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Synthesis of novel quinazoline derivatives as a potential multipotent therapeutics against Alzheimer's disease
Tošnerová, Daniela ; Karabanovich, Galina (advisor) ; Matouš, Petr (referee)
1 ABSTRACT Charles University, Faculty of Pharmacy in Hradec Králové Department of: Organic and Bioorganic Chemistry Mentor: Ing. Galina Karabanovich, Ph.D. Consultant: Ing. Barbora Svobodová, Ph.D. Student: Daniela Tošnerová Title of Thesis: Synthesis of novel quinazoline derivatives as a potential multipotent therapeutics against Alzheimer's disease Alzheimer's disease (AD) is a severe neurologic disorder. Current treatments only temporarily delay the progression of disease. The main limiting factor for developing of new therapeutic compounds is the simultaneous presence of multiple pathologies. Thus, a new group of potential drugs called multi-target directed ligands (MTDLs) emerged as an alternative option to combat AD. To this date, dozens of MTDLs have been published. As part of the experimetnal section of this thesis, a series of small molecules based on quinazoline scaffold was rationally designed with the intention to influence the activity of acetylcholinesterase, butyrylcholinesterase, monoamine oxidase A and B (MAO-A/MAO-B), and the GluN1/GluN2B subunit of N-methyl-D-aspartate receptor (NMDAR). Subsequently twenty-four new quinazoline derivatives were synthesized, and biologically evaluated. The overall results highlighted compound II-6h ((5E)-8-chlor-N-cyklohexyl-3-methyl-1-...
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Derivatives of boronic acids as potential drugs I.
Koucká, Kateřina ; Kučerová, Marta (advisor) ; Zitko, Jan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Student: Kateřina Koucká Supervisor: PharmDr. Marta Kučerová, Ph.D. Consultant: PharmDr. Petr Šlechta Title of diploma thesis: Derivatives of boronic acids as potential drugs I. The thesis includes the design, synthesis, and biological evaluation of boronic acid derivatives. These derivatives were prepared as hybrid compounds containing an amide linker, combining mainly pyrazinoic acids with 4-aminophenylboronic acid. Pyrazinamide is used as 1st line antituberculosis drug and 4-aminophenylboronic acid is a bioisoster of 4-aminobenzoic acid, which is a crucial precursor in the folate pathway. Bioisosteric replacement of the carboxylic group with boronic acid could afford the ability of the compounds to form a reversible covalent bond toward a potential biological target. The presented compounds were synthesized in a two-step reaction. The first step was the condensation of 4-aminophenylboronic acid pinacol ester with different derivatives of (hetero)aryl carboxylic acids, that underwent previous activation. The second step was the deprotection of boronic acid pinacol ester to obtain free boronic acids derivatives. The obtained compounds were screened for their in vitro...
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Factorization of quaternion and dual quaternion polynomials
Molnár, Michal ; Šír, Zbyněk (advisor) ; Vršek, Jan (referee)
In this thesis we provide basic algorithms for factorization of polynomials over quater- nions and dual quaternions. In the case of quaternions, we translate the art of finding roots of given polynomial into factorization. In the case of dual quaternions, we analyse the case of motion polynomials. We show when it is possible to find a factorization of such polynomial into linear terms and give a workaround if it is not. All of this is supplied with geometric interpretations. More specifically, we use the factorizations to construct mechanical linkages. 1
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A platform for creating and sharing interactive educational materials based on data from knowledge graphs
Matějík, Jakub ; Nečaský, Martin (advisor) ; Stenchlák, Štěpán (referee)
In this thesis, we will explore the possibilities of Solid technology and the use of Solid for application implementation. This application will be used to create mind maps and social networking for teachers and students. In order to do this, we will analyze the features of Solid for designing a social network application and its features and suitable use cases. Based on this analysis and user requirements, we will design the architecture along with the operations to make them convenient for the user. Next, we will learn about the concepts in Linked Data and analyze knowledge bases for use in our application. The result is implementing a proof-of-concept application that allows the intuitive creation of mind maps and their sharing within classes. 1
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Legal context and implications: analysis of blockchain regulation in selected jurisdictions
Bőhm, Erik ; Kučera, Zdeněk (advisor) ; Lederer, Vít (referee)
1 Legal context and implications: analysis of blockchain regulation in selected jurisdictions Abstract Blockchain technology has become a transformative force, offering transparency, security and efficiency across industries. However, its rapid growth brings regulatory challenges. This paper examines blockchain regulation, focusing on the European Union (EU) framework and comparative analysis with selected jurisdictions around the world. At the outset, the thesis seeks to clarify the basic concepts of blockchain and its regulatory implications. It tries to introduce the issues and frame the most important terms in a non- technical way. The thesis then examines EU legislation, including contemporary and forthcoming secondary regulations such as the Markets in Cryptoassets Regulation (MiCAR), and explores their objectives, challenges and implications for innovation and market participants. In addition, the paper conducts a comparative analysis of blockchain regulation in various jurisdictions, including the United States, the Cayman Islands and Singapore. By comparing regulatory regimes, it identifies trends, best practices, and ultimately a plethora of differences. It offers insight into regulatory preferences and implications for stakeholders, with an emphasis on business corporations and entrepreneurs in...
