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  • Articles  (1,923)
  • Annual Reviews
  • De Gruyter
  • 2000-2004  (1,923)
  • Chemistry and Pharmacology  (1,712)
  • Technology  (211)
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  • Articles  (1,923)
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  • 1
    Electronic Resource
    Electronic Resource
    BIOPHYSICAL INJURY MECHANISMS IN ELECTRICAL SHOCK TRAUMA (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 477-509 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Electrical shock trauma tends to produce a very complex pattern of injury, mainly because of the multiple modes of frequency-dependent tissue-field interactions. Historically, Joule heating was thought to be the only cause of electrical injuries to tissue by commercial-frequency electrical shocks. In the last 15 years, biomedical engineering research has improved the understanding of the underlying biophysical injury mechanisms. Besides thermal burns secondary to Joule heating, permeabilization of cell membranes and direct electroconformational denaturation of macromolecules such as proteins have also been identified as tissue-damage mechanisms. This review summarizes the physics of tissue injury caused by contact with commercial-frequency power lines, as well as exposure to lightning and radio frequency (RF), microwave, and ionizing radiation. In addition, we describe the anatomic patterns of the resultant tissue injury from these modes of electromagnetic exposures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.477
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  • 2
    Electronic Resource
    Electronic Resource
    NEUROENGINEERING MODELS OF BRAIN DISEASE (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 577-606 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The techniques of computational simulation have begun to be applied to modeling neurological disease and mental illness. Such neuroengineering models provide a conceptual bridge between molecular/cellular pathology and cognitive performance. We consider models of Alzheimer's disease, Parkinson's disease, and schizophrenia. Each of these diseases involves a disorder of neuromodulation coupled with underlying neuronal pathology. Parallels arising between these models suggests that a common set of computational mechanisms may account for functional loss across a spectrum of brain diseases. In particular, we focus on attractor-based network dynamics and how they arise from neural architectures, on mechanisms for linking sequences of attractor states and their role in cognition, and on the role of neuromodulation in controlling these processes. These studies suggest new approaches to understanding the forebrain circuits underlying cognition, and point toward a new tool for dissecting the pathophysiology of brain disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.577
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  • 3
    Electronic Resource
    Electronic Resource
    CARTILAGE TISSUE REMODELING IN RESPONSE TO MECHANICAL FORCES (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 691-713 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Recent studies suggest that there are multiple regulatory pathways by which chondrocytes in articular cartilage sense and respond to mechanical stimuli, including upstream signaling pathways and mechanisms that may lead to direct changes at the level of transcription, translation, post-translational modifications, and cell-mediated extracellular assembly and degradation of the tissue matrix. This review focuses on the effects of mechanical loading on cartilage and the resulting chondrocyte-mediated biosynthesis, remodeling, degradation, and repair of this tissue. The effects of compression and tissue shear deformation are compared, and approaches to the study of mechanical regulation of gene expression are described. Of particular interest regarding dense connective tissues, recent experiments have shown that mechanotransduction is critically important in vivo in the cell-mediated feedback between physical stimuli, the molecular structure of newly synthesized matrix molecules, and the resulting macroscopic biomechanical properties of the tissue.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.691
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  • 4
    Electronic Resource
    Electronic Resource
    BIOMECHANICS OF CARDIOVASCULAR DEVELOPMENT (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 1-25 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract It long has been known that mechanical forces play a role in the development of the cardiovascular system, but only recently have biomechanical engineers begun to explore this field. This paper reviews some of this work. First, an overview of the relevant biology is discussed. Next, a mechanical theory is presented that can be used to model developmental processes. The theory includes the effects of finite volumetric growth and active contractile forces. Finally, applications of this and other theories to problems of cardiovascular development are discussed, and some future directions are suggested. The intent is to stimulate further interest among engineers in this important area of research.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.1
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  • 5
    Electronic Resource
    Electronic Resource
    MICROENGINEERING OF CELLULAR INTERACTIONS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 227-256 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Tissue function is modulated by an intricate architecture of cells and biomolecules on a micrometer scale. Until now, in vitro cellular interactions were mainly studied by random seeding over homogeneous substrates. Although this strategy has led to important discoveries, it is clearly a nonoptimal analog of the in vivo scenario. With the incorporation-and adaptation-of microfabrication technology into biology, it is now possible to design surfaces that reproduce some of the aspects of that architecture. This article reviews past research on the engineering of cell-substrate, cell-cell, and cell-medium interactions on the micrometer scale.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.227
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  • 6
    Electronic Resource
    Electronic Resource
    THREE-DIMENSIONAL ULTRASOUND IMAGING (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 457-475 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Two-dimensional viewing of three-dimensional anatomy by conventional ultrasound limits our ability to quantify and visualize a number of diseases and is partly responsible for the reported variability in diagnosis. Over the past two decades, many investigators have addressed this limitation by developing three-dimensional imaging techniques, including three-dimensional ultrasound imaging. In this paper we describe the development of a number of three-dimensional ultrasound imaging systems that make use of B mode, color Doppler, and power Doppler. In these systems, the conventional ultrasound transducer is scanned mechanically or by a freehand technique. The ultrasound images are digitized and then reconstructed into a three-dimensional volume, which can be viewed and manipulated interactively by the diagnostician with a variety of image-rendering techniques. These developments as well as future trends are discussed with regard to their applications and limitations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.457
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  • 7
    Electronic Resource
    Electronic Resource
    MICRODEVICES IN MEDICINE1 (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 551-576 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The application of microelectromechanical systems (MEMS) to medicine is described. Three types of biomedical devices are considered, including diagnostic microsystems, surgical microsystems, and therapeutic microsystems. The opportunities of MEMS miniaturization in these emerging disciplines are considered, with emphasis placed on the importance of the technology in providing a better outcome for the patient and a lower overall health care cost. Several case examples in each of these areas are described. Key aspects of MEMS technology as it is applied to these three areas are described, along with some of the fabrication challenges.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.551
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  • 8
    Electronic Resource
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    MAGNETIC RESONANCE STUDIES OF BRAIN FUNCTION AND NEUROCHEMISTRY (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 633-660 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract In the short time since its introduction, magnetic resonance imaging (MRI) has rapidly evolved to become an indispensable tool for clinical diagnosis and biomedical research. Recently, this methodology has been successfully used for the acquisition of functional, physiological, and biochemical information in intact systems, particularly in the human body. The ability to map areas of altered neuronal activity in the brain, often referred to as functional magnetic resonance imaging (fMRI), is probably one of the most significant recent achievements that rely on this methodology. This development has permitted the examination of functional specialization in human and animal brains with unprecedented spatial resolution, as demonstrated by mapping at the level of orientation and ocular dominance columns in the visual cortex. These functional imaging studies are complemented by the ability to study neurochemistry using magnetic resonance spectroscopy, allowing the determination of metabolic processes that support neurotransmission and neurotransmission rates themselves.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.633
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  • 9
    Electronic Resource
    Electronic Resource
    THOMAS MCMAHON: A Dedication in Memoriam (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. xv 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Thomas A. McMahon (1943-1999) was a pioneer in the field of biomechanics. He made primary contributions to our understanding of terrestrial locomotion, allometry and scaling, cardiac assist devices, orthopedic biomechanics, and a number of other areas. His work was frequently characterized by the use of simple mathematical models to explain seemingly complex phenomena. He also validated these models through creative experimentation. McMahon was a successful inventor and also published three well-received novels. He was raised in Lexington, Massachussetts, attended Cornell University as an undergraduate, and earned a PhD at MIT. From 1970 until his death, he was a member of the faculty of Harvard University, where he taught biomedical engineering. He is fondly remembered as a warm and gentle colleague and an exemplary mentor to his students.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.0
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  • 10
    Electronic Resource
    Electronic Resource
    CARDIAC ENERGY METABOLISM: Models of Cellular Respiration (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 57-81 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The heart requires a large amount of energy to sustain both ionic homeostasis and contraction. Under normal conditions, adenosine triphosphate (ATP) production meets this demand. Hence, there is a complex regulatory system that adjusts energy production to meet this demand. However, the mechanisms for this control are a topic of active debate. Energy metabolism can be divided into three main stages: substrate delivery to the tricarboxylic acid (TCA) cycle, the TCA cycle, and oxidative phosphorylation. Each of these processes has multiple control points and exerts control over the other stages. This review discusses the basic stages of energy metabolism, mechanisms of control, and the mathematical and computational models that have been used to study these mechanisms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.57
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  • 11
    Electronic Resource
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    NEW DNA SEQUENCING METHODS (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 195-223 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The Human Genome Project and other major genomic sequencing projects have pushed the development of sequencing technology. In the past six years alone, instrument throughput has increased 15-fold. New technologies are now on the horizon that could yield massive increases in our capacity for de novo DNA sequencing. This review presents a summary of state-of-the-art technologies for genomic sequencing and describes technologies that may be candidates for the next generation of DNA sequencing instruments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.195
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  • 12
    Electronic Resource
    Electronic Resource
    COMPUTER MODELING AND SIMULATION OF HUMAN MOVEMENT (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 245-273 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Recent interest in using modeling and simulation to study movement is driven by the belief that this approach can provide insight into how the nervous system and muscles interact to produce coordinated motion of the body parts. With the computational resources available today, large-scale models of the body can be used to produce realistic simulations of movement that are an order of magnitude more complex than those produced just 10 years ago. This chapter reviews how the structure of the neuromusculoskeletal system is commonly represented in a multijoint model of movement, how modeling may be combined with optimization theory to simulate the dynamics of a motor task, and how model output can be analyzed to describe and explain muscle function. Some results obtained from simulations of jumping, pedaling, and walking are also reviewed to illustrate the approach.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.245
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  • 13
    Electronic Resource
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    SOFT LITHOGRAPHY IN BIOLOGY AND BIOCHEMISTRY (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 335-373 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Soft lithography, a set of techniques for microfabrication, is based on printing and molding using elastomeric stamps with the patterns of interest in bas-relief. As a technique for fabricating microstructures for biological applications, soft lithography overcomes many of the shortcomings of photolithography. In particular, soft lithography offers the ability to control the molecular structure of surfaces and to pattern the complex molecules relevant to biology, to fabricate channel structures appropriate for microfluidics, and to pattern and manipulate cells. For the relatively large feature sizes used in biology (〉=50 mum), production of prototype patterns and structures is convenient, inexpensive, and rapid. Self-assembled monolayers of alkanethiolates on gold are particularly easy to pattern by soft lithography, and they provide exquisite control over surface biochemistry.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.335
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  • 14
    Electronic Resource
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    PEPTIDE AGGREGATION IN NEURODEGENERATIVE DISEASE (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 4 (2002), S. 155-174 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract In the not-so-distant past, insoluble aggregated protein was considered as uninteresting and bothersome as yesterday's trash. More recently, protein aggregates have enjoyed considerable scientific interest, as it has become clear that these aggregates play key roles in many diseases. In this review, we focus attention on three polypeptides: beta-amyloid, prion, and huntingtin, which are linked to three feared neurodegenerative diseases: Alzheimer's, "mad cow," and Huntington's disease, respectively. These proteins lack any significant primary sequence homology, yet their aggregates possess very similar features, specifically, high beta-sheet content, fibrillar morphology, relative insolubility, and protease resistance. Because the aggregates are noncrystalline, secrets of their structure at nanometer resolution are only slowly yielding to X-ray diffraction, solid-state NMR, and other techniques. Besides structure, the aggregates may possess similar pathways of assembly. Two alternative assembly pathways have been proposed: the nucleation-elongation and the template-assisted mode. These two modes may be complementary, not mutually exclusive. Strategies for interfering with aggregation, which may provide novel therapeutic approaches, are under development. The structural similarities between protein aggregates of dissimilar origin suggest that therapeutic strategies successful against one disease may have broad utility in others.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.4.092801.094202
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  • 15
    Electronic Resource
