924 research outputs found

    Does observability affect prosociality?

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    The observation of behaviour is a key theoretical parameter underlying a number of models of prosociality. However, the empirical findings showing the effect of observability on prosociality are mixed. In this meta-analysis, we explore the boundary conditions that may account for this variability, by exploring key theoretical and methodological moderators of this link. We identified 117 papers yielding 134 study level effects (Total N = 788, 164) and found a small but statistically significant, positive association between observability and prosociality (r = .141, 95% CI = .106, .175). Moderator analysis showed that observability produced stronger effects on prosociality (1) in the presence of passive observers (i.e., people whose role was to only observe participants) vs perceptions of being watched, (2) when participants decisions were consequential (vs non-consequential), (3) when the studies were performed in the laboratory (as opposed to in the field/online), (4) when studies used repeated measures (instead of single games) and (5) when studies involved social dilemmas (instead of bargaining games). These effects show the conditions under which observability effects on prosociality will be maximally observed. We describe the theoretical and practical significance of 14 these results

    The chemopreventive polyphenol Curcumin prevents hematogenous breast cancer metastases in immunodeficient mice

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    Dissemination of metastatic cells probably occurs long before diagnosis of the primary tumor. Metastasis during early phases of carcinogenesis in high risk patients is therefore a potential prevention target. The plant polyphenol Curcumin has been proposed for dietary prevention of cancer. We therefore examined its effects on the human breast cancer cell line MDA-MB-231 in vitro and in a mouse metastasis model. Curcumin strongly induces apoptosis in MDA- MB- 231 cells in correlation with reduced activation of the survival pathway NF kappa B, as a consequence of diminished I kappa B and p65 phosphorylation. Curcumin also reduces the expression of major matrix metalloproteinases (MMPs) due to reduced NF kappa B activity and transcriptional downregulation of AP-1. NF kappa B/p65 silencing is sufficient to downregulate c-jun and MMP expression. Reduced NF kappa B/AP-1 activity and MMP expression lead to diminished invasion through a reconstituted basement membrane and to a significantly lower number of lung metastases in immunodeficient mice after intercardiac injection of 231 cells (p=0.0035). 68% of Curcumin treated but only 17% of untreated animals showed no or very few lung metastases, most likely as a consequence of down-regulation of NF kappa B/AP-1 dependent MMP expression and direct apoptotic effects on circulating tumor cells but not on established metastases. Dietary chemoprevention of metastases appears therefore feasible. Copyright (c) 2007 S. Karger AG, Basel

    Representative Proteomes: A Stable, Scalable and Unbiased Proteome Set for Sequence Analysis and Functional Annotation

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    The accelerating growth in the number of protein sequences taxes both the computational and manual resources needed to analyze them. One approach to dealing with this problem is to minimize the number of proteins subjected to such analysis in a way that minimizes loss of information. To this end we have developed a set of Representative Proteomes (RPs), each selected from a Representative Proteome Group (RPG) containing similar proteomes calculated based on co-membership in UniRef50 clusters. A Representative Proteome is the proteome that can best represent all the proteomes in its group in terms of the majority of the sequence space and information. RPs at 75%, 55%, 35% and 15% co-membership threshold (CMT) are provided to allow users to decrease or increase the granularity of the sequence space based on their requirements. We find that a CMT of 55% (RP55) most closely follows standard taxonomic classifications. Further analysis of this set reveals that sequence space is reduced by more than 80% relative to UniProtKB, while retaining both sequence diversity (over 95% of InterPro domains) and annotation information (93% of experimentally characterized proteins). All sets can be browsed and are available for sequence similarity searches and download at http://www.proteininformationresource.org/rps, while the set of 637 RPs determined using a 55% CMT are also available for text searches. Potential applications include sequence similarity searches, protein classification and targeted protein annotation and characterization

    Auxetic foam for snowsport safety devices

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    Skiing and snowboarding are popular snow-sports with inherent risk of injury. There is potential to reduce the prevalence of injuries by improving and implementing snow-sport safety devices with the application of advanced materials. This paper investigates the application of auxetic foam to snow-sport safety devices. Composite pads - consisting of foam covered with a semi-rigid shell - were investigated as a simple model of body armour and a large 70 x 355 x 355 mm auxetic foam sample was fabricated as an example crash barrier. The thermo-mechanical conversion process was applied to convert open-cell polyurethane foam to auxetic foam. The composite pad with auxetic foam absorbed around three times more energy than the conventional equivalent under quasi-static compression with a concentrated load, indicating potential for body armour applications. An adapted thermo-mechanical process - utilising through-thickness rods to control in-plane compression - was applied to fabricate the large sample with relatively consistent properties throughout, indicating further potential for fabrication of a full size auxetic crash barrier. Further work will create full size prototypes of snow-sport safety devices with comparative testing against current products

    Hormone replacement therapy before breast cancer diagnosis significantly reduces the overall death rate compared with never-use among 984 breast cancer patients

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    Nine hundred and eighty-four breast cancer patients were interviewed regarding exogenous hormonal use. This represents a random sample of breast cancer patients in Southern Sweden referred to the Department of Oncology at Lund for treatment between 1978 and 1997 (excluding 1980 and 1981) with a 100% follow-up. Ever-use of hormone replacement therapy (HRT) prior to diagnosis was significantly associated with a longer overall survival in women with their breast cancer diagnosed at ages 45 and above, relative risk (RR) of dying 0.73 (95% confidence interval (CI) 0.62-0.87; P = 0.0005). Ever use of HRT prior to breast cancer diagnosis was significantly positively associated with overall longer survival after adjustment for T-stage, N-stage, M-stage, year of diagnosis and age at diagnosis, RR of dying 0.78 (95% CI 0.65-0.93; P = 0.006). Hormone replacement therapy use and oestrogen receptor positivity were independently significantly associated with overall longer survival, P = 0.005 and P < 0.0001, respectively, in one model. HRT use and progesterone receptor positivity were also independently significantly associated with longer overall survival, P = 0.003 and P = 0.0003, respectively, in another model. The mode of diagnosis was known in 705 women. Mammography screening was not more common among HRT users compared with never-users, where this information was available. Both mammography screening and HRT use were independently associated with longer survival, P = 0.002 and P = 0.038 respectively

