272 research outputs found

    Effective Rheology of Bubbles Moving in a Capillary Tube

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    We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

    Assessment of the Red Cell Proteome of Young Patients with Unexplained Hemolytic Anemia by Two-Dimensional Differential In-Gel Electrophoresis (DIGE)

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    Erythrocyte cytosolic protein expression profiles of children with unexplained hemolytic anemia were compared with profiles of close relatives and controls by two-dimensional differential in-gel electrophoresis (2D-DIGE). The severity of anemia in the patients varied from compensated (i.e., no medical intervention required) to chronic transfusion dependence. Common characteristics of all patients included chronic elevation of reticulocyte count and a negative workup for anemia focusing on hemoglobinopathies, morphologic abnormalities that would suggest a membrane defect, immune-mediated red cell destruction, and evaluation of the most common red cell enzyme defects, glucose-6-phosphate dehydrogenase and pyruvate kinase deficiency. Based upon this initial workup and presentation during infancy or early childhood, four patients classified as hereditary nonspherocytic hemolytic anemia (HNSHA) of unknown etiology were selected for proteomic analysis. DIGE analysis of red cell cytosolic proteins clearly discriminated each anemic patient from both familial and unrelated controls, revealing both patient-specific and shared patterns of differential protein expression. Changes in expression pattern shared among the four patients were identified in several protein classes including chaperons, cytoskeletal and proteasome proteins. Elevated expression in patient samples of some proteins correlated with high reticulocyte count, likely identifying a subset of proteins that are normally lost during erythroid maturation, including proteins involved in mitochondrial metabolism and protein synthesis. Proteins identified with patient-specific decreased expression included components of the glutathione synthetic pathway, antioxidant pathways, and proteins involved in signal transduction and nucleotide metabolism. Among the more than 200 proteins identified in this study are 21 proteins not previously described as part of the erythrocyte proteome. These results demonstrate the feasibility of applying a global proteomic approach to aid characterization of red cells from patients with hereditary anemia of unknown cause, including the identification of differentially expressed proteins as potential candidates with a role in disease pathogenesis

    Structural basis of 7SK RNA 5′-γ-phosphate methylation and retention by MePCE

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    Among RNA 5'-cap structures, γ-phosphate monomethylation is unique to a small subset of noncoding RNAs, 7SK and U6 in humans. 7SK is capped by methylphosphate capping enzyme (MePCE), which has a second nonenzymatic role as a core component of the 7SK ribonuclear protein (RNP), an essential regulator of RNA transcription. We report 2.0- and 2.1-Å X-ray crystal structures of the human MePCE methyltransferase domain bound to S-adenosylhomocysteine (SAH) and uncapped or capped 7SK substrates, respectively. 7SK recognition is achieved by protein contacts to a 5'-hairpin-single-stranded RNA region, thus explaining MePCE's specificity for 7SK and U6. The structures reveal SAH and product RNA in a near-transition-state geometry. Unexpectedly, binding experiments showed that MePCE has higher affinity for capped versus uncapped 7SK, and kinetic data support a model of slow product release. This work reveals the molecular mechanism of methyl transfer and 7SK retention by MePCE for subsequent assembly of 7SK RNP

    Conformation-regulated mechanosensory control via titin domains in cardiac muscle

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    The giant filamentous protein titin is ideally positioned in the muscle sarcomere to sense mechanical stimuli and transform them into biochemical signals, such as those triggering cardiac hypertrophy. In this review, we ponder the evidence for signaling hotspots along the titin filament involved in mechanosensory control mechanisms. On the way, we distinguish between stress and strain as triggers of mechanical signaling events at the cardiac sarcomere. Whereas the Z-disk and M-band regions of titin may be prominently involved in sensing mechanical stress, signaling hotspots within the elastic I-band titin segment may respond primarily to mechanical strain. Common to both stress and strain sensor elements is their regulation by conformational changes in protein domains

    Instruments to assess the perception of physicians in the decision-making process of specific clinical encounters: a systematic review

