This work solves the problems with taking care of capital goods in the firm Komponenty, a. s. The work is elaborated from the analysis of present situation in the firm, the heed is oriented to the most important areas, especially the organisation and maintenance activity and taking care of assets. The result of the performed analysis is identification of bad spots. Proposal is submitted in the second part of the work in order to solve the problems found by performing the work. At the end economical evaluation of the proposal and statement of assumptions for the applications of the extended work result to firm use is performed.

Jana Jíchová: Crime and its Perception in Urban Environment ABSTRACT Crime is an important social phenomenon that affects many aspects of the functioning of society and the life of every person. It also represents an important interdisciplinary topic that deals with a number of disciplines, including geography. Logically, there is a thematic and methodological overlap; each of the sciences emphasize on different aspects of crime, using various methods and research approaches, interpretations, and therefore contributes to the knowledge of crime differently. The importance of geography is particularly in the enrichment of the crime research on spatial dimension and contributes to its cognition through analysis of the distribution of crime and studies of perception of crime. Although this type of studies is well established in Western crime research, in the Czech geography is paid to them only little attention. This doctoral thesis introduces geography of crime in the Czech context, discusses its theoretical and methodological developments and its applicability and application in our cities.. More emphasis is put on the concept of fear of crime, which constitutes an essential component of feeling of safety affecting daily life, the use of urban space and spatial mobility of individuals. Better understanding of...

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<p>  </p> <p>  </p> <p>An approach to modify surface flashover of insulators in vacuum by limiting duration of its high-current stage responsible for the damaging effects of a classic flashover was developed. The flashover assembly was made by TorrSeal-gluing copper electrodes (10 x 10 x 0.5 mm) to both side of an alumina ceramic sheet (0.635 mm thick). The modified flashover, referred to as low energy surface flashover (LESF), was achieved by utilization of a high voltage (HV) nanosecond pulser or addition of a resistor in series with the LESF assembly when HV DC was utilized. The duration of LESF was visualized by ICCD fast photography to be 100 – 200 ns accompanying electrical characteristics measurements, which gave insight of a way to control the flashover duration by inserting additional capacitor in parallel with the LESF assembly to increase the stored energy prior to breakdown. The LESF assembly was tested for > 1.5 million consecutive pulses and remained operational, while operation in high energy regime with parallel capacitor (4nF) lead to significant damage after 200 pulses.</p> <p>The igniting capabilities of LESF assembly was demonstrated via successful triggering of vacuum arc and a prototype pulsed plasma accelerator. The plasma plume propagation speed and angular distribution was measured via Langmuir probes. Efforts were made for temporally resolved spectroscopy measurements. </p> <p>The LESF assembly was improved by replacing TorrSeal-gluing with direct bonding of copper to alumina ceramic and changing the configuration from parallel plate to coaxial. The improved assembly was demonstrated to be operational throughout and after an extended test of 10 million pulses. A higher resolution ICCD photography revealed finer LESF discharge features including initial bright line across the insulator developing into a double-jet plasma plume propagating at around 10⁵m/s and later-on point-like attachment of the discharge column to the electrodes. The composition of the plasma and erosion pattern on the LESF assembly was studied via SEM/EDX analysis, which supported the predominant ceramic erosion over copper electrodes erosion.</p>

