincaré) is a popular two-dimensional visualization tool for dynamic systems due to its intuitive display of the dynamic properties of a system from a time series. This book presents the basis of Poincaré plot and focus especially on traditional and new methods for analysing the geometry, temporal and spatial dynamics disclosed by the Poincaré plot to evaluate heart rate variability (HRV). Mathematical descriptors of Poincaré plot have been developed to quantify the autonomic nervous system activity (sympathetic and parasympathetic modulation of heart rate). Poincaré plot analysis has also been used in various clinical diagnostic settings like diabetes, chronic heart failure, chronic renal failure and sleep apnea syndrome. The primary aims of quantification of the Poincaré plots are to discriminate healthy physiological systems from pathological conditions and to classify the stage of a disease. The HRV analysis by Poincaré plot has opened up ample opportunities for important clinical and research applications. Therefore, the present book can be used either for self-study, as a supplement to courses in linear and nonlinear systems, or as a modern monograph by researchers in this field of HRV analysis.
  • 2012From: CRCnetBASE
    edited by Shalaby W. Shalaby, Karen J.L. Burg, Waleed Shalaby.
    "In a carefully crafted, multidisciplinary, skillfully focused format, this book covers attributes of polymers used for vascular, urological, and gynecological materials. It provides a brief analysis of how the use of polymers in vascular and urogenital applications has evolved in the past five decades and outlines their common and specific functional requirements. It features small, readable monographs that provide a brief description of the evolving role of a particular material, and present topics in highly integrated, well-balanced, authoritatively prepared segments on materials processing and in vitro and in vivo evaluation, complete with case studies"-- Provided by publisher.
  • 2012From: CRCnetBASE
    K.J. Blinowska, J. Zygierewicz.
    1. Introductory concepts -- 2. Single channel (univariate) signal -- 3. Multiple channels (multivariate) signals -- 4. Application to biomedical signals.
  • 2011From: ScienceDirect
    2011From: ClinicalKey
    [edited by] Anthony Atala ... [et al.].
    Chapter 1. Molecular Organization of Cells / Jon D. Ahlstrom -- Chapter 2. Cell-ECM Interactions in Repair and Regeneration / M. Petreaca, M. Martins-Green -- Chapter 3. Mechanisms of Blastema Formation in Regenerating Amphibian Limbs / David L. Stocum, Nandini Rao -- Chapter 4. The Molecular Circuitry Underlying Pluripotency in Embryonic Stem Cells and iPS Cells / Harvir Singh, Ali H. Brivanlou -- Chapter 5. How Cells Change their Phenotype / Caroline Beth Sangan, David Tosh -- Chapter 6. Scarless Wound Healing / Allison Nauta, Barrett Larson, Michael T. Longaker, H. Peter Lorenz -- Chapter 7. Somatic Cloning and Epigenetic Reprogramming in Mammals / Heiner Niemann, Wilfried A. Kues, Andrea Lucas-Hahn, Joseph W. Carnwath -- Chapter 8. Engineered Proteins for Controlling Gene Expression / Charles A. Gersbach -- Chapter 9. Genetic Approaches in Human Embryonic Stem Cells and their Derivatives: Prospects for Regenerative Medicine / Junfeng Ji, Bonan Zhong, Mickie Bhatia -- Chapter 10. Embryonic Stem Cells: Derivation and Properties / Junying Yu, James A. Thomson -- Chapter 11. Alternative Sources of Human Embryonic Stem Cells / Svetlana Gavrilov, Virginia E. Papaioannou, Donald W. Landry -- Chapter 12. Stem Cells from Amniotic Fluid / Mara Cananzi, Anthony Atala, Paolo de Coppi -- Chapter 13. Induced Pluripotent Stem Cells / Keisuke Okita, Shinya Yamanaka -- Chapter 14. MSCs in Regenerative Medicine / Arnold I. Caplan -- Chapter 15. Multipotent Adult Progenitor Cells / Philip Roelandt, Catherine M. Verfaillie -- Chapter 16. Hematopoietic Stem Cell Properties, Markers, and Therapeutics / Kuanyin K. Lin, Grant A. Challen, Margaret A. Goodell -- Chapter 17. Mesenchymal Stem Cells / Zulma Gazit, Gadi Pelled, Dima Sheyn, Nadav Kimelman, Dan Gazit -- Chapter 18. Cell Therapy of Liver Disease: From Hepatocytes to Stem Cells / Stephen C. Strom, Ewa C.S. Ellis -- Chapter 19. Cardiac Stem Cells: Biology and Therapeutic Applications / Sarah Selem, Konstantinos E. Hatzistergos, Joshua M. Hare -- Chapter 20. Skeletal Muscle Stem Cells / Benjamin D. Cosgrove, Helen M. Blau -- Chapter 21. Stem Cells Derived from Fat / Adam J. Katz, Alexander F. Mericli -- Chapter 22. Peripheral Blood Stem Cells / Zhan Wang, Gunter Schuch, J. Koudy Williams, Shay Soker -- Chapter 23. Islet Cell Therapy and Pancreatic Stem Cells / Juan Domínguez-Bendala, Antonello Pileggi, Camillo Ricordi -- Chapter 24. Regenerative Medicine for Diseases of the Retina / Deepak A. Lamba, Thomas A. Reh -- Chapter 25. Somatic Cells: Growth and Expansion Potential of T Lymphocytes / Rita B. Effros -- Chapter 26. Mechanical Determinants of Tissue Development / Jonathan A. Kluge, Gary G. Leisk, David L. Kaplan -- Chapter 27. Morphogenesis of Bone, Morphogenetic Proteins, and Regenerative Medicine / A.H. Reddi -- Chapter 28. Physical Stress as a Factor in Tissue Growth and Remodeling / Joel D. Boerckel, Christopher V. Gemmiti, Yash M. Kolambkar, Blaise D. Porter, Robert E. Guldberg -- Chapter 29. Intelligent Surfaces for Cell-Sheet Engineering / Takanori Iwata, Masayuki Yamato, Teruo Okano -- Chapter 30. Applications of Nanotechnology for Regenerative Medicine / Benjamin S. Harrison, Sirinrath Sirivisoot -- Chapter 31. Design Principles in Biomaterials and Scaffolds / Hyukjin Lee, Hyun Jung Chung, Tae Gwan Park -- Chapter 32. Natural Origin Materials for Bone Tissue Engineering - Properties, Processing, and Performance / V.M. Correlo, J.M. Oliveira, J.F. Mano, N.M. Neves, R.L. Reis -- Chapter 33. Synthetic Polymers / M.C. Hacker, A.G. Mikos -- Chapter 34. Biological Scaffolds for Regenerative Medicine / Alexander Huber, Stephen F. Badylak -- Chapter 35. Hydrogels in Regenerative Medicine / Justin M. Saul, David F. Williams -- Chapter 36. Surface Modification of Biomaterials / Andrés J. García -- Chapter 37. Histogenesis in Three-dimensional Scaffolds / Melissa K. McHale, Nicole M. Bergmann, Jennifer L. West -- Chapter 38. Biocompatibility and Bioresponse to Biomaterials / James M. Anderson -- Chapter 39. Designing Tunable Artificial Matrices for Stem Cell Culture / Elizabeth F. Irwin, Jacob F. Pollock, David V. Schaffer, Kevin E. Healy -- Chapter 40. Biomineralization and Bone Regeneration / Jiang Hu, Xiaohua Liu, Peter X. Ma -- Chapter 41. Cell Therapy for Blood Substitutes / Shi-Jiang Lu, Qiang Feng, Feng Li, Erin A. Kimbrel, Robert Lanza -- Chapter 42. Articular Cartilage / Lily Jeng, Francois Ng kee Kwong, Myron Spector -- Chapter 43. Myoblast Transplantation in Skeletal Muscles / Daniel Skuk, Jacques P. Tremblay -- Chapter 44. Clinical Islet Transplantation / Juliet A. Emamaullee, Michael McCall, A.M. James Shapiro -- Chapter 45. Fetal Tissues / Ryan P. Dorin, Chester J. Koh -- Chapter 46. Engineering of Large Diameter Vessels / Masood A. Machingal, Saami K. Yazdani, George J. Christ -- Chapter 47. Engineering of Small-Diameter Vessels / Brett C. Isenberg, Chrysanthi Williams, Robert T. Tranquillo -- Chapter 48. Cardiac Tissue / Milica Radisic, Michael V. Sefton -- Chapter 49. Regenerative Medicine in the Cornea / May Griffith, Per Fagerholm, Neil Lagali, Malcolm A. Latorre, Joanne Hackett, Heather Sheardown -- Chapter 50. Alimentary Tract / Richard M. Day -- Chapter 51. Extracorporeal Renal Replacement / Kimberly A. Johnston, H. David Humes -- Chapter 52. Tissue Engineering of the Reproductive System / Stefano Da Sacco, Laura Perin, Roger E. De Filippo -- Chapter 53. Cartilage Tissue Engineering / Qiongyu Guo, Jennifer H. Elisseeff -- Chapter 54. Functional Tissue Engineering of Ligament and Tendon Injuries / Savio L.-Y. Woo, Alejandro J. Almarza, Sinan Karaoglu, Rui Liang, Matthew B. Fisher -- Chapter 55. Central Nervous System / Brian G. Ballios, M. Douglas Baumann, Michael J. Cooke, Molly S. Shoichet -- Chapter 56. Peripheral Nerve Regeneration / Mahesh C. Dodla, Vivek J. Mukhatyar, Ravi V. Bellamkonda -- Chapter 57. Tissue Engineering of Skin / Fiona Wood -- Chapter 58. Regenerative Medicine of the Respiratory Tract / Martin A. Birchall, Sam Janes, Paolo Macchiarini -- Chapter 59. The Digit: Engineering of Phalanges and Small Joints / Makoto Komura, Jaehyun Kim, Anthony Atala, James J. Yoo, Sang Jin Lee -- Chapter 60. Intracorporeal Kidney Support / Jae Hyun Bae, Tamer Aboushwareb, Anthony Atala, James J. Yoo -- Chapter 61. Ethical Considerations / Ronald M. Green -- Chapter 62. US Stem Cell Research Policy / Josephine Johnston -- Chapter 63. Overview of the FDA Regulatory Process / Kevin J. Whittlesey, Mark H. Lee, Jiyoung M. Dang, Maegen Colehour, Judith Arcidiacono, Ellen Lazarus, David S. Kaplan, Donald Fink, Charles N. Durfor, Ashok Batra, Stephen L. Hilbert, Deborah Lavoie Grayeski, Richard McFarland, Celia Witten.
  • 2014From: ScienceDirect
    edited by Robert Lanza, Robert Langer, Joseph Vacanti.
  • 2000From: ScienceDirect
    edited by Robert P. Lanza, Robert Langer, Joseph Vacanti.
    Tissue engineering in perspective -- Introduction to tissue engineering -- Basis of growth and differentiation -- In vitro control of tissue development -- In vivo synthesis of tissues and organs -- Models for tissue engineering -- Biomaterials in tissue engineering -- Transplantation of engineered cells and tissues -- Fetal tissue engineering -- Gene therapy -- Breast -- Cardiovascular system -- Cornea -- Endocrinology and metabolism -- Gastrointestinal system -- Hematopoietic system -- Kidney and genitourinary system -- Musculoskeletal system -- Nervous system -- Periodontal and dental applications -- Skin -- Womb -- Regulatory issues.
    Also available: Print – 2000
  • edited by Robert Lanza, Robert Langer, Joseph Vacanti.
    Status: Not Checked OutLane Catalog Record
  • v. 1200-, 1990-From: SPIE
  • William Chiyao Yang.
    The overall objective of this thesis was to produce and characterize recombinant transducible (able to enter cells) transcription factors (TFs). TFs are complex, difficult-to-make proteins that regulate gene expression and cell fate. Thus, we wanted to deliver transducible TFs exogenously to cells to change gene expression and alter cell fate. Ectopic expression of a set of pluripotency-regulating TFs (Oct4, Sox2, Klf4, cMyc, Lin28, and Nanog) using viral vectors can reprogram adult cells to pluripotency. The resultant cells are pluripotent and can self-renew indefinitely, just like embryonic stem cells. These induced pluripotent stem cells (iPSCs) hold enormous potential for patient-specific cell-based therapies and disease models. However, viruses integrate foreign DNA into the host cell genome, causing insertional mutagenesis and genomic instability which renders the cell unsuitable for clinical use. A non-viral method of iPSC generation is necessary in order to bring iPSCs from the bench to bedside. Direct delivery of the TFs as recombinant proteins offers one avenue for non-viral iPSC generation. Conjugation of an arginine-rich protein transduction domain (PTD) to the TF cargo enables intracellular delivery of the exogenously administered fusion protein. The overall goal of this multi-investigator project was to develop a protein-based method for iPSC generation using purified recombinant TFs fused with a nona-arginine (R9) PTD. The first step is to efficiently produce TF proteins that are active in controlling downstream target gene expression. Thus, my thesis focuses on the upstream portion of the overall project, the production and characterization of the recombinant transducible TFs. TFs are difficult to produce in live cell cultures due to aggregation and product toxicity. Thus, we used E. coli cell-free protein synthesis (CFPS) to produce these transducible TFs. CFPS decouples protein synthesis from maintenance of host cell health to permit production of toxic proteins and slows the translation rate to favor proper protein folding. Using CFPS, we made R9-Oct4, R9-Sox2, R9-Klf4, R9-cMyc, R9-Lin28, and R9-Nanog. Taking advantage of the flexibility offered by CFPS, we addressed protein truncation and solubility problems to produce full-length and soluble TFs. We then showed that R9-Oct4, R9-Sox2, and R9-Nanog exhibit specific binding to their respective consensus DNA sequence probes. We also demonstrated that R9-Nanog enters cells and that R9-Sox2 both enters the cell and upregulates the expression of its downstream gene targets. Though we made full-length and soluble TFs, the soluble yields were still low. The open nature of CFPS allows us to perturb protein production conditions by adding excipients to enhance soluble production. However, it is often not clear if the excipients facilitate the production of fully functional proteins. Therefore, we developed a filter microplate assay for quantitative analysis of DNA binding (one function of the TFs) to potentially be used as a screen for identifying protein production conditions that enable production of soluble and active protein. We validated this assay by showing specific DNA binding, affinity, and capacity for CFPS-produced Sox2 and Nanog. We also attempted to improve soluble transducible TF production in live E. coli cultures using a solubility fusion partner, the first domain of the E. coli initiation factor 2 (IF2D1). IF2D1 improved both total and soluble expression of the IF2D1-TF-R9 fusion proteins, but when the IF2D1 was removed, the TF-R9 cargo became insoluble even though the un-cleaved IF2D1-TF-R9 exhibited the expected DNA binding activity. Unfortunately, un-cleaved IF2D1-Oct4-R9 and IF2D1-Sox2-R9 were not fully bioactive when administered to cells. They only influenced the expression of a subset of their downstream target genes, suggesting that while the IF2D1 solubility partner improved soluble TF expression, it did not yield functional TFs. In parallel, we sought to quantify the intracellular delivery of the transducible TFs. Using radioactively labeled R9-Sox2 and Sox2, we showed that both proteins bind equally well to the outside of target fibroblast cells, but only R9-Sox2 enters the cell. This observation was confirmed using immunohistochemistry to visualize protein delivery as well as quantitative PCR to show that R9-Sox2 influences intracellular gene expression while Sox2 does not. The prevailing hypothesis for PTD-mediated cellular entry is fluid phase endocytosis of the cationic PTD fusion proteins bound on the cell surface. Our results provide evidence to support a competing hypothesis in the literature that binding of the PTD fusion to the cell surface is not sufficient for internalization. Originally, we sought to quantify both the intracellular delivery and localization of 14C leucine-labeled R9-Sox2. However, we reached the detection limit of 14C leucine radiation at the whole cell level. Thus, an alternative quantification method was necessary to measure endosomal entrapment, cytoplasmic delivery, and nuclear localization. We developed a sandwich enzyme-linked immunosorbent assay (ELISA) for this purpose. We hypothesized that picomolar sensitivity was required to detect the low levels of R9-Sox2 delivered to the nucleus. We identified an antibody pair that was able to detect picomolar concentrations of purified R9-Sox2. But, this sandwich ELISA exhibited a high degree of non-specific binding when it was performed in a mock experimental context by spiking known amounts of purified R9-Sox2 into cytoplasmic and nuclear lysates. We troubleshot non-specific binding by exploring various antibodies and assay conditions, but were not able to reduce non-specific binding to the level that enabled picomolar detection. However, we did identify a condition that enabled nanomolar detection of R9-Sox2 in undiluted cytoplasmic and nuclear lysates, a nearly 40-fold improvement over the sensitivity of 14C leucine radiation. In summary, this work described the production and characterization of recombinant transducible TFs to support a protein-based approach for iPSC generation. Using CPFS, we developed a platform for producing recombinant TFs as well as tools and methods for characterizing TF activity and intracellular localization. These studies also displayed the flexibility and potential offered by CFPS for engineering and producing complex fusion proteins.
  • John Patrick Welsh.
    The Swartz lab has put much effort into understanding the underlying principles of E. coli-based cell-free protein synthesis (CFPS), and the technology has developed into a scalable, affordable platform for producing a wide range of protein targets. Key breakthroughs have included activating central metabolism, stabilization of critical amino acids, controlling the redox environment to produce proteins containing disulfide bonds, and using scale-up technologies to produce proteins at milligram quantities. My work has sought to expand this CFPS technology for producing valuable and complex eukaryotic protein targets by manipulating and optimizing the folding of these proteins in the heterologous CFPS environment. Furthermore, I have sought to apply these advances to specific applications of interest. By modifying a key molecular chaperone native to the eukaryotic endoplasmic reticulum (ER), the Hsp70-family chaperone, BiP, soluble production was increased in CFPS reactions for specific proteins normally secreted through this organelle, namely those from the immunoglobulin superfamily which includes antibodies, T-cell receptors, and many membrane receptors. First, the functional properties of BiP were compared to that of the E. coli Hsp70, DnaK. A fusion protein was then constructed between BiP and the ribosome-binding portion of the E. coli protein, trigger factor, to localize BiP to translating ribosomes. This replicated the native function of BiP, which provides co-translational folding assistance to nascent polypeptides. After verifying its bioactivity, this fusion protein was utilized in CFPS reactions to indicate that the chaperone functions of BiP are specific to proteins normally secreted through the eukaryotic ER, whereas DnaK demonstrates a more general chaperone mechanism. Since the discovery that somatic cells could be reprogrammed back to a pluripotent state through the viral expression of a specific set of transcription factors, there has been great interest in reprogramming using a safer and more clinically relevant protein-based approach. Production of these transcription factor proteins was greatly increased by fusing them to the C-terminus of the solubility partner, IF2 domain 1 (IF2D1). While the fusions provided marginal benefit in molar yields using a CFPS approach, in vivo E. coli expression produced the transcription factors in soluble form. The fusion proteins could be purified in milligram quantities from liter shake-flask cultures, whereas essentially no soluble protein accumulated without the fusion partner. The transcription factor fusions bound specifically to their consensus DNA sequences and partially activated some of their downstream gene targets. Another application utilizing CFPS technology is an enhanced luciferase mutant from the marine copepod, Gaussia princeps (GLuc). GLuc is both the smallest and brightest known luciferase, and previous work from our lab demonstrated that this protein could be produced at higher volumetric yields and specific activities in CFPS compared to conventional protein expression systems. By mutating key residues in the Gaussia luciferase sequence, the luminescence half-life was shown to increase over ten-fold while maintaining the initial specific activity of the wild-type. This improved mutant provides a valuable imaging agent to use in fusions and bioconjugates with other proteins such as those that recognize cell surface markers on cancer cells. In a final application, influenza vaccines were produced using CFPS by isolating specific fragments of the protein hemagglutinin (HA), a viral surface protein. Specific mutations as well as a C-terminal trimerization domain were critical for producing this protein fragment in both its monomeric and native trimeric forms. By using the CFPS platform to incorporate non-natural amino acids (nnAAs) with alkyne functional groups, the HA proteins were covalently 'clicked' to virus-like particles (VLPs) that had surface exposed nnAAs with azide functionality. The VLPs provide an immunogenic delivery platform that efficiently traffics to lymph nodes and allows for co-attachment of other adjuvants in addition to the primary HA antigen. This vaccine platform was characterized and tested in mouse models and compared to both a standard influenza vaccine as well as free HA protein fragments. In summary, CFPS is a valuable and robust method of protein production for a variety of targets. My thesis has sought to use this platform as a means to better understand folding pathways of complex, eukaryotic proteins and improve production of these proteins. To this end, CFPS has been shown to be a valuable method for elucidating and manipulating chaperone function, producing difficult proteins with enhanced function, and as a platform to produce novel vaccines.
