348 research outputs found

    Role of Interfaces in the Proximity Effect in Anisotropic Superconductors

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    We report measurements of the critical temperature of YBCO-Co doped YBCO Superconductor-Normal bilayer films. Depending on the morphology of the S-N interface, the coupling between S and N layers can be turned on to depress the critical temperature of S by tens of degrees, or turned down so the layers appear almost totally decoupled. This novel effect can be explained by the mechanism of quasiparticle transmission into an anisotropic superconductor.Comment: 13 pages, 3 figure

    Amiloride derivatives enhance insulin release in pancreatic islets from diabetic mice

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    BACKGROUND: Amiloride derivatives, commonly used for their diuretic and antihypertensive properties, can also cause a sustained but reversible decrease of intracellular pH (pH(i)). Using dimethyl amiloride (DMA) on normal rodent pancreatic islets, we previously demonstrated the critical influence of islet pH(i )on insulin secretion. Nutrient-stimulated insulin secretion (NSIS) requires a specific pH(i)-range, and is dramatically enhanced by forced intracellular acidification with DMA. Furthermore, DMA can enable certain non-secretagogues to stimulate insulin secretion, and induce time-dependent potentiation (TDP) of insulin release in mouse islets where this function is normally absent. The present study was performed to determine whether pH(i)-manipulation could correct the secretory defect in islets isolated from mice with type 2 diabetes. METHODS: Using two mouse models of type 2 diabetes, we compared a) pHi-regulation, and b) NSIS with and without treatment with amiloride derivatives, in islets isolated from diabetic mice and wild type mice. RESULTS: A majority of the islets from the diabetic mice showed a slightly elevated basal pH(i )and/or poor recovery from acid/base load. DMA treatment produced a significant increase of NSIS in islets from the diabetic models. DMA also enabled glucose to induce TDP in the islets from diabetic mice, albeit to a lesser degree than in normal islets. CONCLUSION: Islets from diabetic mice show some mis-regulation of intracellular pH, and their secretory capacity is consistently enhanced by DMA/amiloride. Thus, amiloride derivatives show promise as potential therapeutic agents for type 2 diabetes

    Observation of Andreev reflection in the c-axis transport of Bi_2Sr_2CaCu_2O_{8+x} single crystals near T_c and search for the preformed-pair state

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    We observed an enhancement of the cc-axis differential conductance around the zero-bias in Au//Bi2_2Sr2_2CaCu2_2O8+x_{8+x} (Bi2212) junctions near the superconducting transition temperature TcT_c. We attribute the conductance enhancement to the Andreev reflection between the surface Cu-O bilayer with suppressed superconductivity and the neighboring superconducting inner bilayer. The continuous evolution from depression to an enhancement of the zero-bias differential conductance, as the temperature approaches TcT_c from below, points to weakening of the barrier strength of the non-superconducting layer between adjacent Cu-O bilayers. We observed that the conductance enhancement persisted up to a few degrees above TcT_c in junctions prepared on slightly overdoped Bi2212 crystals. However, no conductance enhancement was observed above TcT_c in underdoped crystals, although recently proposed theoretical consideration suggests an even wider temperature range of enhanced zero-bias conductance. This seems to provide negative perspective to the existence of the phase-incoherent preformed pairs in the pseudogap state.Comment: 17 pages including 4 figure

    Subharmonic gap structure in d-wave superconductors

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    We present a self-consistent theory of current-voltage characteristics of d-wave/d-wave contacts at arbitrary transparency. In particular, we address the open problem of the observation of subharmonic gap structure (SGS) in cuprate junctions. Our analysis shows that: (i) the SGS is possible in d-wave superconductors, (ii) the existence of bound states within the gap results in an even-odd effect in the SGS, (iii) elastic scattering mechanisms, like impurities or surface roughness, may suppress the SGS, and (iv) in the presence of a magnetic field the Doppler shift of the Andreev bound states leads to a very peculiar splitting of the SGS, which is an unambiguous fingerprint of d-wave superconductivity.Comment: Revtex4, 4 pages, 5 figure

    A Characterization of Scale Invariant Responses in Enzymatic Networks

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    An ubiquitous property of biological sensory systems is adaptation: a step increase in stimulus triggers an initial change in a biochemical or physiological response, followed by a more gradual relaxation toward a basal, pre-stimulus level. Adaptation helps maintain essential variables within acceptable bounds and allows organisms to readjust themselves to an optimum and non-saturating sensitivity range when faced with a prolonged change in their environment. Recently, it was shown theoretically and experimentally that many adapting systems, both at the organism and single-cell level, enjoy a remarkable additional feature: scale invariance, meaning that the initial, transient behavior remains (approximately) the same even when the background signal level is scaled. In this work, we set out to investigate under what conditions a broadly used model of biochemical enzymatic networks will exhibit scale-invariant behavior. An exhaustive computational study led us to discover a new property of surprising simplicity and generality, uniform linearizations with fast output (ULFO), whose validity we show is both necessary and sufficient for scale invariance of enzymatic networks. Based on this study, we go on to develop a mathematical explanation of how ULFO results in scale invariance. Our work provides a surprisingly consistent, simple, and general framework for understanding this phenomenon, and results in concrete experimental predictions

    Connie Myers v. Albertsons, Inc. : Brief of Appellee

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    Appeal of the Judgment of Michael Glasmann Based upon a Jury Verdict Second Judicial District Court Weber County, State of Uta

    Mechanism of insulin gene regulation by the pancreatic transcription factor Pdx-1: Application of pre-mRNA analysis and chromatin immunoprecipitation to assess formation of functional transcriptional complexes

