571 research outputs found

    Charge Lattices and Consistency of 6D Supergravity

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    We extend the known consistency conditions on the low-energy theory of six-dimensional N = 1 supergravity. We review some facts about the theory of two-form gauge fields and conclude that the charge lattice Gamma for such a theory has to be self-dual. The Green-Schwarz anomaly cancellation conditions in the supergravity theory determine a sublattice of Gamma. The condition that this sublattice can be extended to a self-dual lattice Gamma leads to a strong constraint on theories that otherwise appear to be self-consistent.Comment: 15 pages. v2: minor changes; references, additional example added; v3: minor corrections and clarifications added, JHEP versio

    Targeting smoking cessation to high prevalence communities: outcomes from a pilot intervention for gay men

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    BACKGROUND: Cigarette smoking prevalence among gay men is twice that of population levels. A pilot community-level intervention was developed and evaluated aiming to meet UK Government cessation and cancer prevention targets. METHODS: Four 7-week withdrawal-oriented treatment groups combined nicotine replacement therapy with peer support. Self-report and carbon monoxide register data were collected at baseline and 7 weeks. N = 98 gay men were recruited through community newspapers and organisations in London UK. RESULTS: At 7 weeks, n = 44 (76%) were confirmed as quit using standard UK Government National Health Service monitoring forms. In multivariate analysis the single significant baseline variable associated with cessation was previous number of attempts at quitting (OR 1.48, p = 0.04). CONCLUSIONS: This tailored community-level intervention successfully recruited a high-prevalence group, and the outcome data compares very favourably to national monitoring data (which reports an average of 53% success). Implications for national targeted services are considered

    Simultaneous disruption of two DNA polymerases, Polη and Polζ, in Avian DT40 cells unmasks the role of Polη in cellular response to various DNA lesions

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    Replicative DNA polymerases are frequently stalled by DNA lesions. The resulting replication blockage is released by homologous recombination (HR) and translesion DNA synthesis (TLS). TLS employs specialized TLS polymerases to bypass DNA lesions. We provide striking in vivo evidence of the cooperation between DNA polymerase η, which is mutated in the variant form of the cancer predisposition disorder xeroderma pigmentosum (XP-V), and DNA polymerase ζ by generating POLη−/−/POLζ−/− cells from the chicken DT40 cell line. POLζ−/− cells are hypersensitive to a very wide range of DNA damaging agents, whereas XP-V cells exhibit moderate sensitivity to ultraviolet light (UV) only in the presence of caffeine treatment and exhibit no significant sensitivity to any other damaging agents. It is therefore widely believed that Polη plays a very specific role in cellular tolerance to UV-induced DNA damage. The evidence we present challenges this assumption. The phenotypic analysis of POLη−/−/POLζ−/− cells shows that, unexpectedly, the loss of Polη significantly rescued all mutant phenotypes of POLζ−/− cells and results in the restoration of the DNA damage tolerance by a backup pathway including HR. Taken together, Polη contributes to a much wide range of TLS events than had been predicted by the phenotype of XP-V cells

    Structure of Human DNA Polymerase κ Inserting dATP Opposite an 8-OxoG DNA Lesion

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    Background: Oxygen-free radicals formed during normal aerobic cellular metabolism attack bases in DNA and 7,8-dihydro-8-oxoguanine (8-oxoG) is one of the major lesions formed. It is amongst the most mutagenic lesions in cells because of its dual coding potential, wherein 8-oxoG(syn) can pair with an A in addition to normal base pairing of 8-oxoG(anti) with a C. Human DNA polymerase κ (Polκ) is a member of the newly discovered Y-family of DNA polymerases that possess the ability to replicate through DNA lesions. To understand the basis of Polκ\u27s preference for insertion of an A opposite 8-oxoG lesion, we have solved the structure of Polκ in ternary complex with a template-primer presenting 8-oxoG in the active site and with dATP as the incoming nucleotide. Methodology and Principal Findings: We show that the Polκ active site is well-adapted to accommodate 8-oxoG in the syn conformation. That is, the polymerase and the bound template-primer are almost identical in their conformations to that in the ternary complex with undamaged DNA. There is no steric hindrance to accommodating 8-oxoG in the syn conformation for Hoogsteen base-paring with incoming dATP. Conclusions and Significance: The structure we present here is the first for a eukaryotic translesion synthesis (TLS) DNA polymerase with an 8-oxoG:A base pair in the active site. The structure shows why Polκ is more efficient at inserting an A opposite the 8-oxoG lesion than a C. The structure also provides a basis for why Polκ is more efficient at inserting an A opposite the lesion than other Y-family DNA polymerases

    Housing mice in the individually ventilated or open cages—Does it matter for behavioral phenotype?

