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    The influence of backbone fluorination on the dielectric constant of conjugated polythiophenes

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    The ability to modify or enhance the dielectric constant of semiconducting polymers can prove valuable for a range of optoelectronic and microelectronic applications. In the case of organic photovoltaics, increasing the dielectric constant of the active layer has often been suggested as a method to control charge generation, recombination dynamics, and ultimately, the power conversion efficiencies. In this contribution, the impact that the degree and pattern of fluorination has on the dielectric constant of poly(3-octylthiophene) (P3OT), a more soluble analogue of the widely studied conjugated material poly(3-hexylthiophene), is explored. P3OT and its backbone-fluorinated analogue, F-P3OT, are compared along with a block and alternating copolymer version of these materials. It is found that the dielectric constant of the polymer thin films increases as the degree of backbone fluorination increases, in a trend consistent with density functional theory calculations of the dipole moment

    Success Factors of European Syndromic Surveillance Systems: A Worked Example of Applying Qualitative Comparative Analysis

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    Introduction: Syndromic surveillance aims at augmenting traditional public health surveillance with timely information. To gain a head start, it mainly analyses existing data such as from web searches or patient records. Despite the setup of many syndromic surveillance systems, there is still much doubt about the benefit of the approach. There are diverse interactions between performance indicators such as timeliness and various system characteristics. This makes the performance assessment of syndromic surveillance systems a complex endeavour. We assessed if the comparison of several syndromic surveillance systems through Qualitative Comparative Analysis helps to evaluate performance and identify key success factors. Materials and Methods: We compiled case-based, mixed data on performance and characteristics of 19 syndromic surveillance systems in Europe from scientific and grey literature and from site visits. We identified success factors by applying crisp-set Qualitative Comparative Analysis. We focused on two main areas of syndromic surveillance application: seasonal influenza surveillance and situational awareness during different types of potentially health threatening events. Results: We found that syndromic surveillance systems might detect the onset or peak of seasonal influenza earlier if they analyse non-clinical data sources. Timely situational awareness during different types of events is supported by an automated syndromic surveillance system capable of analysing multiple syndromes. To our surprise, the analysis of multiple data sources was no key success factor for situational awareness. Conclusions: We suggest to consider these key success factors when designing or further developing syndromic surveillance systems. Qualitative Comparative Analysis helped interpreting complex, mixed data on small-N cases and resulted in concrete and practically relevant findings

    Cytoplasmic PML promotes TGF-β-associated epithelial–mesenchymal transition and invasion in prostate cancer

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    Epithelial–mesenchymal transition (EMT) is a key event that is involved in the invasion and dissemination of cancer cells. Although typically considered as having tumour-suppressive properties, transforming growth factor (TGF)-β signalling is altered during cancer and has been associated with the invasion of cancer cells and metastasis. In this study, we report a previously unknown role for the cytoplasmic promyelocytic leukaemia (cPML) tumour suppressor in TGF-β signalling-induced regulation of prostate cancer-associated EMT and invasion. We demonstrate that cPML promotes a mesenchymal phenotype and increases the invasiveness of prostate cancer cells. This event is associated with activation of TGF-β canonical signalling pathway through the induction of Sma and Mad related family 2 and 3 (SMAD2 and SMAD3) phosphorylation. Furthermore, the cytoplasmic localization of promyelocytic leukaemia (PML) is mediated by its nuclear export in a chromosomal maintenance 1 (CRM1)-dependent manner. This was clinically tested in prostate cancer tissue and shown that cytoplasmic PML and CRM1 co-expression correlates with reduced disease-specific survival. In summary, we provide evidence of dysfunctional TGF-β signalling occurring at an early stage in prostate cancer. We show that this disease pathway is mediated by cPML and CRM1 and results in a more aggressive cancer cell phenotype. We propose that the targeting of this pathway could be therapeutically exploited for clinical benefit

    A Novel Universal Primer-Multiplex-PCR Method with Sequencing Gel Electrophoresis Analysis

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    In this study, a novel universal primer-multiplex-PCR (UP-M-PCR) method adding a universal primer (UP) in the multiplex PCR reaction system was described. A universal adapter was designed in the 5′-end of each specific primer pairs which matched with the specific DNA sequences for each template and also used as the universal primer (UP). PCR products were analyzed on sequencing gel electrophoresis (SGE) which had the advantage of exhibiting extraordinary resolution. This method overcame the disadvantages rooted deeply in conventional multiplex PCR such as complex manipulation, lower sensitivity, self-inhibition and amplification disparity resulting from different primers, and it got a high specificity and had a low detection limit of 0.1 ng for single kind of crops when screening the presence of genetically modified (GM) crops in mixture samples. The novel developed multiplex PCR assay with sequencing gel electrophoresis analysis will be useful in many fields, such as verifying the GM status of a sample irrespective of the crop and GM trait and so on

    Synthesis, Electrical Measurement, and Field Emission Properties of α-Fe2O3Nanowires

