102 research outputs found
The Effect of UV-A and Various Visible Light Wavelengths Radiations on Expression Level of Escherichia coli Oxidative Enzymes in Seawater
No full textWOS: 000320698100007Background: Light and photosensitizers affectthe survival of bacteria in natural environments. Also light and photosensitizers are used for disinfection of materials such as blood, blood products, and water. Objectives: The present study was aimed toinvestigate the effect of different wavelengths of visible light and UV-A on the synthesis of some oxidative stress enzymes of Escherichia coli (E. coli) in seawater. Materials and Methods: Seawater were filtered by using Whatmann No: 1 filter paper, followed by sterilization in the autoclave. The E. coli W3110 strain was grown at 37 degrees C, centrifuged, and transferred in seawater, then methylene blue was added to the seawater samples, with the exception of control samples. The seawater samples were incubated with white, blue, green, red, and UV-A light sources. Cell extracts were prepared by sonication, and then catalase, superoxide dismutase (SOD), glutathion peroxidase(GP), and glucose-6-phosphate dehydrogenase(G-6-PD) activities were measured. Results: It was found that in all studied wavelengths with or without Methylene Blue (MB), the level of all studied enzymes decreased remarkably when compared to dark controls. It was observed that the synthesis level of SOD, glutathione peroxidase GP, and glucose 6 phosphate dehydrogenase G-6-PD in E. coli decreased significantly in red light with respect to white, blue, and green light in seawater, to which methylene blue was added. In E. coli the decrease was 13% of G-6-PD expression, 10% of GP expression, and 17% of SOD expression in red light with MB after 16-hour incubation in seawater; however, these enzymes decreased to 45%, 84%, and 71% in white light, 33%, 47%, and 54% in blue light, 53%, 53%, and 64% in green light at the same incubation hours, respectively. Also, the enzyme acitivity in red light without MB did not show a significant difference when compared to other light sources. Conclusions: It was shown in the present study that red light among visible light sources has a crucial effect in decreasing the oxidative stress enzymes in seawater containing MB
You Shall Speak My Language : In Defense of Linguistic Specificity and Rigorous Comparativism
No full textIn this article, the author proposes approaching the concept of untranslatability in a dialectical framework, recognizing both its theoretical and methodological benefits and constraints, particularly in the cultural and political contexts. After introducing the idea of rhetorical irony in translation in Kilito’s text, the author provides a critique of academic practice that inadvertently reproduces cultural hierarchies. The author then argues for the need to revisit the pitfalls of the idea of untranslatability in its critique of universal frameworks, which are essential to political struggles, particularly in non-Western context. Conversely, in the last part, the author demonstrates that the need to preserve cultural and linguistic specificity is a fundamental principle of comparative practice in order to avoid being frozen in a historical presentism without the immediate intellectual and historical context. This article makes the case for rigorous comparativism with linguistic expertise, deep cultural knowledge, and a keen sense of historical context. Adopting Kilito’s subject position as non-Western critic, and reverting his postulation, the author proposes: you want to say something about my literature, you shall (and can) speak my language
Beyond World Literature: Reading Ahmet Hamdi Tanpınar Today [Special Issue]
No full textIn view of A.H. Tanpınar as the next Turkish author of world literature, and of his work as a national cultural product of exportation, the articles in this issue contextualize and critically examine such local and global appropriations. They do not make claims to authentic “local” literary categories or hold his work up to the global standards of readability; instead, in their variety and originality, they aspire to create an attentive and continuing dialogue that suggests a healthy future for Tanpınar studies. The article finally argues that in light of Tanpınar’s multiple and contradictory identities, a dialectical approach is necessary to understand his work
Mechanism of CuAAC reaction: In acetic acid and aprotic conditions
