698 research outputs found

    Level Crossing Rate of Macrodiversity System in the Presence of Multipath Fading and Shadowing

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    Macrodiversity system including macrodiversity SC receiver and two microdiversity SC receivers is considered in this paper. Received signal experiences, simultaneously, both, long term fading and short term fading. Microdiversity SC receivers reduces Rayleigh fading effects on system performance and macrodiversity SC receiver mitigate Gamma shadowing effects on system performance. Closed form expressions for level crossing rate of microdiversity SC receivers output signals envelopes are calculated. This expression is used for evaluation of level crossing rate of macrodiversity SC receiver output signal envelope. Numerical expressions are illustrated to show the influence of Gamma shadowing severity on level crossing rate

    Compressive Inverse Scattering II. SISO Measurements with Born scatterers

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    Inverse scattering methods capable of compressive imaging are proposed and analyzed. The methods employ randomly and repeatedly (multiple-shot) the single-input-single-output (SISO) measurements in which the probe frequencies, the incident and the sampling directions are related in a precise way and are capable of recovering exactly scatterers of sufficiently low sparsity. For point targets, various sampling techniques are proposed to transform the scattering matrix into the random Fourier matrix. The results for point targets are then extended to the case of localized extended targets by interpolating from grid points. In particular, an explicit error bound is derived for the piece-wise constant interpolation which is shown to be a practical way of discretizing localized extended targets and enabling the compressed sensing techniques. For distributed extended targets, the Littlewood-Paley basis is used in analysis. A specially designed sampling scheme then transforms the scattering matrix into a block-diagonal matrix with each block being the random Fourier matrix corresponding to one of the multiple dyadic scales of the extended target. In other words by the Littlewood-Paley basis and the proposed sampling scheme the different dyadic scales of the target are decoupled and therefore can be reconstructed scale-by-scale by the proposed method. Moreover, with probes of any single frequency \om the coefficients in the Littlewood-Paley expansion for scales up to \om/(2\pi) can be exactly recovered.Comment: Add a new section (Section 3) on localized extended target

    Inhibition of c-Kit signaling is associated with reduced heat and cold pain sensitivity in humans

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    The tyrosine kinase receptor c-Kit is critically involved in the modulation of nociceptive sensitivity in mice. Ablation of the c-Kit gene results in hyposensitivity to thermal pain, while c-Kit activation produces hypersensitivity to the noxious heat, without altering sensitivity to innocuous mechanical stimuli. In this study we investigated the role of c-Kit signalling in human pain perception. We hypothesized that subjects treated with Imatinib or Nilotinib, potent inhibitors of tyrosine kinases including c-Kit, but also Abl1, PDFGFR{alpha}, and PDFGFR{beta}, that are used to treat chronic myeloid leukemia (CML), would experience changes in thermal pain sensitivity. We examined 31 asymptomatic CML patients (14 male, 17 female) under Imatinib/Nilotinib treatment and compared them to 39 age- and sex-matched healthy controls (12 male, 27 female). We used cutaneous heat and cold stimulation to test normal and noxious thermal sensitivity, and a grating orientation task to assess tactile acuity. Thermal pain thresholds were significantly increased in the Imatinib/Nilotinib-treated group, while innocuous thermal and tactile thresholds were unchanged compared to the control group. In conclusion, our findings suggest that the biological effects of c-Kit inhibition are comparable in mice and humans in that c-Kit activity is required to regulate thermal pain sensitivity, but does not affect innocuous thermal and mechanical sensation. The effect on experimental heat pain observed in our study is comparable to that of several common analgesics, thus modulation of the c-Kit pathway can be used to specifically modulate noxious heat and cold sensitivity in humans

    Covariation Among Vowel Height Effects on Acoustic Measures

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    Covariation among vowel height effects on vowel intrinsic fundamental frequency (IF0), voice onset time (VOT), and voiceless interval duration (VID) is analyzed to assess the plausibility of a common physiological mechanism underlying variation in these measures. Phrases spoken by 20 young adults, containing words composed of initial voiceless stops or /s/ and high or low vowels, were produced in habitual and voluntarily increased F0 conditions. High vowels were associated with increased IF0 and longer VIDs. VOT and VID exhibited significant covariation with IF0 only for males at habitua

