718 research outputs found

    Two Fundamental Concepts in Skeletal Parallel Programming

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    We define the concepts of nesting mode and interaction mode as they arise in the description of skeletal parallel programming systems. We sugegs

    Expression and regulation of neurotrophic and angiogenic factors during human intervertebral disc degeneration

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    Introduction : The degenerate intervertebral disc (IVD) becomes innervated by sensory nerve fibres, and vascularised by blood vessels. This study aimed to identify neurotrophins, neuropeptides and angiogenic factors within native IVD tissue and to further investigate whether pro-inflammatory cytokines are involved in the regulation of expression levels within nucleus pulposus (NP) cells, nerve and endothelial cells. Methods : Quantitative real-time PCR (qRT-PCR) was performed on 53 human IVDs from 52 individuals to investigate native gene expression of neurotrophic factors and their receptors, neuropeptides and angiogenic factors. The regulation of these factors by cytokines was investigated in NP cells in alginate culture, and nerve and endothelial cells in monolayer using RT-PCR and substance P (SP) protein expression in interleukin-1 (IL-1ß) stimulated NP cells. Results : Initial investigation on uncultured NP cells identified expression of all neurotrophins by native NP cells, whilst the nerve growth factor (NGF) receptor was only identified in severely degenerate and infiltrated discs, and brain derived neurotrophic factor (BDNF) receptor expressed by more degenerate discs. BDNF expression was significantly increased in infiltrated and degenerate samples. SP and vascular endothelial growth factor (VEGF) were higher in infiltrated samples. In vitro stimulation by IL-1ß induced NGF in NP cells. Neurotropin-3 was induced by tumour necrosis factor alpha in human dermal microvascular endothelial cells (HDMECs). SP gene and protein expression was increased in NP cells by IL-1ß. Calcitonin gene related peptide was increased in SH-SY5Y cells upon cytokine stimulation. VEGF was induced by IL-1ß and interleukin-6 in NP cells, whilst pleiotrophin was decreased by IL-1ß. VEGF and pleiotrophin were expressed by SH-SY5Y cells, and VEGF by HDMECs, but were not modulated by cytokines. Conclusions : The release of cytokines, in particular IL-1ß during IVD degeneration, induced significant increases in NGF and VEGF which could promote neuronal and vascular ingrowth. SP which is released into the matrix could potentially up regulate the production of matrix degrading enzymes and also sensitise nerves, resulting in nociceptive transmission and chronic low back pain. This suggests that IL-1ß is a key regulatory cytokine, involved in the up regulation of factors involved in innervation and vascularisation of tissues.</p

    Antiretroviral therapy and the prevalence and incidence of diabetes [2] (multiple letters)

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    In the study by Brown et al,1 the authors did not mention several limitations that might have an important impact on the interpretation of the results. First, the study only included men, who were mostly white (approximately 86%). Therefore, the results cannot be extrapolated to women and other ethnic groups. Second, the family history of diabetes was not ascertained in the study participants, and this could have confounded the magnitude of differences in prevalence and incidence of diabetes between the 2 study groups. Third, the reported prevalence and incidence rates of diabetes were likely to be overestimated because the diagnosis of diabetes was not confirmed by a repeated measurement of fasting plasma glucose

    Nonlinear Time Series Analysis of Sunspot Data

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    This paper deals with the analysis of sunspot number time series using the Hurst exponent. We use the rescaled range (R/S) analysis to estimate the Hurst exponent for 259-year and 11360-year sunspot data. The results show a varying degree of persistence over shorter and longer time scales corresponding to distinct values of the Hurst exponent. We explain the presence of these multiple Hurst exponents by their resemblance to the deterministic chaotic attractors having multiple centers of rotation.Comment: 10 pages, 6 figures, accepted for publication in Solar Physics, journal style corrections done in this versio

    Next generation sequencing (NGS) to improve the diagnosis and management of patients with disorders of sex development (DSD).

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    Disorders of sex development (DSDs) are a diverse group of conditions where the chromosomal, gonadal or anatomical sex can be atypical. The highly heterogeneous nature of this group of conditions often makes determining a genetic diagnosis challenging. Prior to next generation sequencing (NGS) technologies, genetic diagnostic tests were only available for a few of the many DSD associated genes, which consequently had to be tested sequentially. Genetic testing is key in establishing the diagnosis, allowing for personalised management of these patients. Pinpointing the molecular cause of a patient's DSD can significantly impact patient management by informing future development needs, altering management strategies and identifying correct inheritance pattern when counselling family members. We have developed a 30 gene NGS panel, designed to be used as a frontline test for all suspected cases of DSD (both 46,XX and 46,XY cases). We have confirmed a diagnosis in 25 of the 80 patients tested to date. Confirmed diagnoses were linked to mutations in AMH, AMHR2, AR, HSD17B3, HSD3B2, MAMLD1, NR5A1, SRD5A2 and WT1 which have resulted in changes to patient management. The minimum diagnostic yield for patients with 46,XY DSD is 25/73. In 34/80 patients only benign or likely benign variants were identified, and in 21/80 patients only variants of uncertain significance, (VOUS) were identified, resulting in a diagnosis not being confirmed in these individuals. Our data supports previous studies, that an NGS panel approach is a clinically useful and cost effective frontline test for patients with DSDs

