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Öğe Synthesis, Biological Evaluation, and Molecular Docking of Combretastatin and Colchicine Derivatives and their hCE1-Activated Prodrugs as Antiviral Agents(Wiley-V C H Verlag Gmbh, 2019) Richter, Michael; Boldescu, Veaceslav; Graf, Dominik; Streicher, Felix; Dimoglo, Anatoli; Bartenschlager, Ralf; Klein, Christian D.Recent studies indicate that tubulin can be a host factor for vector-borne flaviviruses like dengue (DENV) and Zika (ZIKV), and inhibitors of tubulin polymerization such as colchicine have been demonstrated to decrease virus replication. However, toxicity limits the application of these compounds. Herein we report prodrugs based on combretastatin and colchicine derivatives that contain an ester cleavage site for human carboxylesterase, a highly abundant enzyme in monocytes and hepatocytes targeted by DENV. Relative to their parent compounds, the cytotoxicity of these prodrugs was reduced by several orders of magnitude. All synthesized prodrugs containing a leucine ester were hydrolyzed by the esterase in vitro. In contrast to previous reports, the phenylglycine esters were not cleaved by human carboxylesterase. The antiviral activity of combretastatin, colchicine, and selected prodrugs against DENV and ZIKV in cell culture was observed at low micromolar and sub-micromolar concentrations. In addition, docking studies were performed to understand the binding mode of the studied compounds to tubulin.Öğe Part Special Issue: Project Management and Scheduling(Pergamon-Elsevier Science Ltd, 2011) Şerifoğlu, Funda Sivrikaya; Bilge, Ümit…Öğe Microstructural evolution and weldability of AISI 4042 steel(Trans Tech Publications Ltd, 2011) Gülenç, Behçet; Uygur, İlyas; Bayram, İsmail; Durgutlu, Ahmet; Kap, TuncayHigh carbon content and addition of other elements, such as Mn in steel, causes some difficulties in the weldability of these materials. In this study, pre and post heating processes were applied for the multipass welded specimens. Tensile test, notch impact test and hardness measurements were carried out, and microstructural features were examined. The weldability of these steels can be improved with the pre and post heat treatments. Maximum hardness values were obtained for the non-heat treated specimens due to large grain structure and high volume percentage of the pearlite content. Although applied heat treatments caused decrease in hardness values, an increase in tensile properties and toughness values at all temperatures occurred. Changes in these properties were explained in the light of the microstructure of the AISI 4042 steel specimens.Öğe Locating recycling facilities for IT-based electronic waste in Turkey(Elsevier Sci Ltd, 2015) Aras, Necati; Korugan, Aybek; Büyüközkan, Gülçin; Şerifoğlu, Funda Sivrikaya; Erol, İsmail; Velioğlu, Meltem NurtanışTurkey passed a directive on waste electric and electronic equipments in May 2012, which has been in effect since May 2013. This directive, like its counterparts in other countries such as the one in the European Union, holds producers and distributors responsible for the collection and recovery of a wide variety of end-of-use or end-of-life electronic products discarded by the consumers. The collection and recovery activities have to be planned and carried out with the help of municipalities. The success of this directive lies in the establishment of an efficient reverse logistics network design for the collection and recovery operations. An important component of this initiative is to determine the locations and capacities of recycling facilities that will handle the returned products with the objective of minimizing the total cost of opening facilities, operating them, and transporting the discarded products from their collection points to the facilities. We develop a multi-period capacitated facility location-allocation model that is formulated as a mixed-integer linear program. Since there is uncertainty in the number of used products that will be collected from the consumers, we generate a set of scenarios and try to obtain a solution with the objective of minimizing the maximum regret associated with the occurrence of different scenarios. The developed mathematical programming model is solved using estimates of discarded personal computers, inkjet and laserjet printers in 15 major cities of Turkey during the period 2013-2018. These estimates are based on real data that consist of scrapped items of these three types of products from 2007 to 2012. The results indicate that the best locations for opening recycling facilities are the largest three cities-of Turkey, i.e., Ankara, Istanbul, and Izmir. We perform additional experiments to quantify the benefit of constructing a multi-period model rather than a static one. (C) 2015 Elsevier Ltd. All rights reserved.Öğe Client-Contractor Bargaining on Net Present Value in Project Scheduling with Limited Resources(Wiley, 2009) Kavlak, Nursel; Ulusoy, Gündüz; Şerifoğlu, Funda Sivrikaya; Birbil, S. İlkerThe client-contractor bargaining problem addressed here is in the context of a multi-mode resource constrained project scheduling problem with discounted cash flows, which is formulated as a progress payments model. In this model, the contractor receives payments from the client at predetermined regular time intervals. The last payment is paid at the first predetermined payment point right after project completion. The second payment model considered in this paper is the one with payments at activity completions. The project is represented on an Activity-on-Node (AON) project network. Activity durations are assumed to be deterministic. The project duration is bounded from above by a deadline imposed by the client, which constitutes a hard constraint. The bargaining objective is to maximize the bargaining objective function comprised of the objectives of both the client and the contractor. The bargaining objective function is expected to reflect the two-party nature of the problem environment and seeks a compromise between the client and the contractor. The bargaining power concept is introduced into the problem by the bargaining Power Weights used in the bargaining objective function. Simulated annealing algorithm and genetic algorithm approaches are proposed as solution procedures. The proposed solution methods are tested with respect to Solution quality and solution times. Sensitivity analyses are conducted among different parameters used in the model, namely the profit margin. the discount rate, and the bargaining power weights. (C) 2009 Wiley Periodicals, Inc. Naval Research Logistics 56: 93-112, 2009
