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  • Articles  (266,486)
  • Technology  (266,486)
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  • 1
    Electronic Resource
    Electronic Resource
    Should We 'Cure' Aging? A Reply to de Grey (2007)
    Berkeley, Calif. : Berkeley Electronic Press (now: De Gruyter)
    Studies in ethics, law and technology 1.2007, 1, art7 
    Details
    ISSN: 1941-6008
    Source: Berkeley Electronic Press Academic Journals
    Topics: Sociology , Technology
    Notes: This is a reply to the discussion piece Life Span Extension Research and Public Debate: Societal Considerations, Studies in Ethics, Law, and Technology by Audrey de Grey. Having read the article there seem to be four messages. The first being, that longevity/immortality research faces rejection, resistance and neglect from `classic anti-aging' researchers, policy makers, the funding system and the public. The second being that the `pro-aging' trance is illogical; the third being that not pushing for longevity and immortality research is immoral; and the fourth being that so far no valid reason for opposing longevity and immortality has been generated and that we will deal with potential problems if and when they appear. My message in this invited comment is 1) that de Grey is right with his first point; 2) that his second point is debatable and depends on certain assumptions; 3) that his third point is even on weaker feet and debatable (Morals and ethics are social and cultural constructions and depending on ones frame of reference something can be seen as moral and ethical or not. This is a whole different paper as to who decides which morals and ethics are right and wrong and can't be covered here.) and 4) that the longevity and immortality research exhibits the same discourse problems as the other new and emerging technology discourses, namely that its makes light of potential and real social risks that it tailors to a minority of the world and ignores the marginalized majority of the world.
    Type of Medium: Electronic Resource
    URL: http://www.bepress.com/selt/vol1/iss1/art7
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  • 2
    Electronic Resource
    Electronic Resource
    Social Perspectives and Genetic Enhancement: Whose Perspective? Whose Choice? (2007)
    Berkeley, Calif. : Berkeley Electronic Press (now: De Gruyter)
    Studies in ethics, law and technology 1.2007, 1, art3 
    Details
    ISSN: 1941-6008
    Source: Berkeley Electronic Press Academic Journals
    Topics: Sociology , Technology
    Notes: This paper's account of the core issues at stake in relation to genetic enhancement is presented as an alternative to mainstream liberal defenses of enhancement. The mainstream arguments are identified as being associated with reproductive autonomy, individual choice, and a `neutral', passive interpretation of technology. The alternative account is associated with the perspective of `woman' or child-bearer, with a fundamental concern for social justice, and an understanding of society in both a global and a contextual sense. This paper adopts a theoretical framework informed by feminist ethics, particularly a feminist ethic of care. The paper begins by outlining some of the key points of the care perspective, highlighting how this contrasts with a mainstream `justice' perspective, and illustrating how this is reflected in arguments relating to genetic enhancement. The paper then turns to a consideration of how a care perspective might be applied to questions of genetic enhancement, and how this may bring forward new issues. This includes in particular a consideration of IVF technologies and how applying understandings from research into this area brings forward usually unaddressed concerns in considering genetic enhancement. The final section of the paper covers some of the questions that there is space to ask once the narrow focus on individual rights is overcome.
    Type of Medium: Electronic Resource
    URL: http://www.bepress.com/selt/vol1/iss1/art3
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  • 3
    Electronic Resource
    Electronic Resource
    An Argument against Arguments for Enhancement (2008)
    Berkeley, Calif. : Berkeley Electronic Press (now: De Gruyter)
    Studies in ethics, law and technology 1.2008, 1, art12 
    Details
    ISSN: 1941-6008
    Source: Berkeley Electronic Press Academic Journals
    Topics: Sociology , Technology
    Notes: The treatment-enhancement distinction is difficult to make, and defenders of enhancement often base their case on that. Critics of enhancement, however, often have prototypical cases of enhancement-oriented interventions in mind, and the ethics of these can be evaluated on a case by case basis. Things like intelligence enhancement may have adverse effects on equality and utility. If the equality and utility effects of such enhancements were sufficiently severe, then restrictions would be called for. We need to think more about how to make tradeoffs between liberty, equality, and utility--and we need to know more about the extent to which each of these is at stake--before reaching conclusions about the ethics of, and appropriate social policy regarding, human enhancement.
