2,161 research outputs found

    Output peak control of nonhomogeneous markov jump system with unit-energy disturbance

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    This paper considers output peak controller design for discrete nonhomogeneous Markov jump systems under unit-energy disturbance. The mode-dependent output peak feedback controller is designed to ensure that the resulting closed-loop system is stochastically stable and the peak of the output is within a specified range. Furthermore, the optimal energy-to-peak gain indices of the mode-dependent and the mode-independent state feedback controllers are evaluated and compared. A numerical example is presented to illustrate the applicability of the results obtained

    Animal Toxicity of Hairpin Pyrrole-Imidazole Polyamides Varies with the Turn Unit

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    A hairpin pyrrole-imidazole polyamide (1) targeted to the androgen receptor consensus half-site was found to exert antitumor effects against prostate cancer xenografts. A previous animal study showed that 1, which has a chiral amine at the α-position of the Îł-aminobutyric acid turn (Îł-turn), did not exhibit toxicity at doses less than 10 mg/kg. In the same study, a polyamide with an acetamide at the ÎČ-position of the Îł-turn resulted in animal morbidity at 2.3 mg/kg. To identify structural motifs that cause animal toxicity, we synthesized polyamides 1–4 with variations at the α- and ÎČ-positions in the Îł-turn. Weight loss, histopathology, and serum chemistry were analyzed in mice post-treatment. While serum concentration was similar for all four polyamides after injection, dose-limiting liver toxicity was only observed for three polyamides. Polyamide 3, with an α-acetamide, caused no significant evidence of rodent toxicity and retains activity against LNCaP xenografts

    A dc voltage step-up transformer based on a bi-layer \nu=1 quantum Hall system

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    A bilayer electron system in a strong magnetic field at low temperatures, with total Landau level filling factor nu =1, can enter a strongly coupled phase, known as the (111) phase or the quantum Hall pseudospin-ferromagnet. In this phase there is a large quantized Hall drag resistivity between the layers. We consider here structures where regions of (111) phase are separated by regions in which one of the layers is depleted by means of a gate, and various of the regions are connected together by wired contacts. We note that with suitable designs, one can create a DC step-up transformer where the output voltage is larger than the input, and we show how to analyze the current flows and voltages in such devices

    Influence of single nucleotide polymorphisms in factor VIII and von Willebrand factor genes on plasma factor VIII activity: the ARIC Study

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    Factor VIII (FVIII) functions as a cofactor for factor IXa in the contact coagulation pathway and circulates in a protective complex with von Willebrand factor (VWF). Plasma FVIII activity is strongly influenced by environmental and genetic factors through VWF-dependent and independent mechanisms. Single nucleotide polymorphisms (SNPs) of the coding and promoter sequence in the FVIII gene have been extensively studied for effects on FVIII synthesis, secretion, and activity, but impacts of non–disease-causing intronic SNPs remain largely unknown. We analyzed FVIII SNPs and FVIII activity in 10 434 healthy Americans of European (EA) or African (AA) descent in the Atherosclerosis Risk in Communities (ARIC) study. Among covariates, age, race, diabetes, and ABO contributed 2.2%, 3.5%, 4%, and 10.7% to FVIII intersubject variation, respectively. Four intronic FVIII SNPs associated with FVIII activity and 8 with FVIII-VWF ratio in a sex- and race-dependent manner. The FVIII haplotypes AT and GCTTTT also associated with FVIII activity. Seven VWF SNPs were associated with FVIII activity in EA subjects, but no FVIII SNPs were associated with VWF Ag. These data demonstrate that intronic SNPs could directly or indirectly influence intersubject variation of FVIII activity. Further investigation may reveal novel mechanisms of regulating FVIII expression and activity

    Probing of a human proteome microarray with a recombinant pathogen protein reveals a novel mechanism by which hookworms suppress B-cell receptor signaling.

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    Na-ASP-2 is an efficacious hookworm vaccine antigen. However, despite elucidation of its crystal structure and studies addressing its immunobiology, the function of Na-ASP-2 has remained elusive. We probed a 9000-protein human proteome microarray with Na-ASP-2 and showed binding to CD79A, a component of the B-cell antigen receptor complex. Na-ASP-2 bound to human B lymphocytes ex vivo and downregulated the transcription of approximately 1000 B-cell messenger RNAs (mRNAs), while only approximately 100 mRNAs were upregulated, compared with control-treated cells. The expression of a range of molecules was affected by Na-ASP-2, including factors involved in leukocyte transendothelial migration pathways and the B-cell signaling receptor pathway. Of note was the downregulated transcription of lyn and pi3k, molecules that are known to interact with CD79A and control B-cell receptor signaling processes. Together, these results highlight a previously unknown interaction between a hookworm-secreted protein and B cells, which has implications for helminth-driven immunomodulation and vaccine development. Further, the novel use of human protein microarrays to identify host-pathogen interactions, coupled with ex vivo binding studies and subsequent analyses of global gene expression in human host cells, demonstrates a new pipeline by which to explore the molecular basis of infectious diseases.This is the author accepted version. The final version is available at http://dx.doi.org/10.1093/infdis/jiu451

