Interleukin-25 Mediated Induction of Angiogenin-4 Is Interleukin-13 Dependent

The intestinal surface is directly exposed to both commensal microorganisms as well as pathogens with a single layer of epithelium separating luminal microorganisms from internal tissues. Antimicrobial peptides play a crucial role in allowing epithelial cells to contain in the lumen beneficial and pathogenic microorganisms. The commensal dependent, epithelial produced, Th2 cytokine IL-25 can induce IL-13 and potentially the antimicrobial peptide angiogenin-4. Here we show that IL-13 downstream of IL-25 is required to induce angiogenin-4. IL-25 mediated induction of angiogenin-4 is furthermore not dependent on IL-22 or IL-17.     

An Efficacious Multi-Objective Fuzzy Linear Programming Approach for Optimal Power Flow Considering Distributed Generation

This paper proposes a new formulation for the multi-objective optimal power flow (MOOPF) problem for meshed power networks considering distributed generation. An efficacious multi-objective fuzzy linear programming optimization (MFLP) algorithm is proposed to solve the aforementioned problem with and without considering the distributed generation (DG) effect. A variant combination of objectives is considered for simultaneous optimization, including power loss, voltage stability, and shunt capacitors MVAR reserve. Fuzzy membership functions for these objectives are designed with extreme targets, whereas the inequality constraints are treated as hard constraints. The multi-objective fuzzy optimal power flow (OPF) formulation was converted into a crisp OPF in a successive linear programming (SLP) framework and solved using an efficient interior point method (IPM). To test the efficacy of the proposed approach, simulations are performed on the IEEE 30-busand IEEE 118-bus test systems. The MFLP optimization is solved for several optimization cases. The obtained results are compared with those presented in the literature. A unique solution with a high satisfaction for the assigned targets is gained. Results demonstrate the effectiveness of the proposed MFLP technique in terms of solution optimality and rapid convergence. Moreover, the results indicate that using the optimal DG location with the MFLP algorithm provides the solution with the highest quality.     

A Lightweight Radio Propagation Model for Vehicular Communication in Road Tunnels

Radio propagation models (RPMs) are generally employed in Vehicular Ad Hoc Networks (VANETs) to predict path loss in multiple operating environments (e.g. modern road infrastructure such as flyovers, underpasses and road tunnels). For example, different RPMs have been developed to predict propagation behaviour in road tunnels. However, most existing RPMs for road tunnels are computationally complex and are based on field measurements in frequency band not suitable for VANET deployment. Furthermore, in tunnel applications, consequences of moving radio obstacles, such as large buses and delivery trucks, are generally not considered in existing RPMs. This paper proposes a computationally inexpensive RPM with minimal set of parameters to predict path loss in an acceptable range for road tunnels. The proposed RPM utilizes geometric properties of the tunnel, such as height and width along with the distance between sender and receiver, to predict the path loss. The proposed RPM also considers the additional attenuation caused by the moving radio obstacles in road tunnels, while requiring a negligible overhead in terms of computational complexity. To demonstrate the utility of our proposed RPM, we conduct a comparative summary and evaluate its performance. Specifically, an extensive data gathering campaign is carried out in order to evaluate the proposed RPM. The field measurements use the 5 GHz frequency band, which is suitable for vehicular communication. The results demonstrate that a close match exists between the predicted values and measured values of path loss. In particular, an average accuracy of 94% is found with R² = 0.86.     

Employers’ perspective of workplace breastfeeding support in Karachi,Pakistan: a cross-sectional study

Background

Breastfeeding is considered to be an important measure to achieve optimum health outcomes for children, women’s return to work has frequently been found to be a main contributor to the early discontinuation of breastfeeding. The aim of the study is to assess workplace breastfeeding support provided to working mothers in Pakistan.

Method

A workplace based cross-sectional survey was conducted from April through December 2014. Employers from a representative sample of 297 workplaces were interviewed on pre-tested and structured questionnaire. The response rate was 93.7 %. Prevalence of workplace breastfeeding facilities were assessed in the light of World Alliance for Breastfeeding Action (WABA) guidelines.

Results

Among non-physical facilities, all workplaces offered 3 months paid maternity leave, 45 % of the sites were offering task adjustment to mothers during lactation period. Only 15 % of the sites were offering breastfeeding breaks to working mothers. Physical facilities that include a breastfeeding corner, refrigerator for storing breast milk, breast milk pump and nursery for childcare were provided in less than 7 % of the sites. Multinational organizations provided better support compared to national organizations.

Conclusion

Support for continuation of breastfeeding by working women at workplaces is inadequate; hence, women discontinue breastfeeding earlier than planned. Policies need to be developed and enforced, employers and employees need to be educated and supportive environment needs to be created to encourage and facilitate breastfeeding friendly worksite environment.