  • 2011From: Springer
    Charles S. Cox Jr., editor.
  • 2016From: Springer
    Asif Muneer, Ian Pearce, David Ralph, editors.
    Introduction to Prosthetic Devices -- History of Prosthetic Surgery in Urology -- Infection and biofilms -- Patient selection and assessment -- Patient Consent for Surgery -- Theatre preparation and equipment -- Patient preparation for surgery -- Urinary Catheters, Drains and Stomas -- Ureteric Stents -- Prostatic Stents -- Testicular Prosthesis -- Surgery for female urinary incontinence -- Sacral neuromodulation -- The artificial urinary sphincter -- Male urethral slings -- Injectable agents in urology -- Penile reconstructive surgery using grafts -- Penile prosthesis surgery -- Complications of penile prosthesis surgery -- Future developments in prosthetic surgery.
  • Debanti Sengupta.
    There is a tremendous need for muscle regeneration therapies to replace tissue that is lost due to disease or injury. This work is focused on developing engineered replacement therapies for lost or damaged skeletal and cardiovascular muscle tissue. In order to create viable, clinically relevant regenerative therapies, I have used recombinant protein technology to synthesize a family of protein-engineered biomaterials that incorporate critical cues for the recapitulation of in vivo muscle tissue conditions. Crucially, these biomaterials allow the independent tuning of multiple biomaterial properties including cell adhesivity, biomaterial stiffness, and topographical cues. Each of these biomaterial properties impacts muscle cell behavior independently as well as in concert. I have exploited the range of biomaterial tunability available to us to identify biomaterial conditions that enable production of striated muscle tissue using primary human skeletal muscle myoblasts (hMBs) that may be electrically paced. I have further demonstrated that mouse model skeletal muscle cell lines do not accurately recapitulate primary human myoblast behavior in response to biomaterial properties, particularly with respect to integrin-matrix interactions. Importantly, the expression of mature muscle markers that indicate muscle cell differentiation could be accelerated simply by changing biomaterial stiffness and introducing biomaterial microtopography. Finally, as demonstration that this protein-engineered biomaterial strategy may have application in the regeneration of myocardial as well as skeletal muscle tissue, cardiomyocytes derived from human embryonic stem cells exhibited good cell viability and improved contractility on these biomaterials. This thesis represents important advancements in the development of regenerative muscle tissue engineered constructs.
  • 2010From: CRCnetBASE
    edited by Sheldon J. Park, Jennifer R. Cochran.
    "Experimental protein engineering and computational protein design are broad but complementary strategies for developing proteins with altered or novel structural properties and biological functions. By describing cutting-edge advances in both of these fields, Protein Engineering and Design aims to cultivate a synergistic approach to protein science. The first half of the book discusses experimental approaches to protein engineering and starts by describing several high-throughput screening platforms for protein engineering. Key techniques used for diversity generation are also discussed. The next few chapters present examples of therapeutics, enzymes, biomaterials, and other proteins that have been engineered by rational or combinatorial approaches. The section finishes with a chapter on the use of non-natural amino acids in protein engineering. The second half of the book introduces computational protein design, beginning with a chapter on computational and informatics algorithms used in protein engineering. Core components of computational protein design are then discussed in detail, and examples of heuristic protein design are provided. Subsequent chapters present examples of how computational design has played a critical role in advancing the field of protein engineering. Concluding with a chapter outlining current challenges in the field, this book makes computational protein design and diversity-oriented protein engineering widely accessible to a broad audience in academia and industry alike."--Publisher's description.
  • 2008From: Springer
    Pamela Gallagher, Deirdre Desmond, Malcolm MacLachlan, editors.
  • Hoda (Hedi) Razavi.
    Congenital heart defects (CHDs) are structural abnormalities of the heart and the great vessels that affect approximately 1 of 100 children born. Pulmonary artery stenosis is an obstruction which leads to ventilation-perfusion mismatching, right ventricular hypertension, right heart failure and possibly death. These lesions may be difficult to manage, as physicians cannot know a priori whether a particular stenosis should be treated and what the optimal timing for intervention would be. The general purpose of this work has been to quantitatively characterize the developmental effects of a pulmonary artery stenosis on the hemodynamics and structure of the pulmonary arterial system in small animal models. To enable the study of pulmonary arterial hemodynamics, we introduce the application of phase-contrast magnetic resonance imaging (PCMRI) to the pulmonary arteries of rats and quantitatively describe the pulmonary hemodynamic changes that take place with normal postnatal development. We validate the in vivo flow measurements of PCMRI against echocardiography (ultrasound) and fluorescent microspheres and establish the MR technique as consistent and reliable. We describe pulmonary arterial growth trends to consist of a fast growth spurt until adolescence, followed by a continuous yet slower growth until adulthood and show that relative flow to each lung does not change throughout development. To enable the study of the three-dimensional structure of the pulmonary vasculature, we developed new arterial casting, high-resolution micro-Computed Tomography imaging and image analysis techniques that when applied to the normal development of the lung indicate a continual growth of small arterioles [less than]100[Mu]m in lumen size until adulthood. These two novel techniques when applied to the case of a unilateral pulmonary artery stenosis reveal an abrupt reduction of blood flow to the obstructed lung, and an abrupt increase for the contralateral lung. Changes in arterial distensibility relative to pulmonary flow indicate the loss of an initial compensatory mechanism that attempts to maintain the normal homeostatic state but fails at later stages of development. We find that the hypoperfused lung suffers from hypoplasia, as well as severe vascular growth abnormalities of arterial disorganization, loss of vessels, and enlargement of bronchial arteries that result in increased pulmonary vascular resistance. The contralateral lung also exhibits impaired vascular growth due to increased pulmonary flow and pressure. Despite being larger, this lung also suffers from a loss in vessels that under conditions of stress leads to substantial elevation of pulmonary arterial pressures. These results suggest that early intervention in patients with pulmonary artery stenosis may be of utmost importance in halting and reversing such disadvantageous vascular remodelings.
  • Andrea Seba Les.
    An abdominal aortic aneurysm (AAA) is a localized expansion of the abdominal aorta. AAA disease affects 5-7% of Americans over age 60 and AAA rupture kills approximately 9,000 people each year. Currently, there is no effective medical therapy for AAA disease and most AAA patients undergo "watchful waiting" until their AAA reaches the threshold for surgical repair. During the course of my doctorate studies, I used magnetic resonance imaging (MRI) and computational fluid dynamics to investigate exercise as a possible medical therapy for AAA disease and to understand the baseline flow and luminal motion conditions in the aneurysmal abdominal aorta. I imaged 64 patients with small AAAs (< 5 cm) in the supine position using a 1.5T Magnetic Resonance scanner. A 3D gadolinium-enhanced magnetic resonance angiography (MRA) sequence was used to image the aorta, a cardiac-gated phase contrast sequence (PC-MRI) was used to measure blood velocity perpendicular to the aorta at the supraceliac (SC) and infrarenal (IR) levels, and a cardiac-gated cine-FIESTA sequence was used to image luminal wall motion at the SC, IR, and Mid-Aneurysm (MA) locations. This data was used to conduct the following investigations: 1. Finite Element Analysis of blood flow at rest and simulated exercise. The MRA and PC-MRI data were used in combination with finite element analysis to elucidate the hemodynamic factors by which exercise might slow AAA growth in eight patients. Results indicate that mean wall shear stress (MWSS) was lowest in the aneurysm during rest (2.5±2.1 dynes/cm2) and MWSS increased and oscillatory shear index (OSI) decreased at the SC, IR, MA, and suprabifurcation locations during exercise. Mild turbulence existed at rest, while moderate aneurysmal turbulence was present during exercise. We hypothesize that the increased MWSS, decreased OSI, and moderate turbulence present during exercise may attenuate AAA growth. 2. Allometric scaling of mean SC and IR flow. The PC-MRI data were used to derive allometric scaling equations of mean SC and IR flows versus metrics of body size in 36 patients. Results of this investigation revealed that both the SC and IR peak-aligned averaged waveforms had the biphasic shapes characteristic of older adults. Mean SC and IR flows were 51.2±10.3 ml/s and 17.5±5.44 ml/s, respectively. Linear regression of the log-log plots of mean SC and IR flows versus body size revealed that body surface area was the strongest predictor of mean SC (R2=0.29) and IR flow (R2=0.19). 3. Wall motion characterization in the aneurysmal abdominal aorta. The cine-FIESTA luminal wall motion data were used to compute average diameter, strain, elasticity, and stiffness as well as changes in wall elastic properties versus age at the SC, IR, and MA locations in 45 patients. Results revealed that aortic elasticity and stiffness varied exponentially with age, and that the average percent change in diameter was 6.69%, 5.60%, and 2.66% at the SC, IR, and MA locations, respectively. Future work entails comparing morphologic MRI data at study intake and 2- or 3- follow-up, validating our simulated velocity fields against 2D 3-component PC-MRI data, and further developing 3D phase contrast acquisition and post-processing techniques in order to compute patient-specific aortic branch vessel flow splits, as well as for improved velocity field validation.
  • Mindy H. Chang.
    The visual system has a limited capacity for capturing and processing the richness and intricate detail of the surrounding environment. Visual information that arrives in the retina is converted from relative light intensities to patterns of excitation and then transmitted to a hierarchy of visual areas, which process and combine increasingly complex features of the visual signal to form a visual percept. At each stage, the amount of task or stimulus-related information a neuron can encode depends on the separability of its responses to different conditions. Using electrophysiological recordings of extracellular spiking activity from single neurons in awake behaving monkeys, we explored ways to quantify information in neuronal firing rates in order to address specific questions about sensory and cognitive signals in visual cortex and frontal cortex during different behavioral contexts. In the first study, we addressed a question of latency differences in the visual pathways that process color using a passive fixation task. Color processing occurs generally along two separate chromatic pathways, and previous work has indicated that information from the two pathways arrive with a relative lag in primary visual cortex. However, to form a perception of color, these two pathways must converge at some stage of visual processing. We used information theory to examine the timecourse of chromatic information in neurons further up the visual hierarchy in area V4, which has been implicated as an area with an important role in color processing. We found that on average, information specific to each pathway arrived simultaneously in V4, suggesting that color signals from the different pathways converge at some point within or before V4 in the visual hierarchy. In order to select behaviorally relevant information from the large amount of visual information available, shifting the focus of gaze (via saccadic eye movements) and directing attention provide ways to allocate processing resources to selected locations in visual space. Studies have shown that perceptual enhancements at behaviorally selected spatial locations are accompanied by enhanced processing in visual cortex. The mechanisms by which neurons in the brain control the selection of sensory signals remain unclear. Previous works suggest that the control of attention and eye movements, as well as the modulation of sensory representations, originate in a distributed network that includes the frontal eye field (FEF) in frontal cortex. We studied responses of single neurons recorded separately in area V4 and the FEF of monkeys engaged in different visuospatial selection tasks. In addition to firing rate responses, we examined the trial-to-trial response variability, which has been suggested to reflect behavioral state. During natural vision, the eyes make frequent movements to selected targets. To better understand how these gaze shifts influence visual processing, we examined selective visual processing in area V4 during saccade preparation. We found that V4 neurons show transiently enhanced stimulus discrimination at the saccade target. This enhancement is due in part to changes in response magnitude, but may also be facilitated by reduced variability (increased reliability) of sensory representations. The similarity to effects of covert attention and experimental manipulations of FEF activity provides further evidence that the mechanisms driving visual modulation during saccade preparation and covert spatial attention rely on common neural resources. To explore signals that likely modulate visual responses through feedback connections, we examined the role of FEF neurons in the maintenance and selection of spatial information. In a task that required remembering and directing spatial attention to a cued location while withholding eye movements, neurons in the FEF exhibited spatially selective persistent activity, which continuously tracked the location of the cue. Moreover, this maintenance of spatial information correlated with successful deployment of attention. Despite robust visual and cognitive firing rate modulations that predicted behavioral performance on the task, declines in response variability appeared to be most effectively driven by visual stimulation, rather than spatial working memory or attention. This indicates that, at least in the FEF, behavioral engagement alone is not sufficient to drive changes in variability. Instead, changes in response variability may reflect shifts in the balance between feedforward and recurrent sources of excitatory drive.
  • Erin Elizabeth Butler.
    The ability to reach, grasp, transport, and release objects is central to activities of daily living, such as feeding and grooming. However, children with cerebral palsy (CP) often have difficulty with these tasks, limiting their independence. While it is challenging to characterize and quantify specific upper limb movement disorders in CP, it is essential for identifying the underlying neural correlates and etiology, assessing movement disorder subtypes, i.e. spasticity, dystonia, and ataxia, which affect treatment selection, and measuring treatment outcomes. Current methods for measuring upper limb motion deficits are based predominantly on subjective, observational assessments. Thus, we have proposed three-dimensional motion analysis of the upper limbs during a Reach & Grasp Cycle to address the need for a standardized protocol for analysis of upper limb motion. The Reach & Grasp Cycle is a sequence of tasks that incorporates all major joints of the upper limb and simulates a functional task that is feasible yet challenging for individuals with CP. Using a biomechanical model of the trunk and upper limbs, we calculated three-dimensional joint kinematics and temporal-spatial parameters for 30 typically developing (TD) children and 25 children with CP and upper limb involvement, ages 5-18 years, using an optoelectric motion analysis system. Consistent normative data and clinically significant differences in joint motions and temporal-spatial parameters between the CP and TD children suggest the Reach & Grasp Cycle is a repeatable protocol for objective and quantitative clinical evaluation of functional upper limb motor performance. Next, we derived a single score of upper limb pathology from upper limb kinematics called the Pediatric Upper Limb Motion Index (PULMI). The root-mean-square difference was calculated between the data of each child with CP and the average from the TD population for eight kinematic variables over the Reach & Grasp Cycle. The raw value was then scaled such that a PULMI score [greater than or equal to] 100 indicated the absence of upper limb pathology, and every 10 points below 100 corresponded to one standard deviation away from the TD PULMI mean. The PULMI was significantly different between the TD children and children with CP (Wilcoxon Z=-5.06, p< .0001), and between children with spastic CP and dyskinetic CP (Z=-2.47, p< .0135). There was a strong negative correlation between the PULMI and the standard Manual Ability Classification System for all children with CP (Spearman's rho=-.78, p< .0001), indicating good validity of the PULMI. In addition, four key temporal-spatial parameters (movement time, index of curvature during reach, ratio of the peak velocity of the transport and reach phases of the Reach & Grasp Cycle, and total number of movement units) revealed differences in movement patterns between CP and TD children. Furthermore, a multi-variable logistic regression of these temporal-spatial parameters was derived which correctly predicted 19 of 22, or 86%, of movement disorder sub-types (spastic versus dyskinetic CP). This research describes a pediatric upper limb motion index (PULMI) for children with cerebral palsy (CP) that provides information regarding the quality of upper limb motion during a functional sequence of tasks. The PULMI, calculated from upper limb kinematics, and key temporal-spatial parameters of the Reach & Grasp Cycle offer a quantitative approach to analyzing the quality of upper limb function in children with CP and identifying specific types of movement deficits. It is suggested for use in both research and clinical applications.
  • Joseph V. Tranquillo.
    Neural anatomy -- Passive membranes -- Active membranes -- Propagation -- Neural branches -- Synapses -- Networks of neurons -- Extracellular recording and stimulation -- The neural code -- Applications.
  • Douglas Scott Jones, II.
    Ligand-receptor interactions govern nearly all cellular processes, and dysregulation leads to a range of diseases including cancer, autoimmune diseases, and regenerative disorders. As such, new strategies to target ligand-receptor interactions for therapeutic applications are an important area of research. To develop enhanced agonists and antagonists of the Met receptor, a critical target in cancer therapy and regenerative medicine, we engineered a fragment of the natural activating ligand (termed NK1). First, NK1 was evolved for improved stability using directed evolution. Then, using the activation mechanism of Met by NK1, the resulting enhanced stability mutants were rationally engineered for either agonistic or antagonistic activity. Next, the rationally engineered mutants were used as 'molecular tools' to provide further insights into NK1 structure and function. Finally, these insights supported additional rational engineering to generate further enhanced agonistic proteins. The antagonistic and agonistic proteins developed in this thesis hold promise as cancer therapeutics and diagnostics or for regenerative medicine applications, respectively. This work also supports native ligands as a promising starting point for development of therapeutic proteins.
  • Michael Nathaniel Cantor.
    Status: Not Checked OutLane Catalog Record
  • Andrew Bruce Holbrook.