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    BIOMECHANICAL DYNAMICS OF THE HEART WITH MRI (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 4 (2002), S. 321-347 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Magnetic resonance imaging (MRI) provides a noninvasive way to evaluate the biomechanical dynamics of the heart. MRI can provide spatially registered tomographic images of the heart in different phases of the cardiac cycle, which can be used to assess global cardiac function and regional endocardial surface motion. In addition, MRI can provide detailed information on the patterns of motion within the heart wall, permitting calculation of the evolution of regional strain and related motion variables within the wall. These show consistent patterns of spatial and temporal variation in normal subjects, which are affected by alterations of function due to disease. Although still an evolving technique, MRI shows promise as a new method for research and clinical evaluation of cardiac dynamics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.4.020702.153434
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  • 16
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    STRUCTURAL, FUNCTIONAL, AND MOLECULAR MR IMAGING OF THE MICROVASCULATURE (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 29-56 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Magnetic resonance imaging (MRI) is widely applied for functional imaging of the microcirculation and for functional and structural studies of the microvasculature. The interest in the capabilities of MRI in noninvasively monitoring changes in vascular structure and function expanded over the past years, with specific efforts directed toward the development of novel imaging methods for quantification of angiogenesis. Molecular imaging approaches hold promise for further expansion of the ability to characterize the microvasculature. Exciting applications for MRI are emerging in the study of the biology of microvessels and in the evaluation of potential pharmaceutical modulators of vascular function and development, and preclinical MRI tools can serve for the design of mechanism-of-action-based noninvasive clinical methods for monitoring response to therapy. The aim of this review is to provide a current snapshot of recent developments in this rapidly evolving field.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.040202.121606
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  • 17
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    TEMPORAL DYNAMICS OF BRAIN ANATOMY (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 119-145 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The brain changes profoundly in structure and function during development and as a result of diseases such as the dementias, schizophrenia, multiple sclerosis, and tumor growth. Strategies to measure, map, and visualize these brain changes are of immense value in basic and clinical neuroscience. Algorithms that map brain change with sufficient spatial and temporal sensitivity can also assess drugs that aim to decelerate or arrest these changes. In neuroscience studies, these tools can reveal subtle brain changes in adolescence and old age and link these changes with measurable differences in brain function and cognition. Early detection of brain change in patients at risk for dementia; tumor recurrence; or relapsing-remitting conditions, such as multiple sclerosis, is also vital for optimizing therapy. We review a variety of mathematical and computational approaches to detect structural brain change with unprecedented sensitivity, both spatially and temporally. The resulting four-dimensional (4-D) maps of brain anatomy are warehoused in population-based brain atlases. Here, statistical tools compare brain changes across subjects and across populations, adjusting for complex differences in brain structure. Brain changes in an individual can be compared with a normative database comprised of subjects matched for age, gender, and other demographic factors. These dynamic brain maps offer key biological markers for understanding disease progression and testing therapeutic response. The early detection of disease-related brain changes is also critical for possible pre-emptive intervention before the ravages of disease have set in.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.040202.121611
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  • 18
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    COCHLEAR IMPLANTS: Some Likely Next Steps* (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 207-249 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The history of cochlear implants is marked by large improvements in performance, especially over the past two decades and especially due to the development of ever-better processing strategies. Although the progress to date has been substantial, present devices still do not restore normal speech reception, even for top performers and particularly for listening to speech in competition with noise or other talkers. In addition, a wide range of outcomes persists, with some patients receiving little benefit using the same devices that support high levels of speech reception for others. The purpose of this review is to describe some likely possibilities for further improvement, including (a) combined electric and acoustic stimulation of the auditory system for patients with significant residual hearing, (b) use of bilateral implants, (c) a closer replication with implants of the processing steps in the normal cochlea, and (d) applications of knowledge about factors that are correlated with outcomes to help patients presently at the low end of the performance scale.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.040202.121645
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  • 19
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    NEURAL TISSUE ENGINEERING: Strategies for Repair and Regeneration (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 293-347 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Nerve regeneration is a complex biological phenomenon. In the peripheral nervous system, nerves can regenerate on their own if injuries are small. Larger injuries must be surgically treated, typically with nerve grafts harvested from elsewhere in the body. Spinal cord injury is more complicated, as there are factors in the body that inhibit repair. Unfortunately, a solution to completely repair spinal cord injury has not been found. Thus, bioengineering strategies for the peripheral nervous system are focused on alternatives to the nerve graft, whereas efforts for spinal cord injury are focused on creating a permissive environment for regeneration. Fortunately, recent advances in neuroscience, cell culture, genetic techniques, and biomaterials provide optimism for new treatments for nerve injuries. This article reviews the nervous system physiology, the factors that are critical for nerve repair, and the current approaches that are being explored to aid peripheral nerve regeneration and spinal cord repair.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.011303.120731
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  • 20
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    ADVANCES IN QUANTITATIVE ELECTROENCEPHALOGRAM ANALYSIS METHODS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 453-495 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Quantitative electroencephalogram (qEEG) plays a significant role in EEG-based clinical diagnosis and studies of brain function. In past decades, various qEEG methods have been extensively studied. This article provides a detailed review of the advances in this field. qEEG methods are generally classified into linear and nonlinear approaches. The traditional qEEG approach is based on spectrum analysis, which hypothesizes that the EEG is a stationary process. EEG signals are nonstationary and nonlinear, especially in some pathological conditions. Various time-frequency representations and time-dependent measures have been proposed to address those transient and irregular events in EEG. With regard to the nonlinearity of EEG, higher order statistics and chaotic measures have been put forward. In characterizing the interactions across the cerebral cortex, an information theory-based measure such as mutual information is applied. To improve the spatial resolution, qEEG analysis has also been combined with medical imaging technology (e.g., CT, MR, and PET). With these advances, qEEG plays a very important role in basic research and clinical studies of brain injury, neurological disorders, epilepsy, sleep studies and consciousness, and brain function.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.040202.121601
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  • 21
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    FLUID MECHANICS OF HEART VALVES (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 331-362 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Valvular heart disease is a life-threatening disease that afflicts millions of people worldwide and leads to approximately 250,000 valve repairs and/or replacements each year. Malfunction of a native valve impairs its efficient fluid mechanic/hemodynamic performance. Artificial heart valves have been used since 1960 to replace diseased native valves and have saved millions of lives. Unfortunately, despite four decades of use, these devices are less than ideal and lead to many complications. Many of these complications/problems are directly related to the fluid mechanics associated with the various mechanical and bioprosthetic valve designs. This review focuses on the state-of-the-art experimental and computational fluid mechanics of native and prosthetic heart valves in current clinical use. The fluid dynamic performance characteristics of caged-ball, tilting-disc, bileaflet mechanical valves and porcine and pericardial stented and nonstented bioprostheic valves are reviewed. Other issues related to heart valve performance, such as biomaterials, solid mechanics, tissue mechanics, and durability, are not addressed in this review.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.6.040803.140111
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  • 22
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    BIOENGINEERING MODELS OF CELL SIGNALING (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 31-53 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Strategies for rationally manipulating cell behavior in cell-based technologies and molecular therapeutics and understanding effects of environmental agents on physiological systems may be derived from a mechanistic understanding of underlying signaling mechanisms that regulate cell functions. Three crucial attributes of signal transduction necessitate modeling approaches for analyzing these systems: an ever-expanding plethora of signaling molecules and interactions, a highly interconnected biochemical scheme, and concurrent biophysical regulation. Because signal flow is tightly regulated with positive and negative feedbacks and is bidirectional with commands traveling both from outside-in and inside-out, dynamic models that couple biophysical and biochemical elements are required to consider information processing both during transient and steady-state conditions. Unique mathematical frameworks will be needed to obtain an integrated perspective on these complex systems, which operate over wide length and time scales. These may involve a two-level hierarchical approach wherein the overall signaling network is modeled in terms of effective "circuit" or "algorithm" modules, and then each module is correspondingly modeled with more detailed incorporation of its actual underlying biochemical/biophysical molecular interactions.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.31
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  • 23
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    ELECTROPHYSIOLOGICAL MODELING OF CARDIAC VENTRICULAR FUNCTION: From Cell to Organ (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 119-155 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Three topics of importance to modeling the integrative function of the heart are reviewed. The first is modeling of the ventricular myocyte. Emphasis is placed on excitation-contraction coupling and intracellular Ca2+ handling, and the interpretation of experimental data regarding interval-force relationships. Second, data on use of diffusion tensor magnetic resonance (DTMR) imaging for measuring the anatomical structure of the cardiac ventricles are presented. A method for the semi-automated reconstruction of the ventricles using a combination of gradient recalled acquisition in the steady state (GRASS) and DTMR images is described. Third, we describe how these anatomically and biophysically based models of the cardiac ventricles can be implemented on parallel computers.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.119
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    MICROFABRICATED MICRONEEDLES FOR GENE AND DRUG DELIVERY (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 289-313 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract By incorporating techniques adapted from the microelectronics industry, the field of microfabrication has allowed the creation of microneedles, which have the potential to improve existing biological-laboratory and medical devices and to enable novel devices for gene and drug delivery. Dense arrays of microneedles have been used to deliver DNA into cells. Many cells are treated at once, which is much more efficient than current microinjection techniques. Microneedles have also been used to deliver drugs into local regions of tissue. Microfabricated neural probes have delivered drugs into neural tissue while simultaneously stimulating and recording neuronal activity, and microneedles have been inserted into arterial vessel walls to deliver antirestenosis drugs. Finally, microhypodermic needles and microneedles for transdermal drug delivery have been developed to reduce needle insertion pain and tissue trauma and to provide controlled delivery across the skin. These needles have been shown to be robust enough to penetrate skin and dramatically increase skin permeability to macromolecules.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.289
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    TWO-PHOTON EXCITATION FLUORESCENCE MICROSCOPY (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 399-429 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Two-photon fluorescence microscopy is one of the most important recent inventions in biological imaging. This technology enables noninvasive study of biological specimens in three dimensions with submicrometer resolution. Two-photon excitation of fluorophores results from the simultaneous absorption of two photons. This excitation process has a number of unique advantages, such as reduced specimen photodamage and enhanced penetration depth. It also produces higher-contrast images and is a novel method to trigger localized photochemical reactions. Two-photon microscopy continues to find an increasing number of applications in biology and medicine.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.399
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    IMAGING THREE-DIMENSIONAL CARDIAC FUNCTION (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 431-456 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The three-dimensional (3-D) nature of myocardial deformations is dependent on ventricular geometry, muscle fiber architecture, wall stresses, and myocardial-material properties. The imaging modalities of X-ray angiography, echocardiography, computed tomography, and magnetic resonance (MR) imaging (MRI) are described in the context of visualizing and quantifying cardiac mechanical function. The quantification of ventricular anatomy and cavity volumes is then reviewed, and surface reconstructions in three dimensions are demonstrated. The imaging of myocardial wall motion is discussed, with an emphasis on current MRI and tissue Doppler imaging techniques and their potential clinical applications. Calculation of 3-D regional strains from motion maps is reviewed and illustrated with clinical MRI tagging results. We conclude by presenting a promising technique to assess myocardial-fiber architecture, and we outline its potential applications, in conjunction with quantification of anatomy and regional strains, for the determination of myocardial stress and work distributions. The quantification of multiple components of 3-D cardiac function has potential for both fundamental-science and clinical applications.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.431
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    WAVELETS IN TEMPORAL AND SPATIAL PROCESSING OF BIOMEDICAL IMAGES (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 511-550 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract We review some of the most recent advances in the area of wavelet applications in medical imaging. We first review key concepts in the processing of medical images with wavelet transforms and multiscale analysis, including time-frequency tiling, overcomplete representations, higher dimensional bases, symmetry, boundary effects, translational invariance, orientation selectivity, and best-basis selection. We next describe some applications in magnetic resonance imaging, including activation detection and denoising of functional magnetic resonance imaging and encoding schemes. We then present an overview in the area of ultrasound, including computational anatomy with three-dimensional cardiac ultrasound. Next, wavelets in tomography are reviewed, including their relationship to the radon transform and applications in position emission tomography imaging. Finally, wavelet applications in digital mammography are reviewed, including computer-assisted diagnostic systems that support the detection and classification of small masses and methods of contrast enhancement.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.511
