Smeared versus localised sources in flux compactifications

We investigate whether vacuum solutions in flux compactifications that are obtained with smeared sources (orientifolds or D-branes) still survive when the sources are localised. This seems to rely on whether the solutions are BPS or not. First we consider two sets of BPS solutions that both relate to the GKP solution through T-dualities: (p+1)-dimensional solutions from spacetime-filling Op-planes with a conformally Ricci-flat internal space, and p-dimensional solutions with Op-planes that wrap a 1-cycle inside an everywhere negatively curved twisted torus. The relation between the solution with smeared orientifolds and the localised version is worked out in detail. We then demonstrate that a class of non-BPS AdS_4 solutions that exist for IASD fluxes and with smeared D3-branes (or analogously for ISD fluxes with anti-D3-branes) does not survive the localisation of the (anti) D3-branes. This casts doubts on the stringy consistency of non-BPS solutions that are obtained in the limit of smeared sources.Comment: 23 pages; v2: minor corrections, added references, version published in JHE

Fluxes and Warping for Gauge Couplings in F-theory

We compute flux-dependent corrections in the four-dimensional F-theory effective action using the M-theory dual description. In M-theory the 7-brane fluxes are encoded by four-form flux and modify the background geometry and Kaluza-Klein reduction ansatz. In particular, the flux sources a warp factor which also depends on the torus directions of the compactification fourfold. This dependence is crucial in the derivation of the four-dimensional action, although the torus fiber is auxiliary in F-theory. In M-theory the 7-branes are described by an infinite array of Taub-NUT spaces. We use the explicit metric on this geometry to derive the locally corrected warp factor and M-theory three-from as closed expressions. We focus on contributions to the 7-brane gauge coupling function from this M-theory back-reaction and show that terms quadratic in the internal seven-brane flux are induced. The real part of the gauge coupling function is modified by the M-theory warp factor while the imaginary part is corrected due to a modified M-theory three-form potential. The obtained contributions match the known weak string coupling result, but also yield additional terms suppressed at weak coupling. This shows that the completion of the M-theory reduction opens the way to compute various corrections in a genuine F-theory setting away from the weak string coupling limit.Comment: 46 page

Sunscreens - Which and what for?

It is well established that sun exposure is the main cause for the development of skin cancer. Chronic continuous UV radiation is believed to induce malignant melanoma, whereas intermittent high-dose UV exposure contributes to the occurrence of actinic keratosis as precursor lesions of squamous cell carcinoma as well as basal cell carcinoma. Not only photocarcinogenesis but also the mechanisms of photoaging have recently become apparent. In this respect the use of sunscreens seemed to prove to be more and more important and popular within the last decades. However, there is still inconsistency about the usefulness of sunscreens. Several studies show that inadequate use and incomplete UV spectrum efficacy may compromise protection more than previously expected. The sunscreen market is crowded by numerous products. Inorganic sunscreens such as zinc oxide and titanium oxide have a wide spectral range of activity compared to most of the organic sunscreen products. It is not uncommon for organic sunscreens to cause photocontact allergy, but their cosmetic acceptability is still superior to the one given by inorganic sunscreens. Recently, modern galenic approaches such as micronization and encapsulation allow the development of high-quality inorganic sunscreens. The potential systemic toxicity of organic sunscreens has lately primarily been discussed controversially in public, and several studies show contradictory results. Although a matter of debate, at present the sun protection factor (SPF) is the most reliable information for the consumer as a measure of sunscreen filter efficacy. In this context additional tests have been introduced for the evaluation of not only the protective effect against erythema but also protection against UV-induced immunological and mutational effects. Recently, combinations of UV filters with agents active in DNA repair have been introduced in order to improve photoprotection. This article reviews the efficacy of sunscreens in the prevention of epithelial and nonepithelial skin cancer, the effect on immunosuppression and the value of the SPF as well as new developments on the sunscreen market. Copyright (C) 2005 S. Karger AG, Basel

Presence and Seeding Activity of Pathological Prion Protein (PrPTSE) in Skeletal Muscles of White-Tailed Deer Infected with Chronic Wasting Disease

Chronic wasting disease (CWD) is a contagious, rapidly spreading transmissible spongiform encephalopathy (TSE), or prion disease, occurring in cervids such as white tailed-deer (WTD), mule deer or elk in North America. Despite efficient horizontal transmission of CWD among cervids natural transmission of the disease to other species has not yet been observed. Here, we report for the first time a direct biochemical demonstration of pathological prion protein PrPTSE and of PrPTSE-associated seeding activity, the static and dynamic biochemical markers for biological prion infectivity, respectively, in skeletal muscles of CWD-infected cervids, i. e. WTD for which no clinical signs of CWD had been recognized. The presence of PrPTSE was detected by Western- and postfixed frozen tissue blotting, while the seeding activity of PrPTSE was revealed by protein misfolding cyclic amplification (PMCA). Semi-quantitative Western blotting indicated that the concentration of PrPTSE in skeletal muscles of CWD-infected WTD was approximately 2000-10000 -fold lower than in brain tissue. Tissue-blot-analyses revealed that PrPTSE was located in muscle-associated nerve fascicles but not, in detectable amounts, in myocytes. The presence and seeding activity of PrPTSE in skeletal muscle from CWD-infected cervids suggests prevention of such tissue in the human diet as a precautionary measure for food safety, pending on further clarification of whether CWD may be transmissible to humans

Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function

Impact of a mobile phone and web program on symptom and functional outcomes for people with mild-to-moderate depression, anxiety and stress: a randomised controlled trial.

