212 research outputs found
Chemical hybridization approaches applied to natural and synthetic compounds for the discovery of drugs active against neglected tropical diseases
No full textThe Application of Fragment-based Approaches to the Discovery of Drugs for Neglected Tropical Diseases
No full textThe term neglected tropical disease (NTD) is used to describe a diverse collection of communicable diseases prevalent in tropical and subtropical regions, which predominantly affect the poor. This chapter describes how fragment-based approaches are being applied in projects aimed at the discovery of new drugs for NTDs, either alone or in conjunction with high-throughput screening. It presents examples, classified according to pathogen, to highlight the power of fragment-based approaches to reveal binding hot-spots and novel allosteric binding sites, and to identify efficient starting points for drug discovery. The chapter also shows how fragment-based approaches can facilitate optimization of hits identified by other means and enable careful control of drug-like properties during the optimization of a chemical series. Fragment-based approaches, although target-based, have the key advantages that libraries are smaller and more efficiently explore chemical space, and more careful control of physicochemical properties is possible during optimization
Chemical scaffolds with structural similarities to siderophores of nonribosomal peptide–polyketide origin as novel antimicrobials against Mycobacterium tuberculosis and Yersinia pestis
No full textMycobacterium tuberculosis (Mtb) and Yersinia pestis (Yp) produce siderophores with scaffolds of nonribosomal peptide–polyketide origin. Compounds with structural similarities to these siderophores were synthesized and evaluated as antimicrobials against Mtb and Yp under iron-limiting conditions mimicking the iron scarcity these pathogens encounter in the host and under standard iron-rich conditions. Several new antimicrobials were identified, including some with increased potency in the iron-limiting condition. Our study illustrates the possibility of screening compound libraries in both iron-rich and iron-limiting conditions to identify antimicrobials that may selectively target iron scarcity-adapted bacteria and highlights the usefulness of building combinatorial libraries of compounds having scaffolds with structural similarities to siderophores to feed into antimicrobial screening programs.Fil: Ferreras, Julian Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina. Cornell University; Estados Unidos. Universidad Nacional de Misiones. Facultad de Ciencias Exactas Químicas y Naturales. Departamento de Genética; ArgentinaFil: Gupta, Akash. City University of New York; Estados Unidos. University of Yale; Estados UnidosFil: Amin, Neal D.. Cornell University; Estados Unidos. University of California at San Diego; Estados UnidosFil: Basu, Arijit. Birla Institute of Technology; IndiaFil: Sinha, Barij N.. Birla Institute of Technology; IndiaFil: Worgall, Stefan. Cornell University; Estados UnidosFil: Jayaprakash, Venkatesan. Birla Institute of Technology; IndiaFil: Quadri, Luis E. N.. City University of New York; Estados Unido
Discovery of a dual PPARα/γ partial agonist displaying antisteatotic and antidiabetic properties: in silico studies and X-ray structure determination
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Paradigm Shifts and New Worldviews: Kuhn, Laudan and Discovery in Molecular Biology
No full text[Editors\u27 Introduction]
The author poses an alternate set of ideas concerning paradigms, normal science, research traditions and scientific revolution on the basis of the unique and inherently distinctive development of molecular biology and genetics; for, a new set of conceptual tools concerning scientific progress are required for an adequate understanding of how biological processes were elucidated under the scientific auspices of the central dogma of the genetic code. This essay concentrates on a limited study of three aspects in genetics: the study of chromosome structure, dynamics and function, reverse transcriptases, and the discovery of RNA catalysts. In attempting to analyze the key moments of discovery in these processes, Venkatesan distinguishes between Kuhnian and Laudanian notions of science and how molecular biology configures into them and attempt to put forth a set of ideas that may not necessarily conflate the two but provide further insight into their treatises on the nature of scientific revolution of which they discuss at length
Distributed optimization on a wireless sensor network testbed
No full textThe focus of this thesis is to implement various distributed optimization algorithms on a physical wireless sensor network. Distributed optimization refers to optimization of some global function which is not completely known to any single node in a communication network. The global function is some combination of local functions that are available at each node. Therefore the objective is for all nodes to achieve consensus on the global optimum given only local information and communication with neighbors.