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    EXTRACORPOREAL TISSUE ENGINEERED LIVER-ASSIST DEVICES (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 607-632 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The treatment of acute liver failure has evolved to the current concept of hybrid bioartificial liver (BAL) support, because wholly artificial systems have not proved efficacious. BAL devices are still in their infancy. The properties that these devices must possess are unclear because of our lack of understanding of the pathophysiology of liver failure. The considerations that attend the development of BAL devices are herein reviewed. These considerations include choice of cellular component, choice of membrane component, and choice of BAL system configuration. Mass transfer efficiency plays a role in the design of BAL devices, but the complexity of the systems renders detailed mass transfer analysis difficult. BAL devices based on hollow-fiber bioreactors currently show the most promise, and available results are reviewed herein. BAL treatment is designed to support patients with acute liver failure until an organ becomes available for transplantation. The results obtained to date, in this relatively young field, point to a bright future. The risks of using xenogeneic treatments have yet to be defined. Finally, the experience gained from the past and current BAL systems can be used as a basis for improvement of future BAL technology.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.607
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    INTERVENTIONAL AND INTRAOPERATIVE MAGNETIC RESONANCE IMAGING1 (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 661-690 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The goal of the Image Guided Therapy Program, as the name implies, is to develop the use of imaging to guide minimally invasive therapy. The program combines interventional and intraoperative magnetic resonance imaging (MRI) with high-performance computing and novel therapeutic devices. In clinical practice the multidisciplinary program provides for the investigation of a wide range of interventional and surgical procedures. The Signa SP 0.5 T superconducting MRI system (GE Medical Systems, Milwaukee, WI) has a 56-cm-wide vertical gap, allowing access to the patient and permitting the execution of interactive MRI-guided procedures. This system is integrated with an optical tracking system and utilizes flexible surface coils and MRI-compatible displays to facilitate procedures. Images are obtained with routine pulse sequences. Nearly real-time imaging, with fast gradient-recalled echo sequences, may be acquired at a rate of one image every 1.5 s with interactive image plane selection. Since 1994, more than 800 of these procedures, including various percutaneous procedures and open surgeries, have been successfully performed at Brigham and Women's Hospital (Boston, MA).
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.661
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    IN VIVO NEAR-INFRARED SPECTROSCOPY (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 715-754 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Interrogation of tissue with light offers the potential for noninvasive chemical measurement, and penetration with near-infrared wavelengths (750-1000 nm) is greater than with visible light. Specific absorption by clinically relevant compounds such as oxy- and deoxyhemoglobin and the intracellular respiratory enzyme cytochrome oxidase enable in vivo measurement of these to be performed safely and conveniently. This is the basis of in vivo near-infrared spectroscopy (ivNIRS). Multiple scattering of the interrogating beam by tissues leads to an optical path that is considerably longer than the simple physical pathlength and this complicates the analysis. Modeling of photon propagation through tissues with, for example, finite element and Monte Carlo methods, is assisting in improving the ivNIRS methodology. Instrumentation has advanced from simple continuous wave approaches, through time-resolved methods based on either time-domain or frequency-domain approaches, to spatially resolved measurement based on diffuse reflectance. Initial clinical applications were for monitoring the brain in the neonate and fetus and muscle in adults. Currently, use in adults and children for neurological assessments are of growing interest.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.715
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    THE PROCESS AND DEVELOPMENT OF IMAGE-GUIDED PROCEDURES (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 83-108 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Medical imaging has been used primarily for diagnosis. In the past 15 years there has been an emergence of the use of images for the guidance of therapy. This process requires three-dimensional localization devices, the ability to register medical images to physical space, and the ability to display position and trajectory on those images. This paper examines the development and state of the art in those processes.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.83
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    CAN WE MODEL NITRIC OXIDE BIOTRANSPORT? A SURVEY OF MATHEMATICAL MODELS FOR A SIMPLE DIATOMIC MOLECULE WITH SURPRISINGLY COMPLEX BIOLOGICAL ACTIVITIES (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 109-143 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Nitric oxide (NO) is a remarkable free radical gas whose presence in biological systems and whose astonishing breadth of physiological and pathophysiological activities have only recently been recognized. Mathematical models for NO biotransport, just beginning to emerge in the literature, are examined in this review. Some puzzling and paradoxical properties of NO may be understood by modeling proposed mechanisms with known parameters. For example, it is not obvious how NO can survive strong scavenging by hemoglobin and still be a potent vasodilator. Recent models do not completely explain how tissue NO can reach effective levels in the vascular wall, and they point toward mechanisms that need further investigation. Models help to make sense of extremely low partial pressures of NO exhaled from the lung and may provide diagnostic information. The role of NO as a gaseous neurotransmitter is also being understood through modeling. Studies on the effects of NO on O2 transport and metabolism, also reviewed, suggest that previous mathematical models of transport of O2 to tissue need to be revised, taking the biological activity of NO into account.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.109
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    VASCULAR TISSUE ENGINEERING (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 225-243 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The development of a tissue-engineered blood vessel substitute has motivated much of the research in the area of cardiovascular tissue engineering over the past 20 years. Several methodologies have emerged for constructing blood vessel replacements with biological functionality. These include cell-seeded collagen gels, cell-seeded biodegradable synthetic polymer scaffolds, cell self-assembly, and acellular techniques. This review details the most recent developments, with a focus on core technologies and construct development. Specific examples are discussed to illustrate both the benefits and shortcomings of each methodology, as well as to underline common themes. Finally, a brief perspective on challenges for the future is presented.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.225
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    BIOMECHANICS OF TRABECULAR BONE (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 307-333 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Trabecular bone is a complex material with substantial heterogeneity. Its elastic and strength properties vary widely across anatomic sites, and with aging and disease. Although these properties depend very much on density, the role of architecture and tissue material properties remain uncertain. It is interesting that the strains at which the bone fails are almost independent of density. Current work addresses the underlying structure-function relations for such behavior, as well as more complex mechanical behavior, such as multiaxial loading, time-dependent failure, and damage accumulation. A unique tool for studying such behavior is the microstructural class of finite element models, particularly the "high-resolution" models. It is expected that with continued progress in this field, substantial insight will be gained into such important problems as osteoporosis, bone fracture, bone remodeling, and design/analysis of bone-implant systems. This article reviews the state of the art in trabecular bone biomechanics, focusing on the mechanical aspects, and attempts to identify important areas of current and future research.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.307
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    HERMAN P. SCHWAN: A Scientist and Pioneer in Biomedical Engineering (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 4 (2002), S. 1-27 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.4.092001.093625
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    ROLES FOR LEARNING SCIENCES AND LEARNING TECHNOLOGIES IN BIOMEDICAL ENGINEERING EDUCATION: A Review of Recent Advances (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 4 (2002), S. 29-48 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Education in biomedical engineering offers a number of challenges to all constituents of the educational process-faculty, students, and employers of graduates. Although biomedical engineering educational systems have been under development for 40 years, interest in and the pace of development of these programs has accelerated in recent years. New advances in the learning sciences have provided a framework for the reexamination of instructional paradigms in biomedical engineering. This work shows that learning environments should be learner centered, knowledge centered, assessment centered, and community centered. In addition, learning technologies offer the potential to achieve this environment with efficiency. Biomedical engineering educators are in a position to design and implement new learning systems that can take advantage of advances in learning science, learning technology, and reform in engineering education.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.4.091701.125502
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    BIOENGINEERING OF THERAPEUTIC AEROSOLS (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 4 (2002), S. 93-107 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The new field of therapeutic aerosol bioengineering (TAB), driven primarily by the medical need for inhaled insulin, is now expanding to address medical needs ranging from respiratory to systemic diseases, including asthma, growth deficiency, and pain. Bioengineering of therapeutic aerosols involves a level of aerosol particle design absent in traditional therapeutic aerosols, which are created by conventionally spraying a liquid solution or suspension of drug or milling and mixing a dry drug form into respirable particles. Bioengineered particles may be created in liquid form from devices specially designed to create an unusually fine size distribution, possibly with special purity properties, or solid particles that possess a mixture of drug and excipient, with designed shape, size, porosity, and drug release characteristics. Such aerosols have enabled several high-visibility clinical programs of inhaled insulin, as well as earlier-stage programs involving inhaled morphine, growth hormone, beta-interferon, alpha-1-antitrypsin, and several asthma drugs. The design of these aerosols, limited by partial knowledge of the lungs' physiological environment, and driven largely at this stage by market forces, relies on a mixture of new and old science, pharmaceutical science intuition, and a degree of biological-impact empiricism that speaks to the importance of an increased level of academic involvement.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.4.100101.132311
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    MECHANO-ELECTROCHEMICAL PROPERTIES OF ARTICULAR CARTILAGE: Their Inhomogeneities and Anisotropies (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 4 (2002), S. 175-209 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract In this chapter, the recent advances in cartilage biomechanics and electromechanics are reviewed and summarized. Our emphasis is on the new experimental techniques in cartilage mechanical testing, new experimental and theoretical findings in cartilage biomechanics and electromechanics, and emerging theories and computational modeling of articular cartilage. The charged nature and depth-dependent inhomogeneity in mechano-electrochemical properties of articular cartilage are examined, and their importance in the normal and/or pathological structure-function relationships with cartilage is discussed, along with their pathophysiological implications. Developments in theoretical and computational models of articular cartilage are summarized, and their application in cartilage biomechanics and biology is reviewed. Future directions in cartilage biomechanics and mechano-biology research are proposed.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.4.110701.120309
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    ADVANCES IN IN VIVO BIOLUMINESCENCE IMAGING OF GENE EXPRESSION (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 4 (2002), S. 235-260 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract To advance our understanding of biological processes as they occur in living animals, imaging strategies have been developed and refined that reveal cellular and molecular features of biology and disease in real time. One rapid and accessible technology for in vivo analysis employs internal biological sources of light emitted from luminescent enzymes, luciferases, to label genes and cells. Combining this reporter system with the new generation of charge coupled device (CCD) cameras that detect the light transmitted through the animal's tissues has opened the door to sensitive in vivo measurements of mammalian gene expression in living animals. Here, we review the development and application of this imaging strategy, in vivo bioluminescence imaging (BLI), together with in vivo fluorescence imaging methods, which has enabled the real-time study of immune cell trafficking, of various genetic regulatory elements in transgenic mice, and of in vivo gene transfer. BLI has been combined with fluorescence methods that together offer access to in vivo measurements that were not previously available. Such studies will greatly facilitate the functional analysis of a wide range of genes for their roles in health and disease.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.4.111901.093336
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    PHYSICS AND APPLICATIONS OF MICROFLUIDICS IN BIOLOGY (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 4 (2002), S. 261-286 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Fluid flow at the microscale exhibits unique phenomena that can be leveraged to fabricate devices and components capable of performing functions useful for biological studies. The physics of importance to microfluidics are reviewed. Common methods of fabricating microfluidic devices and systems are described. Components, including valves, mixers, and pumps, capable of controlling fluid flow by utilizing the physics of the microscale are presented. Techniques for sensing flow characteristics are described and examples of devices and systems that perform bioanalysis are presented. The focus of this review is microscale phenomena and the use of the physics of the scale to create devices and systems that provide functionality useful to the life sciences.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.4.112601.125916
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    ADVANCES IN PROTEOMIC TECHNOLOGIES (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 4 (2002), S. 349-373 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Proteomics is a rapidly emerging set of key technologies that are being used to identify proteins and map their interactions in a cellular context. With the sequencing of the human genome, the scope of proteomics has shifted from protein identification and characterization to include protein structure, function and protein-protein interactions. Technologies used in proteomic research include two-dimensional gel electrophoresis, mass spectrometry, yeast two-hybrids screens, and computational prediction programs. While some of these technologies have been in use for a long time, they are currently being applied to study physiology and cellular processes in high-throughput formats. It is the high-throughput approach that defines and characterizes modern proteomics. In this review, we discuss the current status of these experimental and computational technologies relevant to the three major aspects of proteomics-characterization of proteomes, identification of proteins, and determination of protein function. We also briefly discuss the development of new proteomic technologies that are based on recent advances in analytical and biochemical techniques, engineering, microfabrication, and computational prowess. The integration of these advances with established technologies is invaluable for the drive toward a comprehensive understanding of protein structure and function in the cellular milieu.