Cette thèse propose trois contributions principales pour l'imagerie en microscopie à fluorescence. (1) Modélisation du système optique : nous avons étudié les approximations gaussiennes des moindres carrés pour les réponses impulsionnelles optiques (PSFs) limitées par la diffraction du microscope en champ large (WFFM), du microscope confocal (LSCM), et du microscope confocal à disque rotatif (DSCM). Les situations paraxiales/non-paraxiales et 2D/3D sont toutes considérées. Les PSFs sont décrites par les intégrales de diffraction de Debye. Nous avons dérivé les paramètres gaussiens optimaux pour la PSF 2D paraxiale du WFFM, sous les normalisations Linf et L1. Pour les autres PSFs, avec la normalisation Linf, des paramètres quasi-optimaux sont explicitement dérivés par l'appariement des séries de Maclaurin. Ces modèles approximatifs gaussiens peuvent être calculés rapidement, et facilitent considérablement la modélisation des objets biologiques. (2) Débruitage des images de fluorescence : les images issues des LSCM et DSCM ont des statistiques purement poissoniennes ou poissoniennes et gaussiennes mélangées (MPG) selon les différents modes d'acquisition du microscope. Deux approches sont proposées pour restaurer une image poissonienne. La première méthode, basée sur les tests d'hypothèses dans le domaine de Haar biorthogonale, est particulièrement appropriée à estimer rapidement les intensités poissoniennes régulières dans des données de grandes tailles. Notre deuxième méthode, basée sur une transformée stabilisatrice de variance (VST), permet de gaussianiser et stabiliser un processus poissonien filtré. Cette VST peut être combinée avec de nombreuses transformées multi-échelles, ce qui conduit aux VSTs multi-échelles (MS-VSTs). Nous montrons que les MS-VSTs permettent de restaurer efficacement des structures saillantes de diverses formes (isotropes, linéiques et curvilignes) avec un (très) faible flux photonique. La MS-VST est également généralisée pour débruiter les données MPG et pour extraire les taches fluorescentes dans les données MPG. (3) Détection super-résolutive : nous avons revu et étendu les résultats des limites de la résolution pour les sources ponctuelles issus des théories de la détection, de l'estimation, et de l'information. En particulier, nous avons proposé d'appliquer la VST pour étudier les limites de la résolution dans le cas d'observations poissoniennes ou MPG. Les résultats sont asymptotiquement consistants et les expressions sont de formes closes. Nous avons également généralisé une approche de super-résolution qui est basée sur l'ajustement de modèle paramètrique et la sélection de l'ordre de modèle pour localiser un nombre inconnu de spots ou de bâtonnets. Cette méthode permet non seulement de localiser les sources ayant des configurations spatiales complexes, mais aussi d'extraire les objets séparés par des distances inférieures à la résolution optique de Rayleigh (super-résolution).

Eine Auswertung der Unfallzahlen der Kommunalen Unfallversicherung Bayerns von 2007 bis 2011 zeigte, dass es innerhalb Bayerns große regionale Unterschiede im fahrradbezogenen Unfallgeschehen auf dem Schulweg gibt. Durch ein mehrstufiges multimethodisches Studiendesign wurde der Frage nachgegangen, ob es in den unfallbelasteten Landkreisen tatsächlich gefährlicher ist mit dem Rad zur Schule zu fahren und nach den Ursachen der räumlichen Diskrepanzen gesucht. Mittels regressionsanalytischer Verfahren konnte ein Großteil der räumlichen Varianz der Unfallraten auf die unterschiedlichen Voraussetzungen zum Radfahren zurückgeführt werden: Je weiter und je hügeliger der Weg zur Schule