Atmospheric artifacts superimposed on interferometric synthetic aperture radar (InSAR) measurements have the potential to greatly impede the accurate estimation of deformation signals. The research presented in this dissertation demonstrates a novel InSAR time series algorithm, called HiRAPS algorithm, for effectively estimating high resolution atmospheric phase screens (APS) from differential InSAR measurements. In summary, the HiRAPS algorithm utilizes short time span differential interferograms and rearranges components of existing advanced InSAR techniques to identify a higher density of scatterers used to create the APS. The improved scatterer density allows one to estimate high spatial frequency atmospheric signals not recovered from existing InSAR time series techniques. The HiRAPS algorithm was tested with simulated and actual data, which contain phase contributions from linear and nonlinear deformation, topographic height errors, and atmospheric artifacts. Simulated differential interferograms were generated to have the same spatial and temporal baselines as the actual differential interferograms formed from RADARSAT-1 data over Phoenix, Arizona. The APS superimposed on simulated differential interferograms were then estimated and compared to simulated APS. The root mean square error (RMSE) between the estimated and simulated APS was calculated to qualitatively assess the different values obtained. The RMSE was 0.26 radians when utilizing the HiRAPS algorithm, compared to an RMSE value of 0.39 radians using an implementation of the permanent scatterer (PS) algorithm. The HiRAPS algorithm also showed its applicability for estimating high spatial frequency atmospheric signals for actual data. Sixty-six SAR images, starting from October 5, 2002 and spanning 5 years, were processed for this research. The APS pixel density obtained using the HiRAPS algorithm was 253 pixels per square kilometer, compared to 14 pixels per square kilometer utilizing the PS algorithm. The APS superimposed on the differential interferograms were estimated with both the proposed and PS algorithms. High resolution APS were estimated with the HiRAPS algorithm, whereas only low resolution APS were obtained with the PS algorithm. After estimating and removing estimated APS, the phase stability of APS-free differential interferograms was examined by identifying the permanent scatterers (PS). The final density of identified PS obtained with the HiRAPS algorithm was 453 PS per square kilometer, whereas the density of detected PS using the generic PS algorithm was 381 PS per square kilometer. The maximum difference in the deformation time series between the HiRAPS algorithm and the PS algorithm was less than 6 mm. However, the HiRAPS algorithm resulted in less apparent noise in the time series than the PS algorithm due to the precise estimation of APS. / text

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Charles Univeristy in Prague, Faculty of Pharmacy in Hradec Králové Department Department of Pharmaceutical Chemistry and Drug Control Author: Marek Tauchman Supervisor: Prof. PharmDr. Martin Doležal, Ph.D. Title of Diploma Thesis: Pyrazine Derivatives as Potential Antituberculosis Drugs II. Tuberculosis still presents serious worldwide problem of today. The situation is complicated especially by increasing proportion of strains resistant to common antituberculotics. Therefore the need of a new compound active against mycobacterial causer of the disease is very actual. Synthesis of compounds derived from pyrazinamide, very effecitve anti-mycobacterial substance, is one of the perspective way of new drugs development. Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Králové, beside others, deals with this problem in a long term. There were synthesized hundreds of compounds containing pyrazine core and they were tested to antimycobacterial activity. The target of this thesis is join this effort and contribute to increase the number of compound that has been studied for antituberculosis activity. At the beginning of thesis, there is a summary of facts about tuberculosis, such as incidence, patogenesis and cure. Next, there are informations about newly developed...

Le récepteur à chimiokine CXCR4 est à ce jour l’un des récepteurs couplés aux protéines G les plus étudiés. Le CXCL12, sa chimiokine endogène induit l’activation de plusieurs voies de signalisation cruciales à plusieurs processus physiologiques. Par ailleurs, dans de nombreux processus pathologiques comme le cancer, le récepteur CXCR4 et/ou son ligand endogène sont surexprimés et facilite la dissémination et le maintien de conditions favorables à la prolifération cancéreuse. Afin d’étudier le récepteur CXCR4 et sa signalisation, notre approche vise à développer des ligands ciblant le CXCR4 en se basant sur CXCL12. Par des études de relation structure-activité et du design rationnel, nous avons conçu des chimères du CXCR4. Ces outils pharmacologiques nous permettent de mieux extraire les déterminants structuraux impliqués dans l’activation du CXCR4 mais aussi d’étudier les voies de signalisation associées à ces nouvelles entités chimiques. Nos données de relation structure-activité ont permis de mettre en évidence deux positions clés sur le N-terminal de nos chimères, la position 3 et la position 7 cruciales pour l’affinité et l’efficacité respectivement. Nous avons pu moduler l’efficacité ainsi que l’affinité de nos chimères en introduisant des acides aminés non naturels capables de potentialiser l’effet pharmacologique. Nous avons également corrélé nos résultats de SAR avec de la dynamique moléculaire réalisée à partir des deux structures cristallographiques du CXCR4. Nos données de dynamique moléculaire montrent des différences structurales importantes au niveau des domaines transmembranaires 3 et 7 en présence ou non de nos chimères. Par ailleurs, nous avons développé un nouveau déterminant avec des propriétés pharmacocinétiques améliorées comparativement au déterminant d’affinité des chimères de première génération. La caractérisation de ce déterminant a par ailleurs révélé son caractère agoniste inverse. Tous ces résultats apportent des éléments clés pour un meilleur design de molécules à visée thérapeutique ciblant le CXCR4.

