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Positivity bounds are powerful tools to constrain effective field theories. Utilizing the partial wave expansion in the dispersion relation and the full crossing symmetry of the scattering amplitude, we derive several sets of generically nonlinear positivity bounds for a generic scalar effective field theory: We refer to these as the P Q, D su , D stu and Dstu bounds. While the P Q bounds and D su bounds only make use of the s ↔ u dispersion relation, the D stu and Dstu bounds are obtained by further imposing the s ↔ t crossing symmetry. In contradistinction to the linear positivity for scalars, these inequalities can be applied to put upper and lower bounds on Wilson coefficients, and are much more constraining as shown in the lowest orders. In particular we are able to exclude theories with soft amplitude behaviour such as weakly broken Galileon theories from admitting a standard UV completion. We also apply these bounds to chiral perturbation theory and we find these bounds are stronger than the previous bounds in constraining its Wilson coefficients.

Cellular senescence has been viewed as a tumor suppression mechanism and also as a contributor to individual aging. Widespread shortening of 3 ′ untranslated regions (3 ′ UTRs) in messenger RNAs (mRNAs) by alternative polyadenylation (APA) has recently been discovered in cancer cells. However, the role of APA in the process of cellular senescence remains elusive. Here, we found that hundreds of genes in senescent cells tended to use distal poly(A) (pA) sites, leading to a global lengthening of 3 ′ UTRs and reduced gene expression. Genes that harbor longer 3 ′ UTRs in senescent cells were enriched in senescence-related pathways. Rras2, a member of the Ras superfamily that participates in multiple signal transduction pathways, preferred longer 3 ′ UTR usage and exhibited decreased expression in senescent cells. Depletion of Rras2 promoted senescence, while rescue of Rras2 reversed senescence-associated phenotypes. Mechanistically, splicing factor TRA2B bound to a core "AGAA" motif located in the alternative 3 ′ UTR of Rras2, thereby reducing the RRAS2 protein level and causing senescence. Both proximal and distal poly(A) signals showed strong sequence conservation, highlighting the vital role of APA regulation during evolution. Our results revealed APA as a novel mechanism in regulating cellular senescence.

BackgroundOccupational stress is an important risk factor for mental health among occupational population. Exploring related mediators of workers’ mental health are important to improve their health and performance. Our study aims to explore the relationships between work stress, positive psychological resources, burnout and well-being.MethodsThe study was performed during the period of June and July in 2015. A questionnaire that consisted of the Effort-reward Imbalance Scale, the Maslach Burnout Inventory-General Survey, the Psychological Capital Questionnaire, the Rosenberg Self-esteem Scale, the Flourishing Scale, as well as demographic and working factors.ResultsPsychological capital mediated the associations of effort-reward imbalance and emotional exhaustion, cynicism, professional efficacy and well-being. Self-esteem mediated the associations of effort-reward imbalance ratio with cynicism, professional efficacy and well-being, and mediated the associations of overcommitment and cynicism, professional efficacy and well-being.ConclusionsThe findings indicated that enhancing positive psychological resources could be considered in developing intervention strategies for psychological health among manufacturing employees.Electronic supplementary materialThe online version of this article (10.1186/s12888-017-1533-6) contains supplementary material, which is available to authorized users.

Genetic susceptibility to type 2 diabetes is primarily due to β cell dysfunction. However, a genetic study to directly interrogate β cell function ex vivo has never been previously performed. We isolated 233,447 islets from 483 Diversity Outbred (DO) mice maintained on a Western-style diet, and measured insulin secretion in response to a variety of secretagogues. Insulin secretion from DO islets ranged greater than 1000-fold even though none of the mice were diabetic. The insulin secretory response to each secretagogue had a unique genetic architecture; some of the loci were specific for one condition, whereas others overlapped. Human loci that are syntenic to many of the insulin secretion quantitative trait loci (QTL) from mice are associated with diabetes-related SNPs in human genome-wide association studies. We report on 3 genes, Ptpn18, Hunk, and Zfp148, where the phenotype predictions from the genetic screen were fulfilled in our studies of transgenic mouse models. These 3 genes encode a nonreceptor type protein tyrosine phosphatase, a serine/threonine protein kinase, and a Krϋppel-type zinc-finger transcription factor, respectively. Our results demonstrate that genetic variation in insulin secretion that can lead to type 2 diabetes is discoverable in nondiabetic individuals.

Background: The effect of probiotic therapy on bacterial vaginosis (BV) is controversial. We conducted a meta-analysis of the efficacy and safety associated with probiotic treatment for BV. Methods: We searched multiple databases covering up to 1 March 2018. Studies published as blinded randomized controlled trials (RCTs), comparing treatment using probiotic versus active or placebo control in BV patients were included, with at least one-month follow-up. Random effects model and trial sequential analysis (TSA) were applied. Results: Ten studies (n = 2321) were included. Compared with placebo, the probiotics-only therapy resulted in a beneficial outcome both in clinical cure rate at the 30th day (risk ratio, RR = 2.57; 95% confidential interval, 95% CI: 1.96 to 3.37), and Nugent score (mean difference, MD = −2.71; 95% CI: −3.41 to −2.00). This effect decreased but remained significant after eight weeks. Probiotics-post-antibiotics therapy had a decreased effect only for a short term and possibly among studies with a mostly black study population. No extra adverse events were observed. The TSA suggested a larger sample size for effective evaluation of the probiotics as a supplementary remedy. Conclusions: Probiotic regimes are safe and may exhibit a short-term and long-term beneficial effect for BV treatment. The ethnic-specific result for the probiotic used after antibiotics is worthy of further study.

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