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排序方式: 共有384条查询结果,搜索用时 15 毫秒
61.
Wieslaw M. Kazmierski Nagaraju Miriyala David K. Johnson Sam Baskaran 《ACS medicinal chemistry letters》2021,12(11):1649
HCV NS5A inhibitors are the backbone of directly acting antiviral treatments against the hepatitis C virus (HCV). While these therapies are generally highly curative, they are less effective in some specific HCV patient populations. In the search for broader-acting HCV NS5A inhibitors that address these needs, we explored conformational restrictions imposed by the [7,5]-azabicyclic lactam moiety incorporated into daclatasvir (1) and related HCV NS5A inhibitors. Unexpectedly, compound 5 was identified as a potent HCV genotype 1a and 1b inhibitor. Molecular modeling of 5 bound to HCV genotype 1a suggested that the use of the conformationally restricted lactam moiety might have resulted in reorientation of its N-terminal carbamate to expose a new interaction with the NS5A pocket located between amino acids P97 and Y93, which was not easily accessible to 1. The results also suggest new chemistry directions that exploit the interactions with the P97–Y93 site toward new and potentially improved HCV NS5A inhibitors. 相似文献
62.
D. Baskaran 《Macromolecular chemistry and physics.》2000,201(8):890-895
Living anionic polymerization of methyl methacrylate is achieved using (1,1‐diphenylhexyl)lithium as initiator in the presence of dilithium triethylene glycoxide as an additive in tetrahydrofuran at –40, –20, 0 and 30°C. High initiator efficiencies and poly(methyl methacrylate)s with narrow molecular weight distributions (1.1 < Mw/Mn < 1.3) were obtained. The efficiency of the dilithium salts of glycol and diethylene glycol as additive in the polymerization of MMA was found to be poor. The beneficial effect of dilithium triethylene glycoxide was attributed to the better coordination with enolate ion pairs providing stabilization to ligand‐complexed ion pairs. As, the polymerization is very fast, the mode of monomer addition and the initiator concentration play a major role in controlling the polymerization in the presence of polydentate dilithium alkoxides. 相似文献
63.
Satish K. Panda Royston K. Y. Tan Tin A. Tun Martin L. Buist Monisha Nongpiur Mani Baskaran Tin Aung Michaël J. A. Girard 《Investigative ophthalmology & visual science》2021,62(13)
PurposeTo evaluate the biomechanical properties of the iris by evaluating iris movement during pupil constriction and to compare such properties between healthy and primary angle-closure glaucoma (PACG) subjects.MethodsA total of 140 subjects were recruited for this study. In a dark room, the anterior segments of one eye per subject were scanned using anterior segment optical coherence tomography imaging during induced pupil constriction with an external white light source of 1700 lux. Using a custom segmentation code, we automatically isolated the iris segments from the AS-OCT images, which were then discretized and transformed into a three-dimensional point cloud. For each iris, a finite element (FE) mesh was constructed from the point cloud, and an inverse FE simulation was performed to match the clinically observed iris constriction in the AS-OCT images. Through this optimization process, we were able to identify the elastic modulus and permeability of each iris.ResultsFor all 140 subjects (95 healthy and 45 PACG of Indian/Chinese ethnicity; age 60.2 ± 8.7 for PACG subjects and 57.7 ± 10.1 for healthy subjects), the simulated deformation pattern of the iris during pupil constriction matched well with OCT images. We found that the iris stiffness was higher in PACG than in healthy controls (24.5 ± 8.4 kPa vs. 17.1 ± 6.6 kPa with 40 kPa of active stress specified in the sphincter region; P < 0.001), whereas iris permeability was lower (0.41 ± 0.2 mm2/kPa s vs. 0.55 ± 0.2 mm2/kPa s; p = 0.142).ConclusionsThis study suggests that the biomechanical properties of the iris in PACG are different from those in healthy controls. An improved understanding of the biomechanical behavior of the iris may have implications for the understanding and management of angle-closure glaucoma. 相似文献
64.
First-trimester ductus venosus, nasal bones, and Down syndrome in a high-risk population 总被引:1,自引:0,他引:1
Prefumo F Sethna F Sairam S Bhide A Thilaganathan B 《Obstetrics and gynecology》2005,105(6):1348-1354
OBJECTIVE: Assessing the role of fetal ductus venosus and nasal bones evaluation in first-trimester screening for Down syndrome. METHODS: This was a prospective cohort study in a tertiary referral fetal medicine unit involving 628 consecutive fetuses undergoing chorionic villus sampling. The indication for chorionic villus sampling was an increased risk (more than 1:300) for trisomy 21 based on maternal age and nuchal translucency screening in 313 cases (54.7%), increased maternal age in 195 (34.1%), and other in 64 (11.2%). Immediately before chorionic villus sampling, an ultrasound examination was performed. The pattern of blood flow in the ductus venosus and the presence or absence of the nasal bones was noted. RESULTS: A satisfactory examination of both ductus venosus and nasal bones was possible in 572 fetuses. Of these, 497 (86.9%) had a normal karyotype, and 47 (8.2%) were affected with Down syndrome. The likelihood ratio for trisomy 21 was 7.05 (95% confidence interval 4.27-11.64) in the case of abnormal ductus venosus flow and 6.42 (95% confidence interval 3.86-10.67) in the case of absent nasal bones. CONCLUSION: In addition to increased fetal nuchal translucency, Down syndrome is significantly associated with first-trimester abnormal flow velocity patterns in the ductus venosus and hypoplasia of the nasal bones. 相似文献
65.
