Books by Subject

Biomedical Engineering

  • 2008From: CRCnetBASE
    Rezaul Begg, Daniel T.H. Lai, Marimuthu Palaniswami.
  • 2014From: ScienceDirect
    edited by Zhongmin Jin.
    1. Fundamentals of computational modelling of biomechanics in the musculoskeletal system -- 2. Finite element modeling in the musculoskeletal system: generic overview -- 3. Joint wear simulation -- 4. Computational modeling of cell mechanics -- 5. Computational modeling of soft tissues and ligaments -- 6. Computatonal modeling of muscle biomechanics -- 7. Computational modelling of articular cartilage -- 8. Computational modeling of bone and bone remodeling -- 9. Modelling fracture processes in bones -- 10. Modelling fatigue of bone cement -- 11. Modelling fracture processes in orthopaedic implants -- 12. Modelling cementless cup fixation in total hip arthroplasty (THA) -- 13. Computational modeling of hip implants -- 14. Computational modelling of knee implants -- 15. Computational modelling of spinal implants -- 16. Finite element modelling of bone tissue scaffolds -- Index.
  • Rashmi Raghu.
    It is well known that blood vessels exhibit viscoelastic properties. Vessel wall viscoelasticity is an important source of physical damping and dissipation in the cardiovascular system. There is a growing need to incorporate viscoelasticity of arteries in computational models of blood flow which are utilized for applications such as disease research, treatment planning and medical device evaluation. However, thus far the use of viscoelastic wall properties in blood flow modeling has been limited. As part of the present work, arterial wall viscoelasticity was incorporated into two computational models of blood flow: (1) a nonlinear one-dimensional (1-D) model and (2) a three-dimensional (3-D) fluid-solid interaction (FSI) model of blood flow. 1-D blood flow model: In blood flow simulations different viscoelastic wall models may produce significantly different flow, pressure and wall deformation solutions. To highlight these differences a novel comparative study of two viscoelastic wall models and an elastic model is presented in this work. The wall models were incorporated in a nonlinear 1-D model of blood flow, which was solved using a space-time finite element method. The comparative study involved the following applications: (i) Wave propagation in an idealized vessel with reflection-free outflow boundary condition; (ii) Carotid artery model with non-periodic boundary conditions; (iii) Subject-specific abdominal aorta model under rest and exercise conditions. 3-D FSI blood flow model: 3-D blood flow models enable physiologic simulations in complex, subject-specific anatomies. In the present work, a viscoelastic constitutive relationship for the arterial wall was incorporated in the 3-D Coupled Momentum Method for Fluid-Solid Interaction problems (CMM-FSI). Results in an idealized carotid artery stenosis geometry show that higher frequency components of flow rate, pressure and vessel wall motion are damped in the viscoelastic case. These results indicate that the dissipative nature of viscoelastic wall properties has an important impact in 3-D simulations of blood flow. Future work will include simulations of blood flow in patient-specific geometries such as aortic coarctation (a congenital disease) to assess the impact of wall viscoelasticity in clinically relevant scenarios. In the present work, arterial viscoelasticity has been incorporated in 1-D and 3-D computational models of blood flow. The biomechanical effects of wall viscoelasticity have been investigated through idealized and subject-specific blood flow simulations. These contributions are significant and suggest the potential importance of wall viscoelasticity in blood flow simulations for clinically relevant applications.
  • Joanna Lankester.
    The rapid rise in obesity in the US over the last several decades parallels a decrease in infectious disease incidence and a rise in antimicrobial usage. The role of the microbiome--which is influenced by both disease and by biocidal chemicals--on body weight is of increasing interest. We desired to quantify effects of changes in disease patterns and microbiome shifts on body weight of the population; however, no population-level model of body weight existed. Drawing from a collection of literature describing models of individual body weight, a model was built to quantify weight changes across the population using publicly available data from the National Health and Nutrition Examination Survey (NHANES). The model used an energy balance perspective, quantifying energy intake and expenditure. First, dietary data was obtained to describe energy intake. Dietary data comes primarily from self-report and is notoriously inaccurate as individuals tend to under-estimate their food consumption. A dataset was obtained from a study where participants had completed dietary recall surveys and had had energy expenditure measured. Using this as a "training dataset", Chapter 3 describes two predictive models developed which adjust dietary intake to a more biologically plausible range. The models were validated, with a simulation of NHANES data, for their ability to produce estimates within bounds established a priori. They produced substantially more realistic estimates than those derived from the raw data. With better estimates of energy intake, a simulation model of body weight in a population was built (Chapter 4). A population was drawn from NHANES which represented a realistic cross-section of the U.S. population based on age, sex, and survey sampling weights. Energy intake and expenditure were tracked for each individual in the model, and an excess or deficiency of energy was converted to a gain or loss of body weight. The effect of ageing on the weight distribution of the population was calculated. The excess energy necessary to produce the shift in the body weight distribution of the US population over a 20-year period was estimated. The effect of an infectious agent's alteration of energy intake and expenditure and associated body weight was also calculated. Finally, the relationship between NHANES data on triclosan and body mass index (BMI) was studied (Chapter 5). Triclosan is a biocide that likely affects the gut microbiome. The effect of triclosan on BMI in a linear regression was studied with triclosan expressed in two ways: (1). as a binary variable (present vs. absent) and (2). in quartiles (in order to assess whether increased quantity of triclosan led to a trend in BMI). Triclosan presence was found to be associated with an increase in BMI. By quartile, BMI was higher in lower levels of triclosan compared to higher levels, suggesting the possibility of multiple mechanisms of action.
  • Lampros C. Kourtis.
    A new method to evaluate bone rigidity and strength using tomographic bone images obtained via QCT (Quantitative Computed Tomography) is introduced. A newly developed computer program named VA-BATTS is used for image processing, bone segmentation, mesh creation, material assignment and calculation of far field normal and shear stresses as well as other cross sectional properties. In order to calculate torsional and transverse shear stresses in prismatic bodies having inhomogenous material properties, a new two-dimensional finite element formulation to estimate is presented. The formulation combines the torsional and transverse shear problem solutions and adds terms to account for the material inhomogeneity into one Weak Form of the problem, further discretized to yield a numerical approximation of the shear stresses problem. Results were validated using analytical models as well as three dimensional commercial code test cases yielding mean errors over the entire domain of less than 1%. This semi-automated application is publicly distributed and can be downloaded from VA-BATTS implements an elliptical stress failure criterion to predict bone strength. To validate, fifty-two fresh frozen femurs were tested under combined three-point bending and torsion to failure. VA-BATTS was able to predict bone failure under combined bending and torsion (R2=0.68) as well as bone torsional (R2=0.80) and bending (R2=0.50) rigidity. Using multivariate analysis that combined the elliptical stress failure and the torsional and bending rigidities, the prediction confidence level was raised (R2=0.87), comparable to existing more complex three dimensional finite element studies. The elliptical stress criterion suggests that the distal femur is weaker, in absolute terms, than the midshaft femur suggesting an explanation of the increased rate of distal femur fractures in patients with Spinal Cord Injury. In general, the newly introduced method proved to yield more accurate predictions compared to DXA derived Bone Mineral Density measurements (R2=0.56). Fracture patterns were analyzed to show mostly spiral patterns where torsional loads were applied. In addition, the accuracy of three point bending experiments was examined. Three parameters that may introduce errors in the predictions - transverse shear, local deformation (indentation) as well as cross sectional deformation effect -- were studied using a parametric finite element model. The model shows that depending on the geometric properties of the bone, errors as high as 75% may be introduced in the estimation of the bone elastic modulus. Bone rigidity estimates may now be corrected using the correction factors supplied in this study.
  • pt. A-B, C, 2009, 2011.From: ScienceDirect
    pt. B, 2009From: ScienceDirect
    pt. C, 2011From: ScienceDirect
    edited by Michael L. Johnson, Ludwig Brand.
  • Edith Merle Arnold.
    Walking and running rely on the complex coordination of the neurological, muscular, and skeletal systems. The role of muscles in this system is to produce force, a task that is dramatically affected by the dynamics of muscle fibers. In walking and running, we do not know how fiber dynamics affect force generation because experimental tools are ill suited to these measurements. Computer models can be powerful tools for estimating muscle dynamics that cannot be measured experimentally. During my doctoral research I created a model based on state-of-the-art muscle architecture data that estimates fiber lengths and velocities during movement. I used this model to create simulations of muscle fiber dynamics for five subjects walking and running at multiple speeds. Analysis of my simulations revealed how walking or running speed affects force generation, explained how running enables some muscles to produce more force than they do in walking, and yielded normative muscle fiber lengths and velocities of eleven muscles during walking and running. The results support the hypothesis that the walk-to-run transition in human gait is related to the force generation ability of the plantarflexors, offer insights into dynamic properties of muscles that have not yet been measured during walking and running, and permit comparisons among muscles with diverse architecture. The model and simulations created as part of this work can be applied to many other research areas in biomechanics and have been made freely available at
  • 2014From: Springer
    Eisei Noiri, Norio Hanafusa, editors.
    This pocket-sized manual serves as a concise and ideal reference work for therapeutic approaches using apheresis. Covering both basic theory and clinical details to facilitate improved treatment and patient outcomes, the text considers a variety of diseases, including myasthenia gravis, multiple sclerosis, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, nephrotic syndrome, TTP/TMA, dilated cardiomyopathy, and many other conditions. The book also reviews the growing trend toward adopting this unique therapy for a wide range of health management issues such as morbid obesity and/or type 2 diabetes, and for lowering LDL-cholesterol (cholesterol apheresis) in patients unresponsive to medication or lifestyle modification.
  • 2007From: CRCnetBASE
    edited by Terje A. Skotheim, John R. Reynolds.
    Conductive polymers as organic nanometals -- Conducting polymer fibre for smart fabric and interactive textile applications -- Inkjet printing and patterning of PEDOT-PSS -- Printing organic electronics on flexible substrates -- Light emitting polymers -- Organic electro-optic materials -- Conjugated polymer electronics -- Electrical bistable polymer films and their applications in memory devices -- Electroactive polymers for batteries and supercapacitors -- Conjugated polymer based photovoltaic devices -- Biomedical applications of ICPs -- Biosensors based on conducting electroactive polymers -- Optical biosensors based on conjugated polymers -- Conducting polymers for MEMS and other micro-devices -- Corrosion protection using conducting polymers -- Artificial muscles.
  • Jayodita Chetan Sanghvi.
    Significant progress has been made in experimentally discovering and understanding the molecular mechanisms of various cellular processes, from metabolism to cell division. However, integrating this knowledge into a comprehensive understanding of cellular physiology remains a challenge. We have attempted to synthesize the scientific community's knowledge of cell biology into one system by building the first computational model of the life cycle of a single cell. Our model describes Mycoplasma genitalium, the simplest known self-replicating organism. The model accounts for all known gene functions and molecular interactions. This "whole-cell" model provides a better understanding of basic cellular physiology and cell-to-cell variation. Furthermore, this model can be used to make systems level predictions and biological discoveries that would not have been possible without this integrated view of a cell. In order to represent all of the known gene functions of M. genitalium, we divided the genes into 28 functional groups describing cellular processes such as replication, transcription, translation, metabolism, supercoiling, and cytokinesis. We developed independent computational models for each of these cellular processes using the mathematical representation best fit for the given process, such as linear optimization, ordinary differential equations, and probabilistic and stochastic methods. To integrate the system, information was passed between these sub-modules at each second of the simulated cell cycle. Data and parameters for the model were acquired from hundreds of publications in the literature. The model was fit, benchmarked, and tested such that the cell grows and divides according to our understanding of cell physiology. The whole-cell model outputs the counts, actions, and interactions of every molecule at every time point of the cell cycle. It has made novel predictions about various aspects of cellular biology including protein occupation of the chromosomes, energy usage, and non-transcriptional forms of cell-cycle regulation. We performed an experimental study, measuring the growth rates of single-gene disruption M. genitalium strains, and found that 84% of the model predicted growth rates matched the experimental results, thus validating the predictive power of the model. The remaining 16% of growth rates indicated misrepresentations in the model--opportunities for biological discovery. We were able to predict biological behavior that would reconcile most of these discrepancies, and in three cases the model was able to predict refined kinetic parameters of compensatory metabolic reactions in the system. We performed kinetic assays to validate the accuracy of all three self-refining model predictions. This thesis presents the first gene-complete model of an organism that has been experimentally validated. Using the model to guide and support future experimentation, we hope to continue to discover previously unknown cellular physiology. Overall, the whole cell model enables a view of the entire inner workings of a cell, an integrated understanding that is difficult to achieve by experimentation alone. We hope that expansions of this model will continue to enable discovery of cellular biology, will increase our understanding of prokaryotes and higher organisms, will elucidate multifaceted behaviors like complex disease states, and will serve as predictive tools to guide synthetic biology.
  • Joshua Dale Webb.
    The shoulder bones provide few constraints on motion. Therefore, stability must be maintained by muscles and ligaments. Shoulder mobility allows versatility of function, but makes the shoulder prone to injury. A better understanding of the role of muscle in shoulder mechanics is needed to improve the treatment of shoulder injuries and pathologies. Computational models provide a valuable framework for characterizing joint mechanics. Previous shoulder models have used simple representations of muscle architecture and geometry that may not capture the details needed to fully understand muscle function. The purpose of this dissertation was to create a detailed 3D finite element model of the deltoid and the four rotator cuff muscles. This model was then used to characterize the muscle contributions to joint motion and stability. The model was constructed from magnetic resonance images of a healthy shoulder. From the images, the 3D geometry of the muscles, tendons and bones was acquired. A finite element mesh was constructed and the 3D trajectories of the muscle fibers were mapped onto the finite element mesh. A hyperelastic, transversely-isotropic material model was used to represent the nonlinear stress-strain relationship of muscle. Bone motions were prescribed and the resulting muscle deformations were simulated using an implicit finite element solver. To characterize muscle contributions to joint motion, we calculated moment arms for each modeled muscle fiber. We found that 3D models predicted substantial variability in moment arms across fibers within each muscle, which is not generally represented in line segment models. We also discovered that for muscles with large attachment regions, such as deltoid, the line segment models under constrained the muscle paths in some cases. As a result, line segment based moment arms changed more with joint rotation than moment arms predicted by the 3D models. Glenohumeral instability is common, and difficult to treat. To better understand the mechanics of instability we used the 3D model to investigate the role of the muscles in stabilizing the glenohumeral joint by simulating joint translations. We found that at the neutral position, anterior deltoid provides the largest potential to resist anterior translation which counters the conclusions of conventional line segment models. This is the result of compression generated by muscle contact, which must be considered when characterizing the ability of muscle to resist joint translation. This dissertation provides a new computational method for analyzing shoulder mechanics, and demonstrates the importance of 3D analysis when investigating the complex function of shoulder muscles.
  • 2015From: Springer
    edited by Fabio A. Guarnieri.
    This book presents a unique approach not found in any other text for those looking to improve the clinical results of refractive surgery by gaining a better understanding of corneal biomechanics and the instrumentation related to it. Written by leading experts in the field, this book provides authoritative coverage of the interactions of the cornea and the bioinstrumentation, such as corneal topography, pachymetry, aberrometers, tonometry and optical coherence tomography. Organized in an easy-to-read manner, Corneal Biomechanics and Refractive Surgery is designed for refractive surgeons and general ophthalmologists alike and describes the biomechanical role of the corneal tissue and how each part is affected in refractive surgery. Additionally, showing what the bioinstrumentation can measure, how models can improve understanding of the interaction between biomechanics, bioinstrumentation, and refractive surgery, and how these models and bioinstrumentation together can improve the refractive results, are also discussed.
  • editor, Barry N. Feinberg.
    PrintStatus: Not Checked OutLane Catalog Record
    v. 1. General principles.
  • Rostam Dinyari.
    In age-related macular degeneration (AMD) and retinitis pigmentosa (RP), two leading causes of blindness, the photoreceptor layer of the retina is degenerated while the rest of the retina is well preserved. The function of the photoreceptors is very similar to that of solar cells. Upon receiving light, they activate the inner layers of the retina by producing electrical and chemical signals. These signals are then processed and compressed by a complex circuit of retinal neurons (horizontal cells, bipolar cells, amacrine cells, and ganglion cells) and sent to the brain. The brain perceives these data as sight. Electronic retinal implant systems seek to restore sight in AMD and RP by electrical stimulation of the surviving retinal neurons. Currently the more dominant systems consist of a microelectrode array, which is placed directly on the ganglion cells (epiretinal). In this approach, a camera mounted on goggles captures video which is then processed by a pocket computer. The power and data are then transmitted wirelessly to an extraocular receiver unit. Through an intraocular cable, the receiver unit sends appropriate electrical stimuli to the array of microelectrodes. The electrodes then stimulate the ganglion cells by passing current pulses through the tissue. These stimulations are perceived by the brain as spots of light. The epiretinal approach has some disadvantages. Because the electrodes directly stimulate the ganglion cells, the image processing and data compression capabilities of the retina are not utilized. Placing the extraocular receiver unit and connecting it via a cable to the microelectrode array significantly complicates the surgical procedure and increases the chance of post surgical complications. Additionally, the perceived images are independent of the eye movements. We have developed an integrated photovoltaic monolithic silicon retinal implant that requires no electrical power or data connection. In our design, a miniature camera captures video that is processed by a pocket computer before being projected into the eye at a near-infrared wavelength ([Lambda] = 905 nm) onto the silicon implant located in the subretinal space (area in the back of the retina). The implant consists of a two-dimensional array of photovoltaic pixels. The projected image is provided in pulsed fashion and each pixel element consists of up to three series-connected photovoltaic cells such that the pixels deliver current pulses that are sufficiently strong to stimulate the remaining functional neural cells. The current pulses are interpreted as visual images by the brain. Placing the implant in the subretinal space allows for utilization of the existing image processing and data compression functions of the retina. Each pixel receives both power and data directly through laser radiation. This eliminates the need for a separate wireless receiver unit and simplifies the surgical procedures and reduces the post-surgical risks. Additionally, in this approach, eye movements change the perceived images. The novelty of the work reported here is the integration of photovoltaic devices in a MEMS process that allows the implant to deform to the natural curvature of the eye, while also providing isolation between the bodies of the three series-connected subpixels that make up each pixel. This was achieved by patterning the implants into an array of pixels connected together by deformable silicon flexures. In addition, the trenches also provide electrical isolation between the three series-connected photovoltaic subpixels. Curving the implant is advantageous since the complete implant is in focus, resulting in optimum quality of vision perceived. Curved implants can also be substantially larger than planar implants and can hence cover a larger part of the field of view. A curvable implant also causes no mechanical strain or abnormality in the eye. Usage of three series-connected subpixels per pixel improves the impedance matching to the surrounding tissue and enhances the injected current per pixel allowing for higher resolution implants. Fabricated implant with a resolution of 64 pixels/mm2 can inject sufficient current for neural activation at safe optical intensities. Additionally, the exchange of nutrients and waste, which is necessary for the survival of the retinal cells, is provided by diffusion through the trenches that define the silicon devices.
