A Study of Wolf Pack Algorithm for Test Suite Reduction

Modern smart meter programs are iterating at an ever-increasing rate, placing higher demands on the software testing of smart meters. How to reduce the cost of software testing has become a focus of current research. The reduction of test overhead is the most intuitive way to reduce the cost of software testing. Test suite reduction is one of the necessary means to reduce test overhead. This paper proposes a smart meter test suite reduction technique based on Wolf Pack Algorithm. First, the algorithm uses the binary optimization set coverage problem to represent the test suite reduction of the smart meter program; then, the Wolf Pack Algorithm is improved by converting the positions of individual wolves into a 0/1 matrix; finally, the optimal test case subset is obtained by iteration. By simulating different smart meter programs and different size test suites, the experimental result shows that the Wolf Pack Algorithm achieves better results compared to similar algorithms in terms of the percentage of obtaining both the optimal solution and the optimal subset of test overhead

Activated IL-23/IL-17 pathway closely correlates with increased Foxp3 expression in livers of chronic hepatitis B patients

<p>Abstract</p> <p>Background</p> <p>Foxp3 protein plays a critical role in mediating the inflammatory response and can inhibit the proinflammatory IL-23/IL-17 pathway. However, the molecular interplay of Foxp3 and the IL-23/IL-17 pathway in patients with chronic hepatitis B (CHB) remains unclear. To this end, we analyzed the expression patterns of Foxp3- and IL-23/IL-17 pathway-related proinflammatory cytokines in 39 patients with acute-on-chronic liver failure, 71 patients with CHB and 32 healthy controls.</p> <p>Results</p> <p>Foxp3 expression was found to be elevated in and mainly expressed by the CD4⁺T cell sub-population of peripheral blood mononuclear cells and liver tissues of patients with hepatitis B. The intrahepatic expression of Foxp3 strongly correlated with the copies of HBV DNA and the concentration of surface antigen, HBsAg. IL-23/IL-17 pathway-related proinflammatory cytokines were also found to be significantly increased in patients' liver tissues, as compared to healthy controls. Moreover, Foxp3 expression was strikingly correlated with the production of these cytokines in liver tissues of CHB patients.</p> <p>Conclusions</p> <p>The closely-correlated increase of Foxp3 and IL-23/IL-17 pathway activity in HBV-infected livers suggests that the proinflammatory IL-23/IL-17 pathway had not been effectively suppressed by the host immune machinery, such as Treg (Foxp3) cells. Constitutive activation of the IL-23/17 pathway, thus, may support the chronic hepatitis B state.</p

Effects of Telbivudine Treatment on the Circulating CD4+ T-Cell Subpopulations in Chronic Hepatitis B Patients

CD4+ T cells serve as master regulators of the adaptive immune response to HBV. However, CD4+ T-cell subsets are heterogeneous, and it remains unknown how the antiviral agents affect the different CD4+ T cell subtypes. To this end, the expressions of signature transcription factors and cytokines of CD4+ T-cell subtypes were examined in hepatitis B patients before and after treatment with telbivudine. Results showed that, upon the rapid HBV copy decrease induced by telbivudine treatment, the frequencies and related cytokines of Th17 and Treg cells were dramatically decreased, while those for Th2 cells were dramatically increased. No obvious changes were observed in Th1 cell frequencies; although, IFN-γ expression was upregulated in response to telbivudine treatment, suggesting another cell source of IFN-γ in CHB patients. Statistical analyses indicated that Th17 and Tr1 (a Treg subtype) cells were the most sensitive subpopulations of the peripheral blood CD4+ T cells to telbivudine treatment over 52 weeks. Thus, Th17 and Tr1 cells may represent a suitable and effective predictor of responsiveness during telbivudine therapy. These findings not only improve our understanding of hepatitis pathogenesis but also can aid in future development of appropriate therapeutic strategies to control viral hepatitis

Extracts of Salvia-Nelumbinis Naturalis Ameliorate Nonalcoholic Steatohepatitis via Inhibiting Gut-Derived Endotoxin Mediated TLR4/NF- κ

Nonalcoholic steatohepatitis (NASH) is featured by the presence of hepatic steatosis combined with inflammation and hepatocellular injury. Gut-derived endotoxin plays a crucial role in the pathogenesis of NASH. Salvia-Nelumbinis naturalis (SNN), a formula of Traditional Chinese Medicine, has been identified to be effective for NASH, but the mechanisms were not thoroughly explored. In the present study, a NASH model was generated using C57BL/6 mice fed a high fat diet (HFD) supplemented periodically with dextran sulfate sodium (DSS) in drinking water for 12 weeks. Mice fed HFD alone (without DSS) or chow diet were used as controls. The NASH mice were given the SNN extracts in the following 4 weeks, while control mice were provided with saline. Mice fed HFD developed steatosis, and DSS supplementation resulted in NASH. The SNN extracts significantly improved metabolic disorders including obesity, dyslipidemia, and liver steatosis and reduced hepatic inflammation, circulating tumor necrosis factor-α (TNF-α), and lipopolysaccharide (LPS) levels. The beneficial effect of the SNN extracts was associated with restoration of intestinal conditions (microbiota, integrity of intestinal barrier) and inhibition of TLR4/NF-κB activation. These results suggest that the SNN extracts ameliorate NASH progression, possibly through blocking endotoxin related TLR4/NF-κB activation

