Expected Performance of the ATLAS Experiment - Detector, Trigger and Physics

A detailed study is presented of the expected performance of the ATLAS detector. The reconstruction of tracks, leptons, photons, missing energy and jets is investigated, together with the performance of b-tagging and the trigger. The physics potential for a variety of interesting physics processes, within the Standard Model and beyond, is examined. The study comprises a series of notes based on simulations of the detector and physics processes, with particular emphasis given to the data expected from the first years of operation of the LHC at CERN

Expanding the diversity of mycobacteriophages: insights into genome architecture and evolution.

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists

Microbial communities in placentas from term normal pregnancy exhibit spatially variable profiles

Abstract The placenta is the principal organ nurturing the fetus during pregnancy and was traditionally considered to be sterile. Recent work has suggested that the placenta harbours microbial communities, however the location and possible function of these microbes remain to be confirmed and elucidated. Here, we employed genomic DNA sequencing of multiple variable (V) regions of the bacterial 16S ribosomal gene, to interrogate microbial profiles in term pregnancies, from the basal plate, which is in direct contact with maternal uterine, endothelial, and immune cells; placental villi, which are bathed in maternal blood, and fetal membranes, which encapsulate the amniotic cavity. QIIME, R package “Phyloseq” analysis was used to assess alpha and beta diversity and absolute abundance of the 16S rRNA gene per location. We demonstrate that (1) microbiota exhibit spatially distinct profiles depending on the location within the placenta and (2) “semi-composite” 16S profiles using multiple V regions validated by quantitative PCR analysis confirmed that distinct bacterial taxa dominate in different placental niches. Finally, profiles are not altered by mode of delivery. Together these findings suggest that there is niche-specificity to the placental microbiota and placental microbiome studies should consider regional differences, which may affect maternal, fetal, and/or neonatal health and physiology

Origin of the secondary REE-minerals at the Paratoo copper deposit near Yunta, South Australia

Copyright © 2006 The Mineralogical SocietyThe Paratoo copper deposit, located in the Neoproterozoic to Cambrian Adelaide Geosyncline, South Australia, produced around 360 tons of Cu between 1888 and 1967 from oxidized ores. The deposit is located in the core of a breached, doubly plunging anticline, near a zone of disruption containing brecciated Adelaidean sedimentary rocks and dolerite ('Paratoo Diapir'), and hosted in dolomitic shales of the Neoproterozoic Burra Formation. Near the surface, the mineralization resides mainly in deeply weathered quartz-magnetite-sulphide (pyrite, chalcopyrite) veins (≥ 10 cm wide). At depth, drill cores reveal disseminated magnetite, pyrite, chalcopyrite, copper sulphide and native copper associated with extensive potassic alteration. K-Na-rich fluids also affected the dolerite in the 'Paratoo diapir', resulting in the precipitation of K-feldspar, dravite and K-bearing chabazite-Na. The most likely scenario for the genesis of the Paratoo deposit involves circulation of basinal fluids, focusing into the 'Paratoo Diapir', and ore precipitation through neutralization by fluid-rock interaction with the dolomitic shales hosting the mineralization. The Paratoo deposit is deeply weathered, with malachite and chrysocolla (± tenorite and cuprite) containing the bulk of the copper recovered from the shallow workings. A diverse assemblage of secondary REE-bearing carbonate minerals, including the new species decrespignyite-(Y) and paratooite-(La), is associated with the weathered base metal and magnetite ores. Whole-rock geochemical analyses of fresh and mineralized host rock and of vein material reveals that the mineralization is associated with a strong, albeit highly variable, enrichment in light rare earth elements (LREE). This association indicates that REE and base metals were introduced by the same hydrothermal fluid. The strong negative Ce anomaly found in secondary REE minerals and mineralized rock samples suggests an upgrade of the REE contents in the weathering zone, insoluble Ce4+ being left behind. The Fe-oxide-REE-base metal association at Paratoo is also characteristic of the giant Mesoproterozoic Fe oxide copper gold deposit of Olympic Dam, located 350 km to the NW. A similar association is found in the Palaeozoic deposits of the Mt Painter Inlier, 300 km to the NNE. The widespread occurrence of this elemental association in the Province probably reflects the geochemistry of the basement, which contains numerous Mesoproterozoic granites enriched in REE and U.J. Brugger, J. Ogierman, A. Pring, H. Waldron and U. Kolitsc