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    MASS TRANSPORT IN ARTERIES AND THE LOCALIZATION OF ATHEROSCLEROSIS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 79-118 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Atherosclerosis is a disease of the large arteries that involves a characteristic accumulation of high-molecular-weight lipoprotein in the arterial wall. This review focuses on the mass transport processes that mediate the focal accumulation of lipid in arteries and places particular emphasis on the role of fluid mechanical forces in modulating mass transport phenomena. In the final analysis, four mass transport mechanisms emerge that may be important in the localization of atherosclerosis: blood phase controlled hypoxia, leaky endothelial junctions, transient intercellular junction remodeling, and convective clearance of the subendothelial intima and media. Further study of these mechanisms may contribute to the development of therapeutic strategies for atherosclerotic diseases.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.040202.121529
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    SELECTED METHODS FOR IMAGING ELASTIC PROPERTIES OF BIOLOGICAL TISSUES (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 57-78 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract For millennia, physicians have used palpation as a part of the physical examination to detect pathology. The ubiquitous presence of "stiffer" tissue associated with pathology often represents an early warning sign for disease, as in the cases of breast or prostate cancer. Very often tumors are found at surgery that were occult even with modern imaging instruments. This implies that methods for estimating "hardness" of tissues would add a weapon to the medical armamentarium. To this end, this review discusses several methods of estimating tissue hardness using internal or external means of applying stress (force per unit area) and several associated methods of detecting the resulting strain (fractional length change) in an effort to image a tissue mechanical property, such as Young's modulus (ratio of stress to strain). Some investigators have developed methods of estimating stiffness or modulus, but most methods result in qualitative images of stiffness. Nevertheless, such estimates may add a great deal of information not currently available to the current field of medical imaging.
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    THE ENGINEERING OF GENE REGULATORY NETWORKS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 179-206 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The rapid accumulation of genetic information and advancement of experimental techniques have opened a new frontier in biomedical engineering. With the availability of well-characterized components from natural gene networks, the stage has been set for the engineering of artificial gene regulatory networks with sophisticated computational and functional capabilities. In these efforts, the ability to construct, analyze, and interpret qualitative and quantitative models is becoming increasingly important. In this review, we consider the current state of gene network engineering from a combined experimental and modeling perspective. We discuss how networks with increased complexity are being constructed from simple modular components and how quantitative deterministic and stochastic modeling of these modules may provide the foundation for accurate in silico representations of gene regulatory network function in vivo.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.040202.121553
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    ENGINEERED NANOMATERIALS FOR BIOPHOTONICS APPLICATIONS: Improving Sensing, Imaging, and Therapeutics (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 285-292 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Advances in chemistry and physics are providing an expanding array of nanostructured materials with unique and powerful optical properties. These nanomaterials provide a new set of tools that are available to biomedical engineers, biologists, and medical scientists who seek new tools as biosensors and probes of biological fluids, cells, and tissue chemistry and function. Nanomaterials are also being used to develop optically controlled devices for applications such as modulated drug delivery as well as optical therapeutics. This review discusses applications that have been successfully demonstrated using nanomaterials including semiconductor nanocrystals, gold nanoparticles, gold nanoshells, and silver plasmon resonant particles.
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    BIOMONITORING WITH WIRELESS COMMUNICATIONS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 383-412 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Wireless biomonitoring, first used in human beings for fetal heart-rate monitoring more than 30 years ago, has now become a technology for remote sensing of patients' activity, blood pulse pressure, oxygen saturation, internal pressures, orthopedic device loading, and gastrointestinal endoscopy. Technical advances in miniaturization and wireless communications have enabled development of monitoring devices that can be made available for general use by individuals/patients and caregivers. New methods for short-range wireless communications not encumbered by radio spectrum restrictions (e.g., ultra-wideband) will enable applications of wireless monitoring without interference in ambulatory subjects, in home care, and in hospitals.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.040202.121653
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    STRUCTURAL, FUNCTIONAL, AND MOLECULAR MR IMAGING OF THE MICROVASCULATURE (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 29-56 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Magnetic resonance imaging (MRI) is widely applied for functional imaging of the microcirculation and for functional and structural studies of the microvasculature. The interest in the capabilities of MRI in noninvasively monitoring changes in vascular structure and function expanded over the past years, with specific efforts directed toward the development of novel imaging methods for quantification of angiogenesis. Molecular imaging approaches hold promise for further expansion of the ability to characterize the microvasculature. Exciting applications for MRI are emerging in the study of the biology of microvessels and in the evaluation of potential pharmaceutical modulators of vascular function and development, and preclinical MRI tools can serve for the design of mechanism-of-action-based noninvasive clinical methods for monitoring response to therapy. The aim of this review is to provide a current snapshot of recent developments in this rapidly evolving field.
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    MODELING TOTAL HEART FUNCTION (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 147-177 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Computational models of the electrical and mechanical function of the heart are reviewed. These models attempt to explain the integrated function of the heart in terms of ventricular anatomy, the structure and material properties of myocardial tissue, the membrane ion channels, and calcium handling and myofilament mechanics of cardiac myocytes. The models have established the computational framework for linking the structure and function of cardiac cells and tissue to the integrated behavior of the intact heart, but many more aspects of physiological function, including metabolic and signal transduction pathways, need to be included before significant progress can be made in understanding many disease processes.
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    MULTIAXIAL MECHANICAL BEHAVIOR OF BIOLOGICAL MATERIALS (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 251-284 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: For native and engineered biological tissues, there exist many physiological, surgical, and medical device applications where multiaxial material characterization and modeling is required. Because biological tissues and many biocompatible elastomers are incompressible, planar biaxial testing allows for a two-dimensional (2-D) stress-state that can be used to fully characterize their three-dimensional (3-D) mechanical properties. Biological tissues exhibit complex mechanical behaviors not easily accounted for in classic elastomeric constitutive models. Accounting for these behaviors by careful experimental evaluation and formulation of constitutive models continues to be a challenging area in biomechanical modeling and simulation. The focus of this review is to describe the application of multiaxial testing techniques to soft tissues and their relation to modern biomechanical constitutive theories.
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    NEURAL TISSUE ENGINEERING: Strategies for Repair and Regeneration (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 293-347 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Nerve regeneration is a complex biological phenomenon. In the peripheral nervous system, nerves can regenerate on their own if injuries are small. Larger injuries must be surgically treated, typically with nerve grafts harvested from elsewhere in the body. Spinal cord injury is more complicated, as there are factors in the body that inhibit repair. Unfortunately, a solution to completely repair spinal cord injury has not been found. Thus, bioengineering strategies for the peripheral nervous system are focused on alternatives to the nerve graft, whereas efforts for spinal cord injury are focused on creating a permissive environment for regeneration. Fortunately, recent advances in neuroscience, cell culture, genetic techniques, and biomaterials provide optimism for new treatments for nerve injuries. This article reviews the nervous system physiology, the factors that are critical for nerve repair, and the current approaches that are being explored to aid peripheral nerve regeneration and spinal cord repair.
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    BLOOD VESSEL CONSTITUTIVE MODELS-1995-2002 (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 5 (2003), S. 413-439 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Knowledge of blood vessel mechanical properties is fundamental to the understanding of vascular function in health and disease. Analytic results can help physicians in the clinic, both in designing and in choosing appropriate therapies. Understanding the mechanical response of blood vessels to physiologic loads is necessary before ideal therapeutic solutions can be realized. For this reason, blood vessel constitutive models are needed. This article provides a critical review of recent blood vessel constitutive models, starting with a brief overview of the structure and function of arteries and veins, followed by a discussion of experimental techniques used in the characterization of material properties. Current models are classified by type, including pseudoelastic, randomly elastic, poroelastic, and viscoelastic. Comparisons are presented between the various models and existing experimental data. Applications of blood vessel constitutive models are also briefly presented, followed by the identification of future directions in research.
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    BIOMATERIALS: Where We Have Been and Where We are Going (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 41-75 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Since its inception just over a half century ago, the field of biomaterials has seen a consistent growth with a steady introduction of new ideas and productive branches. This review describes where we have been, the state of the art today, and where we might be in 10 or 20 years. Herein, we highlight some of the latest advancements in biomaterials that aim to control biological responses and ultimately heal. This new generation of biomaterials includes surface modification of materials to overcome nonspecific protein adsorption in vivo, precision immobilization of signaling groups on surfaces, development of synthetic materials with controlled properties for drug and cell carriers, biologically inspired materials that mimic natural processes, and design of sophisticated three-dimensional (3-D) architectures to produce well-defined patterns for diagnostics, e.g., biological microelectromechanical systems (bioMEMs), and tissue engineering.
