The diploma thesis analyzes the impact of financial crisis, the decline in the economic system of Kazakhstan and in particular the impact on the banking system. The work is divided into three parts, which analyzing the impact of the crisis on the economy in the world and Kazakhstan, on the banking sector, and each chapter is accompanied by recommendations for their solution, and the overall summary. The first chapter defines the concept of financial crisis, disassembled typology and their origins. In addition, it is characterized by economy, banking and financial sectors in Kazakhstan and cause a crisis in the Republic. The second chapter analyzes the impact of financial crisis on the banking system in Kazakhstan, including an analysis of the banking sector itself. Subsequently, is evaluated the impact of the crisis by monitoring of bank assets, the quality of loans, deposits, foreign debt and rating. The third chapter is devoted to the consequences and lessons for the economy and banking sector of Kazakhstan and the various approaches to solving the crisis in the countries of the Commonwealth of Independent States. At the conclusion of the work were reviewed and accepted hypotheses set out in the introduction.

ABSTRACT Equilibrium unfolding, single- and double-jump kinetic studies were conducted to determine the unfolding and refolding pathway of glutaredoxin 2. Structural changes for wild-type glutaredoxin 2 were monitored by far-ultraviolet circular dichroism and intrinsic tryptophan fluorescence for equilibrium unfolding and intrinsic tryptophan fluorescence for single- and double-jump kinetics studies. Glutaredoxin 2 possesses two tryptophan residues in domain 2. In order to monitor changes in domain 1, cysteine 9 at the active site cysteines, situated in domain 1, was labelled with an extrinsic fluorophore, AEDANS, and a mutant was created (Y58W glutaredoxin 2). The AEDANS labelled protein displayed decreased alpha-helical secondary structure and conformational stability. A high degree of cooperativity and similar conformational stability was observed during the two-state transition of the urea-induced equilibrium unfolding of both the wild-type and Y58W glutaredoxin 2 proteins therefore Y58W glutaredoxin 2 could be used to assess structural changes in the local environment of domain 1 during unfolding and refolding. Two phases of unfolding, the fast and slow phase, occurred for both the wild-type and Y58W proteins. The slow phase involves structural rearrangements that expose small amounts of surface area while the fast phase represents gross structural unfolding exposing large amounts of surface area. The isomerization of the Val48-Pro49 peptide bond to the trans conformation occurs during the slow phase and this isomerization is coupled to conformational unfolding of the protein. The structural separation of these phases could be represented by two structural units (unit x and unit y), these units do not represent domain 1 and 2. The units could also result in parallel refolding pathways with the folding of the x unit involving the fast and slow refolding phases and the folding of the y unit of structure is represented by the medium phase of refolding. The fast and slow phases are further separated as the fast phase represents the gross structural folding of glutaredoxin 2 for species with the Val48-Pro49 peptide bond in the native cis conformation. The development of the slow phase after extended unfolding delay periods during double-jump refolding studies, as well as the acceleration of the rate of the phase by the peptidyl prolyl isomerase hFKBP-12 proved that the phase involves a proline peptide bond iv isomerization. This phase represents a slow isomerization coupled with conformational folding similar to the slow unfolding phase. Complex unfolding and refolding kinetics indicated the involvement of kinetic intermediates during (un)folding.