Measurement of HbA1c and HbA2 by Capillarys 2 Flex Piercing HbA1c programme for simultaneous management of diabetes and screening for thalassemia

Introduction: Thalassemia could interfere with some assays for haemoglobin A1c (HbA1c) measurement, therefore, it is useful to be able to screen for thalassemia while measuring HbA1c. We used Capillarys 2 Flex Piercing (Capillarys 2FP) HbA1c programme to simultaneously measure HbA1c and screen for thalassemia. Materials and methods: Samples from 498 normal controls and 175 thalassemia patients were analysed by Capillarys 2FP HbA1c programme (Sebia, France). For method comparison, HbA1c was quantified by Premier Hb9210 (Trinity Biotech, Ireland) in 98 thalassaemia patients samples. For verification, HbA1c from eight thalassaemia patients was confirmed by IFCC reference method. Results: Among 98 thalassaemia samples, Capillarys 2FP did not provide an HbA1c result in three samples with HbH due to the overlapping of HbBart’s with HbA1c fraction; for the remaining 95 thalassaemia samples, Bland-Altman plot showed 0.00 ± 0.35% absolute bias between two systems, and a significant positive bias above 7% was observed only in two HbH samples. The HbA1c values obtained by Capillarys 2FP were consistent with the IFCC targets (relative bias below ± 6%) in all of the eight samples tested by both methods. For screening samples with alpha (α-) thalassaemia silent/trait or beta (β-) thalassemia trait, the optimal HbA2 cut-off values were ≤ 2.2% and > 2.8%, respectively. Conclusions: Our results demonstrated the Capillarys 2FP HbA1c system could report an accurate HbA1c value in thalassemia silent/trait, and HbA2 value (≤ 2.2% for α-thalassaemia silent/trait and > 2.8% for β-thalassemia trait) and abnormal bands (HbH and/or HbBart’s for HbH disease, HbF for β-thalassemia) may provide valuable information for screening

Global Mapping of H3K4me1 and H3K4me3 Reveals the Chromatin State-Based Cell Type-Specific Gene Regulation in Human Treg Cells

Regulatory T cells (Treg) contribute to the crucial immunological processes of self-tolerance and immune homeostasis. Genomic mechanisms that regulate cell fate decisions leading to Treg or conventional T cells (Tconv) lineages and those underlying Treg function remain to be fully elucidated, especially at the histone modification level. We generated high-resolution genome-wide distribution maps of monomethylated histone H3 lysine 4 (H3K4me1) and trimethylated H3K4 (H3K4me3) in human CD4+CD25+FOXP3+ Tregs and CD4+CD25+FOXP3− activated (a)Tconv cells by DNA sequencing-by-synthesis. 2115 H3K4me3 regions corresponded to proximal promoters; in Tregs, the genes associated with these regions included the master regulator FOXP3 and the chemokine (C-C motif) receptor 7 (CCR7). 41024 Treg-specific H3K4me1 regions were identified. The majority of the H3K4me1 regions differing between Treg and aTconv cells were located at promoter-distal sites, and in vitro reporter gene assays were used to evaluate and identify novel enhancer activity. We provide for the first time a comprehensive genome-wide dataset of lineage-specific H3K4me1 and H3K4me3 patterns in Treg and aTconv cells, which may control cell type-specific gene regulation. This basic principle is likely not restricted to the two closely-related T cell populations, but may apply generally to somatic cell lineages in adult organisms

Exploration of signals of positive selection derived from genotype-based human genome scans using re-sequencing data.

We have investigated whether regions of the genome showing signs of positive selection in scans based on haplotype structure also show evidence of positive selection when sequence-based tests are applied, whether the target of selection can be localized more precisely, and whether such extra evidence can lead to increased biological insights. We used two tools: simulations under neutrality or selection, and experimental investigation of two regions identified by the HapMap2 project as putatively selected in human populations. Simulations suggested that neutral and selected regions should be readily distinguished and that it should be possible to localize the selected variant to within 40 kb at least half of the time. Re-sequencing of two ~300 kb regions (chr4:158Mb and chr10:22Mb) lacking known targets of selection in HapMap CHB individuals provided strong evidence for positive selection within each and suggested the micro-RNA gene hsa-miR-548c as the best candidate target in one region, and changes in regulation of the sperm protein gene SPAG6 in the other

