Synthesis, biological evaluation and molecular docking studies of novel 3,5- disubstituted 2,4-thiazolidinediones derivatives

Thiazolidinediones (TZDs) are a new class of antidiabetic drugs, having an insulin sensitizing effect in patients with type 2 diabetes. We report here the synthesis A series of thirteen 2,4-thiazolidinedione derivatives. The 2,4-thiazolidinedione ring\u27s fifth position was used as a site for Knoevenagel condensation to generate the compounds listed in the title. The synthesised derivatives were characterised using a variety of physicochemical and spectral analyses, including IR, Mass, 1H-NMR, 13C-NMR, and elemental analysis. By using the carrageenan-induced rat paw edoema method, the alloxan-induced diabetes in wistar rats method, and the FRAP (ferric reducing antioxidant power) method, respectively, the derivatives were examined for their in vivo anti-diabetic, in vivo anti-inflammatory, and in vitro free radical scavenging activities. Some of the compounds showed promise as powerful anti-inflammatory, anti-free radical, and anti-diabetic medications. The most effective anti-diabetic compounds, NB7, NB12, and NB13, were docked using MOE software to study some potential structural insights into the potential binding patterns with the target PPAR active sites (PDB ID: 2PRG). The dichloro derivative chemical NB-7 has demonstrated strong anti-inflammatory and antioxidant potential in the current investigation in addition to having the highest anti-diabetic efficacy

Resummed prediction for Higgs boson production through bbˉb\bar{b} annihilation at N3^3LL

We present an accurate theoretical prediction for the production of Higgs boson through bottom quark annihilation at the LHC up to next-to-next-to-next-to leading order (N$^3$LO) plus next-to-next-to-next-to-leading logarithmic (N$^3$LL) accuracy. We determine the third order perturbative Quantum Chromodynamics (QCD) correction to the process dependent constant in the resummed expression using the three loop bottom quark form factor and third order quark soft distribution function. Thanks to the recent computation of N$^3$LO corrections to this production cross-section from all the partonic channels, an accurate matching can be obtained for a consistent predictions at N$^3$LO+N$^3$LL accuracy in QCD. We have studied in detail the impact of resummed threshold contributions to inclusive cross-sections at various centre-of-mass energies and also discussed their sensitivity to renormalization and factorization scales at next-to-next-to leading order (NNLO) matched with next-to-next-to leading logarithm (NNLL). At N$^3$LO+N$^3$LL, we predict the cross-section for different centre-of-mass energies using the recently available results in \cite{Duhr:2019kwi} as well as study the renormalization scale dependence at the same order.Comment: 19 pages, 4 figures, 2 table

Survey of Trending Techniques for Detection of Emerging Topics in Computer Science within Social Media

With the advent of Internet there has been a significant and exponential growth in information available to users. The availability of resources like smart mobile phone, low cost data plans and improvement in mobile communication infrastructure has further increased the reach and availability of information. The Internet allowed creation of websites and applications that significantly kept on adding data. The data generated through these websites can be structured (relational database), unstructured (digital images, video, audio files) or semi-structured (word document). The growth of Internet and WWW services gave user a liberty to create his own data, which then can be shared with the world. The development of User-Generated Content (UGC) [2] such as blogs, wikis, forums, tweets, discussions, posts, chats, podcasts, advertisements and other form of media led to the shift of information exchange from media conglomerates to individual user. With this huge amount of data, we address the problem of trending the emerging topics. Identify trending of these emerging topics allows us to know the probable trend of computer science research topics or other relevant research topics in future

Synthesis and evaluation of sulphonamide clubbed thiophenes as dihydrogen pteroate synthase inhibitors

Background. Derivatives of thiophene and sulphonamide showed various pharmacological activities including antimicrobial and dihydrofolate reductase (DHFR) inhibition activity. Dihydrofolate reductase and dihydropteroate synthetase enzymes are responsible for bacterial growth and cell proliferation of cancer cells. Method: In the first step, thiophene was synthesized from cyclohexanone, sulphur and ethyl cyanoacetate by Gewald reaction. Second step involved cyclization of ethyl 2-aminothiophene-3-carboxylate conducted using formamide. In the third step, the carbonyl group was replaced by chlorine in the presence of POCl3. Then the chlorine group was removed by substituted sulphonamide. A series of derivatives were synthesized and evaluated for antimicrobial, anti-oxidant and DHFR inhibition activity. Newly synthesized derivatives of sulphonamide clubbed thiophene showed moderate to excellent antimicrobial and DHFR inhibition activity. Results. A series of thiophene clubbed sulphonamide conjugates were designed, synthesized and their structures were characterized using 1H NMR, 13C NMR, IR and HR-MS spectral analysis. The antioxidant activity was performed by DPPH and hydrogen peroxide method. Among these derivatives, the compounds a and b showed comparable anti-oxidant activity 76.29% and 73.25% respectively against DPPH as compared to standard drug ascorbic acid (82.68%). Remaining conjugates displayed significant anti-oxidant activity. The docking study was performed using Molegro virtual docker (MVD) molecular docking suggested a remarkable binding pose for all the thiophene linked sulphonamide derivatives. Conclusion. Compounds with electron donating groups showed potential activity. The binding affinity of these derivatives against dihydropteroate synthetase (DHTS) and dihydrofolate reductase (DHFR) enzymes were confirmed by molecular docking studies. The ADME and toxicity profile was studied. The compounds can serve as potential DHFR and DHTS inhibitors

