783 research outputs found

    Variable frame based Max-Weight algorithms for networks with switchover delay

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    This paper considers the scheduling problem for networks with interference constraints and switchover delays, where it takes a nonzero time to reconfigure each service schedule. Switchover delay occurs in many telecommunication applications such as satellite, optical or delay tolerant networks (DTNs). Under zero switchover delay it is well known that the Max-Weight algorithm is throughput-optimal without requiring knowledge of the arrival rates. However, we show that this property of Max-Weight no longer holds when there is a nonzero switchover delay. We propose a class of variable frame based Max-Weight (VFMW) algorithms which employ the Max-Weight schedule corresponding to the beginning of the frame during an interval of duration dependent on the queue sizes. The VFMW algorithms dynamically adapt the frame sizes to the stochastic arrivals and provide throughput-optimality without requiring knowledge of the arrival rates. Numerical results regarding the application of the VFMW algorithms to DTN and optical networks demonstrate a good delay performance.National Science Foundation (U.S.) (NSF grant CNS-0626781)National Science Foundation (U.S.) (NSF grant CNS-0915988)United States. Army Research Office (ARO Muri grant number W911NF-08-1-0238

    Comorbid Medical Conditions as Predictors of Overall Survival in Glioblastoma Patients

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    Glioblastoma (GBM) is an aggressive central nervous system tumor with a poor prognosis. This study was conducted to determine any comorbid medical conditions that are associated with survival in GBM. Data were collected from medical records of all patients who presented to VCU Medical Center with GBM between January 2005 and February 2015. Patients who underwent surgery/biopsy were considered for inclusion. Cox proportional hazards regression modeling was performed to assess the relationship between survival and sex, race, and comorbid medical conditions. 163 patients met inclusion criteria. Comorbidities associated with survival on individual-characteristic analysis included: history of asthma (Hazard Ratio [HR]: 2.63; 95% Confidence Interval [CI]: 1.24–5.58; p = 0.01), hypercholesterolemia (HR: 1.95; 95% CI: 1.09–3.50; p = 0.02), and incontinence (HR: 2.29; 95% CI: 0.95–5.57; p = 0.07). History of asthma (HR: 2.22; 95% CI: 1.02–4.83; p = 0.04) and hypercholesterolemia (HR: 1.99; 95% CI: 1.11–3.56; p = 0.02) were associated with shorter survival on multivariable analysis. Surgical patients with GBM who had a prior history of asthma or hypercholesterolemia had significantly higher relative risk for mortality on individual-characteristic and multivariable analyses

    Persistency of Turkish export shocks: a quantile autoregression (QAR) approach

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    This study analyzes the persistency of total and disaggregated Turkish exports for different shock magnitudes using the quantile autoregression (QAR) method in line with Koenker and Xiao (J Am Stat Assoc 99:775–787, 2004). The results suggest that the persistence of shocks are not similar across different quantiles of Total Exports and disaggregated export sectors, indicating an asymmetry in the case of negative and positive shocks across different export sectors. The persistency behavior of Total Exports as well as Food and Beverages, Chemicals, Basic Metals, Raw Materials, Motor Vehicles and Radio & TV exports are asymmetric to negative versus positive shocks, which cannot be captured by traditional unit root tests. Thus, sound interpretation of QAR results is necessary for policy makers to identify shock characteristics and thereby pursue appropriate policies for overcoming adverse impacts on the economy. © 2015, Springer Science+Business Media New York

    Structure-based design and synthesis of antiparasitic pyrrolopyrimidines targeting pteridine reductase 1

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    The treatment of Human African Trypanosomiasis remains a major unmet health need in sub-Saharan Africa. Approaches involving new molecular targets are important and pteridine reductase 1 (PTR1), an enzyme that reduces dihydrobiopterin in Trypanosoma spp. has been identified as a candidate target and it has been shown previously that substituted pyrrolo[2,3-d]pyrimidines are inhibitors of PTR1 from T. brucei (J. Med. Chem. 2010, 53, 221-229). In this study, 61 new pyrrolo[2,3-d]pyrimidines have been prepared, designed with input from new crystal structures of 23 of these compounds complexed with PTR1, and evaluated in screens for enzyme inhibitory activity against PTR1 and in vitro antitrypanosomal activity. 8 compounds were sufficiently active in both screens to take forward to in vivo evaluation. Thus although evidence for trypanocidal activity in a stage I disease model in mice was obtained, the compounds were too toxic to mice for further development

