Design and synthesis of ligands targeting MIF family enzymes and their application in medicinal chemistry

This thesis addresses several aspects of the design and synthesis of ligands targeting the macrophage migration inhibitory factor (MIF) proteins family and their application in medicinal chemistry. The human MIF family in humans consists of MIF, its functional homolog D-dopachrome tautomerase (D-DT, also known as MIF-2), and the relatively unknown protein named DDT-like (DDTL). In this work we implement new drug design modalities and contribute to the development of therapeutic strategies against cancer and inflammatory diseases. Through thorough literature research, exploration of novel synthetic approaches, structure-activity relationship studies, and cell-based studies, we made a step forward toward understanding the function of MIF family enzymes in cells. Despite no MIF or D-DT targeted drugs being available on the market currently, due to the fact that creating the drug with promising efficacy and safety profile remains challenging, our work demonstrates the potential for future clinical studies in the field

A Survey of CUDA-based Multidimensional Scaling on GPU Architecture

The need to analyze large amounts of multivariate data raises the fundamental problem of dimensionality reduction which is defined as a process of mapping data from high-dimensional space into low-dimensional. One of the most popular methods for handling this problem is multidimensional scaling. Due to the technological advances, the dimensionality of the input data as well as the amount of processed data is increasing steadily but the requirement of processing these data within a reasonable time frame still remains an open problem. Recent development in graphics hardware allows to perform generic parallel computations on powerful hardware and provides an opportunity to solve many time-constrained problems in both graphical and non-graphical domain. The purpose of this survey is to describe and analyze recent implementations of multidimensional scaling algorithms on graphics processing units and present the applicability of these algorithms on such architectures based on the experimental results which show a decrease of execution time for multi-level approaches

The moving boundary problem in the presence of a dipole magnetic field

An exact analytic solution is obtained for a uniformly expanding, neutral, infinitely conducting plasma sphere in an external dipole magnetic field. The electrodynamical aspects related to the radiation and transformation of energy were considered as well. The results obtained can be used in analyzing the recent experimental and simulation data.Comment: 17 pages, 1 figure, Submitted to J. Phys. A, Math. and Genera

An exact solution of the moving boundary problem for the expansion of a plasma cylinder in a magnetic field

An exact analytic solution has been obtained for a uniformly expanding, neutral, infinitely conducting plasma cylinder in an external uniform and constant magnetic field. The electrodynamical aspects related to the emission and transformation of energy have been considered as well. The results obtained can be used in analysing the recent experimental and simulation data.Comment: 5 pages, 1 figur

Epigenetic regulation in macrophage migration inhibitory factor (MIF)-mediated signaling in cancer and inflammation

Epigenetic mechanisms are important for the regular development and maintenance of the tissue-specific expression of cytokine genes. One of the crucial cytokines involved in cancer and inflammation is macrophage migration inhibitory factor (MIF), which triggers the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling pathways by binding to CD74 and other receptors. Altered expression of this cytokine and altered activity states of the connected pathways are linked to inflammatory disease and cancer. Therapeutic strategies based on epigenetic mechanisms have the potential to regulate MIF-mediated signaling in cancer and inflammation

An exact solution of the moving boundary problem for the relativistic plasma expansion in a dipole magnetic field

An exact analytic solution is obtained for a uniformly expanding, neutral, highly conducting plasma sphere in an ambient dipole magnetic field with an arbitrary orientation of the dipole moment in the space. Based on this solution the electrodynamical aspects related to the emission and transformation of energy have been considered. In order to highlight the effect of the orientation of the dipole moment in the space we compare our results obtained for parallel orientation with those for transversal orientation. The results obtained can be used to treat qualitatively experimental and simulation data, and several phenomena of astrophysical and laboratory significance.Comment: 7 pages, 2 figures. arXiv admin note: substantial text overlap with arXiv:physics/060323

Кристаллохимические особенности простейших и смешанно–слоистых оксидов висмута

The family of bismuth ferroelectrics with a layered structure have for more than half a century caused great interest of researchers from theoretical and practical viewpoints. Theoretical interest is due to the specific structure of the compounds with high-temperature blurred ferroelectric transition, while practical one stems from the possibility of obtaining multifunctional materials. This work deals with the crystallochemical analysis of the least−studied species of the family, i.e., the simplest compositions of the “Bi2O3 − second oxide” type and complex precipitation structures, i.e., compounds with the so−called mixed−layered lattice structure.We suggest crystallochemical formulae to describe the compositions of the abovementioned structure types. We expect these formulae to provide for a more focused synthesis of new compounds of the family.Семейство висмутсодержащих сегнетоэлектриков со слоистой структурой уже более полувека вызывает устойчивый интерес исследователей как с теоретической, так и с практической точки зрения. Теоретический интерес обусловлен своеобразной структурой соединений, имеющих  высокую температуру размытого сегнетоэлектрического перехода, практический — возможностью получения многофункциональных материалов. Дан кристаллохимический анализ наименее изученных разновидностей семейства, а именно: простейшим составам типа «Bi2O3 — второй оксид» и сложным структурам прорастания — соединениям с так называемым смешанно− слоистым строением решеток. Для описания составов рассмотренных типов структур предложены кристаллохимические формулы, которые должны способствовать более целенаправленному  синтезу новых соединений семейства. Показано, что образование смешанно−слоистых структур срастания (прорастания) определяется условиями синтеза и не представляет исключительного явления. Вопрос об устойчивости (степени неустойчивости) таких сложных структурных образований остается открытым. Существование подобных  соединений вызывает интерес, который обусловлен очевидной возможностью синтеза новых составов семейства с многофункциональными свойствами. Кроме того, подобные системы представляют интерес и для физики твердого тела в целом как объекты исследования и получения дополнительной информации, касающейся размытых фазовых переходов

Automated, Accelerated Nanoscale Synthesis of Iminopyrrolidines

Miniaturization and acceleration of synthetic chemistry is an emerging area in pharmaceutical, agrochemical, and materials research and development. Herein, we describe the synthesis of iminopyrrolidine-2-carboxylic acid derivatives using chiral glutamine, oxo components, and isocyanide building blocks in an unprecedented Ugi-3-component reaction. We used I-DOT, a positive-pressure-based low-volume and non-contact dispensing technology to prepare more than 1000 different derivatives in a fully automated fashion. In general, the reaction is stereoselective, proceeds in good yields, and tolerates a wide variety of functional groups. We exemplify a pipeline of fast and efficient nanomole-scale scouting to millimole-scale synthesis for the discovery of a useful novel reaction with great scope

Photoplastic effects in chalcogenide glasses: A review

A synopsis of the various photoinduced changes of rheological, mechanical and elastic properties is presented in the first part of the article. After a critical appraisal of a large body of experimental data it suggested that the photoviscous effect, that is, the athermal decrease of viscosity of a non-crystalline chalcogenide upon illumination is the key for a plethora of photoinduced effects reported so far in the literature under different names. Morphic effects (shape or surface morphology) may ap-pear either in the presence or absence of external mechanical stimuli leading to the fabrication of a variety of technologically important photoprocessed structures. A few representative examples of photoplastic effects are described, in the second part of the paper, in some detail based on information provided by in situ Raman scattering and nanoindentation experiments.Comment: 12 pages, 10 figure