    Type of Medium: Electronic Resource
    URL: http://www.bepress.com/selt/vol1/iss1/art12
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  • 4
    Electronic Resource
    Electronic Resource
    Preserving Humanity - and Technology? A Response to de Grey (2008)
    Berkeley, Calif. : Berkeley Electronic Press (now: De Gruyter)
    Studies in ethics, law and technology 1.2008, 1, art11 
    Details
    ISSN: 1941-6008
    Source: Berkeley Electronic Press Academic Journals
    Topics: Sociology , Technology
    Notes: Aubrey de Grey's enthusiasm may or may not be infectious, but it is certainly palpable. And it adds a dimension to the discussion the priority that should be given to life-extension/anti-ageing research of which he seems to be unaware. For on the cusp of developments in emerging technologies we find ourselves button-holed by enthusiasts whose ``transhumanist" visions importunately press upon us the most radical understanding of their implications. My suspicion is that the transhumanist mini-insurgency is partly responsible for the general failure of the policy establishment to summon up the courage and vision to address the implications of emerging technologies at all. The insurgents' effort at ``branding" these technologies as transhumanist (like that of the Raelian flying-saucer cult, a decade ago, to claim cloning as their own) does no favors to the technology. The irony is that de Grey and his fellow-visionaries, far from generating consensus enthusiasm for emerging technology applications, are making them too hot to handle.
    Type of Medium: Electronic Resource
    URL: http://www.bepress.com/selt/vol1/iss1/art11
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  • 5
    Electronic Resource
    Electronic Resource
    Genetic Enhancement and Procreative Autonomy (2008)
    Berkeley, Calif. : Berkeley Electronic Press (now: De Gruyter)
    Studies in ethics, law and technology 1.2008, 1, art9 
    Details
    ISSN: 1941-6008
    Source: Berkeley Electronic Press Academic Journals
    Topics: Sociology , Technology
    Notes: Liberal eugenics according to one version is distinguished from authoritarian eugenics on the basis that the choice of enhancement is devolved to parents. The argument for liberal eugenics combines a commitment to the right of parents to autonomy - in reproductive decisions and in the upbringing of children - and a parity claim that there is no morally significant difference between ante-natal and post-natal alterations of a child. The article reviews the putative constraints on parental choice, and assesses some criticisms of the parity claim. It concludes that a liberal commitment to social justice is in tension with a liberal commitment to parental choice, but judges that the former commitment does not entail the authoritarian eugenics which is represented as the alternative to liberal eugenics.
    Type of Medium: Electronic Resource
    URL: http://www.bepress.com/selt/vol1/iss1/art9
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  • 6
    Electronic Resource
    Electronic Resource
    Liberal Freedoms: Enhancement Is/nt Eugenics? (2007)
    Berkeley, Calif. : Berkeley Electronic Press (now: De Gruyter)
    Studies in ethics, law and technology 1.2007, 1, art8 
    Details
    ISSN: 1941-6008
    Source: Berkeley Electronic Press Academic Journals
    Topics: Sociology , Technology
    Notes: Genomics and the technologies arising out of the science are often heralded as a means of securing cures for diseases which have proved resistant to the progress of medicine. These, generally hereditary diseases, with advances in genomic science are becoming more understood, but as of yet the possibilities of effective cures, whether through for example somatic or germ-line gene therapy, remain elusive. This has not stopped despite speculation and debate on potential future applications such as the use of genetic technologies in enhancing humans. Curative applications and enhancement applications are inextricably linked however both through the social contexts in which these technologies are to be deployed and the discourses which inform and frame the debates on their use. This article seeks to explore these links and in doing so aims to investigate some of the wider dimensions of the enhancement debate.
    Type of Medium: Electronic Resource
    URL: http://www.bepress.com/selt/vol1/iss1/art8
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  • 7
    Electronic Resource
    Electronic Resource
    In Support of Human Enhancement (2008)
    Berkeley, Calif. : Berkeley Electronic Press (now: De Gruyter)
    Studies in ethics, law and technology 1.2008, 1, art10 
    Details
    ISSN: 1941-6008
    Source: Berkeley Electronic Press Academic Journals
    Topics: Sociology , Technology
    Notes: This short comment presents arguments in support of human enhancement.What is enhancement? Surely it is a procedure that improves our functioning: any intervention which increases our general capabilities for human flourishing. We exclude from consideration those procedures often termed ``enhancements" that are of dubious overall benefit (for example breast or penis augmentation, or the taking of anabolic steroids to increase muscle mass). Equally we are not talking of ``designer" modifications which are more akin to aesthetic or fashion preferences than to improvements: hair colour, eye colour, or physique. An enhancement (as we are using the term) is something of benefit to the individual.
    Type of Medium: Electronic Resource
    URL: http://www.bepress.com/selt/vol1/iss1/art10
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  • 8
    Electronic Resource
    Electronic Resource
    Life Span Extension Research and Public Debate: Societal Considerations (2007)
    Berkeley, Calif. : Berkeley Electronic Press (now: De Gruyter)
    Studies in ethics, law and technology 1.2007, 1, art5 
    Details
    ISSN: 1941-6008
    Source: Berkeley Electronic Press Academic Journals
    Topics: Sociology , Technology
    Notes: The pace of a given strand of scientific research, whether purely curiosity-driven or motivated by a particular technological goal, is strongly influenced by public attitudes towards its value. In the case of research directed to the radical postponement of aging and the consequent extension of healthy and total lifespans, public opinion is entrenched in a "pro-aging trance" - a state of resolute irrationality. This arises from the entirely rational attitude to a grisly, inevitable and relatively far-off fate: putting it out of one's mind allows one to make the most of what time one has, free of preoccupation with one's demise, and it is immaterial how irrational the arguments that one uses to achieve this are, e.g. by persuading oneself that aging is not such a bad thing after all. As biotechnology increasingly nears the point where aging will no longer be inevitable, however, this studied fatalism has become a core part of the problem, making people reluctant to join the crusade to hasten that technology's arrival. An effective way to address this hesitation is to promote debate about the reasons people give for fearing the defeat of aging, most of which are sociological. Such debate exposes people to the glaring flaws in their own logic. Thus, the more the debate is sustained and promoted, the harder it is for those flaws to be ignored.
