The status of the quantum dissipation-fluctuation relation and Langevin equation

I examine the arguments which have been given for quantum fluctuation-dissipation theorems. I distinguish between a weak form of the theorem, which is true under rather general conditions, and a strong form which requires a Langevin equation for its statement. I argue that the latter has not been reliably derived.Comment: 9 page

Community responses to seawater warming are conserved across diverse biological groupings and taxonomic resolutions

Temperature variability is a major driver of ecological pattern, with recent changes in average and extreme temperatures having significant impacts on populations, communities and ecosystems. In the marine realm, very few experiments have manipulated temperature in situ, and current understanding of temperature effects on community dynamics is limited. We developed new technology for precise seawater temperature control to examine warming effects on communities of bacteria, microbial eukaryotes (protists) and metazoans. Despite highly contrasting phylogenies, size spectra and diversity levels, the three community types responded similarly to seawater warming treatments of +3°C and +5°C, highlighting the critical and overarching importance of temperature in structuring communities. Temperature effects were detectable at coarse taxonomic resolutions and many taxa responded positively to warming, leading to increased abundances at the community-level. Novel field-based experimental approaches are essential to improve mechanistic understanding of how ocean warming will alter the structure and functioning of diverse marine communities

Identification of 2-Aminothiazole-4-Carboxylate Derivatives Active against Mycobacterium tuberculosis H37Rv and the β-Ketoacyl-ACP Synthase mtFabH

Background Tuberculosis (TB) is a disease which kills two million people every year and infects approximately over one-third of the world's population. The difficulty in managing tuberculosis is the prolonged treatment duration, the emergence of drug resistance and co-infection with HIV/AIDS. Tuberculosis control requires new drugs that act at novel drug targets to help combat resistant forms of Mycobacterium tuberculosis and reduce treatment duration. Methodology/Principal Findings Our approach was to modify the naturally occurring and synthetically challenging antibiotic thiolactomycin (TLM) to the more tractable 2-aminothiazole-4-carboxylate scaffold to generate compounds that mimic TLM's novel mode of action. We report here the identification of a series of compounds possessing excellent activity against M. tuberculosis H37Rv and, dissociatively, against the β-ketoacyl synthase enzyme mtFabH which is targeted by TLM. Specifically, methyl 2-amino-5-benzylthiazole-4-carboxylate was found to inhibit M. tuberculosis H37Rv with an MIC of 0.06 µg/ml (240 nM), but showed no activity against mtFabH, whereas methyl 2-(2-bromoacetamido)-5-(3-chlorophenyl)t​hiazole-4-carboxylateinhibited mtFabH with an IC50 of 0.95±0.05 µg/ml (2.43±0.13 µM) but was not active against the whole cell organism. Conclusions/Significance These findings clearly identify the 2-aminothiazole-4-carboxylate scaffold as a promising new template towards the discovery of a new class of anti-tubercular agents

Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model

Exosomes are endosome-derived small membrane vesicles that are secreted by most cell types including tumor cells. Tumor-derived exosomes usually contain tumor antigens and have been used as a source of tumor antigens to stimulate anti-tumor immune responses. However, many reports also suggest that tumor-derived exosomes can facilitate tumor immune evasion through different mechanisms, most of which are antigen-independent. In the present study we used a mouse model of delayed-type hypersensitivity (DTH) and demonstrated that local administration of tumor-derived exosomes carrying the model antigen chicken ovalbumin (OVA) resulted in the suppression of DTH response in an antigen-specific manner. Analysis of exosome trafficking demonstrated that following local injection, tumor-derived exosomes were internalized by CD11c+ cells and transported to the draining LN. Exosome-mediated DTH suppression is associated with increased mRNA levels of TGF-β1 and IL-4 in the draining LN. The tumor-derived exosomes examined were also found to inhibit DC maturation. Taken together, our results suggest a role for tumor-derived exosomes in inducing tumor antigen-specific immunosuppression, possibly by modulating the function of APCs. © 2011 Yang et al

The effectiveness of exercise interventions for people with Parkinson's disease: a systematic review and meta-analysis

