New approaches in order to enlarge the grain size of bulk CdZnTe (CZT) crystals

For the few decades, II-VI compound semiconductors are gaining attention because of its numerous applications in the field of detector technology, photovoltaic, nuclear medicine, astronomy etc. In the recent past, materials scientists focused their attention for the growth of CdTe/CdZnTe single crystals because it doesn\u27t require any specialized cooling and detects higher energy photos as in comparison with the existing Ge, Si and Hgl(2) detectors. In the present study, we are going to discuss five main approaches in order to get good quality CZT crystal and we have successfully grown the CZT crystal by adopting these approaches. They are: i) oscillatory Bridgman technique previous to the growth process, ii) modifying the thermal environments in a Bridgman geometry using a Pt tube as a cold finger in order to reduce the growth velocity iii) growth from the vapour phase using Bridgman geometry with a pyrolitic boron nitride (PBN) crucible to locate the feed material, and with a special temperature profile, iv) microgravity experiments in the FOTON M3 mission using magnetic field prior to the growth process and v) growth by a boron oxide encapsulation. The detailed discussions are given in the following sections

Parametric Probabilistic Seismic Performance Assessment Framework for Ordinary Standard Bridges

This paper focuses on the assembly and implementation of a full-fledged parametric probabilistic seismic performance assessment framework for ordinary standard bridges (OSBs) in California. The framework stems from the performance-based earthquake engineering (PBEE) assessment methodology developed under the auspices of the Pacific Earthquake Engineering Research (PEER) Center. It involves a sequential execution of analytical steps to arrive at estimates of performance measures which, for example as considered in this study, are the mean return periods (MRPs) of exceedances for a selected set of limit-states (LSs). Improvements from state-of-the-art literature related to various stages of the PEER PBEE assessment framework are incorporated. This includes: (1) introduction of an improved intensity measure (IM), i.e., average spectral acceleration over a period range, for probabilistic seismic hazard analysis (PSHA), (2) conditional mean spectrum (CMS)-based site-specific risk-consistent ground motions selection for ensemble nonlinear time-history analyses involved in probabilistic seismic demand hazard analysis (PSDemHA), (3) introduction of material strain-based engineering demand parameters (EDPs), (4) identification of practical damage LSs, and (5) development of strain-based fragility functions required in probabilistic seismic damage hazard analysis (PSDamHA) for the considered LSs. Four distinct testbed OSBs are selected for the study. A two-dimensional design parameter space is defined in terms of typical primary design variables involved in seismic design of OSBs, i.e., the column diameter and the column longitudinal steel reinforcement ratio. Computational models of the as-designed bridges as well as their re-designs spawned by varying the primary design variables subject to practical constraints are assessed using the implemented framework. For each testbed OSB, and for each of the considered LSs, a smooth surface is fitted to the MRPs computed for all the re-designs of the bridge in the primary design parameter space. Topologies of these surfaces are explored. Feasible design domains in the two-dimensional design parameter space are identified. Safety of the as-designed version and feasibility domain for the re-designs of each testbed OSB are examined and discussed.Support of this research by the California Department of Transportation under Grant No. 65A0594, Task No. 2880 is gratefully acknowledged. Opinions and findings in this study are those of the authors and do not necessarily reflect the views of the sponsor

modMine: flexible access to modENCODE data.

In an effort to comprehensively characterize the functional elements within the genomes of the important model organisms Drosophila melanogaster and Caenorhabditis elegans, the NHGRI model organism Encyclopaedia of DNA Elements (modENCODE) consortium has generated an enormous library of genomic data along with detailed, structured information on all aspects of the experiments. The modMine database (http://intermine.modencode.org) described here has been built by the modENCODE Data Coordination Center to allow the broader research community to (i) search for and download data sets of interest among the thousands generated by modENCODE; (ii) access the data in an integrated form together with non-modENCODE data sets; and (iii) facilitate fine-grained analysis of the above data. The sophisticated search features are possible because of the collection of extensive experimental metadata by the consortium. Interfaces are provided to allow both biologists and bioinformaticians to exploit these rich modENCODE data sets now available via modMine

Rapid De Novo Evolution of X Chromosome Dosage Compensation in Silene latifolia, a Plant with Young Sex Chromosomes

Evidence for dosage compensation in Silene latifolia, a plant with 10-million-year-old sex chromosomes, reveals that dosage compensation can evolve rapidly in young XY systems and is not an animal-specific phenomenon

Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls

Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group

Funder: U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)Funder: National Center for Research Resources under award number 1 C06 RR12463-01, VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the DOD Prostate Cancer Idea Development Award (W81XWH-15-1-0558), the DOD Lung Cancer Investigator-Initiated Translational Research Award (W81XWH-18-1-0440), the DOD Peer Reviewed Cancer Research Program (W81XWH-16-1-0329), the Ohio Third Frontier Technology Validation Fund, the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering and the Clinical and Translational Science Award Program (CTSA) at Case Western Reserve University.Funder: Susan G Komen Foundation (CCR CCR18547966) and a Young Investigator Grant from the Breast Cancer Alliance.Funder: The Canadian Cancer SocietyFunder: Breast Cancer Research Foundation (BCRF), Grant No. 17-194Abstract: Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Funder: Breast Cancer Research Foundation (BCRF); doi: https://doi.org/10.13039/100001006Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

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

Fig. 1 in The Chalcidoidea bush of life: evolutionary history of a massive radiation of minute wasps

Fig. 1. Comparison of properties of the analysed datasets. Datasets (AHE414 and UCEs) are described in Table 1. For each panel, letters above box plots reflect pairwise comparisons of marginal means estimated from the best-fit models; distributions sharing a letter do not differ significantly. Points: raw data (Table S2a). In (e), saturation was assessed by calculating the R2 of the linear regression of uncorrected p-distances against inferred distances in individual gene trees. Highest R2 are for least saturated loci. The scale of the Y axis is reversed to better show decrease in saturation. (f) The convergence of trees as saturation decreases. The Y axis shows the relative RF distance between pairs of trees obtained with either the combined exons or the combined UCEs. The X axis show the absolute value of the difference between the medians of the R2 of the linear regression of uncorrected p-distances against inferred distances in gene trees that were combined to get the compared trees [cf. (e)]. Four comparisons were performed in each case as datasets were analysed with and without partitioning.Published as part of &lt;i&gt;Cruaud, Astrid, Rasplus, Jean-Yves, Zha, Junxia, Burks, Roger, Delvare, Ǵerard, Fusu, Lucian, Gumovsky, Alex, Huber, John T., Jan̆sta, Petr, Mitroiu, Mircea-Dan, Noyes, John S., Noort, Simon van, Baker, Austin, Bohmova, Julie, Baur, Hannes, Blaimer, Bonnie B., Brady, Sean G., Bubeńıkova, Kristyna, Chartois, Marguerite, Copeland, Robert S., Papilloud, Natalie Dale-Skey, Molin, Ana Dal, Dominguez, Chrysalyn, Gebiola, Marco, Guerrieri, Emilio, Kresslein, Robert L., Krogmann, Lars, Lemmon, Emily, Murray, Elizabeth A., Nidelet, Sabine &amp; Nieves-Aldrey, Jośe Luis, 2023, The Chalcidoidea bush of life: evolutionary history of a massive radiation of minute wasps, pp. 1-30 in Cladistics 2023&lt;/i&gt; on page 6, DOI: 10.1111/cla.12561, &lt;a href="http://zenodo.org/record/10115140"&gt;http://zenodo.org/record/10115140&lt;/a&gt