    Screening and association testing of common coding variation in steroid hormone receptor co-activator and co-repressor genes in relation to breast cancer risk: the Multiethnic Cohort

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    <p>Abstract</p> <p>Background</p> <p>Only a limited number of studies have performed comprehensive investigations of coding variation in relation to breast cancer risk. Given the established role of estrogens in breast cancer, we hypothesized that coding variation in steroid receptor coactivator and corepressor genes may alter inter-individual response to estrogen and serve as markers of breast cancer risk.</p> <p>Methods</p> <p>We sequenced the coding exons of 17 genes (<it>EP300, CCND1, NME1, NCOA1, NCOA2, NCOA3, SMARCA4, SMARCA2, CARM1, FOXA1, MPG, NCOR1, NCOR2, CALCOCO1, PRMT1, PPARBP </it>and <it>CREBBP</it>) suggested to influence transcriptional activation by steroid hormone receptors in a multiethnic panel of women with advanced breast cancer (n = 95): African Americans, Latinos, Japanese, Native Hawaiians and European Americans. Association testing of validated coding variants was conducted in a breast cancer case-control study (1,612 invasive cases and 1,961 controls) nested in the Multiethnic Cohort. We used logistic regression to estimate odds ratios for allelic effects in ethnic-pooled analyses as well as in subgroups defined by disease stage and steroid hormone receptor status. We also investigated effect modification by established breast cancer risk factors that are associated with steroid hormone exposure.</p> <p>Results</p> <p>We identified 45 coding variants with frequencies ≥ 1% in any one ethnic group (43 non-synonymous variants). We observed nominally significant positive associations with two coding variants in ethnic-pooled analyses (<it>NCOR2</it>: His52Arg, OR = 1.79; 95% CI, 1.05–3.05; <it>CALCOCO1</it>: Arg12His, OR = 2.29; 95% CI, 1.00–5.26). A small number of variants were associated with risk in disease subgroup analyses and we observed no strong evidence of effect modification by breast cancer risk factors. Based on the large number of statistical tests conducted in this study, the nominally significant associations that we observed may be due to chance, and will need to be confirmed in other studies.</p> <p>Conclusion</p> <p>Our findings suggest that common coding variation in these candidate genes do not make a substantial contribution to breast cancer risk in the general population. Cataloging and testing of coding variants in coactivator and corepressor genes should continue and may serve as a valuable resource for investigations of other hormone-related phenotypes, such as inter-individual response to hormonal therapies used for cancer treatment and prevention.</p

    Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

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    Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

    The long-term prediction of return to work following serious accidental injuries: A follow up study

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    Background Considerable indirect costs are incurred by time taken off work following accidental injuries. The aim of this study was to predict return to work following serious accidental injuries. Method 121 severely injured patients were included in the study. Complete follow-up data were available for 85 patients. Two weeks post trauma (T1), patients rated their appraisal of the injury severity and their ability to cope with the injury and its job-related consequences. Time off work was assessed at one (T2) and three years (T3) post accident. The main outcome was the number of days of sick leave taken due to the accidental injury. Results The patients' appraisals a) of the injury severity and b) of their coping abilities regarding the accidental injury and its job-related consequences were significant predictors of the number of sick-leave days taken. Injury severity (ISS), type of accident, age and gender did not contribute significantly to the prediction. Conclusions Return to work in the long term is best predicted by the patients' own appraisal of both their injury severity and the ability to cope with the accidental injury

    The significance of proline-rich tyrosine kinase2 (Pyk2) on hepatocellular carcinoma progression and recurrence

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    Understanding the precise molecular mechanisms that trigger liver cancer cell migration and invasion could develop novel therapeutic strategies targeting cancer cell invasion to increase the sensitivity to current treatment modalities. In the current study, 49 patients with hepatocellular carcinoma (HCC) were included prospectively. Liver tumour and adjacent non-tumour tissues were detected for the expression of Proline-rich tyrosine kinase 2 (Pyk2), focal adhesion kinase (FAK), ezrin and fibronectin at protein and/or gene levels. Correlation between the expressions of Pyk2/FAK with the clinical pathological data was analysed. Protein expression of Pyk2 was also examined in a nude mice orthotopic liver tumour model with higher metastatic potential. There were 59% (29 out of 49) and 57% (28 out of 49) of HCC patients with higher levels of Pyk2 and FAK protein/gene expression, respectively. We observed a positive correlation between the protein and gene expression levels of Pyk2 and FAK (P=0.000, r=0.875). Overexpression of Pyk2 and FAK was significantly correlated with shorter disease-free survival. Patients with higher levels of Pyk2/FAK had larger tumour size and advanced Edmonson grading. In the animal studies, Pyk2 overexpression was found in infiltrative tumour cells and lung metastatic nodules. In conclusion, overexpression of Pyk2 and FAK was found in nearly 60% of HCC patients and was significantly correlated with poor prognosis. The significance of Pyk2 in HCC invasiveness was confirmed by animal studies. © 2007 Cancer Research UK.published_or_final_versio
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