1,397 research outputs found

    The hydrogenā€“air burning rate near the lean flammability limit

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    This paper investigates the inner structure of the thin reactive layer of hydrogenā€“air fuellean deflagrations close to the flammability limit. The analysis, which employs seven elementary reactions for the chemistry description, uses the ratio of the characteristic radical and fuel concentrations as a small asymptotic parameter, enabling an accurate analytic expression for the resulting burning rate to be derived. The analysis reveals that the steady-state assumption for chemical intermediaries, applicable on the hot side of the reactive layer, fails, however, as the crossover temperature is approached, providing a nonnegligible higher-order correction to the burning rate. The results can be useful, for instance, in future investigations of hydrogen deflagration instabilities near the lean flammability limit

    Bidirectional KCNQ1:Ī²-catenin interaction drives colorectal cancer cell differentiation.

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    The K+ channel KCNQ1 has been proposed as a tumor suppressor in colorectal cancer (CRC). We investigated the molecular mechanisms regulating KCNQ1:Ī²-catenin bidirectional interactions and their effects on CRC differentiation, proliferation, and invasion. Molecular and pharmacologic approaches were used to determine the influence of KCNQ1 expression on the Wnt/Ī²-catenin signaling and epithelial-to-mesenchymal transition (EMT) in human CRC cell lines of varying stages of differentiation. The expression of KCNQ1 was lost with increasing mesenchymal phenotype in poorly differentiated CRC cell lines as a consequence of repression of the KCNQ1 promoter by Ī²-catenin:T-cell factor (TCF)-4. In welldifferentiated epithelial CRC cell lines, KCNQ1 was localized to the plasma membrane in a complex with Ī²-catenin and E-cadherin. The colocalization of KCNQ1 with adherens junction proteins was lost with increasing EMT phenotype. ShRNA knock-down of KCNQ1 caused a relocalization of Ī²-catenin from the plasma membrane and a loss of epithelial phenotype in CRC spheroids. Overexpression of KCNQ1 trapped Ī²-catenin at the plasma membrane, induced a patent lumen in CRC spheroids, and slowed CRC cell invasion. The KCNQ1 ion channel inhibitor chromanol 293B caused membrane depolarization, redistribution of Ī²-catenin into the cytosol, and a reduced transepithelial electrical resistance, and stimulated CRC cell proliferation. Analysis of human primary CRC tumor patient databases showed a positive correlation between KCNQ1:KCNE3 channel complex expression and disease-free survival. We conclude that the KCNQ1 ion channel is a target gene and regulator of the Wnt/Ī²-catenin pathway, and its repression leads to CRC cell proliferation, EMT, and tumorigenesis

    Efficacy and safety profile of boceprevir- or telaprevir-based triple therapy or dual peginterferon alfa-2a or alfa-2b plus ribavirin therapy in chronic hepatitis C: the real-world PegBase observational study.

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    BACKGROUND: The aim of the study was to determine the efficacy and safety of triple therapy with a first-generation protease inhibitor (PI; boceprevir, telaprevir) plus peginterferon alfa-2a or -2b plus ribavirin, and dual therapy (peginterferon alfa-2a or -2b plus ribavirin) in patients with chronic hepatitis C (CHC) in routine clinical practice. METHODS: PegBase was an international, prospective, observational study in which 4441 patients with CHC were enrolled in 27 countries. This analysis focuses on results in 4100 treatment-naĆÆve and previously treated patients treated with PI-based triple therapy or dual therapy, according to the discretion of the investigator and local standards of practice. The primary efficacy outcome was sustained virological response after 12-week follow up (SVR12). RESULTS: SVR12 rates in treatment-naĆÆve genotype (G) 1 patients were 56.6% and 62.9% for recipients of boceprevir plus peginterferon alfa-2a/ribavirin and boceprevir plus peginterferon alfa-2b/ribavirin, respectively, and 65.3% and 58.6% for recipients of telaprevir plus peginterferon alfa-2a/ribavirin and telaprevir plus peginterferon alfa-2b/ribavirin, respectively. In previously treated patients assigned to these four regimens, SVR12 rates were 43.6%, 48.3%, 60.3% and 56.1%, respectively. Among treatment-naĆÆve patients assigned to peginterferon alfa-2a/ribavirin and peginterferon alfa-2b/ribavirin, respectively, SVR12 rates were 49.2% and 41.9% in G1 patients, 75.7% and 83.3% in G2 patients, 65.9% and 65.9% in G3 patients, and 49.7%, and 51.1% in G4 patients. The safety and tolerability of dual and triple therapy were consistent with previous reports. CONCLUSION: The efficacy and safety of first-generation PI-based triple-therapy and dual-therapy regimens in this real-world cohort were broadly comparable to those of previous studies.F. Hoffmann-La Roche Ltd., Basel, Switzerlan

