222 research outputs found

    Interplay between Side Chain Density and Polymer Alignment: Two Competing Strategies for Enhancing the Thermoelectric Performance of P3HT Analogues

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    A series of polythiophenes with varying side chain density was synthesized, and their electrical and thermoelectric properties were investigated. Aligned and non-aligned thin films of the polymers were characterized in the neutral and chemically doped states. Optical and diffraction measurements revealed an overall lower order in the thin films with lower side chain density, also confirmed using polarized optical experiments on aligned thin films. However, upon doping the non-aligned films, a sixfold increase in electrical conductivity was observed for the polythiophene with the lowest side chain density compared to poly(3-hexylthiophene) (P3HT). We found that the improvement in conductivity was not due to a larger charge carrier density but an increase in charge carrier mobility after doping with 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ). On the other hand, doped aligned films did not show the same trend; lower side chain density instead led to a lower conductivity and Seebeck coefficient compared to those for P3HT. This was attributed to the poorer alignment of the polymer thin films with lower side chain density. The study demonstrates that optimizing side chain density is a synthetically simple and effective way to improve electrical conductivity in polythiophene films relevant to thermoelectric applications

    Oestrogen receptor status, pathological complete response and prognosis in patients receiving neoadjuvant chemotherapy for early breast cancer

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    The aim of this study was to ascertain if oestrogen receptor ( ER) status predicts for pathological complete response (pCR) to neoadjuvant chemotherapy in operable breast cancer, and the effects of pCR on survival. Using a single-institution database, 435 patients were identified, who received neoadjuvant chemotherapy for operable breast cancer and were eligible for the analysis. Patients whose tumours were ER negative were more likely to achieve a pCR than patients who were ER positive (21.6 vs 8.1%,

    International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

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    In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authorsā€™ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible

    Enriching Peptide Libraries for Binding Affinity and Specificity Through Computationally Directed Library Design

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    Peptide reagents with high affinity or specificity for their target protein interaction partner are of utility for many important applications. Optimization of peptide binding by screening large libraries is a proven and powerful approach. Libraries designed to be enriched in peptide sequences that are predicted to have desired affinity or specificity characteristics are more likely to yield success than random mutagenesis. We present a library optimization method in which the choice of amino acids to encode at each peptide position can be guided by available experimental data or structure-based predictions. We discuss how to use analysis of predicted library performance to inform rounds of library design. Finally, we include protocols for more complex library design procedures that consider the chemical diversity of the amino acids at each peptide position and optimize a library score based on a user-specified input model.National Institute of General Medical Sciences (U.S.) (Award R01 GM110048

    Salmonella in Broiler Litter and Properties of Soil at Farm Location

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    Contamination of litter in a broiler grow-out house with Salmonella prior to placement of a new flock has been shown to be a precursor of the flock's Salmonella contamination further down the production continuum. In the southern USA, broiler grow-out houses are primarily built on dirt pad foundations that are placed directly on top of the native soil surface. Broiler litter is placed directly on the dirt pad. Multiple grow-out flocks are reared on a single litter batch, and the litter is kept in the houses during downtime between flocks. The effects of environmental determinants on conditions in broiler litter, hence Salmonella ecology within it, has received limited attention. In a field study that included broiler farms in the states of Alabama, Mississippi and Texas we assessed Salmonella in broiler litter at the end of downtime between flocks, i.e. at the time of placement of a new flock for rearing. Here we utilized these results and the U.S. General Soil Map (STATSGO) data to test if properties of soil at farm location impacted the probability of Salmonella detection in the litter. The significance of soil properties as risk factors was tested in multilevel regression models after accounting for possible confounding differences among the farms, the participating broiler complexes and companies, and the farms' geographical positioning. Significant associations were observed between infiltration and drainage capabilities of soil at farm location and probability of Salmonella detection in the litter

    Changes in neuronal activation patterns in response to androgen deprivation therapy: a pilot study

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    <p>Abstract</p> <p>Background</p> <p>A common treatment option for men with prostate cancer is androgen deprivation therapy (ADT). However, men undergoing ADT may experience physical side effects, changes in quality of life and sometimes psychiatric and cognitive side effects.</p> <p>Methods</p> <p>In this study, hormone naĆÆve patients without evidence of metastases with a rising PSA were treated with nine months of ADT. Functional magnetic resonance imaging (fMRI) of the brain during three visuospatial tasks was performed at baseline prior to treatment and after nine months of ADT in five subjects. Seven healthy control patients, underwent neuroimaging at the same time intervals.</p> <p>Results</p> <p>ADT patients showed reduced, task-related BOLD-fMRI activation during treatment that was not observed in control subjects. Reduction in activation in right parietal-occipital regions from baseline was observed during recall of the spatial location of objects and mental rotation.</p> <p>Conclusions</p> <p>Findings, while preliminary, suggest that ADT reduces task-related neural activation in brain regions that are involved in mental rotation and accurate recall of spatial information.</p

