Questions on uncertainties in parton distributions

A discussion is presented of the manner in which uncertainties in parton distributions and related quantities are determined. One of the central problems is the criteria used to judge what variation of the parameters describing a set of partons is acceptable within the context of a global fit. Various ways of addressing this question are outlined

A winner in the Anthropocene: changing host plant distribution explains geographical range expansion in the gulf fritillary butterfly

1. The changing climate is altering species distributions with consequences for population dynamics, resulting in winners and losers in the Anthropocene. 2. Agraulis vanillae, the gulf fritillary butterfly, has expanded its range in the past 100 years in the western U.S.A. Time series analysis is combined with species distribution modelling to investigate factors limiting the distribution of A. vanillae and to predict future shifts under warming scenarios. 3. Time series analyses from the western U.S.A. show that urban development has a positive association with year of colonisation (the host plant Passiflora is an ornamental in gardens). Colonisation was also associated positively and to a lesser extent with winter maximum temperatures, whereas a negative impact of minimum temperatures and precipitation was apparent on population growth rates after establishment. 4. Species distribution models vary by region. In the eastern U.S.A., the butterfly is primarily limited by minimum temperatures in the winter and host availability later in the season. Eastern U.S. projected expansion broadly follows the expectation of poleward distributional shifts, especially for the butterfly's maximum annual extent. Western U.S. distributions are limited by the host plant, which in turn is dependent on urban centres. Projected western U.S. expansion is not limited to a single direction and is driven by urban centres becoming more suitable for the host plant. 5. These results demonstrate the value of combining time series with spatial modelling, at the same time as incorporating biotic interactions, aiming to understand and predict shifting geographical ranges in the Anthropocene

A Qualitative Study of Perceived Risk for HIV Transmission among Police Officers in Dar es Salaam, Tanzania.

Understanding people's views about HIV transmission by investigating a specific population may help to design effective HIV prevention strategies. In addition, knowing the inherent sexual practices of such a population, as well as the risky circumstances that may facilitate HIV transmission, is crucial for the said strategies to become effective. In this article, we report how police officers in Dar es Salaam, Tanzania, perceived the problem of HIV and AIDS in their local context, particularly in relation to unsafe sexual practices. The study was done with the view to recommending ways by which HIV transmission could be minimised within the police force. The study was conducted among members of the police force in Dar es Salaam, Tanzania. Eight focus group discussions (FGDs) were conducted, with a total of 66 participants who were mixed in terms of age, gender, and marital status. Some of these were caregivers to patients with AIDS. Data were analysed using the interpretive description approach. The participants believed that both individual sexual behaviour and work-related circumstances were sources of HIV infection. They also admitted that they were being tempted to engage in risky sexual practices because of the institutional rules that prohibit officers from getting married during their training and for three years after. Nevertheless, as members of the Police Force, they stressed the fact that the risky sexual behaviour that exposes them to HIV is not limited to the force; it is rather a common problem that is faced by the general population. However, they complained, the nature of their job exposes them to road accident victims, subjecting them further to possible infection, especially when they have to handle these road accident casualties without proper protective gear. Individual sexual behaviour and job-related circumstances are worth investigating if proper advice is to be given to the police regarding HIV prevention strategies. In order to improve the lives of these police officers, there is a need to review the existing institutional rules and practices to accommodate individual sexual needs. In addition, improving their working environment may minimize the risk of HIV transmission from handling casualties in emergency situations

Which Distributions (or Families of Distributions) Best Represent Interval Uncertainty: Case of Permutation-Invariant Criteria

In many practical situations, we only know the interval containing the quantity of interest, we have no information about the probability of different values within this interval. In contrast to the cases when we know the distributions and can thus use Monte-Carlo simulations, processing such interval uncertainty is difficult -- crudely speaking, because we need to try all possible distributions on this interval. Sometimes, the problem can be simplified: namely, it is possible to select a single distribution (or a small family of distributions) whose analysis provides a good understanding of the situation. The most known case is when we use the Maximum Entropy approach and get the uniform distribution on the interval. Interesting, sensitivity analysis -- which has completely different objectives -- leads to selection of the same uniform distribution. In this paper, we provide a general explanation of why uniform distribution appears in different situations -- namely, it appears every time we have a permutation-invariant objective functions with the unique optimum. We also discuss what happens if there are several optima

Galaxy And Mass Assembly (GAMA): A forensic SED reconstruction of the cosmic star-formation history and metallicity evolution by galaxy type

