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A procoagulant snake venom serine protease was isolated from the venom of the nose-horned viper (Vipera ammodytes ammodytes). This 34 kDa glycoprotein, termed VaaSP-VX, possesses five kDa N-linked carbohydrates. Amino acid sequencing showed VaaSP-VX to be a chymotrypsin-like serine protease. Structurally, it is highly homologous to VaaSP-6 from the same venom and to nikobin from the venom of Vipera nikolskii, neither of which have known functions. VaaSP-VX does not affect platelets. The specific proteolysis of blood coagulation factors X and V by VaaSP-VX suggests that its blood-coagulation-inducing effect is due to its ability to activate these two blood coagulation factors, which following activation, combine to form the prothrombinase complex. VaaSP-VX may thus represent the first example of a serine protease with such a dual activity, which makes it a highly suitable candidate to replace diluted Russell's viper venom in lupus anticoagulant testing, thus achieving greater reliability of the analysis. As a blood-coagulation-promoting substance that is resistant to serpin inhibition, VaaSP-VX is also interesting from the therapeutic point of view for treating patients suffering from hemophilia.Phlebotomine sandflies are vectors of the humans' and mammals' parasite Leishmania spp. Although the role of gut microbiome in the biological cycle of insects is acknowledged, we still know little about the factors modulating the composition of the gut microbiota of sandflies. We tested whether host species impose a strong structural effect on the gut microbiota of Phlebotomus spp. Sandflies were collected from the island of Leros, Greece, and classified to P. papatasi, P. neglectus, P. tobbi, and P. similis, all being negative to Leishmania spp. The prokaryotic gut microbiota was determined via 16S rRNA gene amplicon sequencing. Phlebotomus species supported distinct microbial communities (p less then 0.001). P. papatasi microbiota was the most distinct over-dominated by three Spiroplasma, Wolbachia and Paenibacillus operational taxonomic units (OTUs), while another Wolbachia OTU prevailed in P. neglectus. Conversely, the microbiota of P. tobbi and P. similis was composed of several less dominant OTUs. Archaea showed low presence with the dominant OTUs belonging to methanogenic Euryarcheota, ammonia-oxidizing Thaumarcheota, and Nanoarchaeota. We provide first insights into the composition of the bacterial and archaeal community of Phlebotomus sandflies and showed that, in the absence of Leishmania, host genotype is the major modulator of Phlebotomus sandfly gut microbiota.Sedative/hypnotic use and homophobic bullying have become a big mental health concern for gay and bisexual men. However, few studies have investigated the mediators and moderators of the association between them. The current study aimed to build a conceptual model to estimate the mediating effect of emotional symptoms and the moderating effect of family support on this association among gay and bisexual men in Taiwan. A total of 500 gay or bisexual men were recruited for the study. Their history of homophobic bullying, their experience of sedative/hypnotic use, their perceived family support, and their current emotional symptoms were evaluated using self-reporting questionnaires. A moderated mediation model was developed to test the mediating effect of emotional symptoms and the moderating effect of family support. A higher level of homophobic bullying was significantly associated with sedative/hypnotic use among gay and bisexual men and this was mediated by a higher severity of emotional symptoms. A moderating effect of family support was identified, wherein the mediating effect of emotional symptoms was weaker when there was a higher level of perceived family support, thus revealing the protective effect of family support. The significant impact of emotional symptoms and family support on the association between homophobic bullying and sedative/hypnotic use was identified. Timely interventions for emotional symptoms and the enhancement of family support are crucial for gay and bisexual men.The emergence of deep-learning methods in different computer vision tasks has proved to offer increased detection, recognition or segmentation accuracy when large annotated image datasets are available. In the case of medical image processing and computer-aided diagnosis within ultrasound images, where the amount of available annotated data is smaller, a natural question arises are deep-learning methods better than conventional machine-learning methods? How do the conventional machine-learning methods behave in comparison with deep-learning methods on the same dataset? Based on the study of various deep-learning architectures, a lightweight multi-resolution Convolutional Neural Network (CNN) architecture is proposed. It is suitable for differentiating, within ultrasound images, between the Hepatocellular Carcinoma (HCC), respectively the cirrhotic parenchyma (PAR) on which HCC had evolved. The proposed deep-learning model is compared with other CNN architectures that have been adapted by transfer learning for the ultrasound binary classification task, but also with conventional machine-learning (ML) solutions trained on textural features. The achieved results show that the deep-learning approach overcomes classical machine-learning solutions, by providing a higher classification performance.Whole slide imaging (WSI) refers to the process of creating a high-resolution digital image of a whole slide. Since digital images are typically produced by stitching image sequences acquired from different fields of view, the visual quality of the images can be degraded owing to shading distortion, which produces black plaid patterns on