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A search is presented for single production of a vector-like quark (T) decaying to a Z boson and a top quark, with the Z boson decaying leptonically and the top quark decaying hadronically. The search uses data collected by the CMS experiment in proton-proton collisions at a center-of-mass energy of 13 TeV in 2016, corresponding to an integrated luminosity of 35.9 fb(-1). The presence of forward jets is a particular characteristic of single production of vector-like quarks that is used in the analysis. For the first time, different T quark width hypotheses are studied, from negligibly small to 30% of the new particle mass. At the 95% confidence level, the product of cross section and branching fraction is excluded above values in the range 0.26-0.04 pb for T quark masses in the range 0.7-1.7 TeV, assuming a negligible width. A similar sensitivity is observed for widths of up to 30% of the T quark mass. The production of a heavy Z' boson decaying to Tt, with T -> tZ, is also searched for, and limits on the product of cross section and branching fractions for this process are set between 0.13 and 0.06pbfor Z' boson masses in the range from 1.5 to 2.5 TeV. (C) 2018 The Author(s). Published by Elsevier B.V.

Bacteriophage lysins and related bacteriolytic enzymes are now considered among the top antibiotic alternatives for solving the mounting resistance problem. Over the past 17 years, lysins have been widely developed against Gram-positive and recently Gram-negative pathogens, and successfully tested in a variety of animal models to demonstrate their efficacy. A lysin (CF-301) directed to methicillin resistant Staphylococcus aureus (MRSA) has effectively completed phase 1 human clinical trials, showing safety in this novel therapeutic class. To validate efficacy, CF-301 is currently the first lysin to enter phase 2 human trials to treat hospitalized patients with MRSA bacteremia or endocarditis. If successful, it could be the defining moment leading to the acceptance of lysins as an alternative to small molecule antibiotics. This article is a detailed account of events leading to the first therapeutic use and ultimate development of phage-encoded lysins as novel anti-infectives.

A search for a new scalar resonance decaying to a pair of Z bosons is performed in the mass range from 130 GeV to 3TeV, and for various width scenarios. The analysis is based on proton-proton collisions recorded by the CMS experiment at the LHC in 2016, corresponding to an integrated luminosity of 35.9 fb(-1) at a center-of-mass energy of 13TeV. The Z boson pair decays are reconstructed using the 4l, 2l2q, and 2l2 nu final states, where l = e or mu. Both gluon fusion and electroweak production of the scalar resonance are considered, with a free parameter describing their relative cross sections. A dedicated categorization of events, based on the kinematic properties of associated jets, and matrix element techniques are employed for an optimal signal and background separation. A description of the interference between signal and background amplitudes for a resonance of an arbitrary width is included. No significant excess of events with respect to the standard model expectation is observed and limits are set on the product of the cross section for a new scalar boson and the branching fraction for its decay to ZZ for a large range of masses and widths.

Epidermodysplasia verruciformis (EV) is an autosomal recessive skin disorder with a phenotype conditional on human beta-papillomavirus (beta-HPV) infection. Such infections are common and asymptomatic in the general population, but in individuals with EV, they lead to the development of plane wart-like and red or brownish papules or pityriasis versicolor-like skin lesions, from childhood onwards. Most patients develop non-melanoma skin cancer (NMSC), mostly on areas of UV-exposed skin, from the twenties or thirties onwards. At least half of the cases of typical EV are caused by biallelic loss-of-function mutations of TMC6/EVER1 or TMC8/EVER2. The cellular and molecular basis of disease in TMC/EVER-deficient patients is unknown, but a defect of keratinocyte-intrinsic immunity to beta-HPV is suspected. Indeed, these patients are not susceptible to other infectious diseases and have apparently normal leukocyte development. In contrast, patients with an atypical form of EV due to inborn errors of T-cell immunity invariably develop clinical symptoms of EV in the context of other infectious diseases. The features of the typical and atypical forms of EV thus suggest that the control of beta-HPV infections requires both EVER1/EVER2-dependent keratinocyte-intrinsic immunity and T cell-dependent adaptive immunity.