    Bestrophin 1 is indispensable for volume regulation in human retinal pigment epithelium cells

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    In response to cell swelling, volume-regulated anion channels (VRACs) participate in a process known as regulatory volume decrease (RVD). Only recently, first insight into the molecular identity of mammalian VRACs was obtained by the discovery of the leucine-rich repeats containing 8A (LRRC8A) gene. Here, we show that bestrophin 1 (BEST1) but not LRRC8A is crucial for volume regulation in human retinal pigment epithelium (RPE) cells. Whole-cell patch-clamp recordings in RPE derived from human-induced pluripotent stem cells (hiPSC) exhibit an outwardly rectifying chloride current with characteristic functional properties of VRACs. This current is severely reduced in hiPSC-RPE cells derived from macular dystrophy patients with pathologic BEST1 mutations. Disruption of the orthologous mouse gene (Best1−/−) does not result in obvious retinal pathology but leads to a severe subfertility phenotype in agreement with minor endogenous expression of Best1 in murine RPE but highly abundant expression in mouse testis. Sperm from Best1−/− mice showed reduced motility and abnormal sperm morphology, indicating an inability in RVD. Together, our data suggest that the molecular identity of VRACs is more complex—that is, instead of a single ubiquitous channel, VRACs could be formed by cell type- or tissue-specific subunit composition. Our findings provide the basis to further examine VRAC diversity in normal and diseased cell physiology, which is key to exploring novel therapeutic approaches in VRAC-associated pathologies

    Cell-Autonomous Death of Cerebellar Purkinje Neurons with Autophagy in Niemann-Pick Type C Disease

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    Niemann-Pick type C is a neurodegenerative lysosomal storage disorder caused by mutations in either of two genes, npc1 and npc2. Cells lacking Npc1, which is a transmembrane protein related to the Hedgehog receptor Patched, or Npc2, which is a secreted cholesterol-binding protein, have aberrant organelle trafficking and accumulate large quantities of cholesterol and other lipids. Though the Npc proteins are produced by all cells, cerebellar Purkinje neurons are especially sensitive to loss of Npc function. Since Niemann-Pick type C disease involves circulating molecules such as sterols and steroids and a robust inflammatory response within the brain parenchyma, it is crucial to determine whether external factors affect the survival of Purkinje cells (PCs). We investigated the basis of neurodegeneration in chimeric mice that have functional npc1 in only some cells. Death of mutant npc1 cells was not prevented by neighboring wild-type cells, and wild-type PCs were not poisoned by surrounding mutant npc1 cells. PCs undergoing cell-autonomous degeneration have features consistent with autophagic cell death. Chimeric mice exhibited a remarkable delay and reduction of wasting and ataxia despite their substantial amount of mutant tissue and dying cells, revealing a robust mechanism that partially compensates for massive PC death

    Circulating anthocyanin metabolites mediate vascular benefits of blueberries:insights from randomized controlled trials, metabolomics, and nutrigenomics

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    Potential health benefits of blueberries may be due to vascular effects of anthocyanins which predominantly circulate in blood as phenolic acid metabolites. We investigated which role blueberry anthocyanins and circulating metabolites play in mediating improvements in vascular function and explore potential mechanisms using metabolomics and nutrigenomics. Purified anthocyanins exerted a dose-dependent improvement of endothelial function in healthy humans, as measured by flow-mediated dilation (FMD). The effects were similar to those of blueberries containing similar amounts of anthocyanins while control drinks containing fiber, minerals, or vitamins had no significant effect. Daily 1-month blueberry consumption increased FMD and lowered 24h-ambulatory-systolic-blood-pressure. Of the 63 anthocyanin plasma metabolites quantified, 14 and 17 correlated with acute and chronic FMD improvements, respectively. Injection of these metabolites improved FMD in mice. Daily blueberry consumption led to differential expression (>1.2-fold) of 608 genes and 3 microRNAs, with Mir-181c showing a 13-fold increase in peripheral blood mononuclear cells. Patterns of 13 metabolites were independent predictors of gene expression changes and pathway enrichment analysis revealed significantly modulated biological processes involved in cell adhesion, migration, immune response, and cell differentiation. Our results identify anthocyanin metabolites as major mediators of vascular bioactivities of blueberries and changes of cellular gene programs
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