01. PhD Thesis
Permanent URI for this collection
Browse
Recent Submissions
Item Embargo CHARACTERIZATION OF A MOLECULAR FUNCTION OF DJ-1 AS CPGA HYDROLASE(Nazarbayev University School of Sciences and Humanities, 2024) Akhmadi, AizhanParkinson’s disease (PD) is a neurodegenerative disorder marked by a steady decrease in motor function due to the death of dopaminergic neurons in the substantia nigra, resulting in the reduced levels of dopamine in the striatum. Most cases of PD are sporadic, though 10- 15% of individuals have hereditary Parkinsonism linked to mutations affecting various proteins. Studying the molecular function of proteins linked to hereditary PD helps in understanding the mechanisms underlying the development and progression of this disease even in individuals with sporadic PD. Therefore, is of utmost biomedical significance. This thesis paper focuses on DJ-1 - a small protein mutated in rare cases of early-onset autosomal recessive Parkinson's disease. While the neuroprotective function of DJ-1 in humans is clearly established, there is no universally accepted mechanism clearly explaining how DJ-1 prevents the premature death of dopaminergic neurons. This uncertainty manifests itself in a very large number of functions that have been suggested for DJ-1 in different systems none of which definitively clarified its role in the genesis and advancement of Parkinson's disease. Our results describe in detail a novel function of DJ-1 as a hydrolase of cyclic 3-phosphoglyceric anhydride (cPGA). Formation of cPGA in glycolysis and cPGA hydrolase activity have been recently suggested based on indirect evidence however neither could be demonstrated in a direct experiment because of instability of cPGA. We synthesized cPGA from 3- phosphoglycerate using a standard dehydrating agent (EDC) in acidic conditions and, for the first time, demonstrated the existence of cPGA in solution by NMR. We established simple procedures for quantitative assessment of cPGA spectrophotometrically after converting it into a thioester. These methods allowed a comprehensive characterization of cPGA as an unstable electrophile with a high propensity to acylate biological nucleophiles. Further, we demonstrate that human DJ-1 and its E. coli homolog YajL are highly efficient cPGA hydrolases and provide evidence that the endogenous cPGA hydrolase activity of DJ-1 is both necessary and sufficient for the protection of proteins from acylation by cPGA. This work establishes cPGA as a novel reactive metabolite that can irreversibly acylate proteins and presents strong evidence that DJ-1 possesses a unique function that inactivates cPGA by hydrolysis. This new and unique function of DJ-1 provides the best explanation of neuroprotection by DJ-1 so far and opens a new and exciting chapter in research of reactive metabolites and their role in neurodegeneration.Item Open Access PRECISE VARIATIONAL CALCULATIONS OF S e , P e , AND De STATES OF FEW-ELECTRON ATOMS(NAZARBAYEV UNIVERSITY SCHOOL OF SCIENCE & HUMANITIES, 2024-06-30) Shomenov, ToreniyazThanks to the advancements in modern computer technology, it is now possible to compute the spectrum of small atoms and molecules with a degree of precision that is comparable with that of high-resolution spectroscopic experiments.Theoretical formulations, derived directly from the fundamental principles of quantum mechanics, have been developed and implemented on high-performance computer (HPC) clusters for conducting large scale quantum mechanical calculations. These computational codes, including those and the formalism summarized in this dissertation, are primarily used to enhance, predict, and validate the total energies corresponding to an angular momentum state of specific systems.Item Embargo MODIFICATION OF NANOMATERIALS WITH INTENSE PULSED ION BEAMS FOR PHOTOCATALYTIC APPLICATIONS(Nazarbayev University School of Sciences and Humanities, 2024-06-04) Abduvalov, AlshynThe world energy problem has been facing harsh challenges in the last few decades due to the increase in energy consumption of the growing world population and decreasing reserves of traditional carbon-based energy resources. Photoelectrochemistry (PEC) based solar water splitting is one of the potential paths for transforming renewable solar energy into green hydrogen fuel to meet energy expectations. In PEC water splitting, hydrogen is generated using semiconductor materials that