Algorithms from the literature that address this problem in different set- tings are introduced, focusing on an incremental subgradient-based algorithm and a broadcast, gossip-based algorithm. These algorithms are applied to lo- calize a light source. This localization problem is formulated as a distributed optimization problem in which the global optimum is the true location of the source, and the local information is comprised of light intensity measurements at each node. Simulation results and results from physical implementations on the testbed are presented for the two different approaches. A modified version of the broadcast algorithm is also presented, and is shown to be supe- rior to the unaltered algorithm in certain settings via simulation and testbed results.Submission published under a 24 month embargo labeled 'U of I only', the embargo will last until 2017-05-01The student, Neeraj Venkatesan, accepted the attached license on 2015-04-23 at 19:16.The student, Neeraj Venkatesan, submitted this Thesis for approval on 2015-04-23 at 19:21.This Thesis was approved for publication on 2015-04-24 at 09:05.DSpace SAF Submission Ingestion Package generated from Vireo submission #8071 on 2015-07-22 at 14:18:45Made available in DSpace on 2015-07-22T22:33:52Z (GMT). No. of bitstreams: 2
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Previous issue date: 2015-04-24Embargo set by: Seth Robbins for item 79905
Lift date: 2017-07-22T22:34:16Z
Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemU of I Only Restriction Lifted for Item 79905 on 2017-07-23T09:15:17Z
Mr. T. M Venkatesan
No full textPresently working as a mentor for 5S, TPM, lean Energy Conservation and six sigma training, Implementation and projects for mfg and service industry. He teaches change Business Management through 5S, LEAN, TPM,Energy Conservation and Six Sigma. He works extensively with several clients. Some of them are Premier Explosives Ltd- Hyderabad, RAK Ceramics Ltd- Samalkot, JNTU- Hyderabad, Rani pettai Engg Collg- Vellore (TamilNadu), BHEL- Hyderabad, Aurobindo Pharma Hyd Ltd, Dr.Reddy Laboratory Ltd – Hyd ,Sonali Castings (P) Ltd –Hyd, Fine Alloy Castings Ltd, Kamal Foot wear – Vijayawada, CII – Hyderabad, Vijayawada, Vizag & Kakinada, Hi-Tech institute of Pharma sciences – Hyd, GMR Airport – Shamshabad, APITCO – Hyd, Roots Industries India Ltd – TamilNadu, Sweet Magic – Vijayawada, Garapati/ Ramcor – Vijayawada, Vilan Garments (P) Ltd – Vijayawada, Ramcor Marketing (P) Ltd. etc.
Mr. T.M.Venkatesan enjoys balancing out a very busy professional life with strong community links through involvement in not-for-profit organizations that can use his skills and enthusiasm. His interests include literature, movies, music, theatre, intricacies of business/financial world. Certified Energy Auditor- Bureau of Energy Efficiency, under Ministry of Power, Govt.of India. Chartered Engineer in Mechanical Engineering. Total Manufacturing Industry experience in Auto Parts 48yrs. From TVS for 12years (A Deming Award Company )and Own Industry for 22yrs.(auto parts to multinationals) Trained in TOC by Dr Goldratt the author of the book The Goal Best Entrepreneur Award from HMA.(Hyderabad Management Association) Best Entrepreneur Award from Govt. of Andhra Pradesh. Exporter from 1991 to Singapore, Indonesia and Srilanka. Visited U.S., Germany, Italy, France, Singapore, Malaysia, Thailand, Indonesia and Srilanka (9 countries). Represented Govt. of Andhra Pradesh in LASVEGAS (U.S) and Govt. of India in Jakarta (Indonesia). Past President of Rotary club Hyderabad - Mega City. BLACK BELT IN SIX SIGMA and Practicing MASTER BLACK BELT and Trained in Lean Sigma by BMG(Longmont. Co., USA)..Trained more than 3000 participants in Manufacturing &Service Industries.
T. M. Venkatesan is currently doing his PhD (Kaizen) (Operations Management-Quality) at VIT Business School, VIT University, and Vellore India. Prior to this he did his M.S (Research) studies at the same Business School and upon obtaining Distinction in M.S he got upgraded to PhD Program. Earlier he was graduated as Mechanical Engineer from Institution of Engineers (India) in the year 1975. He has a total of 50 years industry exposure both in Manufacturing &Training He is a Certified Energy Auditor (Govt. Of India) Certified Quality Examiner with RBNQA (2014) and a Certified Master Trainer for ZED Rating (Quality Council of India), BB in six sigma from Benchmark Six Sigma
He has presented research papers at IIT Kharagpur, IIM Indore, IIM, Trichy. Received Golden Paper Award for his paper @Pondicherry University in 2018, and two research papers on KAIZEN, submitted in Scopus indexed Journal has been accepted for Publicationhttps://www.interscience.in/mentors/1059/thumbnail.jp
An event-related potential (ERP) study of attention allocation in the processing of a fear appeal and its relation to HPV vaccine acceptance
