97 research outputs found

    Carrier-mediated ferromagnetic ordering in Mn ion-implanted p+GaAs:C

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    Highly p-type GaAs:C was ion-implanted with Mn at differing doses to produce Mn concentrations in the 1 - 5 at.% range. In comparison to LT-GaAs and n+GaAs:Si samples implanted under the same conditions, transport and magnetic properties show marked differences. Transport measurements show anomalies, consistent with observed magnetic properties and with epi- LT-(Ga,Mn)As, as well as the extraordinary Hall Effect up to the observed magnetic ordering temperature (T_C). Mn ion-implanted p+GaAs:C with as-grown carrier concentrations > 10^20 cm^-3 show remanent magnetization up to 280 K

    The JAK inhibitor ruxolitinib reduces inflammation in an ILC3-independent model of innate immune colitis

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    Innate immunity contributes to the pathogenesis of inflammatory bowel disease (IBD). However, the mechanisms of IBD mediated by innate immunity are incompletely understood and there are limited models of spontaneous innate immune colitis to address this question. Here we describe a new robust model of colitis occurring in the absence of adaptive immunity. RAG1-deficient mice expressing TNFAIP3 in intestinal epithelial cells (TRAG mice) spontaneously developed 100% penetrant, early-onset colitis that was limited to the colon and dependent on intestinal microbes but was not transmissible to co-housed littermates. TRAG colitis was associated with increased mucosal numbers of innate lymphoid cells (ILCs) and depletion of ILC prevented colitis in TRAG mice. ILC depletion also therapeutically reversed established colitis in TRAG mice. The colitis in TRAG mice was not prevented by interbreeding to mice lacking group 3 ILC nor by depletion of TNF. Treatment with the JAK inhibitor ruxolitinib ameliorated colitis in TRAG mice. This new model of colitis, with its predictable onset and colon-specific inflammation, will have direct utility in developing a more complete understanding of innate immune mechanisms that can contribute to colitis and in pre-clinical studies for effects of therapeutic agents on innate immune-mediated IBD

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

    W and WSi(x) Ohmic Contacts on p- And n-Type GaN

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    W and WSi ohmic contacts on both p- and n-type GaN have been annealed at temperatures from 300-1000 *C. There is minimal reaction (< 100 ~ broadening of the metal/GaN interface) even at 1000 *C. Specific contact resistances in the 10-5 f2-cm2 range are obtained for WSiX on Si-implanted GaN with a peak doping concentration of- 5 x 1020 cm-3, after annealing at 950 `C. On p-GaN, leaky Schottky diode behavior is observed for W, WSiX and Ni/Au contacts at room temperature, but true ohmic characteristics are obtained at 250 - 300 *C, where the specific contact resistances are typically in the 10-2 K2-cm2 range. The best contacts for W and WSiX are obtained after 700 *C annealing for periods of 30- 120 sees. The formation of &WzN interracial phases appear to be important in determining the contact quality
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