can absorb sunlight and decompose water molecules into hydrogen and oxygen gases. Fabrication of highly effective, stable, and economically viable semiconductor photoelectrode materials, to increase their performance, and enhancing their photocatalytic activity has been proved to be a vital task for PEC solar water decomposition. Among all the suitable materials, WO3 has been reputed as a promising photoelectrode in the last decade due to the many criteria that it fits. The main current problems in WO3, based PEC water splitting systems are their low solar to hydrogen efficiencies and poor photocatalytic properties. Developing and applying new methods of surface modifications and engineering are favorable strategies to enhance photocatalytic properties of WO3. This thesis work is devoted to the study of surface modification of WO3 photoelectrodes with intense pulsed ion beam (IPIB) irradiation for photocatalytic properties enhancement and studying the effect of IPIB irradiation on solid state dewetting shape formation of plasmonic Ag nanoparticles (NPs). The thesis also reports strategies of combining plasmonic nanoparticles and downshifting photoluminescent NPs with WO3. IPIB irradiation is a method for modification of surfaces of materials with few hundreds keV energetic ions that penetrate deep into 1-2 micrometers. The outcomes of experiments show that surface engineering of WO3 photoelectrode with IPIB can enhance its photocatalytic properties and promote charge-carrier characteristics. The IPIB also gives opportunity to study shape formations of silver NPs and results exhibit huge influence of super-fast annealing on sphericity of the silver NPs. Simultaneous use of plasmonic NPs and fluorescent materials also proven to be effective method of photoactivity enhancement of WO3 thin films.Item Open Access VALUATION OF SOME NONLINEAR FINANCIAL CONTRACTS BY FINITE ELEMENT METHOD(Nazarbayev University School of Science and Humanities, 2024-06-07) Kazbek, RakhymzhanThis thesis proposes a methodology for dealing with nonlinear financial derivative models using the finite element method (FEM). Financial engineering solutions are in high demand to mimic realistic market scenarios. Significantly, the nonlinear partial differential equations (PDE) seen in security pricing theory make it almost impossible to develop explicit solutions. Therefore, one resorts to numerical approximations. The literature contains articles dealing with nonlinear contracts using the finite difference method (FDM), which practitioners frequently use. This thesis aims to provide some computational gain in time and an accurate solution to nonlinear contracts in the derivative market. The generality of the approach is extendable to other types of American and European nonlinear contracts. For nonlinear models, conventional FEM and Isogeometric analysis (IGA) are designed to be compared with benchmark results. The second-order P2-FEM performs better convergence properties than FDM and P1-FEM for convertible bond models. Moreover, the incorporation of an adaptive grid leads to the use of a few spatial discretizations. Usually, PDE models seen in financial engineering consist of convection-dominated or degenerate terms. The naive approach relies on stabilization techniques, as they allow for mitigating spurious oscillations. Alternatively, we use a relatively new approach, demonstrated by IGA-NURBS-based finite element technology, where the monotonic convergence is achieved with uniform and non-uniform grids without any stabilization techniques and validated within the benchmark region. Numerical experiments were conducted among well-known conventional FEM and FDM methods. The presence of the IGA framework has showcased the classical results by using fitted curve approximation. IGA demonstrates notable results based on the linear case, where the exact solution was achieved using a lesser number of grids than those by FEM and/or FDM. The post-processing Greek values are essential, as is the price of the contracts. The literature on computing the Greek values by FDM or finite volume methods (FVM) is vast. Specific models that consider frictionless markets may encounter challenges in accurately representing real-world scenarios. To satisfy the request of the derivative market, one shall consider the nonlinear pricing models that incorporate the specific request seen in financial derivative