     

Molecular designing,virtual screening and docking study of novel curcumin analogue as mutation (S769L and K846R) selective inhibitor for EGFR

The somatic mutations in ATP binding cleft of the tyrosine kinase binding domain of EGFR are known to occur in 15–40% of non-small cell lung cancer (NSCLC) patients. Although first and second generation anti-EGFR inhibitors are widely used to treat these patients, their therapeutic efficacy is modest and often results in adverse effects or drug resistance. Therefore, there is a need to develop novel as well as safe anti-EGFR drugs. The rapid emergence of computational drug designing provided a great opportunity to both discover and predict the efficacy of novel EGFR inhibitors from plant sources. In the present study, we designed several chemical analogues of edible curcumin (CUCM) compound and assessed their drug likeliness, ADME and toxicity properties using a diverse range of advanced computational methods. We also have examined the structural plasticity and binding characteristics of EGFR wild-type and mutant forms (S769L and K846R) against ligand molecules like Gefitinib, native CUCM, and different CUCM analogues. Through multidimensional experimental approaches, we conclude that CUCM-36 ((1E,4Z,6E)-1-(3,4-Diphenoxyphenyl)-5-hydroxy-7-(4-hydroxy-3-phenoxyphenyl)-1,4,6-heptatrien-3-one) is the best anti-EGFR compound with high drug-likeness, ADME properties, and low toxicity properties. CUCM-36 compound has demonstrated better affinity towards both wild-type (ΔG is ?8.5?kcal/Mol) and mutant forms (V769L & K846R; ΔG for both is >?9.20?kcal/Mol) compared to natural CUCM and Gefitinib inhibitor. This study advises the future laboratory assays to develop CUCM-36 as a novel drug compound for treating EGFR positive non-small cell lung cancer patients.     

The genetic association study of TP53 polymorphisms in Saudi obese patients

Obesity is a multifactorial metabolic disorder characterized by low grade chronic inflammation. Rare and novel mutations in genes which are vital in several key pathways have been reported to alter the energy expenditure which regulates body weight. The TP53 or p53 gene plays a prominent role in regulating various metabolic activities such as glycolysis, lipolysis, and glycogen synthesis. Recent genome-wide association studies reported that tumor suppressor gene p53 variants play a critical role in the predisposition of type 2 diabetes and obesity. Till date, no reports are available from the Arabian population; hence the present study was intended to assess the association between p53 variants with risk of obesity development in the Saudi population. We have selected three p53 polymorphisms, rs1642785 (C > G), and rs9894946 (A > G), and rs1042522 (Pro72Arg; C > G) and assessed their association with obesity risk in the Saudi population. Phenotypic and biochemical parameters were also evaluated to check their association with p53 genotypes and obesity. Genotyping was carried out on 136 obese and 122 normal samples. We observed that there is significantly increased prevalence p52 Pro72Arg (rs1042522) polymorphism in obese persons when compared to controls at GG genotype in overall comparison (OR: 2.169, 95% CI: 1.086-4.334, p = 0.02716). Male obese subjects showed three-fold higher risk at GG genotype (OR: 3.275, 95% CI: 1.230-8.716, p = 0.01560) and two-fold risk at G allele (OR: 1.827, 95% CI: 1.128-2.958, p = 0.01388) of p53 variant Pro72Arg respectively. This variant has also shown significant influence on cholesterol, LDL level, and random insulin levels in obese subjects (p ≤ 0.05). In conclusion, p53 Pro72Arg variant is highly prevalent among obese individuals and may act as a genetic modifier for obesity development among Saudis.     

Pervasive gene conversion in chromosomal inversion heterozygotes

Chromosomal inversions shape recombination landscapes, and species differing by inversions may exhibit reduced gene flow in these regions of the genome. Though single crossovers within inversions are not usually recovered from inversion heterozygotes, the recombination barrier imposed by inversions is nuanced by noncrossover gene conversion. Here, we provide a genomewide empirical analysis of gene conversion rates both within species and in species hybrids. We estimate that gene conversion occurs at a rate of 1 × 10^–5 to 2.5 × 10^–5 converted sites per bp per generation in experimental crosses within Drosophila pseudoobscura and between D. pseudoobscura and its naturally hybridizing sister species D. persimilis. This analysis is the first direct empirical assessment of gene conversion rates within inversions of a species hybrid. Our data show that gene conversion rates in interspecies hybrids are at least as high as within‐species estimates of gene conversion rates, and gene conversion occurs regularly within and around inverted regions of species hybrids, even near inversion breakpoints. We also found that several gene conversion events appeared to be mitotic rather than meiotic in origin. Finally, we observed that gene conversion rates are higher in regions of lower local sequence divergence, yet our observed gene conversion rates in more divergent inverted regions were at least as high as in less divergent collinear regions. Given our observed high rates of gene conversion despite the sequence differentiation between species, especially in inverted regions, gene conversion has the potential to reduce the efficacy of inversions as barriers to recombination over evolutionary time.