Zebrafish retinal stem cell differentiation mechanisms are disrupted by embryonic ethanol exposure

poster abstractPrenatal alcohol exposure can lead to a wide range of developmental abnormalities, which are included under the umbrella term fetal alcohol spectrum disorder (FASD). To understand the genesis of FASD defects, the zebrafish is important mechanistic animal model, particularly for retinal development. Previous work from our laboratory showed that ethanol treatment during gastrulation through somitogenesis in zebrafish embryos could recapitulate human ocular defects including microphthalmia, optic nerve hypoplasia, and photoreceptor defects. Ethanol-treated embryos showed increased retinal proliferation in the outer nuclear layer (ONL), inner nuclear layer (INL), and ciliary marginal zone (CMZ). Retinoic acid (RA) and folic acid (FA) co-supplementation rescued most ethanol-induced retinal defects, suggesting that nutrient deficiencies contribute to FASD. To better understand the genesis of ethanol-induced retinal cell differentiation defects, effects of ethanol exposure on retinal stem cell populations in the CMZ and Müller glial cell populations were examined. Ethanol treated retinas had an expanded CMZ, and a reduced expression domain for the cell cycle exit marker, cdkn1c. Ethanol treated retinas also showed reduced GFAP-positive Müller glial cells, which are a stem cell population in the central retina. At 72 hpf, the ONL of ethanol exposed fish showed few photoreceptors expressing terminal differentiation markers. Importantly, these poorly differentiated photoreceptors co-expressed the bHLH differentiation factor, neuroD, indicating that ethanol exposure produced immature and undifferentiated photoreceptors. Reduced differentiation along with increased progenitor marker expression and proliferation suggest cell cycle exit disruption due to ethanol exposure. Ethanol exposure severely disrupted Wnt and Notch signaling, which are critical for stem cell behavior and differentiation. These defects were rescued by Wnt signaling agonist, RA, and FA treatments. These results suggest ethanol disrupted retinal cell differentiation mechanisms. Further analysis of underlying molecular mechanisms will provide insight into the ethanol-induced retinal defects and potential therapeutic targets

Comparative Analysis of External Links of video Using Apriori and RFP

Recently popularity of video sharing site is increased. People can watch video from any other site other than video sharing site. To increase popularity of video external links concept is introduced. Now in video sharing site through external link is video or audio content can be embedded into external website. User can copy that URL of that embedded link & post on their own blog or website. In this paper our intension is study of relevancy of videos and & increase the popularity & measure the quantification. With the results collected from two major video sharing site like Youtube & Youku we observed that these links have an various impact on popularity. Overall, videos which are collected from external links are analyzed and accuracy & popularity is measured DOI: 10.17762/ijritcc2321-8169.15079

Ethanol-induced Retinal Defects are Rescued by Retinoic Acid Supplement in Developing Zebrafish Embryos

poster abstractFetal Alcohol Spectrum Disorder (FASD) is caused by prenatal alcohol exposure, producing a spectrum of defects including facial abnormalities, sensory (visual and auditory) deficits, impaired fine motor skills and learning deficits including mental retardation. Our laboratory has used a zebrafish model for FASD that exposes embryos to ethanol during early development (midblastula transition through somitogenesis). Children diagnosed with FASD frequently show severe eye defects ranging from small eyes, underdeveloped optic nerve, and cataract. Zebrafish embryos exposed to ethanol showed defects similar to human eye birth defects. Presence of ethanol affected the differentiation of many retinal cell types including, retinal ganglion cells and photoreceptors. We hypothesize that ethanol may affect retinal patterning by competing with Retinaldehyde dehydrogenase (Raldh), reducing retinoic acid (RA) synthesis and signaling. Co-treatment of embryos with ethanol and 10-9 M RA could rescue the photoreceptor and retinal ganglion cell differentiation defects in the retina. RA plays a crucial role in the dorso-ventral patterning of the retina, and the enzymes involved in RA biosynthesis are expressed in the ventral retina during mid-somitogenesis stage. Our experiments showed that ethanol exposure during that critical time window when Raldh is expressed in the ventral retina causes severe defects in retinal cell specification. No defects were induced by ethanol exposure at the earlier stages. Presence of RA during photoreceptor differentiation could rescue ethanol-induced photoreceptor differentiation defects. Future work will dissect molecular mechanisms underlying ethanol defects, including retinoic acid-mediated eye development mechanisms. Determining the effects of ethanol exposure on retinal morphogenesis and differentiation will help identify potential therapeutic targets for ocular defects in this regrettably frequent birth defect syndrome

Single incision laparoscopic cystectomy for a huge fimbrial cyst: a rare case report

A case of huge fimbrial cyst is presented, occurring in a 26 year old female. She presented in outpatient department with an incidental diagnosis of a huge cystic mass diagnosed during her routine medical check-up. She was asymptomatic. Ultrasound and CT scan showed an abdominopelvic cystic mass in left adnexa and a right dermoid cyst. Single incision laparoscopic surgery was performed and a huge right fimbrial cyst of 35 cm was noted along with left dermoid cyst. We did bilateral cystectomy through single port laparoscopy.  Although there are a few case reports on huge fimbrial cysts which were managed traditionally by laparotomy and recently multiport laparoscopic surgeries, the technique of single incision laparoscopic surgery for proved benign cysts has been described here