Seasonal variation in oxygenated organic molecules in urban Beijing and their contribution to secondary organic aerosol

Oxygenated organic molecules (OOMs) are crucial for atmospheric new particle formation and secondary organic aerosol (SOA) growth. Therefore, understanding their chemical composition, temporal behavior, and sources is of great importance. Previous studies on OOMs mainly focus on environments where biogenic sources are predominant, yet studies on sites with dominant anthropogenic emissions, such as megacities, have been lacking. Here, we conducted long-term measurements of OOMs, covering four seasons of the year 2019, in urban Beijing. The OOM concentration was found to be the highest in summer (1.6 x 10(8) cm(-3)), followed by autumn (7.9 x 10(7) cm(-3)), spring (5.7 x 10(7) cm(-3)) and winter (2.3 x 10(7) cm(-3)), suggesting that enhanced photo-oxidation together with the rise in temperature promote the formation of OOMs. Most OOMs contained 5 to 10 carbon atoms and 3 to 7 effective oxygen atoms (nO(eff) = nO - 2 x nN). The average nO(eff )increased with increasing atmospheric photo-oxidation capacity, which was the highest in summer and the lowest in winter and autumn. By performing a newly developed workflow, OOMs were classified into the following four types: aromatic OOMs, aliphatic OOMs, isoprene OOMs, and monoterpene OOMs. Among them, aromatic OOMs (29 %-41 %) and aliphatic OOMs (26 %-41 %) were the main contributors in all seasons, indicating that OOMs in Beijing were dominated by anthropogenic sources. The contribution of isoprene OOMs increased significantly in summer (33 %), which is much higher than those in the other three seasons (8 %-10 %). Concentrations of isoprene (0.2-5.3 x 10(7) cm(-3)) and monoterpene (1.1-8.4 x 10(6) cm(-3)) OOMs in Beijing were lower than those reported at other sites, and they possessed lower oxygen and higher nitrogen contents due to high NO, levels (9.5-38.3 ppbv - parts per billion by volume) in Beijing. With regard to the nitrogen content of the two anthropogenic OOMs, aromatic OOMs were mainly composed of CHO and CHON species, while aliphatic OOMs were dominated by CHON and CHON2 ones. Such prominent differences suggest varying formation pathways between these two OOMs. By combining the measurements and an aerosol dynamic model, we estimated that the SOA growth rate through OOM condensation could reach 0.64, 0.61, 0.41, and 0.30 mu g m(-3) h(-1) in autumn, summer, spring, and winter, respectively. Despite the similar concentrations of aromatic and aliphatic OOMs, the former had lower volatilities and, therefore, showed higher contributions (46 %-62 %) to SOA than the latter (14 %-32 %). By contrast, monoterpene OOMs and isoprene OOMs, limited by low abundances or high volatilities, had low contributions of 8 %-12 % and 3 %-5 %, respectively. Overall, our results improve the understanding of the concentration, chemical composition, seasonal variation, and potential atmospheric impacts of OOMs, which can help formulate refined restriction policy specific to SOA control in urban areas.Peer reviewe

Vulto-van Silfhout-de Vries syndrome caused by de novo variants of DEAF1 gene: a case report and literature review

Vulto-van Silfhout-de Vries syndrome (VSVS; MIM 615828) is an extremely rare autosomal dominant disorder with unknown incidence. It is always caused by de novo heterozygous pathogenic variants in the DEAF1 gene, which encodes deformed epidermal autoregulatory factor-1 homology. VSVS is characterized by mild to severe intellectual disability (ID) and/or global developmental delay (GDD), seriously limited language expression, behavioral abnormalities, somnipathy, and reduced pain sensitivity. In this study, we present a Chinese boy with moderate GDD and ID, severe expressive language impairment, behavioral issues, autism spectrum disorder (ASD), sleeping dysfunction, high pain threshold, generalized seizures, imbalanced gait, and recurrent respiratory infections as clinical features. A de novo heterozygous pathogenic missense variant was found in the 5th exon of DEAF1 gene, NM_021008.4 c.782G&gt;C (p. Arg261Pro) variant by whole exome sequencing (WES). c.782G&gt;C had not been previously reported in genomic databases and literature. According to the ACMG criteria, this missense variant was considered to be “Likely Pathogenic”. We diagnosed the boy with VSVS both genetically and clinically. At a follow-up of 2.1 years, his seizures were well controlled after valproic acid therapy. In addition, the child’s recurrent respiratory infections improved at 3.5 years of age, which has not been reported in previous individuals. Maybe the recurrent respiratory infections like sleep problems reported in the literature are not permanent but may improve naturally over time. The literature review showed that there were 35 individuals with 28 different de novo pathogenic variants of DEAF1-related VSVS. These variants were mostly missense and the clinical manifestations were similar to our patient. Our study expands the genotypic and phenotypic profiles of de novo DEAF1