We apply the spectral energy distribution-fitting code ProSpect to multiwavelength imaging for $\sim$7,000 galaxies from the GAMA survey at $z<0.06$, in order to extract their star-formation histories. We combine a parametric description of the star formation history with a closed-box evolution of metallicity where the present-day gas-phase metallicity of the galaxy is a free parameter. We show with this approach that we are able to recover the observationally-determined cosmic star formation history (CSFH), an indication that stars are being formed in the correct epoch of the Universe, on average, for the manner in which we are conducting SED fitting. We also show the contribution to the CSFH of galaxies of different present-day visual morphologies, and stellar masses. This analysis suggests that half of the mass in present-day elliptical galaxies was in place 11 Gyr ago, whereas in other morphological types the stellar mass formed later, up to 6 Gyr ago for present-day irregular galaxies. Similarly, the most massive galaxies in our sample were shown to have formed half their stellar mass by 10.5 Gyr ago, whereas the least massive galaxies formed half their stellar mass as late as 4 Gyr ago (the well-known effect of "galaxy downsizing"). Finally, our metallicity approach allows us to follow the average evolution in gas-phase metallicity for populations of galaxies, and extract the evolution of the cosmic metal mass density in stars and in gas, producing results in broad agreement with observations of metal densities in the Universe

Ecological effects of extreme drought on Californian herbaceous plant communities

Understanding the consequences of extreme climatic events is a growing challenge in ecology. Climatic extremes may differentially affect varying elements of biodiversity, and may not always produce ecological effects exceeding those of "normal" climatic variation in space and time. We asked how the extreme drought years of 2013- 2014 affected the cover, species richness, functional trait means, functional diversity, and phylogenetic diversity of herbaceous plant communities across the California Floristic Province. We compared the directions and magnitudes of these drought effects with expectations from four "pre-drought" studies of variation in water availability: (1) a watering experiment, (2) a long- Term (15-yr) monitoring of interannual variability, (3) a resampling of historic (57-yr- old) plots within a warming and drying region, and (4) natural variation in communities over a broad geographic gradient in precipitation. We found that the drought was associated with consistent reductions in species richness and cover, especially for annual forbs and exotic annual grasses, but not with changes in functional or phylogenetic diversity. Except for total cover and cover of exotic annual grasses, most drought effects did not exceed quantitative expectations based on the four pre-drought studies. Qualitatively, plant community responses to the drought were most concordant with responses to pre-drought interannual rainfall variability in the 15-yr monitoring study, and least concordant with responses to the geographic gradient in precipitation. Our results suggest that, at least in the short term, extreme drought may cause only a subset of community metrics to respond in ways that exceed normal background variability

Inhibition of interferon-signalling halts cancer-associated fibroblast-dependent protection of breast cancer cells from chemotherapy

Background Triple negative breast cancers (TNBC) have poor prognoses despite aggressive treatment with cytotoxic chemotherapy. Cancer-associated fibroblasts (CAFs) are prominent in tumour stroma. Our hypothesis was that CAFs modulate chemotherapy sensitivity. Methods TNBC cells and breast fibroblasts were cultured; survival after chemotherapeutics was assessed using luciferase or clonogenic assays. Signalling was investigated using transcriptomics, reporters, recombinant proteins and blocking antibodies. Clinical relevance was investigated using immunohistochemistry. Results Breast CAFs dose-dependently protected TNBC cell lines MDA-MB-231 and MDA-MB-157, but not MDA-MB-468s, from chemotherapy. CAF-induced protection was associated with interferon (IFN) activation. CAFs were induced to express IFNβ1 by chemotherapy and TNBC co-culture, leading to paracrine activation in cancer cells. Recombinant IFNs were sufficient to protect MDA-MB-231 and MDA-MB-157 but not MDA-MB-468 cells. In TNBC patients, IFNβ1 expression in CAFs correlated with cancer cell expression of MX1, a marker of activated IFN signalling. High expression of IFNβ1 (CAFs) or MX1 (tumour cells) correlated with reduced survival after chemotherapy, especially in claudin-low tumours (which MDA-MB-231 and MDA-MB-157 cells represent). Antibodies that block IFN receptors reduced CAF-dependent chemoprotection. Conclusions CAF-induced activation of IFN signalling in claudin-low TNBCs results in chemoresistance. Inhibition of this pathway represents a novel method to improve breast cancer outcomes

Population-Level Benefits from Providing Effective HIV Prevention Means to Pregnant Women in High Prevalence Settings