  • 2010From: CRCnetBASE
    William S. Kisaalita.
    "This book is based upon cutting-edge research conducted in the authors lab (Cellular Bioengineering), which over the past decade has developed a number of sophisticated techniques to facilitate use of 3D cell based assays or biosensors. This book uses data from peer-reviewed publications to conclusively justify use of 3D cell cultures in cell-based biosensors (assays) for (HTS). The majority of assays performed in accelerated drug discovery processes are biochemical in nature, but there is a growing demand for live cell-based assays. Unlike biochemical ones, cellular assays are functional approximations of in vivo biological conditions and can provide more biologically relevant information"--Provided by publisher.
  • Min-Sun Son.
    Meniscal degeneration often precedes cartilage degeneration, and effective detection and treatment can be critical in preventing osteoarthritis. The meniscus is a heterogeneous tissue, and obtaining information on the varying characteristics of meniscal regions is important in investigating such strategies. However, no current method exists that can detect such meniscal heterogeneity in the tissue matrix. In addition, the lack of quantitative information on meniscal heterogeneity hinders the development an effective, long-term solution that can treat degeneration in the meniscus. The purpose of this dissertation was thus 1) to find quantitative characteristics that defined meniscal heterogeneity and 2) to evaluate non-invasive diagnostic methods that could reflect the matrix tissue properties and detect meniscal heterogeneity. To accomplish the first goal, gene expression profiles of meniscal cells were statistically analyzed to identify quantitative markers that could distinguish between different regions of the meniscus, describing its heterogeneous properties. This information was then used to evaluate cell sources for meniscal tissue engineering, demonstrating the potential application of these quantitative markers in developing an effective treatment for meniscal degeneration. Secondly, in order to detect meniscal heterogeneity, which is reflected in the changing tissue properties within the tissue, magnetic resonance imaging was used. The potential of the imaging parameters T1[rho] and T2 relaxation times in detecting various meniscal tissue properties, including the matrix composition and mechanical properties, was examined. Ultimately, such information would be useful in identifying internal degenerative changes that take place in the matrix of the tissue prior to macroscopic injuries. In this study, both T1[rho] and T2 relaxation times showed variation with tissue properties but were highly correlated with one another, indicating that only one imaging parameter might be necessary as a diagnostic tool in a clinical setting. In addition, an exploratory aim visualized the internal secondary collagen network in the meniscus and examined its deformation in different mechanical loading positions. This work significantly adds to the understanding of the heterogeneous properties of the meniscus and the potential of magnetic resonance imaging parameters as detection markers. It contributes to the advancement of diagnosis and treatment strategies for meniscal degeneration, which has further implications for preventing osteoarthritis progression.
  • 2015From: Springer
    Dagmar Kainmueller.
    Segmentation of anatomical structures in medical image data is an essential task in clinical practice. Dagmar Kainmueller introduces methods for accurate fully automatic segmentation of anatomical structures in 3D medical image data. The author's core methodological contribution is a novel deformation model that overcomes limitations of state-of-the-art Deformable Surface approaches, hence allowing for accurate segmentation of tip- and ridge-shaped features of anatomical structures. As for practical contributions, she proposes application-specific segmentation pipelines for a range of anatomical structures, together with thorough evaluations of segmentation accuracy on clinical image data. As compared to related work, these fully automatic pipelines allow for highly accurate segmentation of benchmark image data. Contents Deformable Meshes for Accurate Automatic Segmentation Omnidirectional Displacements for Deformable Surfaces (ODDS) Coupled Deformable Surfaces for Multi-object Segmentation From Surface Mesh Deformations to Volume Deformations Segmentation of Anatomical Structures in Medical Image Data Target Groups Academics and practitioners in the fields of computer science, medical imaging, and automatic segmentation. The Author Dagmar Kainmueller works as a research scientist at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, with a focus on bio image analysis. The Editor The series Aktuelle Forschung Medizintechnik - Latest Research in Medical Engineering is edited by Thorsten M. Buzug.
  • 2007From: Springer
    Jasjit S. Suri, Aly A. Farag [editors].
  • James Francis Nishimuta.
    Osteoarthritis is a debilitating disease that affects 27 million Americans. Major risk factors for osteoarthritis include mechanical injury and obesity. Prolonged exposure to mechanical overload in the knee joint, either by injury, malalignment, or obesity, is associated with early onset of osteoarthritis. Recent evidence demonstrates that adipose tissue is a metabolically active and produces systemic biofactors known as adipokines associated with numerous diseases including cardiovascular disease, hypertension, insulin resistance, rheumatoid arthritis, and osteoarthritis. Interestingly, obesity is a significant risk factor for hand osteoarthritis, suggesting a biologic link between obesity and osteoarthritis that is perhaps mediated through adipokines. While many studies investigating in vitro osteoarthritic degradation have focused on cartilage tissue, the menisci has received relatively little attention despite it's important functional role in joint stability and load transfer in the knee. The purpose of this thesis was to explore the relative susceptibility of cartilage and meniscal tissue degradation to in vitro mechanical overload and adipokine exposure using an immature bovine tissue explant model. To explore the injury response, explants of cartilage and meniscal tissues were compressed at various strain rates to create a spectrum of peak injury forces and cultured for up to nine days post-injury. To investigate whether adipose tissue and adipokines can biochemically induce changes in cartilage and meniscal tissues, explants of cartilage and meniscal tissue were incubated with infrapatellar fat pad or individual adipokines and assessed for altered matrix metabolism. Overall, results indicate that, while mechanically robust, meniscal tissue is vulnerable to biologic damage induced by mechanical overload and adipokines. We also demonstrate for the first time that meniscal tissue is more catabolically sensitive to adipokines than cartilage tissue. These results provide evidence that obesity-driven degradation of knee joint could be biochemically mediated and suggest meniscal degradation as a possible early event in osteoarthritis development.
  • 2013From: Springer
    Sibel Yildirim.
    Dental Evolution -- Tooth development -- Dental Pulp is a Connective Tissue -- Dental Pulp Stem Cells (DPSC) -- Isolation methods of DPSC -- Characterization of DPSC -- Reprogramming of DPSC to induced pluripotent stem cells (iPSC) -- Immunomodulatory effects of DPSC -- Dental Pulp is a Complex Adaptive System.
  • Daniel McConnell Aukes.
    A balance between complexity and functional capabilities has been explored since the first years of multi-fingered robotic hands. In an age where DC motors are the de facto standard for actuation in robotics, the problem of needing to operate in a human-sized world puts severe constraints and limits on actuator size and placement in hands. While many successful examples of fully-actuated designs exist, these designs generally reflect the trade-offs and sacrifices imposed by such constraints. In that light, underactuation, employing fewer actuators than degrees of freedom, has gained attention as a method to achieve many of the functional capabilities of fully-actuated hands with fewer constraints on actuators and transmissions. Underactuated hands also have distinct advantages over fully actuated hands, especially when used on mobile robots, due to their reduced weight and control complexity, and the potential for increased robustness. However there is typically a trade-off in terms of reduced controllability or manipulability when handling grasped objects. When designing underactuated hands, extra care must be taken during the design process to ensure that such hands will grasp a wide range of object sizes and shapes robustly, particularly when friction is low and uncertain. Despite these concerns, underactuated hands have become increasingly popular in robotic and prosthetic applications. Robotic hands are also a venue in which novel, secondary mechanisms are often found. Devices such as differentials, valves, clutches, and low-power, shape-changing actuators have been used to improve grasp robustness on a wider range of objects and allow users more grasping and manipulation options. However, the location and placement of secondary actuators has not been studied in a comprehensive way with respect to the types of actuation methods possible. This is due in part to the lack of general analytic tools which enable designers to rapidly investigate their designs prior to the prototyping stage. Additionally, much of the analysis in the field of robotic hands is done once basic design choices have already been made, making subsequent analyses specific only to a set of design parameters specific to those choices. The same point can be made regarding quality metrics, which suffer from fragmented utilization due to the many different emphases placed on different design requirements. The primary goal of this thesis is to provide a framework for the analysis and evaluation of underactuated robotic hands. The first chapter discusses both the broad motivations for studying robotic hands and the specific contributions of this thesis. The next chapter reviews relevant designs from literature, analyses that have accompanied them, uses of secondary devices in underactuated hands, and the progress that dynamics simulators have made towards representing reality. In the next chapters, the issues related to modeling abstract, generic hand designs is discussed, and a kinematic framework is introduced to derive the force relationships between actuator and grasped object for many mechanisms commonly encountered in underactuated hands. Chapter 6 discusses difficulties associated with solving static force equations, and several methods are introduced to accomplish this. The last of these options relies on three-dimensional rigid-body dynamic simulations to evaluate the performance of compliant, underactuated mechanisms which may encounter conditions such as coulomb friction in contact and and damping at the joints. In the next chapters, these force relationships are derived and discussed for specific hand designs in the context of a force-field representation, and several performance metrics are derived which measure a hand's ability both to acquire and retain objects. The benefits of secondary actuation mechanisms are then discussed with two specific examples. First is the SRI/Stanford/Meka hand, a tendon-driven, compliant, underactuated hand capable of locking individual joints. Second is a mechanism implemented on the Seabed Hand, which increases the range of graspable objects and allows users to selectively change grasp properties based on their specific control needs. Finally, the impacts of friction are discussed, and the trends from simulations are compared with experimental data. From these experiments the benefits of secondary mechanisms can be demonstrated in a frictional world as well.
  • Prasheel Vashdev Lillaney.
    Using hybrid x-ray/MR (XMR) systems for image guidance during interventional procedures can enhance the diagnosis and treatment of neurologic, oncologic, cardiovascular, and other disorders. XMR suites have become more available, with various vendors offering dual-modality solutions. These systems combine the three-dimensional imaging capabilities and excellent soft tissue contrast provided by MR with the high spatial/temporal resolution and accurate device tracking provided by x-ray. To eliminate system compatibility concerns, the suites typically have long travel distances between MR and x-ray components. As a result, switching between modalities requires shuttling the patient several meters from one system to the other. Because patients typically have critically placed monitoring systems and intravenous lines for drug delivery and anesthesia, the cumbersome shuttling process impedes repeated switching between the modalities. To circumvent the hurdles associated with alternating between modalities, we proposed a close proximity hybrid system design in which a c-arm fluoroscopy unit is placed immediately adjacent to a closed bore MR system with a minimum distance of 1.2 meters between the x-ray and MR imaging field of views. Placing the x-ray system so close to the MR bore requires an x-ray tube capable of operating in a relatively strong MR fringe field environment. Existing rotating anode x-ray tube designs fail within MR fringe field environments because the magnetic fields alter the electron trajectories in the x-ray tube and act as a brake on the induction motor, reducing the rotation speed of the anode. In my work, I have developed (1) techniques to correct for the altered electron trajectories and (2) a novel motor design that eliminates the reduced rotation speed of the anode. Altering electron trajectories between the cathode and anode affects the location, size, and shape of the x-ray tube focal spot on the anode. I proposed a combination of approaches to control the trajectories. First, I derived an active magnetic shielding design using constrained optimization techniques that minimizes power consumption and heat deposition in the external deflection coils. I then adapted my shielding design to include rare earth permanent magnets, to further reduce the power and size requirements of the coils. Finally, I designed a split-focusing cup that controls the electron trajectories via electrostatic mechanisms, providing an alternative that is more space efficient and MR-compatible. High rotation speed of the anode is needed for sufficient instantaneous heat loading on the target area, to achieve the needed x-ray tube output. There is currently no available motor design to rotate the anode in the expected magnetic environment. To solve this problem, I designed a new motor that operates efficiently within the fringe field. The design is analogous to a modified three-pole brushed DC motor, with the radial component of the MR fringe field replacing the permanent magnet stator field used in conventional brushed DC motors. The motor support bearings provide rotating electrical contacts, while feedback signals from a position sensor control electrical commutation. A vacuum compatible prototype of the proposed motor design was assembled, and its performance was evaluated at various field strengths and orientations. Combining the control mechanisms for the electron trajectories with the new motor design yields a robust x-ray tube capable of operating in fringe fields with magnitudes on the order of 0.1 to 0.2 T.
  • Jae-Woong Jeong.
    Optical MEMS (Micro-Electro-Mechanical Systems) is an enabling technology that realizes miniaturized optical systems with high functionality and excellent performance. In this dissertation, two novel miniaturized optical systems are presented for applications in optical communication and biomedical imaging. In Part I, a multi-functional MEMS tunable optical filter are described, which is a key element for dynamic wavelength provisioning in reconfigurable optical networks and communication systems. This filter is built based on MEMS platform technology that allows large vertical mirrors (311 [mu]m x 450 [mu]m x 40 [mu]m) to be micro-assembled on actuated platforms to enable compact tunable optical filters with large apertures and high-quality optical mirrors with very low scattering losses. Besides, electrostatic combdrive actuators connected to the MEMS platforms provide independent and continuous control of the center wavelength and the optical bandwidth. The filter has been tested by integrating it in a 10Gb/s communication system. The performance of the MEMS tunable filter is demonstrated for amplified spontaneous emission (ASE) rejection and wavelength selection. In PART II, a 3-D MEMS scanning system utilizing 2-D lateral and 1-D vertical MEMS scanners is introduced for use in miniature in vivo dual-axis confocal (DAC) microendoscopes, which is an emerging biomedical-imaging technology with high resolution, good tissue penetration, large field of view, and ability to provide both reflectance and fluorescence contrast images. Both MEMS scanners are fabricated exclusively by front-side processing to enable compact and robust structures that facilitate handling and packaging for miniaturized optical instrumentation. Co-operation of a 2-D lateral scanner and a 1-D vertical scanner enables fast 3-D microscopy over a volume that measures 340[mu]m by 236[mu]m by 286[mu]m. This part describes the principle of the all-MEMS-based 3-D scanning DAC microscopy that gives the functionality of OCT (real-time vertical cross-section imaging) to a confocal microscope.
  • Paul J. Csonka.
    Over the last several years advances and miniaturization of technology have allowed legged robots to move from the research laboratory to the real world, as evidenced by the large number of flexible platforms only recently available. These platforms are successful, but fall short of capitalizing on the biggest advantage of legs: the ability for high speed locomotion over unstructured terrain. Additionally, no current articulated legged robot is able to perform both static and truly dynamic locomotion, as the actuation technology is not conducive to these two very different regimes of operation. Currently, machines that are dynamic are unable to walk or position themselves accurately, and machines that function very well with static motions are unable to move dynamically. The bipedal robot TRIP (Tendonized Running Inspired Platform) was built to study dynamic maneuvering and control of an articulated legged robot with high-inertia legs. Each leg includes an inelastic tendon which couples ankle joint rotations to knee joint rotations, resulting in simplified effective dynamics and control, and a high degree of passive stabilization with dynamic maneuvers. A hybrid pneumatic-electric actuator was built and tested while driving a knee joint; this actuator is capable of precise positioning, as well as highly energetic thrusting. It will be shown that static and dynamic maneuvers are attainable with a tendon-coupled ankle, and that a tendon allows simpler dynamic control through the concept of impulse compensation, and through the use of passive stabilization from the kinematics resulting from the tendon. Second, it will be shown that the hybrid actuator is superior in some respects to current available technology, both by specification, and by experimental results of static and dynamic maneuvers achieved through its use. And third, using a general heuristic-based control algorithm developed for various sized bipedal machines, dynamic maneuvers are possible with a high leg-to-body moment of inertia ratio, which would show that the control strategy takes into account the dynamics of the legs during high speed locomotion.
  • Lewis A. Marshall.
