21 research outputs found

    Electronic structure of the candidate 2D Dirac semimetal SrMnSb2: a combined experimental and theoretical study

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    SrMnSb2_2 is suggested to be a magnetic topological semimetal. It contains square, 2D Sb planes with non-symmorphic crystal symmetries that could protect band crossings, offering the possibility of a quasi-2D, robust Dirac semi-metal in the form of a stable, bulk (3D) crystal. Here, we report a combined and comprehensive experimental and theoretical investigation of the electronic structure of SrMnSb2_2, including the first ARPES data on this compound. SrMnSb2_2 possesses a small Fermi surface originating from highly 2D, sharp and linearly dispersing bands (the Y-states) around the (0,π\pi/a)-point in kk-space. The ARPES Fermi surface agrees perfectly with that from bulk-sensitive Shubnikov de Haas data from the same crystals, proving the Y−-states to be responsible for electrical conductivity in SrMnSb2_2. DFT and tight binding (TB) methods are used to model the electronic states, and both show good agreement with the ARPES data. Despite the great promise of the latter, both theory approaches show the Y-states to be gapped above EF_F, suggesting trivial topology. Subsequent analysis within both theory approaches shows the Berry phase to be zero, indicating the non-topological character of the transport in SrMnSb2_2, a conclusion backed up by the analysis of the quantum oscillation data from our crystals.Comment: 26 pages, 10 figures, revised submission to SciPost after including changes requested by referees. All referee reports are open and can be viewed here: https://scipost.org/submissions/1711.07165v2

    GEneSTATION 1.0: A Synthetic Resource of Diverse Evolutionary and Functional Genomic Data for Studying The Evolution of Pregnancy-Associated Tissues and Phenotypes

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    Mammalian gestation and pregnancy are fast evolving processes that involve the interaction of the fetal, maternal and paternal genomes. Version 1.0 of the GEneSTATION database (http://genestation.org) integrates diverse types of omics data across mammals to advance understanding of the genetic basis of gestation and pregnancy-associated phenotypes and to accelerate the translation of discoveries from model organisms to humans. GEneSTATION is built using tools from the Generic Model Organism Database project, including the biology-aware database CHADO, new tools for rapid data integration, and algorithms that streamline synthesis and user access. GEneSTATION contains curated life history information on pregnancy and reproduction from 23 high-quality mammalian genomes. For every human gene, GEneSTATION contains diverse evolutionary (e.g. gene age, population genetic and molecular evolutionary statistics), organismal (e.g. tissue-specific gene and protein expression, differential gene expression, disease phenotype), and molecular data types (e.g. Gene Ontology Annotation, protein interactions), as well as links to many general (e.g. Entrez, PubMed) and pregnancy disease-specific (e.g. PTBgene, dbPTB) databases. By facilitating the synthesis of diverse functional and evolutionary data in pregnancy-associated tissues and phenotypes and enabling their quick, intuitive, accurate and customized meta-analysis, GEneSTATION provides a novel platform for comprehensive investigation of the function and evolution of mammalian pregnancy

    Evaluation of quality of life in adults with neurofibromatosis 1 (NF1) using the Impact of NF1 on Quality Of Life (INF1-QOL) questionnaire

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    Background Neurofibromatosis 1 (NF1) is an inherited, multi-system, tumour suppressor disorder with variable complications that cause psychological distress and social isolation. The study aim was to develop and validate a disease-specific questionnaire to measure quality of life (QOL) in NF1 that is suitable both as an assessment tool in clinical practice and in clinical trials of novel therapy. Methods The Impact of NF1 on Quality of Life (INF1-QOL) questionnaire was developed by a literature search for common terms, focus group (n=6), semi-structured interviews (n=21), initial drafts (n =50) and final 14 item questionnaire (n=50). Bivariate correlations between items, exploratory factor analysis, correlations with severity and EuroQol were employed. Results INF1-QOL showed good internal reliability (Cronbach’s alpha 0.87), mean total INF1-QOL score was 8.64 (SD 6.3), median 7.00, range 0-30 (possible range 0-42); no significant correlations with age or gender. The mean total EuroQol score was 7.38 (SD 2.87), median 6.5, mean global EuroQol score was 76.34 (SD 16.56), median 80. Total INF1-QOL score correlated with total EuroQol r=0.82, p<0.0001. The highest impact on QOL was moderate or severe problems with anxiety and depression (32%) and negative effects of NF1 on role and outlook on life (42%). The mean inter-relater reliability for grading of clinical severity scores was 0.71 (range 0.65-0.79), and intra-class correlation was 0.92. The mean clinical severity score was 1.95 (SD 0.65) correlating r=0.34 with total INF1-QOL score p<0.05 and correlated 0.37 with total EuroQol score p<0.01. The clinical severity score was mild in 17 (34%), moderate in 16 (32%) and 17 (34%) individuals had severe disease. Conclusions INF1-QOL is a validated, reliable disease specific questionnaire that is easy and quick to complete. Role and outlook on life and anxiety and depression have the highest impact on QOL indicating the variability, severity and unpredictability of NF1. INFI-QOL correlates moderately with clinical severity. The moderate relationship between INF1-QOL and physician rated severity emphasizes the difference between clinical and patient perception. INFI-QOL will be useful in individual patient assessment and as an outcome measure for clinical trials

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    Co-Production Performance Evaluation of a Novel Solar Combi System for Simultaneous Pure Water and Hot Water Supply in Urban Households of UAE

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    Water is the most desirable and sparse resource in Gulf cooperation council (GCC) region. Utilization of point-of-use (POU) water treatment devices has been gaining huge market recently due to increase in knowledge of urban population on health related issues over contaminants in decentralized water distribution networks. However, there is no foolproof way of knowing whether the treated water is free of contaminants harmful for drinking and hence reliance on certified bottled water has increased worldwide. The bottling process right from treatment to delivery is highly unsustainable due to huge energy demand along the supply chain. As a step towards sustainability, we investigated various ways of coupling of membrane distillation (MD) process with solar domestic heaters for co-production of domestic heat and pure water. Performance dynamics of various integration techniques have been evaluated and appropriate configuration has been identified for real scale application. A solar combi MD (SCMD) system is experimentally tested for single household application for production 20 L/day of pure water and 250 L/day of hot water simultaneously without any auxiliary heating device. The efficiency of co-production system is compared with individual operation of solar heaters and solar membrane distillation

    Impulse voltage breakdown of argon+SF6 mixtures under non-uniform electric fields

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    This experimental study addresses the behavior of binary mixtures of argon and sulfur hexafluoride in a rod-plane electrode configuration when subjected to impulse voltages. Positive-polarity, standard lightning impulse voltages (1.2-/spl mu/s/50-/spl mu/s) with different magnitudes were employed throughout the experiments. The percentage of SF/sub 6/ in Ar was varied from 1% to 90% at a total gas pressure of 50 kPa and 100 kPa. The breakdown voltage of each gas mixture was recorded at 50% breakdown probability. Similar to our theoretical as well as experimental studies under static electric fields it is observed that the breakdown strength of Ar has increased dramatically when mixed with a small percentage of SF/sub 6/. However, the breakdown voltages did increase monotonically but not dramatically for higher SF/sub 6/ percentages
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