Differential Regulation of Interferon Signaling Pathways in CD4+ T Cells of the Low Type-2 Obesity-Associated Asthma Phenotype

In the era of personalized medicine, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as asthma phenotypes including obesity-associated asthma, are urgently needed. Peripheral blood was drawn from 10 obese, non-atopic asthmatic adults with a high body mass index (BMI; 36.67 ± 6.90); 10 non-obese, non-atopic asthmatic adults with normal BMI (23.88 ± 2.73); and 10 healthy controls with normal BMI (23.62 ± 3.74). All asthmatic patients were considered to represent a low type-2 asthma phenotype according to selective clinical parameters. RNA sequencing (RNA-Seq) was conducted on peripheral blood CD4⁺ T cells. Thousands of differentially expressed genes were identified in both asthma groups compared with heathy controls. The expression of interferon (IFN)-stimulated genes associated with IFN-related signaling pathways was specifically affected in obese asthmatics, while the gap junction and G protein-coupled receptor (GPCR) ligand binding pathways were enriched in both asthma groups. Furthermore, obesity gene markers were also upregulated in CD4⁺ T cells from obese asthmatics compared with the two other groups. Additionally, the enriched genes of the three abovementioned pathways showed a unique correlation pattern with various laboratory and clinical parameters. The specific activation of IFN-related signaling and viral infection pathways might provide a novel view of the molecular mechanisms associated with the development of the low type-2 obesity-associated asthma phenotype, which is a step ahead in the development of new stratified therapeutic approaches.     

Sintering,microwave properties,and circulator applications of textured Sc-substituted M-type ferrite thick films

Sc³⁺ substituted M-type ferrites are effective microwave magnetic materials with a ferromagnetic resonance frequency in the range of 20 GHz–50 GHz. We report on the fabrication of oriented ferrite thick films as microwave components for application in the K_a-band at 30 GHz. Films of BaFe_11.5.Sc_0.5O₁₉ were prepared by screen-printing on alumina substrates, drying in an external magnetic field, and sintering at 900 °C. Low-temperature sintering is achieved through use of a mixed BBSZ/CuO sintering aid. A strong anisotropy of the sintered ferrite films is revealed by XRD analysis. Microwave properties of the films were determined in a coplanar waveguide setup. The ferromagnetic resonance frequency of the films is at 30 GHz and the textured films possess good nonreciprocal properties which scale with film thickness. The films were tested in a Y-junction circulator, and represent promising materials for self-biased microwave components fabricated in thick film technology.     

Approaches for the combined use of risk analysis and testing: a systematic literature review

Risk analysis and testing are conducted for different purposes. Risk analysis and testing nevertheless involve processes that may be combined to the benefit of both. We may use testing to support risk analysis and risk analysis to support testing. This paper surveys literature on the combined use of risk analysis and testing. First, the existing approaches are identified through a systematic literature review. The identified approaches are then classified and discussed with respect to main goal, context of use and maturity level. The survey highlights the need for more structure and rigor in the definition and presentation of approaches. Evaluations are missing in most cases. The paper may serve as a basis for examining approaches for the combined use of risk analysis and testing, or as a resource for identifying the adequate approach to use.     

Complementary Dual Approach for In Silico Target Identification of Potential Pharmaceutical Compounds in Cystic Fibrosis

Cystic fibrosis is a genetic disease caused by mutation of the CFTR gene, which encodes a chloride and bicarbonate transporter in epithelial cells. Due to the vast range of geno- and phenotypes, it is difficult to find causative treatments; however, small-molecule therapeutics have been clinically approved in the last decade. Still, the search for novel therapeutics is ongoing, and thousands of compounds are being tested in different assays, often leaving their mechanism of action unknown. Here, we bring together a CFTR-specific compound database (CandActCFTR) and systems biology model (CFTR Lifecycle Map) to identify the targets of the most promising compounds. We use a dual inverse screening approach, where we employ target- and ligand-based methods to suggest targets of 309 active compounds in the database amongst 90 protein targets from the systems biology model. Overall, we identified 1038 potential target–compound pairings and were able to suggest targets for all 309 active compounds in the database.     

