On Semiclassical Limits of String States

We explore the relation between classical and quantum states in both open and closed (super)strings discussing the relevance of coherent states as a semiclassical approximation. For the closed string sector a gauge-fixing of the residual world-sheet rigid translation symmetry of the light-cone gauge is needed for the construction to be possible. The circular target-space loop example is worked out explicitly.Comment: 12 page

Informing investment to reduce inequalities: a modelling approach

Background: Reducing health inequalities is an important policy objective but there is limited quantitative information about the impact of specific interventions. Objectives: To provide estimates of the impact of a range of interventions on health and health inequalities. Materials and methods: Literature reviews were conducted to identify the best evidence linking interventions to mortality and hospital admissions. We examined interventions across the determinants of health: a ‘living wage’; changes to benefits, taxation and employment; active travel; tobacco taxation; smoking cessation, alcohol brief interventions, and weight management services. A model was developed to estimate mortality and years of life lost (YLL) in intervention and comparison populations over a 20-year time period following interventions delivered only in the first year. We estimated changes in inequalities using the relative index of inequality (RII). Results: Introduction of a ‘living wage’ generated the largest beneficial health impact, with modest reductions in health inequalities. Benefits increases had modest positive impacts on health and health inequalities. Income tax increases had negative impacts on population health but reduced inequalities, while council tax increases worsened both health and health inequalities. Active travel increases had minimally positive effects on population health but widened health inequalities. Increases in employment reduced inequalities only when targeted to the most deprived groups. Tobacco taxation had modestly positive impacts on health but little impact on health inequalities. Alcohol brief interventions had modestly positive impacts on health and health inequalities only when strongly socially targeted, while smoking cessation and weight-reduction programmes had minimal impacts on health and health inequalities even when socially targeted. Conclusions: Interventions have markedly different effects on mortality, hospitalisations and inequalities. The most effective (and likely cost-effective) interventions for reducing inequalities were regulatory and tax options. Interventions focused on individual agency were much less likely to impact on inequalities, even when targeted at the most deprived communities

Integrating Ion Mobility Mass Spectrometry with Molecular Modelling to Determine the Architecture of Multiprotein Complexes

Current challenges in the field of structural genomics point to the need for new tools and technologies for obtaining structures of macromolecular protein complexes. Here, we present an integrative computational method that uses molecular modelling, ion mobility-mass spectrometry (IM-MS) and incomplete atomic structures, usually from X-ray crystallography, to generate models of the subunit architecture of protein complexes. We begin by analyzing protein complexes using IM-MS, and by taking measurements of both intact complexes and sub-complexes that are generated in solution. We then examine available high resolution structural data and use a suite of computational methods to account for missing residues at the subunit and/or domain level. High-order complexes and sub-complexes are then constructed that conform to distance and connectivity constraints imposed by IM-MS data. We illustrate our method by applying it to multimeric protein complexes within the Escherichia coli replisome: the sliding clamp, (β2), the γ complex (γ3δδ′), the DnaB helicase (DnaB6) and the Single-Stranded Binding Protein (SSB4)

Radiative Transfer for Exoplanet Atmospheres

Remote sensing of the atmospheres of distant worlds motivates a firm understanding of radiative transfer. In this review, we provide a pedagogical cookbook that describes the principal ingredients needed to perform a radiative transfer calculation and predict the spectrum of an exoplanet atmosphere, including solving the radiative transfer equation, calculating opacities (and chemistry), iterating for radiative equilibrium (or not), and adapting the output of the calculations to the astronomical observations. A review of the state of the art is performed, focusing on selected milestone papers. Outstanding issues, including the need to understand aerosols or clouds and elucidating the assumptions and caveats behind inversion methods, are discussed. A checklist is provided to assist referees/reviewers in their scrutiny of works involving radiative transfer. A table summarizing the methodology employed by past studies is provided.Comment: 7 pages, no figures, 1 table. Filled in missing information in references, main text unchange

