744 research outputs found

    Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions.

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    We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies

    Perspective from a Younger Generation -- The Astro-Spectroscopy of Gisbert Winnewisser

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    Gisbert Winnewisser's astronomical career was practically coextensive with the whole development of molecular radio astronomy. Here I would like to pick out a few of his many contributions, which I, personally, find particularly interesting and put them in the context of newer results.Comment: 14 pages. (Co)authored by members of the MPIfR (Sub)millimeter Astronomy Group. To appear in the Proceedings of the 4th Cologne-Bonn-Zermatt-Symposium "The Dense Interstellar Medium in Galaxies" eds. S. Pfalzner, C. Kramer, C. Straubmeier, & A. Heithausen (Springer: Berlin

    Phenotypic Variation and Bistable Switching in Bacteria

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    Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

    Adolescents' experiences of being food-hypersensitive: a qualitative study

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    <p>Abstract</p> <p>Background</p> <p>Experiencing or being at risk of adverse reactions to certain food items is a common health issue, especially among children and adolescents. Research has shown that living with the risk of food reactions and always having to take measures to avoid certain food in one's diet has a negative impact on quality of life. The aim of this study was to illuminate adolescents' experiences of being food hypersensitive.</p> <p>Methods</p> <p>Three focus group interviews and six individual interviews were carried out with all together 17 adolescents, 14–18 years of age, who had exclusion diets at school due to food hypersensitivity. The interviews were taped and transcribed verbatim and a qualitative content analysis was carried out.</p> <p>Results</p> <p>Five categories with subcategories, and one pervading theme, emerged. The categories were: <it>Perceiving oneself as being particular</it>, <it>Feeling constrained</it>, <it>Experiencing others' ignorance</it>, <it>Keeping control</it>, and <it>Feeling it's okay</it>. A pervading theme was conceptualised as <it>Striving to normalise the experience of being food-hypersensitive</it>. The adolescents regarded themselves as competent and courageous, but also described how they avoided the extra attention it implied to ask for special food considerations taken into account. Their self-conceptions were probably essential for their management of and attitude toward the hypersensitivity condition. They felt deprived, and those at risk of severe food reactions experienced insecurity and fear. Feelings of being disregarded were expressed, as well as facing unreliability and a lack of understanding from others. The continual work of constant vigilance and decision-making was described as time-consuming and frustrating. However, the adolescents also experienced considerate and supportive surroundings and were at pains to tone down the negative experiences and consequences of being food-hypersensitive.</p> <p>Conclusion</p> <p>Food avoidance by itself, and not only the somatic food reactions, brings about consequences with significant impacts on adolescents' lives. The findings from this study have implications for all of those who deal with adolescents who are food-hypersensitive, and not only health professionals. A deeper insight into adolescents' experiences gives an understanding which can improve the care-givers' efforts.</p

    At-risk registers integrated into primary care to stop asthma crises in the UK (ARRISA-UK): study protocol for a pragmatic, cluster randomised trial with nested health economic and process evaluations

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    Background: Despite effective treatments and long-standing management guidelines, there are approximately 1400 hospital admissions for asthma weekly in the United Kingdom (UK), many of which could be avoided. In our previous research, a secondary analysis of the intervention (ARRISA) suggested an improvement in the management of at-risk asthma patients in primary care. ARRISA involved identifying individuals at risk of adverse asthma events, flagging their electronic health records, training practice staff to develop and implement practice-wide processes of care when alerted by the flag, plus motivational reminders. We now seek to determine the effectiveness and cost-effectiveness of ARRISA in reducing asthma-related crisis events. Methods: We are undertaking a pragmatic, two-arm, multicentre, cluster randomised controlled trial, plus health economic and process evaluation. We will randomise 270 primary care practices from throughout the UK covering over 10,000 registered patients with ‘at-risk asthma’ identified according to a validated algorithm. Staff in practices randomised to the intervention will complete two 45-min eLearning modules (an individually completed module giving background to ARRISA and a group-completed module to develop practice-wide pathways of care) plus a 30-min webinar with other practices. On completion of training at-risk patients’ records will be coded so that a flag appears whenever their record is accessed. Practices will receive a phone call at 4 weeks and a reminder video at 6 weeks and 6 months. Control practices will continue to provide usual care. We will extract anonymised routine patient data from primary care records (with linkage to secondary care data) to determine the percentage of at-risk patients with an asthma-related crisis event (accident and emergency attendances, hospitalisations and deaths) after 12 months (primary outcome). We will also capture the time to crisis event, all-cause hospitalisations, asthma control and any changes in practice asthma management for at-risk and all patients with asthma. Cost-effectiveness analysis and mixed-methods process evaluations will also be conducted. Discussion: This study is novel in terms of using a practice-wide intervention to target and engage with patients at risk from their asthma and is innovative in the use of routinely captured data with record linkage to obtain trial outcomes. Trial registration: ISRCTN95472706. Registered on 5 December 2014

    Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

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    The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

    Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

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    The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

    Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

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    The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO

    Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy

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    A search for new physics is performed in events with two same-sign isolated leptons, hadronic jets, and missing transverse energy in the final state. The analysis is based on a data sample corresponding to an integrated luminosity of 4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of 7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of 140 increase in integrated luminosity over previously published results. The observed yields agree with the standard model predictions and thus no evidence for new physics is found. The observations are used to set upper limits on possible new physics contributions and to constrain supersymmetric models. To facilitate the interpretation of the data in a broader range of new physics scenarios, information on the event selection, detector response, and efficiencies is provided.Comment: Published in Physical Review Letter
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