SYNTHESIS OF BIS-BENZIMIDAZOLES N-ALKYL ANTI-INFECTIOUS DERIVATES

Objective: The objective of this work is to synthesize new molecules with biological characteristics against some infectious germs. Methods: The method of synthesis is based on the exploitation of the reactivity of the position-1 of the benzimidazole. It consisted of reacting the bis-benzimidazole 5 with the 1,2-dicloroethane in a solution of NaOH 2N (6,4%). The compound 6 is refluxed with ethanol with the different thioaryls to lead to compounds 7. Results: Thus, a series of molecules derived from bis-benzimidazoles were synthesized including N-alkylated 6 and 7a-d. The characterization of these newly synthesized compounds was performed by NMR (1H and 13C) and mass spectroscopy methods. Conclusion: The purified and characterized compounds 6 and 7a-d allow the development of a new chemical class of anti-infectives

Acne and smoking: is there a relationship?

BACKGROUND: There are contradictory reports on the relationship between acne vulgaris and cigarette smoking. The objective of this study was to examine the relation between acne and cigarette smoking in a case-control study. METHODS: A questionnaire on smoking habits was offered to 350 patients with acne vulgaris and 350 patients suffering from skin diseases other than acne, aged 15 – 40 years, attending in a skin clinic in Tehran, Iran. The patients completed the questionnaires anonymously in the waiting room. RESULTS: Two hundred and ninety-three patients with acne (response rate 83.7 %) and 301 patients with other skin diseases (response rate 86.0 %) completed the questionnaires. Twelve acne patients (4.1 %) and 27 control patients (9.0 %) were current smokers (odds ratio = 0.43, 95% confidence limits 0.22 – 0.87, p < 0.05). But after adjustment for sex, this difference was not significant (odds ratio: 0.61, 95% CI: 0.30–1.26, p > 0.05, Mantel-Haenszel test). CONCLUSION: An association between acne and cigarette smoking was not found in this study

The intellectual influence of economic journals: quality versus quantity

The evaluation of scientific output has a key role in the allocation of research funds and academic positions. Decisions are often based on quality indicators for academic journals, and over the years, a handful of scoring methods have been proposed for this purpose. Discussing the most prominent methods (de facto standards) we show that they do not distinguish quality from quantity at article level. The systematic bias we find is analytically tractable and implies that the methods are manipulable. We introduce modified methods that correct for this bias, and use them to provide rankings of economic journals. Our methodology is transparent; our results are replicable

Predicting Important Residues and Interaction Pathways in Proteins Using Gaussian Network Model: Binding and Stability of HLA Proteins

A statistical thermodynamics approach is proposed to determine structurally and functionally important residues in native proteins that are involved in energy exchange with a ligand and other residues along an interaction pathway. The structure-function relationships, ligand binding and allosteric activities of ten structures of HLA Class I proteins of the immune system are studied by the Gaussian Network Model. Five of these models are associated with inflammatory rheumatic disease and the remaining five are properly functioning. In the Gaussian Network Model, the protein structures are modeled as an elastic network where the inter-residue interactions are harmonic. Important residues and the interaction pathways in the proteins are identified by focusing on the largest eigenvalue of the residue interaction matrix. Predicted important residues match those known from previous experimental and clinical work. Graph perturbation is used to determine the response of the important residues along the interaction pathway. Differences in response patterns of the two sets of proteins are identified and their relations to disease are discussed

CD4 receptor diversity in chimpanzees protects against SIV infection

Human and simian immunodeficiency viruses (HIV/SIV) use CD4 as the primary receptor to enter target cells. Here, we show that the chimpanzee CD4 is highly polymorphic, with nine coding variants present in wild populations, and that this diversity interferes with SIV envelope (Env)-CD4 interactions. Testing the replication fitness of SIVcpz strains in CD4+ T cells from captive chimpanzees, we found that certain viruses were unable to infect cells from certain hosts. These differences were recapitulated in CD4 transfection assays, which revealed a strong association between CD4 genotypes and SIVcpz infection phenotypes. The most striking differences were observed for three substitutions (Q25R, Q40R, P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles. In-silico modeling and site-directed mutagenesis identified charged residues at the CD4-Env interface and clashes between CD4- and Env-encoded glycans as mechanisms of inhibition. CD4 polymorphisms also reduced Env-mediated cell entry of monkey SIVs, which was dependent on at least one D1 domain glycan. CD4 allele frequencies varied among wild chimpanzees, with high diversity in all but the western subspecies, which appeared to have undergone a selective sweep. One allele was associated with lower SIVcpz prevalence rates in the wild. These results indicate that substitutions in the D1 domain of the chimpanzee CD4 can prevent SIV cell entry. Although some SIVcpz strains have adapted to utilize these variants, CD4 diversity is maintained to protect chimpanzees against infection with SIVcpz and other SIVs to which they are exposed

Modified residual soil for the fine-grained layer of capillary barriers

[THIS THESIS CONSISTS OF TWO (2) PARTS – THIS IS PART 1]. Capillary barrier, which is commonly defined as an earthen cover system consisting of a fine-grained soil overlying coarse-grained soil, has potential to be used as a slope protection technique. The contrast in hydraulic properties of the fine-grained layer and coarse-grained layer under unsaturated conditions impedes the downward water movement into the underlying protected system as demonstrated in this study. The Bukit Timah residual soil has been considered to be a suitable material for the fine-grained layer of capillary barrier system. Although residual soils are abundant in Singapore, it has high fine contents that cause the residual soil to have a low permeability and high shrinkage characteristics upon drying. In order to improve the hydraulic properties and the volumetric shrinkage characteristics, the residual soil was mixed with coarse-grained contents (i.e., gravelly sand or medium sand) or lime at different percentages. Results of the laboratory tests showed that the saturated permeabilities of the residual soil-gravelly sand mixtures and the residual soil-medium sand mixtures increased with the increase in the coarse-grained contents, while the saturated permeabilities of the residual soil-lime mixtures decreased with the increase in the lime percentages. The air-entry values of the soil-water characteristic curves (SWCCs) of the residual soil-gravelly sand mixtures and the residual soil-medium sand mixtures decreased with the increase in the coarse-grained contents and increased with the increase in the lime percentages. The permeability functions of the soil mixtures became steeper with the increase in the percentages of coarse-grained content and lime.MASTER OF ENGINEERING (CEE