Swati Singh

Communication networks are all about providing means to communicate that is for (exchanging the user information). The user information can be viewed as user traffic akin to the traffic on the road that moves across the road network. The fastest growth of data communication Networks over the past decades has resulted in the development of sophisticated tools to diagnose, debug

There is an urgent need for a more effective vaccine against Mycobacterium tuberculosis (Mtb). Although CD4+ T cells play a central role in host immunity to Mtb, recent evidence suggests a critical role of CD8+ T cells in combating Mtb. In the present study, we have predicted HLA antigen class I binding peptides of DosR operon using an in-silico approach. This method is useful as an initial computational filtration of probable epitopes based on their binding ability and antigenicity. CD8+ epitopes were predicted by software NetMHC 3.4 and BIMAS. Self-peptides were found and excluded by indigenously developed Perl script. Antigenicity of promiscuous peptides was predicted using a VaxiJen server. The top VaxiJen scoring antigenic peptides were docked to globally relevant HLA allele using CABS dock and Hex program. A total of 1436 overlapping nonamer peptides were generated which gave 46 promiscuous epitopes, 25 were predicted to be antigenic. Rv2627 epitope "SAFRPPLV" which gave the highest Vaxijen score of 1.9157 and showed binding to all the three HLA loci. The top VaxiJen scoring antigenic peptides were docked and had significant interactions with residues of the HLA class I molecule indicating them to be good cytotoxic T lymphocyte epitopes. Our study has generated several promiscuous antigenic peptides capable of binding to major histocompatibility complex class I with high affinity. These epitopes can become part of a postexposure multivalent subunit vaccine upon experimental validation.

Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, is an intracellular bacterium capable of surviving and persisting within host mononuclear cells. The host response against tubercle bacilli is dominated by fine-tuned interaction of innate and adaptive immune responses. Toll-like receptors (TLRs) play a critical role in the formation of this immune response by facilitating in elaboration of protective T helper type 1 (Th1) cytokines and microbicidal molecules, but the intracellular persistence of M. tuberculosis in the phagosome and processing and presentation of TLR ligands by host antigen-presenting cell leads to continuous and chronic TLR2 signaling. The prolonged stimulation of TLR ultimately results in elaboration of immunosuppressive cytokines and downregulation of antigen presentation by major histocompatibility complex (MHC) class II and therefore becomes beneficial for M. tuberculosis, resulting in its continued survival inside macrophages. A...

ABSTRACT Aims and objectives Characterization of proteins associated with the mycobacterial cell wall is critical to understanding bacterial survival and immune modulation in the host. A variety of mycobacterial products are able to recognize and activate mammalian toll-like receptors (TLRs) mediating the secretion of antibacterial effector molecules. Mycobacterium tuberculosis MymA Rv3083 protein is a cell wall-associated protein which is up-regulated upon infection of macrophages. The objective of the present study is to understand the role of Rv3083 protein as a TLR agonist and its contribution in activating macrophages. Methods The MymA (Rv3083) gene was cloned and expressed. The purified 55.5 kDa recombinant protein was used to stimulate phorbol myristate acetate (PMA) differentiated THP-1 macrophage cell line. Cell surface markers of Rv3083 stimulated THP-1 cells were done using flow cytometry for TLR2, TLR4, HLA-DR and co-stimulatory molecules CD40, CD64 and CD80. Cytokines TNF-α, IL-10 and IL-12 were assayed in the culture supernatant using ELISA. Results Stimulation of THP-1 macrophages for 48 and 72 h with rRv3083 protein resulted in significantly increased expression of TLR2. A significant up-regulation was also seen in the expression of co-stimulatory molecules CD40, CD80 and antigen-presenting molecule HLA-DR on THP-1 cells. These macrophages also produced a significant quantity of proinflammatory TH1 cytokines TNF-α and IL-12, but not IL-10 at 48 and 72 h post-stimulation. Conclusion The cell wall-associated M. tuberculosis rRv3083 protein acts as an agonist of TLR2 and thereby activates macrophages to produce a TH1 immune response. Acknowledgements The financial support of OSDD-CSIR and the research fellowships of ICMR to I. Saraav and S. Singh is duly acknowledged.