Thesis advisor: Mary F. Roberts / Secreted phosphatidylinositol-specific phospholipase Cs (PI-PLCs) are often virulence factors in pathogenic bacteria. Understanding how these enzymes interact with target membranes may provide novel methods to control bacterial infections. In this work, two typical PI-PLC enzymes, from Bacillus thuringiensis (Bt) and Staphylococcus aureus (Sa), were studied and their membrane binding properties were examined and correlated with enzymatic activity. BtPI-PLC is kinetically activated by allosteric binding of a phosphatidylcholine (PC) molecule. MD simulations of the protein in solution suggested correlated loop and helix motions around the active site could regulate BtPI-PLC activity. Vesicle binding and enzymatic studies of variants of two proline residues, Pro245 and Pro254, that were associated with these motions showed that loss of the correlated motions between the two halves of PI-PLC were more critical for enzymatic activity than for vesicle binding. Furthermore, loss of enzyme activity could be rescued to a large extent with PC present in a vesicle. This suggests that binding to PC changes the enzyme conformation to keep the active site accessible. SaPI-PLC shows 41.3% sequence similarity with BtPI-PLC but has very different ways its activity is regulated. While it is kinetically activated by PC it does not in fact bind to that phospholipid. Enzymatic and membrane interaction assays showed that SaPI-PLC has evolved a complex, apparently unique way to control its access to PI or GPI-anchored substrate. (i) An intramolecular cation-pi latch facilitates soluble product release under acidic conditions without dissociation from the membrane. (ii) There is a cationic pocket on the surface of enzyme that likely modulates the location of the protein. (iii) Dimerization of protein is enhanced in membranes containing phosphatidylcholine (PC), which acts not by specifically binding to the protein, but by reducing anionic lipid interactions with the cationic pocket that stabilizes monomeric protein. SaPI-PLC activity is modulated by competition between binding of soluble anions or anionic lipids to the cationic sensor and transient dimerization on the membrane depleted in anionic phospholipids. This protein also served as a way to test the hypothesis that a cation-pi box provides for PC recognition site. This structural motif was engineered into SaPI-PLC by forming N254Y/H258Y. This variant selectively binds PC-enriched vesicles and the enzyme binding behavior mimics that of BtPI-PLC. Itaconic acid (ITA) is a metabolite synthesized in macrophages and related cell lines by a cis-aconitate decarboxylase (cADC). cADC activity is dramatically increased upon macrophage stimulation. In this work, the cell line RAW264.7 was used to show that cADC activity upon stimulation requires de novo protein synthesis. MS analyses of partially purified RAW264.7 protein extracts from stimulated cells show a large increase for immunoresponsive gene 1 protein (IRG1) and siRNA knockdown of the IRG1 reduces cADC activity upon stimulation. Suspected active site residues of IRG1 were identified by mutagenesis studies of the recombinant protein based on a homology structure model of fungal cADC. The cloning and overexpression of this enzyme should help clarify the cofactor-independent decarboxylation mechanism of this mammalian enzyme as well as open up future studies into the specific role of ITA in the mammalian immune system and cancers. / Thesis (PhD) — Boston College, 2013. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Cette thèse a pour objectif d’analyser les relations internationales de la Russie par le biais de sa démographie. Ce choix se justifie par l’ampleur des changements socio-politiques du pays depuis la fin de l’URSS, et par la gravité de la situation démographique russe depuis 1991. Le pays connaît un déclin démographique durable, et l’hétérogénéité démographique régionale se renforce. La question devient alors un enjeu politique majeur. Ce déclin démographique a des impacts sur le territoire, l’économie et l’armée, redéfinissant ainsi la puissance russe. Les théories des relations internationales montrent la complexité du lien démographie/relations internationales d’un Etat. Le facteur démographique semble peu intégré par les décideurs, mais apporte un complément d’analyse qui relativise le discours de politique étrangère russe. Le critère démographique pourrait jouer un rôle plus important sur des enjeux internationaux de la Russie. Il lui offre même des opportunités. La démographie a un rôle ambigu dans les politiques chinoise et asiatique de Moscou. Le déclin démographique russe a participé à une redéfinition des relations entre la Russie et les pays de la CEI. Les liens migratoires avec la Russie sont le résultat d’une interdépendance démographique qui devient économique et ensuite politique. La réalité démographique de l’espace post-soviétique favorise une politique de soft power de Moscou en Asie centrale, notamment au Kazakhstan. Le déclin démographique russe a donc contribué à un changement de la politique étrangère et de la place de la Russie dans le monde / This thesis aims to analyse Russia’s international relations through its demographics. The choice is justified by the scale of socio-political changes in the country since the end of USSR and by the seriousness of the Russian demographic situation since 1991. The country is facing a lasting demographic decline and the regional demographic disparity has been accentuated. The question becomes therefore a major political issue. This demographic decline has impacts on the territory, the economy and the army, redefining thus the Russian power. International relations theories show the complexity of the connection between demographics and international relations of a State. The demographic factor seems less integrated by leaders but it offers further analysis that puts Russian foreign policy rhetoric into perspective. The demographic criteria could have a larger influence on Russia’s international issues. It offers also opportunities. Demography plays an ambiguous role in Moscow’s Chinese and Asian policies. The Russian demographic decline has had an impact on the redefinition of the relations between Russia and CIS countries. Migration ties with Russia are the result of a demographic interdependence that becomes an economic and then political one. The demographic reality in the post-Soviet area favours a soft power based policy for Moscow in Central Asia, especially in Kazakhstan. The Russia demographic reality has contributed to a shift within Russian foreign policy and a change of position for Russia in the world.

