Books by Subject

Biomedical Engineering

  • Digital
    Narayan Yoganandan, Alan M. Nahum, John W. Melvin, The Medical College of Wisconsin Inc on behalf of Narayan Yoganandan, editors.
    Springer2015
    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.
  • Digital
    edited by Ashutosh Tiwari and Anis N. Nordin.
    Wiley2014
    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.
  • Digital
    edited by Ashutosh Tiwari, Biosensors and Bioelectronics Centre, Linkping University, Sweden.
    Wiley2014
    "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.
  • Digital
    edited by Roger Narayan, Paolo Colombo ; volume editors Michael Halbig, Sanjay Mathur.
    Wiley2013
  • Digital
    editors, Yoshihiro Ito, RIKEN Institute, Wako-shi, Saitama, Japan, Xuesi Chen, Chinese Academy of Sciences, Changchun, Jilin, China, Inn-Kyu Kang, Kyungpook National University, Daegu, South Korea.
    Am Chem Socv. 1, 2017
    Am Chem Socv. 2, 2017
  • Digital
    edited by Venkatram Prasad Shastri, George Altankov, Andreas Lendlein.
    Springer2010
    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.
  • Digital
    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.
  • Digital
    Fábio J. Ayres, Rangaraj M. Rangayyan, and J.E. Leo Desautels.
    Atypon2010
    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.
  • Digital
    edited by Ashish S. Verma, Anchal Singh.
    ScienceDirect2014
    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.
  • Digital
    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.
  • Digital
    Nadey Hakim (ed.).
    Springer2009
  • Digital
    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.
  • Digital
    [edited by] Joseph Webster, Jr., Douglas Murphy.
    ClinicalKey2019
  • Digital
    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.
  • Digital
    Fan-Gang Zeng, Arthur N. Popper, Richard R. Fay, editors.
    Springer2011
    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.
  • Digital
    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.
  • Digital
    edited by T. Clive Lee and Peter F. Niederer.
    ProQuest Ebook Central2010
    Introduction to chapter I: Biomechanics / Gijsbertus J. Verkerke, Pascal Verdonck and T. Clive Lee -- Introduction to chapter II: Bioelectronics / Richard B. Reilly and T. Clive Lee -- Introduction to chapter III: Medical informatics for biomedical engineering / Paul McCullagh and T. Clive Lee -- Introduction to chapter IV: Biomaterials and tissue engineering / Fergal J. O'Brien and Brian O'Connell -- Introduction to chapter V: Medical imaging / Peter Niederer and T. Clive Lee -- Introduction to chapter VI: Rehabilitation engineering / Tadej Bajd and T. Clive Lee.
  • Digital
    Charles S. Lessard.
  • Digital
    [edited by] Julian Jones and Alexis G. Clare.
    Wiley2012
    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.
  • Digital
    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.
  • Digital
    edited by Anthony B. Brennan, Chelsea M. Kirschner.
    Wiley2014
    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.
  • Digital
    Robert B. Heimann and Hans D. Lehmann.
    Wiley2015
  • Digital
    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.
  • Digital/Print
    Stefanos Zenios, Josh Makower, Paul Yock.
    Digital : ProQuest Safari2010
    Print2010
    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.
  • Print
    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 ebiodesign.org. Readers can access this material quickly, easily, and at the most relevant point in the text from within the ebook"--Provided by publisher.
  • Digital
    Minoru Taya, Makoto Mizunami, Shûhei Nomura, Elizabeth Van Volkenburgh.
    Cambridge2016
    From experts in engineering and biology, this is the first book to integrate sensor and actuator technology with bioinspired design.
  • Digital
    ANSI2009Click fulltext button, Click guest acess (upper right) and Search for standard number 10993-1
  • Digital
    ANSI2006Click fulltext button, Click guest acess (upper right) and Search for standard number 10993-2
  • Digital
    ANSI2003Click fulltext button, Click guest acess (upper right) and Search for standard number 10993-3
  • Digital
    ANSI2009Click fulltext button, Click guest acess (upper right) and Search for standard number 10993-5
  • Digital
    ANSI2010Click fulltext button, Click guest acess (upper right) and Search for standard number 10993-13
  • Digital
    edited by Véronique Migonney.
    Wiley2014
    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.
  • Digital
    edited by Peter X. Ma, University of Michigan.
    Cambridge2014
    Knovel2014
    "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.
  • Digital
    editors S. Rodil, A. Almaguer, K. Anselme, J. Castro.
    Cambridge2012
  • Digital
    volume editor, Sanjukta Deb.
    Karger2015
    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.
  • Digital
    Antonio Merolli, Thomas J. Joyce, (eds.) ; foreword by Frédéric Schuind.
    Springer2009
  • Digital
    edited by Susmita Bose, Amit Bandyopadhyay, Roger Narayan.
    Wiley2013
    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.
  • Digital
    edited by Susmitya Bose, Amit Bandyopadhyay Roger Narayan.
    Wiley2014
    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.
  • Digital
    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.
  • Digital
    Ghias Kharmanda, Abdelkhalak El Hami.
    Wiley2017
  • Digital
    Dominique G. Poitout, editor.
    Springer2016
    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.
  • Digital
    Mark R. Pitkin.
    Springer2011
    Floating Skeleton Concept -- Sanomechanics -- Biomechanics for Life -- SanomechanicsTM Exercises -- About Forces and Moments in Locomotion -- Sanomechanics for Respiration.
  • Digital
    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.
  • Digital
    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.
  • Digital
    Jaroslav Šebestík, Milan Reiniš, Jan Ježek.
    Springer2012
    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. .
  • Digital
    edited by Ashutosh Tiwari, Murugan Ramalingam, Hisatoshi Kobayashi, Anthony P.F. Turner.
    Wiley2012
    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.
  • Digital
    edited by Sarah J. Hurst.
    Springer2011
    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.
  • Digital
    Joseph V. Tranquillo.
    Atypon2014
    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.
  • Digital
    Phillip Weinfurt.
    Atypon2010
    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.
  • Digital
    edited by João F. Mano.
    Wiley2012
    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.
  • Digital
    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.