Tuberculosis remains a great health threat to the world among infectious diseases particularly with the advent of human immunodeficiency virus and emergence of drug resistant strains. In the light of the inconsistent efficacy imparted by the only currently available pre-exposure vaccine bacillus Calmette-Guerin BCG, the development of an improved TB vaccine is a very high international research priority. Vaccine candidates currently in clinical trials are also pre-exposure vaccines that aim to prevent active tuberculosis during an individual's lifetime. According to World Health Organization approximately a third of the world's population is latently infected with Mycobacterium tuberculosis. Dormancy or latency of Mycobacteria is associated with the formation of granuloma with poorly perfused interior leading to expression of genes which help them survive in this hostile environment. A group of about 50 genes belonging to the DosR regulon also known as latency antigens are expressed by Mycobacteria when they are persisting in the immuno-competent host. An understanding of the immunological effects produced by products of these latency induced genes may help in making a more potent vaccine. Incorporation of latency antigens into improved (live or subunit) vaccines may enhance the impact of these vaccines in which BCG priming can be followed by multisubunit protein boosting. These vaccines could act as post exposure vaccines for containment and prevention of latent TB activation. This heterologous boosting of BCG-primed immunity will be able to stimulate the known immune correlates of protective immunity against M. tuberculosis i.e. TH1 cells (CD4(+) and CD8(+) T cells) mediated immune responses with cytokines such as IFN-γ and TNF-α⋅ In our review we have analysed and compared the immunogenic potential of various latency-associated antigens of the DosR regulon in line with the current strategy of developing a recombinant post exposure booster vaccine.

Voice in the city is culturally and historically specific text that balances this victimization with different modes of protest and participates in creating a new feminist ideology in Indian literatures in English. Appropriating the alternatives myth of Indian femininity as embodied in Goddess kali. The city is the novel is an extension of these images in its abrogating of orthodox male authority and in its potency of a frightening female sexuality.

ABSTRACT: Parvati techno cast (Guj) pvt. ltd. (688, GIDC estate Makarpura, Vadodara, 390010) is the company which manufacture different mechanical components (100gm to 200kg weight) by using casting. Also manufacturing engineering services include machining of components which are produced by casting. At present situation company is having less productivity due to ineffective utilization of plant layout, less space for storage, material handling problems etc. Owner of the company wants to implement new semi-automatic machining shop. So our objective is to improve productivity in the best and effective manner without compromising quality of products. In this paper, to accomplish our objective by effectively utilization of plant area, changing in plant layout, process layout, applying work and motion study, reducing non-productive time and applying ergonomics for various working position. . KEYWORDS: Plant layout, Productivity, Work study, Material handling, Ergonomic.

Abstract: Nowadays, manufacturing industries throughout the world are interested in lean manufacturing philosophy. This project is based on lean manufacturing tools like 5S, Kaizen and Visualization. 5S is tool to ensuring systematic organizational environment, Kaizen is continuous improvement through small steps to obtain economical result of the organization and Visualization is technique of creating images, diagrams or animations of firm’s activity which are helpful and effective way of communication for all people connected with firm. This project is intended to utilize these tools and come up with integrated approach. Also to reduce abnormality in organization by applying ergonomics for various working positions of employees which improve the productivity, by applying it at pipe manufacturing industry “Sandvik Asia Pvt. Ltd, Mehsana, Gujarat”. Owner of firm is also interested to implement this concept; hence as an industrial perspective this project will give us knowledge that ...

Abstract: Small – scale industries are the foundational pillars of Indian economy. Here we are doing a case study on Chartered rubber product to improve its productivity. They are following various orthodox customs, improper utilization of available space & inaccurate arrangement of machineries with respect to one another. Hence they are taking a lot of time for undertaking various tasks, and also more human effort is required. Thus with the help of SLP technique & with the help of various quality control tools, the non-value adding activities are eliminated. Thus the Productivity has been increased with reduced human efforts & employees work satisfaction. Keywords: Systematic Layout Planning, Plant Layout, Productivity Improvement

Abstract- This paper attempts to find out the life cycle cost of a centrifugal pump in order to increase its monetary efficiency. So in this concerned study mean time between failures (MTBF) and mean time to repair (MTTR) are the major factors stressed upon. Here basically emphasis is on calculating all the costs and not only on the acquisition costs. Life cycle cost analysis is a probability based analysis not depending on perfect costs. Keywords- Life Cycle Cost, Monetary Efficiency, Analysis, Failure