AN ABSTRACT OF THE DISSERTATION OF BELAN M. KHALIL, for the Doctor of Philosophy degree in Plant Biology, presented July 11, 2018, at Southern Illinois University Carbondale. TITLE: ANALYSIS OF THE CIS-REGULATORY ELEMENT LEXICON IN UPSTREAM GENE PROMOTERS OF ARABIDOPSIS THALIANA AND ORYZA SATIVA. MAJOR PROFESSOR: Dr Matt Geisler Gene expression in plants is partly regulated through an interaction of trans-acting factors with the promoter regions of the gene. Trans-acting factor binding sites consist of short nucleotide sequences most often present in the upstream promoter region. These binding sites, the cis-regulatory elements (CREs), vary in structure, complexity and function. In binding to trans-acting factors, CREs connect genes to signalling and regulatory pathways that affect plant growth, development, and response to the environment. As words in a language, CREs and thus promoters can be analyzed by looking for spelling (patterns of nucleotides) associated with meaning (functions). Considering CREs as words in a language, this kind of analysis provides a great opportunity for comprehensive understanding of promoter language. Identification and characterization of CREs are challenging either experimentally or bioinformatically, and has previously been accomplished by discovering degenerate words, with ambiguous nucleotides. This kind of result implicitly makes a hypothesis that binding of a specific trans-acting factor is somewhat promiscuous (or sloppy) and that all words represented by a degenerate pattern are equally good at binding. In this study, we unpack the “degeneracy hypothesis” by systematically considering each combination of letters independently for CRE function. Our results demonstrate that not all degenerate combinations of published CREs have the same effect on gene expression. A systematic search and comparison of all 65,536 possible 8 bp CRE words were searched in the 500 bp and 1000 bp upstream promoters of all genes in Arabidopsis thaliana and Oryza sativa, respectively. The function of each CRE was evaluated by statistically comparing the presence or absence of the element in the promoter with that genes response (induction or suppression) to stimuli in 1691 public availability transcriptomes of differential gene expression data. Arabidopsis, a model dicot plant had a much larger number of such data sets, than rice, however rice was chosen as a comparison as it had the largest number of datasets for a monocot, the most distantly related plant group with sufficient data available. A comprehensive list of 8 bp words associated with differential gene expression, linguistically known as lexicon, was retrieved for both species by establishing that the presence of a CRE significantly increased the likelihood for differential expression by at least one stimulus. The lexicons were composed of 641 and 856 CREs respectively in Arabidopsis and rice, and there were only 78 shared CREs between the two lexicons. The CRE lexicon was then characterized for their strength and breadth of response, occurrence frequency, sequence complexity, and sequence conservation between two species. In Arabidopsis, evening element (EE) showed the strongest response to a cold stress transcriptome (p-value 10-99). In rice, the element AAACCCTA showed strongest response to a tissue specific transcriptome (p-value 10-79). The breadth of response varied between the two species due to number of transcriptomes used in the study. The element AAACCCTA and GCGGCGGA significantly correlated to 197 and 58 transcriptomes in both Arabidopsis and rice, respectively. On the other side of the breadth scale there were also