A psychophysical study of echolocation in the blinded rat

LD2668 .T4 1966 B435Master of Scienc

Genetic mechanisms of critical illness in COVID-19.

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

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

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

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

Measurement of the cross-section for electroweak production of dijets in association with a Z boson in pp collisions at s√=13TeV with the ATLAS detector

The cross-section for the production of two jets in association with a leptonically decaying Z boson (Zjj) is measured in proton–proton collisions at a centre-of-mass energy of 13 TeV, using data recorded with the ATLAS detector at the Large Hadron Collider, corresponding to an integrated luminosity of 3.2 fb−1. The electroweak Zjj cross-section is extracted in a fiducial region chosen to enhance the electroweak contribution relative to the dominant Drell–Yan Zjj process, which is constrained using a data-driven approach. The measured fiducial electroweak cross-section is σEW Zjj = 119±16(stat.)±20(syst.)±2(lumi.) fb for dijet invariant mass greater than 250 GeV, and 34.2±5.8(stat.)±5.5(syst.)±0.7(lumi.) fb for dijet invariant mass greater than 1 TeV. Standard Model predictions are in agreement with the measurements. The inclusive Zjj cross-section is also measured in six different fiducial regions with varying contributions from electroweak and Drell–Yan Zjj production

Flexibles Fotolithographisches Prozesscenter (FFP). Teilprojekt: Qualifizierung Modul 6000 Ergebnisbericht

Available from TIB Hannover: FR 5128+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

"What We Breathe Impacts Our Health : Improving Understanding of the Link between Air Pollution and Health"

Air pollution contributes to the premature deaths of millions of people each year around the world, and air quality problems are growing in many developing nations. While past policy efforts have succeeded in reducing particulate matter and trace gases in North America and Europe, adverse health effects are found at even these lower levels of air pollution. Future policy actions will benefit from improved understanding of the interactions and health effects of different chemical species and source categories. Achieving this new understanding requires air pollution scientists and engineers to work increasingly closely with health scientists. In particular, research is needed to better understand the chemical and physical properties of complex air pollutant mixtures, and to use new observations provided by satellites, advanced in situ measurement techniques, and distributed micro monitoring networks, coupled with models, to better characterize air pollution exposure for epidemiological and toxicological research, and to better quantify the effects of specific source sectors and mitigation strategies

Calcitonin gene-related peptide:physiology and pathophysiology

Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide. Discovered 30 years ago, it is produced as a consequence of alternative RNA processing of the calcitonin gene. CGRP has two major forms (α and β). It belongs to a group of peptides that all act on an unusual receptor family. These receptors consist of calcitonin receptor-like receptor (CLR) linked to an essential receptor activity modifying protein (RAMP) that is necessary for full functionality. CGRP is a highly potent vasodilator and, partly as a consequence, possesses protective mechanisms that are important for physiological and pathological conditions involving the cardiovascular system and wound healing. CGRP is primarily released from sensory nerves and thus is implicated in pain pathways. The proven ability of CGRP antagonists to alleviate migraine has been of most interest in terms of drug development, and knowledge to date concerning this potential therapeutic area is discussed. Other areas covered, where there is less information known on CGRP, include arthritis, skin conditions, diabetes, and obesity. It is concluded that CGRP is an important peptide in mammalian biology, but it is too early at present to know if new medicines for disease treatment will emerge from our knowledge concerning this molecule

Reservoir quality of Cenozoic carbonate buildups and coral reef terraces

Almost half of SE Asia's considerable hydrocarbon reserves are contained in carbonates. The majority of these reservoirs are Miocene buildups up to tens of kilometres across. However, with the exception of a few fields, there is little detailed data on how local depositional and diagenetic conditions influence the considerable heterogeneities in reservoir quality often encountered. This study focuses on factors influencing the facies, diagenetic and reservoir variability of comparable Modern, Quaternary and Neogene reef associated deposits from the Tukang Besi Archipelago, Central Indonesia.The Archipelago includes large atolls, a number of smaller buildups and 4 main islands each with modern rimmed shelves or fringing reefs. On the islands, over ten late Neogene and Quaternary coral reef terraces have been uplifted to maximum heights of ~300 m. Analysis of the modern deposits allows initial reservoir potential to be assessed and related to local environmental conditions. The influence of diagenesis on final reservoir quality is evaluated for the depositional facies exposed in the uplifted terraces. The overall spatial distribution of effective porosity across the area is strongly dependent on local energy conditions, water depth, carbonate producers, size of atolls or islands, climate and local meteoric diagenetic processes. This evaluation of spatial variability in carbonate reservoir characteristics provides much needed analogue data as the hydrocarbon industry focuses on improving recovery from existing fields and exploring for new reserves