    High Intensity Focused Ultrasound (HIFU) is a promising technique for non-invasively destroying tissue deep inside the body, without damage to the skin or intervening tissue. The technique has been performed under both ultrasound and magnetic resonance imaging (MRI) guidance in multiple organ systems, including the uterus, prostate, and brain. Treating unresectable cancers and metastases in the liver is another potential application for HIFU. However the method is currently limited to breath-hold treatments under general anesthesia. The purpose of this work is to build a system for a less-invasive free-breathing MRI-guided real time liver ablation. The three key elements to the system are 1) real-time temperature imaging suitable for the free breathing liver, 2) rapid focal spot localization, and 3) beam steering during free-breathing. For in vivo temperature imaging in the presence of motion, liver motion in 5 normal volunteers was studied. The maximum velocity of the liver was found to be 10.8 mm/s in the superior-inferior direction and 4.23 mm/sec in the anterior-posterior direction. A pulse sequence that allows for high speed, high resolution MR-thermometry utilizing the proton resonant frequency shift (PRF shift) thermometry technique with referenceless image reconstruction was developed. The sequence utilizes outer volume suppression and readout-segmented EPI trajectories to increase the frame rate while not sacrificing resolution. Ablations in a moving phantom moving at speeds of 13 mm/s are compared to static ablations and found to have good agreement. Additionally, SNR characteristics were measured in the liver of normal volunteers, where the average standard deviation was 1.48 degrees C. A HIFU focus must be visualized prior to performing the actual ablation. In static ablations, a non-lethal thermal test spot is performed to calibrate the focus. However, in the liver, perfusion and the need to steer the beam with the motion makes this technique difficult and still require significant energy. The use of MR acoustic radiation force imaging (MR-ARFI) was investigated as a method for visualizing the focus without the high power of a test spot but with the same location accuracy as the thermometry images. The MR-ARFI sequence is a single shot spin echo sequence with an identical readout trajectory to the thermometry sequence that can localize tissue focus displacement in two acquisitions. MR-ARFI displacement maps were compared to foci in ablation thermometry images in both phantoms and in porcine livers. MR-ARFI was found to be effective in focus targeting calibration, with a standard deviation error of only 1.13 mm between displacement and thermal foci in vivo. Using these two sequences and an MR-tracking sequence for HIFU transducer localization, a technique for steering a HIFU focus to a specific target was developed. A lookup table of transducer location, target location, and respiration value measured by an external respiratory belt is created prior to an ablation. The focus location is varified using the gated MR-ARFI pulse sequence discussed prior. During the ablation, the focus is steered based on the lookup table and the current respiration value. This method is investigated by performing steered HIFU ablations in moving phantom experiments and compared to non-steered moving ablations and static ablations. Utilizing this technique, steered HIFU ablations required 1039 J to reach a temperature of 15 degrees C, compared to 7480 J and 921 J for non-steered and static ablations, respectively.
  • Wang Rui.
    How the human brain processes phonemes has been a subject of interest for linguists and neuroscientists for a long time. Electroencephalography (EEG) offers a promising approach to observe neural activities of phoneme processing in the brain, thanks to its high temporal resolution, low cost and noninvasiveness. The studies on Mismatch Negativity (MMN) effects in EEG activities in the 1990s suggested the existence of a language-specific central phoneme representation in the brain. Recent findings using magnetoencephalograph (MEG) also suggested that the brain encodes the complex acoustic-phonetic information of speech into the representations of phonological features before the lexical information is retrieved. However, very little success has yet been reported in classifying the brain activities associated with phoneme processing. In my work, I proposed a classification framework which incorporates Principal Components Analysis (PCA), cross-validation and support vector machine (SVM) methods. The initial classification rates were not very good. Progress was made by using bootstrap aggregation (Bagging) scheme and introducing phase calculations. To calculate phase, I computed the Discrete Fourier Transform (DFT) of the original time-domain signal and kept the angles of the finite sample of frequencies. The resulting EEG spectral representation contains only the phase and frequency information and ignores the amplitudes. Using this method, the accurate rate of classifying averaged test samples of eight consonants improved from 41% to 51%. Furthermore, the qualitative analysis of the similarities between the EEG representations, derived from the confusion matrices, illustrates the invariance of brain and perceptual representation of phonemes. For brain and perceptual representation of consonants, voicing is the most distinguishable feature among voicing, continuant and place of articulation. And the feature vowel-height is more robust than vowel-backness in both brain and perceptual representation of vowels. By extending and further refining these methods, it is likely significant classification of other phonemes and features can be made.
  • 2011From: Springer
    Ira S. Cohen, Glenn R. Gaudette, editors.
    Inducing embryonic stem cells to become cardiomyocytes / Alexander M. Becker, Michael Rubart, and Loren J. Field -- Regenerating function in vivo with myocytes derived from embryonic stem cells / Priya R. Baraniak and Todd C. McDevitt -- Excitation-contraction coupling, functional properties, and autonomic and hormonal regulation in human embryonic stem cell derived cardiomyocytes / Oshra Sedan and Ofer Binah -- Embryonic stem cell derivatives for cardiac therapy : advantages, limitations, and long-term prospects / Michal Weiler-Sagie and Lior Gepstein -- Methods for differentiation of bone-marrow-derived stem cells into myocytes / Shinji Makino and Keiichi Fukuda -- Homing, survival, and paracrine effects of human mesenchymal stem cells / Sergey Doronin -- Bone marrow cell therapy after myocardial infarction : what have we learned from the clinical trials and where are we going? / Kai C. Wollert -- Evidence for the existence of resident cardiac stem cells / Isotta Chimenti ... [et al.] -- Multiple sources for cardiac stem cells and their cardiogenic potential / Antonio Paolo Beltrami, Daniela Cesselli, and Carlo Alberto Beltrami -- Skeletal muscle stem cells in the spotlight : the satellite cell / Zipora Yablonka-Reuveni and Kenneth Day -- Regenerating mechanical function in vivo with skeletal myoblasts / Todd K. Rosengart and Muath Bishawi -- Methods for inducing pluripotency / Raymond L. Page, Christopher Malcuit, and Tanja Dominko -- Inducible pluripotent stem cells for cardiac regeneration / Naama Zeevi-Levin and Joseph Itskovitz-Eldor -- Induced pluripotent cells for myocardial infarction repair / Timothy J. Nelson and Andre Terzic -- Substrates of cardiac reentrant arrhythmias : the possible role of tissue regeneration and replacement / André G. Kléber -- Integration of stem cells into the cardiac syncytium : formation of gap junctions / Peter R. Brink, Ira S. Cohen, and Richard T. Mathias -- Bradyarrhythmia therapies : the creation of biological pacemakers and restoring atrioventricular node function / Richard B. Robinson -- Tachyarrhythmia therapies : approaches to atrial fibrillation and postinfarction ventricular arrhythmias / J. Kevin Donahue and Kenneth R. Laurita -- Long-term prospects for arrhythmia treatment : advantages and limitations of gene and cell therapies / Michael R. Rosen -- Regenerating blood vessels / Tracy A. Gwyther and Marsha W. Rolle -- Regenerating heart valves / Benedikt Weber and Simon P. Hoerstrup -- Tissue engineering strategies for cardiac regeneration / Amandine F.G. Godier-Furnémont ... [et al.] -- Methods of cell delivery for cardiac repair / Sarah Fernandes and Hans Reinecke -- Tracking of stem cells in vivo / Yingli Fu and Dara L. Kraitchman -- Assessing regional mechanical function after stem cell delivery / Jacques P. Guyette and Glenn R. Gaudette.
  • 2012From: ScienceDirect
    David L. Stocum.
  • 2012From: Springer
    edited by Rahul Jandial, Mike Y. Chen ; associate editors, Bihong T. Chen, Joseph Ciacci.
    Frontiers of spinal cord and spine repair : experimental approaches for repair of spinal cord injury / Choya Yoon and Mark H. Tuszynski -- Stem cell based strategies for spinal cord injury repair / Alexa Reeves and Hans S. Keirstead -- Strategies for endogenous spinal cord repair : HPMA hydrogel to recruit migrating endogenous stem cells / Araceli Espinosa-Jeffrey ... [et al.] -- Stem cells and spinal cord injury repair / Soheila Karimi-Abdolrezaee and Eftekhar Eftekharpour -- Chronic pain following spinal cord injury / Radi Masri and Asaf Keller -- Repair of radiation damage and radiation injury to the spinal cord / Timothy E. Schultheiss -- Malignancies of the spinal cord / J. Dawn Waters, Encarnacion Maria Navarro Peran, and Joseph Ciacci -- Molecular basis of intervertebral disc degeneration / Dipika Gopal ... [et al.] -- Bioceramics for osteogenesis, molecular and cellular advances / Hande Demirkiran -- Cell-based therapies for spinal fusion / Ronke Olabisi -- Clinical efficacy of stem cell mediated osteogenesis and bioceramics for bone tissue engineering / Josh Neman ... [et al.] -- Progenitor cells : role and usage in bone tissue engineering approaches for spinal fusion / Lonnissa H. Nguyen ... [et al.].
    Also available: Print – 2012
  • 2011From: Springer
    Gustav Steinhoff, editor.
  • 2014From: ScienceDirect
    [edited by] Giuseppe Orlando, Jan Lerut, Shay Soker, Robert J. Stratta.
    Principles of regenerative medicine and cell,tissue and organ bioengineering -- Kidney -- Liver -- Heart -- Small bowel -- Endocrine pancreas and islets of langerhans -- Lung -- Composite tissues allotranplantation -- Immunosuppression-free transplantation in the regenerative medicine era.
  • 2015From: Springer
    Juichi Ito, editor.
    Preface -- Part 1: Current siguation of the regenerative medicine -- Chapter 1: Current siguation of the regenerative medicine -- Part 2: Development and regeneration of the ear.- Chapter 2: The innner ear -- Chapter 3: Regeneration of the Soft Tissue Defects of the External Auditory Meatus -- Chapter 4: Regeneration of the Tympanic Membrane -- Chapter 5: An approach in regenerative medicine for the treatment of intractable otitis media -- Chapter 6: Peripheral Nerve Regeneration by Tissue Engineering for Prevention of Misdirection -- Part 3: Development and regeneration of the nose and the paranasal sinuses -- Chapter 7: Development and regeneration of the nose and the paranasal sinuses -- Part 4: Development and regeneration of the oral cavity and the pharynx -- Chapter 8: Development and regeneration of the oral cavity and the pharynx -- Part 5: Development and regeneration of the larynx -- Chapter 9: Laryngeal Development -- Chapter 10: Laryngeal framework regeneration -- Chapter 11: Vocal folds Development -- Chapter 12: Regeneration of the vocal fold -- Part 6: Development and regeneration of the head & neck -- Chapter 13: Cranial bone regeneration -- Chapter 14: Salivary gland development and regeneration -- Chapter 15: Regeneration of the Trachea -- Chapter16: Future perspective.
  • 2011From: Springer
    Niranjan Bhattacharya, Phillip Stubblefield (editors).
    A massive wastage of the global resources -- Placenta as a source of stem cells and as a key organ for fetomaternal tolerance -- Placenta and umbilical cord in traditional Chinese medicine -- Use of umbilical venous blood on assessing the biochemical variations of acid-base, nutritional and metabolic parameters on growth-retarded fetuses, in comparison with gestational control cases: a study -- Umbilical cord blood transfusion and its therapeutic potentialities -- Autologous placental blood transfusion for the therapy of anemic neonates -- Cord blood: a massive waste of a life-saving resource: a perspective on its current and potential uses -- Clinical experience of cord blood autologous transfusion -- Emergency use of human cord blood -- Hemoglobin-based oxygen carriers in trauma care: the US multicenter prehospital trial -- Placental umbilical cord blood as a true blood substitute with an edge -- Implications of feto-maternal cell transfer in normal pregnancy -- Early reports on the prognostic implications and immunotherapeutic potentials of Cd34 rich cord whole blood transfusion in advanced breast cancer with severe anemia -- Anti-inflammatory effects of human cord blood and its potential implications in neurological disorders -- Transforming "waste" into gold: identification of novel stem cells resources with therapeutic potential in neuromuscular disorders -- Human umbilical cord blood cells for stroke -- Placental umbilical cord blood transfusion for stem cell therapy in neurological diseases -- Umbilical cord and its blood: a perspective on its current and potential use in ophthalmology -- Umbilical vein grafts for lower limb revascularization -- Cord blood stem cells in angiogenesis. Endothelial progenitor cells from cord blood: magic bullets against ischemia? -- Therapeutic potential of placental umbilical cord blood in cardiology -- Stem cell therapy for heart failure using cord blood -- Human umbilical cord blood mononuclear cells in the treatment of acute myocardial infarction -- Umbilical cord-derived mesenchymal stem cells -- Cord blood stem cell expansion ex vivo: current status and future strategies -- Embryonic-like stem cells and the importance of human umbilical cord blood for regenerative medicine -- Use of non-hematopoietic stem cells of fetal origin from cord blood, umbilical cord, and placenta in regeneration medicine -- Animal studies of cord blood and regeneration -- Immune privilege of cord blood -- Combination cellular therapy for regenerative medicine: the stem cell niche -- Use of cord blood in regenerative medicine -- Comparisons between related and unrelated cord blood collection and/or banking for transplantation or research: the UK NHS blood and transplant experience -- Donor and collection-related variables affecting product quality in ex utero cord blood banking -- Cord blood as a source of hematopoietic progenitors for transplantation -- Amniotic fluid and placenta stem cells -- Use of amniotic membrane, amniotic fluid, and placental dressing in advanced burn patients -- Clinical use of amniotic fluid in osteoarthritis: a source of cell therapy -- A study and follow-up (1999-2009) of human fetal neuronal tissue transplants at a heterotopic site outside the brain in cases of advanced idiopathic Parkinsonism -- Ethical issues surrounding umbilical cord blood donation and banking.
  • 2008From: CRCnetBASE
    B.S. Dhillon.
    Basic mathematical concepts -- Introduction to reliability technology, human error, and quality -- Medical device safety and quality assurance -- Medical device software quality assurance and risk assessment -- Medical device maintenance and sources for obtaining medical device-related failure data -- Human error in health care -- Health care human error reporting systems and models for predicting human reliability and error in health care -- Patient safety -- Introduction to quality in health care -- Quality methods for use in health care.
  • 2017From: CRCnetBASE
    edited by Pedro Encarnação and Albert M. Cook.
    1. Fundamentals of Robotic Assistive Technologies -- 2. Human-Robot Interaction for Rehabilitation Robots -- 3. Assistive Robotic Manipulators -- 4. Upper and Lower Limb Robotic Prostheses -- 5..Smart Wheelchairs for Assessment and Mobility -- 6. Exoskeletons as an Assistive Technology for Mobility and Manipulation -- 7. Robotic Systems for Augmentative Manipulation to Promote Cognitive Development, Play, and Education -- 8. Social Assistive Robots for Children with Complex Disabilities -- 9. Robots Supporting Care for Elderly People -- 10. Ethical and Social Implications of the Use of Robots in Rehabilitation Practice.
  • Emel Demircan.
    Potential benefits from human motion understanding range from rehabilitation and physical therapy to ergonomics design, sports training, and computer animation. Robotics-based reconstruction and synthesis of human motion is a powerful tool to study human motion. Understanding human motion requires accurate modeling of the kinematics, dynamics, and control of the human musculoskeletal system to provide the bases for the analysis, characterization, and reconstruction of their movements. These issues have much in common with the problems found in the studies of articulated body systems in robotics research. Task-based methods used in robotics may be leveraged to provide novel musculoskeletal modeling methods and physiologically accurate performance predictions. However, reproducing and synthesizing the basis of human movements in common robotics frameworks bring the following compelling challenges: Scaling detailed musculoskeletal models to the human subject. Reconstruction and redundancy resolution of human motion in presence of constraints. Characterization of human postural behaviors and dynamic skills. The analysis, control, and reconstruction approaches developed in this thesis deal with these challenges. In motion analysis, methodologies are developed to characterize human postural behaviors and dynamic skills in a unified framework including task, posture, and additional constraints such as contact with the environment and physiological capacity. Information, which is gained from musculoskeletal models that are mapped into the motion of the human, is exploited in a task-oriented simulation and control framework. Task-driven human performance metrics, including the criteria for operational space acceleration characteristics and human muscular effort, are developed and analyzed for human skills. Using these metrics, optimization criteria are introduced that take into account human skeletal kinematics, muscle activation, physiology, and dynamics, and that correlate to the observed motion characteristics. In motion control, algorithms are developed to control human musculoskeletal systems in real-time. A marker space control structure is established for the reconstruction of human motion by direct tracking of marker trajectories. Dynamic consistency between marker space tasks, posture, and additional constraints is achieved by recursive projections into the null spaces of higher priority tasks. The human motion control hierarchy is established in marker space following the natural tree-like branching structure of the human musculoskeletal model. The marker space reconstruction methodology allows computing full human motion dynamics in real-time. In addition, an approach for resolving muscle redundancies is developed based on a new hybrid electromyography and conventional computed muscle control method. These methodologies are validated through three-dimensional dynamic simulations of musculoskeletal models scaled to the subjects. Extensive motion capture experiments are conducted on human subjects of various skill levels including a tai chi master, an elite college-level golfer, a novice golfer, and a professional American footballer for several dynamic movements. Using real-world experimental data, dynamic simulations are exemplarily created and analyzed for golf swings, throwing motions, and gait. The robotics-based reconstruction and synthesis approaches introduced in this thesis provide an important basis for understanding natural human motion. These tools are applicable to efficient robot control and human performance prediction. Another important application is the synthesis of novel motion patterns in the areas of robotics research, athletics, rehabilitation, physical therapy, and computer animation.
  • 2011From: Springer
    edited by Ashok Kumar Hemal, Mani Menon.
    The History of Robotic Surgery -- Robotic Instrumentation and Operating Room Setup -- Port Placement in Robotic Urologic Surgery -- Achieving Efficiency in the Operating Room: Step by Step -- Laparoscopy vs. Robotics: Ergonomics -- Does It Matter? -- Anesthetic Considerations for Robotic Urologic Surgery -- The Development of a Robotic Urology Program in the UK -- Robotic Urologic Surgery: How to Make an Effective Robotic Program -- Witnessing the Transition of Open to Robotic Surgery -- Patient-Side Surgeons: The Unsung Heroes of Robotic Surgery -- Training in Robotic Urologic Surgery -- Animal Laboratory Training: Current Status and How Essential Is It? -- Training of Operating Room Technician and Nurses in Robotic Surgery -- Impact of Virtual Reality Simulators in Training of Robotic Surgery -- Training, Credentialing, and Hospital Privileging for Robotic Urological Surgery -- Research in Urologic Oncology in an Era of Minimally Invasive Surgery -- Databases and Data Management for Robotic Surgery -- The Role of Scientific Journals in Disseminating New Technology -- Predicting Robotic Utilization in Urologic Disease: An Epidemiology-Based Model -- Development of the Vattikuti Institute Prostatectomy: Historical Perspective and Technical Nuances -- Transferring Knowledge of Anatomical Dissection from the Laboratory to the Patient: An Australian Perspective -- Robot-Assisted Radical Prostatectomy: A Prostate Surgeon's Perspective -- Cautery-Free Technique of Robot-Assisted Radical Prostatectomy: Impact on Nerve Preservation and Long-Term Outcome on Recovery of Sexual Function -- Current Concepts in Cavernosal Neural Anatomy and Imaging and Their Implications for Nerve-Sparing Radical Prostatectomy -- Robot-Assisted Radical Prostatectomy for Large Glands and Median Lobe -- Extraperitoneal Robot-Assisted Radical Prostatectomy: Simulating the Gold Standard -- The Retrograde Extraperitoneal Approach: Robotic Retrograde Extraperitoneal Laparoscopic Prostatectomy (RRELP). Technical Modifications for Robotic Prostatectomy -- Robotic Radical Prostatectomy: Cancer Control and Implications of Margin Positivity -- Techniques to Improve Urinary Continence Following Robot-Assisted Radical Prostatectomy -- Penile Rehabilitation After Robotic Radical Prostatectomy: The Best Strategy -- Laparoscopy or Robotic Radical Prostatectomy: Pros and Cons -- Complications of Robotic Prostatectomy -- Robotic Urologic Surgery: Robotic-Assisted Adrenalectomy -- Robot-Assisted Laparoscopic Radical Nephrectomy and Nephroureterectomy -- Robot-Assisted Partial Nephrectomy -- Robotic Urologic Surgery: Robot-Assisted Partial Nephrectomy -- Robotic Donor Nephrectomy: Technique and Outcomes -- An European Perspective -- Robot-Assisted Laparoscopic Pyeloplasty -- Robotic Surgery for Urolithiasis -- Ureteral Reconstruction Utilizing Robotic-Assisted Techniques -- Robotic or Laparoscopic Renal Surgery: Pros and Cons -- Robot-Assisted Radical Cystectomy in Male: Technique of Spaces -- Robotic-Assisted Laparoscopic Anterior Pelvic Exenteration for Bladder Cancer in the Female -- Robotic-Assisted Laparoscopic Extended Pelvic Lymph Node Dissection for Bladder Cancer -- Robot-Assisted Intracorporeal Ileal Conduit -- Robotic Urinary Diversion: Technique, Current Status, and Outcomes -- Robotic Bladder Surgery Complications: Prevention and Management -- Robotic Surgery for Ureteral Anomalies in Children -- Robotic Surgery of the Kidney in Children -- Robotic Bladder Surgery in Children -- Robotic Surgery in Urogynecology -- Robotic Repair of Vesico-vaginal Fistula -- Robotic Surgery in Male Infertility (Robotic-Assisted Microsurgery) -- Treater to Target: Experiences of a Prostate Cancer Participant -- My Prostate Cancer -- Telementoring and Telesurgery in Urology -- Robotic Systems: Past, Present, and Future.