    Springer2014
    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.
  • Digital
    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.
  • Digital
    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.
  • Digital
    edited by Avraham Rasooly and Keith E. Herold.
    Springerv. 1, 2009
    Springerv. 2, 2009
    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.].
  • Digital
    Erik Mosekilde, Olga Sosnovtseva, Amin Rostami-Hodjegan, editors.
    Springer2012
  • Digital
    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.
  • Digital
    Gail Baura.
  • Digital
    CRCnetBasev. 29, 2005
  • Digital
    Robert J. Roselli, Kenneth R. Diller.
    Springer2011
    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.
  • Digital
    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.
  • Digital
    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.
  • Digital
    editors, Kaushal Rege, Sheba Goklany.
    World Scientific2017
    Optically modulated theranostic nanoparticles -- Gene therapy treatments for cancer -- Nanocarrier based pulmonarygene delivery for lung cancer: therapeutic and imaging approaches -- Quantitative contrast enhanced ultrasound imaging in cancer therapy -- Multifunctional dendritic nanoparticles as a nanomedicine platform -- Oral drug delivery systems for gastrointestinal cancer therapy -- Cancer therapeutics with light : role of nanoscale and tissue engineering in photodynamic therapy -- Targeted contrast agents for 1h MRI of tumor microenvironment -- Solid lipid nanoparticles and nanostructured lipid carriers as anti-cancer delivery systems for therapy and diagnostics.
  • Digital
    Jay R. Goldberg.
    Atypon2012
    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.
  • Digital
    edited by Guruprasad Madhavan, Barbara Oakley, Luis Kun ; editorial by Joachim Nagel ; foreword by Robert Langer ; introduction by Bruce Alberts ; afterword by Shu Chien.
    Springer2008
    ProQuest Ebook Central2008Limited to 1 simultaneous users
    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.
  • Digital
    edited by Mohamed Al-Rubeai.
    Springer2009
    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.
  • Digital
    Donald McEachron.
    Atypon2012
    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.
  • Digital
    Keith R. Pine, Brian H. Sloan, Robert J. Jacobs.
    Springer2015
    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.
  • Digital
    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.
  • Digital
    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.
  • Digital
    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.
  • Digital
    Ozkan Ufuk Nalbantoglu and Khalid Sayood.
    Atypon2011
    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.
  • Digital
    edited by Zhongmin Jin.
    ScienceDirect2014
    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.
  • Digital
    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.
  • Digital
    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.
  • Digital
    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 https://simtk.org/home/va-batts. 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.
  • Digital/Print
    edited by Michael L. Johnson, Ludwig Brand.
    Digital : ScienceDirectpt. A, 2009
    Digital : ScienceDirectpt. B, 2009
    Digital : ScienceDirectpt. C, 2011
  • Digital
    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 simtk.org.
  • Digital
    Eisei Noiri, Norio Hanafusa, editors.
    Springer2014
    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.
  • Digital
    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.
  • Digital
    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.
  • Digital
    edited by Fabio A. Guarnieri.
    Springer2015
    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.
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    editor, Barry N. Feinberg.
    Status: Not Checked OutLane Catalog Record
    v. 1. General principles.
  • Digital
    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.
  • Digital
    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.
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    Dagmar Kainmueller.
    Springer2015
    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.
  • Digital
    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.
  • Digital
    Sibel Yildirim.
    Springer2013
    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.
  • Digital
    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.
  • Digital
    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.
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    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.
  • Digital
    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.
  • Digital
    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.
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    Patrick Langdon, John Clarkson, Peter Robinson editors.
    Springer2008
  • Digital
    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.
  • Digital
    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.
  • Digital
    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.
  • Digital
    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.
  • Digital
    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.
  • Digital
    editors, Martin J. Stoddart, April M. Craft, Girish Pattappa, Oliver F.W. Gardner.
    ScienceDirect2018
    Developmental Biology and Musculoskeletal Tissue Engineering: Principles and Applications focuses on the regeneration of orthopedic tissue, drawing upon expertise from developmental biologists specializing in orthopedic tissues and tissue engineers who have used and applied developmental biology approaches. Musculoskeletal tissues have an inherently poor repair capacity, and thus biologically-based treatments that can recapitulate the native tissue properties are desirable. Cell- and tissue-based therapies are gaining ground, but basic principles still need to be addressed to ensure successful development of clinical treatments. Written as a source of information for practitioners and those with a nascent interest, it provides background information and state-of-the-art solutions and technologies. Recent developments in orthopedic tissue engineering have sought to recapitulate developmental processes for tissue repair and regeneration, and such developmental-biology based approaches are also likely to be extremely amenable for use with more primitive stem cells.
  • Digital
    Xiaolu Zhu, Rangaraj M. Rangayyan, Anna L. Ells.
    Atypon2011
    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.

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