TAM Receptors Are Not Required for Zika Virus Infection in Mice

Summary: Tyro3, Axl, and Mertk (TAM) receptors are candidate entry receptors for infection with the Zika virus (ZIKV), an emerging flavivirus of global public health concern. To investigate the requirement of TAM receptors for ZIKV infection, we used several routes of viral inoculation and compared viral replication in wild-type versus Axl−/−, Mertk−/−, Axl−/−Mertk−/−, and Axl−/−Tyro3−/− mice in various organs. Pregnant and non-pregnant mice treated with interferon-α-receptor (IFNAR)-blocking (MAR1-5A3) antibody and infected subcutaneously with ZIKV showed no reliance on TAMs for infection. In the absence of IFNAR-blocking antibody, adult female mice challenged intravaginally with ZIKV showed no difference in mucosal viral titers. Similarly, in young mice that were infected with ZIKV intracranially or intraperitoneally, ZIKV replication occurred in the absence of TAM receptors, and no differences in cell tropism were observed. These findings indicate that, in mice, TAM receptors are not required for ZIKV entry and infection. : TAM receptors have been implicated as entry receptors for the Zika virus. In this study, Hastings et al. used genetic knockout mouse models to demonstrate that they are not necessary for the infection of mice via multiple routes of viral challenge. These results suggest the existence of redundant entry receptors for ZIKV in mice. Keywords: viral entry, flavivirus, neurotropic virus, CNS, pregnancy, congenital infectio

The dual Syk/JAK inhibitor cerdulatinib antagonizes B-cell receptor and microenvironmental signaling in chronic lymphocytic leukemia

Purpose: B-cell receptor (BCR)-associated kinase inhibitors such as ibrutinib have revolutionised the treatment of chronic lymphocytic leukemia (CLL). However, these agents are not curative and resistance is already emerging in a proportion of patients. Interleukin-4 (IL-4), expressed in CLL lymph nodes, can augment BCR-signalling and reduce the effectiveness of BCR-kinase inhibitors. Therefore simultaneous targeting of the IL-4- and BCR-signalling pathways by cerdulatinib, a novel dual Syk/JAK inhibitor currently in clinical trials (NCT01994382), may improve treatment responses in patients. Experimental Design: PBMCs from CLL patients were treated with cerdulatinib alone or in combination with venetoclax. Cell death, chemokine and cell signalling assay were performed and analysed by flow cytometry, immunoblotting, Q-PCR and ELISA as indicated. Results: at concentrations achievable in patients, cerdulatinib inhibited BCR- and IL-4-induced downstream signalling in CLL cells using multiple read outs and prevented anti-IgM- and nurse-like cell (NLC)-mediated CCL3/CCL4 production. Cerdulatinib induced apoptosis of CLL cells, in a time- and concentration dependent manner, and particularly in IGHV unmutated samples with greater BCR-signalling capacity and response to IL-4, or samples expressing higher levels of sIgM, CD49d+ or ZAP70+. Cerdulatinib overcame anti-IgM, IL-4/CD40L or NLC-mediated protection by preventing upregulation of MCL-1- and BCL-XL, however BCL-2 expression was unaffected. Furthermore in samples treated with IL-4/CD40L, cerdulatinib synergised with venetoclax in vitro to induce greater apoptosis than either drug alone. Conclusion: cerdulatinib is a promising therapeutic for the treatment of CLL either alone or in combination with venetoclax, with the potential to target critical survival pathways in this currently incurable disease<br/