    Top and Bottom Seesaw from Supersymmetric Strong Dynamics

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    We propose a top and bottom seesaw model with partial composite top and bottom quarks. Such composite quarks and topcolor gauge bosons are bound states from supersymmetric strong dynamics by Seiberg duality. Supersymmetry breaking also induces the breaking of topcolor into the QCD gauge coupling. The low energy description of our model reduces to a complete non-minimal extension of the top seesaw model with bottom seesaw. The non-minimal nature is crucial for Higgs mixings and the appearance of light Higgs fields. The Higgs fields are bound states of partial composite particles with the lightest one compatible with a 125 GeV Higgs field which was discovered at the LHC.Comment: Minor changes, Published Versio

    Novel Role of Endothelial Derived Exosomal HSPA12B in Regulating Macrophage Inflammatory Responses in Polymicrobial Sepsis

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    Endothelial cell dysfunction contributes to sepsis induced initiate immune response and the infiltration of immune cells into organs, resulting in organ injury. Heat shock protein A12B (HSPA12B) is predominantly expressed in endothelial cells. The present study investigated whether endothelial HSPA12B could regulate macrophage pro-inflammatory response during sepsis. Wild type (WT) and endothelial cell-specific HSPA12B deficient (HSPA12B–/–) mice were subjected to CLP sepsis. Mortality and cardiac function were monitored. Higher mortality, worsened cardiac dysfunction, and greater infiltrated macrophages in the myocardium and spleen were observed in HSPA12B–/– septic mice compared with the WT septic mice. The serum levels of TNF-α and IL-1ÎČ were higher and the levels of IL-10 were lower in HSPA12B–/– septic mice than in WT septic mice. Importantly, endothelial exosomes contain HSPA12B which can be uptaken by macrophages. Interestingly, endothelial exosomal HSPA12B significantly increases IL-10 levels and decreases TNF-α and IL-1ÎČ production in LPS-stimulated macrophages. Mechanistic studies show that endothelial exosomal HSPA12B downregulates NF-ÎșB activation and nuclear translocation in LPS stimulated macrophages. These data suggest that endothelial HSPA12B plays a novel role in the regulation of macrophage pro-inflammatory response via exosomes during sepsis and that sepsis induced cardiomyopathy and mortality are associated with endothelial cell deficiency of HSPA12B

    Two loop electroweak corrections to Bˉ→XsÎł\bar B\rightarrow X_s\gamma and Bs0→Ό+Ό−B_s^0\rightarrow \mu^+\mu^- in the B-LSSM

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    The rare decays Bˉ→XsÎł\bar B\rightarrow X_s\gamma and Bs0→Ό+Ό−B_s^0\rightarrow \mu^+\mu^- are important to research new physics beyond standard model. In this work, we investigate two loop electroweak corrections to Bˉ→XsÎł\bar B\rightarrow X_s\gamma and Bs0→Ό+Ό−B_s^0\rightarrow \mu^+\mu^- in the minimal supersymmetric extension of the SM with local B−LB-L gauge symmetry (B-LSSM), under a minimal flavor violating assumption for the soft breaking terms. In this framework, new particles and new definition of squarks can affect the theoretical predictions of these two processes, with respect to the MSSM. Considering the constraints from updated experimental data, the numerical results show that the B-LSSM can fit the experimental data for the branching ratios of Bˉ→XsÎł\bar B\rightarrow X_s\gamma and Bs0→Ό+Ό−B_s^0\rightarrow \mu^+\mu^-. The results of the rare decays also further constrain the parameter space of the B-LSSM.Comment: 33 pages, 9 figures, Published in EPJ

    Molecular excitation in the Interstellar Medium: recent advances in collisional, radiative and chemical processes

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    We review the different excitation processes in the interstellar mediumComment: Accepted in Chem. Re

    Gender difference in knowledge of tuberculosis and associated health-care seeking behaviors: a cross-sectional study in a rural area of China

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    <p>Abstract</p> <p>Background</p> <p>Tuberculosis (TB) detection under the national TB control program in China follows passive case-finding guidelines, which could be influenced by the accessibility of health service and patient's health-care seeking behaviors. One intriguing topic is the correlation between men and women's knowledge on TB and their health-care seeking behaviors.</p> <p>Methods</p> <p>Two cross-sectional studies were separately carried out in Yangzhong County, a rural area of China. One study, by using systematic sampling method, including 1,200 subjects, was conducted to investigate the TB knowledge among general population. Another study in the same source population screened 33,549 people aged 15 years or over among 20 stratified cluster-sampled villages for identifying prolonged cough patients at households and individual interviews were then carried out. Gender difference in the knowledge of TB and health-care seeking behaviors was analyzed particularly.</p> <p>Results</p> <p>Among general population, only 16.0% (men 17.1% vs. women 15.0%) knew the prolonged cough with the duration of 3 weeks or longer was a symptom for suspicious TB. Fewer women than men knew the local appointed health facility for TB diagnosis and treatment as well as the current free TB service policy. Moreover, women were less likely to learn information about TB and share it with others on their own initiatives. On the contrary, after the onset of the prolonged cough, women (79.2%) were more likely to seek health-care than men (58.6%) did. However, a large part of women preferred to visit the lower level non-hospital health facilities at first such as village clinics and drugstores.</p> <p>Conclusion</p> <p>TB and DOTS program were not well known by rural Chinese. Gender issues should be considered to reduce diagnostic delay of TB and improve both men and women's access to qualified health facility for TB care. Strengthening awareness of TB and improving the accessibility of health-care service is essential in TB control strategy, especially under the current vertical TB control system.</p
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