The rockefeller university

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.

A search is presented for new high-mass resonances decaying into electron or muon pairs. The search uses proton-proton collision data at a centre-of-mass energy of 13TeV collected by the CMS experiment at the LHC in 2016, corresponding to an integrated luminosity of 36 fb(-1). Observations are in agreement with standard model expectations. Upper limits on the product of a new resonance production cross section and branching fraction to dileptons are calculated in a model-independent manner. This permits the interpretation of the limits in models predicting a narrow dielectron or dimuon resonance. A scan of different intrinsic width hypotheses is performed. Limits are set on the masses of various hypothetical particles. For the Z(SSM)' (Z(psi)') particle, which arises in the sequential standard model (superstring-inspired model), a lower mass limit of 4.50 (3.90) TeV is set at 95% confidence level. The lightest Kaluza-Klein graviton arising in the Randall-Sundrum model of extra dimensions, with coupling parameters k/(M) over bar (Pl) of 0.01, 0.05, and 0.10, is excluded at 95% con fi dence level below 2.10, 3.65, and 4.25TeV, respectively. In a simpli fi ed model of dark matter production via a vector or axial vector mediator, limits at 95% con fi dence level are obtained on the masses of the dark matter particle and its mediator.

The lateral-line neuromast of the zebrafish displays a restricted, consistent pattern of innervation that facilitates the comparison of microcircuits across individuals, developmental stages, and genotypes. We used serial blockface scanning electron microscopy to determine from multiple specimens the neuromast connectome, a comprehensive set of connections between hair cells and afferent and efferent nerve fibers. This analysis delineated a complex but consistent wiring pattern with three striking characteristics: each nerve terminal is highly specific in receiving innervation from hair cells of a single directional sensitivity; the innervation is redundant; and the terminals manifest a hierarchy of dominance. Mutation of the canonical planar-cell-polarity gene vangl2, which decouples the asymmetric phenotypes of sibling hair-cell pairs, results in randomly positioned, randomly oriented sibling cells that nonetheless retain specific wiring. Because larvae that overexpress Notch exhibit uniformly oriented, uniformly innervating hair-cell siblings, wiring specificity is mediated by the Notch signaling pathway.

High-throughput genomic technologies yield about 20,000 variants in the protein-coding exome of each individual. A commonly used approach to select candidate disease-causing variants is to test whether the associated gene has been previously reported to be disease-causing. In the absence of known disease-causing genes, it can be challenging to associate candidate genes with specific genetic diseases. To facilitate the discovery of novel gene-disease associations, we determined the putative biologically closest known genes and their associated diseases for 13,005 human genes not currently reported to be disease-associated. We used these data to construct the closest disease-causing genes (CDG) server, which can be used to infer the closest genes with an associated disease for a user-defined list of genes or diseases. We demonstrate the utility of the CDG server in five immunodeficiency patient exomes across different diseases and modes of inheritance, where CDG dramatically reduced the number of candidate genes to be evaluated. This resource will be a considerable asset for ascertaining the potential relevance of genetic variants found in patient exomes to specific diseases of interest.

Diverse biological systems utilize fluctuations ("noise'') in gene expression to drive lineage-commitment decisions. However, once a commitment is made, noise becomes detrimental to reliable function, and the mechanisms enabling post-commitment noise suppression are unclear. Here, we find that architectural constraints on noise suppression are overcome to stabilize fate commitment. Using single-molecule and time-lapse imaging, we find that-after a noise-driven event-human immunodeficiency virus (HIV) strongly attenuates expression noise through a non-transcriptional negative-feedback circuit. Feedback is established through a serial cascade of post-transcriptional splicing, whereby proteins generated from spliced mRNAs autodeplete their own precursor unspliced mRNAs. Strikingly, this auto-depletion circuitry minimizes noise to stabilize HIV's commitment decision, and a noisesuppression molecule promotes stabilization. This feedback mechanism for noise suppression suggests a functional role for delayed splicing in other systems and may represent a generalizable architecture of diverse homeostatic signaling circuits.

Feeding is a complex motivated behavior controlled by a distributed neural network that processes sensory information to generate adaptive behavioral responses. Accordingly, studies using appetitive Pavlovian conditioning confirm that environmental cues that are associated with food availability can induce feeding even in satiated subjects. However, in mice, appetitive conditioning generally requires intensive training and thus can impede molecular studies that often require large numbers of animals. To address this, we developed and validated a simple and rapid context-induced feeding (Ctx-IF) task in which cues associated with food availability can later lead to increased food consumption in sated mice. We show that the associated increase in food consumption is driven by both positive and negative reinforcement and that spaced training is more effective than massed training. Ctx-IF can be completed in ~1 week and provides an opportunity to study the molecular mechanisms and circuitry underlying non-homeostatic eating. We have used this paradigm to map brain regions that are activated during Ctx-IF with cFos immunohistochemistry and found that the insular cortex, and other regions, are activated following exposure to cues denoting the availability of food. Finally, we show that inhibition of the insular cortex using GABA agonists impairs performance of the task. Our findings provide a novel assay in mice for defining the functional neuroanatomy of appetitive conditioning and identify specific brain regions that are activated during the development of learned behaviors that impact food consumption.

Background: Due to rapid research progress in reproductive biology and reproductive clinical endocrinology, many human infertility treatments are close to potential breakthroughs and translational applications. We here review current barriers, where such breakthroughs will likely come from, what they will entail, and their potential clinical applications. Main text: The radical nature of change will primarily benefit older women, reduce fertility treatment costs and thereby expand access to treatment. A still widely overlooked prerequisite for implantation and normal pregnancy maintenance is timely development of maternal immunological tolerance toward an implanting paternal semiallograft, if malfunctioning associated with implantation failure and pregnancy loss, while premature termination of tolerance appears associated with premature labor, pre-eclampsia/eclampsia and gestoses of pregnancy. Common denominators between pregnancy and invasive malignancies have again been attracting attention, suggesting that, like in malignant tumors, degrees of embryo aneuploidy may affect invasiveness and ability to "disarm" the immune system's innate response against implanting embryos. Linking tolerance to implantation, we offer evidence that the so-called "implantation window" is likely immunological rather than hormonally defined. Conclusions: Because many here outlined treatment changes will disproportionally benefit older women, they will exert a pronounced effect on society, as increasing numbers of women at grandparental ages will become mothers.

We generated a large collection of temperature-sensitive lethal mutants in the unicellular green alga Chlamydomonas reinhardtii, focusing on mutations specifically affecting cell cycle regulation. We used UV mutagenesis and robotically assisted phenotypic screening to isolate candidates. To overcome the bottleneck at the critical step of molecular identification of the causative mutation ("driver"), we developed MAPS-SEQ (meiosis-assisted purifying selection sequencing), a multiplexed genetic/bioinformatics strategy. MAPS-SEQ allowed us to perform multiplexed simultaneous determination of the driver mutations from hundreds of neutral "passenger" mutations in each member of a large pool of mutants. This method should work broadly, including in multicellular diploid genetic systems, for any scorable trait. Using MAPS-SEQ, we identified essential genes spanning a wide range of molecular functions. Phenotypic clustering based on DNA content analysis and cell morphology indicated that the mutated genes function in the cell cycle at multiple points and by diverse mechanisms. The collection is sufficiently complete to allow specific conditional inactivation of almost all cell-cycle-regulatory pathways. Approximately seventy-five percent of the essential genes identified in this project had clear orthologs in land plant genomes, a huge enrichment compared with the value of similar to 20% for the Chlamydomonas genome overall. Findings about these mutants will likely have direct relevance to essential cell biology in land plants.