Mgb2 Nonlinear Properties Investigated under Localized High RF Magnetic Field Excitation

In order to increase the accelerating gradient of Superconducting Radio Frequency (SRF) cavities, Magnesium Diboride (MgB2) opens up hope because of its high transition temperature and potential for low surface resistance in the high RF field regime. However, due to the presence of the small superconducting gap in the {\pi} band, the nonlinear response of MgB2 is potentially quite large compared to a single gap s-wave superconductor (SC) such as Nb. Understanding the mechanisms of nonlinearity coming from the two-band structure of MgB2, as well as extrinsic sources, is an urgent requirement. A localized and strong RF magnetic field, created by a magnetic write head, is integrated into our nonlinear-Meissner-effect scanning microwave microscope [1]. MgB2 films with thickness 50 nm, fabricated by a hybrid physical-chemical vapor deposition technique on dielectric substrates, are measured at a fixed location and show a strongly temperature-dependent third harmonic response. We propose that at least two mechanisms are responsible for this nonlinear response, one of which involves vortex nucleation and penetration into the film. [1] T. M. Tai, X. X. Xi, C. G. Zhuang, D. I. Mircea, S. M. Anlage, "Nonlinear Near-Field Microwave Microscope for RF Defect Localization in Superconductors", IEEE Trans. Appl. Supercond. 21, 2615 (2011).Comment: 6 pages, 6 figure

The value of serum B-subunit of human chorionic gonadotropin level in prediction of treatment response to methotrexate in management of ectopic pregnancy; a systematic review and meta-analysis

Background: No consensus has been reached on prognostic value of serum concentration of β (beta) subunit of human chorionic gonadotropin (β-hCG) in treatment response to methotrexate in management of ectopic pregnancy. Therefore, the present study aimed to evaluate this subject through a systematic review and meta-analysis. Materials and Methods: An extensive literature search on online databases was performed. All studies performed on ectopic pregnancy patients treated by methotrexate from all age groups were included. After collecting data, random effect models were used to calculate t he pooled standardized mean difference (SMD) of β-hCG level in treatment success and treatment failure groups. Finally, pooled performance screening characteristics of serum β-hCG level were assessed in different cut offs. Results: Finally, 51 articles were included in meta-analysis. Overall treatment success rate of methotrexate was 84 95% confidence interval (CI): 84-85 percent. A negative association was found between serum β-hCG level and the treatment response before intervention (SMD= -1.10, 95% CI: -1.39 to -0.88). In addition, pooled sensitivity, specificity, and prognostic odds ratio of β-hCG in the 2000 mIU/mL cut off were: 0.75 (0.65-0.82), 0.68 (0.58-0.82), and 6.0 (5.0-8.0), respectively. Conclusion: The present meta-analysis showed that serum β-hCG concentration before treatment could predict success of methotrexate in management of ectopic pregnancy

Metabolic network reconstruction of Chlamydomonas offers insight into light-driven algal metabolism

A comprehensive genome-scale metabolic network of Chlamydomonas reinhardtii, including a detailed account of light-driven metabolism, is reconstructed and validated. The model provides a new resource for research of C. reinhardtii metabolism and in algal biotechnology

The completion of the Mammalian Gene Collection (MGC)

Since its start, the Mammalian Gene Collection (MGC) has sought to provide at least one full-protein-coding sequence cDNA clone for every human and mouse gene with a RefSeq transcript, and at least 6200 rat genes. The MGC cloning effort initially relied on random expressed sequence tag screening of cDNA libraries. Here, we summarize our recent progress using directed RT-PCR cloning and DNA synthesis. The MGC now contains clones with the entire protein-coding sequence for 92% of human and 89% of mouse genes with curated RefSeq (NM-accession) transcripts, and for 97% of human and 96% of mouse genes with curated RefSeq transcripts that have one or more PubMed publications, in addition to clones for more than 6300 rat genes. These high-quality MGC clones and their sequences are accessible without restriction to researchers worldwide

Evidence for Transcript Networks Composed of Chimeric RNAs in Human Cells

The classic organization of a gene structure has followed the Jacob and Monod bacterial gene model proposed more than 50 years ago. Since then, empirical determinations of the complexity of the transcriptomes found in yeast to human has blurred the definition and physical boundaries of genes. Using multiple analysis approaches we have characterized individual gene boundaries mapping on human chromosomes 21 and 22. Analyses of the locations of the 5′ and 3′ transcriptional termini of 492 protein coding genes revealed that for 85% of these genes the boundaries extend beyond the current annotated termini, most often connecting with exons of transcripts from other well annotated genes. The biological and evolutionary importance of these chimeric transcripts is underscored by (1) the non-random interconnections of genes involved, (2) the greater phylogenetic depth of the genes involved in many chimeric interactions, (3) the coordination of the expression of connected genes and (4) the close in vivo and three dimensional proximity of the genomic regions being transcribed and contributing to parts of the chimeric RNAs. The non-random nature of the connection of the genes involved suggest that chimeric transcripts should not be studied in isolation, but together, as an RNA network

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

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