    Purified DNA serves as a template for a wide array of analysis techniques, ranging from sequencing to PCR and hybridization assays. DNA analysis can be used for clinical diagnosis, for forensic investigation, and for a range of research purposes. These analysis techniques improve each year, but they are all constrained by the availability of purified DNA. DNA is typically derived from raw biological samples that contain a host of other molecular species, including proteins, lipids and metal ions. These species can inhibit analysis of the DNA, so purification of DNA from complex sample matrices is a necessary precursor to analysis. Typically, DNA purification is performed using either liquid-liquid extraction or solid-phase extraction, both of which require manual labor, involve toxic chemicals, and are difficult to miniaturize. Isotachophoresis (ITP) is an alternative method for DNA purification that does not rely on specialized surface chemistry or toxic chemical species. Instead, ITP uses electric fields to selectively pre-concentrate DNA from a raw sample, and simultaneously separate it from inhibiting species. ITP purification of DNA has been demonstrated from human serum, plasma, and whole blood, and the same technique has been used to purify RNA from bacteria in human blood and urine. Until recently, the parameters governing extraction efficiency, throughput, and separation quality in ITP purification were not well established. This thesis is focused on rational analysis for designing and optimizing ITP systems for rapid, high quality DNA purification.
  • 2008From: Springer
    Patrick Langdon, John Clarkson, Peter Robinson editors.
  • Kathryn Elizabeth Keenan.
    Human articular cartilage can degrade, losing functional quality and eventually exposing bone surfaces; when significantly advanced, this cartilage degradation can be diagnosed as osteoarthritis (OA). Currently, knee OA can be diagnosed only when the disease is advanced and the patient is suffering from pain. There is no cure for knee OA, nor are there prevent preventative therapies; current treatment strategies relieve the pain of OA or completely replace the knee joint. To evaluate potential therapies and treatments, we need a method that can identify and measure changes to cartilage prior to the onset of degradation. Magnetic resonance imaging (MRI) is a potentially powerful tool to non-invasively evaluate the progression of knee OA by mapping MR image parameters to molecular and material properties that are known to change with disease. The goal of this dissertation was to determine MR image parameters that can be used to evaluate the progression of OA. We examined the biphasic and viscoelastic models of cartilage to determine cartilage material properties from indentation creep tests. We compared initial elastic modulus and cartilage macromolecules to MRI parameters, specifically T2 and T1rho relaxation times and T1rho dispersion. We determined that a predictive model based on T1rho relaxation time maps, which accounts for T2 relaxation time and the effects of age, may estimate longitudinal trends in GAG content in the same person. In addition, a simple T1rho dispersion estimate has the potential for substantial clinical impact by measuring changes in cartilage initial elastic modulus and macromolecules non-invasively. This work is an important step toward developing clinical methods for evaluating cartilage functional condition, and in turn, to advance work towards preventing and treating knee OA.
  • Minsub Chung.
    Many cellular processes including cell-cell communications and regulated membrane transport are mediated by membrane proteins and depend upon the ability of lipid membranes to be a differentially permeable barrier. However, the roles and function of membrane proteins are often difficult to study due to the complexity of the native membranes and lack of reliable and flexible artificial model lipid membranes. Supported lipid bilayers (SLB) have been used as a model system to study biological membrane behavior and the structure and function of membrane proteins and receptors in a simpler context apart from the complex cellular environment. Although SLBs have the advantages of simple formation, easy handling and are well-suited for investigation by a suite of surface sensitive methods due to their planar geometry, the close proximity of the lower leaflet to the solid support often leads to unfavorable interactions with integral membrane proteins. This causes distortion of the protein conformation and possible loss of its reactivity and function. Moreover, this interaction with the substrate often traps proteins and reduces their mobility in the membranes. Recognizing this limitation, we have developed a new model membrane architecture in which the DNA-tethered lipid bilayer is either to fixed DNA on a surface or to laterally mobile DNA displayed on a supported bilayer. This separates the lipid membranes from surface interactions and provides a more favorable environment for integral membrane protein with large globular domains. With mobile DNA hybrid tethers, stable tethered bilayers were made with specific lipid composition, while those with fixed tethers are stable regardless of membrane composition. The mobile tethers between a tethered and a supported lipid bilayer offer a particularly interesting architecture for studying the dynamics of membrane-membrane interactions. By careful choice of composition, improved stability was obtained and we can investigate the lateral segregation of DNA hybrids when different lengths are present. Based on a theoretical model, the effects of population, length and affinity of DNA complexes are simulated and described. This model system captures some of the essential physics of synapse formation and is a step toward understanding lipid membrane behavior in a cell-to-cell junction. To demonstrate the excellent environment provided by DNA-tethered membranes for studying transmembrane proteins free from any surface interactions, the behavior of a transmembrane protein, the photosynthetic reaction center, reconstituted in the DNA-tethered membranes is investigated. Inspired by DNA-mediated membrane fusion studies of our group, we applied the DNA-machinery to achieve fusion of small (~ 100 nm) proteoliposomes for delivery of membrane proteins to either giant vesicles or DNA-tethered planar lipid membrane patches. The diffusion behavior of delivered proteins is measured and compared with those in supported bilayers. Also, the protein activity and orientation before and after fusion is analyzed. This will offer a feasible method to incorporate intact membrane proteins to already formed model membranes. In addition, the behavior of proteins during the fusion event will provide insight into the mechanism of DNA-mediated lipid membrane fusion. The geometry of our model membrane system directly mimics that of a neuronal synapse. We expect that this architecture will be readily transferable to other model membrane fusion systems, including systems using reconstituted SNARE proteins. Consequently, it will be of considerable interest to a wide range of researchers.
  • Tracy Curtis Holmes, II.
    Developing novel therapies for gram-negative bacterial infections and glioblastoma multiforme I. cloning and characterization of the guadinomine biosynthetic gene cluster II. developing a novel chemo-sensitizing agent to treat glioblastoma. This thesis explores the development of novel therapies for the treatment of two complicated problems: Gram-negative bacterial infections and glioblastoma multiforme, the most aggressive form of brain cancer. Part I of the thesis summarizes the current body of knowledge regarding guadinomines, their biosynthesis and implications for developing novel anti-infective agents. Part II of the thesis summarizes the development of the small molecule, ERW1227B, and its ability to sensitize glioblastoma cells to standard therapies. Part I. Guadinomines are a recently discovered family of anti-infective compounds produced by Streptomyces sp. K01-0509. They are the first microbial metabolites shown to inhibit the Type III Secretion System (TTSS) of Gram-negative bacteria. The TTSS is required for the virulence of many pathogenic Gram-negative bacteria including Escherichia coli, Salmonella spp., Yersinia spp., Chlamydia spp., Vibrio spp., and Pseudomonas spp. Inhibition of the TTSS can mitigate virulence which is important considering that Gram-negative bacteria infect millions each year, leading to considerable morbidity and mortality. The guadinomine (gdn) biosynthetic gene cluster has been sequenced, and encodes a chimeric multimodular polyketide synthase -- nonribosomal peptide synthetase spanning 26 open reading frames and 51.2 kb. It also encodes enzymes responsible for the biosynthesis of the unusual aminomalonyl-ACP extender unit and the signature carbamoylated cyclic guanidine. Its identity was established by genetic inactivation of the cluster, as well as heterologous expression and analysis of enzymes in the biosynthetic pathway. Identifying the guadinomine gene cluster provides critical insight into the biosynthesis of these biologically important compounds. Part II. Glioblastomas display variable phenotypes that include increased drug-resistance associated with enhanced migratory and anti-apoptotic characteristics. These shared characteristics contribute to failure of clinical treatment regimens. Identification of novel compounds that both promote cell death and impair cellular motility is a logical strategy to develop more effective clinical protocols. Previously, we described the ability of the small molecule, KCC009, a tissue transglutaminase inhibitor, to sensitize glioblastoma cells to chemotherapy. In the current study, we synthesized a series of related compounds that show variable ability to promote cell death and impair motility in glioblastomas, irrespective of their ability to inhibit TG2. Each compound has a 3-bromo-4,5-dihydroisoxazole component that presumably reacts with a nucleophilic cysteine thiol residue in one (or more) target protein(s) that have affinity for the small molecule. Our studies focused on the effects of the compound, ERW1227B. Treatment of glioblastoma cells with ERW1227B was associated with both down-regulation of the PI-3 kinase/Akt pathway, which enhanced cell death; as well as disruption of focal adhesions and intracellular actin fibers, which impaired cellular mobility. Bioassays as well as time-lapse photography of glioblastoma cells treated with ERW1227B showed cell death and rapid loss of cellular motility. Mice studies with in vivo glioblastoma models demonstrated the ability of ERW1227B to sensitize tumor cells to cell death after treatment with either chemotherapy or radiation. The above findings identify ERW1227B as a potential novel therapeutic agent in the treatment of glioblastomas.
  • Aaron Sheng-Chieh Wang.
    Trauma patients require rapid diagnosis and treatment of hemorrhage. In the hospital, experienced sonographers can reliably diagnose vascular injury using duplex ultrasound. In trauma settings, such as the battlefield, a portable ultrasound device with an automated algorithm to detect bleeding would be useful for medics. Thus, an increasing interest in computer-aided bleed detection led to efforts in quantifying sonographic signatures of abnormalities at the site of vascular injury. However, since trauma patients often present with large areas of injury, there is a need to develop and evaluate bleed detection strategies for ultrasound that more efficiently assess a large vascular tree. The goal of this Ph.D. research dissertation is to address this need. The studies primarily focused on the upper extremity vasculature, specifically the brachial bifurcation, because the leading cause of preventable deaths due to vascular trauma has been exsanguinations from extremity injuries. The overall approach was to characterize normal blood flow with a well-established power law model and identify flows that deviate from the model. The power law states that blood flow is proportional to the vessel diameter raised to a power index k, where k is defined by the bifurcation geometry. A bleed detection metric, called the "flow split deviation" (FSD), was defined to quantify the flow deviations from the power law. Validation of this approach was undertaken in four steps. The first involved demonstrating that the power law model appropriately describes the normal brachial bifurcation and flows in man. The utility of the bleed metric was then evaluated with 3D computational models of bleeds. Finally, the proposed detection algorithm was applied on the early proof of concept humans in arteriovenous fistulas (AVF) of dialysis patients and in in vivo rabbit bleed models. A study with normal human subjects was used to determine that the best-fit k for the brachial bifurcation was 2.75, which is in agreement with other vasculatures previously studied. A k=2.75 power law was then shown to adequately predict forearm blood flows for both resting and exercise physiological states. The correlation coefficient R between predicted and measured normal flows was 0.98. Computational models suggested that FSD was a good indicator of the severity of bleed downstream from the bifurcation. In the patient case study, the bleed metric easily distinguished between normal arms and those with newly placed wrist AVFs, which caused on average an order of magnitude increase in flow deviations. Introduction of different femoral bleed rates in rabbits demonstrated good sensitivity and specificity of the bleed metric when applied to moderate lower extremity bleeds. Bifurcation FSDs can serve as a quantitative signature of bleeding and, moreover, as a strategic way to survey large vascular trees by following abnormal branch points to the likely source of hemorrhage. This approach can complement other quantitative sonographic methods to create a comprehensive, automated, ultrasound-based algorithm for vascular trauma detection.
  • Eric Cocker.
    A central goal in neuroscience is to explain animal behavior in terms of causal cellular processes. It has been a longstanding challenge, however, to simultaneously track behavior and the cellular dynamics driving it. In this thesis, I discuss how a series of one- and two-photon fluorescence microscopes, based on gradient refractive index (GRIN) lenses, were developed to meet this challenge. The predominant difficulty in the design of these microscopes was how to take a traditional bench top microscope and shrink it to a size small enough for a mouse to easily carry on its head, a limit of 3 grams. We chose mice as our design target due to the wide availability of genetically modified mouse models for the study of cognitive functions, animal behaviors, and disorders of the nervous system. The earlier devices, relying on fiber optics to bring light to and from the animal, met with limited success but still provided useful insight in the development of the surgical techniques and analytical tools necessary for later successful experiments. In contrast, our latest system fully integrates the entire light pathway onto the head of mouse, eliminating many of the remaining roadblocks to truly freely-moving imaging. This device has enabled novel observations of both microcirculatory and neuronal calcium dynamics in the cerebellum of freely-moving mice at frame rates up to 100 Hz. As the genetic toolbox for mice continues to mature, these miniaturized microscopes will facilitate a wide set of future studies of how cellular function in the brain varies across different behavioral and physiological states.
  • 2011From: Atypon
    Xiaolu Zhu, Rangaraj M. Rangayyan, Anna L. Ells.
    Fundus images of the retina are color images of the eye taken by specially designed digital cameras. Ophthalmologists rely on fundus images to diagnose various diseases that affect the eye, such as diabetic retinopathy and retinopathy of prematurity. A crucial preliminary step in the analysis of retinal images is the identification and localization of important anatomical structures, such as the optic nerve head (ONH), the macula, and the major vascular arcades. Identification of the ONH is an important initial step in the detection and analysis of the anatomical structures and pathological features in the retina. Different types of retinal pathology may be detected and analyzed via the application of appropriately designed techniques of digital image processing and pattern recognition. Computer-aided analysis of retinal images has the potential to facilitate quantitative and objective analysis of retinal lesions and abnormalities. Accurate identification and localization of retinal features and lesions could contribute to improved diagnosis, treatment, and management of retinopathy.
  • Limor Freifeld.
    Visual inputs are high-dimensional, dynamic, and may consist of significant levels of noise. Nevertheless, visual processing systems in many animals are capable of efficiently extracting information out of these signals to guide behavior. Flies, in particular, use visual information to guide behavior in challenging conditions such as during rapid flight maneuvers. In this dissertation we examine how early visual processing cells in the visual system of the Fruit Fly, Drosophila, achieve this feat. In particular, we focus on cells that provide inputs to motion detecting circuits and assess how these cells balance the goal of facilitating computational specializations with the goal of efficiently capturing all visual information. In these studies, we used two-photon calcium imaging in vivo to monitor the responses of specific cells in the fly visual system to visual stimuli. Using this system, we found that two first order interneurons providing inputs to pathways specialized for the detection of moving bright and dark edges nevertheless similarly encode information about both brightening and darkening. However, an in depth study of the functional properties of one of these interneurons revealed that it responds differently to bright and dark moving objects of different sizes in a manner that could facilitate the downstream specialization. Furthermore, via genetic and pharmacological manipulations it was found that GABAergic circuits providing lateral and feedback inputs to this cell enhance its responses to dark stimuli and thus enable it to relay critical information for the downstream pathway. These circuits were found to give rise to a center-surround antagonistic, anisotropic and spatiotemporally coupled RF structure in this cell. Interestingly, our studies uncovered deep similarities between the function of early visual processing cells in the fly and in vertebrate retinas. This suggests that different systems have converged on a similar set of solutions for addressing the challenge of efficiently using the resources available to the nervous system to process visual signals.
  • Katherine Muterspaugh Steele.
    This dissertation presents the first three-dimensional musculoskeletal simulations of individuals with cerebral palsy and has contributed to our understanding of how muscle contributions, joint loads, and the effects of muscle weakness change in individuals with cerebral palsy and crouch gait. The simulations created for these analyses have been made freely-available for researchers and clinicians to download, use, and evaluate at This work has provided insight into the underlying dynamics of crouch gait and created pathways to improve treatment. The first objective of this dissertation was to examine how individual muscles contribute to motion during crouch gait. We evaluated how muscles contribute to joint and mass center accelerations to support and propel the body during crouch gait and how these contributions change with crouch severity. The results of these analyses indicated that crouch gait uses similar muscles to support and propel the body as unimpaired gait; however, larger and more sustained muscle activity is required during crouch gait, which contributes to the inefficiencies of this gait pattern. The second objective of this dissertation was to examine how the compressive tibiofemoral force changes in individuals with cerebral palsy and crouch gait. Knee pain is common among individuals with crouch gait and the results of this study demonstrated that tibiofemoral load increases quadratically with crouch severity. Individuals who walk in a severe crouch gait experience three-times the tibiofemoral load than during unimpaired gait. The elevated tibiofemoral forces during crouch gait could contribute to cartilage degeneration and knee pain. The final objective of this dissertation was to examine how muscle weakness may contribute to crouch gait. We used musculoskeletal simulations to determine how much muscle groups can be weakened and still reproduce mild and moderate crouch gait. The results of this analysis demonstrated that crouch gait requires greater quadriceps strength but less hip abductor and ankle plantarflexor strength than unimpaired gait; suggesting that these latter muscles may be better targets for strength training programs. We also performed a meta-analysis of individuals with crouch gait who had participated in strength training programs. This analysis demonstrated that outcomes after strength training are inconsistent, even among individuals with cerebral palsy and crouch gait. Hamstring spasticity was associated with poor outcomes after strength training and may be a contraindication for strength training. The long term goal of the work presented in this dissertation is to improve quality of life for individuals with cerebral palsy. The freedom to walk, explore, and interact with the world is a skill that many of us take for granted every day. Through the combination of musculoskeletal modeling and simulation, experimental studies, and clinical outcomes we can help individuals with gait pathologies achieve this freedom throughout their life.
  • Michael Zabala.