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    <p>Abstract</p> <p>Background</p> <p>The measurement of processes and outcomes that reflect the complexity of the decision-making process within specific clinical encounters is an important area of research to pursue. A systematic review was conducted to identify instruments that assess the perception physicians have of the decision-making process within specific clinical encounters.</p> <p>Methods</p> <p>For every year available up until April 2007, PubMed, PsycINFO, Current Contents, Dissertation Abstracts and Sociological Abstracts were searched for original studies in English or French. Reference lists from retrieved studies were also consulted. Studies were included if they reported a self-administered instrument evaluating physicians' perceptions of the decision-making process within specific clinical encounters, contained sufficient description to permit critical appraisal and presented quantitative results based on administering the instrument. Two individuals independently assessed the eligibility of the instruments and abstracted information on their conceptual underpinnings, main evaluation domain, development, format, reliability, validity and responsiveness. They also assessed the quality of the studies that reported on the development of the instruments with a modified version of STARD.</p> <p>Results</p> <p>Out of 3431 records identified and screened for evaluation, 26 potentially relevant instruments were assessed; 11 met the inclusion criteria. Five instruments were published before 1995. Among those published after 1995, five offered a corresponding patient version. Overall, the main evaluation domains were: satisfaction with the clinical encounter (n = 2), mutual understanding between health professional and patient (n = 2), mental workload (n = 1), frustration with the clinical encounter (n = 1), nurse-physician collaboration (n = 1), perceptions of communication competence (n = 2), degree of comfort with a decision (n = 1) and information on medication (n = 1). For most instruments (n = 10), some reliability and validity criteria were reported in French or English. Overall, the mean number of items on the modified version of STARD was 12.4 (range: 2 to 18).</p> <p>Conclusion</p> <p>This systematic review provides a critical appraisal and repository of instruments that assess the perception physicians have of the decision-making process within specific clinical encounters. More research is needed to pursue the validation of the existing instruments and the development of patient versions. This will help researchers capture the complexity of the decision-making process within specific clinical encounters.</p

    Supernova remnants: the X-ray perspective

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    Supernova remnants are beautiful astronomical objects that are also of high scientific interest, because they provide insights into supernova explosion mechanisms, and because they are the likely sources of Galactic cosmic rays. X-ray observations are an important means to study these objects.And in particular the advances made in X-ray imaging spectroscopy over the last two decades has greatly increased our knowledge about supernova remnants. It has made it possible to map the products of fresh nucleosynthesis, and resulted in the identification of regions near shock fronts that emit X-ray synchrotron radiation. In this text all the relevant aspects of X-ray emission from supernova remnants are reviewed and put into the context of supernova explosion properties and the physics and evolution of supernova remnants. The first half of this review has a more tutorial style and discusses the basics of supernova remnant physics and thermal and non-thermal X-ray emission. The second half offers a review of the recent advances.The topics addressed there are core collapse and thermonuclear supernova remnants, SN 1987A, mature supernova remnants, mixed-morphology remnants, including a discussion of the recent finding of overionization in some of them, and finally X-ray synchrotron radiation and its consequences for particle acceleration and magnetic fields.Comment: Published in Astronomy and Astrophysics Reviews. This version has 2 column-layout. 78 pages, 42 figures. This replaced version has some minor language edits and several references have been correcte

    First measurement of the |t|-dependence of coherent J/ψ photonuclear production

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    The first measurement of the cross section for coherent J/ψ photoproduction as a function of |t|, the square of the momentum transferred between the incoming and outgoing target nucleus, is presented. The data were measured with the ALICE detector in ultra-peripheral Pb–Pb collisions at a centre-of-mass energy per nucleon pair sNN=5.02TeV with the J/ψ produced in the central rapidity region |y|<0.8, which corresponds to the small Bjorken-x range (0.3−1.4)×10−3. The measured |t|-dependence is not described by computations based only on the Pb nuclear form factor, while the photonuclear cross section is better reproduced by models including shadowing according to the leading-twist approximation, or gluon-saturation effects from the impact-parameter dependent Balitsky–Kovchegov equation. These new results are therefore a valid tool to constrain the relevant model parameters and to investigate the transverse gluonic structure at very low Bjorken-x.publishedVersio

    Sirtuin Deacetylases as Therapeutic Targets in the Nervous System

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    Resolving the strange behavior of extraterrestrial potassium in the upper atmosphere

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    It has been known since the 1960s that the layers of Na and K atoms, which occur between 80 and 105 km in the Earth's atmosphere as a result of meteoric ablation, exhibit completely different seasonal behavior. In the extratropics Na varies annually, with a pronounced wintertime maximum and summertime minimum. However, K varies semiannually with a small summertime maximum and minima at the equinoxes. This contrasting behavior has never been satisfactorily explained. Here we use a combination of electronic structure and chemical kinetic rate theory to determine two key differences in the chemistries of K and Na. First, the neutralization of K+ ions is only favored at low temperatures during summer. Second, cycling between K and its major neutral reservoir KHCO3 is essentially temperature independent. A whole atmosphere model incorporating this new chemistry, together with a meteor input function, now correctly predicts the seasonal behavior of the K layer
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