4,008 research outputs found

    Functional Effects of cMyBP-C Phospho-Mimics in Permeabilized Trabeculae

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    Symposium: Client Counseling and Moral Responsibility

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    Cochran served as moderator and presented an introduction to this symposium titled Client Counseling and Moral Responsibility . It is based on papers and discussion presented at the Professional Responsibility Section panel at the annual meeting of the American Association of Law Schools in Washington, D.C., on January 4, 2003. Members of the panel, Professors Deborah Rhode, Paul Tremblay, and Thomas Shaffer presented three different approaches to moral issues that arise in the client counseling relationship: the directive approach, client-centered counseling and the collaborative model. Under the directive model, a lawyer asserts control of moral issues that arise during legal representation. Client-centered counseling is designed to craft legal solutions which satisfy client interests. Under the collaborative model, the lawyer and client resolve moral issues together through moral discourse. Each provides a different combination of answers to the following questions: 1) Who controls the important decisions in the relationship? and 2) Are the interests of people other than the client taken into consideration in making those decisions

    Functional Differences between the N-Terminal Domains of Mouse and Human Myosin Binding Protein-C

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    The N-terminus of cMyBP-C can activate actomyosin interactions in the absence of Ca2+, but it is unclear which domains are necessary. Prior studies suggested that the Pro-Ala rich region of human cMyBP-C activated force in permeabilized human cardiomyocytes, whereas the C1 and M-domains of mouse cMyBP-C activated force in permeabilized rat cardiac trabeculae. Because the amino acid sequence of the P/A region differs between human and mouse cMyBP-C isoforms (46% identity), we investigated whether species-specific differences in the P/A region could account for differences in activating effects. Using chimeric fusion proteins containing combinations of human and mouse C0, Pro-Ala, and C1 domains, we demonstrate here that the human P/A and C1 domains activate actomyosin interactions, whereas the same regions of mouse cMyBP-C are less effective. These results suggest that species-specific differences between homologous cMyBP-C isoforms confer differential effects that could fine-tune cMyBP-C function in hearts of different species

    Calcium ionophore (A-23187) induced peritoneal eicosanoid biosynthesis: a rapid method to evaluate inhibitors of arachidonic acid metabolism in vivo

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    The present investigation characterizes calcium ionophore (A-23187) induced peritoneal eicosanoid biosynthesis in the rat. Intraperitoneal injection of A-23187 (20 μg/rat) stimulated marked biosynthesis of 6-keto-PGF1α (6-KPA), TxB2, LTC4 and LTB4, with no detectable changes on levels of PGE2. Levels of all eicosanoids decreased rapidly after a peak which was seen as early as 5 min. Enzyme markers of cellular contents of neutrophils and mononuclear cells, MPO and NAG respectively, decreased rapidly after ionophore injection; this was followed by increases after 60 min. Indomethacin, a selective cyclooxygenase inhibitor, and zileuton and ICI D-2138, two selective 5-lipoxygenase inhibitors attenuated prostaglandin and leukotriene pathways respectively. Oral administration of zileuton (20 mg/kg, p.o.) inhibited LTB4 biosynthesis for up to 6 h suggesting a long duration of pharmacological activity in the rats consistent with its longer half-life. The rapid onset and the magnitude of increases in levels of eicosanoids render the ionophore induced peritoneal eicosanoid biosynthesis a useful model to evaluate pharmacological profiles of inhibitors of eicosanoid pathways in vivo

    Technology Assessment of High Capacity Data Storage Systems: Can We Avoid a Data Survivability Crisis?

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    This technology assessment of long-term high capacity data storage systems identifies an emerging crisis of severe proportions related to preserving important historical data in science, healthcare, manufacturing, finance and other fields. For the last 50 years, the information revolution, which has engulfed all major institutions of modem society, centered itself on data-their collection, storage, retrieval, transmission, analysis and presentation. The transformation of long term historical data records into information concepts, according to Drucker, is the next stage in this revolution towards building the new information based scientific and business foundations. For this to occur, data survivability, reliability and evolvability of long term storage media and systems pose formidable technological challenges. Unlike the Y2K problem, where the clock is ticking and a crisis is set to go off at a specific time, large capacity data storage repositories face a crisis similar to the social security system in that the seriousness of the problem emerges after a decade or two. The essence of the storage crisis is as follows: since it could take a decade to migrate a peta-byte of data to a new media for preservation, and the life expectancy of the storage media itself is only a decade, then it may not be possible to complete the transfer before an irrecoverable data loss occurs. Over the last two decades, a number of anecdotal crises have occurred where vital scientific and business data were lost or would have been lost if not for major expenditures of resources and funds to save this data, much like what is happening today to solve the Y2K problem. A pr-ime example was the joint NASA/NSF/NOAA effort to rescue eight years worth of TOVS/AVHRR data from an obsolete system, which otherwise would have not resulted in the valuable 20-year long satellite record of global warming. Current storage systems solutions to long-term data survivability rest on scalable architectures having parallel paths for data migration

    Defining Acute Lung Disease in Children With the Oxygenation Saturation Index

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    Objective: To evaluate whether a formula could be derived using oxygen saturation (Spo2) to replace Pao2 that would allow identification of children with acute lung injury and acute respiratory distress syndrome. Definitions of acute lung injury and acute respiratory distress syndrome require arterial blood gases to determine the Pao2/Fio2 ratio of 300 (acute lung injury) and 200 (acute respiratory distress syndrome). Design: Post hoc data analysis of measurements abstracted from two prospective databases of randomized controlled trials. Setting: Academic pediatric intensive care units. Patients: A total of 255 children enrolled in two large prospective trials of therapeutic intervention for acute lung disease: calfactant and prone positioning. Interventions: Data were abstracted including Pao2, Paco2, pH, Fio2, and mean airway pressure. Repeated-measures analyses, using linear mixed-effects models, were used to build separate prediction equations for the Spo2/Fio2 ratio, oxygenation index [(Fio2 × Mean Airway Pressure)/Pao2], and oxygen saturation index [(Fio2 × Mean Airway Pressure)/Spo2]. A generalization of R2 was used to measure goodness-of-fit. Generalized estimating equations with a logit link were used to calculate the sensitivity and specificity for the cutoffs of Pao2/Fio2 ratio of 200 and 300 and equivalent values of Spo2/Fio2 ratio, oxygenation index, and oxygen saturation index. Measurements and Main Results: An Spo2/Fio2 ratio of 253 and 212 would equal criteria for acute lung injury and acute respiratory distress syndrome, respectively. An oxygenation index of 5.3 would equal acute lung injury criteria, and an oxygenation index of 8.1 would qualify for acute respiratory distress syndrome. An oxygen saturation index, which includes the mean airway pressure and the noninvasive measure of oxygenation, of 6.5 would be equivalent to the acute lung injury criteria, and an oxygen saturation index of 7.8 would equal acute respiratory distress syndrome criteria. Conclusions: Noninvasive methods of assessing oxygenation may be utilized with reasonable sensitivity and specificity to define acute lung injury and acute respiratory distress syndrome, and, with prospective validation, have the potential to increase the number of children enrolled into clinical trials
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