Higgs mass and vacuum stability in the Standard Model at NNLO

We present the first complete next-to-next-to-leading order analysis of the Standard Model Higgs potential. We computed the two-loop QCD and Yukawa corrections to the relation between the Higgs quartic coupling (lambda) and the Higgs mass (Mh), reducing the theoretical uncertainty in the determination of the critical value of Mh for vacuum stability to 1 GeV. While lambda at the Planck scale is remarkably close to zero, absolute stability of the Higgs potential is excluded at 98% C.L. for Mh < 126 GeV. Possible consequences of the near vanishing of lambda at the Planck scale, including speculations about the role of the Higgs field during inflation, are discussed.Comment: 35 pages, 8 figures. Final published version, misprints fixed, figures update

Treatment of Problem Alcohol Use in Women of Childbearing Age: Results of a Brief Intervention Trial

Studies suggest that 14% of women age 18 to 40 drink alcohol above recommended limits. Of special concern is the increasing use of alcohol by women during pregnancy. This article reports 48 month follow-up data from a subanalysis of a trial for early alcohol treatment (Project TrEAT) focused on women of childbearing age. Methods : Project TrEAT was conducted in the offices of 64 primary care, community-based physicians from 10 Wisconsin counties. Of 5979 female patients ages 18 to 40 who were screened for problem drinking, 205 were randomized into an experimental group ( n = 103) or control group ( n = 102). The intervention consisted of two 15 min, physician-delivered counseling visits that included advice, education, and contracting by using a scripted workbook. A total of 174 subjects (85%) completed the 48 month follow-up procedures. Results : No significant differences were found between the experimental and control groups at baseline for alcohol use, age, socioeconomic status, smoking, depression or anxiety, conduct disorder, lifetime drug use, or health care utilization. The trial found a significant treatment effect in reducing both 7 day alcohol use ( p = 0.0039) and binge drinking episodes ( p = 0.0021) over the 48 month follow-up period. Women in the experimental group who became pregnant during the follow-up period had the most dramatic decreases in alcohol use. A logistic regression model based on a 20% or greater reduction in drinking found an odds ratio of 1.93 (confidence interval 1.07–3.46) in the sample exposed to physician intervention. Age, smoking, depression, conduct disorder, antisocial personality disorder, and illicit drug use did not reduce drinking significantly. No significant differences were found in health care utilization and health status between groups. Conclusions : This trial provides the first direct evidence that brief intervention is associated with sustained reductions in alcohol consumption by women of childbearing age. The results have enormous implications for the U.S. health care system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66074/1/j.1530-0277.2000.tb04570.x.pd

PKCε Stimulated Arginine Methylation of RIP140 for Its Nuclear-Cytoplasmic Export in Adipocyte Differentiation

Receptor interacting protein 140 (RIP140) is a versatile transcriptional co-repressor that plays roles in diverse metabolic processes including fat accumulation in adipocytes. Previously we identified three methylated arginine residues in RIP140, which rendered its export to the cytoplasm; but it was unclear what triggered RIP140 arginine methylation.In this study, we determined the activated PKCepsilon as the specific trigger for RIP140 arginine methylation and its subsequent export. We identified two PKCepsilon-phosphorylated residues of RIP140, Ser-102 and Ser-1003, which synergistically stimulated direct binding of RIP140 by 14-3-3 that recruited protein arginine methyl transferase 1 to methylate RIP140. The methylated RIP140 then preferentially recruited exportin 1 for nuclear export. As a result, the nuclear gene-repressive activity of RIP140 was reduced. In RIP140 null adipocyte cultures, the defect in fat accumulation was effectively rescued by the phosphorylation-deficient mutant RIP140 that resided predominantly in the nucleus, but less so by the phospho-mimetic RIP140 that was exported to the cytoplasm.This study uncovers a novel means, via a cascade of protein modifications, to inactivate, or suppress, the nuclear action of an important transcription coregulator RIP140, and delineates the first specific phosphorylation-arginine methylation cascade that could alter protein subcellular distribution and biological activity

