496 research outputs found

    DNET: A communications facility for distributed heterogeneous computing

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    This document describes DNET, a heterogeneous data communications networking facility. DNET allows programs operating on hosts on dissimilar networks to communicate with one another without concern for computer hardware, network protocol, or operating system differences. The overall DNET network is defined as the collection of host machines/networks on which the DNET software is operating. Each underlying network is considered a DNET 'domain'. Data communications service is provided between any two processes on any two hosts on any of the networks (domains) that may be reached via DNET. DNET provides protocol transparent, reliable, streaming data transmission between hosts (restricted, initially to DECnet and TCP/IP networks). DNET also provides variable length datagram service with optional return receipts

    Renormalization of Coulomb interactions in s-wave superconductor Nax_xCoO2_2

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    We study the renormalized Coulomb interactions due to retardation effect in Nax_xCoO2_2. Although the Morel-Anderson's pseudo potential for a1ga_{1g} orbital μa1g\mu^*_{a1g} is relatively large because the direct Coulomb repulsion UU is large, that for interband transition between a1ga_{1g} and ege_g' orbitals μa1g,eg\mu^*_{a1g,eg'} is very small since the renormalization factor for pair hopping JJ is square of that for UU. Therefore, the s-wave superconductivity due to valence-band Suhl-Kondo mechanism will survive against strong Coulomb interactions. The interband hopping of Cooper pairs due to shear phonons is essential to understand the superconductivity in Nax_xCoO2_2.Comment: 2pages, 2figures, Proceedings of ICM in Kyoto, 200

    Unification of bulk and interface electroresistive switching in oxide systems

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    We demonstrate that the physical mechanism behind electroresistive switching in oxide Schottky systems is electroformation, as in insulating oxides. Negative resistance shown by the hysteretic current-voltage curves proves that impact ionization is at the origin of the switching. Analyses of the capacitance-voltage and conductance-voltage curves through a simple model show that an atomic rearrangement is involved in the process. Switching in these systems is a bulk effect, not strictly confined at the interface but at the charge space region.Comment: 4 pages, 3 figures, accepted in PR

    Changes in CD4+ cells’ miRNA expression following exposure to HIV-1

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    Background: MiRNAs inhibit HIV-1 expression by either modulating host innate immunity or by directly interfering with viral mRNAs. Here, we investigated the miRNA profile that discriminates different classes of HIV-1 infected patients from multiple exposed uninfected individuals. Methods: The expression levels of 377 miRNAs were selectively analyzed in CD4+ cells isolated from whole blood of HIV-1 \ue9lite LTNP (\ue9LTNP), naive, and multiply exposed uninfected individuals (MEU). MiRNA extraction was performed by the mirVana miRNA Isolation Kit (Ambion) and their expression was subsequently examined by real-time PCR-based arrays. The expression of miRNAs was also determined in primary culture of CD4+T cells and monocyte-macrophages infected in vitro by R5 strains. Expression of Dicer and Drosha was evaluated by real-time PCR. Results: We only considered miRNAs that were expressed in the 70% of patients of at least one class and varied by at least 1 log10 from healthy controls. Out of 377 miRNAs, 26 were up-regulated, while 88 were down-regulated. Statistical analysis showed that 21 miRNAs significantly differentiated \ue9LTNP from MEU and 23 miRNAs distinguished naive from MEU, while only 1 (miR-155) discriminated \ue9LTNP from naive. By hierarchical clustering of the miRNAs according to patient class, \ue9LTNP clustered with naive whereas all MEU subjects grouped together. The Dicer and Drosha expression in the patient classes correlated with miRNA profile changes. Among miRNAs differentially expressed in patient classes, 32 were detected in in vitro infection model: the most of the up-regulated miRNAs were expressed in monocyte-macrophages, whereas the most of the down-regulated miRNAs were expressed in T lymphocytes. Conclusions: These findings support that miRNA profile could be the result not only of a productive infection, but also of the exposure to HIV products that leave a signature in immune cells. These data provide some intriguing issues relative to the development of HIV vaccines targeting viral proteins

    Prevalence, Metabolic Features, and Prognosis of Metabolically Healthy Obese Italian Individuals: The Cremona Study