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    The homeodomain factor Pdx-1 regulates an array of genes in the developing and mature pancreas, but whether regulation of each specific gene occurs by a direct mechanism (binding to promoter elements and activating basal transcriptional machinery) or an indirect mechanism (via regulation of other genes) is unknown. To determine the mechanism underlying regulation of the insulin gene by Pdx-1, we performed a kinetic analysis of insulin transcription following adenovirus-mediated delivery of a small interfering RNA specific for pdx-1 into insulinoma cells and pancreatic islets to diminish endogenous Pdx-1 protein, insulin transcription was assessed by measuring both a long half-life insulin mRNA (mature mRNA) and a short half-life insulin pre-mRNA species by real-time reverse transcriptase-PCR. Following progressive knock-down of Pdx-1 levels, we observed coordinate decreases in pre-mRNA levels (to about 40% of normal levels at 72 h). In contrast, mature mRNA levels showed strikingly smaller and delayed declines, suggesting that the longer half-life of this species underestimates the contribution of Pdx-1 to insulin transcription. Chromatin immunoprecipitation assays revealed that the decrease in insulin transcription was associated with decreases in the occupancies of Pdx-1 and p300 at the proximal insulin promoter. Although there was no corresponding change in the recruitment of RNA polymerase II to the proximal promoter, its recruitment to the insulin coding region was significantly reduced. Our results suggest that Pdx-1 directly regulates insulin transcription through formation of a complex with transcriptional coactivators on the proximal insulin promoter. This complex leads to enhancement of elongation by the basal transcriptional machinery. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc

    Quasiclassical description of transport through superconducting contacts

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    We present a theoretical study of transport properties through superconducting contacts based on a new formulation of boundary conditions that mimics interfaces for the quasiclassical theory of superconductivity. These boundary conditions are based on a description of an interface in terms of a simple Hamiltonian. We show how this Hamiltonian description is incorporated into quasiclassical theory via a T-matrix equation by integrating out irrelevant energy scales right at the onset. The resulting boundary conditions reproduce results obtained by conventional quasiclassical boundary conditions, or by boundary conditions based on the scattering approach. This formalism is well suited for the analysis of magnetically active interfaces as well as for calculating time-dependent properties such as the current-voltage characteristics or as current fluctuations in junctions with arbitrary transmission and bias voltage. This approach is illustrated with the calculation of Josephson currents through a variety of superconducting junctions ranging from conventional to d-wave superconductors, and to the analysis of supercurrent through a ferromagnetic nanoparticle. The calculation of the current-voltage characteristics and of noise is applied to the case of a contact between two d-wave superconductors. In particular, we discuss the use of shot noise for the measurement of charge transferred in a multiple Andreev reflection in d-wave superconductors

    Definition of remission and relapse in polymyalgia rheumatica: data from a literature search compared with a Delphi-based expert consensus

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    OBJECTIVE: To compare current definitions of remission and relapse in polymyalgia rheumatica (PMR) with items resulting from a Delphi-based expert consensus. METHODS: Relevant studies including definitions of PMR remission and relapse were identified by literature search in PubMed. The questionnaire used for the Delphi survey included clinical (n=33), laboratory (n=54) and imaging (n=7) parameters retrieved from a literature search. Each item was assessed for importance and availability/practicability, and limits were considered for metric parameters. Consensus was defined by an agreement rate of ≥80%. RESULTS: Out of 6031 articles screened, definitions of PMR remission and relapse were available in 18 and 34 studies, respectively. Parameters used to define remission and/or relapse included history and clinical assessment of pain and synovitis, constitutional symptoms, morning stiffness (MS), physician's global assessment, headache, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), blood count, fibrinogen and/or corticosteroid therapy. In the Delphi exercise a consensus was obtained on the following parameters deemed essential for definitions of remission and relapse: patient's pain assessment, MS, ESR, CRP, shoulder and hip pain on clinical examination, limitation of upper limb elevation, and assessment of corticosteroid dose required to control symptoms. CONCLUSIONS: Assessment of patient's pain, MS, ESR, CRP, shoulder pain/limitation on clinical examination and corticosteroid dose are considered to be important in current available definitions of PMR remission and relapse and the present expert consensus. The high relevance of clinical assessment of hips was unique to this study and may improve specificity and sensitivity of definitions for remission and relapse in PMR

    Ex Vivo Activity of Cardiac Glycosides in Acute Leukaemia

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    BACKGROUND: Despite years of interest in the anti-cancerous effects of cardiac glycosides (CGs), and numerous studies in vitro and in animals, it has not yet been possible to utilize this potential clinically. Reports have demonstrated promising in vitro effects on different targets as well as a possible therapeutic index/selectivity in vitro and in experimental animals. Recently, however, general inhibition of protein synthesis was suggested as the main mechanism of the anti-cancerous effects of CGs. In addition, evidence of species differences of a magnitude sufficient to explain the results of many studies called for reconsideration of earlier results. PRINCIPAL FINDINGS: In this report we identified primary B-precursor and T-ALL cells as being particularly susceptible to the cytotoxic effects of CGs. Digitoxin appeared most potent and IC(50) values for several patient samples were at concentrations that may be achieved in the clinic. Significant protein synthesis inhibition at concentrations corresponding to IC(50) was demonstrated in colorectal tumour cell lines moderately resistant to the cytotoxic effects of digoxin and digitoxin, but not in highly sensitive leukaemia cell lines. CONCLUSION: It is suggested that further investigation regarding CGs may be focused on diagnoses like T- and B-precursor ALL
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