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    THE NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 1-26 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.6.062403.131947
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    FRACTAL ANALYSIS OF THE VASCULAR TREE IN THE HUMAN RETINA (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 427-452 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: The retinal circulation of the normal human retinal vasculature is statistically self-similar and fractal. Studies from several groups present strong evidence that the fractal dimension of the blood vessels in the normal human retina is approximately 1.7. This is the same fractal dimension that is found for a diffusion-limited growth process, and it may have implications for the embryological development of the retinal vascular system. The methods of determining the fractal dimension for branching trees are reviewed together with proposed models for the optimal formation (Murray Principle) of the branching vascular tree in the human retina and the branching pattern of the human bronchial tree. The limitations of fractal analysis of branching biological structures are evaluated. Understanding the design principles of branching vascular systems and the human bronchial tree may find applications in tissue and organ engineering, i.e., bioartificial organs for both liver and kidney.
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    BIOMATERIALS: Where We Have Been and Where We are Going (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 41-75 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Since its inception just over a half century ago, the field of biomaterials has seen a consistent growth with a steady introduction of new ideas and productive branches. This review describes where we have been, the state of the art today, and where we might be in 10 or 20 years. Herein, we highlight some of the latest advancements in biomaterials that aim to control biological responses and ultimately heal. This new generation of biomaterials includes surface modification of materials to overcome nonspecific protein adsorption in vivo, precision immobilization of signaling groups on surfaces, development of synthetic materials with controlled properties for drug and cell carriers, biologically inspired materials that mimic natural processes, and design of sophisticated three-dimensional (3-D) architectures to produce well-defined patterns for diagnostics, e.g., biological microelectromechanical systems (bioMEMs), and tissue engineering.
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    TISSUE GROWTH AND REMODELING (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 77-107 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: The growth and remodeling of a tissue depends on certain features in the history of its mechanical environment as well as its genetic makeup. The mechanical environment influences the tissue's developing morphology, the process of simply increasing the size of existing morphological structures, and the formation of the proteins of which the tissue is constructed. The relationships between genetic information, various epigenetic mechanisms and tissue development are discussed. The developmental growth and remodeling of most structural tissues are enhanced by the use of those tissues and retarded by their disuse. The mechanical or mathematical modeling of tissue growth and development using cellular automata models and continuum mechanical models is reviewed.
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    OPTICAL PROJECTION TOMOGRAPHY (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 6 (2004), S. 209-228 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Optical projection tomography is a new approach for three-dimensional (3-D) imaging of small biological specimens. It fills an imaging gap between MRI and confocal microscopy, being most suited to specimens that are from 1 to 10 mm across. The tomographic principles of optical projection tomography (OPT) are explained, its most important applications in biomedical research explored, and comparisons drawn of its pros and cons compared to a number of alternative imaging technologies.
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    CHROMOSOME COHESION, CONDENSATION, AND SEPARATION (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 69 (2000), S. 115-144 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract The faithful segregation of genetic information requires highly orchestrated changes of chromosome structure during the mitotic cell cycle. The linkage between duplicated sister DNAs is established during S phase and maintained throughout G2 phase (cohesion). In early mitosis, dramatic structural changes occur to produce metaphase chromosomes, each consisting of a pair of compacted sister chromatids (condensation). At anaphase onset, a signal is produced to disrupt the linkage between sister chromatids (separation), allowing them to be pulled apart to opposite poles of the cell. This review discusses our current understanding of the three stages of large-scale structural changes of chromosomes in eukaryotic cells. Recent genetic and biochemical studies have identified key components involved in these processes and started to uncover hitherto unexpected functional links between mitotic chromosome dynamics and other important chromosome functions.
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    URL: http://dx.doi.org/10.1146/annurev.biochem.69.1.115
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    PROTEIN GLUCOSYLATION AND ITS ROLE IN PROTEIN FOLDING (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 69 (2000), S. 69-93 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract An unconventional mechanism for retaining improperly folded glycoproteins and facilitating acquisition of their native tertiary and quaternary structures operates in the endoplasmic reticulum. Recognition of folding glycoproteins by two resident lectins, membrane-bound calnexin and its soluble homolog, calreticulin, is mediated by protein-linked monoglucosylated oligosaccharides. These oligosaccharides contain glucose (Glc), mannose (Man), and N-acetylglucosamine (GlcNAc) in the general form Glc1Man7-9GlcNAc2. They are formed by glucosidase I- and II-catalyzed partial deglucosylation of the oligosaccharide transferred from dolichol diphosphate derivatives to Asn residues in nascent polypeptide chains (Glc3Man9GlcNAc2). Further deglucosylation of the oligosaccharides by glucosidase II liberates glycoproteins from their calnexin/calreticulin anchors. Monoglucosylated glycans are then recreated by the UDP-Glc:glycoprotein glucosyltransferase (GT), and thus recognized again by the lectins, only when linked to improperly folded protein moieties, as GT behaves as a sensor of glycoprotein conformations. The deglucosylation-reglucosylation cycle continues until proper folding is achieved. The lectin-monoglucosylated oligosaccharide interaction is one of the alternative ways by which cells retain improperly folded glycoproteins in the endoplasmic reticulum. Although it decreases the folding rate, it increases folding efficiency, prevents premature glycoprotein oligomerization and degradation, and suppresses formation of nonnative disulfide bonds by hindering aggregation and thus allowing interaction of protein moieties of folding glycoproteins with classical chaperones and other proteins that assist in folding.
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    CHANNELING OF SUBSTRATES AND INTERMEDIATES IN ENZYME-CATALYZED REACTIONS (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 70 (2001), S. 149-180 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract The three-dimensional structures of tryptophan synthase, carbamoyl phosphate synthetase, glutamine phosphoribosylpyrophosphate amidotransferase, and asparagine synthetase have revealed the relative locations of multiple active sites within these proteins. In all of these polyfunctional enzymes, a product formed from the catalytic reaction at one active site is a substrate for an enzymatic reaction at a distal active site. Reaction intermediates are translocated from one active site to the next through the participation of an intermolecular tunnel. The tunnel in tryptophan synthase is ~25 A in length, whereas the tunnel in carbamoyl phosphate synthetase is nearly 100 A long. Kinetic studies have demonstrated that the individual reactions are coordinated through allosteric coupling of one active site with another. The participation of these molecular tunnels is thought to protect reactive intermediates from coming in contact with the external medium.
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    ADVANCING OUR KNOWLEDGE IN BIOCHEMISTRY, GENETICS, AND MICROBIOLOGY THROUGH STUDIES ON TRYPTOPHAN METABOLISM (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 70 (2001), S. 1-37 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract I was fortunate to practice science during the last half of the previous century, when many basic biological and biochemical concepts could be experimentally addressed for the first time. My introduction to research involved isolating and identifying intermediates in the niacin biosynthetic pathway. These studies were followed by investigations focused on determining the properties of genes and enzymes essential to metabolism and examining how they were alterable by mutation. The most challenging problem I initially attacked was establishing the colinear relationship between gene and protein. Subsequent research emphasized identification and characterization of regulatory mechanisms that microorganisms use to control gene expression. An elaborate regulatory strategy, transcription attenuation, was discovered that is often based on selection between alternative RNA structures. Throughout my career I enjoyed the excitement of solving basic scientific problems. Most rewarding, however, was the feeling that I was helping young scientists experience the pleasure of performing creative research.
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    REPLISOME-MEDIATED DNA REPLICATION (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 70 (2001), S. 181-208 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract The elaborate process of genomic replication requires a large collection of proteins properly assembled at a DNA replication fork. Several decades of research on the bacterium Escherichia coli and its bacteriophages T4 and T7 have defined the roles of many proteins central to DNA replication. These three different prokaryotic replication systems use the same fundamental components for synthesis at a moving DNA replication fork even though the number and nature of some individual proteins are different and many lack extensive sequence homology. The components of the replication complex can be grouped into functional categories as follows: DNA polymerase, helix destabilizing protein, polymerase accessory factors, and primosome (DNA helicase and DNA primase activities). The replication of DNA derives from a multistep enzymatic pathway that features the assembly of accessory factors and polymerases into a functional holoenzyme; the separation of the double-stranded template DNA by helicase activity and its coupling to the primase synthesis of RNA primers to initiate Okazaki fragment synthesis; and the continuous and discontinuous synthesis of the leading and lagging daughter strands by the polymerases. This review summarizes and compares and contrasts for these three systems the types, timing, and mechanism of reactions and of protein-protein interactions required to initiate, control, and coordinate the synthesis of the leading and lagging strands at a DNA replication fork and comments on their generality.
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    DNA TOPOISOMERASES: Structure, Function, and Mechanism (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 70 (2001), S. 369-413 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract DNA topoisomerases solve the topological problems associated with DNA replication, transcription, recombination, and chromatin remodeling by introducing temporary single- or double-strand breaks in the DNA. In addition, these enzymes fine-tune the steady-state level of DNA supercoiling both to facilitate protein interactions with the DNA and to prevent excessive supercoiling that is deleterious. In recent years, the crystal structures of a number of topoisomerase fragments, representing nearly all the known classes of enzymes, have been solved. These structures provide remarkable insights into the mechanisms of these enzymes and complement previous conclusions based on biochemical analyses. Surprisingly, despite little or no sequence homology, both type IA and type IIA topoisomerases from prokaryotes and the type IIA enzymes from eukaryotes share structural folds that appear to reflect functional motifs within critical regions of the enzymes. The type IB enzymes are structurally distinct from all other known topoisomerases but are similar to a class of enzymes referred to as tyrosine recombinases. The structural themes common to all topoisomerases include hinged clamps that open and close to bind DNA, the presence of DNA binding cavities for temporary storage of DNA segments, and the coupling of protein conformational changes to DNA rotation or DNA movement. For the type II topoisomerases, the binding and hydrolysis of ATP further modulate conformational changes in the enzymes to effect changes in DNA topology.
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    SYNTHESIS AND FUNCTION OF 3-PHOSPHORYLATED INOSITOL LIPIDS (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 70 (2001), S. 535-602 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract The 3-phosphorylated inositol lipids fulfill roles as second messengers by interacting with the lipid binding domains of a variety of cellular proteins. Such interactions can affect the subcellular localization and aggregation of target proteins, and through allosteric effects, their activity. Generation of 3-phosphoinositides has been documented to influence diverse cellular pathways and hence alter a spectrum of fundamental cellular activities. This review is focused on the 3-phosphoinositide lipids, the synthesis of which is acutely triggered by extracellular stimuli, the enzymes responsible for their synthesis and metabolism, and their cell biological roles. Much knowledge has recently been gained through structural insights into the lipid kinases, their interaction with inhibitors, and the way their 3-phosphoinositide products interact with protein targets. This field is now moving toward a genetic dissection of 3-phosphoinositide action in a variety of model organisms. Such approaches will reveal the true role of the 3-phosphoinositides at the organismal level in health and disease.