This is the peer reviewed version of the article, which has been published in final form at doi: 10.1002/mds.21922.. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Parkinson's disease (PD) is a neurodegenerative disorder affecting the physical, psychological, social, and functional status of individuals. Exercise programs may be an effective strategy to delay or reverse functional decline for people with PD and a large body of empirical evidence has emerged in recent years. The objective is to systematically review randomized controlled trials (RCTs) reporting on the effectiveness of exercise interventions on outcomes (physical, psychological or social functioning, or quality of life) for people with PD. RCTs meeting the inclusion criteria were identified by systematic searching of electronic databases. Key data were extracted by two independent researchers. A mixed methods approach was undertaken using narrative, vote counting, and random effects meta-analysis methods. Fourteen RCTs were included and the methodological quality of most studies was moderate. Evidence supported exercise as being beneficial with regards to physical functioning, health-related quality of life, strength, balance and gait speed for people with PD. There was insufficient evidence support or refute the value of exercise in reducing falls or depression. This review found evidence of the potential benefits of exercise for people with PD, although further good quality research is needed. Questions remain around the optimal content of exercise interventions (dosing, component exercises) at different stages of the disease.National Institute of Health Researc

CAD in mammography: lesion-level versus case-level analysis of the effects of prompts on human decisions

Object: To understand decision processes in CAD-supported breast screening by analysing how prompts affect readers’ judgements of individual mammographic features (lesions). To this end we analysed hitherto unexamined details of reports completed by mammogram readers in an earlier evaluation of a CAD tool. Material and methods: Assessments of lesions were extracted from 5,839 reports for 59 cancer cases. Statistical analyses of these data focused on what features readers considered when recalling a cancer case and how readers reacted to CAD prompts. Results: About 13.5% of recall decisions were found to be caused by responses to features other than those indicating actual cancer. Effects of CAD: lesions were more likely to be examined if prompted; the presence of a prompt on a cancer increased the probability of both detection and recall especially for less accurate readers in subtler cases; lack of prompts made cancer features less likely to be detected; false prompts made non-cancer features more likely to be classified as cancer. Conclusion: The apparent lack of impact reported for CAD in some studies is plausibly due to CAD systematically affecting readers’ identification of individual features, in a beneficial way for certain combinations of readers and features and a damaging way for others. Mammogram readers do not ignore prompts. Methodologically, assessing CAD by numbers of recalled cancer cases may be misleading

Assessing the educational potential and language content of touchscreen apps for preschool children

Touchscreen apps have the potential to teach children important early skills including oral language. However, there is little empirical data assessing the educational potential of children's apps in the app market or how apps link to theories of cognitive development to support learning. We compared popular children's apps with a learning goal (N=18) and without (N=26) using systematic evaluation tools to assess the educational potential and app features that may support learning. We also transcribed all utterances in the apps that included language with a learning goal (N=18) and without (N=12) in order to compare a number of psycholinguistic measures relating to accessibility of the language. Apps with a learning goal had higher educational potential, more opportunities for feedback, a higher proportion of ostensive feedback, and age-appropriate language to support learning and language development. Thus, we argue that selecting children's apps based on the presence of a learning goal is a good first step for selecting an educational app for pre-school age children. Nevertheless, app developers could do more to promote exploratory app use, adjust content to a child's performance, and make use of social interactions with characters onscreen in their apps to enhance the educational potential. Children's apps could also make better use of feedback to ensure that it is specific, meaningful and constructive to better facilitate learning

Mapping 6D N = 1 supergravities to F-theory

We develop a systematic framework for realizing general anomaly-free chiral 6D supergravity theories in F-theory. We focus on 6D (1, 0) models with one tensor multiplet whose gauge group is a product of simple factors (modulo a finite abelian group) with matter in arbitrary representations. Such theories can be decomposed into blocks associated with the simple factors in the gauge group; each block depends only on the group factor and the matter charged under it. All 6D chiral supergravity models can be constructed by gluing such blocks together in accordance with constraints from anomalies. Associating a geometric structure to each block gives a dictionary for translating a supergravity model into a set of topological data for an F-theory construction. We construct the dictionary of F-theory divisors explicitly for some simple gauge group factors and associated matter representations. Using these building blocks we analyze a variety of models. We identify some 6D supergravity models which do not map to integral F-theory divisors, possibly indicating quantum inconsistency of these 6D theories.Comment: 37 pages, no figures; v2: references added, minor typos corrected; v3: minor corrections to DOF counting in section