  • Bryan Carl Petzold.
    The mechanics of our skin determine how our skin and specialized mechanically-sensitive neurons within it are stressed and strained when touched. Understanding the interplay between skin mechanics and touch sensitivity is paramount in uncovering the fundamental molecular mechanisms underlying touch sensation and in understanding and treating touch insensitivity due to diseases like peripheral neuropathy. Despite this importance, the interplay between skin mechanics and sensitivity is poorly understood. The organism Caenorhabiditis elegans is an excellent model system in which to test the hypothesis that skin mechanics affect touch sensitivity. C. elegans detects body touch with just six mechanically-sensitive neurons. These neurons are embedded in the outer shell (consisting of the cuticle, hypodermis and body wall muscles) of the body plan, which dominates the overall body mechanics. If skin mechanics are important in touch sensitivity in C. elegans, stiffening or softening the outer shell should alter the ability of the animal to detect applied mechanical stimuli. I demonstrate that a piezoresistive cantilever force clamp system and methods that alter C. elegans body mechanics can be combined to directly test the hypothesis that mechanics modulate touch sensitivity. In particular, I build on prior work demonstrating that genetic mutation of cuticle proteins alters body stiffness, and use optogenetic modulation of body wall muscle tone to demonstrate that the body wall muscles modulate C. elegans body mechanics. Combining piezoresistive cantilevers capable of applying minute forces with these techniques to alter the mechanics of the body allows us to directly quantify the affect of body stiffening or softening on force or indentation depth sensitivity in C. elegans. I find that even small shifts in body stiffness have a significant effect on force sensitivity, with body stiffening leading to a reduction in force sensitivity and vice versa. Further, I demonstrate that indentation depth sensitivity is less affected by changes in body mechanics, suggesting that the mechanically-sensitive neurons involved in body touch in C. elegans respond more directly to applied indentation than to applied force. These findings emphasize the importance of considering skin mechanics in understanding the sense of touch and insensitivity due to diseases like peripheral neuropathy.
  • Yun Chen.
    Continuous wireless monitoring of in vivo biopotential, biochemical, and biomechanical properties has the potential to yield breakthroughs in our understanding of human health and disease. In particular, current technology does not yet allow us to do so at micron (i.e., cellular) scales. We look to create a scalable system of chronically implantable passive sensors with a wireless detection platform to individually address and continuously monitor them. Scaling down the size of resonant sensors poses significant challenges for passive wireless detection. In particular, inherently higher resonant frequencies at smaller sizes push our operation into regimes where traditional approaches fail. Two schemes based on power reflection distortion (PRD) and group delay distortion (GDD) are proposed to operate over a wide range of frequencies. They are shown to be capable of operating in high frequency regimes near and above the readout circuit self-resonance. In addition, we describe a generic finite-difference time-domain (FDTD) framework for analyzing electromagnetic (EM) wave propagation and scattering in an anatomically realistic human phantom with an inhomogeneous dispersive model. Interactions with implantable resonant sensors are studied within this framework. We demonstrate a wireless real-time monitoring system with passive, flexible sensors, which scale down to unprecedented dimensions of 1x1x0.1 cubic mm. This level of scaling is enabled by the presented GDD detection scheme, which overcomes the operating frequency limits of traditional strategies and exhibits insensitivity to lossy tissue environments. We apply this system to capture human pulse waveforms in real-time as well as to continuously monitor in vivo intracranial pressures with sensors down to 2.5x2.5x0.1 cubic mm in proof-of-concept mice studies. Furthermore, printable wireless sensor arrays are introduced and their use in concurrent spatial pressure mapping is shown. Our vision is to extend the passive sensing approach and scale the resonant sensor platform down to intracellular dimensions at the intersection of intracellular delivery limits and integrated circuit fabrication capabilities. We demonstrate a family of 3D multilayer micro-Tag (uTag) structures as a potential platform for resonant tagging and sensing at the cellular level. As a stepping stone towards chronic cellular monitoring, we demonstrate the delivery of uTags into living cells and viability of internalized uTags over a 5-day period. Looking forward, this technology creates exciting opportunities to use remote physiological monitoring as a routine part of biomedical research and patient care. In the future, we foresee that such monitoring will be possible even at the cellular level.
  • Alfonso Pedro Farruggio.
    The "integrase" enzyme of the bacterial virus phiC31 mediates the unidirectional fusion of the phiC31 and host-bacterium genomes. This recombination reaction occurs between two specific DNA sequences (att-sites), and can be performed by the enzyme without accessory factors in a wide variety of cellular environments, including human cells. Although its primary application to date in eukaryotes has been in organisms where the native phiC31 integrase (C31-int) att-sites have been pre-introduced, C31-int can also function on certain endogenous sequences (pseudosites) in animal genomes, albeit with significantly reduced activity. The ability of C31-int to perform pseudosite integration has made it the focus of several whole-animal and tissue-culture gene-therapy studies over the past decade, as there is currently no means to safely maintain the therapeutic DNA that is delivered for gene-therapy. The focus of my graduate work has been to assist these efforts to apply C31-int for gene-therapy. Specifically, I have sought to increase our basic scientific understanding of DNA recognition by C31-int through deletion and chimera studies (Chapters 2-3), and I have also attempted to improve the implementation of C31-int applications in mammals through my contributions to applied C31-int projects (Chapters 4-6). The results from my deletion and chimera studies have helped to clarify that C31-int employs DNA binding domains that are largely modular and have also helped to lay the groundwork for a potential means to derive serine integrases with novel specificities. The results from my contributions to applied C31-int projects have made it possible to reverse the wild-type reaction in mammalian cells (Chapter 4), to produce high-quality mouse induced-pluripotent-stem cells (iPSC) with C31-int (Chapter 5), and to genetically engineer mouse iPSCs (Chapter 6). Although C31-int will still require significant engineering before it is suitable for use in human gene therapy, and although additional work will be required to fully realize the potential of our iPSC-production and -engineering scheme in human cells, my experience with C31-int and related enzymes that I describe in this dissertation has left me optimistic that these are not unreasonable goals.
  • Charles S. Lessard.
  • 2007From: CRCnetBASE
    edited by George K. Knopf, Amarjeet S. Bassi.
  • James Joseph Wagner.
    People with severe physical disabilities who have non-technical backgrounds are unlikely candidates to be able to operate vocational assistive robots. Such robotic devices have been costly, complex, programmable only by experts, and prohibitive to user changes. This dissertation describes the design approach created in the development of a small desktop robot system called the Professional Vocational Assistant Robot (ProVAR). ProVAR deals explicitly with the social aspects of human-robot interaction to help individuals with tetraplegia to use the robot. This design approach was heavily influenced by the theory of Social Responses to Communication Technologies (SRCT) and by psychology research that shows the power of a team in complex command, design and learning scenarios. The SRCT concept holds that people's reactions and interactions with computers and other new media entities follow the same social rules used in human-human interactions. If those reactions can be enhanced, the success of assistive robotic systems dependent on them can also be increased. The leveraging of social responses can increase tolerance for the robotic systems' difficulties, and thus increase the chance of adoption and sustained use of the assistive devices by lay users not experienced in computers, robots, or mechanical control devices. A new theory, growing out of SRCT, was proposed. "Social Responses to Somatic Technology" (SRST) guided the development of ProVAR. It is based on a robot users perception that a somatic, e.g., robotic, technology device is, in fact, a social entity. As does a human social entity, each technological social entity consists of two components: the "body" and the "mind." The ProVAR System was designed with two complete social entities, or personalities; both induce social responses. Each of ProVAR's two personalities is expected to maintain a personal relationship with the users, in this case, with an individual with severe physical disabilities and with the occupational therapist responsible for his/her rehabilitation. ProVAR's graphical user interface, named "Jiminey, " is primarily considered by the user to be a mind: a smart consultant/coach. ProVAR's robotic arm, "Pinocchio, " is primarily perceived by the user to be a body: the down-to-earth do'er itself. Even though each of these social entities does have both a body and a mind, each personality's different dominant characteristic allows the user to perceive that he/she is functioning as a teammate with two other distinct entities. These three partners work together to help manage and take advantage of the special capabilities of the ProVAR System to complete desired tasks. During Experiment 1, ProVAR showed 100% of novice users able independently to execute both preprogrammed tasks and also the more complicated manipulation of existing tasks and creation of new ones. ProVAR's SRST-inspired design is effective, with seven of eight metrics positively ranked by users. One additional finding showed that training first on the user interface alone without the presence of the robotic arm was not time effective. A further examination of the application of the SRST concept of "Social Entity = Body + Mind" was done in Experiment 2, studying the effect of the body and the mind of the robotic arm being perceived not to be co-located but in separate locations. Results showed that usability was ranked higher by the study participants if the arm (the body) was perceived as autonomous, i.e., controlling itself (by its mind) with an internal inboard computer, rather than the arm being remote-controlled, i.e., teleoperated (by its mind), in a computer located in another room.
  • 2006From: ScienceDirect
    2006From: MyiLibrary
    Steven M. Kurtz, Avram Allan Edidin.
    Over the past decade, there has been rapid growth in bioengineering applications in the field of spine implants. This book explains the technical foundation for understanding and expanding the field of spine implants, reviews the major established technologies related to spine implants, and provides reference material for developing and commercializing new spine implants. The editors, who have a track record of collaboration and editing technical books, provide a unified approach to this topic in the most comprehensive and useful book to date. Related website provides the latest information on spine technology including articles and research papers on the latest technology and development. Major technologies reviewed include devices used for fusion (screws, plates, rods, and cages), disc repair and augmentation, total disc replacement, and vertebral body repair and augmentation. Technology landscape, review of published/public domain data currently available, and safety and efficacy of technology discussed in detail.
  • 2006From: Springer
    Nabil Dib, Doris A. Taylor, Edward B. Diethrich (editors).
    Ventricular remodeling in ischemic cardiomyopathy / Stefan Klotz and Daniel Burkhoff -- Myocardial regeneration: which cell and why / Elmostafa El Fahime and Jacques Tremblay -- Cardiac stem cells for myocardial regeneration / Bernardo Nadal-Ginard and Simón Méndez-Ferrer -- A historic recapitulation of myoblast transplantation / Daniel Skuk and Jacques Tremblay -- Myoblast cell transplantation preclinical studies / Doris A. Taylor and Harald Ott -- Skeletal myoblasts: the European experience / Philippe Menasche -- Skeletal myoblasts: the U. S. experience / Edward B. Diethrich -- Progenitor cells for cardiac regeneration / Ana Sánchez and Javier Garcia-Sancho -- Bone marrow derived stem cell for myocardial regeneration: preclinical experience / Bradley Martin and Mark Pittenger -- Bone marrow derived stem cell for myocardial regeneration: clinical experience, surgical delivery / Manual Galiñanes -- Autologous mononuclear bone marrow cell transplantation for myocardial infarction: the German experience / Michael Brehm, Tobias Zeus and Bodo E. Strauer -- Autologous mononuclear bone marrow cell transplantation for myocardial infarction: the Spanish experience / Francisco E. Avilés ... [et al.] -- Mobilizing bone marrow stem cells for myocardial repair after acute myocardial infarction / Steve Ellis and Oussama Wazni -- Percutaneous myoblast transplantation: steps in transplantation research / Nabil Dib -- A porcine model of myocardial infarction for evaluation of cell transplantation / Nabil Dib ... [et al.] -- Tissue engineering for myocardial regeneration / Ravi K. Birla -- The role of pet scan in stem cell therapy / Uchechukwa Sampson ... [et al.] -- The measurement of systolic function in the mammalian heart / Blasé Carabello -- Electrophysiological aspects of cell transplantation / Nicholas S. Peters, Nicolas A.F. Chronos and Fernando Tondato -- Regulatory considerations in manufacturing, product testing, and preclinical development of cellular products for cardiac repair / Ellen Areman, Kim Benton and Richard McFarland.
  • 2006From: ScienceDirect
    edited by Irina Klimanskaya, Robert Lanza.
    In vitro experimentation and research tools -- Tissue engineering and regenerative medicine.
    Also available: Print – 2006
  • Kitchener Daniel Wilson.
    The discovery and isolation of human embryonic stem cells (hESCs), and the more recent generation of induced pluripotent stem cells (iPSCs) from adult cells, has given medical science the tantalizing prospect of one day regenerating organs and tissues in human patients, as well as a revolutionary method for investigating heritable human diseases in a petri dish. This is because hESCs and iPSCs are pluripotent, which enables them to differentiate into virtually any cell type of the human body. However, forcing these cells to change their phenotype is an imperfect science, and is often time-consuming, resource-intensive, and plagued by poor yields. My work over the past four years has therefore attempted to characterize the sets of molecules, both messenger RNAs and microRNAs, that together regulate pluripotency. This has included understanding how the stem cell "transcriptome" changes in the face of external insult (e.g. ionizing radiation), how it changes during differentiation to adult phenotypes such as cardiomyocytes and endothelial cells, and how knowledge from it may be used to induce pluripotency. Taken together, interrogating and ultimately controlling the stem cell transcriptome will be an essential step before we can realize the promise of regenerative therapy.
  • 2011From: Springer
    Krishnarao Appasani, Raghu K. Appasani, editors ; foreword by Sir John B. Gordon.
    pt. 1. Stem cell biology -- pt. 2. Epigenetic and microRNA regulation in stem cells -- pt. 3. Stem cells for therapeutic applications -- pt. 4. Nuclear reprogramming and induced pluripotent stem cells -- pt. 5. Tissue engineering -- pt. 6. Regenerative medicine.
  • 2014From: Springer
    Mohamed Al-Rubeai, Mariam Naciri, editors.
    Use of Human Embryonic Stem Cells in Therapy -- Human Neural Stem Cell-based Cell- and Gene-therapy for Neurological Diseases -- Vascular Stem Cell Therapy -- Bioprocessing of Human Pluripotent Stem Cells for Cell Therapy Applications -- Blood Cell Bioprocessing: The Haematopoietic System and Current Status of In-vitro Production of Red Blood Cells -- Bioprocessing Challenges Associated with the Purification of Cellular Therapies -- Separation Technologies for Stem Cell Bioprocessing.
  • 2010From: Springer Protocols
    edited by Randall J. Lee.
    Stem cells for myocardial repair and regeneration : where are we today? / Randall J. Lee -- Bone marrow-derived endothelial progenitor cells : isolation and characterization for myocardial repair / Masaaki Ii -- Umbilical cells stem cells for myocardial repair and regeneration / Nicholas Greco and Mary J. Laughlin -- Isolation of resident cardiac progenitor cells by Hoechst 33342 staining / Otmar Pfister ... [et al.] -- Mesenchymal stem cell therapy for cardiac repair / Andrew J. Boyle, Ian K. McNiece, and Joshua M. Hare -- Methods for human embryonic stem cells derived cardiomyocytes cultivation, genetic manipulation, and transplantation / Gil Arbel ... [et al.] -- Experimental cell transplantation therapy in rat myocardial infarction model including nude rat preparation / Wangde Dai and Robert A. Kloner -- Large animal model of heart failure for assessment of stem cells / Sharad Rastogi -- Histopathologic assessment of myocardial regeneration / Naima Carter-Monroe ... [et al.] -- Assessment of myocardial angiogenesis and vascularity in small animal models / Matthew L. Springer -- Superparamagnetic iron oxide labeling of stem cells for MRi tracking and delivery in cardiovascular disease / Dorota A. Kedziorek and Dara L. Kraitchman -- Embryonic stem cell biology : insights from molecular imaging / Karim Sallam and Joseph C. Wu -- Genetic fate-mapping for studying adult cardiomyocyte replenishment after myocardial injury / Sunny S.-K. Chan ... [et al.] -- In vitro electrophysiological mapping of stem cells / Seth Weinberg, Elizabeth A. Lipke, and Leslie Tung -- Assessment of cardiac conduction : basic principles of optical mapping / Chunhua Ding and Thomas H. Everett IV -- Surface patterning for generating defined nanoscale matrices / Karen L. Christman and Heather D. Maynard.
  • 2009From: Atypon
    Binseng Wang.
    Technology is essential to the delivery of health care but it is still only a tool that needs to be deployed wisely to ensure beneficial outcomes at reasonable costs. Among various categories of health technology, medical equipment has the unique distinction of requiring both high initial investments and costly maintenance during its entire useful life. This characteristic does not, however, imply that medical equipment is more costly than other categories, provided that it is managed properly. The foundation of a sound technology management process is the planning and acquisition of equipment, collectively called technology incorporation. This lecture presents a rational, strategic process for technology incorporation based on experience, some successful and many unsuccessful, accumulated in industrialized and developing countries over the last three decades. The planning step is focused on establishing a Technology Incorporation Plan (TIP) using data collected from an audit of existing technology, evaluating needs, impacts, costs, and benefits, and consolidating the information collected for decision making. The acquisition step implements TIP by selecting equipment based on technical, regulatory, financial, and supplier considerations, and procuring it using one of the multiple forms of purchasing or agreements with suppliers. This incorporation process is generic enough to be used, with suitable adaptations, for a wide variety of health organizations with different sizes and acuity levels, ranging from health clinics to community hospitals to major teaching hospitals and even to entire health systems. Such a broadly applicable process is possible because it is based on a conceptual framework composed of in-depth analysis of the basic principles that govern each stage of technology lifecycle. Using this incorporation process, successful TIPs have been created and implemented, thereby contributing to the improvement of healthcare services and limiting the associated expenses.
  • 2006From: Springer
    volume editor, Jiří Homola ; with contributions by J. Dostálek ... [et al.].
  • 2016From: Thieme-Connect
    Mario Sanna, Rolien Free, Paul Merkus, Maurizio Falcioni.
    History of auditory implantation -- Surgical anatomy in auditory implantation -- Radiology in auditory implantation -- Instruments and implants -- Cochlear implantation -- Special considerations in pediatric cochlear implantation -- Complications and revision surgery in cochlear implantation -- Auditory brainstem implantation -- Electroacoustic stimulation -- Subtotal petrosectomy in cochlear implantation -- Cochlear implantation in cochlear ossification -- Meningitis and implantation -- Auditory implantation in otosclerosis patients -- Otomastoiditis and cochlear implantation -- Inner ear malformations and implantation -- Neurofibromatosis type 2 and auditory implantation -- Implantation in skull base and temporal bone lesions -- Bone conduction implants -- Active middle ear implants : vibrant soundbridge.