ist, umso weniger Unfälle ereignen sich, wobei vermutet werden kann, dass dieser Zusammenhang Folge der niedrigen Radnutzung ist. Doch auch bei Landkreisen mit ähnlichen Radfahrbedingungen, etwa bei den kreisfreien Mittelstädten Rosenheim und Schweinfurt, lassen sich große Unterschiede im fahrradbezogenen Unfallgeschehen feststellen. Um zu überprüfen, ob auch hierfür die variierende Radnutzung verantwortlich ist, fand im Rahmen einer Fall-Kontroll-Studie eine Messung der Schulwegmobilität in diesen beiden Städten statt, wodurch das jeweilige expositionsbereinigte Unfallrisiko berechnet werden konnte. Die Erhebung zeigte, dass die distanz- und zeitbezogenen Inzidenzraten der beiden Untersuchungsregionen nahezu identisch sind. Dies belegt, dass das Unfallgeschehen hauptsächlich von der Radnutzung abhängt, wobei die Ursachen für die abweichende Radnutzung durch eine Schüler- und Lehrerbefragung empirisch untersucht wurde. Unfallschwerpunkte im Schülerradverkehr sind also statistische Artefakte, da aus der Unfallrate ohne die Kenntnis der Radnutzung auf das Unfallrisiko geschlossen wurde. Regionsunabhängig aber ist das fahrradspezifische Unfallrisiko auf Schulwegen deutlich höher als etwa auf dem Weg zur Arbeit, was die Dringlichkeit verdeutlicht, präventiv tätig zu werden. / Analyzing the number of accidents between 2007 and 2011, registered by the Kommunale Unfallversicherung Bayern, revealed great regional differences in bicycle traffic accidents on the way to school in Bavaria. A multi-stage, multi-methodical study design was set up to find answers to the question, if it is actually more dangerous to cycle to school in districts with high accident rates. The reasons for regional discrepancies in these accident rates were identified, while a varying rate of bicycle use was detected the main cause for interregional differences in the number of accidents.Regression analysis indicated that the majority of spatial variance in accident rates is based on different cycling conditions; the further and more hilly the way to school, the less accidents occur. However, it can be assumed that this correlation is a consequence of lower bicycle use. On the other hand in regions with similar cycling conditions great differences in bicycle traffic accidents can be observed, which the study shows for the district-free, mid-sized cities Rosenheim and Schweinfurt. This case-control-study on the way-to-school mobility measured for the two cities the exposition-adjusted risk of accident and was performed to reveal if this effect is also caused by varying bicycle use rates. The study pinpointed the fact that distance- and time-related incidence rates are almost identical in both study regions,which is an evidence for bicycle use rates mainly affecting the number of accidents. The reasons for differing bicycle usage were examined empirically by questioning pupils and teachers. As a conclusion, accident black spots in pupils` bicycle traffic are statistical artefacts, as the accident risk was gathered from the accident rate without knowing bicycle use rates. However, regardless of the region, cycling to school is remarkably more dangerous than cycling to work, a fact that underlines the urgency to act preventively.

As Mucopolissacaridoses são erros inatos do metabolismo, fazem parte das doenças lisossômicas de depósito e ocorrem devido à deficiência na atividade de enzimas que catalisam a degradação de glicosaminoglicanos. O objetivo desse estudo foi aperfeiçoar o diagnóstico bioquímico das Mucopolissacaridoses dos tipos I, VI e VII, estabelecendo o uso do tampão fosfato de sódio 20 mmol/L pH 7,0 (tampão universal - TU) e outros parâmetros bioquímicos. Nesse trabalho foi aprimorada a técnica de medida de atividade da beta-glicuronidase (GUSB), enzima deficiente na MPS VII, reduzindo a quantidade de reagentes em 4 vezes e a utilização do tamanho dos picotes de sangue impregnado em papel