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Nursing Care in Patients with MRSA
Zajacová, Aneta ; Trojánek, Milan (advisor) ; Jirkovský, Daniel (referee)
The bachelor thesis "Nursing Care in Patients with MRSA" deals with the issue of barrier regimen in the context primarily with golden staphylococcus infection. The aim is to assess the attitudes of nursing staff about nursing care in patients with MRSA, analyze the adherence to contact precautions in the clinical practice and to identify the factors associated with potential non-adherence. The theoretical part of the thesis serves as an introduction to the topic, while the empirical part contains the results of the actual investigation and serves to explore the above objectives. The research method was a self-constructed questionnaire with 33 questions, which was distrubuted among the nursing staff in the surgical and internal inpatient wards of the adult part of Motol University Hospital. Responses from 67 respondents were included and the obtained data were statistically processed. The survey resulted in the following findings: Only 13 respondents (19 %) say that everyone on their ward always adheres to barrier measures. The most common situation where barrier measures are not adhered to is 'acute patient condition' with 27 respondents (40 %) and 'at night' with 12 respondents from the standard ward and only 1 from the ICU. The motivation for more consistent adherence to barrier measures is fear...
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The role of galectins in skin wound healing
Přitasilová, Adriena ; Sedlář, Antonín (advisor) ; Zimolová, Miluše (referee)
Galectins are proteins that bind β-galactosides through their Carbohydrate Recogni- tion Domain (CRD). There have been 16 types discovered in mammals, with only 4 not found in humans. They are present in various cell types and tissues and are involved in numerous physiological functions, such as apoptosis and cell proliferation, as well as in several pathological conditions, including inflammatory skin diseases. For example, anti- bodies against galectin-3 cause skin inflammation in lupus erythematosus. During wound healing in a pig model experiment, an upregulation of galectin-1 in the dermis and its neo-expression in the epidermis were observed, along with an increased level of galectin- 7. Galectin-1 plays a significant role especially in the formation of hypertrophic scars (HTS), which result from excessive collagen deposition during wound healing. HTS are erythematous and thick, causing cosmetic defects that could be addressed by modulating galectin activity during healing. Therefore, the aim of this bachelor thesis is to conduct a systematic literature review on the role of galectins in wound healing, considering both their positive and negative effects, with particular emphasis on the role of galectins and their ligands in the formation and regression of hypertrophic and keloid scars.
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Algorithms for integration of single-cell transcriptomic data
Ševčovičová, Zuzana ; Kolář, Michal (advisor) ; Abaffy, Pavel (referee)
Single-cell transcriptomics represents an innovative technique that allows for the examination of gene expression of individual cells in tissues or other complex biological samples. The data gen- erated through this approach offer crucial insights into various biological domains, such as em- bryology, oncology, and immunology. Understanding the functioning and mutual interactions of individual cells within tissues indeed requires knowledge of their individual expression profiles. Given the novelty of this method and technical challenges faced during data generation, com- parison of different samples may be difficult and affected by various batch effects. Effectively reconciling the information obtained regarding gene expression in distinct biological replicates or technical replicates generated by different methodologies may be onerous. The development of bioinformatics approaches to address this challenge is an ongoing process. The objective of this thesis is to: 1. survey the existing solutions for integration of single-cell transcriptomic data, 2. benchmark these solutions using publicly available datasets, specifically peripheral blood mononuclear cells, and 3. select the most suitable integration method to apply to a tumour microenvironment dataset generated by our laboratory. This bachelor...
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Semi-automatic approach to secondary sex diagnosis Rdss (Santos, 2021): Applicability in an archaeological sample
Galovičová, Tereza ; Brůžek, Jaroslav (advisor) ; Galeta, Patrik (referee)
The new R package rdss (Santos, 2021) aims to facilitate and fast track secondary sex diagnosis in large archaeological assemblages. This thesis is focused on evaluating the applicability of this new package in a real burial site dataset, as it has not yet been evaluated in this way. The applicability of the package was evaluated by comparing the results of sex diagnosis of a set of 307 adult individuals from the burial site at the 3rd church of the Great Moravian settlement in Mikulčice with the results of evaluation of the same set of individuals in previous studies by Stloukal (1967) and Zazvonilova and colleagues (2020). Using four methods of primary sex diagnosis, sex was estimated at a posterior probability level of 0.95 for 234 individuals (76.2% of the evaluated population). Secondary sex diagnosis using the rdss package estimated sex at a posterior probability level of 0.95 for 37 individuals (12.1% of the evaluated population). The total number of estimated individuals was 271 (88.3% of the evaluated population). This yield of sex diagnosis was comparable to the yield in the previous two studies. The three studies were compared using the masculinity index, which showed the same trend of male predominance over female in the population in all three cases. The agreement of the frequencies of...
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Knowledge of paramedical personnels in the areas of prevention and care of pressure ulcers
Rosová, Magdaléna ; Hromádková, Jaroslava (advisor) ; Nikodemová, Hana (referee)
The bachelor thesis "Knowledge of non-medical nursing staff in the field of prevention and treatment of decubitus" deals with the general knowledge of nurses in the field of prevention and treatment of decubitus in the internal and surgical wards of Motol University Hospital. Decubitus represents a widespread and increasingly topical problem in hospitalized patients, where it is essential that non-medical nursing staff are oriented in this area and know the latest trends in prevention and treatment. The aims: The aim of the study is to determine the level of knowledge of nurses in the field of treatment and prevention of decubitus working at the Department of Internal Medicine and Surgery of the 2nd Medical Faculty of Charles University and Motol University Hospital and the 3rd Surgical Clinic of the 1st Medical Faculty of Charles University and Motol University Hospital. The methods: To collect data for the empirical part, a quantitative survey was conducted using a non-standardized questionnaire. The target group was all nurses working in the standard ward and intensive care unit, the Internal Medicine and Surgery Clinics of the 2nd Medical Faculty of Charles University and Motol University Hospital and the 3rd Clinic of the 1st Medical Faculty of Charles University and Motol University Hospital....
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