Background:HIV prevalence among pregnant women in Southern Africa is extremely high. Epidemiological studies suggest that pregnancy increases the risk of HIV sexual acquisition and that HIV infections acquired during pregnancy carry higher risk of mother-to-child transmission (MTCT). We analyze the potential benefits from extending the availability of effective microbicide to pregnant women (in addition to non-pregnant women) in a wide-scale intervention.Methods and Findings:A transmission dynamic model was designed to assess the impact of microbicide use in high HIV prevalence settings and to estimate proportions of new HIV infections, infections acquired during pregnancy, and MTCT prevented over 10 years. Our analysis suggests that consistent use of microbicide with 70% efficacy by 60% of non-pregnant women may prevent approximately 40% and 15% of new infections in women and men respectively over 10 years, assuming no additional increase in HIV risk to either partner during pregnancy (RRHIV/preg = 1). It may also prevent 8-15% MTCT depending on the increase in MTCT risk when HIV is acquired during pregnancy compared to before pregnancy (RRMTCT/preg). Extending the microbicides use during pregnancy may improve the effectiveness of the intervention by 10% (RRHIV/preg = 1) to 25% (RRHIV/preg = 2) and reduce the number of HIV infections acquired during pregnancy by 40% to 70% in different scenarios. It may add between 6% (RRHIV/preg = 1, RRMTCT/preg = 1) and 25% (RRHIV/preg = 2, RRMTCT/preg = 4) to the reduction in the residual MTCT.Conclusion:Providing safe and effective microbicide to pregnant women in the context of wide-scale interventions would be desirable as it would increase the effectiveness of the intervention and significantly reduce the number of HIV infections acquired during pregnancy. The projected benefits from covering pregnant women by the HIV prevention programs is more substantial in communities in which the sexual risk during pregnancy is elevated. © 2013 Dimitrov et al

Accurate reconstruction of insertion-deletion histories by statistical phylogenetics

The Multiple Sequence Alignment (MSA) is a computational abstraction that represents a partial summary either of indel history, or of structural similarity. Taking the former view (indel history), it is possible to use formal automata theory to generalize the phylogenetic likelihood framework for finite substitution models (Dayhoff's probability matrices and Felsenstein's pruning algorithm) to arbitrary-length sequences. In this paper, we report results of a simulation-based benchmark of several methods for reconstruction of indel history. The methods tested include a relatively new algorithm for statistical marginalization of MSAs that sums over a stochastically-sampled ensemble of the most probable evolutionary histories. For mammalian evolutionary parameters on several different trees, the single most likely history sampled by our algorithm appears less biased than histories reconstructed by other MSA methods. The algorithm can also be used for alignment-free inference, where the MSA is explicitly summed out of the analysis. As an illustration of our method, we discuss reconstruction of the evolutionary histories of human protein-coding genes.Comment: 28 pages, 15 figures. arXiv admin note: text overlap with arXiv:1103.434

Identification of candidate mediators of chemoresponse in breast cancer through therapy-driven selection of somatic variants

Purpose: More than a third of primary breast cancer patients are treated with cytotoxic chemotherapy, typically without guidance from predictive markers. Increased use of neoadjuvant chemotherapy provides opportunities for identification of molecules associated with treatment response, by comparing matched tumour samples before and after therapy. Our hypothesis was that somatic variants of increased prevalence after therapy promote resistance, while variants with reduced prevalence cause sensitivity. Methods: We performed systematic analyses of matched pairs of cancer exomes from primary oestrogen receptor-positive/HER2-negative breast cancers (n = 6) treated with neoadjuvant epirubicin/cyclophosphamide. We identified candidate genes as mediators of chemotherapy response by consistent subclonal changes in somatic variant prevalence through therapy, predicted variant impact on gene function, and enrichment of specific functional pathways. Influence of candidate genes on breast cancer outcome was tested using publicly available breast cancer expression data (n = 1903). Results: We identified 14 genes as the strongest candidate mediators of chemoresponse: TCHH, MUC17, ARAP2, FLG2, ABL1, CENPF, COL6A3, DMBT1, ITGA7, PLXNA1, S100PBP, SYNE1, ZFHX4, and CACNA1C. Genes contained somatic variants showing prevalence changes in up to 4 patients, with up to 3 being predicted as damaging. Genes coding for extra-cellular matrix components or related signalling pathways were significantly over-represented among variants showing prevalence changes. Expression of 5 genes (TCHH, ABL1, CENPF, S100PBP, and ZFHX4) was significantly associated with patient survival. Conclusions: Genomic analysis of paired pre- and post-therapy samples resulting from neoadjuvant therapy provides a powerful method for identification of mediators of response. Genes we identified should be assessed as predictive markers or targets in chemo-sensitization