    Type of Medium: Electronic Resource
    URL: http://www.bepress.com/selt/vol1/iss1/art5
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  • 9
    Electronic Resource
    Electronic Resource
    Medical Nanorobotics: Breaking the Trance of Futility in Life Extension Research (A Reply to de Grey) (2007)
    Berkeley, Calif. : Berkeley Electronic Press (now: De Gruyter)
    Studies in ethics, law and technology 1.2007, 1, art6 
    Details
    ISSN: 1941-6008
    Source: Berkeley Electronic Press Academic Journals
    Topics: Sociology , Technology
    Notes: Biogerontologist Aubrey de Grey has suggested that one of the reasons we as a society invest so little in research on combating aging is because we are in an intellectual trance. We think the effort will be futile: aging is immutable, so why try? A healthy skepticism can be a good thing but it is a major mistake to bet against the irresistible force of inexorable technological progress. Over the next few decades, nanotechnology will come to play a pivotal role in the solution to the problem of human aging. Medical nanorobotics, if it can be made to work, can unquestionably offer convenient solutions to all known causes of age-related damage and most likely can also successfully address any new causes of senescence that remain undiscovered today.
    Type of Medium: Electronic Resource
    URL: http://www.bepress.com/selt/vol1/iss1/art6
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  • 10
    Electronic Resource
    Electronic Resource
    Enhancement in Sport, and Enhancement outside Sport (2007)
    Berkeley, Calif. : Berkeley Electronic Press (now: De Gruyter)
    Studies in ethics, law and technology 1.2007, 1, art2 
    Details
    ISSN: 1941-6008
    Source: Berkeley Electronic Press Academic Journals
    Topics: Sociology , Technology
    Notes: Sport is one of the first areas in which enhancement has become commonplace. It is also one of the first areas in which the use of enhancement technologies has been heavily regulated. Some have thus seen sport as a testing ground for arguments about whether to permit enhancement. However, I argue that there are fairness-based objections to enhancement in sport that do not apply as strongly in some other areas of human activity. Thus, I claim that there will often be a stronger case for permitting enhancement outside of sport than for permitting enhancement in sport. I end by considering some methodological implications of this conclusion.
    Type of Medium: Electronic Resource
    URL: http://www.bepress.com/selt/vol1/iss1/art2
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  • 11
    Electronic Resource
    Electronic Resource
    Athlete or Guinea Pig? Sports and Enhancement Research (2007)
    Berkeley, Calif. : Berkeley Electronic Press (now: De Gruyter)
    Studies in ethics, law and technology 1.2007, 1, art1 
    Details
    ISSN: 1941-6008
    Source: Berkeley Electronic Press Academic Journals
    Topics: Sociology , Technology
    Notes: Bioethics has paid little attention to the issues raised by health in athletic competition, with the single exception of the use of prohibited performance enhancements. However, in competitive athletics, the treatment and prevention of athletic injury and the development of training programs designed to maximize athletic achievement share many characteristics with medical innovation and clinical research, and should be understood to constitute enhancement research.Athletes should, in at least some circumstances, be viewed as vulnerable research subjects, akin to desperate patients. Competitive athletes are often encouraged to sacrifice long-term health benefits for short-term gains; cultural mythology about sports and high-stakes financial investments at the organizational level in team sports exercise great influence on individual athletes' range of choices. Technological advances in training, equipment, and injury treatment serve to raise the bar in competitive athletics, in turn increasing not only the risks of harm but the level of expectation with regard to performance, injury, and recovery. It is common for athletes to seek, and teams to offer, intensive and innovative training regimens from which data are gathered, thus transforming innovation into research.As technology continues to enhance the prospects for athletic enhancement, it is time for bioethics to take a closer look at the way competitive athletics highlights the troubling questions posed by enhancement research.