the images. A shading correction method for brightfield WSI is presented, which is simple but robust not only against typical image artifacts caused by specks of dust and bubbles, but also against fixed-pattern noise, or spatial variations in pixel values under uniform illumination. The proposed method comprises primarily of two steps. The first step constructs candidates of a shading distortion model from a stack of input image sequences. The second step selects the optimal model from the candidates. The proposed method was compared experimentally with two previous state-of-the-art methods, regularized energy minimization (CIDRE) and background and shading correction (BaSiC) and showed better correction scores, as smooth operations and constraints were not imposed when estimating the shading distortion. The correction scores, averaged over 40 image collections, were as follows proposed method, 0.39 ± 0.099; CIDRE method, 0.67 ± 0.047; BaSiC method, 0.55 ± 0.038. Based on the quantitative evaluations, we can confirm that the proposed method can correct not only shading distortion, but also fixed-pattern noise, compared with the two previous state-of-the-art methods.As a new information provider of autonomous navigation, the on-orbit landmark observation offers a new means to improve the accuracy of autonomous positioning and attitude determination. A novel autonomous navigation method based on the landmark observation and the inertial system is designed to achieve the high-accuracy estimation of the missile platform state. In the proposed method, the navigation scheme is constructed first. The implicit observation equation about the deviation of the inertial system output is derived and the Kalman filter is applied to estimate the missile platform state. Moreover, the physical observability of the landmark and the mathematical observability of the navigation system are analyzed. Finally, advantages of the proposed autonomous navigation method are demonstrated through simulations compared with the traditional celestial-inertial navigation system and the deeply integrated celestial-inertial navigation system.Extremophilic microorganisms are considered being very promising candidates for biotechnological production of various products including polyhydroxyalkanoates (PHA). The aim of this work was to evaluate the PHA production potential of a novel PHA-producing thermophilic Gram-positive isolate Aneurinibacillus sp. H1. This organism was capable of efficient conversion of glycerol into poly(3-hydroxybutyrate) (P3HB), the homopolyester of 3-hydroxybutyrate (3HB). In flasks experiment, under optimal cultivation temperature of 45 °C, the P3HB content in biomass and P3HB titers reached 55.31% of cell dry mass and 2.03 g/L, respectively. Stenoparib in vitro Further, the isolate was capable of biosynthesis of PHA copolymers and terpolymers containing high molar fractions of 3-hydroxyvalerate (3HV) and 4-hydroxybutyrate (4HB). Especially 4HB contents in PHA were very high (up to 91 mol %) when 1,4-butanediol was used as a substrate. Based on these results, it can be stated that Aneurinibacillus sp. H1 is a very promising candidate for production of PHA with tailored material properties.Classical swine fever (CSF) caused by the CSF virus (CSFV) is one of the most important swine diseases, resulting in huge economic losses to the pig industry worldwide. Systematic vaccination is one of the most effective strategies for the prevention and control of this disease. Two main CSFV vaccines, the modified live vaccine (MLV) and the subunit E2 vaccine, are recommended. In Taiwan, CSF cases have not been reported since 2006, although systemic vaccination has been practiced for 70 years. Here, we examined the sero-dynamics of the piglets born from sows that received either the CSFV MLV or the E2 vaccine and investigated in the field the correlation between the porcine reproductive and respiratory syndrome virus (PRRSV) loads and levels of CSFV antibody. A total of 1398 serum samples from 42 PRRSV-positive farms were evaluated to determine the PRRSV loads by real-time PCR and to detect CSFV antibody levels by commercial ELISA. Upon comparing the two sow vaccination protocols (CSFV MLV vaccination at 4 wr industrial pork production in the field.Achievement of microscopic tumor clearance (R0) after pancreatic ductal adenocarcinoma (PDAC) surgery is determined by cancer biology rather than operative technique. Fibroblasts are known to play pro-cancer roles; however, a small subset was recently found to play anti-cancer roles. Therefore, we hypothesized that intratumor fibroblasts contribute to curative resection and a better survival of PDAC. Utilizing a large, publicly available PDAC cohort, we found that fibroblast composition was associated with R0 curative resection. A high amount of fibroblasts in PDACs was significantly associated with a higher amount of mature vessels, but not with blood angiogenesis. A high amount of fibroblasts was also associated with a higher infiltration of anti-cancer immune cells, such as CD8+ T-cells and dendritic cells, together with higher inflammatory signaling, including IL2/STAT5 and IL6/JAK/STAT3 signaling. Further, the fibroblast composition was inversely associated with cancer cell composition in the bulk tumor, along with an inverse association with proliferative characteristics, such as MYC signaling and glycolysis. The patients with high-fibroblast PDACs showed an improved prognosis. In conclusion, we found that PDACs with high fibroblasts were associated with a higher R0 resection rate, resulting in a better prognosis. These findings may be due to less aggressive biology with a higher vascularity and anti-cancer immunity, and a low cancer cell component.

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