1,400 research outputs found

    Fundamental groups of Galois closures of generic projections

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    Uncertainties Related to Extreme Event Statistics of Sewer System Surcharge and Overflow

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    Претензионная работа по топливу для предприятий энергетики

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    Background and aims: CREB (cAMP response element binding protein) transcription factors are key regulators of homeostatic functions in the liver, and CRE binding is increased in hepatic inflammation. During chronic hepatitis B virus (HBV) infection, mutations or deletions in the pre-S region are frequently observed. These mutations can affect the pre-S2/S promoter controlling HBV envelope protein expression (hepatitis B surface antigen (HBsAg)) and have been associated with worsened clinical outcome. We aimed to test if CREB activation impacts on HBsAg expression. Methods: The effect of the CREB inducer protein kinase A (PKA) was tested by coexpression with HBV wild-type vector in vitro. Luciferase reporter gene constructs were cloned to identify novel regulatory regions for the HBV pre-S2/S promoter. Electrophoretic mobility shift assay (EMSA) gelshift and supershift experiments were conducted to confirm DNA transcription factor binding. Results: Coexpression of HBV and PKA resulted in HBV-S mRNA induction and enhanced small envelope protein expression. We identified a CREB binding motif in the transcribed part of the pre-S2 region, contributing to basal S promoter activity via binding of activating transcription factor 2 (ATF2). A second CREB motif closely linked to the S-ATG showed a similar binding pattern involving ATF2 and CREB1, without appearing essential for basal promoter activity. Moreover, a sequence in the pre-S2 region is responsible for further transcriptional induction via CREB activators such as PKA and forskolin. EMSA experiments indicate that CREB1 and ATF4 are involved in complex formation conferring PKA dependent promoter activation. Conclusions: Our data suggest a novel mechanism by which HBV may utilise CREB/PKA signal transduction pathways of hepatocytes to enhance its HBsAg expression during homeostasis and hepatic inflammation

    "Sensory Fit Panel" – Development of a new Advertising Claim Support method to assess aesthetic diaper fit performance in an objective, reliable and reproducible way

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    For the product design of diapers, the fit on the baby plays a significant role. In particular, innovation in the areas of fit and freedom of movement have become increasingly important as lower order needs like leakage are sufficiently met by most products. Today’s methods to measure diaper fit focus on technical measurements (engineering and technical fit) and parents’ subjective perceptions. While these methods are useful tools for product development purposes, they are not seen as sufficient for Advertising Claim Support needs. However, when a new fit innovation should be advertised, particularly when this is done in a competitive way, a robust technical support is needed to defend this claim in case of challenges by competitors or regulatory bodies. For this purpose, methods need to be objective and technically sound in order to be acceptable to advertising regulatory bodies. Independent, objective ratings would substantiate claims on a more reliable and reproducible base. To meet this need, the diaper fit sensory panel method was developed. This test reapplies the established sensory methodology used, e.g. to assess taste or smell in food and beverages

    Molecular alterations in triple-negative breast cancer-the road to new treatment strategies.

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    Triple-negative breast cancer is a heterogeneous disease and specific therapies have not been available for a long time. Therefore, conventional chemotherapy is still considered the clinical state of the art. Different subgroups of triple-negative breast cancer have been identified on the basis of protein expression, mRNA signatures, and genomic alterations. Important elements of triple-negative breast cancer biology include high proliferative activity, an increased immunological infiltrate, a basal-like and a mesenchymal phenotype, and deficiency in homologous recombination, which is in part associated with loss of BRCA1 or BRCA2 function. A minority of triple-negative tumours express luminal markers, such as androgen receptors, and have a lower proliferative activity. These biological subgroups are overlapping and currently cannot be combined into a unified model of triple-negative breast cancer biology. Nevertheless, the molecular analysis of this disease has identified potential options for targeted therapeutic intervention. This has led to promising clinical strategies, including modified chemotherapy approaches targeting the DNA damage response, angiogenesis inhibitors, immune checkpoint inhibitors, or even anti-androgens, all of which are being evaluated in phase 1-3 clinical studies. This Series paper focuses on the most relevant clinical questions, summarises the results of recent clinical trials, and gives an overview of ongoing studies and trial concepts that will lead to a more refined therapy for this tumour type

    Emotion recognition from faces with in- and out-group features in patients with depression

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    Background Previous research has shown that context (e.g. culture) can have an impact on speed and accuracy when identifying facial expressions of emotion. Patients with a major depressive disorder (MDD) are known to have deficits in the identification of facial expressions, tending to give rather stereotypical judgments. While healthy individuals perceive situations which conflict with their own cultural values more negatively, this pattern would be even stronger in MDD patients, as their altered mood results in stronger biases. In this study we investigate the effect of cultural contextual cues on emotion identification in depression. Methods Emotional faces were presented for 100 ms to 34 patients with an MDD and matched controls. Stimulus faces were either covered by a cap and scarf (in-group condition) or by an Islamic headdress (niqab; out-group condition). Speed and accuracy were evaluated. Results Results showed that across groups, fearful faces were identified faster and with higher accuracy in the out-group than in the in-group condition. Sadness was also identified more accurately in the out-group condition. In comparison, happy faces were more accurately (and tended to be faster) identified in the in-group condition. Furthermore, MDD patients were slower, yet not more accurate in identifying expressions of emotion compared to controls. Limitations All patients were on pharmacological treatment. Participants’ political orientation was not included. The experiment differs from real life situations. Conclusion While our results underline findings that cultural context has a general impact on emotion identification, this effect was not found to be more prominent in patients with MDD.NWO016-155-082Action Contro

    Reversible and Irreversible Interactions of Poly(3-hexylthiophene) with Oxygen Studied by Spin-Sensitive Methods

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    Understanding of degradation mechanisms in polymer:fullerene bulk-heterojunctions on the microscopic level aimed at improving their intrinsic stability is crucial for the breakthrough of organic photovoltaics. These materials are vulnerable to exposure to light and/or oxygen, hence they involve electronic excitations. To unambiguously probe the excited states of various multiplicities and their reactions with oxygen, we applied combined magneto-optical methods based on multifrequency (9 and 275 GHz) electron paramagnetic resonance (EPR), photoluminescence (PL), and PL-detected magnetic resonance (PLDMR) to the conjugated polymer poly(3-hexylthiophene) (P3HT) and polymer:fullerene bulk heterojunctions (P3HT:PCBM; PCBM = [6,6]-phenyl-C61-butyric acid methyl ester). We identified two distinct photochemical reaction routes, one being fully reversible and related to the formation of polymer:oxygen charge transfer complexes, the other one, irreversible, being related to the formation of singlet oxygen under participation of bound triplet excitons on the polymer chain. With respect to the blends, we discuss the protective effect of the methanofullerenes on the conjugated polymer bypassing the triplet exciton generation
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