    Gli effetti squelch binaurale e ombra nei bambini con impianto cocleare monolaterale e protesi acustica controlaterale

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    Lo scopo di questo studio è stato quello di indagare il grado di effetto squelch binaurale (BSE) e di effetto ombra (HSE) nei bambini che fanno uso di impianto cocleare (CI) e protesi acustica controlaterale (HA). Sono stati arruolati 19 bambini con CI che indossavano regolarmente una HA. Per valutare la performance vocale in presenza di rumore è stato utilizzato un test di identificazione vocalica. Il test è stato eseguito in tre condizioni di ascolto: (1) ascolto bimodale con sorgente di rumore sul lato HA; (2) ascolto con CI con sorgente di rumore sul lato HA; (3) ascolto con CI con sorgente di rumore sul lato CI. I valori medi di BSE e di HSE osservati sono 11.8% e 17.1% rispettivamente. L’analisi statistica condotta ha evidenziato una differenza significativa sia nel confronto tra le tre condizioni di ascolto che per l’analisi post-hoc (p < 0.001). In conclusione, la maggioranza dei bambini con CI hanno mostrato BSE ed HSE con un miglioramento significativo nella percezione vocale in presenza di rumore

    BRCA1 and BRCA2 mutations in Turkish breast/ovarian families and young breast cancer patients

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    To date, BRCA1 and BRCA2 mutations in breast and/or ovarian patients have not been characterized in the Turkish population. We investigated the presence of BRCA mutations in 53 individuals with a personal and family history of breast and/or ovarian cancer, and 52 individuals with a personal history of breast cancer diagnosed below age 50 without additional family history. We have identified 11 mutations (nine BRCA1 and two BRCA2) using combined techniques involving protein truncation test, direct sequencing and heteroduplex analysis. We found eight out of 53 patients (15.1%) with a family history to carry BRCA gene mutations (seven BRCA1 and one BRCA2). Of these, four were found in 43 families presenting only breast cancer histories, and four were found in families presenting ovarian cancer with or without breast cancer. We also demonstrated two BRCA1 and one BRCA2 mutations in three out of 52 (5.8%) early-onset breast cancer cases without additional family history. Three of nine BRCA1 and both BRCA2 mutations detected in this study were not reported previously. These mutations may be specific to the Turkish population. The BRCA1 5382insC mutation, specific to Ashkenazi and Russian populations, was found twice in our study group, representing a possible founder mutation in the Turkish population. © 2000 Cancer Research Campaig

    Lepton polarization asymmetry in radiative dileptonic B-meson decays in MSSM

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    In this paper we study the polarization asymmetries of the final state lepton in the radiative dileptonic decay of B meson (\bsllg) in the framework of Minimal Supersymmetric Standard Model (MSSM) and various other unified models within the framework of MSSM e.g. mSUGRA, SUGRA (where condition of universality of scalar masses is relaxed) etc. Lepton polarization, in addition of having a longitudinal component (\pl), can have two other components, \pt and \pn, lying in and perpendicular to the decay plane, which are proportional to \ml and hence are significant for final state being μ+ μ−\mu^+ ~ \mu^- or τ+τ˜−\tau^+ \~\tau^-. We analyse the dependence of these polarization asymmetries on the parameters of the various models.Comment: typos corrected to match with published versio

    Chromatin profiling of cortical neurons identifies individual epigenetic signatures in schizophrenia

