The rockefeller university

The differential production cross sections of B-+/- mesons are measured via the exclusive decay channels B-+/- -> J/psi K-+/- -> mu(+)mu K--(+/-) as a function of transverse momentum in pp and Pb-Pb collisions at a center-of-mass energy root s(NN) = 5.02 TeV per nucleon pair with the CMS detector at the LHC. The pp(Pb - Pb) data set used for this analysis corresponds to an integrated luminosity of 28.0 pb(-1) (351 mu b(-1)). The measurement is performed in the B-+/- meson transverse momentum range of 7 to 50 GeV/c, in the rapidity interval vertical bar y vertical bar < 2.4. In this kinematic range, a strong suppression of the production cross section by about a factor of 2 is observed in the Pb-Pb system in comparison to the expectation from pp reference data. These results are found to be roughly compatible with theoretical calculations incorporating beauty quark diffusion and energy loss in a quark-gluon plasma.

Background: Adolescence is the most vulnerable period, the period of greatest susceptibility to the development of addiction, for all those who are exposed to psychoactive substances. Despite a substantial experience of psychoactive usage prevention programmes (including educational work and even random urine tests), their success has so far been limited. Aims: To describe the results of educational and urine testing drug programmes among all the students and staff at in a private high school in order to identify and curtail drug use in its early stages and so save lives. Methods: During six years (April 2008 to April 2014) of studies in a private high school, urine samples for substance abuse (cannabinoids, cocaine, heroin, morphine, oxycontin, methadone, benzodiazepine, amphetamines, and ethanol) were collected and tested among all grades (9th-12th) and staff. The tests were done every few months in a random manner, and involved everyone. Positive tests were re-checked and were defined as positive if no medical prescriptions had been written. Results: During this period we performed 19 tests (about three per year) among all available students on each occasion (with numbers of participants ranging from 37 to 137). Reviewing all the 19 test times during the six years, only four students showed positive results for cannabinoids (two of them only once, the other two more than once). Conclusions: The programme results indicated minimum substance usage among adolescent children. Our finding was limited to a private high school with a selected population group, where all students and staff members agreed to participate in the programme when registering for admission to the school or, for staff members, when taking up employment. Based on our observational non-controlled study, future programmes, including controlled studies, can now be recommended.

Although bacterial bioactive metabolites have been one of the most prolific sources of lead structures for the development of small-molecule therapeutics, very little is known about the environmental factors associated with changes in secondary metabolism across natural environments. Large-scale sequencing of environmental microbiomes has the potential to shed light on the richness of bacterial biosynthetic diversity hidden in the environment, how it varies from one environment to the next, and what environmental factors correlate with changes in biosynthetic diversity. In this study, the sequencing of PCR amplicons generated using primers targeting either ketosynthase domains from polyketide biosynthesis or adenylation domains from nonribosomal peptide biosynthesis was used to assess biosynthetic domain composition and richness in soils collected across the Australian continent. Using environmental variables collected at each soil site, we looked for environmental factors that correlated with either high overall domain richness or changes in the domain composition. Among the environmental variables we measured, changes in biosynthetic domain composition correlate most closely with changes in latitude and to a lesser extent changes in pH. Although it is unclear at this time the exact mix of factors that may drive the relationship between biosynthetic domain composition and latitude, from a practical perspective the identification of a latitudinal basis for differences in soil metagenome biosynthetic domain compositions should help guide future natural product discovery efforts.

A measurement of the differential cross sections for a W boson produced in association with jets in the muon decay channel is presented. The measurement is based on 13 TeV proton-proton collision data corresponding to an integrated luminosity of 2.2 fb(-1), recorded by the CMS detector at the LHC. The cross sections are reported as functions of jet multiplicity, jet transverse momentum pT, jet rapidity, the scalar pT sum of the jets, and angular correlations between the muon and each jet for different jet multiplicities. The measured cross sections are in agreement with predictions that include multileg leading-order (LO) and next-to-LO matrix element calculations interfaced with parton showers, as well as a next-to-next-to-LO calculation for the W boson and one jet production.