    Rupture of the anterior cruciate ligament (ACL) is one of the most common injuries to the knee. Unfortunately, individuals who experience this injury are likely to develop osteoarthritis of the knee much earlier than would be expected due to the normal ageing process, and this remains true even after surgical reconstruction of the ligament. Research has suggested that a major contributing factor to the development of premature osteoarthritis is altered knee mechanics which change the loading conditions of the cartilage in the joint. Furthermore, it has been shown that altered knee mechanics are present following rupture of the ACL and persist after reconstruction surgery. Despite initial reports, there still remains a need for a comprehensive understanding of both altered knee mechanics in both ACL deficient and ACL reconstructed knees as well as changes in cartilage morphology following ACL injury. Therefore, the goal of this dissertation is to address the question of the relationship between certain changes in knee mechanics and cartilage morphology as they relate to the development of osteoarthritis following both ACL injury and reconstruction. The first study presented involves an analysis of the knee mechanics in individuals with unilateral ACL deficiencies. This group was important in that they were free of knee pain and had no sign of osteoarthritis on MRI over a time frame that ranged up to three decades from injury. This provided a unique opportunity to explore the potential for a protective functional adaption. The results of this study suggest that alteration in knee mechanics may act as a protective mechanism against osteoarthritis development since when subjects were separated into "Short Term" and "Long Term", based upon the time from injury, only those in the "Long Term" group demonstrated a relationship between the external knee flexion moment, which is representative of the interaction between quadriceps and hamstrings muscle to control rotation and translation during walking. This is indicative of an adaptive control mechanism present in some subjects who were able to last many years after the injury without reconstruction surgery. These results suggest the potential for new methods for rehabilitation following ACL injury. The second study presented involves an analysis of the knee mechanics of individuals with unilateral ACL reconstructions during gait, stair ascent, and stair descent at two years from surgery. The results demonstrate a reduction in the external joint moments of ACL reconstructed knees and an increase in the joint moments of uninjured contralateral knees during each activity compared to healthy controls. This suggests two things: 1.) compensation for residual muscle weakness in the affected limb is needed by the contralateral knee during ambulation and 2.) a decrease in daily joint loading in ACL reconstructed knees and an increase in joint loading in contralateral knees. Decreased loading of the ACL reconstructed knee may seem counterintuitive to what was expected in patients who will likely develop premature osteoarthritis in this knee. However, this finding is consistent with the suggestion that changes in joint kinematics and even decreased joint loading following the injury may contribute to the initial cartilage breakdown. Note: Taken together the results of study 1 and 2 suggest that the interaction between muscle function and kinematics should be further considered in the development of knee OA in this population. The third and final study involves articular cartilage morphology analysis of individuals with unilateral ACL reconstructions at two and four years from surgery. The results illustrate differences between cartilage thickness of ACL reconstructed and healthy contralateral knees at both times of testing. The findings show significantly thinner cartilage in the lateral tibial compartment of ACL reconstructed knees at two years from surgery. These differences became more pronounced at four years from surgery and include the addition of a significantly thicker medial region of the tibia of ACL reconstructed knees compared to healthy contralateral knees. The results indicate that patterns of cartilage thickness change are detectable as early two years following ACL reconstruction, and these patterns become more pronounced at 4 years which suggests cartilage begins a degenerative pathway substantially in advance of clinically detectable OA. This finding is important since it provides a basis for assessing early interventions to reduce the risk of knee OA following ACL injury. This dissertation helps to further the understanding of altered knee mechanics following both ACL rupture and reconstruction. In addition, a possible pattern of OA initiation has been reported. Each of these studies will benefit future studies with the ultimate goal of a complete understanding of OA initiation and development in ACL ruptured and reconstructed knees.
  • Thais Russomano, Gustavo Dalmarco, and Felipe Prehn Falcão.
  • Edwina S. Lai.
    The development of atherosclerosis, a chronic inflammatory disease of the arteries, can usually be attributed to specific regions of the blood vessel. In the straight segments of an artery, endothelial cells (ECs) align with the unidirectional blood flow which commonly occurs in these simple geometries. The elongated and aligned ECs are generally found to have a healthy, athero-resistant phenotype. In contrast, branches or curved vessel geometries have regions of disturbed flow, characterized by low shear stress and high shear stress gradients. In these regions of complicated flow patterns, ECs are non-aligned and have a cobblestone cellular morphology. The non-aligned ECs elicit biological properties that promote atherosclerosis, as the location of atherosclerotic fatty plaque is often found at these bends, branches, or bifurcations. Therefore, this correlation highly suggests that the morphology and biological function are inextricably linked in ECs. The ability to regulate both EC morphology and motility, with the aim to influence EC biology, might be highly beneficial in the prevention or treatment of vascular disease. In this dissertation, anisotropic matrices of collagen nanofibrils were fabricated with a simple flow processing technique and used to investigate fundamental cell-matrix interactions with ECs. The aligned fibrils were able to regulate both the morphology and biology of ECs, thereby suggesting the nanofibrillar collagen can be a useful tool to maintain vascular homeostasis. The ECs elongated and organized their actin cytoskeleton along the direction of the aligned collagen fibrils, as demonstrated by organized actin, microtubule networks, and focal adhesions. The nanofibrillar collagen also promoted increased cellular migration along the direction of the nanofibrils. The quantification of monocyte adhesion and expression level of adhesion molecules, known testing indicators of atherosclerosis development, suggested the aligned nanofibrils also promoted an athero-resistant phenotype in the ECs. ECs are subject to biophysical cues in vivo, either in the form of surface topography (provided by the basement membrane of the ECM) or the hemodynamic effects of blood flow. The combination of these cues regulate the organization and immunogenicity of ECs and is representative of the in vivo environment. Therefore, we also investigated the endothelial behavior when both types of cues (topography and flow) were simultaneously present. At physiological levels of high shear stress (14-17 dynes/cm2), the matrix-aligned ECs were able to resist reorientation despite shear flow perpendicular to the matrix direction. The anisotropic collagen matrix could preserve the alignment and elongation of ECs as well as promote an athero-resistant phenotype after exposure to antagonistic perpendicular flow. The ability of the anisotropic nanofibrillar collagen to regulate cell morphology and especially EC immunogenicity highlights its potential in the treatment of vascular diseases. Therefore, an aligned conduit of collagen nanofibrils was fabricated to address the need for a small-diameter vascular graft capable of regulating cellular function. The vascular graft was designed to have a mechanical integrity comparable to that of native vessels and was able to regulate EC attachment, morphology, and phenotype. In addition, the aligned collagen grafts could support an anti-thrombogenic surface modification, providing short-term patency in the carotid artery model of Sprague-Dawley rats.
  • Jonathan Joi-Mun Wong.
    The heart is an essential heterogeneous organ that depends on strong coupling between electrical, chemical, and mechanical dynamics to properly function as a pump that supplies blood to the rest of the body. Cardiac arrhythmias are common disorders characterized by irregular beating of the heart that lead to serious clinical conditions. It is estimated that approximately 2.2 million adults in the United States are affected by atrial fibrillation, a prevalent arrhythmia. Unfortunately, a clinician often does not have enough information to diagnose a patient's heart condition to determine the optimal treatment procedure. This is an area that computational mechanics can address. While development of mechanical and electrophysiological models of cardiac tissue primarily started in the 1950s, fully-coupled models have only more recently been developed due to factors regarding computational cost, difficulty in quantifying material properties, and difficulty in integrating complex models in a cohesive and efficient manner. Therefore, in order for simulation tools to have impact in the clinical or experimental setting, these tools must be efficient, fast, robust, and accessible. The focus of this thesis is to develop methods of addressing the aforementioned issues and then illustrate how efficient electromechanical finite element models can be developed for the heart such that their use in the clinical and experimental setting can be realized in several examples. In this thesis, a global-local variable splitting formulation borrowed from the field of plasticity is used to address the issues of complex model integration, and to maintain numerical stability at low costs. Through careful examination of classical phenomenological models and detailed biophysical ionic models of the electrophysiology of the heart, almost all models can be reformulated into this global-local splitting framework. The numerical properties of cost-expensive ionic models are briefly analyzed within the context of this framework. Use of implicit-time stepping in tandem with a simple iteration and error tolerance based adaptive time-stepping algorithm allows for reduction of computation time from hours to minutes. Flexibility and modularity of the framework are illustrated through the development of electrical, electro-chemical, electro-chemical-mechanical, and opto-electro-mechanical models of cardiac tissue. The heart is modeled efficiently using custom finite element ventricular cell models for physiological electrical simulations and large deformation excitation-contraction dry-pumping simulations of the heart. The results accurately model the physiological condition of the heart. The flexibility and multiscale nature of the framework is also leveraged in developing novel optical-induced cardiac cell excitation models of new genetically engineered Channelrhodpsin-2 (ChR2) cardiac myocytes. An ionic model was developed for these particular bio-engineered stem cells, calibrated with experimental data from collaborators, and was able to predict the electrical excitation behavior of the cells to a reasonable degree of accuracy. This model was then combined with ionic pacemaker cell models and also with ventricular cell models into respective finite elements to simulate experiments and predict future therapies using ChR2 genetically modified cardiac tissue. The thesis also addresses difficulties relating to identification and characterization of material parameter identification in inhomogeneous cardiac tissue. Metrics for determining smoothness in electrical conduction in tissue cultures were validated with stochastic finite element models of microelectrode array cell conduction experiments. The results indicate that these metrics are useful in characterizing different conduction patterns based on two metrics borrowed from texture analysis. Difficulties in obtaining structural fiber data from clinical images were addressed by developing an algorithmic method for designating approximate physiologically accurate fiber distributions for the heart using only geometrical information obtained from MRI scans of the surfaces of the heart. Poisson interpolation is used and results in a smooth continuous rotating fiber description that matches experimentally obtained fiber directions from MRI scans. The main benefits of this algorithm are its simplicity of implementation, physiologically accuracy, and generality in interpolating fiber distributions. Lastly, the thesis demonstrates possible benefits of GPU computing in order to achieve near-real-time electrical simulations of arrhythmias in the heart. The assembly and solver routines from the finite element code, FEAP from Berkeley, were ported to the GPU using CUDA. Even with a minimally optimized proof-of-concept, the GPU-only finite element code achieves performance comparable to twelve cores using only one GPU. To increase the overall efficiency of the method, current sparse matrix vector multiplication GPU algorithms are analyzed, and possible alternative algorithms are developed specifically with unstructured finite element meshes in mind. Altogether, the different methods developed in this thesis have been shown to be effective in addressing issues related to efficiency, numerical stability, modularity, and flexibility in real computational applications of the heart. Special consideration was taken in designing the different methods to be compatible with one another, such that a majority of the methods could be integrated and the benefits of each method could be leveraged with each other to gain maximum efficiency. While these developed methods can still be improved, the thesis work as a whole serves to demonstrate and highlight future uses for computational models within experimental and clinical settings.
  • Hesaam Esfandyarpour.
    The Human Genome Project was accomplished by a reduction in the cost of DNA sequencing by three orders of magnitude. Further cost reductions are required for sequencing to become a standard tool in clinical medicine and to enable personalized medicine via individual genome sequencing. The current cost varies between $50k to $100k over a period of months; depend on the technology, accuracy and read-length. It is desired to reduce the cost to $1000 per genome to enable profiling of individuals genome. To achieve this goal, a highly integrated platform with simplified chemistry is required. In this dissertation, we introduce a novel method for DNA sequencing based on electrical detection of polymerization reaction, called "Thermo/pH sequencing". Our proposed method is based on the direct measurement of the heat release or the pH modulation (change of H+ ion concentration in the solution) during DNA extension. For high throughput DNA sequencing, DNA strands are immobilized to small micron-size beads in a microfluidic platform. The DNA-beads are in a reaction mixture in contact with an array of sensitive micro-machined heat or pH sensors, which detect the electrical signature from incorporation of a complementary base (dNTP) in the presence of appropriate reagents (DNA polymerase, and polymerase reaction buffer). This results to a label-free, long-read and fast chemistry; 10x reduction in reagent cost with 10x increase in throughput can potentially yield to significant improvement in the cost of genome sequencing to less than $1000. In addition, substituting optical detection set-up with microelectronic sensor reduces the capital cost of sequencing instruments from $500k to less than $50k. We demonstrate the proof of concept for this technology at large scale. Then we describe the development of an appropriate microfluidic platform and two micromachined electrical biosensors that employ electrical detection for heat or pH detection. Both versatile platforms can be multiplexed and have the potential of providing rapid and inexpensive measurements without any compromise in the sensitivity, making them good potential candidates for use in the clinical setting. We report a chip-based integrated differential microfluidic nanocalimeters with on-chip injection and multiplexing unit, capable of characterizing the heat of reaction with unprecedented 2-nW resolution in 1 Hz bandwidth for nanoliter scale samples. We successfully demonstrate DNA Thermosequencing with sequential injection of different nucleotides into the integrated microfluidic calorimeter device. In addition, the device can serve as a powerful tool to characterize a variety of the biomedical processes, such as metabolic activities of microorganisms, living cells and catalyzed reactions. We also present a microfabricated device in microfluidics for pH sequencing, called nanoneedle biosensor. The key element for this device is a 10nm wide gap on the end of the needle of total diameter about 100nm. Any change in the population of molecules in this gap results in a change of impedance across the gap; single molecule detection should be possible. In addition, DNA-beads can be allocated iv near the sensors to measure the pH change during DNA extension. The design, fabrication, testing, optimization and a modified structure of the device for higher signal to noise ratio are presented. Toward an integrated sequencer platform, automation and reduced labor cost, higher throughput, accuracy and efficiency for genomics and proteomics analysis; further integration and optimization of the presented systems are required. We envision the integration of our CMOS-compatible devices with a CMOS integrated circuitry into a high throughput gene sequencer or proteomics system. The proteomics system enables multiplex analysis using an array of micro-channels for probing clinically relevant samples such as the human serum for various protein and nucleic acid biomarkers for cancer detection, and also the detection of pathogenic bacteria in solution.
  • John G. Webster, editor in chief.
  • Monica Elise Ortiz.
    Evolution has selected for organisms that benefit from genetically encoded cell-cell communication. We observe cell-cell communication throughout every scale in nature, from simple single-celled bacteria to complex multicellular mammals. Engineers have begun to repurpose elements of natural communication systems to coordinate their own population-level behaviors, including oscillations and programmed pattern formation. Existing engineered systems, however, rely on small, system-specific biomolecules to send messages among cells. However, such molecules are capable of sending only a single message, typically "regulate transcription.'' Thus, the information transmission capacity of such biological communication systems is fundamentally limited. Through this thesis, I demonstrated the decoupling of messages from a common communication channel via the autonomous transmission of numerous arbitrary genetic messages. To do so, I engineered a cell-cell communication platform using bacteriophage M13 gene products to autonomously package and deliver heterologous DNA messages of varying lengths and encoded functions. Further, I increased the range of engineered DNA messaging across semisolid media by coupling message transmission or receipt to active cellular chemotaxis. Through this coupling, I demonstrated that our system is adaptable to different contexts by creating simple patterns. Finally, using recombinase-mediated logic gates developed within the Endy laboratory, I demonstrated the ability to program bacteria by transmitting logic gates to surrounding cells. Overall, this work significantly enhances the suite of cell-cell communication tools available to engineers. I have shown that a variety of DNA messages can be transmitted among cells and have moved the field of synthetic biology closer to designing synthetic ecologies with more complex communication schemes and varied behaviors.
  • Sarah Jean Moore.
    Proteins and peptides are an incredibly versatile class of biological molecules, with a vast array of naturally occurring functions. In cancer, the natural roles of proteins become incorrectly regulated, and the presence of cancer-related proteins on tumor cells can be detected and targeted for diagnosis and treatment. This thesis decribes novel engineered peptides for molecular recognition of cell surface receptors expressed in cancers, and application of these engineered peptides as diagnostic agents to identify solid tumors in mouse models. For this work. three different cystine-knot peptides were used for development and engineering: Agatoxin (AgTx), Agouti-related protein (AgRP), and Ecballium elaterium trypsin inhibitor-II (EETI). In addition, two protein receptors were employed as model tumor targets relevant for molecular imaging of cancer: carbonic anhydrase IX (CA IX) and tumor associated integrin receptors. New methods were developed towards engineering AgTx and AgRP to bind CA IX, and work to produce these peptides for further study and their limitations are described. In a parallel line of research, to further understand the promise of using knottin peptides in cancer imaging, the influence of amino acid loops on tissue biodistribution was examined using engineered AgTx, AgRP, and EETI peptides that bind tumor target integrins in mouse xenograft models. Finally, an engineered EETI knottin peptide that binds tumor-associated integrins was shown to specifically target and illuminate brain tumors in mouse models of medulloblastoma. Importantly, the protein engineering methods and molecular imaging applications described here have promise for influencing the clinical outcome of cancer patients through image-guided surgical resection, disease staging and management, and monitoring the effectiveness of therapeutic treatments.
  • 2015From: Springer
    Luiz E. Bertassoni, Paulo G. Coelho, editors.
    This book offers a comprehensive overview of current challenges and strategies to regenerate load-bearing and calcified human tissues, including bone, cartilage,tendon, ligaments and dental structures (dentin, enamel, cementum and periodontal ligament). Tissue engineering has long held great promises as an improved treatment option for conditions affecting mineralized and load-bearing structures in the body. Although significant progress has been achieved in recent years, a number of challenges still exist. Scaffold vascularization, new biofabrication methods (3D printing, lithography, microfabrication), peptide conjugation methods, interface engineering, scaffold mechanical properties, iPS cells, organs-on-a-chip, are some of the topics discussed in this book. More specially, in the first section readers will find an overview of emerging biofabrication methods. In section 2, applied strategies for regeneration of (2.1) bone, cartilage and ligament, as well as (2.2) dentin, cementum, enamel and periodontal ligament are discussed across 14 chapters. While other volumes have addressed the regeneration of individual tissues, or exclusively focused on different regenerative strategies, the focus of this work is to bring together researchers integrating backgrounds in materials sciences, engineering, biology, mechanics, fluidics, etc, to address specific challenges common to regeneration of several load-bearing and calcified tissues. Therefore, this book provides a unique platform to stimulate progress in the regeneration of functional tissue substitutes. We envision that this book will represent a valuable reference source for university and college faculties, post-doctoral research fellows, senior graduate students, and researchers from R&D laboratories in their endeavors to fabricate biomimetic load bearing tissues.
