1,982 research outputs found

    The Case | Diabetic nephropathy in a nondiabetic smoker?

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    Terahertz Response of Field-Effect Transistors in Saturation Regime

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    We report on the broadband THz response of InGaAs/GaAs HEMTs operating at 1.63 THz and room temperature deep in the saturation regime. We demonstrate that responses show linear increase with drain-to-source voltage (or drain bias current) and reach very high values up to 170V/W. We also develop a phenomenological theory valid both in the ohmic and in the saturation regimes.Comment: 11 pages, 3 figure

    Epigenetic Chromatin Silencing: Bistability and Front Propagation

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    The role of post-translational modification of histones in eukaryotic gene regulation is well recognized. Epigenetic silencing of genes via heritable chromatin modifications plays a major role in cell fate specification in higher organisms. We formulate a coarse-grained model of chromatin silencing in yeast and study the conditions under which the system becomes bistable, allowing for different epigenetic states. We also study the dynamics of the boundary between the two locally stable states of chromatin: silenced and unsilenced. The model could be of use in guiding the discussion on chromatin silencing in general. In the context of silencing in budding yeast, it helps us understand the phenotype of various mutants, some of which may be non-trivial to see without the help of a mathematical model. One such example is a mutation that reduces the rate of background acetylation of particular histone side-chains that competes with the deacetylation by Sir2p. The resulting negative feedback due to a Sir protein depletion effect gives rise to interesting counter-intuitive consequences. Our mathematical analysis brings forth the different dynamical behaviors possible within the same molecular model and guides the formulation of more refined hypotheses that could be addressed experimentally.Comment: 19 pages, 5 figure

    A Role for FACT in Repopulation of Nucleosomes at Inducible Genes

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    Xenobiotic drugs induce Pleiotropic Drug Resistance (PDR) genes via the orthologous Pdr1/Pdr3 transcription activators. We previously identified the Mediator transcription co-activator complex as a key target of Pdr1 orthologs and demonstrated that Pdr1 interacts directly with the Gal11/Med15 subunit of the Mediator complex. Based on an interaction between Pdr1 and the FACT complex, we show that strains with spt16 or pob3 mutations are sensitive to xenobiotic drugs and display diminished PDR gene induction. Although FACT acts during the activation of some genes by assisting in the nucleosomes eviction at promoters, PDR promoters already contain nucleosome-depleted regions (NDRs) before induction. To determine the function of FACT at PDR genes, we examined the kinetics of RNA accumulation and changes in nucleosome occupancy following exposure to a xenobiotic drug in wild type and FACT mutant yeast strains. In the presence of normal FACT, PDR genes are transcribed within 5 minutes of xenobiotic stimulation and transcription returns to basal levels by 30–40 min. Nucleosomes are constitutively depleted in the promoter regions, are lost from the open reading frames during transcription, and the ORFs are wholly repopulated with nucleosomes as transcription ceases. While FACT mutations cause minor delays in activation of PDR genes, much more pronounced and significant defects in nucleosome repopulation in the ORFs are observed in FACT mutants upon transcription termination. FACT therefore has a major role in nucleosome redeposition following cessation of transcription at the PDR genes, the opposite of its better-known function in nucleosome disassembly

    Statistical Modeling of the Default Mode Brain Network Reveals a Segregated Highway Structure

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    We investigate the functional organization of the Default Mode Network (DMN) – an important subnetwork within the brain associated with a wide range of higher-order cognitive functions. While past work has shown the whole-brain network of functional connectivity follows small-world organizational principles, subnetwork structure is less well understood. Current statistical tools, however, are not suited to quantifying the operating characteristics of functional networks as they often require threshold censoring of information and do not allow for inferential testing of the role that local processes play in determining network structure. Here, we develop the correlation Generalized Exponential Random Graph Model (cGERGM) – a statistical network model that uses local processes to capture the emergent structural properties of correlation networks without loss of information. Examining the DMN with the cGERGM, we show that, rather than demonstrating small-world properties, the DMN appears to be organized according to principles of a segregated highway – suggesting it is optimized for function-specific coordination between brain regions as opposed to information integration across the DMN. We further validate our findings through assessing the power and accuracy of the cGERGM on a testbed of simulated networks representing various commonly observed brain architectures

    An epidemiologic study of early biologic effects of benzene in Chinese workers.

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    Benzene is a recognized hematotoxin and leukemogen, but its mechanisms of action in humans are still uncertain. To provide insight into these processes, we carried out a cross-sectional study of 44 healthy workers currently exposed to benzene (median 8-hr time-weighted average; 31 ppm), and unexposed controls in Shanghai, China. Here we provide an overview of the study results on peripheral blood cells levels and somatic cell mutation frequency measured by the glycophorin A (GPA) gene loss assay and report on peripheral cytokine levels. All peripheral blood cells levels (i.e., total white blood cells, absolute lymphocyte count, platelets, red blood cells, and hemoglobin) were decreased among exposed workers compared to controls, with the exception of the red blood cell mean corpuscular volume, which was higher among exposed subjects. In contrast, peripheral cytokine levels (interleukin-3, interleukin-6, erythropoietin, granulocyte colony-stimulating factor, tissue necrosis factor-alpha) in a subset of the most highly exposed workers (n = 11) were similar to values in controls (n = 11), suggesting that benzene does not affect these growth factor levels in peripheral blood. The GPA assay measures stem cell or precursor erythroid cell mutations expressed in peripheral red blood cells of MN heterozygous subjects, identifying NN variants, which result from loss of the GPA M allele and duplication of the N allele, and N phi variants, which arise from gene inactivation. The NN (but not N phi) GPA variant cell frequency was elevated in the exposed workers compared with controls (mean +/- SD, 13.9 +/- 8.4 mutants per million cells versus 7.4 +/- 5.2 per million cells, (respectively; p = 0.0002), suggesting that benzene produces gene-duplicating but not gene-inactivating mutations at the GPA locus in bone marrow cells of exposed humans. These findings, combined with ongoing analyses of benzene macromolecular adducts and chromosomal aberrations, will provide an opportunity to comprehensively evaluate a wide range of early biologic effects associated with benzene exposure in humans

    Water induced sediment levitation enhances downslope transport on Mars

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    On Mars, locally warm surface temperatures (~293 K) occur, leading to the possibility of (transient) liquid water on the surface. However, water exposed to the martian atmosphere will boil, and the sediment transport capacity of such unstable water is not well understood. Here, we present laboratory studies of a newly recognized transport mechanism: “levitation” of saturated sediment bodies on a cushion of vapor released by boiling. Sediment transport where this mechanism is active is about nine times greater than without this effect, reducing the amount of water required to transport comparable sediment volumes by nearly an order of magnitude. Our calculations show that the effect of levitation could persist up to ~48 times longer under reduced martian gravity. Sediment levitation must therefore be considered when evaluating the formation of recent and present-day martian mass wasting features, as much less water may be required to form such features than previously thought

    Curricular orientations to real-world contexts in mathematics

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    A common claim about mathematics education is that it should equip students to use mathematics in the ‘real world’. In this paper, we examine how relationships between mathematics education and the real world are materialised in the curriculum across a sample of eleven jurisdictions. In particular, we address the orientation of the curriculum towards application of mathematics, the ways that real-world contexts are positioned within the curriculum content, the ways in which different groups of students are expected to engage with real-world contexts, and the extent to which high-stakes assessments include real-world problem solving. The analysis reveals variation across jurisdictions and some lack of coherence between official orientations towards use of mathematics in the real world and the ways that this is materialised in the organisation of the content for students
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