Alcohol use as a risk factor for tuberculosis – a systematic review

<p>Abstract</p> <p>Background</p> <p>It has long been evident that there is an association between alcohol use and risk of tuberculosis. It has not been established to what extent this association is confounded by social and other factors related to alcohol use. Nor has the strength of the association been established. The objective of this study was to systematically review the available evidence on the association between alcohol use and the risk of tuberculosis.</p> <p>Methods</p> <p>Based on a systematic literature review, we identified 3 cohort and 18 case control studies. These were further categorized according to definition of exposure, type of tuberculosis used as study outcome, and confounders controlled for. Pooled effect sizes were obtained for each sub-category of studies.</p> <p>Results</p> <p>The pooled relative risk across all studies that used an exposure cut-off level set at 40 g alcohol per day or above, or defined exposure as a clinical diagnosis of an alcohol use disorder, was 3.50 (95% CI: 2.01–5.93). After exclusion of small studies, because of suspected publication bias, the pooled relative risk was 2.94 (95% CI: 1.89–4.59). Subgroup analyses of studies that had controlled for various sets of confounders did not give significantly different results and did not explain the significant heterogeneity that was found across the studies.</p> <p>Conclusion</p> <p>The risk of active tuberculosis is substantially elevated in people who drink more than 40 g alcohol per day, and/or have an alcohol use disorder. This may be due to both increased risk of infection related to specific social mixing patterns associated with alcohol use, as well as influence on the immune system of alcohol itself and of alcohol related conditions.</p

Deep-Inelastic Inclusive ep Scattering at Low x and a Determination of alpha_s

A precise measurement of the inclusive deep-inelastic e^+p scattering cross section is reported in the kinematic range 1.5<= Q^2 <=150 GeV^2 and 3*10^(-5)<= x <=0.2. The data were recorded with the H1 detector at HERA in 1996 and 1997, and correspond to an integrated luminosity of 20 pb^(-1). The double differential cross section, from which the proton structure function F_2(x,Q^2) and the longitudinal structure function F_L(x,Q^2) are extracted, is measured with typically 1% statistical and 3% systematic uncertainties. The measured partial derivative (dF_2(x,Q^2)/dln Q^2)_x is observed to rise continuously towards small x for fixed Q^2. The cross section data are combined with published H1 measurements at high Q^2 for a next-to-leading order DGLAP QCD analysis.The H1 data determine the gluon momentum distribution in the range 3*10^(-4)<= x <=0.1 to within an experimental accuracy of about 3% for Q^2 =20 GeV^2. A fit of the H1 measurements and the mu p data of the BCDMS collaboration allows the strong coupling constant alpha_s and the gluon distribution to be simultaneously determined. A value of alpha _s(M_Z^2)=0.1150+-0.0017 (exp) +0.0009-0.0005 (model) is obtained in NLO, with an additional theoretical uncertainty of about +-0.005, mainly due to the uncertainty of the renormalisation scale.Comment: 68 pages, 24 figures and 18 table

A structural comparison of human serum transferrin and human lactoferrin

The transferrins are a family of proteins that bind free iron in the blood and bodily fluids. Serum transferrins function to deliver iron to cells via a receptor-mediated endocytotic process as well as to remove toxic free iron from the blood and to provide an anti-bacterial, low-iron environment. Lactoferrins (found in bodily secretions such as milk) are only known to have an anti-bacterial function, via their ability to tightly bind free iron even at low pH, and have no known transport function. Though these proteins keep the level of free iron low, pathogenic bacteria are able to thrive by obtaining iron from their host via expression of outer membrane proteins that can bind to and remove iron from host proteins, including both serum transferrin and lactoferrin. Furthermore, even though human serum transferrin and lactoferrin are quite similar in sequence and structure, and coordinate iron in the same manner, they differ in their affinities for iron as well as their receptor binding properties: the human transferrin receptor only binds serum transferrin, and two distinct bacterial transport systems are used to capture iron from serum transferrin and lactoferrin. Comparison of the recently solved crystal structure of iron-free human serum transferrin to that of human lactoferrin provides insight into these differences

Impact of vital signs screening & clinician prompting on alcohol and tobacco screening and intervention rates: a pre-post intervention comparison