    Also available: Print – 2015
  • Sheng Ding.
    Recombinant proteins have been used widely in both basic research and biomedical applications including protein therapeutics and biomaterials. Many efforts have been devoted to the investigation of novel synthetic strategies for producing recombinant proteins for various applications, which is the focus of this dissertation. In the first section, a biosynthetic strategy was developed to produce collagenous proteins with post-translational modifications in E. coli. Collagen is the most abundant protein in human, and plays a dominant role in maintaining the biological and structural integrity. Recombinant expression of collagens and fragments of collagens is often difficult as their stability requires appropriate proline hydroxylation. Prolyl 4-hydroxylases (P4H) are ascorbate-dependent oxygenases that play key roles in collagen folding by catalyzing the post-translational hydroxylation of specific proline residues on target proteins to form (2S, 4R)-4-hydroxyproline. Thus far, the study of these post-translational modifications has been limited by the lack of a prokaryotic recombinant expression system for producing hydroxylated proteins. Unlike eukaryotic cells such as yeast and insect cells, bacterial cytoplasm cannot activate P4H, which requires an ascorbate co-factor that bacteria do not produce. By introducing a biosynthetic shunt to produce ascorbate-like molecules in E. coli cells that heterologously express human P4H, we have created a strain of E. coli that produces collagenous proteins with (2S, 4R)-4-hydroxyproline. Different levels of proline hydroxylation can be obtained by tuning culture conditions. We have verified that hydroxylation of collagenous materials produced in the new system leads to an increase in thermostability. Using this new system, we have observed hydroxylation patterns indicative of a processive catalytic mode for P4H that is active even in the absence of ascorbate. Our results provide insights into P4H enzymology, and create a foundation for better understanding how post-translational hydroxylation affects proteins. Further, we applied the novel E. coli expression system to produce a collagenous protein, adiponectin, which has many beneficial effects on obesity-related metabolic and cardiovascular disorders, and reverses insulin insensitivity. By introducing key post-translational modification enzymes to E. coli, we have endowed the expression system with capabilities of making necessary modifications on adiponectin for its correct assembly, and thus obtained biomimetic adiponectins. High-molecular weight (HMW) multimers of adiponectin have been obtained, and their biological activities of suppressing endothelial cell apoptosis have been confirmed with in vitro cell assays. In section 2, modular protein polymers have been created through genetic engineering and enzymatically crosslinked into hydrogels with tunable properties. The many challenges currently faced in regenerative medicine research require the development of new, modular biomaterial systems that can serve as scaffolds for cellular maintenance, expansion and growth, and which can be tuned by the user to mimic any necessary aspects of natural ECM to an optimal degree. Toward this goal, we have created a family of block co-polypeptides comprising amino acid sequence elements that allow mild enzymatic crosslinking into gels. These new families of protein polymers were designed to be linear, random coil, and contain either lysine or glutamine, which have the recognition substrates for transglutaminase (TG) crosslinking, evenly spaced along the protein backbone. Crosslinking occurred within two minutes upon the addition of TG under physiological conditions, as determined by particle tracking microrheology. The material properties of the gel can be tuned with the hydrogel composition to mimic cellular microenvironment of different tissues. Furthermore, in order to introduce biofunctionalities into the hydrogels, a versatile expression vector has been engineered that allows the insertion of bioactive protein domains into these block co-polypeptide. For example, a cell adhesion signal based on the RGD sequence from human fibronectin was incorporated. The RGD-containing hydrogel was successful in enhancing cell adhesion, and were also proven to be compatible with the culture of mesenchymal stem cells. The specific nature of these protein polymer precursors of the modular hydrogel composition allows tailoring of mechanical and biochemical properties, rendering these gels valuable for various tissue engineering applications.
  • 2007From: Springer
    Felix Bronner, Mary C. Farach-Carson and Antonios G. Mikos (eds.).
  • 2014From: Wiley
    edited by Rebecca A. Bader, David A. Putnam.
    Polymers have played a critical role in the rational design and application of drug delivery systems that increase the efficacy and reduce the toxicity of new and conventional therapeutics. Beginning with an introduction to the fundamentals of drug delivery, Engineering Polymer Systems for Improved Drug Delivery explores traditional drug delivery techniques as well as emerging advanced drug delivery techniques. By reviewing many types of polymeric drug delivery systems, and including key points, worked examples and homework problems, this book will serve as a guide to for specialists and non-
  • 2010From: Springer Protocols
    edited by Kursad Turksen.
    Isolation of adult mouse stem keratinocytes using magnetic cell sorting (MACS) / Corina Lorz [and others] -- Functional investigations of keratinocyte stem cells and progenitors at a single-cell level using multiparallel clonal microcultures / Nicolas O. Furtunel [and others] -- Growth and stratification of epithelial cells in minimal culture conditions / Federica Riva [and others] -- Matched cultures of keratinocytes and fibroblasts derived from normal and NER-deficient mouse models / Alex Pines and Claude Backendorf -- Establishment of spontaneously immortalized keratinocyte lines from wild-type and mutant mice / Julia Reichelt and Ingo Haase -- Study of epidermal differentiation in human kertinocytes cultured in autocrine conditions / Frédéric Minner, Franc̦oise Herphelin, and Yves Poumay -- Directed differentiation of human embryonic stem cells to epidermal progenitors / Christian M. Metallo [and others] -- Expression and analysis of exogenous proteins in epidermal cells / Lina Dagnino, Ernest Ho, and Wing Y. Change -- Using siRNA knockdown in HaCaT cells to study transcriptional control of epidermal proliferation potential / Julie Wells and Xing Dai -- RNA interference in keratinocytes and an organotypic model of human epidermis / Cory L. Simpson, Shin-ichiro Kojima, and Spiro Getsios -- Scanning for transcription factor binding by a variant EMSA / Igor Gurevich, Carmen Zhang, and Brian J. Aneskievich -- Chromatin immunoprecipitation for identifying transcription factor targets in kertinocytes / Kori Ortt and Satrajit Sinha -- Gene expression profiling of mouse epidermal keratinocytes / Ramón García-Escudero and Jesús M. Paramio -- Analysis of tissue-specific gene expression using laser capture microdissection / Martin Ruetze [and others] --Comprehensive transcriptional profiling of human epidermis, reconstituted epidermal equivalents, and cultured keratinocytes using DNA microarray chips / Din-Dar Lee [and others] -- Molecular profiling of the epidermis : a proteomics approach / Jianjun Shen and Susan M. Fischer -- Detection of gene expression in embryonic tissues and stratified epidermis by in situ hybridization / Maria I. Morasso -- Embryonic mammary anlagen analysis using immunolabelling of whole mounts / Heena Panchal, Olivia Wansbury, and Beatrice A. Howard -- Whole-mount assays for gene induction and barrier formation in the developing epidermis / Carolyn Byrne [and others] -- Tetracycline-regulated gene expession in transgenic mouse epidermis / Rose-Anne Romano and Satrajit Sinha -- A versatile murine 3D organotypic model to evaluate aspects of wound healing and epidermal organization / Eve Kandyba, Malcolm Hodgins, and Patricia Martin -- Optical and biochemical dissection of connexin and disease-linked connexin mutants in 3D organotypic epidermis / Stéphanie Langlois, Jared M. Churko, and Dale W. Laird -- Cytokine release in tissue-engineered epidermal equivalents after prolonged mechanical loading / Lisette H. Cornelissen [and others] -- Three-dimensional human tissue models of wounded skin / Christophe Egles, Jonathan A. Garlick, and Yulia Shamis -- In vivo transplantation of genetically modified mouse embryonic epidermis / Ana Belén Martínez-Cruz [and others] -- A transplant model for human epidermal skin regeneration / Sophie Paquet-Fifield [and others] -- Identification of epithelial stem cells in vivo and in vitro using keratin 19 and brdU / Danielle Larouche [and others] -- Isolation and culture of hair follicle pluripotent stem (hfPS) cells and their use for nerve and spinal cord regeneration / Yasuyuki Amoh and Robert M. Hoffman -- Limiting dilution analysis of murine epidermal stem cells using an in vivo regeneration assay / Lauren R. Strachan and Ruby Ghadially.
  • 2014From: Springer Protocols
    edited by Kursad Turksen, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
    Differentiation of Human Induced Pluripotent Stem Cells into a Keratinocyte Lineage / Igor Kogut, Dennis R. Roop, and Ganna Bilousova -- Differentiation of Epidermal Keratinocytes from Human Embryonic Stem Cells / Fahad K. Kidwai, Tong Cao, and Kai Lu -- Protocol for Serial Cultivation of Epithelial Cells Without Enzymes or Chemical Compounds / Dongxia Ye and Antonio Peramo -- Growth and Differentiation of HaCaT Keratinocytes / Van G. Wilson -- Transgene Delivery to Cultured Keratinocytes Via Replication-Deficient Adenovirus Vectors / Vincent P. Ramirez and Brian J. Aneskievich -- Analyzing the Global Chromatin Structure of Keratinocytes by MNase-Seq / Jason M. Rizzo and Satrajit Sinha -- Analysis and Meta-Analysis of Transcriptional Profiling in Human Epidermis / Claudia Mimoso, Ding-Dar Lee, Jiri Zavadil, Marjana Tomic-Canic, and Miroslav Blumenberg -- Compound Screening and Transcriptional Profiling in Human Primary Keratinocytes: A Brief Guideline / Raphaela Rid, Harald Hundsberger, and Kamil Önder -- Preparation of Primary Cultures of Mouse Epidermal Keratinocytes and the Measurement of Phospholipase D Activity / Lakiea J. Bailey, Vivek Choudhary, Purnima Merai, and Wendy B. Bollag -- Lipid Rafts and Detergent-Resistant Membranes in Epithelial Keratinocytes / Kathleen P. McGuinn and Mỹ G. Mahoney -- MMP-2, 9 and TIMP-1, 2 Assays in Keratinocyte Cultures / Takashi Kobayashi -- Reactive Oxygen Species (ROS) Protection Via Cysteine Oxidation in the Epidermal Cornified Cell Envelope / Wilbert P. Vermeij and Claude Backendorf -- Modified Methods for Growing 3-D Skin Equivalents: An Update / Rebecca Lamb and Carrie A. Ambler -- A Novel Three-Dimensional Cell Culture Method to Analyze Epidermal Cell Differentiation In Vitro / Yoji Okugawa and Yohei Hirai -- Reconstruction of Normal and Pathological Human Epidermis on Polycarbonate Filter / Evelyne De Vuyst, Céline Charlier, Séverine Giltaire, Valérie De Glas, Catherine Lambert de Rouvroit, and Yves Poumay -- Methods for the Preparation of an Autologous Serum-Free Cultured Epidermis and for Autografting Applications / John J. Wille, Jeremy J. Burdge, and Jong Y. Park -- Human Keratinocyte Cultures in the Investigation of Early Steps of Human Papillomavirus Infection / Laura M. Griffin, Louis Cicchini, Tao Xu, and Dohun Pyeon -- Preparation and Delivery of 4-Hydroxy-Tamoxifen for Clonal and Polyclonal Labeling of Cells of the Surface Ectoderm, Skin, and Hair Follicle / Christine Chevalier, Jean-François Nicolas, and Anne-Cécile Petit -- Microdissection and Visualization of Individual Hair Follicles for Lineage Tracing Studies / Inês Sequeira, Emilie Legué, Suzanne Capgras, and Jean-François Nicolas -- Isolation and Characterization of a Stem Cell Side-Population from Mouse Hair Follicles / Paula L. Miliani de Marval, Sun Hye Kim, and Marcelo L. Rodriguez Puebla -- Multi-Scale Mathematical Modeling and Simulation of Cellular Dynamical Process / Shinji Nakaoka -- Erratum.
  • 2008From: CRCnetBASE
    editors, Alexiy Ya. Chebykin, Gregory Z. Bedny, and Waldemar Karwowski.
    Ecological ergonomics / Marvin J. Dainoff -- Integrating cognitive and digital human models for virtual product design / Daniel W. Carruth and Vincent G. Duffy -- Time study during vocational training / Gregory Z. Bedny and Waldemar Karwowski -- The laws of ergonomics applied to design and testing of workstations / V.F. Venda, V.K. Kalin, and A.Y. Trofimov -- Day-to-day monitoring of an operator's functional state and fitness-for-work : a psychophysiological and engineering approach / Oleksandr Burov -- Identification of mental modules ; Identification of neural modules / Saul Sternberg -- The new interface of brain, mind, and machine : will the emergent whole be greater than the sum of the parts? / Chris Berka ... [et al.] -- The interaction of sleep and memory / Jeffrey M. Ellenbogen -- Attention, selection for action, error processing, and safety / Magdalena Fafrowicz and Tadeusz Marek -- Activity theory : comparative analysis of Eastern and Western approaches / Waldemar Karwowski, Gregory Z. Bedney, and Olexiy Y. Chebykin -- Discourse in activity / Harry Daniels -- Movements of the cane prior to locomotion judgments : the informer fallacy and the training fallacy versus the role of exploration / Gregory Burton and Jennifer Cyr -- Emotional intelligence : a novel approach to operationalizing the construct / E.L. Nosenko -- Emotional regulation of the learning process / Olexiy Y. Chebykin and S.D. Maksymenko -- Emotional resources of the professional trainer / G.V. Lozhkin -- Good judgment : the intersection of intelligence and personality / Robert Hogan, Joyce Hogan and Paul Barrett -- Relational self in action : relationships and behavior / Susan E. Cross and Kari A. Terzino.
  • 2008From: CRCnetBASE
    Jan Dul, Bernard Weerdmeester.
    Posture and movement -- Information and operation -- Environmental factors -- Work organization jobs and tasks -- The ergonomic approach -- Sources of additional information.
  • 2009From: ScienceDirect
    editors, Robert Lanza ... [et al.].
    Introduction to stem cells -- Basic biology/mechanisms -- Tissue and organ development -- Methods -- Applications -- Regulation and ethics.
  • Laura Astolfi and Fabio Babiloni.
  • 2011From: Atypon
    Monique Frize.
    Increasingly, biomedical scientists and engineers are involved in projects, design, or research and development that involve humans or animals. The book presents general concepts on professionalism and the regulation of the profession of engineering, including a discussion on what is ethics and moral conduct, ethical theories and the codes of ethics that are most relevant for engineers. An ethical decision-making process is suggested. Other issues such as conflicts of interest, plagiarism, intellectual property, confidentiality, privacy, fraud, and corruption are presented. General guidelines, the process for obtaining ethics approval from ethics Review Boards,and the importance of obtaining informed consent from volunteers recruited for studies are presented. A discussion on research with animals is included. Ethical dilemmas focus on reproductive technologies, stem cells, cloning, genetic testing, and designer babies. The book includes a discussion on ethics and the technologies of body enhancement and of regeneration. The importance of assessing the impact of technology on people, society, and on our planet is stressed. Particular attention is given to nanotechnologies, the environment, and issues that pertain to developing countries. Ideas on gender, culture, and ethics focus on how research and access to medical services have, at times, been discriminatory towards women. The cultural aspects focus on organ transplantation in Japan, and a case study of an Aboriginal child in Canada; both examples show the impact that culture can have on how care is provided or accepted. The final section of the book discusses data collection and analysis and offers a guideline for honest reporting of results, avoiding fraud, or unethical approaches. The appendix presents a few case studies where fraud and/or unethical research have occurred.
  • Polina A. Segalova.
    Abdominal aortic aneurysms (AAA's) are characterized by a permanent and irreversible enlargement of the abdominal aorta to at least 150 percent its expected normal size. Endovascular treatment of AAA's with endografts has gained tremendous popularity in the last decade, largely due to decreased perioperative mortality and faster recovery times, when compared to open surgical repair. Although endografts are an appealing treatment option for many patients, some device design and safety issues have yet to be addressed. One of the biggest problems with endografts is their tendency to shift their position in the patient anatomy over time. The forces that cause this shift and their relation to endograft design are not well understood. In addition, the degree of blood damage due to the insertion of an endograft into the abdominal aorta has not been quantified. The following studies were completed in order to investigate the issues described above. 1. Calculation of endograft displacement force in patient-specific device models. This study used electron-beam computed tomography (CT) image data to generate patient-specific anatomical models using novel segmentation techniques. The patient models were then virtually modeled to represent three different endograft designs, based on aortic stent-graft devices already available in the U.S. or currently in clinical trials. Computational Fluid Dynamics (CFD) simulations were run to characterize the hemodynamic factors for each patient and a total displacement force was calculated for each model. Results show that the location of the device bifurcation impacts the overall displacement force, with proximal bifurcation endograft designs generating a lesser force than distal bifurcation designs. 2. Characterization of blood damage due to endograft placement. Patient-specific computational models were created to represent endograft features that partially obstruct blood flow to the renal arteries, which is sometimes necessary to attain complete exclusion of the aneurysm after deploying the device. Findings show that the insertion of an endograft causes a two-fold increase in blood damage. However, the magnitude of blood damage is within acceptable safety standards. 3. Benchtop testing of red blood cell damage. A benchtop experimental setup was created to measure the damage to red blood cells under various flow conditions and flow obstructions. Samples were characterized at different time points using light scatter methods to determine cell volume and hemoglobin concentration. Results indicate that significant damage to red blood cells occurs only after prolonged exposure (> 103 seconds) to high shear (> 4000 dynes/cm2) conditions. In addition, the presence of flow obstructions creates red blood cell fragments, instead of destroying the cells entirely. Future directions for this work include additional CFD modeling of devices in more patients treated with different aortic stent graft designs to derive statistical significance relative to various design and anatomical features and extend the analysis to the evaluation of devices used for the treatment of thoracic aortic aneurysms (TAA's). Follow-up studies on device migration studies can also be completed in the cohort of patients where the endograft displacement forces were calculated. Further, blood damage models that incorporate the fragmentation of red blood cells can be developed.