    Type of Medium: Electronic Resource
    URL: http://www.bepress.com/selt/vol1/iss1/art1
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  • 12
    Electronic Resource
    Electronic Resource
    Virtue Ethics and Prenatal Genetic Enhancement (2007)
    Berkeley, Calif. : Berkeley Electronic Press (now: De Gruyter)
    Studies in ethics, law and technology 1.2007, 1, art4 
    Details
    ISSN: 1941-6008
    Source: Berkeley Electronic Press Academic Journals
    Topics: Sociology , Technology
    Notes: In this paper I argue that the virtue ethics tradition can enhance the moral discourse on the ethics of prenatal genetic enhancements in distinctive and valuable ways. Virtue ethics prescribes we adopt a much more provisional stance on the issue of the moral permissibility of prenatal genetic enhancements. A stance that places great care on differentiating between the different stakes involved with developing different phenotypes in our children and the different possible means (environmental vs. genetic manipulation) available to parents for pursuing legitimate concerns of parental love and virtue. Key components of the virtue ethics account of morality, such as the Aristotelian account of happiness, love and the doctrine of the mean, provide an adequate basis for rejecting the claim that it is morally impermissible for parents to pursue (safe and effective) prenatal enhancements. Furthermore, there is good reason to believe that a virtue ethics account of morality could actually support the stronger claim that utilising such interventions can (in certain contexts) be morally required.
    Type of Medium: Electronic Resource
    URL: http://www.bepress.com/selt/vol1/iss1/art4
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  • 13
    Electronic Resource
    Electronic Resource
    Generous Funding for Interventive Aging Research Now? (2008)
    Berkeley, Calif. : Berkeley Electronic Press (now: De Gruyter)
    Studies in ethics, law and technology 1.2008, 1, art13 
    Details
    ISSN: 1941-6008
    Source: Berkeley Electronic Press Academic Journals
    Topics: Sociology , Technology
    Notes: This article examines Aubrey de Grey's case for allocating substantial funding to interventive biogerontological research immediately. The conclusion is that the case is inconclusive and that scientific analyses of costs and probabilities would be needed to defend it properly.
    Type of Medium: Electronic Resource
    URL: http://www.bepress.com/selt/vol1/iss1/art13
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  • 14
    Electronic Resource
    Electronic Resource
    Airway Wall Mechanics (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 47-72 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The dimensions, composition, and stiffness of the airway wall are important determinants of airway cross-sectional area during dynamic collapse in a forced expiration or when airway smooth muscle is constricted. Under these circumstances, airway caliber is determined by an interaction between the forces acting to open the airway (parenchymal tension and wall stiffness) and those acting to close it (smooth-muscle force and surface tension at the inner gas-liquid interface). Experimental measurements and theoretical models of the airway tube law (relationship between cross-sectional area and transmural pressure) are presented. Data are presented for the elastic properties of the wall tissue. Simulations of airway constriction in normal and asthmatic airways are discussed. To the extent possible, comparisons are presented between the various models and existing experimental data.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.47
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  • 15
    Electronic Resource
    Electronic Resource
    A Dedication in Memoriam of Dr. Richard Skalak (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 1-18 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Richard Skalak (1923-1997) played a leadership role in the formative decades of the discipline of biomedical engineering through his technical contributions in biomechanics, his educational influence on students, and his service to many developing societies and journals. But always, the distinguishing marks of his involvement with any activity or person were his generosity, respect and tolerance for others, integrity, and curiosity. These very qualities are what first brought him as a traditional engineer trained in engineering mechanics into the young field of biomedical engineering in the 1960s, and they are what led him to new approaches to cellular and molecular engineering, tissue engineering, and orthopedic biomechanics. His technical papers and lectures on blood cell mechanics, pulmonary circulation, dental implants, and tissue growth were models of clarity and often pointed the way to new areas of exploration, while his personal writings offer advice on life, academic organizations, and the pursuit of significant work. He would be deeply appreciative that this first volume of the Annual Review of Biomedical Engineering is dedicated to his memory.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.1
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  • 16
    Electronic Resource
    Electronic Resource
    Tissue Engineering: Orthopedic Applications (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 19-46 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Because of an aging population and increased occurrence of sports-related injuries, musculoskeletal disorders have become one of the major health concerns in the United States. Current treatments, although fairly successful, do not provide the optimum therapy. These treatments typically rely on donor tissues obtained either from the patient or from another source. The former raises the issue of supply, whereas the latter poses the risk of rejection and disease transfer. This has prompted orthopedic surgeons and scientists to look for viable alternatives. In recent years, tissue engineering has gained increasing support as a method to treat orthopedic disorders. Because it uses principles of engineering, biology, and chemistry, tissue engineering may provide a more effective approach to the treatment of musculoskeletal disorders than traditional methods. This chapter presents a review of current methods and new tissue-engineering techniques for the treatment of disorders affecting bone, ligament, and cartilage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.19
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  • 17
    Electronic Resource
    Electronic Resource
    Engineering and Material Considerations in Islet Cell Transplantation (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 103-127 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The successful application and optimization of cell transplantation will require quantitative engineering design and analysis of cells and materials in which relevant biological processes remain complex and incompletely defined. This report primarily reviews the engineering and material considerations in islet cell transplantation, including established biological constraints and biohybrid devices for cell delivery, as well as available barrier materials and the associated processing strategies directed at the control of solute transport, barrier permeability, and host responses at the biological-material interface. Also described are current areas of investigation with particular promise as enabling technologies for accelerating the clinical effectiveness of islet cell transplantation.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.103
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  • 18
    Electronic Resource
    Electronic Resource
    Bioreactors for Hematopoietic Cell Culture (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 129-152 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Hematopoietic cell culture, or ex vivo expansion of hematopoietic cells, is an enabling technology with many potential applications in bone-marrow transplantation, immunotherapy, gene therapy, and the production of blood products. Hematopoietic cultures are complex, with many different cell types at different stages of development present at any given point in time and never in steady state. Moreover, these cells interact strongly with each other and the environment through cytokines (growth factors) and adhesion molecules, as well as through their metabolism. Despite these significant challenges, cell products produced in bioreactors have shown promise in recent phase 1 clinical trials.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.129
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  • 19
    Electronic Resource
    Electronic Resource