D-aminoacyl-tRNA deacylase (DTD) removes D-amino acids mischarged on tRNAs and is thus implicated in enforcing homochirality in proteins. Previously, we proposed that selective capture of D-aminoacyl-tRNA by DTD's invariant, cross-subunit Gly-cisPro motif forms the mechanistic basis for its enantioselectivity. We now show, using nuclear magnetic resonance (NMR) spectroscopy-based binding studies followed by biochemical assays with both bacterial and eukaryotic systems, that DTD effectively misedits Gly-tRNAGly. High-resolution crystal structure reveals that the architecture of DTD's chiral proofreading site is completely porous to achiral glycine. Hence, L-chiral rejection is the only design principle on which DTD functions, unlike other chiral-specific enzymes such as D-amino acid oxidases, which are specific for D-enantiomers. Competition assays with elongation factor thermo unstable (EF-Tu) and DTD demonstrate that EF-Tu precludes Gly-tRNAGly misediting at normal cellular concentrations. However, even slightly higher DTD levels overcome this protection conferred by EF-Tu, thus resulting in significant depletion of Gly-tRNAGly. Our in vitro observations are substantiated by cell-based studies in Escherichia coli that show that overexpression of DTD causes cellular toxicity, which is largely rescued upon glycine supplementation. Furthermore, we provide direct evidence that DTD is an RNA-based catalyst, since it uses only the terminal 2'-OH of tRNA for catalysis without the involvement of protein side chains. The study therefore provides a unique paradigm of enzyme action for substrate selection/specificity by DTD, and thus explains the underlying cause of DTD's activity on Gly-tRNAGly. It also gives a molecular and functional basis for the necessity and the observed tight regulation of DTD levels, thereby preventing cellular toxicity due to misediting.

To evaluate the effect of oral supplementation with omega-3 (ω-3) fatty acids (FAs) in improving contrast sensitivity (CS) of patients with moderate meibomian gland dysfunction (MGD). In this prospective study, 60 patients with moderate MGD were allocated alternately to treatment and control groups. Both groups received warm compresses, lid massage, and artificial tear substitutes. The treatment group also received oral supplements of 1.2 g ω-3 FAs per day. All parameters were recorded at baseline and at 12 weeks and included Ocular Surface Disease Index scores, CS testing at 3, 6, 12, and 18 cycles per degree (cpd), tear break-up time, Schirmer test I without anesthesia, corneal and conjunctival staining scores, and meibum quality and expressibility. At the end of 12 weeks, significant improvement in CS was seen in the treatment group in 7 of the 8 testing conditions (3, 6, 12, and 18 cpd photopic and 6, 12, and 18 cpd mesopic), whereas in the placebo group, significant improvement...

ABSTRACT In the present study, satellite based mapping and morphogenetic analysis of eastern part of Tripura has been attempted. Landforms are delineated based on conjugate analysis of satellite imaged and satellite derived digital elevation data. Further, landforms were classified based on hierarchical three-tier classification system where genesis is used as criteria to classify the landforms in the first level followed by nature of their dissection and the geometric forms of the landform in second and third level respectively. During the analysis, it has been observed that most of the landforms are structural in origin and their orientations are guided by the geological lineaments although the variations in the dissection pattern of the landforms are related to the changes in the underlying lithology. The implementation of quantitative analysis using hypsometric integral and ruggedness index of geomorphic parameters indicates that the landforms are immature but have been evolving towards maturity.

α-Amylases hydrolyze α- 1,4-glycosidic bonds during assimilation of biological macromolecules. The amino acid sequences of these enzymes in thousands of diverse organisms are known and the 3D structures of several proteins have been solved. The 3D structure analysis of these universal enzymes from diverse organisms has been studied by the generation of phylogenetic trees and structure based sequence analysis to generate a metric for the degree of conservation that is responsible for individual speciation. Greater similarities are observed between reference NCBI tree and structure based phylogenetic tree compared to sequence based phylogenetic tree indicating that structures truly represent the functional aspects of proteins than from the sequence information alone. We report differences in the profile specific conserved and insertion/deletion regions, factors responsible for the Ca(2+) and Cl(-) ion binding and the disulfide connectivity pattern that discriminate the enzymes over evolution.

The 5' amino-labeled DNA probe complementary to mga gene of Streptococcus pyogenes was immobilized on carboxylated multiwall carbon…

ABSTRACT Climacteric fruit ripening has been characterized by oxidative burst and involve active oxidative metabolism with generation of reactive oxygen species (ROS). In the present paper, the papaya fruit ripening was found to be associated with increase in polygalacturonase (PG), pectate lyase (PEL), catalase (CAT), ascorbate peroxidase (APX), H2O2 and lipid peroxidation concomitant with decrease in the activities of superoxide dismutase (SOD) and guaiacol peroxidase (GPX). Furthermore, a cDNA (903 bp) of GPX from unripe papaya fruit pulp was isolated and cloned. On BLAST analysis, the deduced protein exhibited homology with various peroxidases and specific hits for plant heme peroxidase family namely heme and calcium binding domains. GPX of papaya was modeled and docked with various substrates and inhibitors among which guaiacol and cysteine were found to be the best substrate and inhibitor, respectively.

