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New Advances in High-quality Screening by Capillary Electrophoresis: A Unified Platform for Thermodynamic and Kinetic Characterization of Protein-Small Molecule Interactions / High-quality Screening by Capillary ElectrophoresisGavina, Jennilee 12 1900 (has links)
<p> The development of high-quality screening assays for the identification of biologically active ligands is critical in drug discovery. This thesis is aimed at developing new advances m capillary electrophoresis (CE) for the characterization of the conformational stability and enzymatic activity of protein targets with small molecules. CE provides a convenient platform for unbiased assessment of multiple thermodynamic and kinetic parameters associated with biomolecular interactions involving regulatory protein or isomerase enzymes, where various sample pretreatment steps can be integrated directly in-capillary during analysis. The first two chapters of the thesis (Chapters II, III) outline the development of dynamic ligand exchange-affinity capillary electrophoresis (DLEACE) as a novel strategy for the screening of allosteric ligands based on the differential stability of urea-induced unfolding of various apolholo-protein states of cAMP receptor protein constructs. This work introduced a label-free and multivariate approach for ligand selection based on complementary thermodynamic parameters that allowed for determination of the dissociation constant of protein-ligand interactions over a wide dynamic range (> 10^4, Kd = nM-mM). The subsequent two chapters of the thesis (Chapters IV, V) describe the development of a novel kinetic assay for unbiased characterization of isomerase activity associated with D/L-amino acid metabolism using hydroxyproline epimerase as a model system. Stereoselective resolution of various hydroxyproline isomers was accomplished via off-line or on-line chemical derivatization with dynamic complexation usmg chiral selector(s) in order to screen potential inhibitors for putative epimerase and racemase activity. The integration of both thermodynamic and kinetic strategies for differentiation of mutant from wild-type enzymes was important for revealing the function of a catalytic acid/base cysteine pair in the epimerase active site. Overall, this thesis outlines an integrative framework based on CE for high-quality screening, which is relevant in reducing the high attrition rate of lead candidates in drug development. </p> / Thesis / Doctor of Philosophy (PhD)
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K problémům členění na významy v překladovém slovníku / On Sense Division in a Bilingual DictionaryHagenhoferová, Lucie January 2014 (has links)
This thesis deals with the dividing the dictionary entry into several "sub-meanings", i.e. with the sense division, and with the closely related ordering of these "sub-meanings", i.e. with the sense ordering, with the bilingual passive German-Czech dictionary in the centre of interest. This thesis deals shortly also with the discriminating the senses by different means, i.e. with the sense discrimination. With these three subjects chronologically following the lexicographic decisions the matter of equivalence and the understanding of the term of meaning are correlated. In the theoretical part of this thesis the specifics of the sense division and the sense ordering in the monolingual and in the bilingual lexicography are introduced, in the practical part of this thesis the possibilities of the sense division and the sense ordering are exemplified with ten chosen substantive lemmas prepared for the Large German-Czech Academic Dictionary in progress. For every lemma the most suitable arrangement of the lemma is suggested, which is then compared with the corresponding dictionary entry in the source dictionary Duden - Deutsches Universalwörterbuch. The differences between the arrangements of the microstructure illustrate the necessity of the revision and eventual modification of the adopted structure...
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Určování astronomických tížnicových odchylek přímým měřením / Determination of astronomical vertical deflections by field observationsPetrová, Kateřina January 2017 (has links)
This thesis deals with use of the measuring system MAAS-1 for direct determination of vertical deviations at the points specified field. The main input data are geographical and astronomical coordinates of points. The aim of this thesis is to complete the processing of data measured in the locality.
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Návrh předpjatého komorového mostu / Design of prestressed box gireder bridgeHofírek, Radovan January 2013 (has links)
This thesis deals with bridging of a lowland valley and the creek Dolanský in the section Jánovce – Jablonov on the Slovak motorway D1. Four variants of the bridge have been developed. Subsequently prestressed single box gilder with large overhangs that are supported by precast struts was selected as the most suitable variant. The construction of the bridge will take place in a formwork suspended on overhead launching scaffolding. The static assessment according to the Europan standard has been drawn up for this variant. The load of the bridge is projected according to the ČSN EN 1991-2 - Traffic loads on bridges and the dimensoin of concrete structures according to the ČSN EN 1992-2 - Concrete bridges - Design and detailing rules. The calculation of load is done using computer software SCIA Engineer 10.1 and Midas Civil.
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Porovnání spolehlivostních metod při stanovení návrhové únosnosti mostu / Comparison of reliability methods in determining the design resistance of a bridgeŠplíchal, Bohumil January 2022 (has links)
This thesis deals with the topic of assessing the design load-bearing capacity of a prestressed concrete railway bridge structure. The determination of the structure’s load-bearing capacity is carried out using probabilistic nonlinear analysis using the finite element method. Load-bearing capacity is determined for the recommended limit states. A fully probabilistic approach is compared to other reliability semi-probabilistic methods, such as the ECoV method according to Červenka and Eigen ECoV, and deterministic methods, like partial safety factor method, or the method according to ČSN EN 1992-2. The results are evaluated in terms of accuracy, consistency and time consumption for each method.
