2,105 research outputs found

    Cross-cultural effects of color, but not morphological masculinity, on perceived attractiveness of men's faces

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    This is the post-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2012 ElsevierMuch attractiveness research has focused on face shape. The role of masculinity (which for adults is thought to be a relatively stable shape cue to developmental testosterone levels) in male facial attractiveness has been examined, with mixed results. Recent work on the perception of skin color (a more variable cue to current health status) indicates that increased skin redness, yellowness, and lightness enhance apparent health. It has been suggested that stable cues such as masculinity may be less important to attractiveness judgments than short-term, more variable health cues. We examined associations between male facial attractiveness, masculinity, and skin color in African and Caucasian populations. Masculinity was not found to be associated with attractiveness in either ethnic group. However, skin color was found to be an important predictor of attractiveness judgments, particularly for own-ethnicity faces. Our results suggest that more plastic health cues, such as skin color, are more important than developmental cues such as masculinity. Further, unfamiliarity with natural skin color variation in other ethnic groups may limit observers' ability to utilize these color cues

    A randomized phase II study of lapatinib + pazopanib versus lapatinib in patients with HER2+ inflammatory breast cancer

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    This multi-center Phase II study evaluated lapatinib, pazopanib, and the combination in patients with relapsed HER2+ inflammatory breast cancer. In Cohort 1, 76 patients were randomized 1:1 to receive lapatinib 1,500 mg + placebo or lapatinib 1,500 mg + pazopanib 800 mg (double-blind) once daily until disease progression, unacceptable toxicity, or death. Due to high-grade diarrhea observed with this dose combination in another study (VEG20007), Cohort 1 was closed. The protocol was amended such that an additional 88 patients (Cohort 2) were randomized in a 5:5:2 ratio to receive daily monotherapy lapatinib 1,500 mg, lapatinib 1,000 mg + pazopanib 400 mg, or monotherapy pazopanib 800 mg, respectively. The primary endpoint was overall response rate (ORR). Secondary endpoints included duration of response, progression-free survival (PFS), overall survival, and safety. In Cohort 1, ORR for the lapatinib (n = 38) and combination (n = 38) arms was 29 and 45 %, respectively; median PFS was 16.1 and 14.3 weeks, respectively. Grade ≥3 adverse events (AEs) were more frequent in the combination arm (71 %) than in the lapatinib arm (24 %). Dose reductions and interruptions due to AEs were also more frequent in the combination arm (45 and 53 %, respectively) than in the lapatinib monotherapy arm (0 and 11 %, respectively). In Cohort 2, ORR for patients treated with lapatinib (n = 36), lapatinib + pazopanib (n = 38), and pazopanib (n = 13) was 47, 58, and 31 %, respectively; median PFS was 16.0, 16.0, and 11.4 weeks, respectively. In the lapatinib, combination, and pazopanib therapy arms, grade ≥3 AEs were reported for 17, 50, and 46 % of patients, respectively, and the incidence of discontinuations due to AEs was 0, 24, and 23 %, respectively. The lapatinib–pazopanib combination was associated with a numerically higher ORR but no increase in PFS compared to lapatinib alone. The combination also had increased toxicity resulting in more dose reductions, modifications, and treatment delays. Activity with single-agent lapatinib was confirmed in this population

    The airtightness and air leakage characteristics of new UK holiday homes

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    It is estimated that in the UK, 200,000 residents live in park and holiday homes all year round, the majority of which are elderly and on low incomes. As these homes are often thermally inefficient and leaky, these residents are some of the most susceptible in society to fuel poverty. Despite this, there is a dearth of empirical data available on the in situ fabric performance of these homes. This paper presents the results obtained from undertaking a series of pressurisation tests and leakage identification on new build holiday homes. While the sample size reported is small, the results indicate almost a factor of two variation in the airtightness performance of the homes. In spite of this, all of the homes achieved an air permeability significantly lower than the default value incorporated within the industry standard Energy Efficiency Rating Calculator, suggesting that a much lower figure may be more appropriate. The results also suggest that the use of the air permeability metric within the Calculator potentially biases the performance of holiday homes due to their particular form factor, and that this bias could be mitigated against by adopting the air leakage metric within any future revisions to the Calculator

    LGP2 plays a critical role in sensitizing mda-5 to activation by double-stranded RNA.