No full textProtonation of copper-triazolide is a distinctive and final part in CuAAC reaction which has kinetic importance such that it can even affect the product distribution. In the context of this study, the protonation mechanism of copper-triazolide was investigated with quantum mechanical calculations to have a deeper understanding of the mechanism. In aprotic conditions where the alkyne is considered as proton donor, the key finding of DFI' calculations performed in this study is that the activation energy barrier for the protonation step is greater than the cycloaddition step. In the absence of a strong proton donor the final protonation step is coupled with the alkyne deprotonation step in the catalytic cycle, which slows down the reaction. A conceivable pathway for acetic acid promoted CuAAC reaction on the basis of experimental and computational studies was also sought. With acetate as ligand, cycloaddition is a facile reaction and the energetics shows that it speeds up the cycloaddition step. Acetic acid in CuAAC reaction provides proton for the final protonation step in the catalytic cycle, decouples the protonation/deprotonation step by acting as a strong proton donor in the last step and facilitates protonation. The energetics presented herein are in accordance with the experimental proposals on rate-determining step in aprotic conditions and decreased reaction times obtained in the experiments in the presence of acetic acid. (C) 2016 Elsevier B.V. All rights reserved
The Molecular Basis of Drug Resistance against Hepatitis C Virus NS3/4A Protease Inhibitors
No full textCo-author Aysegul Ozen is a student in the Biochemistry Molecular Pharmacology program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.Hepatitis C virus (HCV) infects over 170 million people worldwide and is the leading cause of chronic liver diseases, including cirrhosis, liver failure, and liver cancer. Available antiviral therapies cause severe side effects and are effective only for a subset of patients, though treatment outcomes have recently been improved by the combination therapy now including boceprevir and telaprevir, which inhibit the viral NS3/4A protease. Despite extensive efforts to develop more potent next-generation protease inhibitors, however, the long-term efficacy of this drug class is challenged by the rapid emergence of resistance. Single-site mutations at protease residues R155, A156 and D168 confer resistance to nearly all inhibitors in clinical development. Thus, developing the next-generation of drugs that retain activity against a broader spectrum of resistant viral variants requires a comprehensive understanding of the molecular basis of drug resistance. In this study, 16 high-resolution crystal structures of four representative protease inhibitors - telaprevir, danoprevir, vaniprevir and MK-5172 - in complex with the wild-type protease and three major drug-resistant variants R155K, A156T and D168A, reveal unique molecular underpinnings of resistance to each drug. The drugs exhibit differential susceptibilities to these protease variants in both enzymatic and antiviral assays. Telaprevir, danoprevir and vaniprevir interact directly with sites that confer resistance upon mutation, while MK-5172 interacts in a unique conformation with the catalytic triad. This novel mode of MK-5172 binding explains its retained potency against two multi-drug-resistant variants, R155K and D168A. These findings define the molecular basis of HCV N3/4A protease inhibitor resistance and provide potential strategies for designing robust therapies against this rapidly evolving virus
Evaluating the Role of Macrocycles in the Susceptibility of Hepatitis C Virus NS3/4A Protease Inhibitors to Drug Resistance
No full textCo-author Aysegul Ozen is a student in the Biochemistry & Molecular Pharmacology program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.The hepatitis C virus (HCV) infects an estimated 150 million people worldwide and is the major cause of viral hepatitis, cirrhosis, and liver cancer. The available antiviral therapies, which include PEGylated interferon, ribavirin, and one of the HCV NS3/4A protease inhibitors telaprevir or boceprevir, are ineffective for some patients and cause severe side effects. More potent NS3/4A protease inhibitors are in clinical development, but the long-term effectiveness of these drugs is challenged by the development of drug resistance. Here, we investigated the role of macrocycles in the susceptibility of NS3/4A protease inhibitors to drug resistance in asunaprevir, danoprevir, vaniprevir, and MK-5172, with similar core structures but varied P2 moieties and macrocyclizations. Linear and macrocyclic analogues of these drugs were designed, synthesized, and tested against wild-type and drug-resistant variants R155K, V36M/R155K, A156T, and D168A in enzymatic and antiviral assays. Macrocyclic inhibitors were generally more potent, but the location of the macrocycle was critical for retaining activity against drug-resistant variants: the P1-P3 macrocyclic inhibitors were less susceptible to drug resistance than the linear and P2-P4 macrocyclic analogues. In addition, the heterocyclic moiety at P2 largely determined the inhibitor resistance profile, susceptibility to drug resistance, and the extent of modulation by the helicase domain. Our findings suggest that to design robust inhibitors that retain potency to drug-resistant NS3/4A protease variants, inhibitors should combine P1-P3 macrocycles with flexible P2 moieties that optimally contact with the invariable catalytic triad of this enzyme