Background Mobile phone-based psychological interventions enable real time self-monitoring and self-management, and large-scale dissemination. However, few studies have focused on mild-to-moderate symptoms where public health need is greatest, and none have targeted work and social functioning. This study reports outcomes of a CONSORT-compliant randomised controlled trial (RCT) to evaluate the efficacy of myCompass, a self-guided psychological treatment delivered via mobile phone and computer, designed to reduce mild-to-moderate depression, anxiety and stress, and improve work and social functioning. Method Community-based volunteers with mild-to-moderate depression, anxiety and/or stress (N= 720) were randomly assigned to the myCompass program, an attention control intervention, or to a waitlist condition for seven weeks. The interventions were fully automated, without any human input or guidance. Participants’ symptoms and functioning were assessed at baseline, post-intervention and 3-month follow-up, using the Depression, Anxiety and Stress Scale and the Work and Social Adjustment Scale. Results Retention rates at post-intervention and follow-up for the study sample were 72.1% (n= 449) and 48.6% (n= 350) respectively. The myCompass group showed significantly greater improvement in symptoms of depression, anxiety and stress and in work and social functioning relative to both control conditions at the end of the 7-week intervention phase (between-group effect sizes ranged from d= .22 to d= .55 based on the observed means). Symptom scores remained at near normal levels at 3-month follow-up. Participants in the attention control condition showed gradual symptom improvement during the post-intervention phase and their scores did not differ from the myCompass group at 3-month follow-up. Conclusions The myCompass program is an effective public health program, facilitating rapid improvements in symptoms and in work and social functioning for individuals with mild-to-moderate mental health problems

A meta-analytic review of stand-alone interventions to improve body image

Objective Numerous stand-alone interventions to improve body image have been developed. The present review used meta-analysis to estimate the effectiveness of such interventions, and to identify the specific change techniques that lead to improvement in body image. Methods The inclusion criteria were that (a) the intervention was stand-alone (i.e., solely focused on improving body image), (b) a control group was used, (c) participants were randomly assigned to conditions, and (d) at least one pretest and one posttest measure of body image was taken. Effect sizes were meta-analysed and moderator analyses were conducted. A taxonomy of 48 change techniques used in interventions targeted at body image was developed; all interventions were coded using this taxonomy. Results The literature search identified 62 tests of interventions (N = 3,846). Interventions produced a small-to-medium improvement in body image (d+ = 0.38), a small-to-medium reduction in beauty ideal internalisation (d+ = -0.37), and a large reduction in social comparison tendencies (d+ = -0.72). However, the effect size for body image was inflated by bias both within and across studies, and was reliable but of small magnitude once corrections for bias were applied. Effect sizes for the other outcomes were no longer reliable once corrections for bias were applied. Several features of the sample, intervention, and methodology moderated intervention effects. Twelve change techniques were associated with improvements in body image, and three techniques were contra-indicated. Conclusions The findings show that interventions engender only small improvements in body image, and underline the need for large-scale, high-quality trials in this area. The review identifies effective techniques that could be deployed in future interventions

Methods to study splicing from high-throughput RNA Sequencing data

The development of novel high-throughput sequencing (HTS) methods for RNA (RNA-Seq) has provided a very powerful mean to study splicing under multiple conditions at unprecedented depth. However, the complexity of the information to be analyzed has turned this into a challenging task. In the last few years, a plethora of tools have been developed, allowing researchers to process RNA-Seq data to study the expression of isoforms and splicing events, and their relative changes under different conditions. We provide an overview of the methods available to study splicing from short RNA-Seq data. We group the methods according to the different questions they address: 1) Assignment of the sequencing reads to their likely gene of origin. This is addressed by methods that map reads to the genome and/or to the available gene annotations. 2) Recovering the sequence of splicing events and isoforms. This is addressed by transcript reconstruction and de novo assembly methods. 3) Quantification of events and isoforms. Either after reconstructing transcripts or using an annotation, many methods estimate the expression level or the relative usage of isoforms and/or events. 4) Providing an isoform or event view of differential splicing or expression. These include methods that compare relative event/isoform abundance or isoform expression across two or more conditions. 5) Visualizing splicing regulation. Various tools facilitate the visualization of the RNA-Seq data in the context of alternative splicing. In this review, we do not describe the specific mathematical models behind each method. Our aim is rather to provide an overview that could serve as an entry point for users who need to decide on a suitable tool for a specific analysis. We also attempt to propose a classification of the tools according to the operations they do, to facilitate the comparison and choice of methods.Comment: 31 pages, 1 figure, 9 tables. Small corrections adde