  • v. 1-, 2006-From: Atypon
  • 2011From: ScienceDirect
    edited by Christopher Voigt.
    Also available: Print – 2011
  • 2011From: ScienceDirect
    edited by Christopher Voigt.
    Also available: Print – 2011
  • 2007From: Springer
    edited by Mohamed Al-Rubeai and Martin Fussenegger.
  • 2012From: Springer
    Christoph Wittmann, Sang Yup Lee, editors.
    Preface / Christoph Wittmann and Sang Yup Lee -- 1. Genome-scale network modeling / Sang Yup Lee, Seung Bum Sohn, Hyun Uk Kim, Jong Myoung Park, Tae Yong Kim, Jeffrey D. Orth, and Bernhard Ø. Palsson -- 2. Kinetic modeling of metabolic networks / Daniel C. Zielinski and Bernhard Ø. Palsson -- 3. Design of superior cell factories based on systems wide omics analysis / Katsunori Yoshikawa, Chikara Furusawa, Takashi Hirasawa, and Hiroshi Shimizu -- 4. Technologies for bio-systems engineering / Sonja Billerbeck, Sven Dietz, Gaspar Morgado, and Sven Panke -- 5. Systems metabolic engineering of Escherichia coli for chemicals, materials, biofuels, and pharmaceuticals / Dokyun Na, Jin Hwan Park, Yu-Sin Jang, Jeong Wook Lee, and Sang Yup Lee -- 6. Systems metabolic engineering of Corynebacterium glutamicum for biobased production of chemicals, materials and fuels / Judith Becker, Stefanie Kind, and Christoph Wittmann -- 7. Towards a synthetic biology of the stress-response and the tolerance phenotype: systems understanding and engineering of the Clostridium acetobutylicum stress-response and tolerance to toxic metabolites / Eleftherios T. Papoutsakis and Keith V. Alsaker -- 8. Model-based design of superior cell factory: an illustrative example of Penicillium chrysogenum / I. Emrah Nikerel, Peter J.T. Verheijen, Walter M. van Gulik, and Joseph J. Heijnen -- 9. Bridging omics technologies with synthetic biology in yeast industrial biotechnology / António Roldão, Il-Kwon Kim, and Jens Nielsen -- 10. Design of superior cell factories for a sustainable biorefinery by synthetic bioengineering / Tomohisa Hasunuma, Fumio Matsuda, and Akihiko Kondo -- 11. Systems-level analysis of cancer metabolism / Paulo A. Gameiro, Christian M. Metallo, and Gregory Stephanopoulos.
  • 2013From: Springer Protocols
    edited by Hal S. Alper.
    Genome-scale model management and comparison / Stephan Pabinger and Zlatko Trajanoski -- Automated genome annotation and metabolic model reconstruction in the SEED and model SEED / Scott Devoid [and others] -- Metabolic model refinement using phenotypic microarray data / Pratish Gawand [and others] -- Linking genome-scale metabolic modeling and genome annotation / Edik M. Blais, Arvind K. Chavali, and Jason A. Papin -- Resolving cell composition through simple measurements, genome-scale modeling, and a genetic algorithm / Ryan S. Senger and Hadi Nazem-Bokaee -- Guide to integrating transcriptional regulatory and metabolic networks using PROM (probabilistic regulation of metabolism) / Evangelos Simeonidis, Sriram Chandrasekaran, and Nathan D. Price -- Kinetic modeling of metabolic pathways : application to serine biosynthesis / Kieran Smallbone and Natalie J. Stanford -- Computational tools for guided discovery and engineering of metabolic pathways / Matthew Moura, Linda Broadbelt, and Keith Tyo -- Retrosynthetic design of heterologous pathways / Pablo Carbonell, Anne-Gaelle Planson, and Jean-Loup Faulon -- Customized optimization of metabolic pathways by combinatorial transcriptional engineering / Yongbo Yuan, Jing Du, and Huimin Zhao -- Adaptive laboratory evolution for strain engineering / James Winkler, Luis H. Reyes, and Katy C. Kao -- Trackable multiplex recombineering for gene-trait mapping in E. coli / Thomas J. Mansell, Joseph R. Warner, and Ryan T. Gill -- Identification of mutations in evolved bacterial genomes / Liam Royce [and others] -- Discovery of posttranscriptional regulatory RNAs using next generation sequencing technologies / Grant Gelderman and Lydia M. Contreras -- 13C-based metabolic flux analysis : fundamentals and practice / Tae Hoon Yang -- Nuclear magnetic resonance methods for metabolic fluxomics / Shilpa Nargund [and others] -- Using multiple tracers for 13C metabolic flux analysis / Maciek R. Antoniewicz -- Isotopically nonstationary 13C metabolic flux analysis / Lara J. Jazmin and Jamey D. Young -- Sample preparation and biostatistics for integrated genomics approaches / Hein Stam [and others] -- Targeted metabolic engineering guided by computational analysis of single-nucleotide polymorphisms (SNPs) / D.B.R.K. Gupta Udatha [and others] -- Linking RNA measurements and proteomics with genome-scale models / Christopher M. Gowen and Stephen S. Fong -- Comparative transcriptome analysis for metabolic engineering / Shuobo Shi, Tao Chen, and Xueming Zhao -- Merging multiple omics datasets in silico : statistical analyses and data interpretation / Kazuharu Arakawa and Masaru Tomita.
  • 2014From: CRCnetBASE
    edited by Todd A. Kuiken, Aimee E. Schultz Feuser, Ann K. Barlow.
    "This reference covers clinical and bioengineering aspects of muscle reinnervation, a popular new technique at the boundary of biomedical and rehabilitation engineering and neuroscience. With contributions from pioneers in the field, the book provides a review of muscle reinnervation from a biomedical engineering and clinical perspective. It describes neuroscience and other related neuroprosthetic techniques. A companion website offers a wide range of videos and multimedia material to aid in comprehension and application"--Provided by publisher.
  • Mandy Miller Koop.
    Hypokinesia is one of the most disabling movement abnormalities caused by Parkinson's disease (PD). It is a clinical term that refers to the general reduction of mobility experienced by people with Parkinson's disease (PWPD). Hypokinesia affects movements in three ways: 1) movements are slow 2) movements are performed with reduced amplitude compared to what is required for the task and 3) it takes longer for PWPD to initiate movements. All of these impairments affect the ability of PWPD to perform common daily activities and can cause feelings of frustration and anger that may lead to altered self esteem, depression, and a reduction in their quality of life. Although effective treatments do exist for well-selected patients, there are many avenues open for improving current treatments, identifying new treatments, and understanding mechanisms of hypokinesia that could potentially lead to more effective therapies and greatly impact the lives of PWPD. In this dissertation we sought to improve current treatments and provide opportunities for future treatments for hypokinesia by addressing three important clinical questions relating to hypokinesia. First, are there immediate improvements in hypokinesia from a surgical procedure called deep brain stimulation (DBS) that can be measured during surgery and used to help guide surgical decisions and optimize clinical outcomes? Second, can we determine what types of movements are affected by hypokinesia in early stage, untreated PD in order to provide an objective metric used to assess an emerging treatment for PD? Third, might perceptual deficits that are linked to sensory processing impairments play a role in the manifestation of hypokinesia? If so, targeting these deficits may provide new and better therapies. We addressed these questions by using the quantitative and computational techniques outlined in the next three paragraphs. A common treatment for advanced PD is a surgical procedure called DBS. The surgery is performed on awake patients, and it entails surgically implanting electrodes (leads) that provide chronic stimulation to the affected brain area that controls movement. Although the treatment is almost always effective, the degree of improvement in hypokinesia varies among patients. The accuracy of the placement of the DBS lead in the affected area is believed to have the most effect on the improvement of hypokinesia. We suggest that using quantitative measurements of hypokinesia to evaluate the efficacy of the location of the DBS lead in improving hypokinesia during the surgical procedure might therefore improve the overall clinical outcomes. The surgical team would then have objective, accurate measurements of the degree of improvement in hypokinesia during the surgery, when the lead's position in the brain could be modified to achieve optimal results. Therefore, we designed a prospective study to measure upper extremity hypokinesia using a quantitative measure of angular velocity. Analysis of 98 DBS procedures performed on 61 patients showed that on average there was an 81% improvement in quantitative measures of hypokinesia from implanting and activating the DBS lead (p< 0.03). This study demonstrated that objective, high-resolution, accurate measurements of improvements in hypokinesia from intra-operative DBS are possible in this highly constrained environment and could therefore be used to help guide surgical decisions and optimize clinical outcomes. PD has no cure, but treatments in the near future may include disease-slowing medications. Although few studies have characterized the motor control abnormalities of very early stage PD, when symptoms are mild and usually unilateral, this group is the most targeted for potential disease-modifying therapeutics. In this study, we asked if quantitative measures of finger, limb, and postural movement velocity could detect hypokinesia in 20 patients with very early stage, untreated PD. The results revealed evidence of significant finger and limb hypokinesia of the patient group's more affected side when compared to the non-dominant side of 19 age-matched healthy adults (HAs) (p=0.001 and p< 0.001, respectively). Furthermore, the patient group's limb movement velocity on the more affected side was significantly slower than their less affected side (p=0.005), highlighting the importance of using an outcome measure that is lateralized in studies of very early stage PD. In contrast to our previous study that revealed significant postural hypokinesia in patients with advanced PD, we did not detect postural hypokinesia in patients with very early stage, untreated PD. Based on these findings, we suggest that the use of quantitative lateralized measures of hypokinesia would be useful in neuroprotective clinical studies of very early stage, untreated PD and may improve the chances of detecting a disease-modifying effect of potential neuroprotective therapeutics. Detecting such a therapy would have a large impact by improving the lives of PWPD. Although hypokinesia is considered a movement abnormality, new research is suggesting that perceptual deficits may play a role in the manifestation of abnormal movements in PWPD. Motor control theory posits that a sensorimotor integration process (SIP) is used by the central nervous system to perceive and control movement by combining internally generated predictions of movement parameters with the processing of sensory feedback. A previous study examining the SIP demonstrated that HAs overestimated their limb position in the direction of movement, and that the error and its variance (VOE) depended on movement duration. Using quantitative measures of hypokinesia, we asked if PWPD showed errors in perceived limb position and if the dependence on movement duration was different from HAs. We used an established computational model of the SIP to explore mechanisms for the error and VOE as a function of movement duration. Twenty PWPD, off medication, and 20 age-matched HAs were asked to estimate the position of their hand after performing 50, slow, non-visually guided wrist flexion or extension movements for a random period of time (< 4.0 sec). Both groups overestimated the amount they moved; however, the PWPD's error and VOE were larger (p< 0.001). More specifically, HAs exhibited increasing error/VOE for small movement durations that reduced/stabilized for longer movement durations. PWPD, however, showed increasing error/VOE with increasing movement duration that did not significantly improve/stabilize. The results from the model revealed an 88% increase in the variance (noise) in the sensory feedback parameter in PWPD compared to HAs, which suggests the PWPD's SIP could no longer effectively access sensory feedback information to correct errors in other components of the SIP due to the large amount of noise in this signal. This study provides experimental evidence that perceptual deficits may play a role in hypokinesia and computational evidence that abnormal processing of sensory feedback in PWPD's SIP could contribute to increased perceptual error in limb position after non-visually guided movements. The work in this dissertation quantified the immediate improvements in hypokinesia from intra-operative DBS, the presences of hypokinesia in early stage, untreated PD, and the degree of perceptual deficits and their dependency on movement duration in PD. Furthermore, this research has provided evidence for possible mechanisms for hypokinesia. Taken together, this work has the possibly to provide immediate improvements for current treatments and provides several platforms for future therapies to treat hypokinesia and improve the lives of PWPD.
  • 2009From: Springer
    Mark W. Kroll, Jeffrey D. Ho, editors.
    Conducted electrical weapons: a user's perspective / Greg Meyer -- The scientific history / Robert A. Stratbucker -- Conducted electrical weapons and resolution of use-of-force encounters / Charles Mesloh, Mark Henych, and Ross Wolf -- Nonlethal weapons: the broader context / Peter J. Cuenca and John G. McManus -- Transcutaneous muscle stimulation / James D. Sweeney -- Current flow in the human body / Dorin Panescu and Robert A. Stratbucker -- Animal studies / John G. Webster -- CEW research models: animal and human studies / Theodore C. Chan and Gary M. Vilke -- Cardiac arrhythmias / Derek J. Dosdall and Raymond E. Ideker -- Electrocardiographic effects of the CEW / Jeffrey D. Ho -- Serum and skin effects of CEW application / Jeffrey D. Ho -- Electrocardiographic effects of the CEW / Robert Reardon -- Rhabdomyolysis / Ronald Moscati and Samuel Cloud -- Effects of CEWs on respiration / Donald M. Dawes -- Neuroendocrine effects of CEWs / Donald M. Dawes and Mark W. Kroll -- Electroporation of cardiac and nerve cells / Vadim V. Fedorov, Leonid Livshitz, Geran Kostecki, and Igor R. Efimov -- Eye and head injuries / S. Robert Witherspoon, Andreas K. Lauer, and Jonathan L. Marinaro -- CEW effects with illegal stimulant intoxication / Patrick Tchou -- Alcohol and the CEW / Ronald Moscati and Jeffrey D. Ho -- Conducted electrical weapons and implantible cardiac devices / Subba Reddy Vanga, James L. Vacek. Loren Berenhom and Dhanunjaya R. Lakkireddy -- Risk management and the CEW / Greg Bingham -- The New York City experience / Michael D. White and Justin Ready -- Impact of CEW and other types of force and resistance on officer and suspect injuries / Michael R. Smith, Robert J. Kaminski, Jeffrey Rojek, Geoffrey P. Alpert, and James Mathis -- Field statistics overview / James E. Brewer and Mark W. Kroll -- Sudden in-custody death / Samuel J. Stratton -- Stimulant abuse and sudden cardiac death / Steven B. Karch -- The systemic role of illicit drugs and their toxicology / Joshua Gunn, Michael A. Evans, and M. Scott Kriger -- Excited delirium syndrome / Vincent J. M. Di Maio and Theresa G. Di Maio -- Biochemical brain markers in excited delirium deaths / Deborah C. Mash -- Sudden unexpected death in custody (SUDIC) / Charles V. Wetli -- Legal basics for the CEW -- Science and logic meet the law / Michael A. Brave -- Appendix A: Excited delirium checklist -- Appendix B: Electrocution diagnosis checklist.
  • 2011From: CRCnetBASE
    editors, R.M. Natal Jorge, João Manuel R.S. Tavares, Marcos Pinotti Barbosa, Alan Peter Slade.
  • Junhee Seok.
    Translation of knowledge from basic science to medicine is essential to improving both clinical research and practice. In this translation, high-throughput genomic approaches can greatly accelerate our understanding of molecular mechanisms of diseases. A successful high-throughput genomic study of disease requires, first, comprehensive and efficient platforms to collect genomic data from clinical samples, and second, computational analysis methods that utilize databases of prior biological knowledge together with experimental data to derive clinically meaningful results. In this thesis, we discuss the development of a new microarray platform as well as computational methods for knowledge-based analysis along with their applications in clinical research. First, we and other colleagues have developed a new high-density oligonucleo-tide array of the human transcriptome for high-throughput and cost-efficient analysis of patient samples in clinical studies. This array allows comprehensive examination of gene expression and genome-wide identification of alternative splicing, and also pro-vides assays for coding SNP detection and non-coding transcripts. Compared with high-throughput mRNA sequencing technology, we show that this array is highly re-producible in estimating gene and exon expression, and sensitive in detecting expres-sion changes. In addition, the exon-exon junction feature of this array is shown to im-prove detection efficiency for mRNA alternative splicing when combined with an ap-propriate computational method. We implemented the use of this array in a multi-center clinical program and have obtained comparable levels of high quality and re-producible data. With low costs and high throughputs for sample processing, we antic-ipate that this array platform will have a wide range of applications in high-throughput clinical studies. Second, we investigated knowledge-based methods that utilize prior know-ledge from biology and medicine to improve analysis and interpretation of high-throughput genomic data. We have developed knowledge-based methods to enrich our prior knowledge, illustrate dynamic response to external stimulus, and identify distur-bances in cellular pathways by chemical exposure, as well as discover hidden biological signatures for the prediction of patient outcomes. Finally, we applied a knowledge-based approach in a large scale genomic study of trauma patients. Cooperating with clinical information, prior knowledge improved the interpretation of common and dif-ferential genomic response to injury, and provided efficient risk assessment for patient outcomes. The clinical and genomic data as well as analysis results in this trauma study were systematically organized and provided to research communities as new knowledge of traumatic injury. The microarray platform and knowledge-based methods presented in this thesis provide appropriate research tools for high-throughput translational medicine in a large clinical setting. This thesis is expected to advance understanding and treatment for dis-eases, and finally, improve public health.
  • 2013From: Springer
    Philippe A. Liverneaux, Stacey H. Berner, Michael S. Bednar, Sijo J. Parekattil, Gustavo Mantovani Ruggiero, Jesse C. Selber, editors.
    Part 1. GENERAL -- History of Microsurgery / Yoshikazu Ikuta -- History of Telesurgery / James Wall and Jacques Marescaux -- Description of Robots / Jesse Creed Selber -- Instruments / Sijo Joseph Parekatti and Michael Moran -- Robot Installation in Telemicrosurgery / Thierry Lequint, Kiyohito Naito, Eric Nectoux, Sybille Facca and Philippe Liverneaux -- Part 2. TRAINING -- Earthworms / Gustavo Mantovani Ruggiero -- Vessels / Joo-Yup Lee and Alexander Y. Shin -- Nerves / Stacey H. Berner -- Part 3. EXPERIMENTAL RESEARCH -- Free Tissue Transfer / Stacey H. Berner -- Tele-endomicrosurgery / Sybille Facca, Kiyohito Naito, Thierry Lequint, Eric Nectoux and Philippe Liverneaux -- Brachial Plexus Repair / Gustavo Mantovani Ruggiero and Philippe Liverneaux -- Tendon Transfer / Michael S. Bednar -- Part 4. CLINICAL APPLICATIONS -- Nerve Entrapment / Jose Carlos Garcia Jr. -- Nerve Repair / Stacey H. Berner -- Brachial Plexus / Kiyohito Naito, Mickaël Ohana, Thierry Lequint, Sybille Facca and Philippe Liverneaux -- Skin Flaps / Thomas Lauwers, Tom Van Mulken and Darren Booi -- Muscle Flaps / Jesse Creed Selber and John C. Pedersen -- Head and Neck / Jesse Creed Selber -- Urology / Sijo Joseph Parekattil -- Part 5. PERSPECTIVES -- Supermicrosurgery / Takeshi Todokoro and Isao Koshima -- Network / Catherine Jane Mohr.
  • 2007From: Springer
    Steffen Leonhardt, Thomas Falck, Petri Mähönen (eds.).
  • Sanaz Saatchi.