  • Erica M. Cherry.
    Magnetic drug targeting (MDT) is a noninvasive medical technique that has been proposed for treating diseases that are localized in the body. Currently, drugs meant to treat such conditions are inefficient and often damage healthy tissue because they spread throughout the blood stream. MDT combats this problem by steering the majority of the medicine to the right location in the body. An ideal MDT treatment would involve chemically binding the drug to magnetic particles, injecting the particles into the bloodstream, magnetically steering them through the arterial network, and trapping them near the diseased area so the drug they carry has time to diffuse into the surrounding tissue. There is still much to learn about how to manufacture drug-coated magnetic particles, image these particles in vivo, and control them using magnetic fields. This thesis focuses on understanding the dynamics of magnetic particles moving through the blood stream. A preliminary simulation and experiment were performed to determine realistic ranges of particle, flow, and magnetic field parameters within which MDT could work. Based on the results, an expanded simulation was performed and used to predict optimal conditions for successful magnetic drug targeting. The preliminary simulation and experiment evaluated the feasibility of stopping magnetic particles in a straight tube flow with conditions similar to those in a large artery. It was found that unrealistically high magnetic field gradients were needed to control particles small enough to safely inject into the circulatory system because the fluid drag force on the particles was too large to overcome with magnetic force. Composite spheres, made of micron-sized magnetic particles embedded in agarose (which could potentially be broken up in vivo), were much easier to control magnetically in the same setup. In order to develop an understanding of the dynamics of a cluster of small magnetic particles moving through the circulatory system, an expanded simulation was developed to track the motion of such a cluster in an artery-like flow. The hope was that the presence of an extended cloud of particles would reduce the average drag force per particle and thus small particles would be easier to control magnetically. Three unclosed forces needed to be modeled for this simulation. First, the viscous force on the particles was computed by formulating a non-Newtonian model for blood. Extensive simulations showed that non-Newtonian arterial flows differed significantly from Newtonian ones even in large arteries. Second, the interparticle magnetic force was calculated by developing a numerical method that summed magnetic interactions between grid cells instead of individual particle pairs. This approach is much more efficient than summing the forces for all particle pairs and is accurate as long as the grid is well-resolved and the local gradients of magnetic particle concentration are nonzero. Finally, the dispersion coefficient of the particles caused by their interactions with blood cells was computed by performing a separate Monte Carlo simulation of particles moving through a field of red blood cells with variable shear rate, hematocrit, and particle terminal velocity. The results of the expanded simulation showed that it was possible, but not easy, to slow down a particle cluster moving through a straight artery and somewhat easier to steer a particle cluster down one branch of an arterial bifurcation. In both cases, diffusion prevented successful control of the particle cluster long-term.
  • 2006From: Springer
    Hans-Joachim Bungartz, Michael Schäfer (eds.)
  • Timothy Ryan Julian.
    This dissertation examines the factors that influence fomite-mediated (e.g., indirect contact) transmission of viral gastrointestinal and respiratory illness. Specifically, the dissertation investigates virus transfer between surfaces and virus recovery from surfaces, models human-fomites interactions to estimate exposure and infection risk, and elucidates causal links between microbial contamination and illness in child care centers. Indirect contact transmission refers to person-to-person transmission of disease via an intermediate fomite (e.g., inanimate object acting as a carrier of infectious disease). The role of indirect contact in disease spread is poorly understood in part because the transmission route of viral pathogens is often difficult to determine. Transmission of respiratory and gastrointestinal viruses can occur through multiple routes (e.g., direct contact, indirect contact, airborne, and common vehicle), and the relative contribution of each route to total disease burden is unclear. The first study in this dissertation examines virus transfer between skin and surfaces, a necessary step in fomite-mediated transmission of viral disease. In the study, transfer of virus between fingerpads and fomites is explored in a laboratory setting. Bacteriophage (fr, MS2, and PHIX174) are used as proxies for pathogenic virus, and over 650 unique transfer events are collected from 20 different volunteers. The study concludes that approximately one quarter (23%) of recoverable virus is readily transferred from a contaminated surface (e.g., a fomite) to an uncontaminated surface (e.g., a finger) on contact. Using the large data set, the direction of transfer (from fingerpads-to-fomite or fomite-to-fingerpad) and virus species are demonstrated to both significantly influence the fraction of virus transferred by approximately 2-5%. To investigate the relative importance of factors contributing to fomite-mediated transmission, a child's risk of illness from exposure to a contaminated fomite is modeled. Specifically, the model estimates a child's exposure to rotavirus using a stochastic-mechanistic framework. Simulations of a child's contacts with the fomite include intermittent fomite-mouth, hand-mouth, and hand-fomite contacts based on activities of a typical child under six years of age. In addition to frequency of contact data, parameters estimated for use in the model include virus concentration on surface; virus inactivation rates on hands and the fomite; virus transfer between hands, fomite, and the child's mouth; and the surface area of objects and hands in contact. From the model, we conclude that a child's median ingested dose from interacting with a rotavirus-contaminated ball ranges from 2 to 1,000 virus over a period of one hour, with a median value of 42 virus. These results were heavily influenced by selected values of model parameters, most notably, the concentration of rotavirus on fomite, frequency of fomite-mouth contacts, frequency of hand-mouth contacts, and virus transferred from fomite to mouth. The model demonstrated that mouthing of fomite is the primary exposure route, with hand mouthing contributions accounting for less than one-fifth of the child's dose over the first 10 minutes of interaction. Based on the findings from the model that concentration of virus on a fomite influences a child's risk of illness, we investigate methods to recover virus from fomites. In a literature review and subsequent meta analysis, we demonstrate that the outcome currently used to describe virus contamination, positivity rate, is biased by the authors' selected sampling methods. We follow up, in the laboratory, with a comparison of the identified methods and demonstrate that polyester-tipped swabs prewetted in 1/4-strength Ringer's solution or saline solution is the most efficient sampling method for virus recovery tested. The recommended method is compatible with plaque assay and quantitative reverse-transcription polymerase chain reaction, two techniques used to quantify virus. The link between hand / fomite contamination and infection risk was explored in a field study at two child care centers over four months. Both respiratory and gastrointestinal disease incidence were tracked daily, while hand and environmental surface contamination were monitored weekly between February 2009 and June 2009. Microbial contamination was determined using quantitative densities of fecal indicator bacteria (e.g. Escherichia coli, enterococci, and fecal coliform) on hands and fomites as well as presence/absence of viral pathogens (e.g. enterovirus and norovirus). Health was monitored daily by childcare staff, who tracked absences, illness-related absences, and symptomatic respiratory and gastrointestinal illness. The resultant data suggests that increases in microbial contamination led to increases in symptomatic respiratory illness four to six days later, in agreement with typical incubation periods for respiratory illness. Similarly, respiratory illness led to increases in microbial contamination on hands during presentation of symptoms, and on fomites in the following three days.
  • 2008From: CRCnetBASE
    edited by Gerald F. Harris, Peter A. Smith, Richard M. Marks.
  • 2012From: Atypon
    Thanh M. Cabral and Rangaraj M. Rangayyan.
    Fractal analysis is useful in digital image processing for the characterization of shape roughness and gray-scale texture or complexity. Breast masses present shape and gray-scale characteristics in mammograms that vary between benign masses and malignant tumors. This book demonstrates the use of fractal analysis to classify breast masses as benign masses or malignant tumors based on the irregularity exhibited in their contours and the gray-scale variability exhibited in their mammographic images. A few different approaches are described to estimate the fractal dimension (FD) of the contour of a mass, including the ruler method, box-counting method, and the power spectral analysis (PSA) method. Procedures are also described for the estimation of the FD of the gray-scale image of a mass using the blanket method and the PSA method.
  • 2011From: Springer
    Carlos Hernández ... [et al.], editors.
    Introduction: From Brains to the Machines of the Future / Ricardo Sanz, Carlos Hernández and Jaime Gómez-Ramirez -- Emergent Feature Sensitivity in a Model of the Auditory Thalamocortical System / Martin Coath, Robert Mill, Susan L. Denham and Thomas Wennekers -- STDP Pattern Onset Learning Depends on Background Activity / James Humble, Steve Furber, Susan L. Denham and Thomas Wennekers -- Emergence of Small-World Structure in Networks of Spiking Neurons Through STDP Plasticity / Gleb Basalyga, Pablo M. Gleiser and Thomas Wennekers -- Coupling BCM and Neural Fields for the Emergence of Self-organization Consensus / Mathieu Lefort, Yann Boniface and Bernard Girau -- Alpha and Theta Rhythm Abnormality in Alzheimer's Disease: A Study Using a Computational Model / Basabdatta Sen Bhattacharya, Damien Coyle and Liam P. Maguire -- Oscillatory Neural Network for Image Segmentation with Biased Competition for Attention / Tapani Raiko and Harri Valpola -- Internal Simulation of Perceptions and Actions / Magnus Johnsson and David Gil -- Building Neurocognitive Networks with a Distributed Functional Architecture / Marmaduke Woodman, Dionysios Perdikis, Ajay S. Pillai, Silke Dodel and Raoul Huys, et al. -- Reverse Engineering for Biologically Inspired Cognitive Architectures: A Critical Analysis / Andreas Schierwagen -- Competition in High Dimensional Spaces Using a Sparse Approximation of Neural Fields / Jean-Charles Quinton, Bernard Girau and Mathieu Lefort -- Informational Theories of Consciousness: A Review and Extension / Igor Aleksander and David Gamez -- Hippocampal Categories: A Mathematical Foundation for Navigation and Memory / Jaime Gómez-Ramirez and Ricardo Sanz -- The Role of Feedback in a Hierarchical Model of Object Perception / Salvador Dura-Bernal, Thomas Wennekers and Susan L. Denham -- Machine Free Will: Is Free Will a Necessary Ingredient of Machine Consciousness? / Riccardo Manzotti -- Natural Evolution of Neural Support Vector Machines / Magnus Jändel -- Self-conscious Robotic System Design Process - From Analysis to Implementation / Antonio Chella, Massimo Cossentino and Valeria Seidita -- Simulating Visual Qualia in the CERA-CRANIUM Cognitive Architecture / Raúl Arrabales, Agapito Ledezma and Araceli Sanchis -- The Ouroboros Model, Selected Facets / Knud Thomsen.
    Also available: Print – 2011
  • 2012From: Springer
    Natasha Maurits.
    1. Introduction -- 2. Carpal Tunnel Syndrome, Electroneurography, Electromyography, and Statistics -- 3. Tremor, Polymyography, and Spectral Analysis -- 4. Epilepsia, Electroencephalography, Filtering, and Feature Extraction -- 5. Multiple Sclerosis, Evoked Potentials, and Enhancing Signal-to-Noise Ratio -- 6. Cortical Myoclonus, EEG-EMG, Back-Averaging, and Coherence Analysis -- 7. Psychogenic Movement Disorders, Bereitschaftspotential, and Event-Related Potentials -- 8. Brain Tumor, Preoperative Function Localization, and Source Localization -- 9. Neuromuscular Diseases, Ultrasound, and Image Analysis -- 10. Cerebrovascular Disease, Ultrasound, and Hemodynamical Flow Parameters -- 11. Spinal Dysfunction, Transcranial Magnetic Stimulation, and Motor Evoked Potentials.
  • Gary Shambat.
    Photonic nanocavities are wavelength-scale dielectric structures that possess remarkable properties due to their intrinsic small sizes and high quality factors. Simply by modifying the device materials and optical properties, one can realize nanocavities for diverse applications ranging from lasers to quantum optics and even biosensing. In this dissertation work, two drastically different functions of nanocavities are presented, both of which make them more practical for real-world adoption. The first part of this dissertation will focus on engineered optical devices for interconnect applications in computing and communications. We have shown that heavily doped germanium on silicon can be used as a CMOS-compatible light source with peak emission at 1.5 microns. Microdisk resonators were fabricated and shown to sustain cavity resonances through both photoluminescence (PL) and electroluminescence (EL) measurements. To access these microresonators, we developed a coupling process using a tapered optical fiber and further showed the versatility of these fibers by using them to tune the cavity wavelength. High performance optical sources were then demonstrated in a gallium arsenide platform containing embedded quantum dots (QDs). We have developed a new platform for efficiently driving photonic crystal (PC) cavities using a lithographically defined, lateral p-i-n junction. With our lateral junction we have demonstrated a world record low threshold laser with a threshold power of only 208 nW at 50K. At room temperature we find that these same devices behave as ultra-fast light-emitting diodes which can be directly modulated at up to 10 GHz with operational energies below 1 fJ/bit. Additional active photonic devices incorporating a lateral junction such as electro-optic modulators and photodetectors were also created using this same platform. The second part of this dissertation describes the demonstration of a whole new class of tools geared towards biomedical photonics that marry PC cavities to the tips of optical fibers. The form factor of the optical fiber lends itself to operation of the tool in exotic environments never before accessible to a nanocavity. Fiber-cavity hybrid devices were constructed using a custom epoxy-based assembly procedure which successfully relocates the small semiconductor templates containing nanocavities. The completed device, called a fiberPC, was then used as a sensor to detect gold nanoparticles through optical readout. We have used our probes to interrogate single human prostate cells with internalized PC cavities showing, for the first time, resonant photonic modes inside biological cells. The beams can be loaded in cells and tracked for days at a time, with cells undergoing regular division and migration. Furthermore, we present in vitro label-free protein sensing with our probes as a path towards quantitative, real-time biomarker detection in single cells. The developed tool may find future applications in drug screening, cancer detection, and fundamental cell biology.
  • Remy Durand.
    Functional brain imaging techniques such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) have emerged over the last several decades as powerful methods for understanding brain function and neuropsychiatric disorders. However, due to an inability to precisely and distinctly control the heterogeneous population of circuit elements in the brain, understanding the fundamental physiological mechanisms of these imaging modalities and realizing their potential for functional brain mapping has been limited. Optogenetics is a novel technique that allows for cell-type specific, reversible focal control within the mammalian brain with millisecond-timescale precision. In this thesis, I have utilized the unique cell-type specific neuromodulatory capacity of optogenetics to demonstrate and characterize, for the first time, the effect of direct stimulation of a subclass of excitatory neurons on the in vivo functional hemodynamic response of a rodent brain as measured with functional magnetic resonance imaging (fMRI). I have then used this technique, which we have called ofMRI, to perform large-scale functional mapping of distinct neural circuits that are specified by cell-type, cell-body location, and projection topology. To complement ofMRI studies, I have also developed the use of PET imaging and the radiotracer [18F]-fluorodeoxyglucose (FDG) to further characterize the metabolic and hemodynamic response resulting from activation of genetically-specified neurons in the mammalian brain. Additionally, I have constructed an automated, parallelized all-optical ex vivo system for modulation and recording of distinct neural circuits relevant to neuropsychiatric disorders using voltage sensitive dye imaging (VSDI). Combining the highly specific and rapid control of optogenetics with the biological process sensitivity of PET, the spatial and temporal resolution of BOLD fMRI, and the neural circuit analysis capabilities of optical imaging has the potential to vastly increase our understanding of the roles of neural circuits in both normal and diseased brain states.
  • 2007From: Springer
    Duane Knudson.
  • 2010From: Atypon
    Gerald E. Miller.
    Transport processes represents important life sustaining elements in all humans. These include mass transfer processes, including gas exchange in the lungs, transport across capillaries and alveoli, transport across the kidneys, and transport across cell membranes. These mass transfer processes affect how oxygen and carbon dioxide are exchanged in your bloodstream, how metabolic waste products are removed from your blood, how nutrients are transported to tissues, and how all cells function throughout the body. A discussion of kidney dialysis and gas exchange mechanisms is included. Another element in biomedical transport processes is that of momentum transport and fluid flow. This describes how blood is propelled from the heart and throughout the cardiovascular system, how blood elements affect the body, including gas exchange, infection control, clotting of blood, and blood flow resistance, which affects cardiac work. A discussion of the measurement of the blood resistance to flow (viscosity), blood flow, and pressure is also included. A third element in transport processes in the human body is that of heat transfer, including heat transfer inside the body towards the periphery as well as heat transfer from the body to the environment. A discussion of temperature measurements and body protection in extreme heat conditions is also included.
  • 2009From: Springer
    Ulrich Meyer, Thomas Meyer, Jörg Handschel, Hans Peter Wiesmann, (eds.).
  • 2006From: Springer
    edited by Jan A. Nolta.
    Also available: Print – 2006
  • 2014From: Springer
    György Marko-Varga, editor.
