Nazarbayev University

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    THE AXL INHIBITOR TP-0903 AND ARTESUNATE SYNERGISE TO INDUCE REACTIVE OXYGEN SPECIES, DNA DAMAGE AND APOPTOSIS IN TRIPLE NEGATIVE BREAST CANCER CELLS

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    Triple Negative Breast Cancer (TNBC) is an aggressive, often rapidly growing form of breast cancer. TNBC usually displays a basal molecular phenotype that associates with epithelial mesenchymal transition (EMT), a cellular program that confers chemoresistance and metastasis. Approximately 56% of TNBC cases show a basal-like gene expression profile and roughly 46% of TNBC patients have distant metastasis. In general, the absence of molecular targets in TNBC is the main obstacle for the development of an effective therapy. For example, TNBC does not respond to endocrine and anti-human epidermal receptor (HER2) treatments as it does not express estrogen and progesterone receptors (ESR/PgR) and human epidermal receptor 2 (HER2). In addition, though initially TNBC is more responsive to cytotoxic drugs compared to other subtypes, TNBC presents a higher relapse rate. Therefore, new anti-TNBC treatment strategies are urgently needed. Drug combination therapy for TNBC could rely on protocols whereby EMT reversal sensitizes TNBC to anti-cancer compounds that are effective against epithelial tumors. Recently, the anti-malaria compound Artesunate (ART) has been shown to exert cytotoxicity in breast cancer by generating reactive oxygen species (ROS) and DNA double strand breaks (DSBs). However, the effect was more pronounced in tumors of epithelial than mesenchymal origin. In this project, the hypothesis was to verify whether EMT inhibition could sensitize TNBC cell lines to ART cytotoxicity. To address this, two aims were pursued. Aim 1 verified whether receptor tyrosine kinase (RTK) AXL inhibitors TP-0903/R428 and AXL/ZEB1 knockdown sensitised TNBC cell lines to ART-generated ROS, DNA damage and apoptosis. Aim 2 was to test whether TP-0903 and AXL/ZEB1 knockout in TNBC cell lines suppressed expression of superoxide dismutase 1/2 (SOD1/2), glutathione peroxidase 8 (GPX8) and catalase (CAT)..

    GEOTHERMAL ENERGY POTENTIAL IN THE EASTERN SYR DARYA SEDIMENTARY BASIN, SOUTH KAZAKHSTAN

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    Since Kazakhstan is one of the world’s top polluters in terms of CO2 per capita emissions, the Strategy of Sustainable Energy of Future Kazakhstan until 2050 recommends a substantial reliance on renewable energy sources. Geothermal energy can be used in Kazakhstan's decarbonization agenda in addition to solar and wind energies. This research provides an initial evaluation of the geothermal energy potential in the Eastern Syr Darya sedimentary basin. The regional temperature distribution maps were produced with the input of depth-temperature profiles that represent the geothermal gradients of each observed area. Integration of temperature distribution maps with heat content and available water salinity indicated that the Arys and Shaulder areas, where salt layers are absent, are promising regions for geothermal energy extraction. Elevated geothermal gradients are potentially explained by the recent tectonic activities, particularly, strike-slip faulting and compressional tectonic regimes. An examination of the water chemistry determined the surface water and lateral groundwater flow recharge zones of the Eastern Syr Darya aquifers. Implementing experience in other countries, geothermal energy in the Eastern Syr Darya can be successfully extracted for electricity generation and heat supply

    I-V MODELS WITH THE TEMPERATURE DEPENDENCE OF GAN HEMT UTILIZING FEEDFORWARD NEURAL NETWORKS, RADIAL BASIS NEURAL NETWORKS, AND GENERALIZED REGRESSION NEURAL NETWORKS

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    This work contains aim to propose effective and reliable I-V models with temperature dependence to explain the characteristic of Gallium Nitride (GaN) High Electron Mobility Transistor (HEMT). Machine learning (ML) algorithms which are most useful in less time consumption by excluding multiple calculations were applied. Within algorithms of ML such as Feed Forward Neural Networks, Radial Basis Neural Networks, and Generalized Neural Networks developed by the MATLAB programming tool. During the calculations of the given dataset, network training was conducted by utilizing the Levenberg-Marquardt backpropagation algorithm. The number of hidden layers and the neurons they contain, the initialization methods for the weights and biases, and some other crucial parameters all play a significant role in determining the accuracy and effectiveness of the model. However, in order to provide the validity of the model, elapsed time and the capabilities of the proposed model are also assessed via various learning algorithms. As performance evaluation criteria, the suggested network model used means squared error (MSE), mean absolute error (MAE), Coefficient of Determination R2, and regression analysis. Therefore, between all these proposed neural networks’ architecture the comparison was analyzed to find out which of them is well fitting to model the behavior of the GaN HEMT that is grown on Silicon. It is predicted in several research works that the Artificial Neural Network ensures good generalization performance under change of the parameters of GaN HEMT