No full textThe present study had two general aims. The primary purpose was to test whether varying the level of threat content in a fear appeal affects attention allocation to the communication. It was predicted that a high threat fear appeal would capture and sustain more attention than a low threat fear appeal and that this increase would facilitate deeper message processing. The second objective was to examine the effect of dispositional and personal relevance factors on the decision to obtain a vaccine that protects against strains of the Human Papillomavirus (HPV). To test these hypotheses, a sample of college women (n = 72) were randomly assigned to listen to either a high threat or low threat fear communication about HPV. A dual-task paradigm was used to measure attention allocation in real-time wherein participants listened to the fear appeal while completing an unrelated visual stimulus discrimination task. Measures of P300, an event-related potential (ERP) component believed to reflect resource allocation, were obtained during message exposure. A follow-up interview was conducted 6-weeks after the experimental session to assess vaccine uptake, information seeking behavior, and knowledge retention about HPV. Women who expressed intentions to obtain the HPV vaccine were more likely to have made plans to get the vaccine or were already vaccinated at the time of follow-up (OR = 29.18, CI = 1.53 to 557.53, p < .05). The high threat fear appeal was associated with more knowledge retention about HPV at the time of follow-up than the low threat communication, β = .38, p < .05. The results also suggest that attention allocation during message exposure was positively associated with HPV knowledge retention (β = .23, p < .05) and the likelihood of having obtained or made plans to obtain the vaccine (OR = 1.02, CI = 1.004 to 1.04, p < .05). In the high threat condition, number of sexual partners was positively associated with intentions to consult a doctor about HPV (β = .33, p < .05) and to talk to friends about the vaccine (β = .32, p < .05). However, lack of sexual activity, parental disapproval, and concerns over vaccine safety were the most cited reasons for not wanting or being unsure about the vaccine. The present study has made a significant methodological contribution by incorporating a dual-task paradigm and a real-time measure of attention allocation to assess message processing.Ph.D.Includes abstractVitaIncludes bibliographical referencesby AArathi Meenakshi Venkatesa
DESIGN, IN-SILICO DOCKING AND PREDICTIVE ADME PROPERTIES OF SOME THIAZOLIDINE-2, 4-DIONES DERIVATIVES AS PPARγ MODULATORS
No full textObjectives: Thiazolidinediones a promising and privileged scaffold in medicinal chemistry that has been popularly recognized for its antidiabetic activity. The objective of the current study is to explore the effects of substitution replacing the acidic hydrogen of thiazolidinedione ring.Methods: The protocol adopted was (i) In silico enumeration of small chemical library, (ii) molecular docking simulation and (iii) selection of hits based on predicted ADME/TOX properties to support further synthetic enumeration of chemical compounds for biological evaluation.Results: The results of the present study showed that all the designed compounds were found to be potent PPARγ modulators and shows promising lead like properties from the calculated ADME/TOX parameters. Rosiglitazone was taken as a standard for the comparison of In silico studies.Conclusion: The design strategy adopted has predicted improved potency, less toxicity and a better binding mode prediction towards PPARγ.Keywords: PPARγ, Pharmacokinetic parameters, Schrodinger, Structure-activity relationship, Molecular docking simulation, Pharmacokinetic parameter
Designing and In Silico Evaluation of Some Non-Nucleoside <i>MbtA</i> Inhibitors: On Track to Tackle Tuberculosis
No full textThe WHO database shows that mycobacterium tuberculosis has become an epidemic worldwide due to its pathogenicity and virulence, which have magnified its infectiousness. The situation becomes grimmer with the prevalence of MDR-TB, XDR-TB, emergence of cross-resistance, ineffectiveness of novel therapeutic targets, failure of novel medications in clinical trials, currently available drugs losing their therapeutic efficacy, lack of drug discovery efforts due to poor ROI, and the existence of co-infections; i.e., HIV, TB, COVID, and HIV-TB-COVID. Following our prior studies described by Stirret et al. in 2008, Ferreras et al. in 2011, and Shyam et al. in 2021, herein we focus on exploring pyrazoline-based mycobactin analogs (non-specific mycobactin biosynthesis inhibitors) targeting the MbtA enzyme (first step of mycobactin biosynthesis) with a hope of finding a more potent analog showing a high affinity for MbtA. The design strategy involves retaining the structural features of mycobacterial siderophores. Herein, a small library (12 molecules) of mycobactin analogs were designed, keeping the necessary skeleton (diaryl-substituted pyrazoline (DAP)) intact and assessed their stability using in silico tools. In order to determine the binding modes and inhibitory profiles of the designed ligands, docking was carried out in the active pocket of MbtA (analogous with the homologous structure with PDB ID: 1MDB). The best energy conformation (lowest score) of each docked ligand was represented graphically. The ADMET profile of each molecule was analyzed. The best molecule that revealed a good ADMET profile was taken up for MD simulation study (45 ns). Results revealed that the designed compounds GV08 (−8.80 kcal/mol, 352.58 nM), GV09 (−8.61 kcal/mol, 499.91 nM), GV03 (−8.59 kcal/mol, 508.51 nM), and GV07 (−8.54 kcal/mol, 553.44 nM) had a good docking score and inhibition constant. Of these, GV08 showed a good ADME profile with all the major parameters lying in the acceptable ranges. They also showed the least toxicity with no hepatotoxicity and skin sensitization. MD simulation studies of GV08 also suggest that it was stable throughout the course of simulation. This could be justified by RMSD, RMSF, and H-bond plots. The future scope invalidates these findings through synthesis, characterization, and intracellular activity
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