    Implanted Electrochemical Glucose Sensors for the Management of Diabetes (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 153-175 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract By maintaining a near normal (70-120 mg/dL) glucose concentration, diabetic patients can drastically reduce the likelihood of the occurrence of diabetes complications. In the near future, subcutaneously implanted electrochemical glucose sensors will be available to provide frequent or continuous information on which timely treatment decisions, such as insulin injection or glucose source intake, can be based, as well as timely alarm signals. The currently engineered devices are of three types: (a) innocuous microsensors, with actively mass-transporting areas 〈10-3 cm2, replaced twice a week by the patient; (b) self-contained, surgeon-implanted, transmitter-containing packages of 〉1 cm2 area, operating for 〉100 days; and (c) devices transporting subcutaneous fluid to an external sensor, based on implanted microfiltration or microdialysis fibers or on iontophoretic transport of the subcutaneous fluid through the skin.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.153
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  • 20
    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 
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    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.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.477
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  • 21
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    NEUROENGINEERING MODELS OF BRAIN DISEASE (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 577-606 
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    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.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.577
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  • 22
    Electronic Resource
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    CARTILAGE TISSUE REMODELING IN RESPONSE TO MECHANICAL FORCES (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 691-713 
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    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.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.691
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  • 23
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    BIOMECHANICS OF CARDIOVASCULAR DEVELOPMENT (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 1-25 
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    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.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.1
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    MICROENGINEERING OF CELLULAR INTERACTIONS (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 227-256 
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    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.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.227
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    THREE-DIMENSIONAL ULTRASOUND IMAGING (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 457-475 
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    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.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.457
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    MICRODEVICES IN MEDICINE1 (2000)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 2 (2000), S. 551-576 
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    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.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.551
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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 
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    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.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.2.1.633
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    THOMAS MCMAHON: A Dedication in Memoriam (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. xv 
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    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.
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    CARDIAC ENERGY METABOLISM: Models of Cellular Respiration (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 57-81 
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    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.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.57
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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.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.3.1.195
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    COMPUTER MODELING AND SIMULATION OF HUMAN MOVEMENT (2001)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 3 (2001), S. 245-273 
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    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.
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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 
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    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.
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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.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.4.092801.094202
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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.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.4.020702.153434
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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.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.040202.121606
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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.
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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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    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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    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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    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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    Transport of Molecules, Particles, and Cells in Solid Tumors (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 241-263 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Extraordinary advances in molecular biology and biotechnology have led to the development of a vast number of therapeutic anti-cancer agents. To reach cancer cells in a tumor, a blood-borne therapeutic molecule, particle, or cell must make its way into the blood vessels of the tumor and across the vessel wall into the interstitium, which it then must migrate through. Unfortunately, tumors often develop in ways that hinder these steps. The goal of research in this area is to analyze each of these steps experimentally and theoretically and integrate the resulting information into a unified theoretical framework. This paradigm of analysis and synthesis has fostered a better understanding of physiological barriers in solid tumors and aided in the development of novel strategies to exploit and/or overcome these barriers for improved cancer detection and treatment.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.241
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    Injectable Electronic Identification, Monitoring, and Stimulation Systems (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 177-209 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Historically, electronic devices such as pacemakers and neuromuscular stimulators have been surgically implanted into animals and humans. A new class of implants made possible by advances in monolithic electronic design and implant packaging is small enough to be implanted by percutaneous injection through large-gauge hypodermic needles and does not require surgical implantation. Among these, commercially available implants, known as radio frequency identification (RFID) tags, are used for livestock, pet, laboratory animal, and endangered-species identification. The RFID tag is a subminiature glass capsule containing a solenoidal coil and an integrated circuit. Acting as the implanted half of a transcutaneous magnetic link, the RFID tag is powered by and communicates with an extracorporeal magnetic reader. The tag transmits a unique identification code that serves the function of identifying the animal. Millions of RFID tags have been sold since the early 1980s. Based on the success of the RFID tags, research laboratories have developed injectable medical implants, known as micromodules. One type of micromodule, the microstimulator, is designed for use in functional-neuromuscular stimulation. Each microstimulator is uniquely addressable and could comprise one channel of a multichannel functional-neuromuscular stimulation system. Using bidirectional telemetry and commands, from a single extracorporeal transmitter, as many as 256 microstimulators could form the hardware basis for a complex functional-neuromuscular stimulation feedback-control system. Uses include stimulation of paralyzed muscle, therapeutic functional-neuromuscular stimulation, and neuromodulatory functions such as laryngeal stimulation and sleep apnea.
