TR Dizin İndeksli Yayınlar Koleksiyonu / TR Dizin Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14365/4
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Article In Silico Approach for Identification of PI3K/MTOR Dual Inhibitors for Multiple Myeloma Treatment(Istanbul Univ, 2023-04-14) Masalaci, Ilke; Akdogan, Yaren; Mutlu, Ozge; Eyvaz, Hande; Kiraz, YagmurObjective: Multiple myeloma is a hematologic malignancy in which targeting phosphoinositide 3 kinase (PI3K) and/or the mammalian target of rapamycin (mTOR) individually has been shown to have anti-proliferative effects, however, inhibiting both proteins simultaneously has been reported to have more effective results for its treatment. The aim of this study is to determine the molecular interactions and predicted inhibitory effects of 40 different dual inhibitors on mTOR, PI3K delta, and PI3K gamma to propose potentially the most effective dual inhibitor that targets the PI3K delta and PI3K gamma isoforms as well as the mTOR proteins since those isoforms are known to be predominant in multiple myeloma patients. Therefore, the focus in this study is built around the specific targeting of the PI3K delta and PI3K gamma isoforms from the multiple myeloma perspective. Materials and Methods: In silico docking experiments were conducted to determine the binding energies for different ligands that target mTOR, PI3K delta, and PI3K gamma. Protein-dual inhibitor complexes and the amino acids and bond types were visualized to identify molecular interactions. The absorption, distribution, metabolism, and excretion properties of dual inhibitors were analyzed and evaluated. Results: The binding affinity values were found to be between -7 and -9.9 kcal/mol. The toxicity prediction values of the selected dual inhibitors were obtained from the Pro-Tox-II web tool and classified according to the globally harmonized system of classification of labeling of chemicals. Conclusion: Correspondingly, among all dual inhibitors, Vistusertib is determined to be a promising compound against multiple myeloma cells by inhibiting both PI3K delta and PI3K gamma as well as mTORC1/2.Article The Question of Interaction Between Tax and Criminal Proceedings in Turkiye in Terms of Ecthr Jurisprudence(Istanbul Univ, 2022-08-29) Bahceci, BarisThis study deals with the question of harmonization between tax and criminal proceedings in Turkish law resulting from the condition of sufficiently close in substance and in time as applied within the scope of Article 4 of Protocol No. 7 (P7-4) of the European Convention on Human Rights (ECHR). In this context, the study first examines the developmental line of jurisprudence regarding the European Court of Human Rights (ECtHR) and then examines how the elements of substance and time have been interpreted, starting with the Glantz and Nykanen judgments against Finland in 2014 and ending with the Kristjansson judgment against Iceland in 2021. Afterward, the study finds aspects of the case-law as created by the ECtHR to be incompatible with Turkish law. Because no legal regulation exists in Turkish law that provides a connection between substance and time, the final section proposes a solution to the identified problems. In this context, a systematic distinction has been made between crimes that do and do not require knowledge of tax techniques. The study recommends with regard to the first type of crime that an investigation into deliberateness be carried out by the tax court with its expert knowledge of tax techniques in order to avoid a repetitive evaluation, and then based on the result, the criminal court should determine the real person or entity who perpetrated the crime. With regard to the second type of crime, no knowledge of tax technique is required for the investigation into intent and thus in conclusion and unlike with the first case, the tax court is recommended to take the criminal court decision into account.