18 research outputs found

    Band gap bowing of binary alloys: Experimental results compared to theoretical tight-binding supercell calculations for CdZnSe

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    Compound semiconductor alloys of the type ABC find widespread applications as their electronic bulk band gap varies continuously with x, and therefore a tayloring of the energy gap is possible by variation of the concentration. We model the electronic properties of such semiconductor alloys by a multiband tight-binding model on a finite ensemble of supercells and determine the band gap of the alloy. This treatment allows for an intrinsic reproduction of band bowing effects as a function of the concentration x and is exact in the alloy-induced disorder. In the present paper, we concentrate on bulk CdZnSe as a well-defined model system and give a careful analysis on the proper choice of the basis set and supercell size, as well as on the necessary number of realizations. The results are compared to experimental results obtained from ellipsometric measurements of CdZnSe layers prepared by molecular beam epitaxy (MBE) and photoluminescence (PL) measurements on catalytically grown CdZnSe nanowires reported in the literature.Comment: 7 pages, 6 figure

    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 hospitalization2–4 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

    Genetic mechanisms of critical illness in COVID-19.

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    Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

    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

    Antegrade percutaneous balloon dilation of ureteral strictures after failed pelviureteric or ureterovesical reimplantation in children

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    OBJECTIVES: To assess the morbidity and success rate of percutaneous treatment of the postoperative ureteric strictures in children. MATERIALS AND METHODS: Between January 1994 and December 2003, 12 children were treated by antegrade percutaneous balloon dilation for postoperative ureteric strictures. Stenosis occurred at the pelviureteric junction in 5 cases and ureterovesical junction in 7 cases. The 10 boys and 2 girls were between 3 months and 14 years old (mean, 5 years +/- 4.7 years). General anesthesia was used in 10 cases for nephrostomy catheter placement. Five ureteral stents were used additionally for nephrostomy drainage with a 6-F catheter. Both nephrostomy and ureteric stents were in place for 28.5 +/- 12 days, then removed after control antegrade pyelography. RESULTS: Dilation was technically successful in 9 of our patients. Two peroperative complications occurred. Postoperative results were evaluated by ultrasonography, intravenous urography, antegrade pyelography, and diethylene triamine pentaacetic acid renography that confirmed no obstacle in all 5 cases of pelviureteric stricture with a follow-up of 4 +/- 2.9 years and in 4 cases of ureterovesical junction with a follow-up of 4.7 +/- 2.8 years. Three unsuccessful results were reported: in 2 cases, the guide wire could not be advanced over the stenotic ureterovesical junction and in 1 case an early restenosis occurred that eventually required surgery. CONCLUSIONS: Although the main treatment of the postoperative ureteral strictures is surgical, the percutaneous antegrade balloon dilation seems to be an alternative to surgery with a low morbidity rate and short hospitalization period

    Photocatalytic Efficiency Tuning by the Surface Roughness of TiO2 Coatings on Glass Prepared by the Doctor Blade Method

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    A set of opaque films were prepared with Degussa P25® or Hombikat UV100® TiO2 powders by the doctor blade method on glass slides with different compositions of polyethylene glycol of 20 kDa (PEG20), and they were characterized by spectroscopy, microscopy and photochemical kinetics measurements. After annealing treatment at 450 °C, about 5–7% C atom was incorporated into the films, as a consequence of the degradation of the organic complexing agents, inducing a small reduction of the energy band gap of TiO2 (i.e. 3.02 ≤ Eg (eV) ≤ 3.08). All films were about 15 ± 2 μm thick but their micro-morphological characteristics depended on the content of PEG20, showing different patterns of cracks and aggregates that produce intense light scattering and retransmission phenomena with the result of a three-dimensional excitation of the TiO2 particles in the thick film. Back-face excitation with UVA light (365 ± 42 nm) of the opaque films in contact with an aqueous solution produced both surface-bound and free hydroxyl radicals (HO•), as detected using a coumarin solution as a radical dosimeter. The photogeneration efficiency of HO• decreased with the surface roughness of the films, which varied between 135 and 439 nm depending on the film's composition.Fil: Tulli, Fiorella Giovanna. Universidad Nacional de Santiago del Estero; Argentina. Universidad Nacional de Santiago del Estero. Instituto de Bionanotecnología del Noa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Bionanotecnología del Noa; ArgentinaFil: Morales, Jesús Marcelo Nicolás. Universidad Nacional de Santiago del Estero; Argentina. Universidad Nacional de Santiago del Estero. Instituto de Bionanotecnología del Noa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Bionanotecnología del Noa; ArgentinaFil: Salas, Esteban Eduardo. Universidad Nacional de Santiago del Estero; Argentina. Universidad Nacional de Santiago del Estero. Instituto de Bionanotecnología del Noa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Bionanotecnología del Noa; ArgentinaFil: Moran Vieyra, Faustino Eduardo. Universidad Nacional de Santiago del Estero. Instituto de Bionanotecnología del Noa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Bionanotecnología del Noa; Argentina. Universidad Nacional de Santiago del Estero. Facultad de Agronomía y Agroindustrias; ArgentinaFil: Borsarelli, Claudio Darío. Universidad Nacional de Santiago del Estero. Instituto de Bionanotecnología del Noa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Bionanotecnología del Noa; Argentina. Universidad Nacional de Santiago del Estero. Facultad de Agronomía y Agroindustrias; Argentin

    Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

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    Mapping the human genetic architecture of COVID-19

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    The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease
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