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    THE SIGNAL RECOGNITION PARTICLE (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 70 (2001), S. 755-775 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract The signal recognition particle (SRP) and its membrane-associated receptor (SR) catalyze targeting of nascent secretory and membrane proteins to the protein translocation apparatus of the cell. Components of the SRP pathway and salient features of the molecular mechanism of SRP-dependent protein targeting are conserved in all three kingdoms of life. Recent advances in the structure determination of a number of key components in the eukaryotic and prokaryotic SRP pathway provide new insight into the molecular basis of SRP function, and they set the stage for future work toward an integrated picture that takes into account the dynamic and contextual properties of this remarkable cellular machine.
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    MECHANISMS OF VIRAL MEMBRANE FUSION AND ITS INHIBITION (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 70 (2001), S. 777-810 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract Viral envelope glycoproteins promote viral infection by mediating the fusion of the viral membrane with the host-cell membrane. Structural and biochemical studies of two viral glycoproteins, influenza hemagglutinin and HIV-1 envelope protein, have led to a common model for viral entry. The fusion mechanism involves a transient conformational species that can be targeted by therapeutic strategies. This mechanism of infectivity is likely utilized by a wide variety of enveloped viruses for which similar therapeutic interventions should be possible.
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    ATP-DEPENDENT NUCLEOSOME REMODELING (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 71 (2002), S. 247-273 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract It has been a long-standing challenge to decipher the principles that enable cells to both organize their genomes into compact chromatin and ensure that the genetic information remains accessible to regulatory factors and enzymes within the confines of the nucleus. The discovery of nucleosome remodeling activities that utilize the energy of ATP to render nucleosomal DNA accessible has been a great leap forward. In vitro, these enzymes weaken the tight wrapping of DNA around the histone octamers, thereby facilitating the sliding of histone octamers to neighboring DNA segments, their displacement to unlinked DNA, and the accumulation of patches of accessible DNA on the surface of nucleosomes. It is presumed that the collective action of these enzymes endows chromatin with dynamic properties that govern all nuclear functions dealing with chromatin as a substrate. The diverse set of ATPases that qualify as the molecular motors of the nucleosome remodeling process have a common history and are part of a superfamily. The physiological context of their remodeling action builds on the association with a wide range of other proteins to form distinct complexes for nucleosome remodeling. This review summarizes the recent progress in our understanding of the mechanisms underlying the nucleosome remodeling reaction, the targeting of remodeling machines to selected sites in chromatin, and their integration into complex regulatory schemes.
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    EUKARYOTIC RIBONUCLEASE P: A Plurality of Ribonucleoprotein Enzymes (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 71 (2002), S. 165-189 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract Ribonuclease P (RNase P) is an essential endonuclease that acts early in the tRNA biogenesis pathway. This enzyme catalyzes cleavage of the leader sequence of precursor tRNAs (pre-tRNAs), generating the mature 5' end of tRNAs. RNase P activities have been identified in Bacteria, Archaea, and Eucarya, as well as organelles. Most forms of RNase P are ribonucleoproteins, i.e., they consist of an essential RNA subunit and protein subunits, although the composition of the enzyme in mitochondria and chloroplasts is still under debate. The recent purification of the eukaryotic nuclear RNase P has demonstrated a significantly larger protein content compared to the bacterial enzyme. Moreover, emerging evidence suggests that the eukaryotic RNase P has evolved into at least two related nuclear enzymes with distinct functions, RNase P and RNase MRP. Here we review current information on RNase P, with emphasis on the composition, structure, and functions of the eukaryotic nuclear holoenzyme, and its relationship with RNase MRP.
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    DNA REPLICATION IN EUKARYOTIC CELLS (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 71 (2002), S. 333-374 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract The maintenance of the eukaryotic genome requires precisely coordinated replication of the entire genome each time a cell divides. To achieve this coordination, eukaryotic cells use an ordered series of steps to form several key protein assemblies at origins of replication. Recent studies have identified many of the protein components of these complexes and the time during the cell cycle they assemble at the origin. Interestingly, despite distinct differences in origin structure, the identity and order of assembly of eukaryotic replication factors is highly conserved across all species. This review describes our current understanding of these events and how they are coordinated with cell cycle progression. We focus on bringing together the results from different organisms to provide a coherent model of the events of initiation. We emphasize recent progress in determining the function of the different replication factors once they have been assembled at the origin.
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    URL: http://dx.doi.org/10.1146/annurev.biochem.71.110601.135425
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    METABOLISM AND THE CONTROL OF CIRCADIAN RHYTHMS (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 71 (2002), S. 307-331 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract The core apparatus that regulates circadian rhythm has been extensively studied over the past five years. A looming question remains, however, regarding how this apparatus is adjusted to maintain coordination between physiology and the changing environment. The diversity of stimuli and input pathways that gain access to the circadian clock are summarized. Cellular metabolic states could serve to link physiologic perception of the environment to the circadian oscillatory apparatus. A simple model, integrating biochemical, cellular, and physiologic data, is presented to account for the connection of cellular metabolism and circadian rhythm.
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    THE LA PROTEIN (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 71 (2002), S. 375-403 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract Ubiquitous in eukaryotic cells, the La protein associates with the 3' termini of many newly synthesized small RNAs. RNAs bound by the La protein include all nascent transcripts made by RNA polymerase III as well as certain small RNAs synthesized by other RNA polymerases. Recent genetic and biochemical analyses have revealed that binding by the La protein protects the 3' ends of these RNAs from exonucleases. This La-mediated stabilization is required for the normal pathway of pre-tRNA maturation, facilitates assembly of small RNAs into functional RNA-protein complexes, and contributes to nuclear retention of certain small RNAs. Studies of mutant La proteins have given some insights into how the La protein specifically recognizes its RNA targets. However, many questions remain regarding the molecular mechanisms by which La protein binding influences multiple steps in small RNA biogenesis. This review focuses on the roles of the La protein in small RNA biogenesis and also discusses data that implicate the La protein in the translation of specific mRNAs.
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    MAMMALIAN ABC TRANSPORTERS IN HEALTH AND DISEASE (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 71 (2002), S. 537-592 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract The ATP-binding cassette (ABC) transporters are a family of large proteins in membranes and are able to transport a variety of compounds through membranes against steep concentration gradients at the cost of ATP hydrolysis. The available outline of the human genome contains 48 ABC genes; 16 of these have a known function and 14 are associated with a defined human disease. Major physiological functions of ABC transporters include the transport of lipids, bile salts, toxic compounds, and peptides for antigen presentation or other purposes. We review the functions of mammalian ABC transporters, emphasizing biochemical mechanisms and genetic defects. Our overview illustrates the importance of ABC transporters in human physiology, toxicology, pharmacology, and disease. We focus on three topics: (a) ABC transporters transporting drugs (xenotoxins) and drug conjugates. (b) Mammalian secretory epithelia using ABC transporters to excrete a large number of substances, sometimes against a steep concentration gradient. Several inborn errors in liver metabolism are due to mutations in one of the genes for these pumps; these are discussed. (c) A rapidly increasing number of ABC transporters are found to play a role in lipid transport. Defects in each of these transporters are involved in human inborn or acquired diseases.
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    NUCLEAR ACTIN AND ACTIN-RELATED PROTEINS IN CHROMATIN REMODELING (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 71 (2002), S. 755-781 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract The existence and function of actin in the nucleus has been hotly debated for forty years. Recently, beta-actin was found to be a component of mammalian SWI/SNF-like BAF chromatin remodeling complexes and still more recently other SWI/SNF-related chromatin remodeling complexes in yeast, flies, and man. Although the function of actin in these chromatin remodeling complexes is only starting to be explored, the fact that actin is one of the most regulated proteins in the cell suggests that control of nuclear actin may be a critical regulatory point in the control of chromatin remodeling. Actin rapidly shuttles between the nucleus and the cytoplasm offering additional sites and modes of regulation. In addition, actin-related proteins (Arps) are also components of these chromatin remodeling complexes and have been implicated in transcriptional control in yeast. The observation that the BAF chromatin remodeling complex in which actin was originally identified, is also a human tumor suppressor complex necessary for the actions of the retinoblastoma protein indicates that the study of nuclear actin is likely to contribute to understanding cell growth control.
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    CATALYTIC PROFICIENCY: The Unusual Case of OMP Decarboxylase (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 71 (2002), S. 847-885 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract Enzymes are called upon to differ greatly in the difficulty of the tasks that they perform. The catalytic proficiency of an enzyme can be evaluated by comparing the second-order rate constant (kcat/Km) with the rate of the spontaneous reaction in neutral solution in the absence of a catalyst. The proficiencies of enzymes, measured in this way, are matched by their affinity constants for the altered substrate in the transition state. These values vary from approximately ~109 M-1 for carbonic anhydrase to ~1023 M-1 for yeast orotidine 5'-phosphate decarboxylase (ODCase). ODCase turns its substrate over with a half-time of 18 ms, in a reaction that proceeds in its absence with a half-time of 78 million years in neutral solution. ODCase differs from other decarboxylases in that its catalytic activity does not depend on the presence of metals or other cofactors, or on the formation of a covalent bond to the substrate. Several mechanisms of transition state stabilization are considered in terms of ODCase crystal structures observed in the presence and absence of bound analogs of the substrate, transition state, and product. Very large connectivity effects are indicated by the results of experiments testing how transition state stabilization is affected by the truncation of binding determinants of the substrate and the active site.
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    BIOLOGY OF THE P21-ACTIVATED KINASES (2003)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 72 (2003), S. 743-781 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract The p21-activated kinases (PAKs) 1-3 are serine/threonine protein kinases whose activity is stimulated by the binding of active Rac and Cdc42 GTPases. Our understanding of the regulation and biology of these important signaling proteins has increased tremendously since their discovery in the mid-1990s. PAKs 1-3 are activated by a variety of GTPase-dependent and -independent mechanisms. This complexity reflects the contributions of PAK function in many cellular signaling pathways and the need to carefully control PAK action in a highly localized manner. PAKs serve as important regulators of cytoskeletal dynamics and cell motility, transcription through MAP kinase cascades, death and survival signaling, and cell-cycle progression. Consequently, PAKs have also been implicated in a number of pathological conditions and in cell transformation. We propose here a key role for PAK action in coordinating the dynamics of the actin and microtubule cytoskeletons during directional motility of cells, as well as in other functions requiring cytoskeletal polarization.
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    STRUCTURAL BASIS OF ION PUMPING BY CA2+-ATPASE OF THE SARCOPLASMIC RETICULUM (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 73 (2004), S. 269-292 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: The structures of the Ca2+-ATPase (SERCA1a) have been determined for five different states by X-ray crystallography. Detailed comparison of the structures in the Ca2+ bound form and unbound (but thapsigargin bound) form reveals that very large rearrangements of the transmembrane helices take place accompanying Ca2+ dissociation and binding and that they are mechanically linked with equally large movements of the cytoplasmic domains. The meanings of the rearrangements of the transmembrane helices and those of the cytoplasmic domains as well as the mechanistic roles of phosphorylation are now becoming clear. Furthermore, the roles of critical amino acid residues identified by extensive mutagenesis studies are becoming evident in terms of atomic structure.
