Application of author bibliographic coupling analysis and author keywords ranking in identifying research fronts of Indian Neurosciences research

Probing research fronts identification unfailingly delivers interesting results in any field due to its decisive nature. Citation analysis is an acclaimed method used in this process among which more successful results backing Author Co-citation Analysis (ACA) and Author Bibliographic Coupling Analysis (ABCA). The current study opted to combine author bibliographic coupling network analysis and author keywords to explore and display a graphical representation of prominent research areas’ evolution over the study period in Indian Neuroscience research domain. Application of hierarchical clustering to author bibliographic coupling networks for all non-overlapping consecutive years included in the study period were performed and analysed in VOSviewer mapping software. The powerful Lin/log modularity normalization was chosen for determining distance based similarity while clustering the network units. Results of the study unfolded ten prominent research subfields with more emphasis on Epilepsy’ and ‘Parkinson’s disease’ research. Depression was identified as one of the upcoming prominent area in recent years. Apart from its cruciality in framing national level mental health policies, the study will also prove ABCA to be an effective method in identifying prominent research areas

Rule based heuristic approach for minimizing total flow time in permutation flow shop scheduling

Programiranje radova u proizvodnji je od bitne važnosti u planiranju i funkcioniranju proizvodnog sustava. Unaprijeđeni sustav programiranja značajno utječe na smanjenje troškova i minimalni broj radnih postupaka. U ovom se radu razmatra problem programiranja n/m/F/ΣCi primjenom Decision Tree (DT) algoritma. Budući da je ovaj problem poznat kao veoma NP-hard, u radu se za njegovo rješenje predlaže metodologija temeljena na heuristici. Prednosti DT-a su u tome što je pravilo otpreme u obliku If-then else pravila koja radnici u radionici lako razumiju. Predloženi je pristup testiran na repernim problemima dostupnim u literaturi i uspoređen. Predloženi rad je dodatak tradicionalnim metodama.Production scheduling plays a vital role in the planning and operation of a manufacturing system. Better scheduling system has a significant impact on cost reduction and minimum work-in-process inventory. This work considers the problem of scheduling n/m/F/ΣCi using Decision Tree (DT) algorithm. Since this problem is known to be strongly NP-hard, this work proposes heuristic based methodology to solve it. The advantages of DT’s are that the dispatching rule is in the form of If-then else rules which are easily understandable by the shop floor people. The proposed approach is tested on benchmark problems available in the literature and compared. The proposed work is a complement to the traditional methods

Application of author bibliographic coupling analysis and author keywords ranking in identifying research fronts of Indian Neurosciences research

Probing research fronts identification unfailingly delivers interesting results in any field due to its decisive nature. Citation analysis is an acclaimed method used in this process among which more successful results backing Author Co-citation Analysis (ACA) and Author Bibliographic Coupling Analysis (ABCA). The current study opted to combine author bibliographic coupling network analysis and author keywords to explore and display a graphical representation of prominent research areas’ evolution over the study period in Indian Neuroscience research domain. Application of hierarchical clustering to author bibliographic coupling networks for all non-overlapping consecutive years included in the study period were performed and analysed in VOSviewer mapping software. The powerful Lin/log modularity normalization was chosen for determining distance based similarity while clustering the network units. Results of the study unfolded ten prominent research subfields with more emphasis on Epilepsy’ and ‘Parkinson’s disease’ research. Depression was identified as one of the upcoming prominent area in recent years. Apart from its cruciality in framing national level mental health policies, the study will also prove ABCA to be an effective method in identifying prominent research areas

N-Alkyl, N-Acyl, and Triazolyl Derivatives of Chitosan: Synthesis and Antibacterial Properties