many CREs with very restricted response. There were 291 and 258 CREs in Arabidopsis and rice, respectively, significantly correlated to a single stimulus. Occurrence frequency revealed that the most abundant CREs in Arabidopsis and rice genes were TATA box and TATA box like CREs. The structure of the CREs in the lexicon was also varied. CREs were distributed on seven levels of complexity. Level one comprised CREs having 8 copies of the same nucleotide, level seven comprised CREs having two copies of the same nucleotide. In Arabidopsis, out of 641 CREs, 314 were of level 6 complexity, which means having 3 copies of the same nucleotide. In rice, the majority of the lexicon, 263 CREs were of level 5 complexity, which means having 4 copies of the same nucleotide. Each CRE of the lexicon was correlated to at least one experimental condition in the differential gene expression data, but many were correlated to multiple and often related conditions such as drought, temperature and salinity. Therefore, each CRE was assigned a “meaning”, i.e. the associated stimuli, thus providing a sort of CRE function dictionary in addition to the lexicon itself. Many CREs possessed different meanings (termed homographs in language), and in many cases the meanings of different CREs overlapped like language synonyms. Sharing meanings (synonyms) was often among CREs with strong sequence similarity (homonyms or homophones), however, not in all cases. Analyzed as a linguistic aspect, CRE homonymity and synonymity was applied to explore the hypothesis “all CRE synonyms are also homonyms and all CRE homonyms are also synonyms.” To the end a single CRE was compared to all possible CREs with only one letter mismatch in their sequences are considered as homonyms. The CREs meaning was converted to a matrix of stimuli to generate clusters of synonyms that were analyzed for similarity of spelling (sequence). This analysis showed that not all homonyms are synonyms, however most synonyms are homonyms. Furthermore, despite a search of all one letter mismatches among homonyms, many of the functional homonyms shared smaller 4-5bp core sequence and only varied at the flanks. Synonyms being homonyms in the language of promoters raises a question, how did this evolve? Duplication of transcription factors in the genome generated transcription factor families where each family member shares the same core domain, usually a DNA recognition site. We here propose that CREs also duplicate during gene duplication process building CRE families in parallel. Members of CRE families may show different connectivity and affinity to individual members of transcription factors in a transcription factor family. In environmental sensors and developmental decision panel, this association of two families of interaction factors is called dense overlapping region (or DOR) and is a highly overrepresented network topology in biological systems. This also explains the degeneracy of initially discovered CREs. The fact is only a portion of nucleotide combinations implied by a degenerate CRE is bioactive, it represents an overlap of different members of a CRE family which is part of the process of family expansion and diversification and done as compensatory mutations as the family of transcription factors expanded and diversified. We also extensively studied CREs involved abiotic stress and identifies shared elements among abiotic stresses as well as abiotic stress specific CREs. Furthermore, CREs follow a time-sensitive response rule, which means some CREs participates in gene expression regulation only at a certain period during the course of exposure to the abiotic stress.