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Vliv rekonstrukce prvků krátkodobé životnosti na cenu nemovitosti / Influence of Reconstruction Short Life Structural Members on Estate PriceHlaváčová, Tereza January 2012 (has links)
The master´s thesis deals with the influence of short-term reconstruction on the p rice of real estate. There are discussed the basic concepts, which are necessary for understanding problems, and commonly used methods for valuing property according to the purpose of valuation in the theoretical part. There are analysed these methods for particular house in the practical part – method of valuation, comparative public notice, revenues method, comparative non-promulgation method. They are investigated due to the influence of imitated reconstruction. In conclusion the influences of reconstruction methods are compared each other.
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Sledování respiračních funkcí u pacientů po operaci hrudního koše dle Nusse / Monitoring of the Respiratory Functions in Patients after the Rib Cage Surgery according to NussSvobodová, Jana January 2011 (has links)
Objective: The goal of the thesis "Monitoring of the Respiratory Functions in patients after the Rib Cage Surgery according to Nuss" was to confront the present knowledge about respiratory functions and the strength of respiratory muscles of patients with inherited pectoral deformity pectus excavatum, to compare it with my own measuring and to find out about their development after the surgical correction according to Nuss. Methodology: There were 15 patients being monitored (13 men and 3 women), who underwent spirometric and bodypletysmographic examination and the occlusal mouth pressures were determined before the surgery. The same pulmonary function tests were run in the course of 4 to 10 months (7.1 months on average) on all the patients, the control determination of mouth pressures is available for 13 of them. Results: In the entry tests, compared to adequate values the patients in this file had increased residual lung capacities (RV 142%, p=0.001; ITGV 116.2%, p=0.004; RV%TLC 133.8%, p=0.002; ITGV% 116.1%, p=0.001) at the expense of statistically lower vital lung capacity (VC 81.9%, p=0.0004) and inspiratory reserve capacity (IC 84.2%, p=0.0003), while the total lung capacity remained unaltered (TLC 99.7%, p=0.877). The obstructive parameters of these patients were significantly altered (FEV1 95.7%,...
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Vliv Feldenkraisovy metody na tělesné schéma / The effect of the Feldenkrais method on body schemaBestová, Zuzana January 2012 (has links)
Bibliografic identification BESTOVÁ, Zuzana. The effect of The Feldenkrais method on body schema. Prague: Charles University in Prague, 2nd Faculty of Medicine, Department of rehabilitation and exercise medicine, 2012. 96 pages. Supervisor Mgr. Magdaléna Lepšíková. Abstract The diploma thesis deals with neurophysiological concept of body schema and evaluation of the effect of the Feldenkrais method (FM) on its quality. The research comprises two groups of probands without motor system disorders. The participants passed an investigation of the body schema quality by the following tests: a test of estimation of body dimensions (width of mouth, width of shoulders, width of hips and length of foot), a modification of Petrie's test, a test of proprioception and a test of graphestesia. The examination was accomplished before FM investigation and after the course. The first group (group A) comprised 13 individuals (5 males, 8 females) who participated in a semestral course of FM, the second group of probands (group B) included 17 individuals (3 males, 14 females) underwent a two days long FM program. A significant improvement (p = 0,0027) in the estimation of the length of foot was detected after FM intervention in group B. There was not a significant improvement in any of estimated body dimensions in group A....
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Objektivizace modifikovaného testu "Pracovní křivka podle Emila Kraepelina a Richarda Pauliho" pro manuální činnosti Podtitul: Test lanových svorek / Validation of Kraepelin & and Pauli's Working curve Test modified for hand activities. Subtitle: Test of rope clampsFricová, Jitka January 2016 (has links)
of the Diploma Thesis: The presented diploma thesis is focussed on the standardization of the modified test of Working curve by Emil Kraepelin and Richard Pauli, in agrément with the project PREGnet - basic methodology for ergodiagnostic examination in Czech Republic. The methodology was modified for manipulation activities and termed Test of rope clamps. It handles contraindications in the use of basic test and absence of standardized ergodiagnostic and endotherapeutic tests, tools and procedures in the field of examination and therapy of hand function. The thesis is both theoretical and empirical and it is based on the quantitative type of research. Theoretical part is represented by a literature surfy oriented on the test of Working curve by Emil Kraepelin and Richard Pauli, its modified vision and its practical application. Practical part is composed of a psychometric study determining normative data and development of test documentation. Representative sample was selected by accidental selection method from economically active healthy Czech population. Techniques for quantitative type of research were used for data collection. Collected data were treated and analysed by methods of descriptive statistics. Developed documentation and the normative data for Test of rope clamps can be used in...