Assessment of gas radiative property models in the presence of nongray particles
No full textIn this study, a radiation code based on the method of lines solution of the discrete ordinates method for the prediction of radiative heat transfer in nongray gaseous media is developed by incorporation of two different spectral gas radiative property models, banded spectral line-based weighted sum of gray gases (banded SLW) and gray wide band (GWB) approximation in the presence of nongray absorbing-emitting-scattering particles. The aim is to introduce an accurate and CPU efficient spectral gas radiation model, which is compatible with spectral fuel/ash particle property models. Input data required for the radiation code and its validation are provided from two combustion tests previously performed in a 300 kWt atmospheric bubbling fluidized bed combustor test rig burning low calorific value Turkish lignite with high volatile matter/fixed carbon (VM/FC) ratio in its own ash. The agreement between wall heat fluxes and source term predictions obtained by global and banded SLW models reveal that global SLW model can be converted to an accurate wide band gas model (banded SLW) which can directly be coupled with spectral particle radiation. Furthermore, assessment of GWB approximation by benchmarking its predictions against banded SLW model shows that GWB gives reasonable agreement with a higher CPU efficiency when the particle absorption coefficient is at least in the same order of magnitude with the gas absorption coefficient
Benchmarking grey particle approximations against nongrey particle radiation in circulating fluidized bed combustors
No full textInvestigation of the effect of grey/nongrey particle property models on radiative heat fluxes and source terms is performed in the dilute zone of the lignite-fired 150kW Middle East Technical University circulating fluidized bed combustor test rig. Predictive accuracy and computational economy of several grey particle models, geometric optics approximation (GOA) with average particle reflectivity (GOA2), GOA with Fresnel solution for particle reflectivity (GOA3), and Planck mean particle properties from spectral Mie solution are tested by benchmarking their predictions against spectrally banded solution of radiative transfer equation (RTE). Comparisons reveal that all grey models lead to accurate and CPU efficient radiative heat flux predictions. On the other hand, only GOA3 and Planck mean properties are in favorable agreement with the benchmark solution for both incident fluxes and source terms. These findings indicate that grey particle approximation with GOA3 is a more practical choice in solution of RTE as it eliminates the need for spectral calculations
Structural basis and distal effects of Gag substrate coevolution in drug resistance to HIV-1 protease
No full textFirst author Aysegul Ozen is a doctoral student in the Biochemistry and Molecular Pharmacology program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.Drug resistance mutations in response to HIV-1 protease inhibitors are selected not only in the drug target but elsewhere in the viral genome, especially at the protease cleavage sites in the precursor protein Gag. To understand the molecular basis of this protease-substrate coevolution, we solved the crystal structures of drug resistant I50V/A71V HIV-1 protease with p1-p6 substrates bearing coevolved mutations. Analyses of the protease-substrate interactions reveal that compensatory coevolved mutations in the substrate do not restore interactions lost due to protease mutations, but instead establish other interactions that are not restricted to the site of mutation. Mutation of a substrate residue has distal effects on other residues' interactions as well, including through the induction of a conformational change in the protease. Additionally, molecular dynamics simulations suggest that restoration of active site dynamics is an additional constraint in the selection of coevolved mutations. Hence, protease-substrate coevolution permits mutational, structural, and dynamic changes via molecular mechanisms that involve distal effects contributing to drug resistance
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