Radioactive foil analysis of 1.5 GeV proton bombardment of a Hg target

The number of reactant nuclei in a series of foils surrounding a container of Hg that has been bombarded by 1.5 GeV protons is calculated and compared to experimental measurements. This is done to aid in the validation of the Hg cross sections used in the design studies of the Spallation Neutron Source (SNS). It was found that the calculations match the measurements to within the uncertainties inherent in the analysis

Autoimmune and infectious skin diseases that target desmogleins

Desmosomes are intercellular adhesive junctions of epithelial cells that contain two major transmembrane components, the desmogleins (Dsg) and desmocollins (Dsc), which are cadherin-type cell–cell adhesion molecules and are anchored to intermediate filaments of keratin through interactions with plakoglobin and desmoplakin. Desmosomes play an important role in maintaining the proper structure and barrier function of the epidermis and mucous epithelia. Four Dsg isoforms have been identified to date, Dsg1–Dsg4, and are involved in several skin and heart diseases. Dsg1 and Dsg3 are the two major Dsg isoforms in the skin and mucous membranes, and are targeted by IgG autoantibodies in pemphigus, an autoimmune disease of the skin and mucous membranes. Dsg1 is also targeted by exfoliative toxin (ET) released by Staphylococcus aureus in the infectious skin diseases bullous impetigo and staphylococcal scalded skin syndrome (SSSS). ET is a unique serine protease that shows lock and key specificity to Dsg1. Dsg2 is expressed in all tissues possessing desmosomes, including simple epithelia and myocardia, and mutations in this gene are responsible for arrhythmogenic right ventricular cardiomyopathy/dysplasia. Dsg4 plays an important adhesive role mainly in hair follicles, and Dsg4 mutations cause abnormal hair development. Recently, an active disease model for pemphigus was generated by a unique approach using autoantigen-deficient mice that do not acquire tolerance against the defective autoantigen. Adoptive transfer of Dsg3−/− lymphocytes into mice expressing Dsg3 induces stable anti-Dsg3 IgG production with development of the pemphigus phenotype. This mouse model is a valuable tool with which to investigate immunological mechanisms of harmful IgG autoantibody production in pemphigus. Further investigation of desmoglein molecules will continue to provide insight into the unsolved pathophysiological mechanisms of diseases and aid in the development of novel therapeutic strategies with minimal side effects

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

Competitive authoritarianism Hybrid regime change in Peru and Ukraine in comparative perspective

Presented at the annual meeting of the American Political Science Association, San Francisco, 30 August - 2 September 2001SIGLEAvailable from British Library Document Supply Centre-DSC:8491.303(355) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

EFFECT OF MIXING CONDITIONS ON FLOCCULATION KINETICS OF WASTEWATERS CONTAINING PROTEINS AND OTHER BIOLOGICAL COMPOUNDS USING FIBROUS MATERIALS AND POLYELECTROLYTES

The application of a combined system of a polyelectrolyte, carboxymethyl cellulose (CMC), and highly fibrillated fibrous materials, cellulose triacetate fibrets (CTF), for the recovery of proteins and other biological compounds from model and actual biological systems has been demonstrated . In the present work, reaction batches were scaled-up to a one-liter agitated vessel, with a standard configuration. The effect of mixing conditions on the adsorption and flocculation process was studied. It was observed that flocculation time was very fast, occurring within the period of polymer addition. Long term shearing did not result in floc breakage and the values of percentage light transmission and protein concentration of the final filtrate remained the same during the incubation period. Increasing the shear rate resulted in improved process efficiency, up to an optimum value, above which performance was poorer. Perikinetic and orthokinetic rate parameters were calculated and results analyzed in view of these parameters