<p>Abstract</p> <p>Background</p> <p>Though screening and intervention for alcohol and tobacco misuse are effective, primary care screening and intervention rates remain low. Previous studies have increased intervention rates using vital signs screening for tobacco misuse and clinician prompts for screen-positive patients for both alcohol and tobacco misuse. This pilot study's aims were: (1) To determine the feasibility of combined vital signs screening for tobacco and alcohol misuse, (2) To assess the impact of vital signs screening on alcohol and tobacco screening and intervention rates, and (3) To assess the additional impact of tobacco assessment prompts on intervention rates.</p> <p>Methods</p> <p>In five outpatient practices, nurses measuring vital signs were trained to routinely ask a single tobacco question, a prescreening question that identified current drinkers, and the single alcohol screening question for current drinkers. After 4-8 weeks, clinicians were trained in tobacco intervention and nurses were trained to give tobacco abusers a tobacco questionnaire which also served as a clinician intervention prompt. Screening and intervention rates were measured using patient exit interviews (n = 622) at baseline, during the "screening only" period, and during the tobacco prompting phase. Changes in screening and intervention rates were compared using chi square analyses and test of linear trends. Clinic staff were interviewed regarding patient and staff acceptability. Logistic regression was used to evaluate the impact of nurse screening on clinician intervention, the impact of alcohol intervention on concurrent tobacco intervention, and the impact of tobacco intervention on concurrent alcohol intervention.</p> <p>Results</p> <p>Alcohol and tobacco screening rates and alcohol intervention rates increased after implementing vital signs screening (p < .05). During the tobacco prompting phase, clinician intervention rates increased significantly for both alcohol (12.4%, p < .001) and tobacco (47.4%, p = .042). Screening by nurses was associated with clinician advice to reduce alcohol use (OR 13.1; 95% CI 6.2-27.6) and tobacco use (OR 2.6; 95% CI 1.3-5.2). Acceptability was high with nurses and patients.</p> <p>Conclusions</p> <p>Vital signs screening can be incorporated in primary care and increases alcohol screening and intervention rates. Tobacco assessment prompts increase both alcohol and tobacco interventions. These simple interventions show promise for dissemination in primary care settings.</p

A cre-inducible DUX4 transgenic mouse model for investigating facioscapulohumeral muscular dystrophy

The Double homeobox 4 (DUX4) gene is an important regulator of early human development and its aberrant expression is causal for facioscapulohumeral muscular dystrophy (FSHD). The DUX4-full length (DUX4-fl) mRNA splice isoform encodes a transcriptional activator; however, DUX4 and its unique DNA binding preferences are specific to old-world primates. Regardless, the somatic cytotoxicity caused by DUX4 expression is conserved when expressed in cells and animals ranging from fly to mouse. Thus, viable animal models based on DUX4-fl expression have been difficult to generate due in large part to overt developmental toxicity of low DUX4-fl expression from leaky transgenes. We have overcome this obstacle and here we report the generation and initial characterization of a line of conditional floxed DUX4-fl transgenic mice, FLExDUX4, that is viable and fertile. In the absence of cre, these mice express a very low level of DUX4-fl mRNA from the transgene, resulting in mild phenotypes. However, when crossed with appropriate cre-driver lines of mice, the double transgenic offspring readily express DUX4-fl mRNA, protein, and target genes with the spatiotemporal pattern of nuclear cre expression dictated by the chosen system. When cre is expressed from the ACTA1 skeletal muscle-specific promoter, the double transgenic animals exhibit a developmental myopathy. When crossed with tamoxifen-inducible cre lines, DUX4-mediated pathology can be induced in adult animals. Thus, the appearance and progression of pathology can be controlled to provide readily screenable phenotypes useful for assessing therapeutic approaches targeting DUX4-fl mRNA and protein. Overall, the FLExDUX4 line of mice is quite versatile and will allow new investigations into mechanisms of DUX4-mediated pathophysiology as well as much-needed pre-clinical testing of DUX4-targeted FSHD interventions in vivo

The tenth data release of the Sloan digital sky survey: First spectroscopic data from the SDSS-iii apache point observatory galactic evolution experiment

The Sloan Digital Sky Survey (SDSS) has been in operation since 2000 April. This paper presents the tenth public data release (DR10) from its current incarnation, SDSS-III. This data release includes the first spectroscopic data from the Apache Point Observatory Galaxy Evolution Experiment (APOGEE), along with spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS) taken through 2012 July. The APOGEE instrument is a near-infrared R ~ 22,500 300-fiber spectrograph covering 1:514-1:696 μm. The APOGEE survey is studying the chemical abundances and radial velocities of roughly 100,000 red giant star candidates in the bulge, bar, disk, and halo of the Milky Way. DR10 includes 178,397 spectra of 57,454 stars, each typically observed three or more times, from APOGEE. Derived quantities from these spectra (radial velocities, effective temperatures, surface gravities, and metallicities) are also included. DR10 also roughly doubles the number of BOSS spectra over those included in the ninth data release. DR10 includes a total of 1,507,954 BOSS spectra, comprising 927,844 galaxy spectra; 182,009 quasar spectra; and 159,327 stellar spectra, selected over 6373.2 deg2.This is an author-created, un-copyedited version of an article accepted for publication in The Astrophysical Journal Supplement Series. The publisher is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at http://dx.doi.org/10.1088/0067-0049/211/2/17. The accepted version will be under embargo until the 18th March 2015