    This book offers a valuable resource that allows students, researchers, educators and the general public to learn about proteomics and genomics. Chromosomes form the basis for our genetic heritage and are the code for protein synthesis. The Human Genome Map was presented in 2002, and the Proteome Sequence Map is currently being created by a global consortia initiative. Proteome and genome building blocks already form the basis of scientific research areas and shape major areas of the pharmaceutical and biomedical industries. The book provides background information on and our current understanding of these gene and protein areas, and explains in detail how cutting-edge science is using these resources to develop new medicines and new diagnostics for patient treatment and care. The book will benefit all students and researchers who need a good understanding of genomics and proteomics within the clinical field. Its content is also suitable for a broad readership, including those not specialized in this field. Dr. Marko-Varga is head of Div. Clinical Protein Science & Imaging at the Biomedical Center, Dept. of Measurement Technology and Industrial Electrical Engineering, Lund University. He's also Professor at the 1st Department of Surgery, Tokyo Medical University, Tokyo, Japan.
  • Richard S. Gaster.
    Nanotechnology has the unique capability of manipulating and sensing matter at the molecular scale with unprecedented speed, sensitivity, and throughput. The medical application of nanotechnology, nanomedicine, has leveraged nanoscience tools for the advancement of medical diagnostics, therapy, and basic science research. In this work, arrays of magnetically responsive nanosensors, originally developed for use as read heads in computer hard disk drives, have been utilized to achieve in-depth proteomic studies for the advancement of medical diagnostics and therapy. In particular, this dissertation will focus on the following four topics of applying magnetic nanotechnology to science and medicine. First, the application of magnetic nanosensor arrays to early cancer diagnostics and monitoring response to chemotherapy. The utility of magnetic nanosensors as a molecular diagnostics tool capable of profiling a patient's disease state and leveraging a patient's unique molecular signature will be demonstrated. Second, this report will discuss a novel mathematical model expressly developed to describe the kinetic interactions of magnetically labeled biomolecules binding to capture agents immobilized on a surface. Third, a novel autoassembly immunoassay capable of screening for antibody cross-reactivity in a high-density, high-fidelity, and rapid manner will be described. Finally, this report will address the utility of the autoassembly immunoassay in conjunction with a miniaturized magnetic nanosensor platform for point-of-care diagnostics in a cost-effective and easy-to-use (e.g. wash-free) process that can make a significant contribution to global health.
  • Drew Alexander Hall.
    Nanotechnology has had a transformative effect on medical diagnostics due to the influx of new sensing modalities and transducers. Magnetic nanotechnologies, in particular, have shown significant potential in several areas of nanomedicine such as imaging, therapeutics, and early disease detection. Giant magnetoresistive spin-valve (GMR SV) sensors, commonly used in hard disk drives, coupled with magnetic nanotags have shown great promise as biosensors. In this work, we present several custom designed circuit interface and readout systems tailored to specific application spaces and their unique needs. Taken together, we have demonstrated that innovative electronic circuits play an indispensable role in unlocking the tremendous potential of nanosensors in the biomedical arena. The first system was designed for ultrasensitive early cancer diagnostics and built using off-the-shelf components for an 8x8 array of GMR SV sensors. At the core of this design, we demonstrate a new circuit architecture based on a transimpedance amplifier (TIA) with a carrier suppression technique to reduce the dynamic range requirement and a multiplexing scheme to reduce the readout time. This system is capable of real-time, multiplex detection with a detection limit of 5 femtomolar (fM) and over 6 orders of linear dynamic range. The second system is a miniaturized, portable platform called the nanoLAB. Although there is a growing need for point-of-care (POC) testing for global health, the current options are bulky, slow, expensive, and often not sensitive. The nanoLAB addresses these needs and pushes the state of the art with sensitive 8-plex detection using a wash-free assay that can be run by anyone, anywhere. This platform was tested and validated using human immunodeficiency virus (HIV) biomarkers with detection down to 50 fM in as little as 15 minutes. We also show how a GMR SV biosensor can be integrated into a continuous time sigma delta modulator. This proof-of-concept hybrid sigma delta modulator has a peak SNR of 99.3 dB and a dynamic range of over 92 dB in a 1 kHz bandwidth using the sensor as part of the first integrator. The carrier suppression and multiplexing concepts were also incorporated into the hybrid sigma delta modulator. Lastly, we conclude by describing an integrated platform for a large 16x16 array of GMR SV sensors implemented in a 0.18 [mu]m CMOS technology. Arranged like an imager chip, each of the 16 column level readout channels contains an analog front-end and an analog-to-digital converter. Each readout channel occupies less than 0.2 mm^2 of chip area and consumes 3.4 mW of power. This system is designed as a replacement for optical protein microarrays while being fully quantitative and providing real-time readout.
  • 2010From: Atypon
    Fabrizio De Vico Fallani and Fabio Babiloni.
  • 2017From: Thieme-Connect
    Bernhard Hirt, Harun Seyhan, Michael Wagner, Rainer Zumhasch ; translator: Karen Leube.
    Anatomy and functional anatomy of the hand -- Surface anatomy of the forearm, wrist, and hand structures.
  • 2015From: Cambridge
    [edited by] Sandro Carrara, EPFL, Lausanne, Switzerland, Krzysztof Iniewski, CMOS Emerging Technologies Research, Inc.
  • 2007From: CRCnetBASE
    edited by Frank S. Barnes, Ben Greenebaum.
    Introduction -- 1. Environmental and Occupationally Encountered Electromagnetic Fields / Kjell Hansson Mild and Ben Greenebaum -- 2. Endogenous Electric Fields in Animals / Richard Nuccitelli -- 3. Dielectric Properties of Biological Materials / Camelia Gabriel -- 4. Magnetic Properties of Biological Material / Jon Dobson -- 5. Interaction of Direct Current and Extremely Low-Frequency / Electric Fields with Biological Materials and Systems / Frank S. Barnes -- 6. Magnetic Field Effects on Free Radical Reactions in Biology / Stefan Engström -- 7. Signals, Noise, and Thresholds / James C. Weaver and Martin Bier -- 8. Biological Effects of Static Magnetic Fields / Shoogo Ueno and Tsukasa Shigemitsu -- 9. The Ion Cyclotron Resonance Hypothesis / A.R. Liboff -- 10. Computational Methods for Predicting Field Intensity and Temperature Change / James C. Lin and Paolo Bernardi -- 11. Experimental EMF Exposure Assessment / Sven Kühn and Niels Kuster -- 12. Electromagnetic Imaging of Biological Systems / William T. Joines, Qing H. Liu, and Gary Ybarra.
  • 2014From: Wiley
    edited by Konstantina S. Nikita.
  • 2008From: Springer
    edited by Anil K. Jain, Patrick Flynn, Arun A. Ross.
  • 2012From: CRCnetBASE
    edited by Gilson Khang.
    Pt. 1. Introduction -- pt. 2. Ceramic and metal scaffold -- pt. 3. Intelligent hydrogel -- pt. 4. Electrospinning nanofiber -- pt. 5. Novel biomaterials for scaffold -- pt. 6. Novel fabrication methods for scaffold -- pt. 7. Scaffold for target organ.
  • 2012From: Springer
    Kewal K. Jain.
    Nanotechnologies -- Nanotechnologies for Basic Research Relevant to Medicine -- Nanomolecular Diagnostics -- Nanopharmaceuticals -- Role of Nanotechnology in Biological Therapies -- Nanodevices and Techniques for Clinical Applications -- Nanooncology -- Nanoneurology -- Nanocardiology -- Nanopulmonology -- Nanoorthopedics -- Nano-ophthalmology -- Nanomicrobiology -- Miscellaneous Healthcare Applications of Nanobiotechnology -- Nanobiotechnology and Personalized Medicine -- Nanotoxicology -- Ethical and Regulatory Aspects of Nanomedicine -- Research and Future of Nanomedicine.
  • by Kewal K. Jain.
    PrintStatus: Not Checked OutLane Catalog Record
  • 2009From: CRCnetBASE
    edited by Valery V. Tuchin.
    "This handbook presents methods that improve the accuracy in glucose prediction based on infrared absorption spectroscopy, recent studies on the influence of acute hyperglycemia on cerebral blood flow, and the correlation between diabetes and the thermo-optical response of human skin. It examines skin glucose monitoring by near-infrared spectroscopy (NIR), fluorescence-based glucose biosensors, and a photonic crystal contact lens sensor. The contributors also explore problems of polarimetric glucose sensing in transparent and turbid tissues as well as offer a high-resolution optical technique for noninvasive, continuous, and accurate blood glucose monitoring and glucose diffusion measurement."--BOOK JACKET.
  • 2010From: CRCnetBASE
    edited by Valery V. Tuchin.
  • 2010From: CRCnetBASE
    edited by Robert Splinter.
  • 2013From: Atypon
    Monique Frize.
    The first chapter describes the health care delivery systems in Canada and in the U.S. This is followed by examples of various approaches used to measure physiological variables in humans, either for the purpose of diagnosis or monitoring potential disease conditions; a brief description of sensor technologies is included. The function and role of the clinical engineer in managing medical technologies in industrialized and in developing countries are presented. This is followed by a chapter on patient safety (mainly electrical safety and electromagnetic interference); it includes a section on how to minimize liability and how develop a quality assurance program for technology management. The next chapter discusses applications of telemedicine, including technical, social, and ethical issues. The last chapter presents a discussion on the impact of technology on health care and the technology assessment process.
  • 2013From: Atypon
    Monique Frize.
    Chapter 7 presents some statistics on the occurrence of medical errors and adverse events, and includes some technological solutions. A chapter on electronic medical records follows. The knowledge management process divided into four steps is described; this includes a discussion on data acquisition, storage, and retrieval. The next two chapters discuss the other three steps of the knowledge management process (knowledge discovery, knowledge translation, knowledge integration and sharing). The last chapter briefly discusses usability studies and clinical trials. The two parts consolidate material that supports courses on technology development and management issues in health care institutions. It can be useful for anyone involved in design, development, or research, whether in industry, hospitals, or government.
  • 2013From: Springer
    Paul A. Iaizzo, Richard W. Bianco, Alexander J. Hill, James D. St. Louis, editors.
    Anatomy, Physiology, Congenital Defects, and Disease -- The Anatomy and Function of the Atrioventricular Valves / Michael G. Bateman, Jason L. Quill, Alexander J. Hill, Paul A. Iaizzo -- The Anatomy and Function of the Semilunar Valves / Michael G. Bateman, Jason L. Quill, Alexander J. Hill, Paul A. Iaizzo -- Congenital Heart Defects That Include Cardiac Valve Abnormalities / Roosevelt Bryant III -- Acquired Valve Disease and Processes / Cindy M. Martin -- Valve Repair and Replacement -- History of Heart Valve Repair / Lauren B. Kwasny, Richard W. Bianco, Luis H. Toledo-Pereyra, -- Heart Valve Disease / Ranjit John, Kenneth Liao -- Advanced 3D Imaging and Transcatheter Valve Repair/Implantation / Paul Schoenhagen, Andrew C. Y. To -- Transcatheter Mitral Repair and Replacement / Jason L. Quill, Ana R. Menk, Gilbert H. L. Tang -- Percutaneous Pulmonary Valve Implantation: The First Transcatheter Valve / Silvia Schievano, Andrew M. Taylor, Philipp Bonhoeffer -- Transcatheter Aortic Valve Implantation / Nicolo Piazza, Darren Mylotte -- Tissue-Engineered Heart Valves / Jillian B. Schmidt, Robert T. Tranquillo -- Testing and Regulatory Issues -- In Vitro Testing of Heart Valve Substitutes / Timothy A. Kelley, Sal Marquez, Carl F. Popelar -- Numerical Methods for Design and Evaluation of Prosthetic Heart Valves / Michael J. Schendel, Carl F. Popelar -- Animal Models for Cardiac Valve Research / Sarah E. Ahlberg, Michael G. Bateman, Michael D. Eggen, Jason L. Quill -- The Use of Isolated Heart Models and Anatomic Specimens as Means to Enhance the Design and Testing of Cardiac Valve Therapies / Michael G. Bateman, Alexander J. Hill, Jason L. Quill, Michael D. Eggen -- Successful Development and Regulatory Approval of Replacement Cardiac Valves / Stephen A. Howard, Michael G. Bateman, Timothy G. Laske, Paul A. Iaizzo -- Clinical Trial Requirements for Cardiac Valves / Jenna C. Iaizzo, Anna T. F. Lovas.
  • Ga-Young Suh.
    Hemodynamic conditions are hypothesized to affect the initiation, growth, and rupture of abdominal aortic aneurysms (AAAs), a vascular disease characterized by progressive wall degradation and enlargement of the abdominal aorta. We hypothesized that the progression of AAA may be slowed by altering the hemodynamics in the abdominal aorta through exercise. The aim of the first study in this thesis was to use magnetic resonance imaging (MRI) and computational fluid dynamics (CFD) to quantify flow stagnation and recirculation in AAAs by computing particle residence time (PRT). Specifically, we used gadolinium-enhanced MR angiography (MRA) to obtain images of the vessel lumens, which were used to generate subject-specific models. Phase-contrast MRI was used to measure blood flow at supraceliac and infrarenal locations to prescribe physiologic boundary conditions. CFD was used to simulate pulsatile flow, and PRT, particle residence index, and particle half-life of PRT in the aneurysms were computed. We observed significant regional differences of PRT in the aneurysms with localized patterns that differed depending on aneurysm geometry and infrarenal flow. A saccular aneurysm with the lowest mean infrarenal flow demonstrated the slowest particle clearance. In addition, improvements in particle clearance were observed with increase of mean infrarenal flow. This result motivated the next study to quantify the effect of augmentation of mean infrarenal flow during exercise on reducing chronic flow stasis that may promote increased mural thrombus burden, degradation of the vessel wall, and aneurysm growth. In the second study, we investigated three levels of activity, rest, mild and moderate intensities of lower-limb exercise to quantify the effect of exercise on hemodynamic conditions in AAA subjects. We measured the abdominal aortic blood flow at rest and during dynamic exercise, and quantified mean wall shear stress (MWSS), oscillatory shear index (OSI), and PRT. We observed that an increase in the level of activity correlated with an increase of MWSS and a decrease of OSI at three locations in the abdominal aorta, and these changes were most significant below the renal arteries. As the level of activity increased, PRT in the aneurysm was significantly decreased: 50% of particles were cleared out of AAAs within 1.36 ± 0.43, 0.34 ± 0.10, and 0.22 ± 0.06 s at rest, mild exercise and moderate exercise levels, respectively. Most of the reduction of PRT occurred from rest to the mild exercise level suggesting that mild exercise may be sufficient to reduce flow stasis in AAAs. The third study aimed to correlate hemodynamic characteristics of AAA with its progression, and quantify morphologic changes of aneurysm from study intake to 1.5-3.5-year follow-up of subjects randomized to usual activity or exercise training cohort. We acquired MRA of 16 subjects, and mid-aneurysm wall content data of 12 subjects at each intake and follow-up visit. 3D lumen models were built based on each intake and follow-up MRAs of six subjects. We observed morphologic changes of aneurysm lumen from intake to follow-up MRA of 11 subjects which exhibited local smoothing, shrinkage or expansion. We observed thickening of thrombus burden from follow-up wall content image of seven subjects whose aneurysm lumen was eventually narrowed. Based on 3D model comparison between intake and follow-up, and the correlation of morphologic changes with wall content changes and PRT contour plots computed in the previous study, we suggest that the region of narrowed lumen induced by thrombus buildup may be consistent with the region of long PRT. As a future work, we will extend our research in conjunction with CT data to quantify the changes of aneurysm wall, and increase the number of subjects to find more conclusive results.
  • Anderson N. Nnewihe.
    Breast cancer is the second leading cause of female cancer death in the United States with an average lifetime risk of 1 in 8. Early detection of the disease and subsequent treatment increase the chance of survival. X-ray mammography is the standard imaging technique for breast cancer screening, but it is difficult to identify malignant lesions in women with dense breasts using x-ray mammography. Dynamic-contrast-enhanced (DCE) magnetic resonance imaging (MRI) has provided high sensitivity for breast cancer diagnosis due to its excellent soft tissue contrast, but there have been varied reports on its specificity. A recent study with a small surface coil has shown that high spatial and temporal resolution breast DCE MRI can improve sensitivity and specificity of ductal carcinoma in situ diagnosis by visualizing smaller scale features such as ductal and periductal enhancement. However, a small surface coil is not suitable for screening or bilateral staging exams where volumetric coverage of both breasts is necessary. Conversely, many commercially-available breast coils offer volumetric coverage of the breasts, but the large coil elements limit the signal-to- noise ratio (SNR) and thus the ability to increase spatial and temporal resolution with high parallel imaging acceleration factors. To address these concerns, we have designed and developed a custom-fitted 18-channel, bilateral breast radiofrequency (RF) coil array for providing high-resolution images in clinically-feasible scan times. The purpose of this work was three-fold: outline the construction process of a high- SNR custom-fitted array, benchmark its performance compared to a commercial design, and evaluate its utility for high-resolution clinical breast MRI. By placing a chain of overlapping small coil elements close to the tissue, we were able to obtain high SNR over the entire breast volume for medium-sized women. To reduce the overall exam time, we laid the coil elements in a geometry that facilitated bidirectional parallel imaging. Comparing the custom-fitted array to a commercially-available 8-channel breast array, the results show 3.6 times higher average SNR and superior parallel imaging quality for the custom-fitted array in volunteers. Using parallel imaging and taking advantage of the SNR benefits from the 18-channel coil array, we clinically demonstrated a 10-fold improvement in spatial resolution over the current Stanford Hospital protocol. We have conducted a clinical study comparing the diagnostic quality of high-resolution scans with the 18-channel array versus lower resolution scans in patients with suspicious lesions on mammography. The initial findings show that the improved resolution enables better depiction of overall lesion morphology and tissue interfaces. In summary, we have presented a method for constructing an 18-channel custom-fitted breast RF array and demonstrated its SNR and parallel imaging benefits. In a clinical setting, our initial findings show improved morphology characterization in high-resolution exams with the 18-channel array.