    Letrozole in the neoadjuvant setting: the P024 trial

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    Neoadjuvant chemotherapy trials have consistently reported lower response rates in hormone receptor-positive (HR+) breast cancer when compared with HRāˆ’ cases. Preoperative endocrine therapy has therefore become a logical alternative and has gained considerable momentum from the finding that aromatase inhibitors (AIs) are more effective than tamoxifen for HR+ breast cancer in both the neoadjuvant and adjuvant settings. The most convincing neoadjuvant trial to demonstrate the superiority of an AI versus tamoxifen was the P024 study, a large multinational double-blind trial in postmenopausal women with HR+ breast cancer ineligible for breast-conserving surgery. The overall response rate (ORR) was 55% for letrozole and 36% for tamoxifen (PĀ <Ā 0.001). Significantly more letrozole-treated patients underwent breast-conserving surgery (45 vs. 35%, respectively; PĀ =Ā 0.022). In addition, ORR was significantly higher with letrozole than tamoxifen in the human epidermal growth factor receptor HER1/HER2+ subgroup (PĀ =Ā 0.0004). The clinical efficacy of letrozole in HER2+ breast cancer was confirmed by fluorescent inĀ situ hybridization analysis and was found to be comparable to that of HER2āˆ’ cases (ORR 71% in both subsets). Biomarker studies confirmed the superiority of letrozole in centrally assessed estrogen receptor-positive (ER+) tumors and found a strong relationship with the degree of ER positivity for both agents. Interestingly, letrozole was effective even in marginally ER+ tumors and, unlike tamoxifen, consistently reduced the expression from estrogen-regulated genes (progesterone receptor and trefoil factor 1). Furthermore, when analyzed by Ki67 immunohistochemistry, letrozole was significantly more effective than tamoxifen in reducing tumor proliferation (PĀ =Ā 0.0009). Thus, neoadjuvant letrozole is safe and superior to tamoxifen in the treatment of postmenopausal women with HR+ locally advanced breast cancer

    CD36 deficiency attenuates experimental mycobacterial infection

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    <p>Abstract</p> <p>Background</p> <p>Members of the CD36 scavenger receptor family have been implicated as sensors of microbial products that mediate phagocytosis and inflammation in response to a broad range of pathogens. We investigated the role of CD36 in host response to mycobacterial infection.</p> <p>Methods</p> <p>Experimental <it>Mycobacterium bovis </it>Bacillus Calmette-GuƩrin (BCG) infection in <it>Cd36<sup>+/+ </sup></it>and <it>Cd36<sup>-/- </sup></it>mice, and <it>in vitro </it>co-cultivation of <it>M. tuberculosis</it>, BCG and <it>M. marinum </it>with <it>Cd36<sup>+/+ </sup></it>and <it>Cd36<sup>-/-</sup></it>murine macrophages.</p> <p>Results</p> <p>Using an <it>in vivo </it>model of BCG infection in <it>Cd36<sup>+/+ </sup></it>and <it>Cd36<sup>-/- </sup></it>mice, we found that mycobacterial burden in liver and spleen is reduced (83% lower peak splenic colony forming units, p < 0.001), as well as the density of granulomas, and circulating tumor necrosis factor (TNF) levels in <it>Cd36<sup>-/- </sup></it>animals. Intracellular growth of all three mycobacterial species was reduced in <it>Cd36<sup>-/- </sup></it>relative to wild type <it>Cd36<sup>+/+ </sup></it>macrophages <it>in vitro</it>. This difference was not attributable to alterations in mycobacterial uptake, macrophage viability, rate of macrophage apoptosis, production of reactive oxygen and/or nitrogen species, TNF or interleukin-10. Using an <it>in vitro </it>model designed to recapitulate cellular events implicated in mycobacterial infection and dissemination <it>in vivo </it>(i.e., phagocytosis of apoptotic macrophages containing mycobacteria), we demonstrated reduced recovery of viable mycobacteria within <it>Cd36<sup>-/- </sup></it>macrophages.</p> <p>Conclusions</p> <p>Together, these data indicate that CD36 deficiency confers resistance to mycobacterial infection. This observation is best explained by reduced intracellular survival of mycobacteria in the <it>Cd36<sup>-/- </sup></it>macrophage and a role for CD36 in the cellular events involved in granuloma formation that promote early bacterial expansion and dissemination.</p
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