    Outcomes of Hormone-Receptor Positive, HER2-Negative Breast Cancers by Race and Tumor Biological Features

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    Background: Black women have higher hormone receptor positive (HR+) breast cancer mortality than White women. Early recurrence rates differ by race, but little is known about genomic predictors of early recurrence among HR+ women. Methods: Using data from the Carolina Breast Cancer Study (phase III, 2008-2013), we estimated associations between race and recurrence among nonmetastatic HR+/HER2-negative tumors, overall and by PAM50 Risk of Recurrence score, PAM50 intrinsic subtype, and tumor grade using survival curves and Cox models standardized for age and stage. Relative frequency differences (RFD) were estimated using multivariable linear regression. To assess intervention opportunities, we evaluated treatment patterns by race among patients with high-risk disease. Results: Black women had higher recurrence risk relative to White women (crude hazard ratio = 1.81, 95% confidence interval [CI] = 1.34 to 2.46), which remained elevated after standardizing for clinical covariates (hazard ratio = 1.42, 95% CI = 1.05 to 1.93). Racial disparities were most pronounced among those with high PAM50 Risk of Recurrence score (5-year standardized recurrence risk = 18.9%, 95% CI = 8.6% to 29.1% in Black women vs 12.5%, 95% CI = 2.0% to 23.0% in White women) and high grade (5-year standardized recurrence risk = 16.6%, 95% CI = 11.7% to 21.5% in Black women vs 12.0%, 95% CI = 7.3% to 16.7% in White women). However, Black women with high-grade tumors were statistically significantly less likely to initiate endocrine therapy (RFD = -8.3%, 95% CI = -15.9% to -0.6%) and experienced treatment delay more often than White women (RFD = +9.0%, 95% CI = 0.3% to 17.8%). Conclusions: Differences in recurrence by race appear greatest among women with aggressive tumors and may be influenced by treatment differences. Efforts to identify causes of variation in cancer treatment are critical to reducing outcome disparities

    Multidimensional Conservation Laws: Overview, Problems, and Perspective

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    Some of recent important developments are overviewed, several longstanding open problems are discussed, and a perspective is presented for the mathematical theory of multidimensional conservation laws. Some basic features and phenomena of multidimensional hyperbolic conservation laws are revealed, and some samples of multidimensional systems/models and related important problems are presented and analyzed with emphasis on the prototypes that have been solved or may be expected to be solved rigorously at least for some cases. In particular, multidimensional steady supersonic problems and transonic problems, shock reflection-diffraction problems, and related effective nonlinear approaches are analyzed. A theory of divergence-measure vector fields and related analytical frameworks for the analysis of entropy solutions are discussed.Comment: 43 pages, 3 figure

    Search for lepton-flavor violation at HERA

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    A search for lepton-flavor-violating interactions epμXe p \to \mu X and epτXe p\to \tau X has been performed with the ZEUS detector using the entire HERA I data sample, corresponding to an integrated luminosity of 130 pb^{-1}. The data were taken at center-of-mass energies, s\sqrt{s}, of 300 and 318 GeV. No evidence of lepton-flavor violation was found, and constraints were derived on leptoquarks (LQs) that could mediate such interactions. For LQ masses below s\sqrt{s}, limits were set on λeq1βq\lambda_{eq_1} \sqrt{\beta_{\ell q}}, where λeq1\lambda_{eq_1} is the coupling of the LQ to an electron and a first-generation quark q1q_1, and βq\beta_{\ell q} is the branching ratio of the LQ to the final-state lepton \ell (μ\mu or τ\tau) and a quark qq. For LQ masses much larger than s\sqrt{s}, limits were set on the four-fermion interaction term λeqαλqβ/MLQ2\lambda_{e q_\alpha} \lambda_{\ell q_\beta} / M_{\mathrm{LQ}}^2 for LQs that couple to an electron and a quark qαq_\alpha and to a lepton \ell and a quark qβq_\beta, where α\alpha and β\beta are quark generation indices. Some of the limits are also applicable to lepton-flavor-violating processes mediated by squarks in RR-Parity-violating supersymmetric models. In some cases, especially when a higher-generation quark is involved and for the process epτXe p\to \tau X , the ZEUS limits are the most stringent to date.Comment: 37 pages, 10 figures, Accepted by EPJC. References and 1 figure (Fig. 6) adde
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