Subtyping of Dengue Viruses using Return Time Distribution based Appproach

Dengue virus (DENV) is the causative agent of Dengue Hemorrhagic Fever and Dengue Shock Syndrome, and continues to represent a major public health hazard. DENVs are antigenically classified in four serotypes and each serotype is further divided into respective genotypes. The association between DENV subtypes and the kind & severity of disease caused by them is known. Experimental and computational approaches for subtyping are routinely used for the purpose of diagnosis and treatment of DENV, in addition to the study of phylodynamics. All virus-specific molecular subtyping tools make use of sequence alignments at backend. But as the volume of molecular data increases, alignment-dependent methods become computationally intensive. Hence, the need for alternative efficient approaches for subtyping of viruses becomes apparent. Recently, the concept of Return time distribution (RTD) was proposed and validated for alignment-free clustering and molecular phylogeny. The RTD-based approach is extended here for the subtyping of DENVs. 
Subtyping methodology involves compilation of curated genomic data of known subtypes, computing RTD of these sequences at different levels of k-mers, derivation a distance matrix and clustering. The subtype of the unknown is predicted based on its clustering with known subtypes.
Dataset consisting of 1359 DENV genomes with sequence identity (>92%) were clustered using the RTD based approach at k=5. Serotype specific clades, despite geographical and temporal variation in the dataset, were observed with 100% accuracy. The method was also found to be efficient in terms of time and implementation, apart from accuracy in the subtyping of DENV

Analysis of Next-generation Sequencing Data in Virology - Opportunities and Challenges

Viruses are the most abundant and the smallest organisms, which are relatively simple to sequence. Genome sequence data of viruses for individual species to populations outnumber that of other species. Although this offers an opportunity to study viral diversity at varying levels of taxonomic hierarchy, it also poses challenges for systematic and structured organization of data and its downstream processing. Extensive computational analyses using a number of algorithms and programs have opened exciting opportunities for virus discovery and diagnostics, apart from augmenting our understanding of the intriguing world of viruses. Unravelling evolutionary dynamics of viruses permits improved understanding of phenomena such as quasispecies diversity, role of mutations in host switching and drug resistance, which enables the tangible measurements of genotype and phenotype of viruses. Improved understanding of geno-/serotype diversity in correlation with antigenic diversity will facilitate rational design and development of efficacious vaccines against emerging and re-emerging viruses. Mathematical models developed using the genomic data could be used to predict the spread of viruses due to vector switching and the (re)emergence due to host switching and, thereby, contribute towards designing public health policies for disease management and control

Modelling and Characterization of Power Line Communication Channel

Massive advances in the ?eld of renewable energy sources have created a need for an infrastructure incorporating both renewable and non-renewable energy resources. Also the pressing need of increasing power demand seeks an infrastructure which can ful?ll the growing demands. Smart grid technology is emerging out to resolve such issues. Smart grid communicates with its entities to provide intelligence to the whole electricity delivery system. Thus the communication infrastructure is an essential part of such an emerging technology. Creation of an intelligent system for smart grid requires a reliable communication system. Power line communication is a communication backbone of smart grid system. It is viewed as an alternative for local area network and wireless communication at home premises. It enables communication between various domains of smart grid infrastructure. It serves as a communication media at customer premises and as a last mile communication. Recent advances in power line communication technology has created a large demand for access to network services inside premises. Power line communication has emerged as a strong candidate under such circumstances. Quality of service in power line communication relies heavily on characterization of the medium. This paper analyses the channel characteristics of power line. A transmission line model for high-frequency Power line channel is used to study the transfer characteristics of multibranch power line. In the present thesis, power line communication channel modelling is mainly focused. The channel modelling being essential part of any communication system is analysed thoroughly and observations are drawn from the simulation results obtained. All the simulations are performed in MATLAB simulation environment

Probiotics for woman’s health focus on urogenital infections and reproductive outcomes

Depletion in vaginal Lactobacilli colonization is associated with poor urogenital health and adverse pregnancy outcomes. Probiotic supplements containing lactobacilli, when administered in adequate amounts, increased vaginal and gut colonization of Lactobacilli, reduced the incidence of bacterial vaginosis and other urogenital infections. Probiotic Lactobacilli reduced preterm births and improved fertility rates in women following in vitro fertilization. Probiotics may also improve implantation rate and live-birth rate in women undergoing IVF. The purpose of this review was to critically analyse the available literature for synthesizing evidence on the use of probiotics and its effect on urogenital and reproductive health in women

Clinical pharmacokinetics and pharmacodynamics of vildagliptin 50 mg sustained release tablet formulation in healthy Indian males after single and multiple-dose