  • 2010From: Springer
    Vassilis Cutsuridis, Bruce Graham, Stuart Cobb, Imre Vida, editors.
  • 2014From: Springer
    Dierck Hillmann ; with a foreword by Gereon Hüttmann.
    Holoscopy is a new tomographic imaging modality that combines techniques of digital holography with Fourier-domain optical coherence tomography (FD-OCT). Dierck Hillmann gives a theoretical introduction to the mathematics and physics of holoscopy and develops an efficient numerical reconstruction procedure. Compared to FD-OCT, holoscopy provides unique advantages by enabling tomographic imaging without a limited depth of focus, but results in an increased numerical cost for reconstruction. In further chapters, the author introduces techniques for FD-OCT that are relevant to holoscopy as well. He demonstrates and compares numerical reconstruction methods for FD-OCT and shows how motion and dispersion artifacts in FD-OCT can be numerically compensated. Contents Theoretical Introduction to Optical Coherence Tomography and Digital Holography FD-OCT Signal Processing Using the Non-Equispaced Fast Fourier Transform Motion and Dispersion Correction in FD-OCT Holoscopy Target Groups Academics and practitioners in the fields of computer science, optical coherence tomography, digital holography, and medical imaging. The Author Dierck Hillmann received his doctoral degree in the group of Gereon Hüttmann at the Institute of Biomedical Optics in Lübeck and is currently working for a leading company in the fields of science and photonics. The Editor The series Aktuelle Forschung Medizintechnik is edited by Thorsten M. Buzug.
  • Katerina Blazek.
    Obesity, a condition characterized by excess adipose tissue, is becoming an important public health problem. Not only has the prevalence rate in adults risen steadily since the 1980's, obesity is a strong risk factor for the development of knee osteoarthritis (OA) and general mobility disability. There are currently no disease-modifying treatments for OA, so it is important to develop preventive strategies. However, we must first understand the mechanism of increased risk in the obese population. Knee cartilage and other joint structures respond both to mechanical loads during activities of daily living and to the biological environment within the joint, so the pathway to OA in the obese population therefore likely involves changes in both. The primary goal of this dissertation was to test the hypothesis that aging and obesity are linked to changes in gait mechanics and changes in the relationship between cartilage morphology and joint loads, and that these changes are consistent with increased knee OA risk. We also analyzed whether these changes are also observed in individuals with early asymptomatic knee joint degeneration. Finally, we tested the hypothesis that stair climbing requires adaptive changes that reflect a reduction in muscle strength in the aging obese population and indicate increased mobility disability risk. The results indicate that in obese, but not normal-weight individuals, age was associated with an increased adduction moment, which reflects increased loads on the medial compartment of the knee. Furthermore, the positive relationship between cartilage thickness and ambulatory load in young subjects was significantly weaker in middle-aged obese individuals. The increased OA risk in older obese individuals is therefore likely due to both an increase in ambulatory loads and to a change in the relationship between those ambulatory loads and cartilage properties due to the elevated pro-inflammatory cytokine levels characteristic of obesity. During stair climbing, middle-aged obese individuals also had lower peak knee flexion moments, indicative of quadriceps weakness due to aging and relative to their weight. Finally, the gait and stair climbing mechanics of individuals with early OA were not different from their age- and BMI-matched healthy counterparts, indicating that the gait alterations seen in healthy middle-aged obese individuals are the same as those in obese individuals who have already developed the disease, and are likely risk factors or early functional markers of OA.
  • 2009From: Springer
    edited by John R. Masters and Bernhard Ø. Palsson.
    1. Neural progenitors / Dustin R. Wakeman ... [et al.] -- 2. Multipotent stromal cells (hMSCs) / Margaret Wolfe ... [et al.] -- 3. Endothelium / Sangmo Kwon, Takayuki Asahara -- 4. Lung / Rabindra Tirouvanziam, Megha Makam, Bruno Péault -- 5. Eye / Maria Notara ... [et al.] -- 6. Colon / F. Iovino ... [et al.] -- 7. Spermatogonia / Makoto C. Nagano, Jonathan R. Yeh, Khaled Zohni -- 8. Hair follicle pluripotent stem (hfPS) cells / Robert M. Hoffman -- 9. Pancreas / Fang-Xu Jiang, Grant Morahan -- 10. Prostate / C. Foley ... [et al.].
  • 2012From: Springer
    Jan Schildmann...[et al.], editors.
    Part 1. Historical and Socio-Cultural Contexts in Medical Research / British Responses to Nazi Medical War Crimes / Fiona McClenaghan -- History and its Relevance in the Development and Teaching of Research Ethics / Rael D. Strous -- Human Embryo Research and Islamic Bioethics: A View from Iran / Mansooreh Saniei -- From Farming to Pharming: Transcending of Bodily Existence as a Question of Medical Ethics in an Intercultural Context / Axel Siegemund -- Introduction / Jan Schildmann, Verena Sandow, Oliver Rauprich and Jochen Vollmann -- Part 2. Considerations on Ethical and Legal Regulations for Medical Research / Rethinking the Therapeutic Obligation in Clinical Research / Nunziata Comoretto -- Biomedical Research in Developing Countries and International Human Rights Law / Ilja R. Pavone -- Research Involving Human Subjects and Human Biological Material from a European Patent Law Perspective. Autonomy, Commodification, Patentability / Tomasz Zimny -- The Development and Validation of a Guide for Peruvian Research Ethics Committees to Assist in the Review of Ethical-Scientific Aspects of Clinical Trials / Susy Olave Quispe, Duilio Fuentes Delgado, Gabriela Minaya Martínez, Rosa Surco Ibarra and Martín Yagui Moscoso, et al. -- Part 3. Conflicts in Medical Research / Conflicts of Interest in Medical Research: What can Ethics Contribute? / Verena Sandow, Jan Schildmann and Jochen Vollmann -- Research Ethics in Genomics Research: Feedback of Individual Genetic Data to Research Participants / Annelien L. Bredenoord and Johannes J. M. van Delden -- Regulating "Higher Risk, No Direct Benefit" Studies with Children: Challenging the US Federal Regulations / Anna E. Westra, Jan M. Wit, Rám N. Sukhai and Inez D. de Beaufort -- Part 4. New Developments in Medical Research and Ethical Implications / A Paradigm Change in Research Ethics / Rieke van der Graaf and Johannes J. M. van Delden -- Translation of Cancer Molecular Biomarkers: Ethical and Epistemological Issues / Flavio D'Abramo and Cecilia Guastadisegni -- Rethinking the Ethics of Human Biomedical Non-Interventional Research / Kristi L{tilde}ouk.
  • 2013From: CRCnetBASE
    edited by Hanry Yu, Nur Aida Abdul Rahim.
    "This book covers the full range of available imaging modalities and optical methods used to help evaluate material and biological behavior. It also highlights a wide range of optical and biological applications. Each chapter in the text describes a specific application and discusses relevant instrumentation, governing physical principles, data processing procedures, as well as advantages and disadvantages of each modality. Following a broad introduction to key topics, the main chapters are divided between in vitro and in vivo applications. The final section focuses on methods for data processing and analysis"--Provided by publisher.
  • 2015From: Springer
    John D. Lambris, Kristina N. Ekdahl, Daniel Ricklin, Bo Nilsson, editors.
    1. Thromboinflammation in therapeutic medicine -- 2. Complement interactions with blood cells, endothelial cells and microvesicles in thrombotic and inflammatory conditions -- 3. Role of complement on broken surfaces after trauma -- 4. Complement involvement in periodontitis: molecular mechanisms and rational therapeutic approaches -- 5. The lectin pathway of complement and biocompatibility -- 6. Foreign body reaction to subcutaneous implants -- 7. Molecular characterization of macrophage-biomaterial interactions -- 8. Heparan sulfate proteoglycan metabolism and the fate of grafted tissues -- 9. Xenotransplantation of cells, tissues, organs and the Greman research foundation Transregio Collaborative Research Centre 127 -- 10. Macroencapsulated pig islets correct induced diabetes in primates up to 6 months -- 11. Regulation of instant blood mediated inflammatory reaction (IBMIR) in pancreatic islet xeno-transplantation: points for therapeutic interventions -- 12. Cell surface engineering for reguation of immune reactions in cell therapy -- 13. Complement interception across humoral incompatibility in solid organ transplantation: a clinical perspective -- Index.
    Also available: Print – 2015
  • 2014From: Wiley
    edited by Evgeny Katz.
  • 2013From: Springer
    David Korpas.
    History and development of pacing -- Basic principles of cardiac pacemaker technology -- Heart anatomy and physiology -- Pharmacological treatment of cardiac rhythm disorders -- Pacing modes -- Indications for implantable system treatment -- Leads -- Pacing systems -- Pacemaker timing -- Implantable cardioverter-defibrillators -- Cardiac resynchronization therapy -- Implantation, explantation, and replacement of devices and leads -- Patient follow-up -- Electromagnetic compatibility and technical requirements.
  • Thomas Daniel O'Sullivan.
    Molecular imaging is an established technique used to visualize and quantify functional information about biological processes in living systems. In vivo fluorescence imaging, in particular, is a molecular imaging technique capable of quantitatively imaging one or more fluorophores at high spatial and temporal resolution with high sensitivity, either at microscopic or macroscopic (whole-body) scales. While current fluorescent imaging technologies have led to key advances in the understanding of biology and biochemistry, there are limitations. Modern in vivo fluorescence imagers are bulky, and typically take snapshots, and only sample discrete points of continuous, dynamic processes. In order to overcome these obstacles and enable long-term, continuous fluorescence imaging in live animals, we have miniaturized the components of the optical imaging system, allowing for direct implantation. Miniature fluorescence sensors have been fabricated to match a particular fluorescent probe utilizing semiconductor processing technology and appropriate materials. We present the design and fabrication of a monolithically integrated semiconductor (GaAs-based) sensor for far-red to near infrared (NIR) in vivo fluorescence sensing. The sensor incorporates three basic components of a fluorescence system, including: a 675nm vertical-cavity surface-emitting laser (VCSEL) excitation source, a GaAs PIN photodiode, and a fluorescence emission filter. We have packaged the sensors in several integrated configurations, and developed readout mechanisms that include a system that can be implanted in small rodents. We have utilized this device to demonstrate that in vivo fluorescence imaging is possible with miniaturized, un-cooled semiconductor devices, including a demonstration of sensing in a freely-moving rodent. Such miniaturized, implantable biomedical devices have the potential to accelerate pre-clinical research and revolutionize clinical care by providing an inexpensive means for diagnosis, monitoring disease progression, and evaluating long-term treatment efficacy. By integrating this implantable sensor with the appropriate read-out electronics and wireless telemetry, un-tethered operation can ultimately be achieved.
  • 2014From: Springer
    Gauri Mankekar, editor.
    Hearing loss can vary in type ranging from conductive, mixed to sensorineural, as well as in degree from mild, moderate, severe to profound. There could also be multiple permutations and combinations like moderate mixed hearing loss or severe conductive hearing loss. In addition, the hearing loss could be unilateral or bilateral. While cochlear implants were devised for bilateral profound sensorineural hearing loss, various other devices have been invented for other types of hearing losses. Research continues to design a suitable implant which would amplify sound for patients who cannot be candidates for cochlear implants.
  • Michael Quay Chen.
    The limited ability of the human heart to regenerate has made myocardial infarction and heart failure debilitating conditions. Recently, an approach using pluri- or multi-potent stem cells to repair damaged heart tissue is being explored for its potential to regenerate tissue as a tailored, patient-specific treatment. However, the mechanisms of integration remain unclear, and many cardiac grafting procedures utilizing both embryonic and adult stem cells have been met with limited success. While current evidence suggests that grafts are likely viable in host myocardium, clinical studies have reported pro arrhythmic side-effects following transplantation, which arise from disrupted propagation patterns. These issues may be attributed to grafts lacking cardiac differentiation, or possessing conduction properties inconsistent with the host tissue. Consequently, understanding the role of the electrical environment throughout the engraftment process is necessary, but infeasible due to a lack of proper tools. Elucidating the electrical aspects of stem cell transplantation aims to ensure proper integration of the transplanted cells to prevent aberrant electrical pathways in the heart. In this work, a set of in vitro tools were developed to study the potential mechanisms underlying the risk of arrhythmia following stem cell transplantation. A planar microelectrode array was first used to investigate the possibility of conduction block if undifferentiated or non cardiomyocyte stem cells, such as mesenchymal stem cells, are used as grafts. Conduction in murine cardiomyocytes was purposely blocked by co-culture with non-conducting murine fibroblasts, and a novel mathematical transform known as a co occurrence matrix was developed to quantitatively analyze the uniformity of conduction. The observed sensitivity of cardiomyocyte conduction illustrated the risk of grafting non-cardiomyocyte cell types despite any potential of differentiating into muscle-like cells. Unlike non-conducting fibroblasts, stem cell grafts are expected to electrically conduct if proper cardiac differentiation takes place. However, possible differences in the conduction properties of these grafts may still lead to arrhythmia. To perform a controlled study of such conduction mismatch, an in vitro co-culture system coupled to microelectrode arrays was developed. Spatially separated cultures representing the host and the graft were allowed to gradually merge above the microelectrode array, allowing the measurement of conduction throughout the integration process. Modeled host and graft cell populations were evaluated by analyzing the co occurrence matrix and conduction velocity for the quality and speed of conduction over time. Co cultures between murine cardiomyocytes (host) and murine skeletal myoblasts (graft) exhibited significant differences in conduction despite synchronous electrical activity. In contrast, conduction was well matched when the same host cells were co cultured with murine embryonic stem cells (mESC). A model using murine cardiomyocytes (host) and differentiating human embryonic stem cells (graft) allowed the characterization of conduction properties relevant to current trans-species animal models, and demonstrate the co-culture device as a screening platform for candidate graft cells. The limited region of the graft that supported conduction exhibited differences in the co-occurrence matrix as well as conduction velocity when compared to the host region. In an effort to improve the effects of conduction mismatch, both host and graft cell populations were electrically paced over the length of time the cultures remained viable (4-5 days). Although a difference between conduction velocities between host and graft was still observed, the overall uniformity of conduction improved in paced co-cultures, implying increased cardiac differentiation. A preliminary study of genomic changes due to paced mESCs resulted in a significant upregulation of several important cardiac genes and a significant downregulation of many embryonic genes. Further efforts are currently underway to examine gene expression with paced hESCs to optimize integration in the host-graft model, and ultimately to understand how the electrical environment influences stem cell transplantation.
  • 2012From: Springer
    Rihard Trebše, editor.
    Part 1 -- Introduction / Rihard Trebše -- Joint Replacement: Historical Overview / Rihard Trebše, Anže Mihelič -- Biomaterials in Artificial Joint Replacements / Rihard Trebše -- The Definition of Prosthetic Joint Infections (PJI) / Rihard Trebše, Andrej Trampuž -- Classification of Prosthetic Joint Infections / Rihard Trebše, Anže Mihelič -- The Epidemiology of Total Joint Arthroplasty Infections / David J. Jaekel, Kevin L. Ong, Edmund C. Lau -- Septic Complications in Arthroplasty / Gerold Labek -- Perioperative Antibiotic Prophylaxis in Total Joint Arthroplasty / Nataša Faganeli -- Risk Factors for Prosthetic Joint Infections / René Mihalič, Matevž Topolovec -- Pathogenesis of Prosthetic Joint Infections / Rihard Trebše, Jurij Štalc -- Bacteria-Biomaterial Interactions / Antti Soininen, Emilia Kaivosoja, Jaime Esteban -- Biomaterial-Host Interactions in Aseptic and Septic Conditions / Jukka Pajarinen, Yuya Takakubo, Zygmunt Mackiewicz -- Influence of Wear Particles on Local and Systemic Immune System / Emmanuel Gibon, Stuart B. Goodman -- Diagnostic Evaluations / Rihard Trebše -- Synovial Fluid Cytology / René Mihalič, Dunja Terčič -- Histological Analysis of Periprosthetic Tissue for Detecting Prosthetic Joint Infection / Andrej Cör -- Microbiological Diagnosis of Prosthetic Joint Infection / Jaime Esteban, Concepción Pérez-Jorge, Ramón Pérez-Tanoira -- Microbiological Processing of Samples in the Investigation of Suspected Prosthetic Joint Infection / David G. Partridge, Rob Towsend -- Part 2 -- Molecular Diagnosis of Prosthetic Joint Infection / Jaime Esteban, Diana Molina-Manso, Gema del-Prado -- Current Treatment Strategies in Prosthetic Joint Infections / Rihard Trebše Total Ankle Replacement Infections / Michaela Maria Schneiderbauer -- Periprosthetic Infection Issues with Osseointegrated (OI) Implant Technology in Amputees / Catherine Loc-Carrillo, Alec C. Runyon, James Peter Beck -- The Algorithm for Diagnostic Evaluation and Treatment / Rihard Trebše, Andrej Trampuž -- Bone Grafts and Bone Graft Substitutes in Infected Arthroplasty / Martin Clauss, Thomas Ilchmann.

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