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    Fluid Mechanics of Vascular Systems, Diseases, and Thrombosis (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 299-329 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract The cardiovascular system is an internal flow loop with multiple branches circulating a complex liquid. The hallmarks of blood flow in arteries are pulsatility and branches, which cause wall stresses to be cyclical and nonuniform. Normal arterial flow is laminar, with secondary flows generated at curves and branches. Arteries can adapt to and modify hemodynamic conditions, and unusual hemodynamic conditions may cause an abnormal biological response. Velocity profile skewing can create pockets in which the wall shear stress is low and oscillates in direction. Atherosclerosis tends to localize to these sites and creates a narrowing of the artery lumen-a stenosis. Plaque rupture or endothelial injury can stimulate thrombosis, which can block blood flow to heart or brain tissues, causing a heart attack or stroke. The small lumen and elevated shear rate in a stenosis create conditions that accelerate platelet accumulation and occlusion. The relationship between thrombosis and fluid mechanics is complex, especially in the post-stenotic flow field. New convection models have been developed to predict clinical occlusion from platelet thrombosis in diseased arteries. Future hemodynamic studies should address the complex mechanics of flow-induced, large-scale wall motion and convection of semisolid particles and cells in flowing blood.
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    Cellular Microtransport Processes: Intercellular, Intracellular, and Aggregate Behavior (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 463-503 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Ionic and molecular transfer among cells occurs by a variety of transport processes operative at different length scales. Cell membrane permeability and electrical conductance derive from channel proteins producing pores at the molecular (ultrastructural) scale. Intracellular mobility involves the dynamics of motion through the complex ultrastructure of the cytoplasm. These phenomena unite in the larger-scale (microscopic) process of gross intercellular transfer. When such movement occurs among sufficiently many cells, it in turn begins to reflect their average collective (macroscopic) behavior as bulk tissue. This article surveys selected aspects of intercellular and intracellular transport, with emphasis on detailed mechanistic theory, experimental probes of cellular permeability, and systematic transcendence from small to large length scales.
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    Engineering Design of Optimal Strategies for Blood Clot Dissolution (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 427-461 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Blood clots form under hemodynamic conditions and can obstruct flow during angina, acute myocardial infarction, stroke, deep vein thrombosis, pulmonary embolism, peripheral thrombosis, or dialysis access graft thrombosis. Therapies to remove these clots through enzymatic and/or mechanical approaches require consideration of the biochemistry and structure of blood clots in conjunction with local transport phenomena. Because blood clots are porous objects exposed to local hemodynamic forces, pressure-driven interstitial permeation often controls drug penetration and the overall lysis rate of an occlusive thrombus. Reaction engineering and transport phenomena provide a framework to relate dosage of a given agent to potential outcomes. The design and testing of thrombolytic agents and the design of therapies must account for (a) the binding, catalytic, and systemic clearance properties of the therapeutic enzyme; (b) the dose and delivery regimen; (c) the biochemical and structural aspects of the thrombotic occlusion; (d) the prevailing hemodynamics and anatomical location of the thrombus; and (e) therapeutic constraints and risks of side effects. These principles also impact the design and analysis of local delivery devices.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.427
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    Ultrasound Processing and Computing: Review and Future Directions (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 559-588 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Since the introduction of medical ultrasound in the 1950s, modern diagnostic ultrasound has progressed to see many major diagnostic tools come into widespread clinical use, such as B-mode imaging, color-flow imaging, and spectral Doppler. New applications, such as panoramic imaging, three-dimensional imaging, and quantitative imaging, are now beginning to be offered on some commercial ultrasound machines and are expected to grow in popularity. In this review, we focus on the various algorithms, their processing requirements, and the challenges of these ultrasound modes. Whereas the older, mature B and color-flow modes could be systolically implemented using hardwired components and boards, new applications, such as three-dimensional imaging and image feature extraction, are being implemented more by using programmable processors. This trend toward programmable ultrasound machines will continue, because the programmable approach offers the advantages of quick implementation of new applications without any additional hardware and the flexibility to adapt to the changing requirements of these dynamic new applications.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.559
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    Instrumentation for the Genome Project (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 649-678 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Much of the recent rapid progress in large-scale genomic sequencing has been driven by the dramatic improvements both in the area of biological protocols and in the availability of improved laboratory instrumentation and automation platforms. We discuss recent developments in the area of bioinstrumentation that are contributing to the current revolution in genetic analysis. Examples of systems for laboratory automation are described together with specific single-purpose instruments. Emphasis is placed on those tools that are contributing significantly to the scale-up of genomic mapping and sequencing efforts. In addition, we present a selection of more advanced measurement techniques and instrumentation developments that are likely to contribute significantly to future advances in sequencing and genome analysis.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.649
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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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    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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    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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    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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    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.4.020702.153443
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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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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.040202.121623
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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.