The study of the behavior of embryonic neurons in controlled in vitro conditions require methodologies that take advantage of advanced tissue engineering approaches to replicate elements of the developing brain extracellular matrix. We report here a series of experiments that explore the potential of photo-polymerized gelatin hydrogels to culture primary embryonic neurons. We employed large medullary reticular neurons whose activity is essential for brain arousal as well as a library of gelatin hydrogels that span a range of mechanical properties, inclusion of brain-mimetic hyaluronic acid, and adhesion peptides. These hydrogel platforms showed inherent capabilities to sustain neuronal viability and were permissive for neuronal differentiation, resulting in the development of neurite outgrowth under specific conditions. The maturation of embryonic medullary reticular cells took place in the absence of growth factors or other exogenous bioactive molecules. Immunocytochemistry labeling of neuron-specific tubulin confirmed the initiation of neural differentiation. Thus, this methodology provides an important validation for future studies of nerve cell growth and maintenance.

NusG/RfaH/Spt5 transcription elongation factors are the only transcription regulators conserved across all life. Bacterial NusG regulates RNA polymerase (RNAP) elongation complexes (ECs) across most genes, enhancing elongation by suppressing RNAP backtracking and coordinating r-dependent termination and translation. The NusG paralog RfaH engages the EC only at operon polarity suppressor (ops) sites and suppresses both backtrack and hairpin-stabilized pausing. We used single-particle cryoelectron microscopy (cryo-EM) to determine structures of ECs at ops with NusG or RfaH. Both factors chaperone base-pairing of the upstream duplex DNA to suppress backtracking, explaining stimulation of elongation genome-wide. The RfaHopsEC structure reveals how RfaH confers operon specificity through specific recognition of an ops hairpin in the single-stranded nontemplate DNA and tighter binding to the EC to exclude NusG. Tight EC binding by RfaH sterically blocks the swiveled RNAP conformation necessary for hairpin-stabilized pausing. The universal conservation of NusG/RfaH/Spt5 suggests that the molecular mechanisms uncovered here are widespread.

Circulating extracellular RNAs (exRNAs) have the potential to serve as biomarkers for a wide range of medical conditions. However, limitations in existing exRNA isolation methods and a lack of knowledge on parameters affecting exRNA variability in human samples may hinder their successful discovery and clinical implementation. Using combinations of denaturants, reducing agents, proteolysis, and revised organic extraction, we developed an automated, high-throughput approach for recovery of exRNAs and exDNA from the same biofluid sample. We applied this method to characterize exRNAs from 312 plasma and serum samples collected from 13 healthy volunteers at 12 time points over a 2-month period. Small RNA cDNA library sequencing identified nearly twofold increased epithelial-,muscle-,and neuroendocrine-cell-specific miRNAs in females, while fasting and hormonal cycle showed little effect. External standardization helped to detect quantitative differences in erythrocyte and platelet-specific miRNA contributions and in miRNA concentrations between biofluids. It also helped to identify a study participant with a unique exRNA phenotype featuring a miRNA signature of up to 20-fold elevated endocrine-cell-specific miRNAs and twofold elevated total miRNA concentrations stable for over 1 year. Collectively, these results demonstrate an efficient and quantitative method to discern exRNA phenotypes and suggest that plasma and serum RNA profiles are stable over months and can be routinely monitored in long-term clinical studies.

The CMS muon detector system, muon reconstruction software, and high-level trigger underwent significant changes in 2013-2014 in preparation for running at higher LHC collision energy and instantaneous luminosity. The performance of the modified system is studied using proton-proton collision data at center-of-mass energy root s = 13 TeV, collected at the LHC in 2015 and 2016. The measured performance parameters, including spatial resolution, efficiency, and timing, are found to meet all design specifications and are well reproduced by simulation. Despite the more challenging running conditions, the modified muon system is found to perform as well as, and in many aspects better than, previously. We dedicate this paper to the memory of Prof. Alberto Benvenuti, whose work was fundamental for the CMS muon detector.

A wide range of ecological and environmental factors influence metal bioaccumulation in fish. Studies of mercury and other metal contaminants in invasive Indo-Pacific lionfish are limited, yet consumption of the invasive predator is increasingly utilized as a management strategy. In this study, we examined the effects of body size, body condition, sex, trophic level, carbon source, diet, depth and capture location on mercury concentrations in lionfish collected from Curacao. In addition, we examined whether or not a local petroleum refinery is the source of metal contamination in lionfish. Mercury concentrations ranged from 0.008 to 0.106 mg/kg and we found no effect of the petroleum refinery on metal bioaccumulation in lionfish. Low concentrations of metal contaminants indicate lionfish from Curacao are safe for human consumption.