Reproductive abnormalities in mice expressing omega-3 fatty acid desaturase in their mammary glands

The Caenorhabditis elegans n-3 fatty acid desaturase (Fat-1) acts on a range of 18- and 20-carbon n-6 fatty acid substrates. Transgenic female mice expressing the Fat-1 gene under transcriptional control of the goat β-casein promoter produce milk phospholipids having elevated levels of n-3 polyunsaturated fatty acids (PUFA). However, females from this line were also observed to have impaired reproductive performance characterized by a smaller litter size (2.7 ± 0.6 vs. 7.2 ± 0.7; P < 0.05) than wildtype controls. While there is a close association between PUFA metabolism, prostaglandin biosynthesis, and fertility; reproductive problems in these mice were unanticipated given that the Fat-1 transgene is primarily expressed in the lactating mammary gland. Using multiple approaches it was found that Fat-1 mice have normal ovulation and fertilization rates; however fewer embryos were present in the uterus prior to implantation. Small litter size was also found to be partly attributable to a high incidence of post-implantation fetal resorptions. Embryo transfer experiments revealed that embryos developing from oocytes derived from transgenic ovaries had an increased rate of post-implantation resorption, regardless of the uterine genotype. Ovary transplantation between Fat-1 and C57BL/6 wildtype females revealed that non-ovarian factors also contributed to the smaller litter size phenotype. Finally, surgical removal of the mammary glands from juvenile Fat-1 mice increased the subsequent number of implantation sites per female, but did not lessen the high rate of post-implantation resorptions. In conclusion, we herein report on a system where an exogenous transgene expressed predominately in the mammary gland detrimentally affects female reproduction, suggesting that in certain circumstances the mammary gland may function as an endocrine regulator of reproductive performance

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

Summative supervisor reporting: a quality performance perspective

Objective This study aimed to quality assure Assigned Educational Supervisor (AES) reports, using UK Joint Committee on Surgical Training objective criteria, to evaluate contribution to Annual Review of Competence Progression. Design Consecutive 145 AES reports from 75 trainers regarding 68 Core Surgical Trainees were assessed from 9 hospitals (2 Tertiary centers [77 reports], 7 District General Hospitals [68 reports]). Reports were assessed by independent assessors based on free text related to performance mapped to curricular objectives, operative logbooks, and Clinical Supervisor reports, and overall summary grades assigned ranging from development required, adequate, good to excellent. Setting A core surgical training program serving a single UK (Wales) deanery. Participants Sixty-eight consecutively appointed core surgical trainees and 75 consultant surgeon trainers. Results Summary grades of adequate or above were achieved in 101 of 145 (69.7%) reports. Trainees’ objective setting meetings were completed within 6 weeks of starting placements in 124 of 145 (85.5%). The proportions of AES reports containing free text commentary on curricular objectives, portfolio objectives, and operative logbook development were 128 of 145, 123 of 145, and 55 of 145, respectively. AES report quality was not associated with hospital status, subspecialty, or trainee grade. Female trainers were significantly more likely to provide reports graded as Good or Excellent compared with their male colleagues (7 of 12 vs. 27 of 133, χ2 (2) = 9.389, p = 0.009). AES reports for male trainees were significantly more likely to be rated as further development required (40 of 85, 47.1%) when compared with female trainees (4 of 32, 12.5%, p = 0.007). Conclusions Three in ten AES reports were insufficient to contribute to objective Annual Review of Competence Progression outcomes and a gender gap was apparent related to engagement. AES trainers should provide more focus if this summative tool is to be an effective career progression metric