    Type of Medium: Electronic Resource
    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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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.011303.120723
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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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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.040202.121606
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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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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.040202.121537
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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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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.011303.120714
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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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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.011303.120731
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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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    URL: http://dx.doi.org/10.1146/annurev.bioeng.5.011303.120719
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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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    URL: http://dx.doi.org/10.1146/annurev.bioeng.6.040803.140027
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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
    Type of Medium: Electronic Resource
    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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    URL: http://dx.doi.org/10.1146/annurev.bioeng.6.040803.140100
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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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    URL: http://dx.doi.org/10.1146/annurev.bioeng.6.040803.140250
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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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    URL: http://dx.doi.org/10.1146/annurev.bioeng.6.040803.140210
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    QUANTUM DOTS AS CELLULAR PROBES (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 7 (2005), S. 55-76 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Robust and bright light emitters, semiconductor nanocrystals [quantum dots (QDs)] have been adopted as a new class of fluorescent labels. Six years after the first experiments of their uses in biological applications, there have been dramatic improvements in understanding surface chemistry, biocompatibility, and targeting specificity. Many studies have shown the great potential of using quantum dots as new probes in vitro and in vivo. This review summarizes the recent advances of quantum dot usage at the cellular level, including immunolabeling, cell tracking, in situ hybridization, FRET, in vivo imaging, and other related technologies. Limitations and potential future uses of quantum dot probes are also discussed.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.7.060804.100432
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    INSTRUMENTATION ASPECTS OF ANIMAL PET (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 7 (2005), S. 255-285 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Biological research has been accelerated by the development of noninvasive imaging techniques and by use of genetically engineered mice to model human diseases and normal development. Because these mice can be expensive, noninvasive imaging techniques, such as high-resolution positron emission tomography (PET), that permit longitudinal studies of the same animals are very attractive. Such studies reduce the number of animals used, reduce intersubject variability, and improve the accuracy of biological models. PET provides quantitative measurements of the spatiotemporal distribution of radiotracers and is an extremely powerful tool in using molecular imaging to study biology, to monitor disease intervention, and to establish pharmacokinetics for new drugs. The design of animal PET scanners has improved significantly in the past decade and can provide adequate image resolution and sensitivity to study transgenic mice. This article reviews the fundamental and technical challenges of small-animal PET imaging, with a particular focus on the latest developments and future directions of detector technologies and system design.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.6.040803.140021
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    DETERMINISTIC AND STOCHASTIC ELEMENTS OF AXONAL GUIDANCE (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 7 (2005), S. 187-221 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: An enormous literature has been developed on investigations of the growth and guidance of axons during development and after injury. In this review, we provide a guide to this literature as a resource for biomedical investigators. We first review briefly the molecular biology that is known to regulate migration of the growth cone and branching of axonal arbors. We then outline some important fundamental considerations that are important to the modeling of the phenomenology of these guidance effects and of what is known of their underlying internal mechanisms. We conclude by providing some thoughts on the outlook for future biomedical modeling in the field.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.7.060804.100446
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    BIOCHEMISTRY AND BIOMECHANICS OF CELL MOTILITY (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 7 (2005), S. 105-150 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Cell motility is an essential cellular process for a variety of biological events. The process of cell migration requires the integration and coordination of complex biochemical and biomechanical signals. The protrusion force at the leading edge of a cell is generated by the cytoskeleton, and this force generation is controlled by multiple signaling cascades. The formation of new adhesions at the front and the release of adhesions at the rear involve the outside-in and inside-out signaling mediated by integrins and other adhesion receptors. The traction force generated by the cell on the extracellular matrix (ECM) regulates cell-ECM adhesions, and the counter force exerted by ECM on the cell drives the migration. The polarity of cell migration can be amplified and maintained by the feedback loop between the cytoskeleton and cell-ECM adhesions. Cell migration in three-dimensional ECM has characteristics distinct from that on two-dimensional ECM. The migration of cells is initiated and modulated by external chemical and mechanical factors, such as chemoattractants and the mechanical forces acting on the cells and ECM, as well as the surface density, distribution, topography, and rigidity of the ECM.
