208 research outputs found

    Small Satellite Reliability: A Decade in Review

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    Advances in the small satellite combined with the availability of low-cost launches have led to an increasing number of space missions. As space is more accessible than ever before, new and innovative missions arise. A broad understanding of reliability trends on satellites can guide these future missions towards success. As a result, more and more space industries are focusing on reliability in the early stages of the design. The goal of this paper is to investigate the reliability of small satellites launched over the last three decades. Satellites launched between January 1990 - December 2019 and weighing between 40kg - 500kg are considered for this study. The dataset consists of 866 Earth-orbiting satellites. This study utilizes Kaplan-Meier estimator for calculating non-parametric reliability functions. The reliability results are then used to fit parametric models such as Weibull distribution to identify reliability trends. The dataset is further categorized based on satellite mission, launch year, developer, design life and orbit inclination to analyze their specific reliability trends. Finally, the contribution of satellite subsystems to satellite failure is quantified for this dataset and the subsystems with high(er) propensity for failure are identified. The results obtained in this study shall help in reliability/redundancy allocation of small satellites and its subsystems. It also supports small satellite design decisions, testing strategies and developing reliability growth plans for future missions. Furthermore, understanding the reliability trends in the past decades could potentially improve the reliability of small satellite in this current decade

    Gene expression profile of bladder tissue of patients with ulcerative interstitial cystitis

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    BACKGROUND: Interstitial cystitis (IC), a chronic bladder disease with an increasing incidence, is diagnosed using subjective symptoms in combination with cystoscopic and histological evidence. By cystoscopic examination, IC can be classified into an ulcerative and a non-ulcerative subtype. To better understand this debilitating disease on a molecular level, a comparative gene expression profile of bladder biopsies from patients with ulcerative IC and control patients has been performed. RESULTS: Gene expression profiles from bladder biopsies of five patients with ulcerative IC and six control patients were generated using Affymetrix GeneChip expression arrays (Affymetrix--GeneChip Human Genome U133 Plus 2.0). More than 31,000 of > 54,000 tested probe sets were present (detection p-value < 0.05). The difference between the two groups was significant for over 3,500 signals (t-test p-value < 0.01), and approximately 2,000 of the signals (corresponding to approximately 1,000 genes) showed an IC-to-healthy expression ratio greater than two. The IC pattern had similarities to patterns from immune system, lymphatic, and autoimmune diseases. The dominant biological processes were the immune and inflammatory responses. Many of the up-regulated genes were expressed in leukocytes, suggesting that leukocyte invasion into the bladder wall is a dominant feature of ulcerative IC. Histopathological data supported these findings. CONCLUSION: GeneChip expression arrays present a global picture of ulcerative IC and provide us with a series of marker genes characteristic for this subtype of the disease. Evaluation of biopsies from other bladder patients with similar symptoms (e.g. patients with non-ulcerative IC) will further indicate whether the data presented here will be valuable for the diagnosis of IC

    Swiss students and young physicians want a flexible goal-oriented GP training curriculum.

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    A growing shortage of general practitioners (GPs), in Switzerland and around the world, has forced countries to find new ways to attract young physicians to the specialty. In 2017, Switzerland began to fund hundreds of new study places for medical students. This wave of young physicians will soon finish University and be ready for postgraduate training. We hypothesized that an attractive postgraduate training program would encourage interested young physicians to pursue a GP career. This is a cross-sectional survey of young physicians from the Swiss Young General Practitioners Association (JHaS), members of Cursus Romand de médecine de famille (CRMF), and all current medical students (5 &lt;sup&gt;th&lt;/sup&gt; or 6 &lt;sup&gt;th&lt;/sup&gt; years) (n = 554) in Switzerland, excluding students indicating definitely not to become GPs. We asked all if they were likely to become a GP (Likert: 1-10), and then asked them to score general features of a GP training curriculum, and likely effects of the curriculum on their career choice (Likert scale). They then rated our model curriculum (GO-GP) for attractiveness and effect (Likert Scales, open questions). Most participants thought they would become GPs (Likert: 8 of 10). Over 90% identified the same features as an important part of a curriculum ("yes" or "likely yes"): Our respondents thought the GO-GP curriculum was attractive (7.3 of 10). It was most attractive to those highly motivated to become GPs. After reviewing the curriculum, most respondents (58%) felt GO-GP would make them more likely to become a GP. Almost 80% of respondents thought an attractive postgraduate training program like GO-GP could motivate more young physicians to become GPs. Overall, medical students and young physicians found similar features attractive in the general and GO-GP curriculum, regardless of region or gender, and thought an attractive curriculum would attract more young doctors to the GP specialty. Key points An attractive postgraduate training program in general practice can attract more young physicians to become GPs. In this study cross-sectional survey including medical students (n = 242) and young physicians (n = 312) we presented general features for a curriculum and a model curriculum for general practice training, for evaluation of attractiveness to our study population. General practice training curriculum provides flexibility in choice of rotations, access to short rotations in a wide variety of medical specialties, training in specialty practices as well, mentoring and career guidance by GPs and guidance in choosing courses/certificate programs necessary for general practice. These findings help building attractive postgraduate training programs in general practice and fight GP shortage

    Chromatin and DNA methylation dynamics during retinoic acid-induced RET gene transcriptional activation in neuroblastoma cells

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    Although it is well known that RET gene is strongly activated by retinoic acid (RA) in neuroblastoma cells, the mechanisms underlying such activation are still poorly understood. Here we show that a complex series of molecular events, that include modifications of both chromatin and DNA methylation state, accompany RA-mediated RET activation. Our results indicate that the primary epigenetic determinants of RA-induced RET activation differ between enhancer and promoter regions. At promoter region, the main mark of RET activation was the increase of H3K4me3 levels while no significant changes of the methylation state of H3K27 and H3K9 were observed. At RET enhancer region a bipartite chromatin domain was detected in unstimulated cells and a prompt demethylation of H3K27me3 marked RET gene activation upon RA exposure. Moreover, ChIP experiments demonstrated that EZH2 and MeCP2 repressor complexes were associated to the heavily methylated enhancer region in the absence of RA while both complexes were displaced during RA stimulation. Finally, our data show that a demethylation of a specific CpG site at the enhancer region could favor the displacement of MeCP2 from the heavily methylated RET enhancer region providing a novel potential mechanism for transcriptional regulation of methylated RA-regulated loci

    Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH -Mutant Molecular Profiles

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    Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance
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