Kítósan er líffjölliða sem virk gegn örverum og hefur jafnframt marga aðra ákjósanlega eiginleika eins og lífsamræmanleika og lífniðurbrotshæfni jafnframt því að vera óeitruð. Kítósan og afleiður þess hafa mikið verið rannsakaðar sem bakteríudrepandi efni en þrátt fyrir það er þekking á sambandi byggingar og virkni takmörkuð. Í byrjun miðaði doktorsverkefnið að þvi að skilgreina samband byggingar og virkni fyrir nokkar vel þekktar afleiður kítósans. Í framhaldinu voru nýjar smellefnafræðiaðferðir fyrir smíðið kítosanafleiða og konjúgata þróaðar og notaðar til að smíða nýja gerð fjölliða sem einnig voru rannsakaðar og samband byggingar og virkni ákvarðað. Fyrsti hluti rannsóknarinnar beindist að því að skilgreina vel samband byggingar og bakteríudrepandi virkni fyrir vel þekktar og mikið notaðar kítósanafleiður og flokka þær eftir notagildi. Katjónískar (TACin, TMCNH2/TM, TMCTM/DM og HTCC), anjónísk (CMC) og óhlaðnar (HPC og TGC) afleiður voru smíðaðar út frá kítósan og TBDMS-kítósan byrjunarefnum. Allar þessar afleiður voru efnagreindar með 1H NMR og FT-IR til að ákvarða byggingu og með gelsúluskiljun (GPC) til að ákvarða mólþunga. Kítósanafleiðurnar voru smíðaðar með mismunandi hlutföllum af hvarfefnum þannig að myndefnin voru með setni (DS) frá 0,02 til 1,1. Virkni geng S. aureus, E. coli, og P. aeruginosa var ákörðuð við pH 7,2 og 5,5. Katjónísku afleiðurnar voru virkastar gegn þessum bakteríum sérstaklega við pH 7,2. Samband mill virkni og setni (DS) var líka jákvætt fyrir TACin, TMCNH2/TM, og TMCTM/DM. HPC, sem var með óhlaðinn sethóp, var minna virkt og í því tilviki var neikvætt samband milli virkni og setni. CMC, sem var með anjónískan sethóp, var óvirkt gegn bakteríunum. Núorðið er æ algengara að nota kopar hvataða azíð-alkýn-hringálagningar (CuAAC) smellefnafræði til að smíða ýmiskonar lífefnakonjúgöt, þar með talið kítósan-konjúgöt. Annar hluti doktorsverkefnisins miðaði að því að hanna og smíða nýja gerð kítósanafleiða (kítótríazólan) þar sem öllum C-2 fyrstu gráðu amínóhópunum hefur verið umbreytt í 1,2,3-tríazól hópa. Amínóhópunum í kítósani var fyrst umbreytt í azíð sem voru svo hvörfuð við endastöðu-alkýn í viðurvist Cu (II) hvata og natríum askorbats. Hlutfall umbreytingar azíðs í 1,2,3- tríazól var meira en 90%. Virkni gegn bakteríunum S. aureus og E. coli var mæld við pH 7.2. Tvö katjónísk kítótríazólan efni reyndust talsvert virk (lægsta MIC = 64 µg/mL) en anjónísk kítotríazólan efni voru ekki virk gegn bakteríum. Þessi smellefnafræðiaðferð var líka notuð til að umbreyta fyrstu gráðu amínóhópum í hlutsetnum algengum kítósanafleiðum (TMC, TAC, HTC, HPC, and CMC) í tríazól. Virkni þessara blönduðu kítótríazólanefna gegn S. aureus, E. faecalis, E. coli, and P. aeruginosa við pH 7,2 var einnig mæld. Katjónísk kítótríazólanefnin og blönduð kítótríazólanefnin voru virk gegn bakteríunum, öll nema blönduð kítótríazólan afleidd af CMC, sem skorti virkni. CuAAC hvarfið var einnig notað til að smíða níu vatnsleysanleg kítótríazólanefni með mismunandi katjóníska eða basíska hópa. Metýlimidazól-któtrízólan afleiðan var virkust (lægsta MIC = 256 µg/mL) gegn bakteríunum. Lokahluti rannsóknarinar hafði það markmið að nota smellefnafræðiaðferðina til að tengja örverudrepandi peptíð við kítósan. CRAMP-18 peptíð sem innhélt endastæðan alkýn hóp var smíðað. Kítósan-azíð og HPC-azíð voru smíðuð með lága setni azíðhópa, og smellefnafræðiaðferðin notuð til að tengja CRAMP-18 peptíðið við fjölliðuna. Þessi konjúgöt voru mun virkari geng gram-neikvæðum bakteríum en gegn gram-jákvæðum bakteríum.Chitosan is a biopolymer with significant antimicrobial activity and many attractive properties such as biocompatibility, biodegradability, and non-toxicity. Chitosan and its derivatives have been widely studied as promising new