    Abdominal aortic aneurysms (AAA) are described by a pathological dilation of at least 150% in the abdominal aorta. Aneurysm pathogenesis is characterized by extracellular matrix (ECM) remodeling, smooth muscle cell (SMC) apoptosis, and inflammatory cell infiltration. Overall, the structural organization and integrity of the vessel wall is lost. In order to better understand the mechanism of AAA development, a novel microscopy technology, in combination with an AAA animal model, were used to visualize and quantify the microstructural and cellular changes in the vessel wall. Therefore, the goals of this work were to introduce Immunofluorescent Array Tomography (IAT), a novel three-dimensional high resolution microscopy technology, to the field of cardiovascular research, and to apply IAT to describe the vessel wall microarchitecture of a healthy aorta, as well as to investigate the spatial and temporal changes in tissue and cellular content, structure, and organization during AAA development. The purpose of the initial studies was two-fold: to develop the methods needed to enable the application of IAT to murine blood vessels and to investigate the microarchitecture of the healthy murine aorta. The anterior and posterior regions of the infrarenal aorta of 8 to 10 week old C57BL6 mice were evaluated. Staining and custom image analysis methods were developed. Antibody selection, primary antibody concentration, co-staining with multiple primary antibodies, and the multi-cycle staining design were optimized to produce positive and specific staining of elastin, smooth muscle cell actin (SMCA), and collagen type I. Algorithms were developed and applied to the healthy murine aorta to quantify volume fractions (VF) of medial elastin (27.5 ± 0.99%), SMCA (18.4 ± 0.67%), and nuclei (6.1 ± 0.14%), as well as adventitial collagen type I (22.3 ± 1.7%). Elastin thickness (1.6 ± 0.35 [Mu]m), spacing between elastin lamellae (3.5 ± 0.13 [Mu]m), elastin fragmentation (4.2 x 10-3 ± 1.6 x 10-4 # of objects/elastin area ([Mu]m)), media wall thickness (20.4 ± 3.1 [Mu]m), nuclei aspect ratio (3.2 ± 0.21 [Mu]m), and nuclei amount (17.3 ± 0.69 nuclei) were also quantified. The 3D microstructure and cellular morphology of the anterior and posterior infrarenal murine aorta were qualitatively and quantitatively described using IAT. IAT was then used to investigate the spatial and temporal remodeling of vessel wall microarchitecture and cellular morphology during AAA development in the murine elastase perfusion model. Infrarenal aortas of C57BL6 mice (N=20) were evaluated at 0, 7 and 28 days after elastase or heat-inactivated elastase perfusion. Custom algorithms quantified VFs of elastin, SMCA, and adventitial collagen type I, as well as elastin thickness, elastin fragmentation, media thickness, and nuclei amount. 3D renderings depicted elastin and collagen type I degradation, and dynamic changes in SMC phenotype, morphology, and amount. Elastin degradation was described by a 37.5% (p < 0.01) loss in VF, 48.9% decrease in thickness, and a 449.7% (p < 0.001) increase in fragmentation over 28 days. SMCA VF decreased 78.3% (p < 0.001) from Day 0 to Day 7, and increased 139.7% (p < 0.05) from Day 7 to Day 28. Media thickness increased 61.1% and medial nuclei amount increased 159.1% (p < 0.01) over 28 days. Adventitial collagen type I VF decreased 64.1% (p < 0.001) over 28 days. IAT and custom image analysis algorithms have enabled robust quantification of vessel wall content, microstructure, and organization to help elucidate the unique dynamics of major tissue constituent remodeling during AAA development. In conclusion, the methodologies needed to enable the application of IAT to cardiovascular research have been developed, the healthy murine vessel wall microarchitecture has been qualitatively and quantitatively described, and the unique dynamics of vascular remodeling during aneurysm development have been investigated.
  • 2011From: Springer
    Norbert Pallua, Christoph V. Suschek, editors.
    BASICS AND PRINCIPLES: Scaffolds: Micro and Nano Technology -- Biomimetic Materials -- Natural and Synthetic Scaffolds: Adhesion, ECM, Structure, Function, Modification -- Cells: Sources, Growth, Differentiation, Trans-Differentiation -- Embryonic Stem Cells: Sources and Characterization -- Adult Stem Cells: Sources and Characterization -- Isolation and Growth -- Differentiation and Plasticity -- Regulation Mechanisms: Key Signaling Molecules -- Cell and Organ preservation -- Engineering Technologies: Animal Models for Evaluation of Tissue Engineering Constructs -- Biomedical Imaging and Image Processing -- Bioreactors for Tissue Engineering -- Drug delivery -- Gene Therapy -- OROGANS: Liver -- Musculoskeletal Tissues -- Lung -- CNS -- Peripheral Nervous System -- Nephrons -- Biohybrid organs -- Heart and Cardiovascular Engineering -- Eye/Retina -- Respiratory Systems Engineering -- Ear -- Skin -- TISSUE TYPES: Adipose Tissue -- Blood Substitutes -- Angiogenesis and Vascularization -- Bone Tissue -- Brain Tissues -- Cartilage Tissue -- Pancreatic Tissues -- Tendons -- Tissue Engineering in Reproductive Medicine, of Heart Valves, in Oral and Maxillofacial Surgery -- Uro-Gital System/Bladder Tissue.
  • 2006.From: CRCnetBASE
    edited by Joseph D. Bronzino.
    Biomolecular engineering in oligonucleotide applications -- Gene therapy -- Bio-nanorobotics: state of the art and future challenges -- sect. IV. Bionanotechnology. DNA as a scaffold for nano-structure assembly -- Directed evolution of proteins for device applications -- Semiconductor quantum dots for molecular and cellular imaging -- Bionanotechnology for bioanalysis -- Nano-hydroxyapatite for biomedical applications -- Nanotechnology provides new tools for biomedical optics -- Nanomaterials perspectives and possibilities in nanomedicine -- Biomedical nanoengineering for nanomedicine -- Physiogenomics: integrating systems engineering and nanotechnology for personalized medicine -- Bionanotechnology patenting: challenges and opportunities -- sect. V. Tissue engineering. Fundamentals of stem cell tissue engineering -- Growth factors and morphogens: signals for tissue engineering -- Extracellular matrix: structure, function, and applications to tissue engineering -- Esophagus: a tissue engineering challenge -- Tissue engineered vascular grafts -- Cardiac tissue engineering: matching native architecture and function to develop safe and efficient therapy -- Tissue engineering of heart valves -- Tissue engineering, stem cells and cloning for the regeneration of urologic organs -- Hepatic tissue engineering for adjunct and temporary liver support -- Tissue engineering of renal replacement therapy -- The bioengineering of dental tissues -- Tracheal tissue engineering -- sect. VI. Prostheses and artificial organs. Artificial heart and circulatory assist devices -- Cardiac valve prostheses -- Vascular grafts -- Artificial lungs and blood-gas exchange devices -- Artificial kidney -- Peritoneal dialysis equipment -- Therapeutic apheresis and blood fractionation -- Liver support systems -- Artificial pancreas -- Nerve guidance channels -- Tracheal, laryngeal, and esophageal replacement devices -- Artificial blood -- Artificial skin and dermal equivalents -- sect. VII. Ethics. Beneficence, nonmaleficence, and medical technology -- Ethical isseus related to clinical research. Mechanical forces on cells -- Cell adhesion -- Cell migration -- Inflammatory and immune responses to tissue engineered devices -- Polymeric scaffolds for tissue engineering applications -- Calcium phosphate ceramics for bone tissue engineering -- Biomimetic materials -- Nanocomposite scaffolds for tissue engineering -- Roles of thermodynamic state and molecular mobility in biopreservation -- Drug delivery -- Gene therapy -- Tissue engineering bioreactors -- Animal models for evaluation of tissue-engineered orthopedic implants -- The regulation of engineered tissues: emerging approaches -- Bioengineering of human skin substitutes -- Nerve regeneration: tissue engineering strategies -- Gene therapy and tissue engineering based on muscle-derived stem cells: potential for musculoskeletal tissue regeneration and repair -- Tissue engineering applications - bone -- Cartilage tissue engineering -- Tissue engineering of the tempormandibular joint -- Engineering smoot muscle -- Sect. I. Molecular biology. Historical perspective and basics of molecular biology -- Systems and technology involving bacteria -- Recombinant DNA technology using mammalian cells -- sect. II. Transport phenomena and biomimetic systems. Biomimetic systems -- Diffusional processes and engineering design -- Microvascular heat transfer -- Perfusion effects and hydrodynamics -- Animal surrogate systems -- Arterial wall mass transport: the possible role of blood phase resistance in the localization of arterial disease -- Control of the microenvironment -- Interstitial transport in the brain: principles for local drug delivery -- sect. III. Biotechnology. Tools for genome analysis -- Vaccine production -- Protein ngineering -- Metabolic engineering -- Monoclonal antibodies and their engineered fragments --
  • 2011From: Springer
    Harold S. Bernstein, editor.
    pt. 1. Stem cells -- pt. 2. Biomaterials and the extracellular environment -- pt. 3. Engineered tissue -- pt. 4. Synthetic organs -- pt. 5. Immune response -- pt. 6. Animal models.
  • 2007From: Springer Protocols
    edited by Hansjörg Hauser, Martin Fussenegger.
    In vitro expansion of tissue cells by conditional proliferation -- Stem cell engineering using transducible Cre recombinase -- Human embryonic stem cells for tissue engineering -- Culture and characterization of human bone marrow mesenchymal stem cells -- Skeletal ("Mesenchymal") stem cells for tissue engineering -- Biomaterials/Scaffolds -- Synthetic hydrogel matrices for guided bladder tissue regeneration -- Generation of multicellular tumor spheroids by the hanging-drop method -- In vitro vascularization of human connective microtissues -- Artificial skin -- Small blood vessel engineering -- Artificial pancreas to treat type 1 Diabetes Mellitus -- Human articular chondrocytes culture -- Cardiomyocytes from human and mouse embryonic stem cells -- Myocardial restoration and tissue engineering of heart structures -- Practical aspects of cardiac tissue engineering with electrical stimulation -- Biological scaffolds for heart valve tissue engineering -- In vitro heart valve tissue engineering.
  • 2007From: CRCnetBASE
    edited by Aldo R. Boccaccini and Julie E. Gough.
    pt. 1. General issues -- pt. 2. Tissue and organ generation.
  • 2013From: Springer
    Karl Knahr, editor.
    Part I: Ceramic-on-Ceramic Articulations -- Technology and Handling of Ceramic Implants -- Long-Term Stability of Ceramic Composite in Total Hip Arthroplasty -- Ceramic-Ceramic Bearing in Difficult Hips (Primary and Revision) -- Alumina-on-Alumina Bearings in Hip Arthroplasty: What Every Surgeon Should Know -- Part II: Metal-on-Metal Articulations -- Metal-on-Metal Resurfacing and the Cost to the Nation: A Conservative Estimate of the Unexpected Costs Required to Implement the New Metal-on-Metal Follow-Up Programme in the UK -- A Clinicopathological Study of Metal-on-Metal Hips Revised for Suspected Adverse Reactions to Metal Debris -- Metal-on-Metal Bearings and Surgical Techniques in Active Patients with Severe Hip Deformity -- The Incidence of Pseudotumour in Metal-on-Metal Hip Resurfacing and the Results of a Screening Tool for Patient Recall -- Part III: Polyethylene - Standard and New Improvements -- New Polys and Large Heads: Clinical Aspects -- The Influence of Head Material on Polyethylene Wear -- Basic Science and Longtime Results of Different Polyethylene Articulations -- Part IV: Large Diameter Heads -- Head Size and Metal-on-Metal Bearings -- Aseptic Loosening of Metal-on-Metal (MOM) Total Hip Arthroplasties (THA) with Large-Diameter Heads -- Large Head Articulations: Benefits and Drawbacks -- Can the Increased Loosening Rate of the Modular-Neck Hip Systems Be Attributed to Geometric Design Parameters? An Alternative Approach Using Finite Element Analysis -- Fracture of the Titanium Neck in a Modular Femoral Component -- Part V: Clinical Aspects -- Wear of Hard-on-Hard Bearings in the Hip: The Influence of Loss of Conformity Under Edge Loading -- Considerations for the Use of Bearing Partners in Total Hip Arthroplasty -- Total Hip Arthroplasty Using a Short, Metaphyseal-Fitting Anatomic Cementless Femoral Component in Patients with Femoral Head Osteonecrosis Who Are Less than 30 Years Old -- Survival of Monoblock Acetabular Cups Versus an Uncemented Modular Cup Design: A Population-Based Study from the Swedish Hip Arthroplasty Register.
  • Catherine Elizabeth Chang.
    Functional magnetic resonance imaging (fMRI) based on blood-oxygen level dependent (BOLD) contrast is a powerful technique for non-invasive measurement of brain activity. Recent fMRI studies have revealed that the spontaneous BOLD fluctuations of the human brain organize into distributed, temporally-coherent networks ("resting-state networks"; RSNs). Examination of RSNs has yielded valuable insight into neural organization and development, and demonstrates potential as a biomarker for conditions such as Alzheimer's disease and depression. However, the accuracy by which the spatio-temporal properties of RSNs can be delineated using fMRI is compromised by the presence of physiological (cardiac and respiratory) noise and vascular hemodynamic variability. Further, our present understanding of how RSNs may interact and support cognitive function has been limited by the fact that the vast majority of studies to-date analyze RSNs in a manner that assumes temporal stationarity. Here, we describe efforts to correct for non-neural physiological influences on the BOLD signal, as well as investigations into the dynamic character of resting-state network connectivity. It is found that low-frequency variations in cardiac and respiratory processes account for significant noise across widespread gray matter regions, and that a constrained deconvolution approach may prove effective for modeling and reducing their effects. Application of the proposed noise-reduction procedure is observed to yield negative correlations between the spontaneous fluctuations of two major RSNs. The relationship between respiratory volume changes and the BOLD signal is further examined by simultaneously monitoring and comparing chest expansion data, end-tidal gas concentrations, and spontaneous BOLD fluctuations. The use of a breath-holding task is proposed for quantifying regional differences in BOLD signal timing that arise from local vasomotor response delays; such non-neural timing delays are found to impact inferences of resting-state connectivity and causality. Finally, a preliminary analysis of non-stationary connectivity between RSNs is performed using wavelet and sliding-window approaches, and it is observed that interactions between networks may reconfigure on time-scales of seconds to minutes.
  • Paul Herag Nuyujukian.
    Neural prostheses translate signals from the brain into useful control signals, manipulating end-effectors such as computer cursors or robotic arms. Their aim is to offer greater interaction with the world for patients suffering from limb dysfunction due to spinal cord injury, neurodegenerative disease, and other conditions leading to limb paralysis. Prior intracortical electrode neural prosthesis studies have demonstrated compelling proof-of-concept systems, but barriers to successful clinical translation still remain, such as performance and robustness. Measures of performance include the speed, accuracy, and bitrate of the system. Robustness refers to the sustained performance of the system within a day and across days. The work presented here demonstrates algorithms and advances for neural prostheses that increase both performance and robustness. The recalibrated feedback intention trained Kalman filter (ReFIT-KF) increased performance by at least twofold compared to previously reported decoders, approaching the speed of natural arm movements. It achieved bitrates of up to 4.5 bits per second (bps) and communication rates of up to 10 words per minute (wpm) when used on a typing task. These results were reliable and repeatable for hours at a time across 4 array-years between two subjects. Utilizing neural spike threshold crossings as a signal source, the ReFIT-KF algorithm also demonstrated sustainable performance without any changes to decoder weights for one year with a degradation rate of 0.05 bps per month. Performance further increased when the ReFIT-KF was combined with an HMM state decoder for the detection of clicks, eliminating the need for hold periods. This combined ReFIT-KF and HMM decoder achieved bitrates of up to 6.5 bps and 15 wpm. Taken together, these findings may help advance neural prostheses closer to clinical viability.
  • Vikash Gilja.
    By restoring the ability to move and communicate with the world, brain machine interfaces (BMIs) offer the potential to improve quality of life for people suffering from spinal cord injury, stroke, or neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). BMIs attempt to translate measured neural signals into the user's intentions and, subsequently, control a computer or actuator. Recently, compelling examples of intra-cortical BMIs have been demonstrated in tetraplegic patients. Although these studies provide a powerful proof-of-concept, clinical viability is impeded by limited performance and robustness over short (hours) and long (days) timescales. We address performance and robustness over short time periods by approaching BMIs as a systems level design problem. We identify key components of the system and design a novel BMI from a feedback control perspective. In this perspective, the brain is the controller of a new plant, defined by the BMI, and the actions of this BMI are witnessed by the user. This simple perspective leads to design advances that result in significant qualitative and quantitative performance improvements. Through online closed loop experiments, we show that this BMI is capable of producing continuous endpoint movements that approach native limb performance and can operate continuously for hours. We also demonstrate how this system can be operated across days by a bootstrap procedure with the potential to eliminate an explicit recalibration step. To examine the use of BMIs over longer timescales, we develop new electrophysiology tools that allow for continuous multi-day neural recording. Through application of this technology, we measure the signal acquisition stability (and instability) of the electrode array technology used in current BMI clinical trials. We also demonstrate how these systems can be used to study BMI decoding over longer time periods. In this demonstration, we present a simple methodology for switching BMI systems on and off at appropriate times. The algorithms and methods demonstrated can be run with existing low power application specific integrated circuits (ASICs), with a defined path towards the development of a fully implantable neural interface system. We believe that these advances are a step towards clinical viability and, with careful user interface design, neural prosthetic systems can be translated into real world solutions.
  • 2012From: Springer Protocols
    edited by Jim M. Dunwell, Andy C. Wetten.
    Employment of cytokinin vectors for marker-free and backbone-free transformation -- Organophosphorus hydrolase: A multifaceted plant genetic marker which is selectable, scorable, and quantifiable in whole seed -- Use of northern blotting for specific detection of small RNA molecules in transgenic plants -- Genetic transformation of the model green alga Chlamydomonas reinhardtii -- A high-efficiency agrobacterium-mediated transformation system of rice (Oryza sativa L.) -- Selection of transgenic rice plants using a herbicide tolerant form of the acetolactate synthase gene -- Visual selection in rice: A strategy for the efficient identification of transgenic calli accumulating transgene products -- Characterization of rice genes using a heterologous full-length cCDNA expression system -- Bioactive bead-mediated transformation of plants with large DNA fragments -- Agrobacterium-mediated transformation of sorghum bicolor using immature embryos -- Split-transgene expression in wheat -- Agrobacterium-mediated transformation of brachypodium distachyon -- Transformation of barley (Hordeum vulgare L.) by agrobacterium tumefaciens infection of in vitro cultured ovules -- Biolistic-mediated production of transgenic oil palm -- Transformation of oil palm using agrobacterium tumefaciens -- Highly efficient transformation protocol for plum (Prunus domestica L.) -- Co-transformation of grapevine somatic embryos to produce transgenic plants free of marker genes -- Initiation and transformation of grapevine embryogenic cultures -- Development of highly efficient genetic transformation protocols for table grape sugraone and crimson seedless -- Cotton pistil drip transformation method -- Enhanced agrobacterium-mediated transformation of embryogenic calli of upland cotton -- Targeted biolistics for improved transformation of impatiens balsamina -- A protocol for transformation of torenia -- Efficient modification of floral traits by heavy-ion beam irradiation on transgenic torenia -- Expression of artificial micrornas in physcomitrella patens -- High frequency of single-copy t-DNA transformants produced after floral dip in CRE-expressing arabidopsis plants -- A developmentally regulated cre-lox system to generate marker-free transgenic Brassica napus plants -- Exploiting multisite gateway and pENFRUIT plasmid collection for fruit genetic engineering -- A one-time inducible transposon to create knockout mutants in rice -- Marker-free gene targeting by recombinase-mediated cassette exchange -- Targeting DNA to a previously integrated transgenic locus using zinc finger nucleases -- Double-strand break-induced targeted mutagenesis in plants -- Combinatorial genetic transformation of cereals and the creation of metabolic libraries for the carotenoid pathway -- Production of a his-tagged canecystatin in transgenic sugarcane -- Plastid transformation as an expression tool for plant-derived biopharmaceuticals -- Use of a callus-specific selection system to develop transgenic rice seed accumulating a high level of recombinant protein -- How to grow transgenic arabidopsis in the field.