Across scientific disciplines, thresholded pairwise measures of statistical dependence between time series are taken as proxies for the interactions between the dynamical units of a network. Yet such correlation measures often fail to reflect the underlying physical interactions accurately. Here we systematically study the problem of reconstructing direct physical interaction networks from thresholding correlations. We explicate how local common cause and relay structures, heterogeneous in-degrees and non-local structural properties of the network generally hinder reconstructibility. However, in the limit of weak coupling strengths we prove that stationary systems with dynamics close to a given operating point transition to universal reconstructiblity across all network topologies.

Results are reported from a search for supersymmetric particles in proton-proton collisions in the final state with a single lepton, multiple jets, including at least one b-tagged jet, and large missing transverse momentum. The search uses a sample of proton-proton collision data at root s = 13 TeV recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 35.9 fb(-1). The observed event yields in the signal regions are consistent with those expected from standard model backgrounds. The results are interpreted in the context of simplified models of supersymmetry involving gluino pair production, with gluino decay into either on- or off-mass-shell top squarks. Assuming that the top squarks decay into a top quark plus a stable, weakly interacting neutralino, scenarios with gluino masses up to about 1.9 TeV are excluded at 95% confidence level for neutralino masses up to about 1 TeV.

B cells undergo rapid cell division and affinity maturation in anatomically distinct sites in lymphoid organs called germinal centers (GCs). Homeostasis is maintained in part by B cell apoptosis. However, the precise contribution of apoptosis to GC biology and selection is not well defined. We developed apoptosis-indicator mice and used them to visualize, purify, and characterize dying GC B cells. Apoptosis is prevalent in the GC, with up to half of all GC B cells dying every 6 hours. Moreover, programmed cell death is differentially regulated in the light zone and the dark zone: Light-zone B cells die by default if they are not positively selected, whereas dark-zone cells die when their antigen receptors are damaged by activation-induced cytidine deaminase.

Males and females use distinct brain circuits to cope with similar challenges. Using RNA sequencing of ribosome-bound mRNA from hippocampal CA3 neurons, we found remarkable sex differences and discovered that female mice displayed greater gene expression activation after acute stress than males. Stress-sensitive BDNF Val66Met mice of both sexes show a pre-stressed translational phenotype in which the same genes that are activated without applied stress are also induced in wild-type mice by an acute stressor. Behaviourally, only heterozygous BDNF Val66Met females exhibit spatial memory impairment, regardless of acute stress. Interestingly, this effect is not observed in ovariectomized heterozygous BDNF Val66Met females, suggesting that circulating ovarian hormones induce cognitive impairment in Met carriers. Cognitive deficits are not observed in males of either genotype. Thus, in a brain region not normally associated with sex differences, this work sheds light on ways that genes, environment and sex interact to affect the transcriptome's response to a stressor.

The APOBEC3 family of cytidine deaminases cause lethal hypermutation of retroviruses via deamination of newly reverse-transcribed viral DNA. Their ability to bind RNA is essential for virion infiltration and antiviral activity, yet the mechanisms of viral RNA recognition are unknown. By screening naturally occurring, polymorphic, non-human primate APOBEC3H variants for biological and crystallization properties, we obtained a 2.24-angstrom crystal structure of pig-tailed macaque APOBEC3H with bound RNA. Here, we report that APOBEC3H forms a dimer around a short RNA duplex and, despite the bound RNA, has potent cytidine deaminase activity. The structure reveals an unusual RNA-binding mode in which two APOBEC3H molecules at opposite ends of a seven-base-pair duplex interact extensively with both RNA strands, but form no protein-protein contacts. CLIP-seq analysis revealed that APOBEC3H preferentially binds to sequences in the viral genome predicted to contain duplexes, a property that may facilitate both virion incorporation and catalytic activity.

Senescence is a terminal differentiation program that halts the growth of damaged cells and must be circumvented for cancer to arise. Here we describe a panel of genetic screens to identify genes required for replicative senescence. We uncover a role in senescence for the potent tumor suppressor and ATM substrate USP28. USP28 controls activation of both the TP53 branch and the GATA4/NFkB branch that controls the senescence-associated secretory phenotype (SASP). These results suggest a role for ubiquitination in senescence and imply a common node downstream from ATM that links the TP53 and GATA4 branches of the senescence response.