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    STRUCTURE AND FUNCTION OF TOLC: The Bacterial Exit Duct for Proteins and Drugs (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 73 (2004), S. 467-489 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: The bacterial TolC protein plays a common role in the expulsion of diverse molecules, which include protein toxins and antibacterial drugs, from the cell. TolC is a trimeric 12-stranded alpha/beta barrel, comprising an alpha-helical trans-periplasmic tunnel embedded in the outer membrane by a contiguous beta-barrel channel. This structure establishes a 140 A long single pore fundamentally different to other membrane proteins and presents an exit duct to substrates, large and small, engaged at specific inner membrane translocases. TolC is open to the outside medium but is closed at its periplasmic entrance. When TolC is recruited by a substrate-laden translocase, the entrance is opened to allow substrate passage through a contiguous machinery spanning the entire cell envelope, from the cytosol to the external environment. Transition to the transient open state is achieved by an iris-like mechanism in which entrance alpha-helices undergo an untwisting realignment, thought to be stabilized by interaction with periplasmic helices of the translocase. TolC family proteins are ubiquitous among gram-negative bacteria, and the conserved entrance aperture presents a possible cheomotherapeutic target in multidrug-resistant pathogens.
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    REGULATION OF TELOMERASE BY TELOMERIC PROTEINS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 73 (2004), S. 177-208 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Telomeres are essential for genome stability in all eukaryotes. Changes in telomere functions and the associated chromosomal abnormalities have been implicated in human aging and cancer. Telomeres are composed of repetitive sequences that can be maintained by telomerase, a complex containing a reverse transcriptase (hTERT in humans and Est2 in budding yeast), a template RNA (hTERC in humans and Tlc1 in yeast), and accessory factors (the Est1 proteins and dyskerin in humans and Est1, Est3, and Sm proteins in budding yeast). Telomerase is regulated in cis by proteins that bind to telomeric DNA. This regulation can take place at the telomere terminus, involving single-stranded DNA-binding proteins (POT1 in humans and Cdc13 in budding yeast), which have been proposed to contribute to the recruitment of telomerase and may also regulate the extent or frequency of elongation. In addition, proteins that bind along the length of the telomere (TRF1/TIN2/tankyrase in humans and Rap1/Rif1/Rif2 in budding yeast) are part of a negative feedback loop that regulates telomere length. Here we discuss the details of telomerase and its regulation by the telomere.
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    PALMITOYLATION OF INTRACELLULAR SIGNALING PROTEINS: Regulation and Function (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 73 (2004), S. 559-587 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Protein S-palmitoylation is the thioester linkage of long-chain fatty acids to cysteine residues in proteins. Addition of palmitate to proteins facilitates their membrane interactions and trafficking, and it modulates protein-protein interactions and enzyme activity. The reversibility of palmitoylation makes it an attractive mechanism for regulating protein activity, and this feature has generated intensive investigation of this modification. The regulation of palmitoylation occurs through the actions of protein acyltransferases and protein acylthioesterases. Identification of the protein acyltransferases Erf2/Erf4 and Akr1 in yeast has provided new insight into the palmitoylation reaction. These molecules work in concert with thioesterases, such as acyl-protein thioesterase 1, to regulate the palmitoylation status of numerous signaling molecules, ultimately influencing their function. This review discusses the function and regulation of protein palmitoylation, focusing on intracellular proteins that participate in cell signaling or protein trafficking.
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    STRUCTURAL ASPECTS OF LIGAND BINDING TO AND ELECTRON TRANSFER IN BACTERIAL AND FUNGAL P450S (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 73 (2004), S. 991-1018 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Cytochrome P450 enzymes are heme-containing monooxygenases that are named after an absorption band at 450 nm when complexed with carbon monoxide. They catalyze a wide variety of reactions and are unique in their ability to hydroxylate nonactivated hydrocarbons. P450 enzymes are involved in numerous biological processes, which include the biosynthesis of lipids, steroids, antibiotics, and the degradation of xenobiotics. In line with the variety of reactions catalyzed, the size of their substrates varies significantly. Some P450s have open active sites (e.g., BM3), and some have shielded active sites that open only transiently (e.g., P450cam), whereas others bind the substrate only when attached to carrier proteins (e.g., Oxy proteins). Structural aspects of both organic and gaseous ligand binding and electron transfer are described.
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    ATP-BINDING CASSETTE TRANSPORTERS IN BACTERIA (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 73 (2004), S. 241-268 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: ATP-binding cassette (ABC) transporters couple ATP hydrolysis to the uptake and efflux of solutes across the cell membrane in bacteria and eukaryotic cells. In bacteria, these transporters are important virulence factors because they play roles in nutrient uptake and in secretion of toxins and antimicrobial agents. In humans, many diseases, such as cystic fibrosis, hyperinsulinemia, and macular dystrophy, are traced to defects in ABC transporters. Recent advances in structural determination and functional analysis of bacterial ABC transporters, reviewed herein, have greatly increased our understanding of the molecular mechanism of transport in this transport superfamily.
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    DIRECTED EVOLUTION OF NUCLEIC ACID ENZYMES (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 73 (2004), S. 791-836 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Just as Darwinian evolution in nature has led to the development of many sophisticated enzymes, Darwinian evolution in vitro has proven to be a powerful approach for obtaining similar results in the laboratory. This review focuses on the development of nucleic acid enzymes starting from a population of random-sequence RNA or DNA molecules. In order to illustrate the principles and practice of in vitro evolution, two especially well-studied categories of catalytic nucleic acid are considered: RNA enzymes that catalyze the template-directed ligation of RNA and DNA enzymes that catalyze the cleavage of RNA. The former reaction, which involves attack of a 2'- or 3'-hydroxyl on the alpha-phosphate of a 5'-triphosphate, is more difficult. It requires a comparatively larger catalytic motif, containing more nucleotides than can be sampled exhaustively within a starting population of random-sequence RNAs. The latter reaction involves deprotonation of the 2'-hydroxyl adjacent to the cleavage site, resulting in cleaved products that bear a 2',3'-cyclic phosphate and 5'-hydroxyl. The difficulty of this reaction, and therefore the complexity of the corresponding DNA enzyme, depends on whether a catalytic cofactor, such as a divalent metal cation or small molecule, is present in the reaction mixture.
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    INCORPORATION OF NONNATURAL AMINO ACIDS INTO PROTEINS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 73 (2004), S. 147-176 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: The genetic code is established by the aminoacylation of transfer RNA, reactions in which each amino acid is linked to its cognate tRNA that, in turn, harbors the nucleotide triplet (anticodon) specific to the amino acid. The accuracy of aminoacylation is essential for building and maintaining the universal tree of life. The ability to manipulate and expand the code holds promise for the development of new methods to create novel proteins and to understand the origins of life. Recent efforts to manipulate the genetic code have fulfilled much of this potential. These efforts have led to incorporation of nonnatural amino acids into proteins for a variety of applications and have demonstrated the plausibility of specific proposals for early evolution of the code.
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    MOLECULAR MECHANISMS OF MAMMALIAN DNA REPAIR AND THE DNA DAMAGE CHECKPOINTS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 73 (2004), S. 39-85 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: DNA damage is a relatively common event in the life of a cell and may lead to mutation, cancer, and cellular or organismic death. Damage to DNA induces several cellular responses that enable the cell either to eliminate or cope with the damage or to activate a programmed cell death process, presumably to eliminate cells with potentially catastrophic mutations. These DNA damage response reactions include: (a) removal of DNA damage and restoration of the continuity of the DNA duplex; (b) activation of a DNA damage checkpoint, which arrests cell cycle progression so as to allow for repair and prevention of the transmission of damaged or incompletely replicated chromosomes; (c) transcriptional response, which causes changes in the transcription profile that may be beneficial to the cell; and (d) apoptosis, which eliminates heavily damaged or seriously deregulated cells. DNA repair mechanisms include direct repair, base excision repair, nucleotide excision repair, double-strand break repair, and cross-link repair. The DNA damage checkpoints employ damage sensor proteins, such as ATM, ATR, the Rad17-RFC complex, and the 9-1-1 complex, to detect DNA damage and to initiate signal transduction cascades that employ Chk1 and Chk2 Ser/Thr kinases and Cdc25 phosphatases. The signal transducers activate p53 and inactivate cyclin-dependent kinases to inhibit cell cycle progression from G1 to S (the G1/S checkpoint), DNA replication (the intra-S checkpoint), or G2 to mitosis (the G2/M checkpoint). In this review the molecular mechanisms of DNA repair and the DNA damage checkpoints in mammalian cells are analyzed.
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    OPIOID RECEPTORS (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 73 (2004), S. 953-990 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Opioid receptors belong to the large superfamily of seven transmembrane-spanning (7TM) G protein-coupled receptors (GPCRs). As a class, GPCRs are of fundamental physiological importance mediating the actions of the majority of known neurotransmitters and hormones. Opioid receptors are particularly intriguing members of this receptor family. They are activated both by endogenously produced opioid peptides and by exogenously administered opiate compounds, some of which are not only among the most effective analgesics known but also highly addictive drugs of abuse. A fundamental question in addiction biology is why exogenous opioid drugs, such as morphine and heroin, have a high liability for inducing tolerance, dependence, and addiction. This review focuses on many aspects of opioid receptors with the aim of gaining a greater insight into mechanisms of opioid tolerance and dependence.
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    MECHANICAL PROCESSES IN BIOCHEMISTRY (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 73 (2004), S. 705-748 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Mechanical processes are involved in nearly every facet of the cell cycle. Mechanical forces are generated in the cell during processes as diverse as chromosomal segregation, replication, transcription, translation, translocation of proteins across membranes, cell locomotion, and catalyzed protein and nucleic acid folding and unfolding, among others. Because force is a product of all these reactions, biochemists are beginning to directly apply external forces to these processes to alter the extent or even the fate of these reactions hoping to reveal their underlying molecular mechanisms. This review provides the conceptual framework to understand the role of mechanical force in biochemistry.
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    USING PROTEIN FOLDING RATES TO TEST PROTEIN FOLDING THEORIES (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 73 (2004), S. 837-859 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: The fastest simple, kinetically two-state protein folds a million times more rapidly than the slowest. Here we review many recent theories of protein folding kinetics in terms of their ability to qualitatively rationalize, if not quantitatively predict, this fundamental experimental observation.
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    THE EXCITEMENT OF DISCOVERY (2004)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 73 (2004), S. 1-37 
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    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: I had the good luck to start research at the dawn of molecular biology when it was possible to ask fundamental questions about the nature of the nucleic acids and how information is transferred in living systems. The search for answers led me into many different areas, often with the question of how molecular structure leads to biological function. Early work in this period provided some of the roots supporting the current explosive developments in life sciences. Here I give a brief account of my development, describe some contributions, and provide a hint of the exhilaration in discovering new things. Most of all, I had the good fortune to have inspiring teachers, stimulating colleagues, and excellent students.
