Measurements of copper-printed mylar bonded to G10 panels

Measurements were made of the position of Cu strip patterns on 100 micro thick mylar sheets bonded to G10, in order to study printing of precision cathode strip patterns on thin mylar and then bonding themylar to G10 sheets. Purpose is to explore cheaper, simpler methods for fabricating precision cathodes for cathode strip chambers for the GEM Detector muon system and other high energy physics detector systems at RHIC and CERN

Early- Onset Stroke and Vasculopathy Associated with Mutations in ADA2

Adenosine deaminase 2 (ADA2) is an enzyme involved in purine metabolism and a growth factor that influences the development of endothelial cells and leukocytes. This study shows that defects in ADA2 cause recurrent fevers, vascular pathologic features, and mild immunodeficiency. Patients with autoinflammatory disease sometimes present with clinical findings that encompass multiple organ systems.(1) Three unrelated children presented to the National Institutes of Health (NIH) Clinical Center with intermittent fevers, recurrent lacunar strokes, elevated levels of acute-phase reactants, livedoid rash, hepatosplenomegaly, and hypogammaglobulinemia. Collectively, these findings do not easily fit with any of the known inherited autoinflammatory diseases. Hereditary or acquired vascular disorders can have protean manifestations yet be caused by mutations in a single gene. Diseases such as the Aicardi-Goutieres syndrome,(2),(3) polypoidal choroidal vasculopathy,(4) sickle cell anemia,(5) livedoid vasculopathy,(6) and the small-vessel vasculitides(7),(8) are examples of systemic ...</p

The ‘mosaic habitat’ concept in human evolution: past and present

The habitats preferred by hominins and other species are an important theme in palaeoanthropology, and the ‘mosaic habitat’ (also referred to as habitat heterogeneity) has been a central concept in this regard for the last four decades. Here we explore the development of this concept – loosely defined as a range of different habitat types, such as woodlands, riverine forest and savannah within a limited spatial area– in studies of human evolution in the last sixty years or so. We outline the key developments that took place before and around the time when the term ‘mosaic’ came to wider palaeoanthropological attention. To achieve this we used an analysis of the published literature, a study of illustrations of hominin evolution from 1925 onwards and an email survey of senior researchers in palaeoanthropology and related fields. We found that the term mosaic starts to be applied in palaeoanthropological thinking during the 1970’s due to the work of a number of researchers, including Karl Butzer and Glynn Isaac , with the earliest usage we have found of ‘mosaic’ in specific reference to hominin habitats being by Adriaan Kortlandt (1972). While we observe a steady increase in the numbers of publications reporting mosaic palaeohabitats, in keeping with the growing interest and specialisation in various methods of palaeoenvironmental reconstruction, we also note that there is a lack of critical studies that define this habitat, or examine the temporal and spatial scales associated with it. The general consensus within the field is that the concept now requires more detailed definition and study to evaluate its role in human evolution

Erratum: Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome (J. Exp. Med. (2020) 217:6 Doi:10.1084/jem.20191804)

The authors regret that in the original version of Table S1, the column for patient 12 was mistakenly duplicated in the column for patient 8. The online Table S1 PDF has been corrected. The error appears only in PDFs downloaded before June 4, 2020

Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome

Autosomal dominant hyper-IgE syndrome (AD-HIES) is typically caused by dominant-negative (DN) STAT3 mutations. Patients suffer from cold staphylococcal lesions and mucocutaneous candidiasis, severe allergy, and skeletal abnormalities. We report 12 patients from 8 unrelated kindreds with AD-HIES due to DN IL6ST mutations. We identified seven different truncating mutations, one of which was recurrent. The mutant alleles encode GP130 receptors bearing the transmembrane domain but lacking both the recycling motif and all four STAT3-recruiting tyrosine residues. Upon overexpression, the mutant proteins accumulate at the cell surface and are loss of function and DN for cellular responses to IL-6, IL-11, LIF, and OSM. Moreover, the patients’ heterozygous leukocytes and fibroblasts respond poorly to IL-6 and IL-11. Consistently, patients with STAT3 and IL6ST mutations display infectious and allergic manifestations of IL-6R deficiency, and some of the skeletal abnormalities of IL-11R deficiency. DN STAT3 and IL6ST mutations thus appear to underlie clinical phenocopies through impairment of the IL-6 and IL-11 response pathways

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

A comparative study of economic growth and instability in the United Kingdom and European Economic Community, 1951–1970

A comparative study of economic growth and instability in the United Kingdom and European Economic Community, 1951–197