Background: Vildagliptin 50 mg once-daily is a clinically established anti-diabetic therapy in combination with a sulphonylurea and renally impaired patients. We developed sustained release (SR) vildagliptin 50 mg tablet formulation for prolongation of dipeptidyl peptidase-4 (DPP-4) inhibition coverage. The present study compares the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of investigational vildagliptin SR 50 mg tablet with Galvus® in healthy Indian adult males after single and multiple-dose administration.Methods: Each randomized, open-label, two-period, cross-over study enrolled 36 healthy Indian adult male subjects for the assessment of single and multiple-dose PK/PD profiles of SR 50 mg vildagliptin under fed condition. The plasma drug concentrations were quantified using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. PK parameters (Cmax (ng/ml), AUC0-18, AUC0-36, and AUC0-τ (ng.hr/ml), Tmax (hour), t1/2 (hour), Tmaxss (hour), Cτss (ng.hr/ml) were calculated using Phoenix® WinNonlin® software. The DPP-4 inhibition was determined in a fluorescence-based assay.Results: Vildagliptin SR tablet showed prolonged PK/PD characters compared to Galvus®. All PK parameters expressed as Mean±SD. The single-dose PK measures were Cmax (58.22±11.31), AUC0-18 (556.92±135.84), AUC0-36 (608.82±159.84), Tmax (6.48±3.78). In the multiple-dose study, PK findings were Cmax (73.20±17.71), AUC0-τ (714.36±303.21), Cτss (4.15±6.51), Tmaxss (5.60±3.12). Vildagliptin SR 50 mg achieved prolonged DPP-4 inhibition (≥80%) for18-20 hours after single and multiple-dose administration as compared to Galvus® (12-13 hours).Conclusions: Investigational vildagliptin SR tablet was found safe, well-tolerated after single and multiple-dose administration. Its extended DPP-4 inhibition profile compared to Galvus® may benefit the patient population on combination therapy with a sulphonylurea and renally impaired patients

Viscum album Exerts Anti-Inflammatory Effect by Selectively Inhibiting Cytokine-Induced Expression of Cyclooxygenase-2

Viscum album (VA) preparations are extensively used as complementary therapy in cancer and are shown to exert anti-tumor activities which involve the cytotoxic properties, induction of apoptosis, inhibition of angiogenesis and several other immunomodulatory mechanisms. In addition to their application in cancer therapy, VA preparations have also been successfully utilized in the treatment of several inflammatory pathologies. Owing to the intricate association of inflammation and cancer and in view of the fact that several anti-tumor phytotherapeutics also exert a potent anti-inflammatory effect, we hypothesized that VA exerts an anti-inflammatory effect that is responsible for its therapeutic benefit. Since, inflammatory cytokine-induced cyclo-oxygenase-2 (COX-2) and prostaglandin E2 (PGE2) play a critical role in the pathogenesis of inflammatory diseases, we investigated the anti-inflammatory effect of VA on regulation of cyclo-oxygenase expression and PGE2 biosynthesis by using human lung adenocarcinoma cells (A549 cells) as a model. A549 cells were stimulated with IL-1β and treated with VA preparation (VA Qu Spez) for 18 hours. PGE2 was analysed in the culture supernatants by enzyme immunoassay. Expression of COX-2 and COX-1 proteins was analyzed by immunoblotting and the expression of COX-2 mRNA was assessed by semi-quantitative RT-PCR. We found that VA Qu Spez inhibit the secretion of IL-1β-induced PGE2 in a dose-dependent manner. Further, we also show that this inhibitory action was associated with a reduced expression of COX-2 without modulating the COX-1 expression. Together these results demonstrate a novel anti-inflammatory mechanism of action of VA preparations wherein VA exerts an anti-inflammatory effect by inhibiting cytokine-induced PGE2 via selective inhibition of COX-2

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Municipal waste management systems for domestic use

© 2017 The Authors. Every year, the average citizen of a developed country produces about half a tonne of waste, thus waste management is an essential industry. Old waste management systems based on the collection of mixed/ sorted waste and transporting it a long way to disposal sites has a significant negative impact on the environment and humans. This paper will review the available waste management systems for house- holds. Biological methods (such as composting or anaerobic digestion) and physicochemical methods (such as burning or pyrolysis) of waste utilization will be considered from the householder’s point of view. The most important features of each system will be discussed and compared. Municipal waste management systems for domestic use could eliminate or significantly reduce the stage of waste collection and transportation. Additionally, they should not require special infrastructure and at the same time should allow garbage to be changed into safe products or energy sources with no harmful emissions. The aim of the work is to identify the best available waste disposal systems for domestic use.This reported work was conducted as part of the“Design Optimisation of the HERU Waste Treatment System”project that wasfunded by Manik Ventures Limited Project ID: 10300