A sociological dilemma: race, segregation, and US sociology

US sociology has been historically segregated in that, at least until the 1960s, there were two distinct institutionally organized traditions of sociological thought – one black and one white. For the most part, however, dominant historiographies have been silent on that segregation and, at best, reproduce it when addressing the US sociological tradition. This is evident in the rarity with which scholars such as WEB Du Bois, E Franklin Frazier, Oliver Cromwell Cox, or other ‘African American Pioneers of Sociology’, as Saint-Arnaud calls them, are presented as core sociological voices within histories of the discipline. This article addresses the absence of African American sociologists from the US sociological canon and, further, discusses the implications of this absence for our understanding of core sociological concepts. With regard to the latter, the article focuses in particular on the debates around equality and emancipation and discusses the ways in which our understanding of these concepts could be extended by taking into account the work of African American sociologists and their different interpretations of core themes

Uncoupling the functions of CALM in VAMP sorting and clathrin-coated pit formation.

CALM (clathrin assembly lymphoid myeloid leukemia protein) is a cargo-selective adaptor for the post-Golgi R-SNAREs VAMPs 2, 3, and 8, and it also regulates the size of clathrin-coated pits and vesicles at the plasma membrane. The present study has two objectives: to determine whether CALM can sort additional VAMPs, and to investigate whether VAMP sorting contributes to CALM-dependent vesicle size regulation. Using a flow cytometry-based endocytosis efficiency assay, we demonstrate that CALM is also able to sort VAMPs 4 and 7, even though they have sorting signals for other clathrin adaptors. CALM homologues are present in nearly every eukaryote, suggesting that the CALM family may have evolved as adaptors for retrieving all post-Golgi VAMPs from the plasma membrane. Using a knockdown/rescue system, we show that wild-type CALM restores normal VAMP sorting in CALM-depleted cells, but that two non-VAMP-binding mutants do not. However, when we assayed the effect of CALM depletion on coated pit morphology, using a fluorescence microscopy-based assay, we found that the two mutants were as effective as wild-type CALM. Thus, we can uncouple the sorting function of CALM from its structural role

Cold-water coral distributions in the Drake Passage area from towed camera observations – initial interpretations

This article is distributed under the terms of the Creative Commons Public Domain. The definitive version was published in PLoS One 6 (2011): e16153, doi:10.1371/journal.pone.0016153.Seamounts are unique deep-sea features that create habitats thought to have high levels of endemic fauna, productive fisheries and benthic communities vulnerable to anthropogenic impacts. Many seamounts are isolated features, occurring in the high seas, where access is limited and thus biological data scarce. There are numerous seamounts within the Drake Passage (Southern Ocean), yet high winds, frequent storms and strong currents make seafloor sampling particularly difficult. As a result, few attempts to collect biological data have been made, leading to a paucity of information on benthic habitats or fauna in this area, particularly those on primarily hard-bottom seamounts and ridges. During a research cruise in 2008 six locations were examined (two on the Antarctic margin, one on the Shackleton Fracture Zone, and three on seamounts within the Drake Passage), using a towed camera with onboard instruments to measure conductivity, temperature, depth and turbidity. Dominant fauna and bottom type were categorized from 200 randomized photos from each location. Cold-water corals were present in high numbers in habitats both on the Antarctic margin and on the current swept seamounts of the Drake Passage, though the diversity of orders varied. Though the Scleractinia (hard corals) were abundant on the sedimented margin, they were poorly represented in the primarily hard-bottom areas of the central Drake Passage. The two seamount sites and the Shackleton Fracture Zone showed high numbers of stylasterid (lace) and alcyonacean (soft) corals, as well as large numbers of sponges. Though data are preliminary, the geological and environmental variability (particularly in temperature) between sample sites may be influencing cold-water coral biogeography in this region. Each area observed also showed little similarity in faunal diversity with other sites examined for this study within all phyla counted. This manuscript highlights how little is understood of these isolated features, particularly in Polar regions.This work was funded by the National Science Foundation’s Antarctic Earth Sciences Program (ANT0636787 awarded to LFR and RGW) and a CenSeam minigrant (awarded to RGW), and RGW is supported by a SOEST Young Investigator Fellowship from the University of Hawaii at Manoa