Raynormark1689

One of the challenges developing a live attenuated tetravalent dengue vaccine (TDV) is to overcome the presumed viral interference that may be preventing the induction of a balanced immune response to all 4 serotypes of the dengue virus (DENV1-4). Our live attenuated TDV candidate was developed from wild-type (wt) parental strains (DENV1/03135, DENV2/99345, DENV3/16562, and DENV4/1036, respectively) using a classical host range mutation strategy the same strategy used for the approved live attenuated smallpox, polio, and MMR vaccines. Our vaccine candidate is expected to mimic natural dengue virus infection, as it provides all the components of dengue virus, including both structural and nonstructural proteins. Therefore, induction of more solid and comprehensive immune responses against pathogenic dengue viruses is also expected. In this study, we evaluated the neutralizing antibody responses for each serotype induced by a single subcutaneous administration of 6 formulations, which were composed of different combinations of vaccine strains and were all of different dosages. These formulations were tested in dengue-naïve cynomolgus macaques. As a result, regardless of the TDV formulation, all the monkeys immunized with TDVs seroconverted to all the 4 serotypes at day 30. Next, we evaluated protection ability of the selected formulations of TDV candidate, no RNAemia was detected from any of the immunized monkeys upon s.c. challenge with wtDENV. The findings of this non-human primate study indicate that our vaccine candidate is very promising; it can be further evaluated for safety and efficacy in human clinical studies.Temperature-induced mineral alterations are extensively used in traditional pharmaceutical industry. Studies on the traditional heating methods for enhancing pharmaceutical properties and on the toxicity of mineral-based medicines are limited. This study focuses on the effect of thermal alterations on mineralogical and chemical changes of biotite with respect to two traditional drugs (Abhrak Bhasma and Abhrak Chendhuram). Samples of the drugs and heat-treated and untreated biotite minerals were characterized using X-ray diffraction analysis, Fourier-transform infra-red spectroscopy, thermogravimetric analysis and differential scanning calorimetry. Total and water-soluble cation concentrations of drugs were measured using atomic absorption spectrometry. The study reveals that the degree of collapsing the biotite structure increased with the thermal oxidation process that produced nanoparticles of crystalline and amorphous iron oxides and secondary silicates. The thermal products of biotite had nano-crystallinity and high water solubility. The study suggests that modern pharmaceuticals can be developed from mineral-based traditional drugs.Phenylenes are a class of conjugated hydrocarbons composed of a special arrangement of six- and four-membered rings. In this paper, the expected values of the atom-bond connectivity (ABC), geometric-arithmetic (GA), and Zagreb indices of this class of conjugated hydrocarbons have been determined. At the end, the comparisons with respect to the random phenylene chains among the expected values of these indices, have been determined explicitly. The graphical profiles of these indices have been shown in order to support our results.Consumers who actively search for better broadband deals may benefit from lower prices or improved service quality compared to those who do not. If, however, consumers differ in their propensity to engage with the market and actively search, these potential benefits may not accrue equally. This paper investigates differences in consumer search activity for telecommunications services across small geographic areas. We exploit rich and novel data from a commercial price comparison site to explore the dispersion of consumer search in the Irish retail broadband market, while controlling for supply-side variations. By linking geo-coded searches to census data on small area socio-economic characteristics, we identify the areas where most search originates and can thus characterise the socio-economic groups to whom the benefits of search are most likely to accrue. We find evidence that areas populated by many highly educated, married people, commuters, mortgage holders, and retirees are among the most active in search. In contrast, those areas in which many older people, farmers, low-skilled workers and students reside give rise to significantly fewer consumer searches.Chemoinformatic studies were carried on some inhibitors of dopamine transporter to develop a predictive and robust QSAR model and also to elucidate binding mode and molecular interactions between the ligands (inhibitors) and the receptor targeting schizophrenia as novel Antipsychotic agents. Density Functional Theory (DFT) approach was utilized to optimize the ligands at B3LYP/6-31G∗ at the ground state and Multi-linear regression of the genetic function approximation (MLR-GFA) method was employed in building Penta-parametric linear equation models. The best model with statistically significant parameters has squared correlation coefficient R2= 0.802, adjusted squared correlation coefficient R2adj = 0.767, Leave one out (LOO) cross-validation coefficient (Q2) = 0.693, lack of fit score (LOF) = 0.406, R2Test = 0.77, Y-randomization test (cR2p) = 0.714, Chi-squared (χ2) =0.026, bootstrapping (Systematic errors = 0.272) and Variance Inflation Factor (VIF) less then 2 . The obtained results were compared with stl as a blueprint in developing novel antipsychotic agents with improved activity for the treatment of schizophrenia mental disorder.Dichapetalum crassifolium Chodat (Dichapetalaceae) is widely distributed in Africa, Tropical Asia and Latin America. Pluripotin cell line As part of our quest for potential bioactive lead compounds for various neglected tropical diseases, we report the anti-schistosomal potential of the crude extracts and chemical constituents of the stems and roots of Dichapetalum crassifolium. Column chromatography of extracts of the stems and roots led to the isolation and identification of three oleanane-type triterpenoids, friedelan-3β-ol (1), friedelan-3-one (2), and maslinic acid (3); the ursane-type tritepenoid, pomolic acid (4) and the dammarane-type tetracyclic triterpenoids, dichapetalin A (5) and dichapetalin M (6). Dichapetalin A was isolated from only the roots. Isolated compounds were identified by comparison of their physico-chemical and spectral data with published data. The highest in vitro anti-schistosomal activity (IC50) of the crude extracts against clinical isolates of Schistosoma haematobium (Bilharz 1852) was 248.6 μg/ml for the ethyl acetate extract of the root while dichapetalin A gave the highest activity at 151.