A Design of Focal-plane Compensation of Aviation Imaging Equipment Based on MS5534C

AbstractThis paper proposes an auto-compensation method for defocusing distance caused by temperature and pressure in aviation imaging equipment. As the host computer, the TMS320F2812 is the core controller and the digital pressure sensor MS5534C from Intersema Company is used as slave computer. The controller acquires the output of the temperature and the pressure from the sensor through MCBSP interface. By the change of temperature and pressure which results in defocusing distance, the software is adopted to compensate the defocusing distance and thereby keeps the stabilization of focal plane in aviation imaging equipment. The design proposal and the software flow is shown in the paper, furthermore the new system has simple interface, small size and real-time function. With many flight tests, the defocusing distance after the compensation of temperature and pressure is far less than the half focal depth of the optical system and it is fully satisfied with the requirements of imaging

Strengthening Primary Healthcare through accelerated advancement of the global pharmacy workforce: a cross-sectional survey of 88 countries

Objective: Advancing the pharmacy workforce contributes to strengthening primary healthcare and accelerating progress towards universal health coverage. This study aimed to identify key enablers to support policy development for national pharmacy workforce advancement. // Design: A cross-sectional country-level questionnaire was distributed from July 2018 to March 2019. // Setting: National-level or country-level pharmacy workforce development policy. // Participants: Professional leadership associations and national agencies of the International Pharmaceutical Federation (FIP). The FIP global database included 129 countries. // Measures: The questionnaire was designed to collate data on the scope of advanced and specialist practice in respondent countries. Multiple correspondence analysis and subsequent cluster analysis were conducted to explore the associations and patterns of country-level attributes of systems in place for the pharmacy workforce advancement in order to develop a general transnational model for country-level advanced practice development. // Results: Eighty-eight countries (68.2% response rate) responded to the questionnaire. Factors that enhance and contribute to advanced practice policy development include the country’s socioeconomic factors and the availability of national practice advancement concepts. The essential advancement concepts include the availability of framework and professional recognition systems, programmes assisting advanced practice development and workforce advancement and recognition opportunities. Cluster analysis identified three clusters of country respondents. First cluster included low-income and middle-income with poor pharmacy advancement implementation, second cluster included a higher socioeconomic status with weaker pharmacy workforce advancement implementation and third cluster included upper middle-income to high-income countries and high rates of pharmacy advancement implementation. // Conclusion: The key factors identified in this study can be used to support a transnational approach to pharmacy workforce advancement. The three clusters identified highlighted that workforce advancement was not an exclusive trait of higher-income countries. Lessons from countries that have already adopted concepts of advancement in pharmacy practice could be adopted to other countries to accelerate the progress of advanced practice globally

A proteogenomic analysis of Shigella flexneri using 2D LC-MALDI TOF/TOF

<p>Abstract</p> <p>Background</p> <p>New strategies for high-throughput sequencing are constantly appearing, leading to a great increase in the number of completely sequenced genomes. Unfortunately, computational genome annotation is out of step with this progress. Thus, the accurate annotation of these genomes has become a bottleneck of knowledge acquisition.</p> <p>Results</p> <p>We exploited a proteogenomic approach to improve conventional genome annotation by integrating proteomic data with genomic information. Using <it>Shigella flexneri </it>2a as a model, we identified total 823 proteins, including 187 hypothetical proteins. Among them, three annotated ORFs were extended upstream through comprehensive analysis against an in-house N-terminal extension database. Two genes, which could not be translated to their full length because of stop codon 'mutations' induced by genome sequencing errors, were revised and annotated as fully functional genes. Above all, seven new ORFs were discovered, which were not predicted in <it>S. flexneri </it>2a str.301 by any other annotation approaches. The transcripts of four novel ORFs were confirmed by RT-PCR assay. Additionally, most of these novel ORFs were overlapping genes, some even nested within the coding region of other known genes.</p> <p>Conclusions</p> <p>Our findings demonstrate that current <it>Shigella </it>genome annotation methods are not perfect and need to be improved. Apart from the validation of predicted genes at the protein level, the additional features of proteogenomic tools include revision of annotation errors and discovery of novel ORFs. The complementary dataset could provide more targets for those interested in <it>Shigella </it>to perform functional studies.</p

Combining blue native polyacrylamide gel electrophoresis with liquid chromatography tandem mass spectrometry as an effective strategy for analyzing potential membrane protein complexes of Mycobacterium bovis bacillus Calmette-Guérin