antibacterial agents, but the relationship between structure and activity is still poorly understood. The Ph.D. project first sought to map the structureantibacterial activity relationship for common and well-known chitosan derivatives. New “click chemistry” based procedures for the synthesis of derivatives and conjugates were then developed, and these novel polymeric compounds were used for further structure-activity relationship (SAR) studies. The first part of the research focused on establishing the SAR for some of the more widely used chitosan derivatives and trying to rank them according to activity and utility. Cationic trimethylated (TACin, TMCNH2/TM, TMCTM/DM, and HTCC), anionic (CMC) neutral (HPC), and TGC chitosans were synthesized using chitosan and TBDMS chitosan as precursors. All these derivatives are characterized by 1H NMR, FT-IR to determine the structure, and gel permeation chromatography (GPC) to determine the molecular weight. The chitosan derivatives were synthesized with different reagent ratios to give products with degree substitution (DS) ranging from 0.02 to 1.1. Most of these derivatives displayed antimicrobial activity against S. aureus, E. coli, and P. aeruginosa at pH 7.2 and 5.5. Cationic derivatives were most active against these bacteria, especially at pH 7.2. The relationship with DS was also positive for TACin, TMCNH2/TM, and TMCTM/DM. HPC, which has a neutral substituent, was less active and had a negative relationship with DS. CMC, which has an anionic substituent, was inactive against the bacteria. Nowadays, it is increasingly common to use copper-catalyzed azide-alkyne cycloaddition (CuAAC) “click chemistry” to prepare bioconjugates, including chitosan derivatives and conjugates. The second part of the thesis work focused on designing and synthesizing a new class of chitosan derivatives where all C-2 primary amino groups have been converted to aromatic 1,2,3-triazoles (Chitotriazolan). The chitosan amines were converted to azides and reacted with terminal alkynes in the presence of Cu (II) catalyst and sodium ascorbate. The conversion of the azide to 1,2,3-triazole was more than 90%. The antibacterial activity was evaluated against S. aureus and E. coli at pH 7.2. Two cationic chitotriazolans exhibited (lowest MIC = 64 µg/mL) antibacterial activity, whereas the anionic chitotriazolans were inactive. The click chemistry strategies were used to convert primary amino groups of partially substituted common chitosan derivatives (TMC, TAC, HTC, HPC, and CMC) to triazole and thus obtain mixed chitotriazolans. The antibacterial activity was evaluated against S. aureus, E. faecalis, E. coli, and P. aeruginosa at pH 7.2. The cationic chitotriazolans and mixed chitoriazolans were active against bacteria, except chitotriazolan derived from CMC, which lacked activity. In addition to preparing water-soluble chitosan derivatives, the CuAAC reaction was further used to synthesize nine chitotriazolans with various quaternary and basic protonable functional groups. These chitotriazolan derivatives were soluble in water. The methylimidazole-chitotriazolan derivative showed significant activity (lowest MIC = 256 µg/mL) against all bacteria and was generally the most active derivative. The final part of the research for the thesis focused on the conjugation of antimicrobial peptides onto the chitosan backbone using the click chemistry procedure. The CRAMP-18 peptide was synthesized with a terminal alkyne group. Chitosan azide and HPC azide were prepared with a low degree of azidation, and a click reaction was performed with the modified CRAMP-18 peptide. The antimicrobial peptide chitosan conjugates were more active against gram-negative bacteria, E. coli, and P. aeruginosa than gram-positive bacteria