    COMPARISON OF 124 MHZ AND 250 MHZ FREQUENCY GROUND PENETRATING RADAR FOR THE DETECTION OF BURIED PIPES

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    The petroleum industry plays a crucial role in the global economy, but the construction and operation of underground pipelines in petroleum fields are associated with significant economic and environmental challenges. This thesis aims to evaluate the efficiency of ground-penetrating radar (GPR) and compare the effectiveness of Cobra Plug-In GPR (124 MHz) and LMX200 GPR (250 MHz) for detecting buried pipes. The study also addresses the problems of identifying buried pipes, including their depth, type, and location. A comprehensive literature review was conducted, and an experimental methodology was proposed. Measurements were taken in three different areas using both GPR systems in the summer and winter, and appropriate data processing and interpretation were presented. Area 1, located at coordinates 51°5’25.58"N, 71°23’14.64"E, contains objects that are buried between depths of 1.8 to 4 meters. In Area 2, situated at coordinates 51°5’20.98"N, 71°23’25.20"E, an empty pipe is buried at a depth of 3 meters in the trench. Area 3, located at coordinates 51° 5'28.11"N, 71°23'33.23"E, has underground utilities that are buried at a depth of 2.2 meters. The study demonstrated the effectiveness of GPR in detecting buried objects and highlighted the importance of the direction of the field survey and the use of different GPR systems. Comparing results obtained using different GPRs showed that 124 MHz and 250 MHz GPRs effectively detect underground pipelines, even in challenging conditions such as frozen soil. The results show that GPR systems are influenced by the geometry of the field survey direction and the impact of surface objects on the GPR image. The present study can inform future research and practices in the field of petroleum engineering, with potential applications for improving pipeline safety, reducing costs, and minimising environmental impact

    INVESTIGATION OF RHEOLOGICAL AND FILTRATION CHARACTERISTICS OF NIO NANOPARTICLES WATER-BASED DRILLING FLUID FOR HPHT DRILLING

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    The demand for drilling deeper wellbores to extract energy resources from deep reservoirs is growing rapidly. Drilling in formations where high temperatures and pressures are encountered is a challenging task. One important aspect of this challenge is to develop drilling fluids, which can function well in such harsh conditions. Use of nanoparticles (NPs) in various areas in petroleum engineering research has gained popularity in recent years. This is partly because of their favorable properties such as strong heat conductivity, large surface area that can significantly improve characteristics of the drilling fluid. The key benefits of using NPs in drilling fluids include a decrease in formation damage, improved heat transmission and lubrication, better control over fluid loss, and enhanced rheological properties. The main objective of this research work was to investigate the effect of using NiO NPs on rheological and fluid filtration characteristics of a water based drilling fluid prepared with this NPs under a wide range of pressure and temperature. NiO NPs were selected because they have already exhibited excellent results in EOR and asphaltene adsorption tests. The NiO NPs were characterization by using transmission electron microscope (TEM) and scanning electron microscopy (SEM). The rheological properties of the drilling fluid samples containing 0, 0.25, 0.5, and 1 wt.% of NiO NPs were measured at temperatures ranging from 25°C to 100°C. Regarding the filtration properties, the drilling fluid samples containing 0, 0.25, 0.5, and 1 wt.% of NiO NPs were tested at 130°C and 500 psi differential pressure. The results obtained from this research work showed that, the filtrate volume and filter cake thickness were lower in the test samples with NiO NPs than in the control sample. The SEM analyses of filter cake demonstrated positive effect of NiO NPs on morphology. The Herschel-Bulkley model fitted best to the experimental shear stress and shear rate data for the smart drilling fluid. The optimum concentration of NiO NPs for both rheological and rheological properties was found to be 0.25 wt%. Overall, adding NiO NPs to a water based drilling fluid enhanced its properties for HPHT condition

    OPTIMIZATION OF ANALYSIS OF POPULAR DOPING SUBSTANCES USING ULTRA HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC) AND GAS CHROMATOGRAPHY - MASS SPECTROMETRY (GC-MS) METHODS