Biomarkers of Response and Resistance to CDK4/6 Inhibitors in Breast Cancer: Hints from Liquid Biopsy and microRNA Exploration

New evidence on the impact of dysregulation of the CDK4/6 pathway on breast cancer (BC) cell proliferation has led to the development of selective CDK4/6 inhibitors, which have radically changed the management of advanced BC. Despite the improved outcomes obtained by CDK4/6 inhibitors, approximately 10% of tumors show primary resistance, whereas acquired resistance appears to be an almost ubiquitous occurrence, leading to treatment failure. The identification of differentially expressed genes or genomic mutational signatures able to predict sensitivity or resistance to CDK4/6 inhibitors is critical for medical decision making and for avoiding or counteracting primary or acquired resistance against CDK4/6 inhibitors. In this review, we summarize the main mechanisms of resistance to CDK4/6 inhibitors, focusing on those associated with potentially relevant biomarkers that could predict patients’ response/resistance to treatment. Recent advances in biomarker identification are discussed, including the potential use of liquid biopsy for BC management and the role of multiple microRNAs as molecular predictors of cancer cell sensitivity and resistance to CDK4/6 inhibitors.     

Adherence preserving refinement of trace-set properties in STAIRS: exemplified for information flow properties and policies

STAIRS is a formal approach to system development with UML 2.1 sequence diagrams that supports an incremental and modular development process. STAIRS is underpinned by denotational and operational semantics that have been proved to be equivalent. STAIRS is more expressive than most approaches with a formal notion of refinement. STAIRS supports a stepwise refinement process under which trace properties as well as trace-set properties are preserved. This paper demonstrates the potential of STAIRS in this respect, in particular that refinement in STAIRS preserves adherence to information flow properties as well as policies.     

精密冲裁节约时间和成本

<正>众所周知,灯具中的所有连接件和变型连接件都固定在灯具中,以确保光源的电气接触。过去,这些传统的冲压件和弯曲件一直都是典型的钣金加工件。当前,它们都在伺服冲压机中进行生产。标准件生产厂商提供的这种专业化的伺服冲压—折弯机可以节约时间和生产成本。照明技术专业厂BJB公司利用Bihler公司生产制造的标准数控冲压设备生产制造符合Meusburger公司标准的钣金件,因此节约了大笔的资金和大量的时间。     

Cognitive performance in rats differing in their inborn anxiety.

There is profound evidence that cognitive processes and anxiety are interrelated. To learn more about this interaction, the authors tested rats bred for either high (HABs) or low (LABs) anxiety-related behavior in a modified hole board task. This task allows parallel investigation of various cognitive processes and possibly related behavioral dimensions, both under baseline conditions and during cognitively stressful situations. The authors provide evidence that the degree of anxiety is differentially associated with enhanced performance for distinct informational processes in rats. As HABs and LABs did not differ in their anxiety-related behavior after habituation, that is, in a familiar environment during appetitive learning, the authors conclude that anxiety behavior in naive HABs may be due to differential cognitive processing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Plasma treatment of wood–polymer composites: A comparison of three different discharge types and their effect on surface properties

Three different discharge types, based on the principle of a dielectric barrier discharge at atmospheric pressure, were investigated with regard to their influence on the adhesion properties of a series of wood–polymer composites. Wood flour (Picea abies L.) filled polypropylene and various proportions of polyethylene were manufactured either through extrusion or injection molding. The composites’ surfaces were activated by coplanar surface barrier discharge, remote plasma, and direct dielectric barrier discharge. The changes in wettability due to the pretreatment were investigated by contact angle measurement using the sessile drop method and calculation of surface free energy (SFE). It could be shown that wettability was improved by all three types of discharge, the contact angle decreased and the SFE correspondingly increased. X‐ray photoelectron spectroscopy revealed an increase in the O/C ratio at the material's surface. An improvement in coating adhesion was demonstrated by crosscut and pulloff tests. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43376.     

CFTR Lifecycle Map—A Systems Medicine Model of CFTR Maturation to Predict Possible Active Compound Combinations

Different causative therapeutics for CF patients have been developed. There are still no mutation-specific therapeutics for some patients, especially those with rare CFTR mutations. For this purpose, high-throughput screens have been performed which result in various candidate compounds, with mostly unclear modes of action. In order to elucidate the mechanism of action for promising candidate substances and to be able to predict possible synergistic effects of substance combinations, we used a systems biology approach to create a model of the CFTR maturation pathway in cells in a standardized, human- and machine-readable format. It is composed of a core map, manually curated from small-scale experiments in human cells, and a coarse map including interactors identified in large-scale efforts. The manually curated core map includes 170 different molecular entities and 156 reactions from 221 publications. The coarse map encompasses 1384 unique proteins from four publications. The overlap between the two data sources amounts to 46 proteins. The CFTR Lifecycle Map can be used to support the identification of potential targets inside the cell and elucidate the mode of action for candidate substances. It thereby provides a backbone to structure available data as well as a tool to develop hypotheses regarding novel therapeutics.