<p>Abstract</p> <p>Background</p> <p>Tuberculosis is an infectious bacterial disease in humans caused primarily by <it>Mycobacterium tuberculosis</it>, and infects one-third of the world's total population. <it>Mycobacterium bovis </it>bacillus Calmette-Guérin (BCG) vaccine has been widely used to prevent tuberculosis worldwide since 1921. Membrane proteins play important roles in various cellular processes, and the protein-protein interactions involved in these processes may provide further information about molecular organization and cellular pathways. However, membrane proteins are notoriously under-represented by traditional two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and little is known about mycobacterial membrane and membrane-associated protein complexes. Here we investigated <it>M. bovis </it>BCG by an alternative proteomic strategy coupling blue native PAGE to liquid chromatography tandem mass spectrometry (LC-MS/MS) to characterize potential protein-protein interactions in membrane fractions.</p> <p>Results</p> <p>Using this approach, we analyzed native molecular composition of protein complexes in BCG membrane fractions. As a result, 40 proteins (including 12 integral membrane proteins), which were organized in 9 different gel bands, were unambiguous identified. The proteins identified have been experimentally confirmed using 2-D SDS PAGE. We identified MmpL8 and four neighboring proteins that were involved in lipid transport complexes, and all subunits of ATP synthase complex in their monomeric states. Two phenolpthiocerol synthases and three arabinosyltransferases belonging to individual operons were obtained in different gel bands. Furthermore, two giant multifunctional enzymes, Pks7 and Pks8, and four mycobacterial Hsp family members were determined. Additionally, seven ribosomal proteins involved in polyribosome complex and two subunits of the succinate dehydrogenase complex were also found. Notablely, some proteins with high hydrophobicity or multiple transmembrane helixes were identified well in our work.</p> <p>Conclusions</p> <p>In this study, we utilized LC-MS/MS in combination with blue native PAGE to characterize modular components of multiprotein complexes in BCG membrane fractions. The results demonstrated that the proteomic strategy was a reliable and reproducible tool for analysis of BCG multiprotein complexes. The identification in our study may provide some evidence for further study of BCG protein interaction.</p

QKI is a critical pre-mRNA alternative splicing regulator of cardiac myofibrillogenesis and contractile function

The RNA-binding protein QKI belongs to the hnRNP K-homology domain protein family, a well-known regulator of pre-mRNA alternative splicing and is associated with several neurodevelopmental disorders. Qki is found highly expressed in developing and adult hearts. By employing the human embryonic stem cell (hESC) to cardiomyocyte differentiation system and generating QKI-deficient hESCs (hESCs-QKIdel) using CRISPR/Cas9 gene editing technology, we analyze the physiological role of QKI in cardiomyocyte differentiation, maturation, and contractile function. hESCs-QKIdel largely maintain normal pluripotency and normal differentiation potential for the generation of early cardiogenic progenitors, but they fail to transition into functional cardiomyocytes. In this work, by using a series of transcriptomic, cell and biochemical analyses, and the Qki-deficient mouse model, we demonstrate that QKI is indispensable to cardiac sarcomerogenesis and cardiac function through its regulation of alternative splicing in genes involved in Z-disc formation and contractile physiology, suggesting that QKI is associated with the pathogenesis of certain forms of cardiomyopathies

The creatine kinase pathway is a metabolic vulnerability in EVI1-positive acute myeloid leukemia

Expression of the MECOM (also known as EVI1) proto-oncogene is deregulated by chromosomal translocations in some cases of acute myeloid leukemia (AML) and is associated with poor clinical outcome. Here, through transcriptomic and metabolomic profiling of hematopoietic cells, we reveal that EVI1 overexpression alters cellular metabolism. A screen using pooled short hairpin RNAs (shRNAs) identified the ATP-buffering, mitochondrial creatine kinase CKMT1 as necessary for survival of EVI1-expressing cells in subjects with EVI1-positive AML. EVI1 promotes CKMT1 expression by repressing the myeloid differentiation regulator RUNX1. Suppression of arginine-creatine metabolism by CKMT1-directed shRNAs or by the small molecule cyclocreatine selectively decreased the viability, promoted the cell cycle arrest and apoptosis of human EVI1-positive cell lines, and prolonged survival in both orthotopic xenograft models and mouse models of primary AML. CKMT1 inhibition altered mitochondrial respiration and ATP production, an effect that was abrogated by phosphocreatine-mediated reactivation of the arginine-creatine pathway. Targeting CKMT1 is thus a promising therapeutic strategy for this EVI1-driven AML subtype that is highly resistant to current treatment regimens. Keywords: AML; RUNX1; CKMT1; cyclocreatine; arginine metabolismNational Cancer Institute (U.S.) (NIH 1R35 CA210030-01)Stand Up To CancerBridge ProjectNational Cancer Institute (U.S.) (David H. Koch Institute for Integrative Cancer Research at MIT. Grant P30-CA14051

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Research on Hybrid Multi-Attribute Three-Way Group Decision Making Based on Improved VIKOR Model

In the era of internet connection and IOT, data-driven decision-making has become a new trend of decision-making and shows the characteristics of multi-granularity. Because three-way decision-making considers the uncertainty of decision-making for complex problems and the cost sensitivity of classification, it is becoming an important branch of modern decision-making. In practice, decision-making problems usually have the characteristics of hybrid multi-attributes, which can be expressed in the forms of real numbers, interval numbers, fuzzy numbers, intuitionistic fuzzy numbers and interval-valued intuitionistic fuzzy numbers (IVIFNs). Since other forms can be regarded as special forms of IVIFNs, transforming all forms into IVIFNs can minimize information distortion and effectively set expert weights and attribute weights. We propose a hybrid multi-attribute three-way group decision-making method and give detailed steps. Firstly, we transform all attribute values of each expert into IVIFNs. Secondly, we determine expert weights based on interval-valued intuitionistic fuzzy entropy and cross-entropy and use interval-valued intuitionistic fuzzy weighted average operator to obtain a group comprehensive evaluation matrix. Thirdly, we determine the weights of each attribute based on interval-valued intuitionistic fuzzy entropy and use the VIKOR method improved by grey correlation analysis to determine the conditional probability. Fourthly, based on the risk loss matrix expressed by IVIFNs, we use the optimization method to determine the decision threshold and give the classification rules of the three-way decisions. Finally, an example verifies the feasibility of the hybrid multi-attribute three-way group decision-making method, which provides a systematic and standard solution for this kind of decision-making problem