Lipoxygenases (LOXs), key enzymes involved in the biosynthesis of leukotrienes, are well known to participate in the inflammatory and immune responses. With the recent reports of involvement of 5-LOX (one of the isozymes of LOX in human) in cancer, there is a need to find out selective inhibitors of 5-LOX for their therapeutic application. In the present study, plant-derived 300 anti-inflammatory and anti-cancerous secondary metabolites (100 each of alkaloids, flavonoids and terpenoids) have been screened for their pharmacokinetic properties and subsequently docked for identification of potent inhibitors of 5-LOX. Pharmacokinetic analyses revealed that only 18 alkaloids, 26 flavonoids, and 9 terpenoids were found to fulfill all the absorption, distribution, metabolism, excretion, and toxicity descriptors as well as those of Lipinski's Rule of Five. Docking analyses of pharmacokinetically screened metabolites and their comparison with a known inhibitor (drug), namely zileuton rev...

Schistosomiasis is a common, neglected parasitic disease caused by Schistosoma mansoni. Availability of two specific drug oxamniquine and praziquintel for treatment of the disease is a major concern. Recently NAD+ dependent lysine deacetylases have been identified as new drug targets in pathogens. Sirtuins are NAD+ dependent lysine deacetylases that are involved in a wide variety of vital cellular processes. Amongst them, members of sirtuin's class1 proteins are considered to be main target of the drugs. Sirtinol and Salermide are two known inhibitors of Schistosoma mansoni Class1sirtuin which is a protein with unknown 3-D structure. Here, we investigate molecular insights of interaction between modeled sirtuin1 structure and it's inhibitors, that were derivatives of Sirtinol and Salermide, to prioritize them for their binding affinities with target. A detailed examination of absorption, distribution, metabolism and toxicity of these inhibitors has also been included in the study. Finally we found two derivatives of Sirtinol to be most appropriate drug candidates for Schistosomiasis.

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder characterized by amyloid beta (Aβ) deposition in brain with subsequent formation of neuritic plaques leading to dementia. A number of therapeutic strategies targeted against Aβ depositions have been rigorously explored which provided successful results corresponding to the existing symptomatic treatments. However, at the same time, several failures corresponding to the disease altering therapies and drugs have also been observed due to potential drawbacks in understanding of the pathogenesis of the disease, development of drug candidates and subsequent designing of clinical trials. Preclinical research, along with experimental and clinical studies, is continuously providing novel information which may reveal multi-target directed ligands and combination therapies for targeting Aβ. Thus, in view of the estimated increase in the number of AD patients globally, the present review attempts to summarize the available evidence dealing with various therapeutic approaches targeting Aβ, focusing specifically on pharmaceutical compounds under various stages of clinical trials. Furthermore, in view of a number of computational advances having significant impact in the field of computer aided drug design, we have also presented results of analysis of natural compounds as potential therapeutic molecules in preventing Aβ plaque formation using in silico approaches.

ABSTRACT Laser-cooled nanomechanical oscillators are promising new tools to manipulate and control ultracold atomic and molecular samples. As an illustration, we show how they can be exploited to entangle and squeeze a lattice of dipolar molecules.

Aromatase, catalyzing final step of estrogen biosynthesis, is considered a key target for the development of drug against estrogen-dependent breast cancer (EDBC). Identification and development of naturally occurring compounds, such as flavonoids, as drugs against EDBC is in demand due to their lesser toxicity when compared to those of synthetic ones. Thus, a three-dimensional quantitative structure-activity relationship, using comparative molecular field analysis (CoMFA) was done on a series of 45 flavonoids against human aromatase. A significant cross-validated correlation coefficient (q(2)) of 0.827 was obtained. The best predictive CoMFA model explaining the biological activity of the training and test sets with correlation coefficient values (r(2)) of 0.916 and 0.710, respectively, when used for virtual screening of a flavanoids database following molecular docking revealed a flavanone namely, 7-hydroxyflavanone beta-D-glucopyranoside showing highest predicted activity of 1.09 μM. In comparison to a well-established inhibitor of aromatase, namely 7-hydroxyflavanone (IC50: 3.8 μM), the derivative identified in the present study, namely 7-hydroxyflavanone beta-D-glucopyranoside exhibited about 3.5 folds higher inhibitory activity against aromatase. The result of virtual screening was further validated using molecular dynamics (MD) simulation analysis. Thus, a 25 ns MD simulation analysis revealed high stability and effective binding of 7-hydroxyflavanone beta-D-glucopyranoside within the active site of aromatase. To the best of our knowledge, this is the first report of CoMFA-based QSAR model for virtual screening of flavonoids as inhibitors of aromatase.