  • 2013From: Springer
    Jozef Bartunek, Marc Vanderheyden, editors.
    Pathophysiology of Heart Failure: Back to Basics -- Heart Failure with Normal Left Ventricular Ejection Fraction -- Basic Principles and Clinical Diagnostics -- 17 Cardiorenal Syndrome Revisited -- Doppler Echocardiography in the Clinical Evaluation of Heart Failure: What Clinicians Need to know and Echocardiographers Should Report -- Back to Earth: 'Common sense' in the Management of Heart Failure -- Atrial Fibrillation and Heart Failure: Rate versus Rhythm Control -- Repetitive ICD Shocks and Incessant VTs in Heart Failure: What to Do? -- Dyssynchronous Heart Failure: From Bench to Bedside -- 18 Telemonitoring and Sensor Technologies in Chronic Heart Failure -- Functional Mitral Regurgitation: the Surgeons's Perspective -- Percutaneous Approaches to Treat Functional Mitral Regurgitation: Current State of Affairs and Future Perspectives -- Tailored Approach to Functional Mitral Regurgitation -- Revascularization and Left Ventricular Reconstruction in a Patient with Ischemic Heart Failure: to STICH or not to STICH? -- Cardiac arrest en Refractory Cardiogenic Shock -- Left Ventricular Assist Devices -- From Bridge to Transplant to Destination Therapy -- Novel Device-based Strategies in Treatment of Chronic Heart Failure -- Total Artificial Heart -- Stem Cell Therapy for Ischemic Heart Disease -- Immunosuppressive Management of the Heart Transplant Recipient.
  • 2015From: ScienceDirect
    edited by Anthony Atala, Julie G. Allickson.
    The landscape of cell tissues and organs / Mahendra Rao -- Landscape of cell banking / Heather C. Hatcher, Anthony Atala and Julie G. Allickson -- Cell banking: process development and cell preservation / Salem Akel -- Clinical development of placental mesenchymal stromal cells / Robert J. Hariri and Steven Fischkoff -- Translation of regenerative medicine products into the clinic in the United States: FDA perspective / Mark H. Lee, Patrick Au, John Hyde, Carmen Gacchina Johnson, Mohammad Heidaran, Safa Karandish, Lynne Boxer, Michael Mendicino, Diana Yoon, Lori Tull, Judith Arcidiacono, Brent McCright, David S. Kaplan, Donald Fink, Charles N. Durfor, Richard McFarland and Celia Witten -- Newborn stem cell banking business models / Thomas Moore, Matthew P. Brown, John R. Chapman, Jesse Kramer, Robert P. Pfotenhauer and Heather L. Brown -- Cell therapy landscape: autologous and allogeneic approaches / Nafees N. Malik and Matthew B. Durdy -- Stem cells and cell therapy: autologous cell manufacturing / Ronnda L. Bartel -- Overview: challenges of process development for cellular therapy / Robert Perry -- Tissue engineering: propagation and potency evaluation / Ivan N. Rich -- Biomaterials in preclinical approaches for engineering skeletal tissues / Márcia T. Rodrigues, Pedro P. Carvalho, Manuela E. Gomes and Rui L. Reis -- Biomaterials in regenerative medicine: considerations in early process development / Alexander M. Tatara, Anthony Ratcliffe, Mark E.K. Wong, F. Kurtis Kasper and Antonios G. Mikos -- Biomaterials in regenerative medicine: challenges in technology transfer from science to process development / Prafulla Chandra, James J. Yoo and Sang Jin Lee -- Paracrine regulation from tissue engineered constructs / Or Gadish and Elazer R. Edelman -- Creating commercial value from biomaterials / Glenn D. Prestwich and Brenda K. Mann -- Manufacturing of regenerative medicine products / Tom Spencer and Deepak Jain -- Regulatory aspects / Joyce L. Frey-Vasconcells -- Global design for clinical trials / Yoshito Ikada -- Biomarkers / Ralf Huss -- Translational animal models for regenerative medicine research / John G. Sharp -- Translational imaging for regenerative medicine / Sneha S. Kelkar and Aaron M. Mohs -- Skin and skin appendage regeneration / Krzysztof Kobielak, Eve Kandyba and Yvonne Leung -- Clinical aspects of regenerative medicine: tendon, ligament, and joint / Steven Sampson, Angie Botto-van Bemden and Danielle Aufiero -- Bone regeneration / Suzanne Stewart, Stephanie J. Bryant, Jaimo Ahn and Kurt D. Hankenson -- Regenerative medicine therapies using adipose-derived stem cells / Jolene E. Valentin, Albert D. Donnenberg, Kacey G. Marra and J. Peter Rubin -- Transplantation of myogenic cells in duchenne muscular dystrophy patients: clinical findings / Daniel Skuk and Jacques P. Tremblay -- Regeneration of the vascular system / Etai Sapoznik, Guoguang Niu, Masashi Nomi, Zhan Wang and Shay Soker -- Hematopoiesis in regenerative medicine / Graça Almeida-Porada and Christopher D. Porada -- The application and future of neural stem cells in regenerative medicine / Shreyasi Das, Brian Tobe, Paul A. Jain, Walter Niles, Alicia Winquist, Lina Mastrangelo and Evan Y. Snyder -- Central nervous system / Anup Tuladhar, Nikolaos Mitrousis, Tobias Führmann and Molly S. Shoichet -- In situ tissue engineering bone regeneration in jaw reconstruction / Robert E. Marx -- Regenerative medicine for diseases of the respiratory system / Mei Ling Lim, Philipp Jungebluth and Paolo Macchiarini -- Renal system / Joao Paulo Zambon, Prafulla Chandra, Anthony Atala and James J. Yoo -- Translational regenerative medicine -- hepatic systems / Abritee Dhal, Dipen Vyas, Emma C. Moran, Daniel B. Deegan, Shay Soker and Pedro M. Baptista -- Advances in neo-innervation of the gut / Khalil N. Bitar, Shreya Raghavan, Sita Somara, Elie Zakhem and Stephen Rego -- Genitourinary system / Mehran Abolbashari, Anthony Atala and James J. Yoo -- Clinical aspects of regenerative medicine: immune system / Erszebet Szilagyi, Premenand Sundivakkam, Tamara Nunez, Kavitha Premenand, Norma Kenyon and Amelia Bartholomew -- Development of appropriate imaging methods to trace cell fate, engraftment, and cell survival / Jesse V. Jokerst and Sanjiv S. Gambhir -- Gap analysis to target therapies / Adrian P. Gee -- Funding for the translation of regenerative medicines / Neil J. Littman, Elona Baum and Alan O. Trounson.
  • 2007From: Springer
    M.Y.H. Bangash ... [et al.].
  • 2011From: Springer
    Karl Knahr, editor.
  • Benjamin David Almquist.
    Electrophysiological tools and biologic delivery systems generally rely on non-optimal methods for gaining access through cellular membranes. Electrophysiological techniques that provide intracellular access, such as patch clamping, result in membrane holes and cell death in a matter of hours, while the delivery of bioactive materials are hampered by low bioavailability following passage through the endosomal pathways. In each case, the lipid bilayer backbone of the cellular membrane presents a formidable barrier to intracellular access. As biological gatekeepers, cell membranes not only physically define everything from whole organisms to individual organelles, they also prevent unobstructed flow of molecules between the inner and outer regions of the membrane. This occurs since the hydrophobic lipid acyl tails form a narrow hydrophobic layer a few nanometers thick, which is highly unfavorable for the passage of most hydrophilic molecules. It is this region that is one of the greatest obstacles to the dream of biotechnology seamlessly and non-destructively integrating synthetic components with biological systems. This thesis contributes to the understanding of how to rationally design devices that interact specifically with this hydrophobic region. In turn, this work begins to establish design guidelines for creating non-destructive, membrane-penetrating bio-inorganic interfaces. The beginning chapters focus on the development of the "stealth" probe platform. In nature, there exist specialized transmembrane proteins capable of incorporating into lipid bilayers by replicating the lipid hydrophilic-hydrophobic-hydrophilic structure. The stealth probe design mimics this structure by creating 2-10nm hydrophobic bands on otherwise hydrophilic structures. However, since current lithographic methods do not possess the necessary resolution, a new fabrication technique using a combination of top-down fabrication with bottom-up self-assembly methods was developed. This approach uses an evaporated chrome-gold-chrome stack and focused ion beam (FIB) milling, where the exposed edge of the embedded gold layer can be specifically functionalized with a hydrophobic thiol-mediated self-assembled monolayer. Chapter 3 explores the propensity for insertion and specific interaction of the stealth probe hydrophobic band with the hydrophobic lipid bilayer core. In order to gain quantitative insight into the interaction behavior, atomic force microscopy was used in conjunction with a new, stacked lipid bilayer testing platform. By using stacks of 100's to 1000's of lipid bilayers, substrate-probe interaction artifacts can be removed while simultaneously allowing precise determination of probe location within a lipid bilayer. It was found that completely hydrophilic probes reside in the hydrophilic hydration region between bilayers, whereas hydrophobically functionalized stealth probes preferred to reside in the bilayer core. This behavior was found to be independent of hydrophobic functionalization, with butanethiol and dodecanethiol both displaying preferential localization. The subsequent chapters explore how the molecular structure of the hydrophobic band and the band thickness affect membrane-probe interface stability. The lipid stack platform provides an easy method of force-clamp testing, which enabled quantitative extrapolation of the unstressed interface strength. A series of tests with various length alkanethiols found that the crystallinity of the molecules in the hydrophobic band is the dominant factor influencing interfacial stability. Surprisingly, hydrophobicity was found to be a secondary factor, although necessary to drive spontaneous membrane integration. Molecular length was also found to play a role in determining the ultimate interfacial strength, with short chain molecules similar in length to amino acid side chains promoting the most stable interfaces. The thickness of the hydrophobic band was found to regulate the interface structure. Bands with thicknesses comparable to that of the host lipid bilayer core likely promote a fused interface geometry, similar in structure to that of transmembrane protein-lipid bilayer interfaces. Thicker bands began to transition to a 'T-junction' interface that is characterized by a lower interface stability. Interestingly, the behavior of 10nm bands were indistinguishable from completely hydrophobic probes, reinforcing the importance of nanoscale patterning for stable membrane integration. Chapter 6 builds on the results of the previous chapters by exploring how various stealth probe geometries influence adhesion behavior. In agreement with force clamp testing, short disordered monolayers displayed strong integration into the bilayer core, while crystalline monolayers displayed extremely weak integration. Preliminary adhesion testing results with human red blood cells demonstrate that the stealth probe geometry holds promise for in vitro and in vivo platforms, expanding the results of this work from simply a biophysical test system to a real world example. Finally, the behavior of two hydrophobic bands either commensurately spaced with the hydrophobic core spacing in the bilayer stack, or incommensurately spaced in order to force one band to reside in the hydrophilic hydration layer, is explored. It was found that the commensurately spaced bands display superior strength to single band tips, which is attributed to the necessity to simultaneously rupture both membrane-hydrophobic band interfaces. Conversely, the incommensurately spaced probes display a significant destabilization of the interface. This is thought to be due to the forced residence of one hydrophobic band in a hydrophilic hydration layer. This result is intriguing for biologic delivery systems, as the nuclear double membrane presents a unique barrier geometry, and a double band system may provide a facile means for penetration.
  • Meredith Marie Lee.
    Although there is a pressing global need for widely-deployable disease detection and monitoring systems, today's options for biochemical analysis are often bulky, slow, expensive, and reliant on trained medical personnel. In contrast, the miniaturization and integration of devices based on arrays of sources, detectors, and active or passive biosensing surfaces provides a means to achieve handheld diagnostic capabilities with a "lab-on-a-chip" that would be vastly less expensive and fully automated. In this thesis, we design, fabricate, and characterize tunable biosensors with compact and low-cost Vertical Cavity Surface Emitting Lasers (VCSELs), integrated detectors, Peltier coolers, photonic crystal slab resonators, and polymer microfluidics. All of the components utilize scalable semiconductor and soft-lithography techniques to significantly reduce the required device footprint, simplify system assembly, and enable large-scale, economical manufacturing. The sensors operate in the visible to near-infrared 650-900 nm wavelength range for low absorption of water, hemoglobin, and other background elements found in tissue or aqueous samples. Moreover, the 670 nm label-free sensors we demonstrate are designed for compatibility with previously characterized monolithically integrated fluorimeters that capitalize on emerging deep-red fluorescent proteins and molecular probes approved for pre-clinical use by the Federal Drug Administration.
  • 2009From: ScienceDirect
    2009From: Knovel
    editor, Steven M. Kurtz.
    A primer on UHMWPE / Steven M. Kurtz -- From ethylene gas to UHMWPE component : the process of producing orthopedic implants / Steven M. Kurtz -- Packaging and sterilization of UHMWPE / Steven M. Kurtz -- The origins of UHMWPE in total hip arthroplasty / Steven M. Kurtz -- The clinical performance of UHMWPE hip replacements / Steven M. Kurtz -- Contemporary total hip arthoplasty : hard-on-hard bearings and highly crosslinked UHMWPE / Steven M. Kurtz, Kevin Ong -- The origins and adaptations of UHMWPE for knee replacements / Steven M. Kurtz -- The clinical performance of UHMWPE in knee replacements / Steven M. Kurtz -- The clinical performance of UHMWPE in shoulder replacements / Stefan M. Gabriel -- The clinical performance of UHMWPE in elbow replacements / Judd S. Day -- Applications of UHMWPE in total ankle replacements / Allyson Ianuzzi, Chimba Mkandawire -- The clinical performance of UHMWPE in the spine / Steven M. Kurtz, Marta L. Villarraga, Allyson Ianuzzi -- Highly crosslinked and melted UHMWPE / Orhun K. Muratoglu -- Highly crosslinked and annealed UHMWPE / John H. Dumbleton, Aiguo Wang, Kate Sutton ...[et al.] -- Highly crosslinked UHMWPE doped with vitamin E / Ebru Oral, Orhun K. Muratoglu -- Vitamin-E-blended UHMWPE biomaterials / Steven M. Kurtz, Pierangiola Bracco, Luigi Costa -- Composite UHMWPE biomaterials and fibers / Steven M. Kurtz -- UHMWPE / hyluronan microcomposite biomaterials / Susan P. James, Rachel (Kurkowski) Oldinski, Min Zhang ...[et al.] -- High pressure crystallized UHMWPEs / Anuj Bellare, Steven M. Kurtz -- Compendium of highly crosslinked UHMWPEs / Steven M. Kurtz -- Mechanisms of crosslinking, oxidative degradation and stabilization of UHMWPE / Luigi Costa, Pierangiola Bracco -- In vivo of UHMWPE / Steven M. Kurtz -- Pathophysiologic reactions to UHMWPE wear particles / Marla J. Steinbeck, Ryan M. Baxter, Theresa A. Freeman -- Characterization of physical, chemical, and mechanical properties of UHMWPE / Stephen Spielgelberg -- Tribological assessment of UHMWPE in the hip / Aaron Essner MS, Aiguo Wang -- Tribological assessment of UHMWPE in the knee / Hani Haider -- Characterization of UHMWPE wear particles / Tipper JL., Richards L., Ingham E. ...[et al.] -- Clinical surveillance of UHMWPE using radiographic methods / Charles R. Bragdon -- ESR insights into macroradicals in UHMWPE / M. Shah Jahan -- Fatigue and fracture of UHMWPE / Francisco J. Medel, Jevan Furmanski -- Development and application of the notched tensile test to UHMWPE / Michael C. Sobieraj, Clare M. Rimnac -- Development and application of the small punch test to UHMWPE / Avram A. Edidin -- Nano- and microindentation testing of UHMWPE / Jeremy L. Gilbert, James D. Wernle -- MicroCT analysis of wear and damage in UHMWPE / Daniel MacDonald, Anton Bowden, Steven M. Kurtz -- Computer modeling and simulation of UHMWPE / Anton E. Bowden, Erin Oneida, Jorgen Bergström.
  • Randy L. King.
    Ultrasound-induced neurostimulation has recently gained increasing attention. Developments in the use of ultrasound to stimulate and modulate neural activity have raised the possibility of using ultrasound as a new investigative and therapeutic tool in brain research. Little is known about the mechanisms by which it affects neural activity or about the range of acoustic parameters and stimulation protocols that elicit responses. In this thesis, conditions are established for transcranial stimulation of the nervous system in vivo, using the mouse somatomotor response. It is reported that (1) continuous-wave stimuli are as effective as or more effective than pulsed stimuli in eliciting responses, and responses are elicited with stimulus onset rather than stimulus offset; (2) stimulation success increases as a function of both acoustic intensity and acoustic duration; (3) interactions of intensity and duration suggest that successful stimulation results from the integration of stimulus amplitude over a time interval of 50 to 150 ms; (4) the motor response elicited appears to be an all-or-nothing phenomenon, meaning stronger stimulus intensities and durations increase the probability of a motor response without affecting the duration or strength of the response; and (5) motor responses, measured by normalized EMG signals in the neck and tail regions, change signifcantly when sonicating rostral and caudal regions of the mouse motor cortex. Taken together our findings present good evidence for being able to target selective parts of the motor cortex with ultrasound neurostimulation in the mouse, steps that should provide encouragement for the development of new applications in larger animal models, including humans.
  • 2015From: Springer
    Pierre Le Béguec, François Canovas, Olivier Roche, Mathias Goldschild, Julien Batard.
    Part I: Press-Fit Concept -- Uncemented Concepts: Parameters to Make a Choice -- The Press-Fit Concept: Principles and Press-Fittable Zones -- The Press-Fit Concept: Practical Application -- The Press-Fit Concept: Implants And Instruments -- Part II: Preoperative Planning -- Radiographic Analysis Of The Femur -- Selection of a Strategy -- Making a Preoperative Template -- Part III: Surgical Technique -- Trochantero-Diaphyseal Femoral Flap -- Femoral Flap and Diaphyseal Primary Fixation -- Endofemoral Approach and Proximal Primary Fixation -- Part IV: Evaluation of the Radiographic Results -- General Considerations -- A-Evaluation of the Radiographic Results ? How? -- Evaluation of Initial and Secondary Bone Stock -- Evaluation of Osseointegration and Secondary Stability -- Global Radiographic Score -- Comparative Elements with the Engh Score -- Part V: Evaluation of the Radiographic Results -- Why? -- The Learning Curve and its Teachings -- Different Types of Primary Stability: Their Impact on the Radiographic Results -- Degree of Osteoporosis: Its Impact on the Radiographic Results -- Affected Initial Bone Stock: Its Impact on the Radiographic Results -- Parameters to Improve Radiographic Results -- Complications and Contraindications -- Numerical Evaluation and Comparative Analysis of Results -- General Conclusions: What You Should and What You Should not Do.