    Managing local supplier networks: conflict or compromise

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    This paper examines conflict management in small firm networks. Informal conflict management strategies used in exchange relationships are identified and analysed. In-depth, semi-structured interviews with 22 small and medium-sized enterprise managers in an industrial district in the south-east of France are analysed. Results point to managers adopting accommodating behaviours in conflicts with clients and compromising and collaborative strategies with local partners. This research reveals the mobilization of local norms in the management of conflicts and also contributes to research concerning coopetition and the possibility that managers of small firms may both separate and integrate coopetition activities

    Suppression of HBV by Tenofovir in HBV/HIV coinfected patients : a systematic review and meta-analysis

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    Background: Hepatitis B coinfection is common in HIV-positive individuals and as antiretroviral therapy has made death due to AIDS less common, hepatitis has become increasingly important. Several drugs are available to treat hepatitis B. The most potent and the one with the lowest risk of resistance appears to be tenofovir (TDF). However there are several questions that remain unanswered regarding the use of TDF, including the proportion of patients that achieves suppression of HBV viral load and over what time, whether suppression is durable and whether prior treatment with other HBV-active drugs such as lamivudine, compromises the efficacy of TDF due to possible selection of resistant HBV strains. Methods: A systematic review and meta-analysis following PRISMA guidelines and using multilevel mixed effects logistic regression, stratified by prior and/or concomitant use of lamivudine and/or emtricitabine. Results: Data was available from 23 studies including 550 HBV/HIV coinfected patients treated with TDF. Follow up was for up to seven years but to ensure sufficient power the data analyses were limited to three years. The overall proportion achieving suppression of HBV replication was 57.4%, 79.0% and 85.6% at one, two and three years, respectively. No effect of prior or concomitant 3TC/FTC was shown. Virological rebound on TDF treatment was rare. Interpretation: TDF suppresses HBV to undetectable levels in the majority of HBV/HIV coinfected patients with the proportion fully suppressed continuing to increase during continuous treatment. Prior treatment with 3TC/FTC does not compromise efficacy of TDF treatment. The use of combination treatment with 3TC/FTC offers no significant benefit over TDF alone

    Affective Man-Machine Interface: Unveiling human emotions through biosignals

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    As is known for centuries, humans exhibit an electrical profile. This profile is altered through various psychological and physiological processes, which can be measured through biosignals; e.g., electromyography (EMG) and electrodermal activity (EDA). These biosignals can reveal our emotions and, as such, can serve as an advanced man-machine interface (MMI) for empathic consumer products. However, such a MMI requires the correct classification of biosignals to emotion classes. This chapter starts with an introduction on biosignals for emotion detection. Next, a state-of-the-art review is presented on automatic emotion classification. Moreover, guidelines are presented for affective MMI. Subsequently, a research is presented that explores the use of EDA and three facial EMG signals to determine neutral, positive, negative, and mixed emotions, using recordings of 21 people. A range of techniques is tested, which resulted in a generic framework for automated emotion classification with up to 61.31% correct classification of the four emotion classes, without the need of personal profiles. Among various other directives for future research, the results emphasize the need for parallel processing of multiple biosignals

    ā€œSavages Who Speak Frenchā€: Folklore, Primitivism and Morals in Robert Hertz

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    Hertz's analysis of the Alpine cult of Saint Besse apparently marks a break from his studies of death, sin and the left to folkloric studies. This analysis helps one to understand the personality of Robert Hertz. His sociological curiosity about folklore reveals his ambiguous position in social sciences at the beginning of the twentieth century. His text appears to be a variation from the Durkheimian norm, but another reading could suggest that Hertz continued and went beyond Durkheimian thought to something between sociology of the modern world and engaged socialism. Through this study, Hertz linked his political ideals, his work in ethnology and his desire for social involvement. The cult of Saint Besse perpetuated as much religious tradition as local identity. The Alpine people were presented in the text as wilful perpetuators of an ideal social order, whose loss for his contemporary city dwellers Hertz feared. The alpine Other, marked by a material and moral backwardness, represented for activist and socialist Hertz one of the paths of balanced social organization that stabilized the identity of a group across time if it fit rather well into the folkloric stereotypes of the beginning of the twentieth century. Finally, by linking events in Herz's life (e.g., the accidental Alpine death of his father), this article suggests that the legend of Saint Besse embodied several recurring motifs in Hertz' career: the accidental deaths of saint and father by falls, the military role of the saint and of Hertz himself
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