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    α-Fe2O3nanowires (NWs) were formed by the thermal oxidation of an iron film in air at 350 °C for 10 h. The rhombohedral structure of the α-Fe2O3NWs was grown vertically on the substrate with diameters of 8–25 nm and lengths of several hundred nm. It was found that the population density of the NWs per unit area (DNWs) can be varied by the film thickness. The thicker the iron film, the more NWs were grown. The growth mechanism of the NWs is suggested to be a combination effect of the thermal oxidation rate, defects on the film, and selective directional growth. The electrical resistivity of a single NW with a length of 800 nm and a diameter of 15 nm was measured to be 4.42 × 103 Ωcm using conductive atomic force microscopy. The field emission characteristics of the NWs were studied using a two-parallel-plate system. A low turn–on field of 3.3 V/μm and a large current density of 10−3 A/cm2(under an applied field of about 7 V/μm) can be obtained using optimal factors ofDNWsin the cathode

    Role of apoptosis-inducing factor (AIF) in programmed nuclear death during conjugation in Tetrahymena thermophila

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    <p>Abstract</p> <p>Background</p> <p>Programmed nuclear death (PND), which is also referred to as nuclear apoptosis, is a remarkable process that occurs in ciliates during sexual reproduction (conjugation). In <it>Tetrahymena thermophila</it>, when the new macronucleus differentiates, the parental macronucleus is selectively eliminated from the cytoplasm of the progeny, concomitant with apoptotic nuclear events. However, the molecular mechanisms underlying these events are not well understood. The parental macronucleus is engulfed by a large autophagosome, which contains numerous mitochondria that have lost their membrane potential. In animals, mitochondrial depolarization precedes apoptotic cell death, which involves DNA fragmentation and subsequent nuclear degradation.</p> <p>Results</p> <p>We focused on the role of mitochondrial apoptosis-inducing factor (AIF) during PND in <it>Tetrahymena</it>. The disruption of <it>AIF </it>delays the normal progression of PND, specifically, nuclear condensation and kilobase-size DNA fragmentation. AIF is localized in <it>Tetrahymena </it>mitochondria and is released into the macronucleus prior to nuclear condensation. In addition, AIF associates and co-operates with the mitochondrial DNase to facilitate the degradation of kilobase-size DNA, which is followed by oligonucleosome-size DNA laddering.</p> <p>Conclusions</p> <p>Our results suggest that <it>Tetrahymena </it>AIF plays an important role in the degradation of DNA at an early stage of PND, which supports the notion that the mitochondrion-initiated apoptotic DNA degradation pathway is widely conserved among eukaryotes.</p

    A Novel Statistical Algorithm for Gene Expression Analysis Helps Differentiate Pregnane X Receptor-Dependent and Independent Mechanisms of Toxicity

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    Genome-wide gene expression profiling has become standard for assessing potential liabilities as well as for elucidating mechanisms of toxicity of drug candidates under development. Analysis of microarray data is often challenging due to the lack of a statistical model that is amenable to biological variation in a small number of samples. Here we present a novel non-parametric algorithm that requires minimal assumptions about the data distribution. Our method for determining differential expression consists of two steps: 1) We apply a nominal threshold on fold change and platform p-value to designate whether a gene is differentially expressed in each treated and control sample relative to the averaged control pool, and 2) We compared the number of samples satisfying criteria in step 1 between the treated and control groups to estimate the statistical significance based on a null distribution established by sample permutations. The method captures group effect without being too sensitive to anomalies as it allows tolerance for potential non-responders in the treatment group and outliers in the control group. Performance and results of this method were compared with the Significant Analysis of Microarrays (SAM) method. These two methods were applied to investigate hepatic transcriptional responses of wild-type (PXR+/+) and pregnane X receptor-knockout (PXR−/−) mice after 96 h exposure to CMP013, an inhibitor of β-secretase (β-site of amyloid precursor protein cleaving enzyme 1 or BACE1). Our results showed that CMP013 led to transcriptional changes in hallmark PXR-regulated genes and induced a cascade of gene expression changes that explained the hepatomegaly observed only in PXR+/+ animals. Comparison of concordant expression changes between PXR+/+ and PXR−/− mice also suggested a PXR-independent association between CMP013 and perturbations to cellular stress, lipid metabolism, and biliary transport

    Cigarettes and alcohol in relation to colorectal cancer: the Singapore Chinese Health Study

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    The relations were examined between colorectal cancer and cigarette smoking and alcohol consumption within the Singapore Chinese Health Study, a population-based, prospective cohort of 63 257 middle-aged and older Chinese men and women enrolled between 1993 and 1998, from whom baseline data on cigarette smoking and alcohol consumption were collected through in-person interviews. By 31 December 2004, 845 cohort participants had developed colorectal cancer (516 colon cancer, 329 rectal cancer). Compared with nondrinkers, subjects who drank seven or more alcoholic drinks per week had a statistically significant, 72% increase in risk of colorectal cancer hazard ratio (HR)=1.72; 95% confidence interval (CI)=1.33–2.22). Cigarette smoking was associated with an increased risk of rectal cancer only. Compared with nonsmokers, HRs (95% CIs) for rectal cancer were 1.43 (1.10–1.87) for light smokers and 2.64 (1.77–3.96) for heavy smokers. Our data indicate that cigarette smoking and alcohol use interact in the Chinese population in an additive manner in affecting risk of rectal cancer, thus suggesting that these two exposures may share a common etiologic pathway in rectal carcinogenesis
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