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    Use of the prohibited and potentially dangerous substances in sports has become an actual problem for sports world. According to the list of sanctioned athletes, provided by Kazakhstan National Anti-Doping Centre. [1][3] Most frequently doped substances among them were: 1) anabolic androgenic steroids (AAS) 2) diuretics 3) metabolic modulators 4) beta-blockers. We will provide gas chromatographic analysis of these substances. Anabolic androgenic steroids are synthetic or human-made variants of the male sex hormone testosterone. They provide several of physiological effects and the most predominant is an anabolic effect. The desire to gain muscles, lose body fat, and improve athletic performance is the most common motivation for anabolic steroid abuse. [2] AAS increases the number of satellite cells, which plays key role in muscle fiber growth by incorporation of them into preexisting fibers to maintain a constant nucleus to cytoplasm ratio. High abuse of AAS is observed among professional bodybuilders and non-professional athlete’s cohort. [4] Diuretics are misused by athletes for several reasons: 1) reduction of body weight to compete in the lower weight category, 2) to minimize fluid retention in the body caused by steroid usage, as well as the concentration of other prohibited drugs in urine, to avoid being tested positive. Loop diuretics are commonly used among our athlete's cohort. These is the type of diuretics binding to the chloride ions binding site in sodium+/potassium+/ chloride- transmembrane domain. It will reduce ability of kidney to concentrate urine and increases athletes’ diuresis. [5] Meldonium (MET-88), it is an active substance of medical product Mildronate. It is used to treat ischemic diseases of the brain and heart. Meldonium inhibits L-carnitine production and promotes its excretion. Athletes found that Meldonium increase endurance performance, improve rehabilitation process after exercise, and enhance activation of CNS function. According to a WADA study, 172 samples have tested positive for meldonium since it was declared a banned substance, spanning a variety of sports and countries. [6] First line therapy of angina pectoris and hypertension are provided by using of the beta-blockers. By binding to beta-1, beta-2 receptors it provides negative inotropic and chronotropic effect. As a result, relaxation of muscle tissue and reduction of the heart rate will occur. [7] That is why, athletes participating in archery, shooting, gymnastics, golf, darts used it to improve their steadiness, equilibrium, and deftness

    HERITAGE UNDERFOOT: EXPLORING GRASSROOTS ACTIVISM AROUND ARKHARLY THROUGH A CRITICAL HERITAGE STUDIES PERSPECTIVE

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    Contemporary heritage practices are largely framed by official discourses rooted in definitions that overemphasize materiality. This thesis project aims to explore a more nuanced way of approaching heritage through the lens of critical heritage studies that posits heritage ultimately to be not primarily an object or site but rather about people and how people ‘use’ the past to help them address certain concerns in the present. The study focuses on grassroots activism around the Arkharly rock art site, revealing the motivations behind their participation and identifying factors that facilitated their success. This heritage movement was essentially a set of actions and practices through which people attempted to address current social issues in Kazakhstan to navigate change. The preservation movement itself was a practice of making meaning, which also fostered well-being, social bonding, and the creation of identities

    PRE-SERVICE TEACHERS' UNDERSTANDING OF INCLUSIVE EDUCATION IN SHYMKENT

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    This study examines pre-service teachers' understanding of the concept of inclusive education. In recent years, the reform of inclusive education has been actively promoted in Kazakhstan. One of the significant participants in the promotion of inclusive education in educational institutions is teachers. In this regard, the training of future teachers requires for the successful development of inclusion in schools, pre-service teachers need a proper understanding of the values of inclusion. This qualitative study aimed to examine pre-service teachers' understanding of their knowledge, attitudes, and readiness to implement inclusive practices in their future classrooms. This study was conducted using an interpretive research paradigm. A qualitative research method was chosen to explore the research questions in depth...

    TEACHERS’ PERCEPTIONS OF THE SOCIAL AND EMOTIONAL CHALLENGES OF CHILDREN WITH SEN IN ALMATY PRIMARY SCHOOLS

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    The Republic of Kazakhstan has initiated essential steps towards education for all. The ongoing shift to inclusive education supports and welcomes children with additional needs to the educational institutions, where mainstream classes are considered to have equal opportunities for everyone. However, the transition period to inclusive education faces some concerns towards adaptation of children with SEN and obstacles that impacts emotional and social aspects in their learning. ...

    EUROPIUM DOPED CARBON DOTS FOR SELECTIVE AND SENSITIVE DETECTION OF TETRACYCLINE

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    Tetracycline (TC) overuse in livestock farms has resulted in its widespread presence in water bodies, which can have a negative impact on the ecosystem and human health. Therefore, the aims of current study are to develop rapid, low-cost, shelf-life stable, sensitive, and selective detection method for TC antibiotic in water. As a result, an optical detection agent based on europium-doped carbon dots (Eu-CDs) was synthesized and extensivity characterized by physical-chemical methods. We found that after optimization process, the linear range of TC detection was found to be 0.01-5 μM, with an impressive limit of detection of 6.5 nM. The selectivity analysis with other antibiotics revealed that Eu-CDs are selective to TC only and show negligible response to other TC derivatives. It was shown that optimal pH for TC detection was ~ 7, and Eu-CDs retain high detection ability even in high sodium chloride (NaCl) solution. These results suggest that Eu-CDs can be used as a quick and effective colorimetric agent for TC detection in water samples

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