markets. The use of standard FDM or/and FEM leads to instability in the post-processing Greeks. In principle, a possible mitigation of such oscillations could be resolved using stabilization techniques. Employing NURBS basis functions with high compact support offers smoother Greek values, which may contribute to more reliable investment and trading strategies for hedging purposes.Item Open Access ALGORITHMIC PROPERTIES OF ROGERS SEMILATTICES(Nazarbayev University School of Sciences and Humanities, 2024-04-25) Tleuliyeva, ZhansayaThe thesis uses various approaches to explore the algorithmic complexity of families of subsets of natural numbers. One of these approaches involves investigating upper semilattices of computable numberings of a given family and their complexity in different hierarchies. These semilattices, known as Rogers semilattices, can help distinguish different structural properties of families of partial computable functions and computably enumerable sets. As a result, by using Rogers semilattices of computable numberings, we can measure the algorithmic complexity of the corresponding family.Item Open Access NEO-TRIBALISM IN KAZAKHSTAN: THE MANIFESTATIONS OF RU-BASED IDENTITY AND THE RETURN OF THE 'BATYRS'(Nazarbayev University School of Sciences and Humanities, 2024-04-30) Yergeshbay, TemirlanThe motivation behind composing this thesis stemmed from the perplexity on why the contemporary settled Kazakh society in Kazakhstan continues to not only align itself with tribal (ru) associations, but also actively participates in tribal activities on a consistent basis. The existing scholarship sheds light on some of the practices and places of memory and the existence of actors, apart from the state, that contribute their own funds for building a variety of commemorative sites in honor of their tribes and tribal warriors. Moreover, the prevailing research literature has predominantly focused on well-known commemorative locations. However, there is limited research on the study of the agency and inner workings of non-state local actors (ru-based associations) as full-fledged actors in the niche of national identity and development of national identity. Therefore, in order to examine the dynamic social processes on the ground, I ask a series of research questions. In particular, what are the manifestations of ru-based identity in Kazakhstan and how is it performed in contemporary society? Does such ru identity pose challenges to the national identity promoted by the state or complement it? The entanglement of the state rhetoric on tribal identity, on the one hand, and the promotion of local agenda by local actors, on the other, exhibit an interesting interweave, where they both feed and respond to each other. Using a firsthand ethnographic study based on tangible primary materials and semi-structured interviews with respondents that represent diverse Kazakh ru, such as Shegir, Qanly, Atyghai, Besterek and Zhaghalbaily, I revealed a compelling form of hybridity, in which there is a movement from 'tribal' towards 'nation-state,' in which the celebrated tribal warriors are portrayed as Kazakh heroes, rather than emphasizing the superiority of one particular ru over all Kazakhs. Findings also suggest that the existence of alternative voices in Kazakhstan exhibits both the agency of local institutions and the presence of local agenda in regions, while their activities ultimately complement the grand narrative of the state on promoting an integral element of national identity, based on promoting Kazakh national heroes.Item Open Access FRACTIONAL FISHER-KPP TYPE EQUATIONS ON STRATIFIED GROUPS.(Nazarbayev University, School of Sciences and Humanities, 2023-08-28) Jabbarkhanov, KhumoyunThis work investigates the fractional space-time behavior of the Fisher-KPP equation with initial boundary values. Notably, fractional versions of Fisher-KPP equations describe complex phenomena in cases where the classical local approach is limited. In this work, we combine different techniques from fractional calculus and non-commutative analysis, which provide new results for various fractional models involving the Fisher-KPP equation. Firstly, we prove that if the initial data lies between 0 and 1, then the global solution also belongs to the interval [0,1]. Secondly, we establish that the solution in the L^2 norm is bounded by the L^2 norm of the initial data. Lastly, we demonstrate that the model exhibits blow-up behavior on a finite time interval under certain conditions. Importantly, the results obtained in the non-commutative analysis cover many previously known results in the commutative case.Item Restricted NATIONALISM FROM THE MARGINS: A CRITICAL STUDY OF ELITIST HISTORIOGRAPHY AND POLITICS IN MĀWARĀʾ AL-NAHR AND KHURĀSĀN (LATER UZBEKISTAN, TAJIKISTAN AND AFGHANISTAN), 1800-1950.