filtro (SPF) para 1,2 mm. Estudamos a cinética da atividade da GUSB determinando o pH ótimo (4,4), Km (1,25 mM), Vmáx (594,48 nmol/h/mL), termoestabilidade (inativação significante da enzima a partir de 60 min a 60 ºC) e tempo e temperatura de armazenamento (até 30 dias à 4, 25 e 37 ºC, acima de 60 dias à -20 ºC) e estabelecemos um intervalo de referência para a atividade da GUSB em amostras de indivíduos saudáveis nessa metodologia (174,4 nmol/h/mL a 781,9 nmol/h/mL). Estabelecemos o uso do TU para determinação das atividades da alfa-iduronidase (IDUA), arilsulfatase B (ASB) e GUSB medindo a atividade enzimática em SPF eluído nesse tampão e correlacionamos com a técnica espectrofluorimétrica já padronizada para cada enzima em SPF de 1,2 mm em amostras de indivíduos saudáveis As correlações foram positivas e os coeficientes de validação da técnica estavam dentro dos limites aceitáveis. As médias de atividade determinadas para indivíduos saudáveis foram: 14,65 + 4,35 nmol/h/mL (IDUA), 22,51 + 5,09 nmol/h/mL (ASB) e 531,92 + 121,05 nmol/h/mL (GUSB). Foram analisados parâmetros bioquímicos envolvidos em estresse oxidativo no plasma de indivíduos com MPS VI e comparados com MPS I e controles saudáveis. A medida da atividade da SOD não diferiu entre os grupos, a atividade de CAT encontrava-se diminuída tanto em MPS VI quanto em MPS I e a dosagem de TBARS estava aumentada em ambas as MPS em relação aos controles. A partir desse estudo, foi possível padronizarmos e aperfeiçoarmos novas técnicas para o diagnóstico laboratorial para a MPS I, VI e VII além de introduzir o estresse oxidativo como um possível marcador no uso da terapia de reposição enzimática. / Mucopolysaccharidoses are inborn errors of metabolism, being part of lysosomal storage diseases and occuring due to deficiency in the activity of enzymes that catalyze the degradation of glycosaminoglycans. The aim of this study was to improve the biochemical diagnosis of Mucopolysaccharidoses of types I, VI and VII, establishing the use of 20 mmol/L sodium phosphate buffer pH 7.0 (universal extraction buffer - UEB) and other biochemical parameters. In this work, the activity measurement technique of beta-glucuronidase (GUSB), enzyme deficient in MPS VII, has been improved, reducing the amount of reagents in 4 times and using the size of dried blood spots (DBS) for 1.2 mm. We studied the kinetics of GUSB activity by determining the optimum pH (4.4), Km (1.25 mM), Vmax (594.48 nmol/h/mL), thermostability (significant inactivation of the enzyme from 60min at 60 ºC) and storage time and temperature (up to 30 days at 4, 25 and 37 °C, above 60 days at -20 °C) and established a reference range for GUSB activity in samples from healthy subjects in this methodology (174.4 nmol/h/mL at 781.9 nmol/h/ mL). We established the use of TU to determine the activities of alpha-iduronidase (IDUA), arylsulfatase B (ASB) and GUSB by measuring the enzymatic activity in DBS eluted in this buffer and correlated with the standardized spectrofluorometric technique for each enzyme in DBS of 1.2 mm in samples from healthy individuals Correlations were positive and the validation coefficients of the technique were within acceptable limits. The activity means determined for healthy individuals were 14.65 ± 4.35 nmol/h/mL (IDUA), 22.51 ± 5.09 nmol/h/mL (ASB) and 531.92 ± 121.05 nmol/h/mL (GUSB). Biochemical parameters involved in oxidative stress in the plasma of individuals with MPS VI and compared to MPS I and healthy controls were analyzed. Measurement of SOD activity did not differ between groups, CAT activity was decreased in both MPS VI and MPS I and the TBARS dosage was increased in both MPS compared to controls. From this study, it was possible to standardize and improve new techniques for laboratory diagnosis for MPS I, VI and VII, besides introducing oxidative stress as a possible marker in the use of enzyme replacement therapy.