Monisha E. Nongpiur Ching-Yu Cheng Roopam Duvesh Saravanan Vijayan Mani Baskaran Chiea-Chuen Khor John Allen Srinivasan Kavitha Rengaraj Venkatesh David Goh Rahat Husain Pui Yi Boey Desmond Quek Ching Lin Ho Tina T. Wong Shamira Perera Tien Yin Wong Subbiah R. Krishnadas Eranga N. Vithana 《Ophthalmology》2018,125(5):664-670
66.
67.
Manesh Kumar Panner Selvam Ashok Agarwal Tnia R. Dias Ana D. Martins Saradha Baskaran Luna Samanta 《Andrologia》2019,51(8)
Semen contains leucocytes and round cells, besides spermatozoa. The objective of this study was to identify whether the proteins from round cells and leucocytes affect the proteomic analysis of spermatozoa. Cryopreserved human sperm samples were divided into four groups: (1) samples with ≥1 × 106/ml leucocytes unprocessed; (2) samples with ≥1 × 106/ml leucocytes processed by 65% density centrifugation; (3) samples with round cells <1 × 106/ml unprocessed; and (4) samples with round cells <1 × 106/ml processed by 65% density centrifugation. Samples from each group (1, 2, 3 and 4) were pooled (n = 5) for quantitative proteomic analysis using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). Comparative analysis revealed nine differentially expressed proteins (DEPs) groups 1 and 2. Moreover, five DEPs were identified between groups 3 and 4. We observed that cylicin‐1, Atlastin‐1 and vesicle transport protein SFT2B are specific to spermatozoa, and none of them were associated with leucocytes. The number of DEPs in spermatozoa of processed and unprocessed cryopreserved semen samples was negligible. Our results indicate that the presence of round cells (<1 × 106/ml) in the seminal ejaculation does not interfere in the accurate detection of spermatozoa proteome by LC‐MS/MS. 相似文献
68.
Silvan S Manoharan S Baskaran N Anusuya C Karthikeyan S Prabhakar MM 《European journal of pharmacology》2011,670(2-3):571-577
Aim was to investigate the chemopreventive potential of apigenin by analyzing the tumor incidence as well as monitoring lipid peroxidation, antioxidants and phase I and phase II detoxification as biomarkers during DMBA induced hamster buccal pouch carcinogenesis. Oral tumors were developed in the buccal pouches of golden Syrian hamsters using topical application of 0.5% DMBA (DMBA) three times a week for 14weeks. Tumor incidence, tumor volume and burden were measured in hamsters treated with 7,12-dimethylbenz(a)anthracene and DMBA+apigenin (2.5mg/kg body weight) treated hamsters. Oral administration of apigenin not only completely prevented the formation of oral tumors, it also brought back the status of lipid peroxidation, antioxidants and phase I and phase II detoxification agents to near normal range during DMBA induced oral carcinogenesis. The present study thus concludes that apigenin might have inhibited oral carcinogenesis by improving the status of antioxidant defense mechanism and modulated the activities of phase I and phase II detoxification cascade toward increased excretion of active metabolite of DMBA, during DMBA induced hamster buccal pouch carcinogenesis. 相似文献
69.
70.
Ronnie George Hemamalini Arvind M Baskaran S Ve Ramesh Prema Raju Lingam Vijaya 《Indian journal of ophthalmology》2010,58(3):243-245
We report the prevalence and risk factors for glaucoma among aphakes and pseudophakes in 3850 subjects who participated in a population-based study in urban south India. The subjects underwent an ophthalmic examination including applanation tonometry, gonioscopy, optic disc evaluation and frequency doubling perimetry. Glaucoma was diagnosed using the International Society of Geographical and Epidemiological Ophthalmology (ISGEO) criteria. Thirty eight, 15 aphakes and 23 pseudophakes (0.99% of 3850 subjects) of the 406 persons who had undergone cataract surgery were diagnosed with glaucoma. Aphakes/pseudophakes were at higher risk of glaucoma as compared to the phakic population (Odds Ratio: 2.71, 95% CI: 1. 94, 3.38, p=0.001). On multivariate analysis, older age and higher intra ocular pressure were risk factors for glaucoma. Blindness attributable to glaucoma was detected in 20% of aphakic and 4.3% of pseudophakic eyes. Glaucoma was a significant cause of morbidity in those who had undergone cataract surgery in this urban population. 相似文献