Chitotriazolan (poly(β(1-4)-2-(1H-1,2,3-triazol-1-yl)-2-deoxy-d-glucose)) derivatives: Synthesis, characterization, and evaluation of antibacterial activity

Here we describe the first synthesis of a new type of polysaccharides derived from chitosan. In these structures, the 2-amino group on the pyranose ring was quantitively replaced by an aromatic 1,2,3-triazole moiety. The 2-amino group of chitosan and di-TBDMS chitosan was converted into an azide by diazo transfer reaction. The chitosan azide and TBDMS-chitosan azide were poorly soluble but could be fully converted to triazoles by “copper-catalysed Huisgen cycloaddition” in DMF or DMSO. The reaction could be done with different alkynes but derivatives lacking cationic or anionic groups were poorly soluble or insoluble in tested aqueous and organic solvents. Derivatives with N,N-dimethylaminomethyl, N,N,N-trimethylammoniummethyl, sulfonmethyl, and phosphomethyl groups linked to the 4-position of the triazole moiety were soluble in water at neutral or basic conditions and could be analyzed by 1H, 13C APT, COSY, and HSQC NMR. The quaternized cationic chitotriazolan's had high activity against S. aureus and E. coli, whereas the anionic chitotriazolan's lacked activity.Rannsóknasjóður Rannís Rannsóknasjóður HÍFinal manuscript to publishe

Synthesis, spectral analysis, DFT studies and Biological application of (E)-3-benzylidene-9-methyl-1,2,3,9-tetrahydro-4H-carbazol-4-one

We have successfully synthesized our desired compound of (E)-3-benzylidene-9-methyl-1,2,3,9-tetrahydro-4H-carbazol-4-one by reacting with 9-methyl-1,2,3,9-tetrahydro-4H-carbazol-4-one and benzaldehyde. Further structure was characterized and confirmed by 1H NMR, 13C NMR, and Mass spectral analysis. Then we have explored the electronic structure of this one by DFT studies through MESP, and FMO analysis. Molecular docking studies were performed with 2 proteins with our compound and found to be good binding energies

Chemoproteomics of an Indole-Based Quinone Epoxide Identifies Druggable Vulnerabilities in Vancomycin-Resistant Staphylococcus aureus

Publisher's version (útgefin grein)The alarming global rise in fatalities from multidrug-resistant Staphylococcus aureus (S. aureus) infections has underscored a need to develop new therapies to address this epidemic. Chemoproteomics is valuable in identifying targets for new drugs in different human diseases including bacterial infections. Targeting functional cysteines is particularly attractive, as they serve critical catalytic functions that enable bacterial survival. Here, we report an indole-based quinone epoxide scaffold with a unique boat-like conformation that allows steric control in modulating thiol reactivity. We extensively characterize a lead compound (4a), which potently inhibits clinically derived vancomycin-resistant S. aureus. Leveraging diverse chemoproteomic platforms, we identify and biochemically validate important transcriptional factors as potent targets of 4a. Interestingly, each identified transcriptional factor has a conserved catalytic cysteine residue that confers antibiotic tolerance to these bacteria. Thus, the chemical tools and biological targets that we describe here prospect new therapeutic paradigms in combatting S. aureus infections.The authors thank the Department of Biotechnology (DBT), Government of India (BT/PR15848/MED/29/1025/2016 to H.C. and S.C.), a Wellcome Trust DBT India Alliance Intermediate Fellowship (IA/I/15/2/502058 to S.S.K.) and a DST-FIST Infrastructure Development Grant (to IISER Pune Biology) for the financial support for our research. The Council for Scientific and Industrial Research (CSIR) and the Department of Science and Technology—Innovation in Science Pursuit for Inspired Research (DST-INSPIRE) for graduate student fellowships.Peer Reviewe