  • Ariel Veronica Dowling.
    The overall goal of this dissertation is to use novel motion analysis systems to investigate the underlying mechanisms that cause an anterior cruciate ligament (ACL) injury and then to explore movement modification methods that might prevent ACL injuries from occurring. Additionally, novel motion analysis systems can provide new information about ACL injuries and therefore should be used to help analyze these injuries from a different perspective. This thesis provides the results from multiple experimental studies that used two novel motion analysis systems to investigate the underlying causes of ACL injury and potential injury prevention methods. Using a markerless motion capture system, the first investigation determined that increasing the coefficient of friction of the shoe-surface condition will change a subject's movement strategies during a sidestep cutting task in specific ways that may increase the risk of ACL injury. This investigation provides a biomechanical basis for the increased incidence of ACL injuries on high friction surfaces, and suggests that females are more at risk for ACL injury when cutting on high friction surfaces. In terms of novel motion analysis systems, there is a need for simple, cost effective methods to identify athletes at a higher risk for ACL injury during jumping tasks. As such, the second study assessed the capacity of a wearable inertial-based system to evaluate ACL injury risk during jumping tasks. The proposed system measured the knee flexion angle and the trunk lean, and demonstrated good concurrent validity and discriminative performance in terms of the known risk factors for ACL injury. This study also reported the angular velocity of the thigh and shank segments during bilateral and unilateral drop jumps for the first time. Furthermore, this study illustrated that there is an association between the coronal segment angular velocity and knee abduction moment, and that the coronal segment angular velocity can differentiate between subjects at higher risk for ACL injury. Recent studies have shown that the incidence of ACL injury can be decreased through the use of intervention programs. Therefore, the objective for the final study was to determine if an independent inertial-based system can be used to modify jump landing mechanics in order to decrease the risk for ACL injury by providing real-time feedback based on known kinematic and kinetic injury risk factors. This study found that the subjects reduced their risk for ACL injury after training with the system because there were significant increases in the maximum knee flexion angle and the maximum trunk lean. The subjects also reduced their risk for injury by decreasing their thigh coronal angular velocity, which was correlated with a decrease in their knee abduction moment. This study suggests that an inertial-based system could be used for interventional training aimed at reducing the risk for ACL injury.
  • Melanie Diane Fox.
    Many children with cerebral palsy walk with a stiff knee gait, or a reduction and delay in swing phase knee flexion, which causes tripping or energy-inefficient compensatory movements. Since over-activity of the rectus femoris muscle is frequently implicated as the cause, a common treatment is transfer of the distal end of the rectus femoris from its insertion on the patella to a location behind the knee. Outcomes, though positive on average, vary among individuals, with some patients demonstrating unimproved or worsened knee flexion postoperatively. This variability is due in part to insufficient understanding of the biomechanical causes of stiff-knee gait and the functional effects of surgical treatment. The goal of this dissertation was to clarify the causes of stiff-knee gait and examine the biomechanical mechanism of improvement following rectus femoris transfer surgery. Swing-phase rectus femoris activity is commonly thought to cause of stiff-knee gait, despite evidence that many patients have excessive knee extension moments in preswing rather than swing phase. We compared the effects of preswing to swing phase activity of the rectus femoris on peak knee flexion in swing by creating and analyzing musculoskeletal simulations of subjects with stiff-knee gait. We found that in six out of ten subjects preswing rectus femoris activity had at least a 90% higher effect on peak knee flexion than swing phase rectus femoris activity, suggesting that preswing rectus femoris activity is an important factor limiting knee flexion in some subjects and should be examined to better determine the factors leading to stiff-knee gait. To understand how other muscles, besides rectus femoris, may limit knee flexion in stiff-knee gait, it is first necessary to understand how muscles coordinate successful swing phase knee flexion in unimpaired gait and how muscle contributions change with walking speed, since many stiff-knee subjects walk slowly. We analyzed simulations of unimpaired subjects walking at different speeds to determine the muscles that accelerated and decelerated knee flexion prior to swing. We found that preswing knee flexion acceleration was achieved primarily by the hip flexor muscles with help from biceps femoris short head, suggesting that weakness in these muscles may contribute to stiff-knee gait. Vasti and soleus decelerated knee flexion, suggesting over-activity in these muscles may contribute to stiff-knee gait. We also investigated the mechanism of improvement following rectus femoris transfer surgery. We altered the geometry of rectus femoris and simulated the dynamics of the swing phase of subjects with stiff-knee gait after different surgical procedures. Analysis of the simulations demonstrated that knee flexion may be improved with a reduction of the knee extension moment generated by the rectus femoris, even if the muscle is not converted to a knee flexor. This dissertation clarifies preswing rectus femoris activity as a cause of stiff-knee gait, demonstrates the functional mechanism of improvement following transfer surgery, and informs future research investigating other potential contributors to stiff-knee gait.
  • Danielle Lurisa Leiske.
    The tear film is the thin layer of fluid that covers the surface of the eye. While the functions of the tear film are numerous, the primary role is to protect the corneal surface. When an individual has dry eye disease the tear film breaks up and exposes the corneal epithelial cells, which leads to ocular irritation. The primary components of the outermost layer of the tear film are meibomian lipids, a mixture of long chain nonpolar lipids. Although this lipid layer is thought to play an important role in tear film stability, little is known about the structure and viscoelasticity of meibum, or how these properties relate to tear film stability in dry eye disease. The primary focus of this work was to understand how meibum behaves at an air-water interface to mimic the in vivo conditions of the tear film lipid layer. At room temperature meibum was found to form a predominantly elastic interfacial film, although the film became more fluid as it was heated to body temperature. Interfacial x-ray scattering at room temperature revealed ordered lattices and multilayers at high levels of compression that contributed to high elasticity. In bulk samples, small angle x-ray scattering identified two populations of lipid lamellar phases with unique melt behavior. Meibum collected from patients with meibomian gland dysfunction, a form of dry eye disease, contained the same crystalline phases; however, the prevalence of those phases was reduced indicating a quantifiable change in lipid composition. To ascertain whether meibum viscoelastic properties are relevant to tear film performance, the effects of surface elasticity on an advancing droplet were studied. While droplets covered with a Newtonian monolayer followed classical hydrodynamics, meibum and other insoluble surfactants with surface shear elasticity induced periodic stick-release of the contact line at low advancing velocities and non-ideal behavior at higher velocities. Finally, to explore how a water soluble surfactant may be used to repair a compromised lipid layer, the interactions between a poly(ethylene oxide)-poly(butylene oxide) block copolymer (EOBO) and a model phospholipid monolayer were studied. The lipids and EOBO remained phase separated at the interface, yet EOBO was able to restore the native lattice spacing and mechanical properties of the lipid monolayer, which could make it a valuable tool for a number of biological applications. Meibomian lipids are a complex natural extract with a number of remarkable properties. Although the lipids present in meibum are diverse, meibum can form an elastic interfacial film with ordered phases in bulk material or at an interface. We have shown a link between meibum structure and elasticity, which both depend on temperature. Major composition changes that occur with disease could alter meibum melt temperature and viscoelasticity, which will ultimately modulate the ability of meibum to stabilize the tear film.
  • Richard Matthew Wiard.
    More than 76 million Americans have hypertension, or high blood pressure, which can shorten life by 10 15 years if left untreated. Hypertension increases the risk of developing cardiovascular diseases (CVD) such as stroke, heart attack, congestive heart failure, or kidney failure that are often debilitating and impact quality of life. Prevention is the key to minimize CVD risk and increase longevity, but accurate prognosis of a future disease is difficult. Elevated blood pressure (BP) is generally the first sign of risk, but measuring pressure alone does not provide insight to where in the body problems may exist. Therefore, other screening tests are needed to more specifically isolate the underlying cause, which would improve the selection process of prescribing medications, or diet and exercise changes. And similar to BP measurements, such hypertensive screening tests may need to be performed at home to improve accuracy, since doctor's visits often trigger physiological responses that falsely elevate and lower BP. To address these concerns this work describes the design and validation of a home based noninvasive system (a bathroom scale) to measure aortic pulse wave velocity (PWV), to assess arterial stiffness, which is a clinical risk factor for certain CV diseases. The purpose of this work was four-fold: to develop a home monitoring device with simple user operation; to develop biomechanical theories as to why forces in the aortic arch can be sensed synchronously at the feet; clinically validate the biomechanical theory; and to demonstrate potential clinical utility of standing PWV measurements for trending and prognosis. The PWV scale is comprised of two different sensing technologies, ballistocardiography and photoplethysmography, which are embedded in the scale to measure pulse arrival times in the aortic arch and the foot--simply by standing on the scale. Using this system, PWV can be routinely determined in less than 30-seconds--significantly faster than commercial systems using trained operators. To validate this PWV system, a novel biomechanical theory was developed called Central Aortic Forces (CAF) to explain how the cardiovascular forces inside the body can be synchronously sensed outside the body. The computational models accurately predicted the amplitude of forces in the aortic arch (2-3 Newtons at rest), which were empirically confirmed in a clinical study; the empirical results agreed within 10% of the theory. To demonstrate trending abilities, a longitudinal PWV study was also performed over a four month duration, with results highly correlated to the applanation methods. Finally, an age study was conducted to characterize arterial aging, which matched well (p< 0.01) in slope and intercept major clinical trials published in the literature using applanation PWV (clinical gold standard). Examples are given on how such a system may improve prognosis to detect early vascular aging in young adults, otherwise masked in standard blood pressure measurements.
  • 2016From: Springer
    Kazuo Tanishita, Kimiko Yamamoto, editors.
    Chapter 1 Introduction -- Chapter 2 Fundamentals of Vascular Bio-fluid and Solid Mechanics -- Chapter 3 Fundamentals of Physiology and Biology of Vascular System -- Chapter 4 Hemodynamics in Physio- and Pathological Vessels -- Chapter 5 Cyclic Stretch-Induced Reorganization of Stress Fibers in Endothelial Cells -- Chapter 6 Mechanical Characterization of Vascular Endothelial Cells Exposed to Fluid Shear Stress -- Chapter 7 Tensile Properties of Smooth Muscle Cells, Elastin, and Collagen Fibers -- Chapter 8 Mechanobiology of Endothelial Cells Related to the Formation of Arterial Disease -- Chapter9 Mechanotransduction of Shear Stress by the Endothelium -- Chapter 10 Mechanobiology of Endothelial Cells Related to the Pathogenesis of Arterial Disease -- Chapter 11 Vascular Engineering of Blood Coagulation -- Chapter 12 Vascular Engine ering to Make Blood-Compatible Surface -- Chapter 13 Vascular Engineering of Circulatory Assist Devices -- Chapter 14 Innovations in Measuring Cellular Mechanics -- Chapter 15 Innovation of Vascular Engineering by Mechano-medicine -- Chapter 16 Integrated Vascular Engineering: Vascularization of Reconstructed Tissue -- Chapter 17 Novel Technology to Assay the Multicellular Network: On-Chip Cellomics Technology.-.
  • 2015From: CRCnetBASE
    edited by Eric M. Brey.
    "The first federally-funded meeting on tissue engineering was in 1988. In this and subsequent meetings, the fields of tissue engineering and regenerative medicine (TERM) have been described as having the potential to revolutionize clinical approaches to the replacement, reconstruction or regeneration of organs and tissues. While TERM research has resulted in new patient treatments, the broad impact on clinical practice envisioned has not been achieved. The development of new TERM therapies that have significant clinical impact requires the ability to control vascularization, the process of new vessel assembly. The circulatory system plays a number of vital roles in regenerating and functioning tissues. It supplies oxygen and nutrients, removes wastes and is a source of multiple cell types required to respond to changing physiological conditions. For nearly every TERM application, the ability to enhance, regenerate or engineer new tissues requires spatial and temporal control over the process of vascularization. While vascularization is being studied in a number of physiologic and pathologic processes, TERM applications present distinct challenges. For example, unique microenvironmental conditions result from biomaterial and cell combinations used in TERM applications that are not encountered in any other system. In addition, clinical applications require vascularization of large tissue volumes within time frames that are much lower than those found during vascularization in development and typical physiologic processes. These requirements place significant constraints on the design of TERM therapies"--Provided by publisher.
  • 2007From: Springer
    edited by Joyce Tombran-Tink, Colin J. Barnstable, Joseph F. Rizzo III.
    1 Retinal prosthetic devices: the needs and future potential -- 2 Spatial-, temporal-, and contract-resolutions obtainable with retina implants -- 3 How to restore reading with visual prostheses -- 4 Subretinal artificial silicon retinal microchip implantation with retinitis pigmentosa -- 5 Development of an intraocular retinal prosthesis to benefit the visually impaired -- 6 Development of a visual prosthesis: a review of the field and an overview of the Boston Retinal Implant Project -- 7 The Minimally Invasive Retina Implant Project -- 8 A retinal implant system based on flexible polymer microelectrode array for electrical stimulation -- 9 Electrode architecture: meeting the challenge of the retina-electrode interface -- 10 Circuit designs that model the properties of the outer and inner retina -- 11 Visual cortex and extraocular retinal stimulation with surface electrode arrays -- 12 Glaucoma drainage devices: advances in design and surgical techniques -- 13 The efficacy and safety of glaucoma drainage devices -- 14 Pellucid marginal corneal degeneration -- 15 Artisan toric lens implantation for correction of postkeratoplasty astigmatism -- 16 Phakic intraocular lenses for the treatment of high myopia -- 17 A telescopic prosthetic device for patients with end-stage AMD -- 18 The use of intracorneal ring segments for keratoconus.
  • 2009From: Springer
    Dorian McGavern, Michael Dustin, editors.
    Two-photon imaging of the immune system: a custom technology platform for high-speed, multicolor tissue imaging of immune responses / Andrew Bullen, Rachel S. Friedman, and Matthew F. Krummel -- Visualizing intermolecular interactions in T cells / Nicholas R.J. Gascoigne ... [et al.] -- Multiscale analysis of T cell activation: correlating in vitro and in vivo analysis of the immunological synapse / Michael L. Dustin -- T cell migration dynamics within lymph nodes during steady state: an overview of extracellular and intracellular factors influencing the basal intranodal T cell motility / Tim Worbs and Reinhold Forster -- Chemoattractant receptor signaling and its role in lymphocyte motility and trafficking / John H. Kehrl, Il-Young Hwang, and Chung Park -- New insights into leukocyte recruitment by intravital microscopy / Alexander Zarbock and Klaus Ley -- Visualizing the molecular and cellular events underlying the initiation of B-cell activation / Naomi E. Harwood and Facundo D. Batista -- Tracking the dynamics of Salmonella specific T cell responses / James J. Moon and Stephen J. McSorley -- Imaging Listeria monocytogenes infection in vivo / Vjollca Konjufca and Mark J. Miller -- Inflammation on the mind: visualizing immunity in the central nervous system / Silvia S. Kang and Dorian B. McGavern -- Multiphoton imaging of cytotoxic T lymphocyte-mediated antitumor immune responses / Alexandre Boissonnas ... [et al.].
    Also available: Print – 2009
  • Pete B. Shull.
    Haptic feedback stimulates the skin and is useful for conveying information across the human body. Combining haptic feedback with movement sensing and computation in real-time can create a rich and diverse system for characterizing and retraining human movement. This thesis presents haptic gait retraining as a conservative treatment for individuals with medial compartment knee osteoarthritis. Wearable haptic feedback devices, which either vibrate or stretch the skin, are worn on the body and used to inform kinematic changes during walking. The focus of gait retraining is to shift loading away from the arthritic medial compartment of the knee by reducing the knee adduction moment - a clinically relevant measure that has been linked to pain, incidence, severity, and progression of medial compartment knee osteoathritis. Thus, training individuals with knee osteoarthritis to walk in a way that reduces the knee adduction moment has the potential to reduce knee pain, improve function, and slow osteoarthritis progression. Four experiments were conducted to explore the viability of haptic gait retraining. During all experiments, subjects walked on an instrumented treadmill while motion capture data was streamed in real-time and wearable haptic feedback was used to inform gait changes. In the first experiment, subjects received feedback of the knee adduction moment measurement and were given freedom to make kinematic changes to lower the knee adduction moment. All subjects demonstrated the ability to make gait modifications to acheive this goal, though some chose awkward gait patterns. In the second experiment, haptic feedback was used to inform changes to the foot progression angle as subjects were trained to ``toe-in'' more than they normally did. Toe-in gait proved to be an easy-to-learn gait pattern which reduced the knee adduction moment and looked natural. The purpose of the third experiment was to train simultaneous changes to multiple kinematic gait parameters. Subjects received haptic feedback for trunk sway, tibia, and foot progression angles to inform new gait patterns based on correlations between the knee adduction moment and each kinematic parameter. Subjects demonstrated large reductions in the knee adduction moment comparable to more invasive surgical interventions such as high tibial osteotomy. In the final experiment individuals with persistent knee pain and clinically diagnosed knee osteoarthritis participated in a six week gait retraining program to assess learning retention and symptom changes. Subjects demonstrated learning retention and at the end of the six weeks reported improvements in knee pain and function, which were significantly greater than from the expected placebo effect. This thesis shows that haptic gait retraining is a promising conservative treatment option for individuals suffering from medial compartment knee osteoarthritis. Haptic gait retraining has the potential to alter walking patterns which could over time reduce knee pain, slow osteoarthritis progression, and ultimately improve quality of life.
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A web-based, decision support system for infectious diseases, epidemiology, microbiology and antimicrobial chemotherapy. The database, updated weekly, currently includes 337 diseases, 224 countries, 1,147 microbial taxa and 306 antibacterial (-fungal, -parasitic, -viral) agents and vaccines.

Over 10,000 notes outline the status of specific infections within each country.

Large number of high quality software and database programming titles from O'Reilly. Other software titles are also available from Sams and Prentice Hall. Limited to 7 concurrent users.Vast collection of software and database programming titles from multiple publishers, including Microsoft Press.Largest provider of engineering-related eBooks; includes titles in computer science and biomedical engineering.Over 4,000 full-text e-books covering scientific and technical information from CRC Press and others. Many handbooks and single volume reference sources.Includes peer-reviewed life science and biomedical research protocols compiled from Methods in Molecular Biology, Methods in Molecular Medicine, Methods in Biotechnology, Methods in Pharmacology and Toxicology, Neuromethods, the Biomethods Handbook, the Proteomics Handbook, and Springer Laboratory Manuals.Contains full text access to selected biomedical and nursing books.

Provides online, full-text access to Springer's journal titles as well as journals from other publishers.

Subjects include: life sciences, chemical sciences, environmental sciences, geosciences, computer science, mathematics, medicine, physics and astronomy, engineering and economics. Also includes eBooks.

Collection of over 8 thousand fulltext titles in engineering, math, and basic and applied biomedical research. Coverage is from 1967 to the present.A library of ebooks on a wide array of topics, digitized and made available online in conjunction with the original publishers.

Stanford Medicine

Lane Medical Library