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Avaliação da Aprendizagem na Disciplina Estrutura Política e Gestão Educacional: Um Estudo Comparativo entre os Cursos Presencial e Semipresencial da UFC/UAB / Assessment of Learning in the Discipline Policy Framework and Management Education: A Comparative Study Between the Classroom and Blended Courses of UFC/ UABSOUSA, Maria Iracema Pinho de January 2012 (has links)
SOUSA, Maria Iracema Pinho. Avaliação da aprendizagem na disciplina Estrutura Política e Gestão Educacional: um estudo comparativo entre os Cursos Presencial e Semipresencial da UFC/UAB. 2012. f. Tese (Doutorado em Educação) – Universidade Federal do Ceará, Faculdade de Educação, Programa de Pós-Graduação em Educação Brasileira Fortaleza-CE, 2012. / Submitted by Liliane oliveira (morena.liliane@hotmail.com) on 2012-08-09T12:40:59Z
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Previous issue date: 2012 / This study had the objective of investigating the process of teaching and learning in a Structure, Politics and Education Management (SPEM) course, trying to compare the blended course (which uses distance learning education – DLE) against the pure classroom course. This comparison was made using the results obtained through the application of an instrument with a evaluation scale about the relationship between the knowledge of the basic education legislation and other aspects that involve this course in the Federal University of Ceará regarding apprenticeship. Two DLE classes from the Language Bachelor’s were followed in the cities of Ipueiras and Russas along with other two, based in Fortaleza, under pure classroom teaching in different semesters. With this purpose a review was made on subjects such as DLE in Brazil, Cyberculture and Technology, Education Legislation and Learning Evaluation, conducting to deeper thoughts on the undergraduate teaching from different areas taking into account the need of some knowledge from them in aspects related to Education legislation with the perspective of their future actions in basic education. The investigation is of both qualitative and quantitative nature, in view of the analysis and search for understanding measurable educational phenomena from the observation of subjects involved in the process of teaching and learning during the course. The selected sample according to the nature of this study comprises undergraduate students from various semesters enrolled in the SPEM course from both the Federal University of Ceará and the Brazil Open University System, for a total of 81 individuals. Data collected revealed the necessity of reading and studying subjects from the SPEM classroom course related to educational legislation and a crucial point. From the results, a brief discussion was made on the aspects that involve the SPEM course in the curriculum at the undergraduate level, considering limits and possibilities of the evaluation in the classroom courses and through virtual means of learning / O estudo teve como objetivo investigar o processo de ensino e aprendizagem na disciplina Estrutura, Política e Gestão Educacional (EPGE) buscando comparar o ensino semipresencial (que faz uso da modalidade de Educação a Distância – EAD) com o ensino presencial. Esta comparação foi feita a partir dos resultados obtidos através da aplicação de instrumento do tipo escala de avaliação sobre a relação entre o conhecimento da legislação para atuar com educação básica e outros aspectos que envolvem a disciplina de graduação nos cursos de Licenciatura da Universidade Federal do Ceará no tocante à aprendizagem. Foram observadas duas turmas de EAD do Curso de Letras com estudantes matriculados nos polos de apoio presencial nos municípios de Ipueiras e Russas, e outras duas turmas de semestres distintos matriculados no mesmo curso de graduação presencial em Fortaleza. Para esse propósito, foi realizada uma revisão de literatura referente a temas tais como: EAD no Brasil, Cibercultura e Tecnologia, Legislação Educacional, Avaliação da Aprendizagem, conduzindo o estudo a uma reflexão mais aprofundada com relação à formação de licenciandos de diferentes áreas tendo em vista a necessidade de algum domínio por parte dos mesmos em temas relacionados à legislação educacional visando perspectivas de suas atuações futuras na educação básica. A natureza da investigação é tanto qualitativa quanto quantitativa, tendo em vista análise e busca na compreensão de fenômenos educacionais mensuráveis decorrentes da observação com os sujeitos envolvidos no processo de ensino e aprendizagem durante a disciplina. A amostra selecionada de acordo com a natureza da investigação foi constituída por estudantes de variados semestres matriculados na disciplina de EPGE das licenciaturas oferecidas pela Universidade Federal do Ceará e também através do Sistema Universidade Aberta do Brasil, totalizando 81 sujeitos. Os dados coletados revelaram como ponto importante a necessidade de leitura e estudo por parte dos estudantes da modalidade semipresencial para conteúdos específicos do programa da disciplina EPGE quanto à legislação educacional. A partir dos resultados da investigação é realizada uma breve discussão sobre os aspectos que envolvem a oferta da disciplina EPGE no currículo de cursos de licenciaturas destinados à formação de professores em nível superior considerando os limites e as possibilidades da avaliação da aprendizagem na forma presencial e em meios virtuais de aprendizagem
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