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    OBJECTIVE: Some obese individuals have normal insulin sensitivity. It is controversial whether this phenotype is associated with increased all-cause mortality risk. RESEARCH DESIGN AND METHODS: Fifteen-year all-cause mortality data were obtained through the Regional Health Registry for 2,011 of 2,074 Caucasian middle-aged individuals of the Cremona Study, a population study on the prevalence of diabetes in Italy. Individuals were divided in four categories according to BMI (nonobese: <30 kg/m\ub2; obese: 6530 kg/m\ub2) and estimated insulin resistance (insulin sensitive: homeostasis model assessment of insulin resistance <2.5; insulin resistant 652.5). RESULTS: Obese insulin-sensitive subjects represented 11% (95% CI 8.1-14.5) of the obese population. This phenotype had similar BMI but lower waist circumference, blood pressure, fasting glucose, triglycerides, and fibrinogen and higher HDL cholesterol than obese insulin-resistant subjects. In the 15-year follow-up, 495 deaths (cardiovascular disease [CVD]: n = 221; cancer: n = 180) occurred. All-cause mortality adjusted for age and sex was higher in the obese insulin-resistant subjects (hazard ratio 1.40 [95% CI 1.08-1.81], P = 0.01) but not in the obese insulin-sensitive subjects (0.99 [0.46-2.11], P = 0.97) when compared with nonobese insulin-sensitive subjects. Also, mortality for CVD and cancer was higher in the obese insulin-resistant subjects but not in the obese insulin-sensitive subjects when compared with nonobese insulin-sensitive subjects. CONCLUSIONS: In contrast to obese insulin-resistant subjects, metabolically healthy obese individuals are less common than previously thought and do not show increased all-cause, cancer, and CVD mortality risks in a 15-year follow-up study

    Association Between Plasma Monocyte Chemoattractant Protein-1 Concentration and Cardiovascular Disease Mortality in Middle-Aged Diabetic and Nondiabetic Individuals

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    OBJECTIVE Monocyte chemoattractant protein-1 (MCP-1/CCL2) is a chemokine involved into the pathogenesis of atherosclerosis and has prognostic value in the acute and chronic phases in patients with acute coronary syndromes. RESEARCH DESIGN AND METHODS MCP-1/CCL2 concentration was measured in plasma fractions of 363 middle-aged overweight/obese individuals (aged 61 \ub1 12 years, BMI 30.1 \ub1 6.6 kg/m2, 15% with type 2 diabetes, and 12% with impaired glucose tolerance) of a population survey carried out in 1990\u20131991 in Lombardy, Italy (Cremona Study), and cardiovascular disease (CVD) mortality was assessed in 2006 through Regional Health Registry files. RESULTS At baseline MCP-1/CCL2 was increased in individuals with type 2 diabetes (P < 0.05) and showed significant correlations with biochemical risk markers of atherosclerosis. After 15 years, among the 363 subjects, there were 82 deaths due to CVD. In univariate analysis age, sex, fasting glucose and insulin, fibrinogen, glucose tolerance status, smoking habit, and MCP-1/CCL2 were associated with CVD mortality. Age, sex, fasting serum glucose, MCP-1/CCL2, and smoking habit maintained an independent association with CVD mortality in multiple regression analysis. In a subgroup of 113 subjects in whom data for C-reactive protein (CRP) were available, its level was not predictive of CVD mortality. CONCLUSIONS In middle-aged overweight/obese individuals MCP-1/CCL2 was independently associated with CVD mortality. Further studies will be necessary to establish its role as a surrogate biomarker and as a potential therapeutic target

    Insulin resistance in type 1 diabetes: what is ‘double diabetes’ and what are the risks?

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    In this review, we explore the concept of ‘double diabetes’, a combination of type 1 diabetes with features of insulin resistance and type 2 diabetes. After considering whether double diabetes is a useful concept, we discuss potential mechanisms of increased insulin resistance in type 1 diabetes before examining the extent to which double diabetes might increase the risk of cardiovascular disease (CVD). We then go on to consider the proposal that weight gain from intensive insulin regimens may be associated with increased CV risk factors in some patients with type 1 diabetes, and explore the complex relationships between weight gain, insulin resistance, glycaemic control and CV outcome. Important comparisons and contrasts between type 1 diabetes and type 2 diabetes are highlighted in terms of hepatic fat, fat partitioning and lipid profile, and how these may differ between type 1 diabetic patients with and without double diabetes. In so doing, we hope this work will stimulate much-needed research in this area and an improvement in clinical practice

    Separating and visualising protein assemblies by means of preparative mass spectrometry and microscopy

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    a b s t r a c t Many multi-protein assemblies exhibit characteristics which hamper their structural and dynamical characterization. These impediments include low copy number, heterogeneity, polydispersity, hydrophobicity, and intrinsic disorder. It is becoming increasingly apparent that both novel and hybrid structural biology approaches need to be developed to tackle the most challenging targets. Nanoelectrospray mass spectrometry has matured over the last decade to enable the elucidation of connectivity and composition of large protein assemblies. Moreover, comparing mass spectrometry data with transmission electron microscopy images has enabled the mapping of subunits within topological models. Here we describe a preparative form of mass spectrometry designed to isolate specific protein complexes from within a heterogeneous ensemble, and to &apos;soft-land&apos; these target complexes for ex situ imaging. By building a retractable probe incorporating a versatile target holder, and modifying the ion optics of a commercial mass spectrometer, we show that we can steer the macromolecular ion beam onto a target for imaging by means of transmission electron microscopy and atomic force microscopy. Our data for the tetradecameric chaperonin GroEL show that not only are the molecular volumes of the landed particles consistent with the overall dimensions of the complex, but also that their gross topological features can be maintained
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