Observation of the Ankle and Evidence for a High-Energy Break in the Cosmic Ray Spectrum

We have measured the cosmic ray spectrum at energies above $10^{17}$ eV using the two air fluorescence detectors of the High Resolution Fly's Eye experiment operating in monocular mode. We describe the detector, PMT and atmospheric calibrations, and the analysis techniques for the two detectors. We fit the spectrum to models describing galactic and extragalactic sources. Our measured spectrum gives an observation of a feature known as the ``ankle'' near $3\times 10^{18}$ eV, and strong evidence for a suppression near $6\times 10^{19}$ eV.Comment: 14 pages, 9 figures. To appear in Physics Letters B. Accepted versio

High prevalence of PRPH2 in autosomal dominant retinitis pigmentosa in france and characterization of biochemical and clinical features.

PURPOSE: To assess the prevalence of PRPH2 in autosomal dominant retinitis pigmentosa (adRP), to report 6 novel mutations, to characterize the biochemical features of a recurrent novel mutation, and to study the clinical features of adRP patients. DESIGN: Retrospective clinical and molecular genetic study. METHODS: Clinical investigations included visual field testing, fundus examination, high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence imaging, and electroretinogram (ERG) recording. PRPH2 was screened by Sanger sequencing in a cohort of 310 French families with adRP. Peripherin-2 protein was produced in yeast and analyzed by Western blot. RESULTS: We identified 15 mutations, including 6 novel and 9 previously reported changes in 32 families, accounting for a prevalence of 10.3% in this adRP population. We showed that a new recurrent p.Leu254Gln mutation leads to protein aggregation, suggesting abnormal folding. The clinical severity of the disease in examined patients was moderate with 78% of the eyes having 1-0.5 of visual acuity and 52% of the eyes retaining more than 50% of the visual field. Some patients characteristically showed vitelliform deposits or macular involvement. In some families, pericentral RP or macular dystrophy were found in family members while widespread RP was present in other members of the same families. CONCLUSIONS: The mutations in PRPH2 account for 10.3% of adRP in the French population, which is higher than previously reported (0%-8%) This makes PRPH2 the second most frequent adRP gene after RHO in our series. PRPH2 mutations cause highly variable phenotypes and moderate forms of adRP, including mild cases, which could be underdiagnosed

Relativistic corrections in (gamma,N) knockout reactions

We develop a fully relativistic DWIA model for photonuclear reactions using the relativistic mean field theory for the bound state and the Pauli reduction of the scattering state which is calculated from a relativistic optical potential. Results for the 12C(gamma,p) and 16O(gamma,p) differential cross sections and photon asymmetries are displayed in a photon energy range between 60 and 257 MeV, and compared with nonrelativistic DWIA calculations. The effects of the spinor distortion and of the effective momentum approximation for the scattering state are discussed. The sensitivity of the model to different prescriptions for the one-body current operator is investigated. The off-shell ambiguities are large in (gamma,p) calculations, and even larger in (gamma,n) knockout.Comment: LaTeX2e, 18 pages, and 6 figure

Legal, medical and lay understanding of embryos in Portugal: alignment with biology?

Pretende-se contribuir para o debate em torno dos processos de circulação de conhecimentos e sentidos entre especialistas e “leigos” no que concerne ao estatuto dos embriões humanos em Portugal. Reflete-se sobre as expectativas e preocupações manifestadas quanto à confiança, qualidade, segurança e eficácia das tecnologias médicas de reprodução assistida. O estudo assenta na realização de entrevistas individuais, com vistas a explorar as complexidades, similitudes e diferenças entre as visões e os valores de juristas, médicos e casais envolvidos em tratamentos de fertilização in vitro. Trata-se de uma análise qualitativa em um estudo de caso. Se os juristas e os médicos enquadram o estatuto dos embriões em categorias de índole biológica, técnica e/ou jurídico-legal, já os casais estabelecem com os mesmos diversas relações ontológicas de índole moral, afetiva e social, pelo que estes podem ser representados como seres éticos face à biologização médico-legal dos embriões.Our aim is to contribute towards the debate about the processes through which knowledge and meanings regarding the status of human embryos circulate among experts and laymen in Portugal. Expectations and concerns expressed regarding the reliability, quality, safety and efficacy of medical technologies for assisted reproduction were assessed. This study is based on data from individual interviews that sought to explore the complexities, similarities and differences among the views and values of jurists, doctors and couples involved in in vitro fertilization treatments. It consists of a qualitative analysis on a case study. If jurists and doctors frame the status of embryos as categories of a biological, technical and/or legal nature, couples establish between themselves a variety of ontological relationships of a moral, affective and social nature. Through these, they can be represented as ethical beings, thus contrasting with the medical-legal biologization of the embryos.To the jurists, doctors and women and men who we interviewed and who shared with us their views and experiences, our sincere thanks. We also thank Helena Lima and Filomena Louro (Scientific Editing Programme, University of Minho) for the translation of the Portuguese text into English; and the revision of David George Elliff. The authors thank the Foundation for Science and Technology (Portuguese Ministry of Science, Technology and Higher Education) for the financial support for this research, through a PhD fellowship (SFRH/BD/10396/2002) and a post-doctoral fellowship (SFRH/BPD/47020/2008).info:eu-repo/semantics/publishedVersio

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe

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