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    Both heritability and environment contribute to risk for schizophrenia. However, the molecular mechanisms of interactions between genetic and non-genetic factors remain unclear. Epigenetic regulation of neuronal genome may be a presumable mechanism in pathogenesis of schizophrenia. Here, we performed analysis of open chromatin landscape of gene promoters in prefrontal cortical (PFC) neurons from schizophrenic patients. We cataloged cell-type-based epigenetic signals of transcriptional start sites (TSS) marked by histone H3-K4 trimethylation (H3K4me3) across the genome in PFC from multiple schizophrenia subjects and age-matched control individuals. One of the top-ranked chromatin alterations was found in the major histocompatibility (MHC) locus on chromosome 6 highlighting the overlap between genetic and epigenetic risk factors in schizophrenia. The chromosome conformation capture (3C) analysis in human brain cells revealed the architecture of multipoint chromatin interactions between the schizophrenia-associated genetic and epigenetic polymorphic sites and distantly located HLA-DRB5 and BTNL2 genes. In addition, schizophrenia-specific chromatin modifications in neurons were particularly prominent for non-coding RNA genes, including an uncharacterized LINC01115 gene and recently identified BNRNA_052780. Notably, protein-coding genes with altered epigenetic state in schizophrenia are enriched for oxidative stress and cell motility pathways. Our results imply the rare individual epigenetic alterations in brain neurons are involved in the pathogenesis of schizophrenia

    A novel form of recessive limb girdle muscular dystrophy with mental retardation and abnormal expression of alpha-dystroglycan

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    Cataloged from PDF version of article.The limb girdle muscular dystrophies are a heterogeneous group of conditions characterized by proximal muscle weakness and disease onset ranging from infancy to adulthood. We report here eight patients from seven unrelated families affected by a novel and relatively mild form of autosomal recessive limb girdle muscular dystrophy (LGMD2) with onset in the first decade of life and characterized by severe mental retardation but normal brain imaging. Immunocytochemical studies revealed a significant selective reduction of α-dystroglycan expression in the muscle biopsies. Linkage analysis excluded known loci for both limb girdle muscular dystrophy and congenital muscular dystrophies in the consanguineous families. We consider that this represents a novel form of muscular dystrophy with associated brain involvement. The biochemical studies suggest that it may belong to the growing number of muscular dystrophies with abnormal expression of α-dystroglycan. © 2003 Published by Elsevier B.V

    Conserved chromosome 2q31 conformations are associated with transcriptional regulation of GAD1 GABA synthesis enzyme and altered in prefrontal cortex of subjects with schizophrenia

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    Little is known about chromosomal loopings involving proximal promoter and distal enhancer elements regulating GABAergic gene expression, including changes in schizophrenia and other psychiatric conditions linked to altered inhibition. Here, we map in human chromosome 2q31 the 3D configuration of 200 kb of linear sequence encompassing the GAD1 GABA synthesis enzyme gene locus, and we describe a loop formation involving the GAD1 transcription start site and intergenic noncoding DNA elements facilitating reporter gene expression. The GAD1-TSS(-50kbLoop) was enriched with nucleosomes epigenetically decorated with the transcriptional mark, histone H3 trimethylated at lysine 4, and was weak or absent in skin fibroblasts and pluripotent stem cells compared with neuronal cultures differentiated from them. In the prefrontal cortex of subjects with schizophrenia, GAD1-TSS(-50kbLoop) was decreased compared with controls, in conjunction with downregulated GAD1 expression. We generated transgenic mice expressing Gad2 promoter-driven green fluorescent protein-conjugated histone H2B and confirmed that Gad1-TSS(-55kbLoop), the murine homolog to GAD1-TSS(-50kbLoop), is a chromosomal conformation specific for GABAergic neurons. In primary neuronal culture, Gad1-TSS(-55kbLoop) and Gad1 expression became upregulated when neuronal activity was increased. We conclude that 3D genome architectures, including chromosomal loopings for promoter-enhancer interactions involved in the regulation of GABAergic gene expression, are conserved between the rodent and primate brain, and subject to developmental and activity-dependent regulation, and disordered in some cases with schizophrenia. More broadly, the findings presented here draw a connection between noncoding DNA, spatial genome architecture, and neuronal plasticity in development and disease
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