We propose a scheme to measure the quantum state of a nanomechanical oscillator cooled near its ground state of vibrational motion. This is an extension of the nonlinear atomic homodyning technique scheme first developed to measure the intracavity field in a micromaser. It involves the use of a detector-atom that is simultaneously coupled to the cantilever via a magnetic interaction and to (classical) optical fields via a Raman transition. We show that the probability for the atom to be found in the excited state is a direct measure of the Wigner characteristic function of the nanomechanical oscillator. We also investigate the backaction effect of this destructive measurement on the state of the cantilever.

Y-box-binding protein 1 (YB-1), a cold shock domain protein, is one of the most conserved nucleic acid-binding proteins. The multifunctional Human YB-1 is a member of a large family of proteins with an evolutionary ancient cold shock domain. The presence of a cold shock domain is a specific feature of Y-box binding proteins and allows attributing them to a wider group of proteins containing a cold shock domain. This protein is involved in a number of cellular processes including proliferation, differentiation, and stress response. The YB-1 performs its function both in the cytoplasm and in the cell nucleus. In this study we present the structure of full length Human YB-1 Protein along with investigation of their nucleic acid binding preferential. The study also focuses on biases for particular purine and pyrimidine bases. The overall goal of this study was to model and validate full length YB-1 protein and to compare it's nucleic acid binding studies with previous reports.

Alzheimer's disease (AD), a progressive neurodegenerative disorder with many cognitive and neuropsychiatric symptoms is biochemically characterized by a significant decrease in the brain neurotransmitter acetylcholine (ACh). Plant-derived metabolites, including alkaloids have been reported to possess neuroprotective properties and are considered to be safe, thus have potential for developing effective therapeutic molecules for neurological disorders, such as AD. Therefore, in the present study, thirteen plant-derived alkaloids, namely pleiocarpine, kopsinine, pleiocarpamine (from Pleiocarpa mutica, family: Annonaceae), oliveroline, noroliveroline, liridonine, isooncodine, polyfothine, darienine (from Polyalthia longifolia, family: Apocynaceae) and eburnamine, eburnamonine, eburnamenine and geissoschizol (from Hunteria zeylanica, family: Apocynaceae) were analyzed for their anti-cholinergic action through docking with acetylcholinesterase (AChE) as target. Among the alkaloids, pleiocarpine showed promising anti-cholinergic potential, while its amino derivative showed about six-fold higher anti-cholinergic potential than pleiocarpine. Pleiocarpine and its amino derivative were found to be better inhibitors of AChE, as compared to commonly used drugs tacrine (brand name: Cognex) and rivastigmine (brand name: Exelon), suggesting development of these molecules as potential therapeutics in future.

Genetic mutations or engineered nucleases that disrupt the HIV co-receptor CCR5 block HIV infection of CD4(+) T cells. These findings have motivated the engineering of CCR5-specific nucleases for application as HIV therapies. The efficacy of this approach relies on efficient biallelic disruption of CCR5, and the ability to efficiently target sequences that confer HIV resistance to the CCR5 locus has the potential to further improve clinical outcomes. We used RNA-based nuclease expression paired with adeno-associated virus (AAV)-mediated delivery of a CCR5-targeting donor template to achieve highly efficient targeted recombination in primary human T cells. This method consistently achieved 8 to 60% rates of homology-directed recombination into the CCR5 locus in T cells, with over 80% of cells modified with an MND-GFP expression cassette exhibiting biallelic modification. MND-GFP-modified T cells maintained a diverse repertoire and engrafted in immune-deficient mice as efficiently as ...

Activated leukocyte cell adhesion molecule ALCAM or CD166 is a type I membrane protein that belongs to the Ig superfamily, and it has five extracellular variable type and constant type Ig domains and a single transmembrane domain. Activated leukocyte cell adhesion molecule is expressed in various tissues, cancers, and cancer-initiating cells. Alterations in expression of ALCAM have been reported in several human tumors, and cell adhesion functions have been proposed to explain its association with cancer. The present study has been done on wide range of ALCAM protein sequences and their homologs from various organisms. In order to decipher the phylogenetic blueprints the proteins from higher organisms to the lower hierarchical order of organisms were selected as the kernel of the investigation. The tree was drawn by Maximum parsimony method while using the bootstrapping as a test of inferred phylogeny. The phylogenetic trees were constructed from multiple aligned sequences showing b...