(School of Sciences and Humanities, 2023) Ahwar, Ahmad JaveedThis dissertation traces the history of national ideas in Māwarāʾ al-Nahr and Khurāsān, later known as Uzbekistan, Tajikistan, and Afghanistan, from the margins. This study follows the transformations of ideas of differences from the early nineteenth century when tribal, clan, sectarian, and regional affiliations prevailed in Māwarāʾ al-Nahr and Khurāsān to the time when Uzbek elites and Soviets in Bukhara, Khwārazm, and Russian Turkistan, and Pashtun nationalist elites in Kabul, laid the foundation of ethnonational-territorial identities of “Uzbek,” “Tajik,” and “Afghan,” and enforced boundaries between them. Furthermore, this dissertation pays particular attention to the de-Persianization projects (in the Bukharan People’s Soviet Republic/later Uzbek and Tajik SSRs and Afghanistan), which met with the insubordination of Tajiks. The existing literature on nation-formation in Central Asia and Afghanistan is either written or indirectly influenced by elite sources. The prevalence of methodological nationalism has contributed to the reification of state-led and elitist nationalisms bearing the interests of the ruling groups in Uzbekistan, Tajikistan, and Afghanistan. Consequently, non-dominant/marginalized groups are represented as either passive or non-existent. Elite nationalism, backed by methodological nationalism, has contributed to the misrepresentation, misinterpretation, and erasure of the history of non-dominant/subaltern groups in the official national historiographies and politics of Māwarāʾ al-Nahr and Khurāsān (later Uzbekistan, Tajikistan, and Afghanistan). This dissertation aims to better understand “non-elite/non-dominant nationalisms” in these countries by bringing enormous materials to light, arguing that it is the elites’ manipulation and control of state resources, media, statistics, and their suppression of non-dominant languages and non-dominant language groups that ensure the triumph of “majority-formation” and early nationalization projects in Uzbekistan and Afghanistan. This dissertation approaches Tajik national consciousness from the position of “subalternity,” considering that Tajiks have been subjects of Uzbek and Afghan khanates for centuries and distinguishes Tajik consciousness from the formation of the Tajik SSR. It is also the dominance of pro-Uzbek Khujandī elites throughout the history of the Tajik SSR and their failure to promote the Tajik cause addressing the interests of Tajiks of the Uzbek SSR and Afghanistan, which adds to the marginality of the Tajik cause. Among other factors, the territorial and ideological constraints imposed by the Soviet regime, the indifference of Khujandī elites to the Tajik cause, and de-Persianization policies of the Uzbek SSR and Afghanistan contributed to the failure of Tajik national consciousness. The comparative and transnational perspective not only helps us rectify iii Anglo-Russian historiographies, which often separates Afghanistan from Central Asian studies but also challenges elitist historiographies that reduce discussions on the Tajik people to the territory of Tajikistan, leaving off the Tajiks of Uzbekistan and Afghanistan unattended. Moreover, this study will place nationalist movements in broader historical and geographical contexts to explain how Tajik national consciousness failed and how Afghans and Uzbeks met with relative success. Furthermore, drawing upon the extensive research of primary sources such as court chronicles, local histories, Western travelogues, and the writings of leading pioneers of nationalism Maḥmūd Ṭarzī, Ṣadr al-Dīn ʿAynī, and ʿAbd al-Raʾūf Fiṭrat, this dissertation argues that the position of indigenous elitist sources (be it the feudal or nationalist one) towards non-dominant group is indistinguishable from the ruling class, pushing non-dominants to the margins. It is in European sources, in contrast to Edward Said’s notion of Orientalism, that non-dominant groups find a voice at times.