<p>The ability to accurately predict binding free energies from computer simulations is an invaluable resource in understanding biochemical processes and drug action. Several methods based on microscopic molecular dynamics simulations exist, and in this thesis the validation, application, and development of the linear interaction energy (LIE) method is presented.</p><p>For a test case of several hydrophobic ligands binding to P450cam it is found that the LIE parameters do not change when simulations are performed with three different force fields. The nonpolar contribution to binding of these ligands is best reproduced with a constant offset and a previously determined scaling of the van der Waals interactions.</p><p>A new methodology for prediction of binding free energies of protein-protein complexes is investigated and found to give excellent agreement with experimental results. In order to reproduce the nonpolar contribution to binding, a different scaling of the van der Waals interactions is neccesary (compared to small ligand binding) and found to be, in part, due to an electrostatic preorganization effect not present when binding small ligands.</p><p>A new treatment of the electrostatic contribution to binding is also proposed. In this new scheme, the chemical makeup of the ligand determines the scaling of the electrostatic ligand interaction energies. These scaling factors are calibrated using the electrostatic contribution to hydration free energies and proposed to be applicable to ligand binding.</p><p>The issue of codon-anticodon recognition on the ribosome is adressed using LIE. The calculated binding free energies are in excellent agreement with experimental results, and further predict that the Leu2 anticodon stem loop is about 10 times more stable than the Ser stem loop in complex with a ribosome loaded with the Phe UUU codon. The simulations also support the previously suggested roles of A1492, A1493, and G530 in the codon-anticodon recognition process.</p>

The ability to accurately predict binding free energies from computer simulations is an invaluable resource in understanding biochemical processes and drug action. Several methods based on microscopic molecular dynamics simulations exist, and in this thesis the validation, application, and development of the linear interaction energy (LIE) method is presented. For a test case of several hydrophobic ligands binding to P450cam it is found that the LIE parameters do not change when simulations are performed with three different force fields. The nonpolar contribution to binding of these ligands is best reproduced with a constant offset and a previously determined scaling of the van der Waals interactions. A new methodology for prediction of binding free energies of protein-protein complexes is investigated and found to give excellent agreement with experimental results. In order to reproduce the nonpolar contribution to binding, a different scaling of the van der Waals interactions is neccesary (compared to small ligand binding) and found to be, in part, due to an electrostatic preorganization effect not present when binding small ligands. A new treatment of the electrostatic contribution to binding is also proposed. In this new scheme, the chemical makeup of the ligand determines the scaling of the electrostatic ligand interaction energies. These scaling factors are calibrated using the electrostatic contribution to hydration free energies and proposed to be applicable to ligand binding. The issue of codon-anticodon recognition on the ribosome is adressed using LIE. The calculated binding free energies are in excellent agreement with experimental results, and further predict that the Leu2 anticodon stem loop is about 10 times more stable than the Ser stem loop in complex with a ribosome loaded with the Phe UUU codon. The simulations also support the previously suggested roles of A1492, A1493, and G530 in the codon-anticodon recognition process.

This thesis describes bioanalytical methods for drug determination in biological matrixes, with drugs in focus used against diseases largely affecting low-income countries. Solid-phase extraction is used for sample cleanup, and processed samples are analyzed by liquid chromatography. Developed bioanalytical methods are validated according to international guidelines. Eflornithine (DFMO) is a chiral drug, used for treating human African trypanosomiasis. A bioanalytical method for determination of DFMO enantiomers in plasma is presented. The enantiomers are detected by evaporative light-scattering detection. The method has been applied to determination of D-DFMO and L-DFMO in rats, after intravenous and oral administration of racemic DFMO. It is concluded that DFMO exhibits enantioselective absorption, with the more potent enantiomer L-DFMO being less favored. Sulfadoxine (SD) and sulfamethoxazole (SM) are sulfa-drugs used for malaria and pneumonia respectively. Two methods are described for simultaneous determination of SD and SM in capillary blood sampled on filter paper. The former method allows direct injection of extracts from dried blood spots (DBS), while for the latter method solid-phase extraction is added. Pre-analytical factors contributing to measurement uncertainty is also discussed, and it is concluded that it is of high importance that homogeneity in type of sampling paper and sampling volume is assured. Piperaquine (PQ) is an antimalarial, increasingly used in artemisinin combination therapy. A method for determination of piperaquine in DBS is presented. By using a monolithic LC column, a very short LC analysis of two minutes per sample is achieved. A method for simultaneous determination of three antiretroviral drugs i.e. lamivudine (3TC), zidovudine (AZT) and nevirapine (NVP), in DBS samples is described. The method is applied to drug determination in two subjects after receiving standard antiretroviral treatment. Conclusion is that the method is suitable for determination of 3TC and NVP, and to some extent for AZT.