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    The DExD/H box RNA helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation associated gene-5 (mda-5) sense viral RNA in the cytoplasm of infected cells and activate signal transduction pathways that trigger the production of type I interferons (IFNs). Laboratory of genetics and physiology 2 (LGP2) is thought to influence IFN production by regulating the activity of RIG-I and mda-5, although its mechanism of action is not known and its function is controversial. Here we show that expression of LGP2 potentiates IFN induction by polyinosinic-polycytidylic acid [poly(I:C)], commonly used as a synthetic mimic of viral dsRNA, and that this is particularly significant at limited levels of the inducer. The observed enhancement is mediated through co-operation with mda-5, which depends upon LGP2 for maximal activation in response to poly(I:C). This co-operation is dependent upon dsRNA binding by LGP2, and the presence of helicase domain IV, both of which are required for LGP2 to interact with mda-5. In contrast, although RIG-I can also be activated by poly(I:C), LGP2 does not have the ability to enhance IFN induction by RIG-I, and instead acts as an inhibitor of RIG-I-dependent poly(I:C) signaling. Thus the level of LGP2 expression is a critical factor in determining the cellular sensitivity to induction by dsRNA, and this may be important for rapid activation of the IFN response at early times post-infection when the levels of inducer are low

    The Angular Correlation Function of Galaxies from Early SDSS Data

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    The Sloan Digital Sky Survey is one of the first multicolor photometric and spectroscopic surveys designed to measure the statistical properties of galaxies within the local Universe. In this Letter we present some of the initial results on the angular 2-point correlation function measured from the early SDSS galaxy data. The form of the correlation function, over the magnitude interval 18<r*<22, is shown to be consistent with results from existing wide-field, photographic-based surveys and narrower CCD galaxy surveys. On scales between 1 arcminute and 1 degree the correlation function is well described by a power-law with an exponent of ~ -0.7. The amplitude of the correlation function, within this angular interval, decreases with fainter magnitudes in good agreement with analyses from existing galaxy surveys. There is a characteristic break in the correlation function on scales of approximately 1-2 degrees. On small scales, < 1', the SDSS correlation function does not appear to be consistent with the power-law form fitted to the 1'< theta <0.5 deg data. With a data set that is less than 2% of the full SDSS survey area, we have obtained high precision measurements of the power-law angular correlation function on angular scales 1' < theta < 1 deg, which are robust to systematic uncertainties. Because of the limited area and the highly correlated nature of the error covariance matrix, these initial results do not yet provide a definitive characterization of departures from the power-law form at smaller and larger angles. In the near future, however, the area of the SDSS imaging survey will be sufficient to allow detailed analysis of the small and large scale regimes, measurements of higher-order correlations, and studies of angular clustering as a function of redshift and galaxy type

    Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

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    Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated

    Transcriptional upregulation of c-MET is associated with invasion and tumor budding in colorectal cancer

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    c-MET and its ligand HGF are frequently overexpressed in colorectal cancer (CRC) and increased c-MET levels are found in CRC liver metastases. This study investigated the role of the HGF/c-MET axis in regulating migration/invasion in CRC, using pre-clinical models and clinical samples. Pre-clinically, we found marked upregulation of c-MET at both protein and mRNA levels in several invasive CRC cells. Down-regulation of c-MET using RNAi suppressed migration/invasion of parental and invasive CRC cells. Stimulation of CRC cells with rh-HGF or co-culture with HGF-expressing colonic myofibroblasts, resulted in significant increases in their migratory/invasive capacity. Importantly, HGF-induced c-MET activation promoted rapid downregulation of c-MET protein levels, while the MET transcript remained unaltered. Using RNA in situ hybridization (RNA ISH), we further showed that MET mRNA, but not protein levels, were significantly upregulated in tumor budding foci at the invasive front of a cohort of stage III CRC tumors (p < 0.001). Taken together, we show for the first time that transcriptional upregulation of MET is a key molecular event associated with CRC invasion and tumor budding. This data also indicates that RNA ISH, but not immunohistochemistry, provides a robust methodology to assess MET levels as a potential driving force of CRC tumor invasion and metastasis

    Kepler eclipsing binary stars. VII. the catalogue of eclipsing binaries found in the entire Kepler data set

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    The primary Kepler Mission provided nearly continuous monitoring of ~200,000 objects with unprecedented photometric precision. We present the final catalog of eclipsing binary systems within the 105 deg2 Kepler field of view. This release incorporates the full extent of the data from the primary mission (Q0-Q17 Data Release). As a result, new systems have been added, additional false positives have been removed, ephemerides and principal parameters have been recomputed, classifications have been revised to rely on analytical models, and eclipse timing variations have been computed for each system. We identify several classes of systems including those that exhibit tertiary eclipse events, systems that show clear evidence of additional bodies, heartbeat systems, systems with changing eclipse depths, and systems exhibiting only one eclipse event over the duration of the mission. We have updated the period and galactic latitude distribution diagrams and included a catalog completeness evaluation. The total number of identified eclipsing and ellipsoidal binary systems in the Kepler field of view has increased to 2878, 1.3% of all observed Kepler targets
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