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    PIERRE M. GALLETTI: A Personal Reflection (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 1-7 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Pierre Galletti, my friend and colleague, passed away on March 8, 1997, having left his mark on the emerging field of biomedical engineering. He was a pioneering researcher, making his impact in such fields as heart-lung bypass, artificial organs, and tissue engineering. He was a dedicated teacher and a mentor to many. He not only provided leadership in the establishment of the medical school at Brown University, but also helped start Morehouse School of Medicine in Atlanta. He was an entrepreneur and an individual who realized that ultimately basic science only impacts patient care when new technology is made available to the public. He served the bioengineering community in many ways, later in life becoming active in public policy, and as the second president of the American Institute for Medical and Biological Engineering, more than anyone focused this organization on its public policy role. He was the consummate biomedical engineer, a person of great vision, a man for all seasons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.1
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    PHYSICOCHEMICAL FOUNDATIONS AND STRUCTURAL DESIGN OF HYDROGELS IN MEDICINE AND BIOLOGY (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 9-29 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Hydrogels are cross-linked hydrophilic polymers that can imbibe water or biological fluids. Their biomedical and pharmaceutical applications include a very wide range of systems and processes that utilize several molecular design characteristics. This review discusses the molecular structure, dynamic behavior, and structural modifications of hydrogels as well as the various applications of these biohydrogels. Recent advances in the preparation of three-dimensional structures with exact chain conformations, as well as tethering of functional groups, allow for the preparation of promising new hydrogels. Meanwhile, intelligent biohydrogels with pH- or temperature-sensitivity continue to be important materials in medical applications.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.9
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    INJURY AND REPAIR OF LIGAMENTS AND TENDONS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 83-118 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract In this chapter, biomechanical methods used to analyze healing and repair of ligaments and tendons are initially described such that the tensile properties of these soft tissues as well as their contribution to joint motion can be determined. The focus then turns to the important mechanical and biological factors that improve the healing process of ligaments. The biomechanics of surgical reconstruction of the anterior cruciate ligament and the key surgical parameters that affect the performance of the replacement grafts are subsequently reviewed. Finally, injury mechanisms and the biomechanical analysis of various treatment techniques for various types of tendon injuries are described.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.83
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    CELL MECHANICS: Mechanical Response, Cell Adhesion, and Molecular Deformation (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 189-226 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract As the basic unit of life, the cell is a biologically complex system, the understanding of which requires a combination of various approaches including biomechanics. With recent progress in cell and molecular biology, the field of cell mechanics has grown rapidly over the last few years. This review synthesizes some of these recent developments to foster new concepts and approaches, and it emphasizes molecular-level understanding. The focuses are on the common themes and interconnections in three related areas: (a) the responses of cells to mechanical forces, (b) the mechanics and kinetics of cell adhesion, and (c) the deformation of biomolecules. Specific examples are also given to illustrate the quantitative modeling used in analyzing biological processes and physiological functions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.189
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    CONTROL MOTIFS FOR INTRACELLULAR REGULATORY NETWORKS1 (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 391-419 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract A number of technological innovations are yielding unprecedented data on the networks of biochemical, genetic, and biophysical reactions that underlie cellular behavior and failure. These networks are composed of hundreds to thousands of chemical species and structures, interacting via nonlinear and possibly stochastic physical processes. A central goal of modern biology is to optimally use the data on these networks to understand how their design leads to the observed cellular behaviors and failures. Ultimately, this knowledge should enable cellular engineers to redesign cellular processes to meet industrial needs (such as optimal natural product synthesis), aid in choosing the most effective targets for pharmaceuticals, and tailor treatment for individual genotypes. The size and complexity of these networks and the inevitable lack of complete data, however, makes reaching these goals extremely difficult. If it proves possible to modularize these networks into functional subnetworks, then these smaller networks may be amenable to direct analysis and might serve as regulatory motifs. These motifs, recurring elements of control, may help to deduce the structure and function of partially known networks and form the basis for fulfilling the goals described above. A number of approaches to identifying and analyzing control motifs in intracellular networks are reviewed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.391
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    THREE-DIMENSIONAL CONFOCAL MICROSCOPY OF THE LIVING HUMAN EYE (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 4 (2002), S. 69-91 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Three-dimensional confocal microscopy of the living eye is a major development in instrumentation for biomicroscopy of the eye. This noninvasive optical technology has its roots in the application of optics to reflected light imaging of the eye. These instrument developments began with Leeuwenhoek's use of his single lens microscope to investigate the structure of the eye. There followed a series of connected instruments: the ophthalmoscope, the slit lamp, the specular microscope, and the clinical confocal microscope. In vivo confocal microscopy produces high contrast, reflected light images or optical sections through the depth of living ocular tissue. Stacks of registered optical sections can be transformed by computer visualization techniques into three-dimensional volume images of ocular tissues: cornea, ocular lens, retina, and optic nerve. The clinical confocal microscope has resulted in new diagnostic techniques and new cellular descriptions of ocular disorders and pathology.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.4.092701.132001
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    DENATURATION OF COLLAGEN VIA HEATING: An Irreversible Rate Process (2002)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 4 (2002), S. 109-128 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Heating therapies are increasingly used in cardiology, dermatology, gynecology, neurosurgery, oncology, ophthalmology, orthopedics, and urology, among other medical specialties. This widespread use of heating is driven primarily by the availability of new technology, not by a detailed understanding of the biothermomechanics. Without basic quantification of the underlying physical and chemical processes in terms of parameters that can be controlled clinically, identification of preferred interventions will continue to be based primarily on trial and error, thus necessitating large clinical studies and years of accumulative experience. Perusal of the literature reveals that much has been learned over the past century about the response of cells, proteins, and tissues to supra-physiologic temperatures; yet, the associated findings are reported in diverse journals and the underlying basic processes remain unidentified. In this review, we seek to contrast various findings on the kinetics of the thermal denaturation of collagen and to encourage investigators to consider the many open problems in part via a synthesis of results from the diverse literatures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.4.101001.131546
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    CRYPTOCHROME: The Second Photoactive Pigment in The Eye and Its Role in Circadian Photoreception (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 69 (2000), S. 31-67 
    Details
    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract Circadian rhythms are oscillations in the biochemical, physiological, and behavioral functions of organisms that occur with a periodicity of approximately 24 h. They are generated by a molecular clock that is synchronized with the solar day by environmental photic input. The cryptochromes are the mammalian circadian photoreceptors. They absorb light and transmit the electromagnetic signal to the molecular clock using a pterin and flavin adenine dinucleotide (FAD) as chromophore/cofactors, and are evolutionarily conserved and structurally related to the DNA repair enzyme photolyase. Humans and mice have two cryptochrome genes, CRY1 and CRY2, that are differentially expressed in the retina relative to the opsin-based visual photoreceptors. CRY1 is highly expressed with circadian periodicity in the mammalian circadian pacemaker, the suprachiasmatic nucleus (SCN). Mutant mice lacking either Cry1 or Cry2 have impaired light induction of the clock gene mPer1 and have abnormally short or long intrinsic periods, respectively. The double mutant has normal vision but is defective in mPer1 induction by light and lacks molecular and behavioral rhythmicity in constant darkness. Thus, cryptochromes are photoreceptors and central components of the molecular clock. Genetic evidence also shows that cryptochromes are circadian photoreceptors in Drosophila and Arabidopsis, raising the possibility that they may be universal circadian photoreceptors. Research on cryptochromes may provide new understanding of human diseases such as seasonal affective disorder and delayed sleep phase syndrome.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biochem.69.1.31
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    IMPORT OF PEROXISOMAL MATRIX AND MEMBRANE PROTEINS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 69 (2000), S. 399-418 
    Details
    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract This review summarizes the progress made in our understanding of peroxisome biogenesis in the last few years, during which the functional roles of many of the 23 peroxins (proteins involved in peroxisomal protein import and peroxisome biogenesis) have become clearer. Previous reviews in the field have focussed on the metabolic functions of peroxisomes (1, 2), aspects of import/biogenesis (3, 4, 5, 6, 7), the role of peroxins in human disease (2, 8), and involvement of the endoplasmic reticulum in peroxisome membrane biogenesis (9, 10, 11) as well as the degradation of this organelle (5, 12). This review refers to some of the earlier work for the sake of introduction and continuity but deals primarily with the more recent progress. The principal areas of progress are the identification of new peroxins, definition of protein-protein interactions among peroxins leading to the recognition of complexes involved in peroxisomal protein import, insight into the biogenesis of peroxisomal membrane proteins, and, of most importance, the elucidation of the role of many conserved peroxins in human disease. Given the rapid progress in the field, this review also highlights some of the unanswered questions that remain to be tackled.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biochem.69.1.399
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    STRUCTURE AND FUNCTION OF HEXAMERIC HELICASES1 (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 69 (2000), S. 651-697 
    Details
    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract Helicases are motor proteins that couple the hydrolysis of nucleoside triphosphate (NTPase) to nucleic acid unwinding. The hexameric helicases have a characteristic ring-shaped structure, and all, except the eukaryotic minichromosomal maintenance (MCM) helicase, are homohexamers. Most of the 12 known hexameric helicases play a role in DNA replication, recombination, and transcription. A human genetic disorder, Bloom's syndrome, is associated with a defect in one member of the class of hexameric helicases. Significant progress has been made in understanding the biochemical properties, structures, and interactions of these helicases with DNA and nucleotides. Cooperativity in nucleotide binding was observed in many, and sequential NTPase catalysis has been observed in two proteins, gp4 of bacteriophage T7 and rho of Escherichia coli. The crystal structures of the oligomeric T7 gp4 helicase and the hexamer of RepA helicase show structural features that substantiate the observed cooperativity, and both are consistent with nucleotide binding at the subunit interface. Models are presented that show how sequential NTP hydrolysis can lead to unidirectional and processive translocation. Possible unwinding mechanisms based on the DNA exclusion model are proposed here, termed the wedge, torsional, and helix-destabilizing models.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biochem.69.1.651
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    REGULATION OF CHROMOSOME REPLICATION (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 69 (2000), S. 829-880 
    Details
    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract The initiation of DNA replication in eukaryotic cells is tightly controlled to ensure that the genome is faithfully duplicated once each cell cycle. Genetic and biochemical studies in several model systems indicate that initiation is mediated by a common set of proteins, present in all eukaryotic species, and that the activities of these proteins are regulated during the cell cycle by specific protein kinases. Here we review the properties of the initiation proteins, their interactions with each other, and with origins of DNA replication. We also describe recent advances in understanding how the regulatory protein kinases control the progress of the initiation reaction. Finally, we describe the checkpoint mechanisms that function to preserve the integrity of the genome when the normal course of genome duplication is perturbed by factors that damage the DNA or inhibit DNA synthesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biochem.69.1.829
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    STRUCTURE AND FUNCTION OF CYTOCHROME bc COMPLEXES (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 69 (2000), S. 1005-1075 
    Details
    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract The cytochrome bc complexes represent a phylogenetically diverse group of complexes of electron-transferring membrane proteins, most familiarly represented by the mitochondrial and bacterial bc1 complexes and the chloroplast and cyanobacterial b6f complex. All these complexes couple electron transfer to proton translocation across a closed lipid bilayer membrane, conserving the free energy released by the oxidation-reduction process in the form of an electrochemical proton gradient across the membrane. Recent exciting developments include the application of site-directed mutagenesis to define the role of conserved residues, and the emergence over the past five years of X-ray structures for several mitochondrial complexes, and for two important domains of the b6f complex.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.biochem.69.1.1005
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