Vitamin A and its derivatives, known as retinoids, are involved in a number of functions in the developing and adult brain (Lane et al., 2005). Roaccutane (13-cis-retinoic acid, 13-cis-RA) is a synthetic retinoid used for the treatment of severe cystic acne, although its use has been controversially associated with adverse psychiatric events including depression. In this thesis, the presence of retinoid receptors in the rat hippocampus was verified and a similar profile of expression was observed in the rat raphe nuclei for the first time. The expression of retinoid receptors in brain regions that are implicitly associated with depression pathology provides proof of concept for retinoids to influence depressive behaviour. The ability of 13-cis-RA treatment to induce a pro-depressive profile in animal models of depression-related behaviour was tested. In the resident-intruder paradigm, adult rats treated for 7 or 14 days with 13-cis-RA (1mg/kg, i.p.) showed reduced aggressive behaviour, with a concomitant increase in flight submit and flight escape behaviours, compared with vehicle-treated controls. These findings are indicative of increased depression-related behaviour. However, chronic treatment did not alter depression-related behaviour in the forced swim test and sucrose consumption anhedonia paradigms The molecular mechanisms mediating 13-cis-RA-induced depression were investigated by examining monoaminergic gene expression, protein levels and neurotransmitter levels in rat brain tissue and plasma and an in vitro model. The majority of serotonergic components (SERT, 5-HT1AR, 5-HT1BR and MAOA) were not altered by chronic 13-cis-RA treatment, with the possible exception of TPH2 gene/protein expression and increased 5-HT levels in platelets. In fact, the expression of D2 dopamine receptor was significantly elevated in the RN46A-B14 cell line (10μM 13-cis-RA, 48 h) and was similarly elevated at the protein level in the juvenile rat hippocampus (1mg/kg/day, i.p., 6 weeks), suggesting dopaminergic pathways may be of importance. There was also a trend in the data to suggest that 13-cis-RA-treated juvenile rats may be more susceptible the molecular alterations than corresponding adult rats. xii

Submitted by PPG Ci?ncias Sociais (csociais-pg@pucrs.br) on 2018-10-25T19:12:11Z No. of bitstreams: 1 M?rcio_Soares_ Rodrigues_Dis.pdf: 1650077 bytes, checksum: f295f0bb4fc140f92ad684e3b5956a9d (MD5) / Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2018-10-26T13:46:49Z (GMT) No. of bitstreams: 1 M?rcio_Soares_ Rodrigues_Dis.pdf: 1650077 bytes, checksum: f295f0bb4fc140f92ad684e3b5956a9d (MD5) / Made available in DSpace on 2018-10-26T13:52:24Z (GMT). No. of bitstreams: 1 M?rcio_Soares_ Rodrigues_Dis.pdf: 1650077 bytes, checksum: f295f0bb4fc140f92ad684e3b5956a9d (MD5) Previous issue date: 2018-02-28 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / The main purpose of this research is to answer the following question: what were the factors that influenced the members of the MDB party to choose between PMDB or PDT when the multiparty system was restored in the late 1970? We intended to answer that question in two parts. First, we will do a historical analysis that goes from the multiparty system period - that began after the ?Estado Novo? regime - until the final moments of the bipartisanship system, in order to, as proposed by Panebianco (2005), prioritize the analysis of the foundation of the political parties, especially the sections of PTB and MDB from Rio Grande do Sul, as well as its development in such an unusual context as an opposing party, seeking to know how power were distributed in both organizations and the consequences of this interaction when the MDB party was extinguished. Then, we will analyze the political history of the MDB members from the elite of Rio Grande do Sul, searching for patterns in their political careers that may elucidate the choices between the two parties, highlighting the MDB leaders that have decided to join PMDB or PDT. Based on the journalistic coverage of the newspapers ?Zero Hora? and ?Folha da Tarde? from that period of time, we will also investigate how those leaders publicly justified their decision, in order to, considering the Panebianco (2005) study of the collective and selective incentives, verify if they use ideological and/or doctrinal arguments to explain their decisions, according to the narrative structured by the main leaders of those two political parties in that time: Leonel Brizola and Pedro Simon. / A presente disserta??o tem como objetivo principal responder ? seguinte quest?o: quais fatores colaboraram para a defini??o dos emedebistas ga?chos pelo PMDB ou PDT quando do retorno ao pluripartidarismo no final da d?cada de 1970? Buscamos responder das seguintes formas. Primeiro, faremos uma an?lise hist?rica do per?odo pluripartid?rio que se inicia ap?s o Estado Novo at? os momentos finais do bipartidarismo, visando assim, conforme proposto por Panebianco (2005), priorizar a an?lise do momento de nascimento das legendas, principalmente as se??es ga?chas do PTB e do MDB, bem como seu desenvolvimento em um contexto t?o at?pico para uma legenda oposicionista, buscando conhecer a estrutura e forma como o poder era distribu?do dentro de ambas ?s organiza??es, assim como a consequ?ncia desta intera??o no momento da extin??o do MDB. Segundo, atrav?s da an?lise da trajet?ria pol?tica da elite emedebista do Rio Grande do Sul, buscaremos encontrar padr?es de carreiras pol?ticas que possam elucidar a escolha da agremia??o a ser adotada com o retorno do pluripartidarismo, priorizando assim aqueles l?deres emedebistas que caminham para o PMDB ou o PDT. Com base na cobertura jornal?stica dos jornais Zero Hora e Folha da Tarde do per?odo, vamos analisar ainda como os l?deres emedebistas justificaram publicamente suas decis?es a respeito dos partidos adotados com a extin??o do MDB, visando assim, com base nos incentivos coletivos e seletivos de Panebianco (2005), verificar se estes utilizam de argumentos ideol?gicos e/ou doutrin?rios para explicar suas decis?es, conforme a narrativa constru?da pelos principais l?deres das duas legendas no per?odo, Leonel Brizola e Pedro Simon.

