150 research outputs found

    Monoclonal antibodies against human astrocytomas and their reactivity pattern

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    The establishment of hybridomas after fusion of X63-Ag8.653 mouse myeloma cells and splenocytes from mice hyperimmunized against human astrocytomas is presented. The animals were primed with 5 × 106 chemically modified uncultured or cultured glioma cells. Six weeks after the last immunization step an intrasplenal booster injection was administrated and 3 days later the spleen cells were prepared for fusion experiments. According to the specificity analysis of the generated antibodies 7 hybridoma products (MUC 7-22, MUC 8-22, MUC 10-22, MUC 11-22, MUC 14-22, MUC 15-22 and MUC 2-63) react with gliomas, neuroblastomas and melanomas as well as with embryonic and fetal cells but do not recognize non-neurogenic tumors. The selected monoclonal antibodies (McAbs) of IgG1 and IgG2a isotypes are not extensively characterized but these antibodies have been demonstrated to be reactive with a panel of glioma cell lines with varying patterns of antigen distribution. Using the McAbs described above and a series of cryosections of glioma biopsies and paraffin sections of the same material as well as glioma cultures established from these, variable antigenic profiles among glioma cell populations could be demonstrated. From these results it is evident that there is not only a distinct degree of antigenic heterogeneity among and within brain tumors, but also that the pattern of antigenic expression can change continuously. Some of the glioma associated antigens recognized by the selected antibodies persist after fixation with methanol/acetone and Karnovsky's fixative and probably are oncoembryonic/oncofetal antigen(s). The data suggest that the use of McAbs recognizing tumor associated oncofetal antigens in immunohistochemistry facilitates objective typing of intracranial malignancies and precise analysis of fine needle brain/tumor biopsies in a sensitive and reproducible manner

    Impact of dislocations and dangling bond defects on the electrical performance of crystalline silicon thin films

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    A wide variety of liquid and solid phase crystallized silicon films are investigated in order to determine the performance limiting defect types in crystalline silicon thin-film solar cells. Complementary characterization methods, such as electron spin resonance, photoluminescence, and electron microscopy, yield the densities of dangling bond defects and dislocations which are correlated with the electronic material quality in terms of solar cell open circuit voltage. The results indicate that the strongly differing performance of small-grained solid and large-grain liquid phase crystallized silicon can be explained by intra-grain defects like dislocations rather than grain boundary dangling bonds. A numerical model is developed containing both defect types, dislocations and dangling bonds, describing the experimental results

    Promoting More Physical Activity and Less Sedentary Behaviour During the COVID-19 Situation – SportStudisMoveYou (SSMY): A Randomized Controlled Trial

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    Objective: To determine the effect of an innovative, online-based intervention, addressing the possible decline of physical activity (PA) and increase of sedentary behavior (SB) during COVID-19 stay at home restrictions in Switzerland. Methods: This study investigated the effect of a two-week, social cognitive theory based, online-video moderate to vigorous (MV)PA or SB intervention on MVPA and SB behaviour and intention via a 3 group by 2 time point parallel randomized controlled trial during the COVID-19 pandemic. Adults (≥18 yo) were recruited over the internet between April 10th and April 19th 2020 (n = 129; 75.2% female; mean age = 29.0 [SD 11.8] years). Both intervention groups received five videos targeting either SB for the SB group or MVPA for the MVPA group and were compared to an attention control group (fruit and vegetable consumption). It was hypothesized that MVPA time and intention would increase for the MVPA group and the SB group would outperform control on SB behaviour and intention indicators. Results: No significant interactions were found for the MVPA group (n = 41) versus control (n = 40). Only one significant interaction was measured for the SB group (n = 48; intention of active breaks F = (2,114) = 5.84, p = 0.004, ηp2 = 0.09). Although mostly non-significant and small effects, the MVPA group showed results pointing in the hypothesized direction on all PA indicators and the SB on all SB indicators, respectively. Conclusion: Considering this study’s limitations (e.g. small intervention dose), video-based online PA and SB interventions seem promising and feasible. This approach is appropriate for COVID-19 and other stay at home situations

    A high Gas6 level in plasma predicts venous thromboembolism recurrence, major bleeding and mortality in the elderly: a prospective multicenter cohort study.

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    Essentials Predictive ability of pro-hemostatic Gas6 for recurrent venous thromboembolism (VTE) is unknown. We measured Gas6 levels in 864 patients with VTE over 3 years. High Gas6 (> 157%) at diagnosis is associated with VTE recurrence, major bleeding and mortality. Gas6 plasma levels measured 12 months after the index VTE are discriminatory for VTE recurrence. SUMMARY: Background Growth arrest-specific gene 6 (Gas6) is a prohemostatic protein with an unknown predictive ability for recurrent venous thromboembolism (VTE). In the elderly, VTE results in higher mortality but does not have a higher rate of recurrence than in younger patients. Consequently, anticoagulation management in the elderly is challenging. Objective To prospectively investigate the performance of Gas6 in predicting VTE recurrence, major bleeding and mortality in the elderly. Methods Consecutive patients aged ≥ 65 years with acute VTE were followed for a period of 3 years. Primary outcomes were symptomatic VTE recurrence, major bleeding, and mortality. Plasma Gas6 was measured with ELISA. Results Gas6 levels were measured in 864 patients at the time of the index VTE (T1) and, in 70% of them, also 12 months later (T2). The Gas6 level at T1 was discriminatory for VTE recurrence (C-statistic, 0.56; 95% confidence interval [CI] 0.51-0.62), major bleeding (0.60, 95% CI 0.55-0.65) and mortality (0.69, 95% CI 0.65-0.73) up to 36 months. VTE recurrence up to 24 months after T2 was discriminated by the Gas6 level at T2 (0.62, 95% CI 0.54-0.71). High Gas6 levels (> 157%) and continuous Gas6 levels at T1 were associated with VTE recurrence up to 6 months and 12 months, respectively. Conclusions In elderly patients, a high Gas6 level is associated with higher risks of VTE recurrence, major bleeding, and death. These findings support further studies to assess the performance of Gas6 in adjusting the length of anticoagulation

    African elephant poaching rates correlate with local poverty, national corruption and global ivory price

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    Poaching is contributing to rapid declines in elephant populations across Africa. Following high-profile changes in the political environment, the overall number of illegally killed elephants in Africa seems to be falling, but to evaluate potential conservation interventions we must understand the processes driving poaching rates at local and global scales. Here we show that annual poaching rates in 53 sites strongly correlate with proxies of ivory demand in the main Chinese markets, whereas between-country and between-site variation is strongly associated with indicators of corruption and poverty. Our analysis reveals a recent decline in annual poaching mortality rate from an estimated peak of over 10% in 2011 to <4% in 2017. Based on these findings, we suggest that continued investment in law enforcement could further reduce poaching, but is unlikely to succeed without action that simultaneously reduces ivory demand and tackles corruption and poverty

    Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

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    Abstract: Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10−10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10−10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis

    Therapeutic implications of cellular and molecular biology of cancer stem cells in melanoma

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