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    FUNCTIONAL ELECTRICAL STIMULATION FOR NEUROMUSCULAR APPLICATIONS * (2005)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 7 (2005), S. 327-360 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Paralyzed or paretic muscles can be made to contract by applying electrical currents to the intact peripheral motor nerves innervating them. When electrically elicited muscle contractions are coordinated in a manner that provides function, the technique is termed functional electrical stimulation (FES). In more than 40 years of FES research, principles for safe stimulation of neuromuscular tissue have been established, and methods for modulating the strength of electrically induced muscle contractions have been discovered. FES systems have been developed for restoring function in the upper extremity, lower extremity, bladder and bowel, and respiratory system. Some of these neuroprostheses have become commercialized products, and others are available in clinical research settings. Technological developments are expected to produce new systems that have no external components, are expandable to multiple applications, are upgradable to new advances, and are controlled by a combination of signals, including biopotential signals from nerve, muscle, and the brain.
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    Automatic Implantable Cardioverter-defibrillators (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 331-346 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Ventricular fibrillation, a loss of synchronus electrical activity in the heart which leads to hemodynamic collapse, is a leading cause of death. Because of the devastating personal and societal effects of this phenomenon, the automatic cardioverter-defibrillator has been developed for automatic detection and termination of the arrhythmia and is in widespread clinical use. Advances in circuits, leads, waveforms, and signal processing along with increased knowledge of the mechanisms of fibrillation have led to continuing improvements in this device, extending its use to many patients. A device has also been developed for the automatic or semiautomatic treatment of atrial fibrillation, an arrhythmia less life-threatening than ventricular fibrillation, but still a serious health problem. Continued improvement of these devices and the development of qualitatively new approaches hold great promise for exciting therapeutic advances in this area.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.331
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    Microfabrication in Biology and Medicine (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 401-425 
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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Microfabrication uses integrated-circuit manufacturing technology supplemented by its own processes to create objects with dimensions in the range of micrometers to millimeters. These objects can have miniature moving parts, stationary structures, or both. Microfabrication has been used for many applications in biology and medicine. These applications fall into four domains: tools for molecular biology and biochemistry, tools for cell biology, medical devices, and biosensors. Microfabricated device structures may provide significantly enhanced function with respect to a conventional device. Sometimes microfabrication can enable devices with novel capabilities. These enhancing and enabling qualities are conferred when microfabrication is used appropriately to address the right types of problems. Herein, we describe microfabrication technology and its application to biology and medicine. We detail several classes of advantages conferred by microfabrication and how these advantages have been used to date.
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    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.401
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    New Strategies for Protein Crystal Growth (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 505-534 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Protein crystallization is the most difficult and time-consuming step in the determination of a protein's atomic structure. As X-ray diffraction becomes a commonly available tool in structural biology, the necessity for rational methodologies and protocols to produce single, high-quality protein crystals has come to the forefront. The basics of protein crystallization conform to the classical understanding of crystallization of small molecules. Understanding the effect of solution variables such as pH, temperature, pressure, and ionicity on protein solubility allows the proper evaluation of the degree of supersaturation present in protein crystallization experiments. Physicochemical measurements such as laser light scattering, X-ray scattering, X-ray diffraction, and atomic force microscopy provide a clearer picture of protein crystal nucleation and growth. This ever deepening knowledge base is generating rational methods to produce protein crystals as well as means to improve the diffraction quality of such protein crystals. Yet, much remains unclear, and the protein crystallization research community will be quite active for many years to come.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.505
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    Imaging Transgenic Animals (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 611-648 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Transgenic and eugenic animals as small as 30 g can be studied noninvasively by radionuclides with resolutions of 1-2 mm, by MRI with resolution of 100 mum and by light fluorescence and bioluminescence with high sensitivities. The technologies of radionuclide emission, magnetic resonance imaging, magnetic resonance spectroscopy, optical tomography, optical fluorescence and optical bioluminescence are currently being applied to small-animal studies. These technologies and examples of their applications are reviewed in this chapter.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.611
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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 
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    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 
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    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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    3-D Visualization in Biomedical Applications (1999)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biomedical Engineering 1 (1999), S. 377-399 
    Details
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Abstract Visualizable objects in biology and medicine extend across a vast range of scale, from individual molecules and cells through the varieties of tissue and interstitial interfaces to complete organs, organ systems, and body parts. These objects include functional attributes of these systems, such as biophysical, biomechanical, and physiological properties. Visualization in three dimensions of such objects and their functions is now possible with the advent of high-resolution tomographic scanners and imaging systems. Medical applications include accurate anatomy and function mapping, enhanced diagnosis, accurate treatment planning and rehearsal, and education/training. Biologic applications include study and analysis of structure-to-function relationships in individual cells and organelles. The potential for revolutionary innovation in the practice of medicine and in biologic investigations lies in direct, fully immersive, real-time multisensory fusion of real and virtual information data streams into online, real-time visualizations available during actual clinical procedures or biological experiments. Current high-performance computing, advanced image processing, and high-fidelity rendering capabilities have facilitated major progress toward realization of these goals. With these advances in hand, there are several important applications of three-dimensional visualization that will have a significant impact on the practice of medicine and on biological research.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.bioeng.1.1.377
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