Cancer is one of the leading causes of death in the world. Approximately one fifth of deaths in the western industrial nations are caused by cancer. Every year several hundreds of thousands of new patients are diagnosed with cancer and several thousands die of cancer. Scientists have been conducting research from different angles for effective prevention, diagnosis and cure of Cancer. Ever since the genetic basis of cancer has been demonstrated, a race has been ignited globally in the scientific community to identify potential oncogenes and tumor suppressor genes. The genetics of the tumors are complex in nature where combinations of loss of function mutations in tumor suppressor genes and gain of function mutations in oncogenes cause cancers. The identification of these genes is extremely important to devise effective therapies to treat cancer. Insertional mutagenesis systems such as sleeping beauty provide an elegant way to identify genes involved in cancers. More and more researchers are adopting the Sleeping Beauty system for their insertional mutagenesis experiments to identify potential cancer causing genes. Given next generation sequence technologies and the vast amount of data they generate requires novel bioinformatics techniques to process, analyze and meaningfully interpret the data. The goal of this project is to develop a publicly available system for researchers worldwide to analyze the sequence data resulting from insertional mutagenesis experiments. This system will identify and annotate all the insertion sites resulting from the sequencing of the experiment. It will also identify the Common Insertion sites (CIS) and genes with Common Insertion Sites (gCIS). The Common Insertion Sites being the regions in the genome that are targeted more often than by chance. The whole system is accessible as a web application for use by researchers worldwide performing insertional mutagenesis experiments.

Copper Indium Gallium DiSelenide absorber layers are fabricated using a two stage manufacturing friendly process. The first step involves the sequential deposition of Copper and Gallium and co-deposition of indium and selenium at 275oC. This is followed by the second stage where the substrate is annealed in the presence of Selenium and a thin layer of copper is deposited to neutralize the excess Indium and Gallium on the surface to form the CIGS absorber layer. The top copper thickness as well as the time of deposition was varied to study the effect of Copper on the performance of the cells. Another recipe was developed for the precursor formation, where Gallium was co-evaporated with Indium and Selenium. A large bandgap shift was seen with this recipe and the open circuit voltage was increased. The performance of CIGS/CdS/ZnO solar cells thus fabricated was characterized using techniques like I-V, C-V, Spectral Response and EDS/SEM. Cells with open circuit voltages of 420-450 mV, short circuit currents of 33-38 mA/cm², fill factors of 58-62% and efficiencies of 9-11% were routinely fabricated.

The detection and annotation of cis-regulatory sequences is a difficult problem. There is currently no generally applicable experimental procedure or computational algorithm to identify the non-coding regions of the genome that serve to activate gene expression in a given cell type. The only indicator of cis-regulatory function is the conservation of a sequence in other genomes. Regions can then be tested one-by-one in transgenic assays but this is time-consuming in vertebrates. Only a limited number of these already validated cis-regulatory sequences have been curated in biological databases. One of the main advantages of the model organism Ciona intestinalis is that cis-regulatory tests can be conducted very easily and the result is observable after one day while the animal follows the chordate body plan. However, a sequence found to be active in this organism can currently not be mapped to genomes of other animals.