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    Individually ventilated caging (IVC) systems for rodents are increasingly common in laboratory animal facilities. However, the impact of such substantial change in housing conditions on animal physiology and behavior is still debated. Most importantly, there arise the questions regarding reproducibility and comparison of previous or new phenotypes between the IVC and open cages. The present study was set up for detailed and systematic comparison of behavioral phenotypes in male and female mice of three widely used inbred strains (C57BL/6JRccHsd, DBA/2JRccHsd, 129S2/SvHSd) after being kept in two housing environments (IVC and open cages) for 6?weeks (since 4?weeks of age) before behavioral testing. The tests addressed exploratory, anxiety-like and stress-related behavior (light-dark box, open field, forced swim test, stress-induced hyperthermia), social approach and species-specific behavior (nest building, marble burying). In all tests, large and expected strain differences were found. Somewhat surprisingly, the most striking effect of environment was found for basal body temperature and weight loss after one night of single housing in respective cages. In addition, the performance in light-dark box and open field was affected by environment. Several parameters in different tests showed significant interaction between housing and genetic background. In summary, the IVC housing did not invalidate the well-known differences between the mouse strains which have been established by previous studies. However, within the strains the results can be influenced by sex and housing system depending on the behavioral tasks applied. The bottom-line is that the environmental conditions should be described explicitly in all publications.Peer reviewe

    Assessment of the quality and variability of health information on chronic pain websites using the DISCERN instrument

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    <p>Abstract</p> <p>Background</p> <p>The Internet is used increasingly by providers as a tool for disseminating pain-related health information and by patients as a resource about health conditions and treatment options. However, health information on the Internet remains unregulated and varies in quality, accuracy and readability. The objective of this study was to determine the quality of pain websites, and explain variability in quality and readability between pain websites.</p> <p>Methods</p> <p>Five key terms (pain, chronic pain, back pain, arthritis, and fibromyalgia) were entered into the Google, Yahoo and MSN search engines. Websites were assessed using the DISCERN instrument as a quality index. Grade level readability ratings were assessed using the Flesch-Kincaid Readability Algorithm. Univariate (using alpha = 0.20) and multivariable regression (using alpha = 0.05) analyses were used to explain the variability in DISCERN scores and grade level readability using potential for commercial gain, health related seals of approval, language(s) and multimedia features as independent variables.</p> <p>Results</p> <p>A total of 300 websites were assessed, 21 excluded in accordance with the exclusion criteria and 110 duplicate websites, leaving 161 unique sites. About 6.8% (11/161 websites) of the websites offered patients' commercial products for their pain condition, 36.0% (58/161 websites) had a health related seal of approval, 75.8% (122/161 websites) presented information in English only and 40.4% (65/161 websites) offered an interactive multimedia experience. In assessing the quality of the unique websites, of a maximum score of 80, the overall average DISCERN Score was 55.9 (13.6) and readability (grade level) of 10.9 (3.9). The multivariable regressions demonstrated that website seals of approval (<it>P </it>= 0.015) and potential for commercial gain (<it>P </it>= 0.189) were contributing factors to higher DISCERN scores, while seals of approval (<it>P </it>= 0.168) and interactive multimedia (<it>P </it>= 0.244) contributed to lower grade level readability, as indicated by estimates of the beta coefficients.</p> <p>Conclusion</p> <p>The overall quality of pain websites is moderate, with some shortcomings. Websites that scored high using the DISCERN questionnaire contained health related seals of approval and provided commercial solutions for pain related conditions while those with low readability levels offered interactive multimedia options and have been endorsed by health seals.</p

    Bus accident severity and passenger injury: evidence from Denmark

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    Purpose Bus safety is a concern not only in developing countries, but also in the U.S. and Europe. In Denmark, disentangling risk factors that are positively or negatively related to bus accident severity and injury occurrence to bus passengers can contribute to promote safety as an essential principle of sustainable transit and advance the vision “every accident is one too many”. Methods Bus accident data were retrieved from the national accident database for the period 2002–2011. A generalized ordered logit model allows analyzing bus accident severity and a logistic regression enables examining occurrence of injury to bus passengers. Results Bus accident severity is positively related to (i) the involvement of vulnerable road users, (ii) high speed limits, (iii) night hours, (iv) elderly drivers of the third party involved, and (v) bus drivers and other drivers crossing in yellow or red light. Occurrence of injury to bus passengers is positively related to (i) the involvement of heavy vehicles, (ii) crossing intersections in yellow or red light, (iii) open areas, (iv) high speed limits, and (v) slippery road surface. Conclusions The findings of the current study provide a comprehensive picture of the bus safety situation in Denmark and suggest the necessity of further research into bus drivers’ attitudes and perceptions of risks and road users’ perceptions of bus operations. Moreover, these findings suggest the need for further training into bus drivers’ hazard recognition skills and infrastructural solutions to forgive possible driving errors

    Increased risk of venous thrombosis by AB alleles of the ABO blood group and Factor V Leiden in a Brazilian population

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    Most cases of a predisposition to venous thrombosis are caused by resistance to activated protein C, associated in 95% of cases with the Factor V Leiden allele (FVL or R506Q). Several recent studies report a further increased risk of thrombosis by an association between the AB alleles of the ABO blood group and Factor V Leiden. The present study investigated this association with deep vein thrombosis (DVT) in individuals treated at the Hemocentro de Pernambuco in northeastern Brazil. A case-control comparison showed a significant risk of thrombosis in the presence of Factor V Leiden (OR = 10.1), which was approximately doubled when the AB alleles of the ABO blood group were present as well (OR = 22.3). These results confirm that the increased risk of deep vein thrombosis in the combined presence of AB alleles and Factor V Leiden is also applicable to the Brazilian population suggesting that ABO blood group typing should be routinely added to FVL in studies involving thrombosis
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