5,251 research outputs found

    A multi-physics approach to simulate the RF heating 3D power map induced by the proton beam in a beam intercepting device

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    The project High Luminosity Large Hadron Collider (HL-LHC) calls for a streaking beam intensity and brightness in the LHC machine. In such a scenario, beam-environment electromagnetic interactions are a crucial topic: they could lead to uneven power deposition in machine equipment. The resulting irregular temperature distribution would generate local thermal gradients, this would create mechanical stresses which could lead to cracks and premature failure of accelerator devices. This work presents a method to study this phenomenon by means of coupled electro-thermomechanical simulations. Further, an example of application on a real HL-LHC device is also discussed

    Hiddenocysta matsuokae gen. nov. et sp. nov. from the Holocene of Vancouver Island, British Columbia, Canada

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    A new dinoflagellate cyst genus and species are described here as Hiddenocysta gen. nov. and Hiddenocysta matsuokae sp. nov. from Holocene sediments in a core from the west coast of Vancouver Island (British Columbia, Canada). The genus Hiddenocysta encompasses spherical to ovoid skolochorate cysts, characterized by a gonyaulacoid plate pattern and a 2P precingular archeopyle. The species H. matsuokae is characterized by a granular wall and slender trifurcate processes with heavily perforated process bases. Two end members are described here based on process morphology and number of processes (formas 1 and 2). Cyst wall chemistry is analyzed using micro-Fourier transform infrared (FTIR) spectroscopy and reveals a unique dinosporin composition consistent with a gonyaulacoid autotrophic feeding strategy

    Enteric helminths promote Salmonella co-infection by altering the intestinal metabolome

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    Intestinal helminth infections occur pre dominantly in regions where exposure to enteric bacterial pathogens is also common. Helminth infections inhibit host immunity against microbial pathogens, which has largely been attributed to the induction of regulatory or type 2 (Th2) immune responses. Here we demonstrate an additional three-way interaction in which helminth infection alters the metabolic environment of the host intestine to enhance bacterial pathogenicity. We show that an ongoing helminth infection increased colonization by Salmonella independently of T regulatory or Th2 cells. Instead, helminth infection altered the metabolic profile of the intestine, which directly enhanced bacterial expression of Salmonella pathogenicity island 1 (SPI-1) genes and increased intracellular invasion. These data reveal a novel mechanism by which a helminth-modified metabolome promotes susceptibility to bacterial co-infection

    Islandinium pacificum sp. nov., a new dinoflagellate cyst from the upper Quaternary of the northeast Pacific

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    Round brown process-bearing cysts (RBPC) produced by dinoflagellates (Dinophyceae) occur as an important part of assemblage diversities in seafloor sediments worldwide. Here a new species, Islandinium pacificum, is described from surface sediment samples from coastal waters of British Columbia (Canada). Additional observations are made on material from the Holocene of Kyuquot Sound (Vancouver Island, Canada) and the Eemian of the Voring Plateau (North Atlantic). The cysts have a smooth wall and bear acuminate processes with barbs. Incubation experiments reveal an affinity with the motile stage Protoperidinium mutsuense. The ecology of the new species is specified

    Duplications of the critical Rubinstein-Taybi deletion region on chromosome 16p13.3 cause a novel recognisable syndrome

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    Background The introduction of molecular karyotyping technologies facilitated the identification of specific genetic disorders associated with imbalances of certain genomic regions. A detailed phenotypic delineation of interstitial 16p13.3 duplications is hampered by the scarcity of such patients. Objectives To delineate the phenotypic spectrum associated with interstitial 16p13.3 duplications, and perform a genotype-phenotype analysis. Results The present report describes the genotypic and phenotypic delineation of nine submicroscopic interstitial 16p13.3 duplications. The critically duplicated region encompasses a single gene, CREBBP, which is mutated or deleted in Rubinstein-Taybi syndrome. In 10 out of the 12 hitherto described probands, the duplication arose de novo. Conclusions Interstitial 16p13.3 duplications have a recognizable phenotype, characterized by normal to moderately retarded mental development, normal growth, mild arthrogryposis, frequently small and proximally implanted thumbs and characteristic facial features. Occasionally, developmental defects of the heart, genitalia, palate or the eyes are observed. The frequent de novo occurrence of 16p13.3 duplications demonstrates the reduced reproductive fitness associated with this genotype. Inheritance of the duplication from a clinically normal parent in two cases indicates that the associated phenotype is incompletely penetrant

    Musashi expression in β-cells coordinates insulin expression, apoptosis and proliferation in response to endoplasmic reticulum stress in diabetes

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    Diabetes is associated with the death and dysfunction of insulin-producing pancreatic β-cells. In other systems, Musashi genes regulate cell fate via Notch signaling, which we recently showed regulates β-cell survival. Here we show for the first time that human and mouse adult islet cells express mRNA and protein of both Musashi isoforms, as well Numb/Notch/Hes/neurogenin-3 pathway components. Musashi expression was observed in insulin/glucagon double-positive cells during human fetal development and increased during directed differentiation of human embryonic stem cells (hESCs) to the pancreatic lineage. De-differentiation of β-cells with activin A increased Msi1 expression. Endoplasmic reticulum (ER) stress increased Msi2 and Hes1, while it decreased Ins1 and Ins2 expression, revealing a molecular link between ER stress and β-cell dedifferentiation in type 2 diabetes. These effects were independent of changes in Numb protein levels and Notch activation. Overexpression of MSI1 was sufficient to increase Hes1, stimulate proliferation, inhibit apoptosis and reduce insulin expression, whereas Msi1 knockdown had the converse effects on proliferation and insulin expression. Overexpression of MSI2 resulted in a decrease in MSI1 expression. Taken together, these results demonstrate overlapping, but distinct roles for Musashi-1 and Musashi-2 in the control of insulin expression and β-cell proliferation. Our data also suggest that Musashi is a novel link between ER stress and the compensatory β-cell proliferation and the loss of β-cell gene expression seen in specific phases of the progression to type 2 diabetes

    Lifestyle Factors in Hypertension Drug Research: Systematic Analysis of Articles in a Leading Cochrane Report

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    Established standards for first-line hypertension management include lifestyle modification and behavior change. The degree to which and how lifestyle modification is systematically integrated into studies of first-line drug management for hypertension is of methodological and clinical relevance. This study systematically reviewed the methodology of articles from a recent Cochrane review that had been designed to inform first-line medical treatment of hypertension and was representative of high quality established clinical trials in the field. Source articles (n=34) were systematically reviewed for lifestyle interventions including smoking cessation, diet, weight loss, physical activity and exercise, stress reduction, and moderate alcohol consumption. 54% of articles did not mention lifestyle modification; 46% contained nonspecific descriptions of interventions. We contend that hypertension management research trials (including drug studies) need to elucidate the benefits and risks of drug-lifestyle interaction, to support the priority of lifestyle modification, and that lifestyle modification, rather than drugs, is seen by patients and the public as a priority for health professionals. The inclusion of lifestyle modification strategies in research designs for hypertension drug trials could enhance current research, from trial efficacy to clinical outcome effectiveness, and align hypertension best practices of a range of health professionals with evidence-based knowledge translation
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