Soil moisture estimation using Sentinel-1 radar data The main aim of this diploma thesis was to find and quantify the relationship between the intensity of backscatter from the Sentinel-1 radar data and the volume soil moisture at the level of agricultural fields. The research was conducted in three areas, in the first part there were two vegetation-free fields near the Thessaloniki (Greece), and information about soil moisture was obtained from own measurements using a thermogravimetric method. The second part drew data from the freely available ISMN database and the research was carried out on agricultural fields during the vegetation season in northwest Germany. The third part used soil moisture data from the Czech Hydrometeorological Institute (ČHMÚ) and the area of interest was two grassed areas of the airport and one agricultural field. Correlation was measured by calculating the determination coefficient and by using the linear regression an equation for calculating the soil moisture from the radar backscatter was compiled. High dependence has been confirmed when VV polarization with constant surface roughness were examined. In the case of surfaces with varying roughness and vegetation cover, only low correlation was found, similarly with using VH polarization. Key words: radar, SAR, Sentinel-1, soil...

With the advance of technology and rapid growth of digital systems, low power high speed analog-to-digital converters with great accuracy are in demand. To achieve high effective number of bits Analog-to-Digital Converter(ADC) calibration as a time consuming process is a potential bottleneck for designs. This dissertation presentsa fully digital background calibration algorithm for a 7-bit redundant flash ADC using split structure and look-up table based correction. Redundant comparators are used in the flash ADC design of this work in order to tolerate large offset voltages while minimizing signal input capacitance. The split ADC structure helps by eliminating the unknown input signal from the calibration path. The flash ADC has been designed in 180nm IBM CMOS technology and fabricated through MOSIS. This work was supported by Analog Devices, Wilmington,MA. While much research on ADC design has concentrated on increasing resolution and sample rate, there are many applications (e.g. biomedical devices and sensor networks) that do not require high performance but do require low power energy efficient ADCs. This dissertation also explores on design of a low quiescent current 100kSps Successive Approximation (SAR) ADC that has been used as an error detection ADC for an automotive application in 350nm CD (CMOS-DMOS) technology. This work was supported by ON Semiconductor Corp, East Greenwich,RI.

Mitochondria are organelles present in eukaryotic cells that play a key role in regulating cells’ metabolic processes as well as cell death. The main function of mitochondria is to produce ATP, by oxidizing nutrients in a process called oxidative phosphorylation (OXPHOS). Besides this, mitochondria also play a critical role in calcium homeostasis, cell signaling, and apoptosis. Mitochondrial dysfunction is implicated in a plethora of diseases including neurodegenerative diseases, metabolic disorders as well as ageing and cancer. The triphenylphosphonium (TPP+) moiety has been used as a carrier to direct a wide variety of therapeutic and diagnostic cargo to mitochondria, in an effort to study and treat mitochondrial dysfunction. Studies in recent years show that TPP+ is not an inert carrier as previously thought. Many TPP+ conjugates have been shown to exert a negative effect on mitochondrial and cellular bioenergetics by decreasing the efficiency of OXPHOS. This phenomenon is called ‘mitochondrial uncoupling’. While mitochondrial uncoupling is undesirable for the TPP+ moiety to function as a carrier of cargo to mitochondria, controlled uncoupling has therapeutic applications in treatment of obesity and cancer. The extent of mitochondrial accumulation as well as potency of mitochondrial uncoupling caused by the TPP+ moiety increases with increasing length of the linker functionality in TPP+ conjugates. Most of the studies to date have focused on altering the linker length of the TPP+-linker-cargo conjugate to optimize the balance between safety and efficacy. However, very little is known about how structural modification of the TPP+ moiety itself affects mitochondrial uncoupling potency. Therefore, there is a need to understand the structure activity relationship (SAR) between modification of TPP+ structure and the effect of these structural changes on mitochondrial uncoupling and uptake. Towards this end, the first goal of this study was to understand the effect of modulating electron density on the phosphorus atom of TPP+ on the potency of uncoupling OXPHOS. Modifications to the TPP+ moiety included substitution of electron withdrawing and donating groups on the phenyl rings of TPP+, and replacing phenyl rings with bulkier napthyl rings. Modified TPP+ moieties were conjugated to five different linkers, which varied in length and lipophilicity, and the effect of these conjugates on mitochondrial bioenergetics was studied. The second goal of the study was to evaluate if the propensity of TPP+ to uncouple mitochondrial respiration can be modulated, independently of mitochondrial uptake. For this purpose, the uptake of modified TPP+-linker conjugates into isolated mitochondria and the uptake of fluorescently labeled modified TPP+-linker conjugates into mitochondria within whole cells was investigated. The ability of modified TPP+ to protect cells from oxidative stress by successfully delivering an anti-oxidant cargo to mitochondria within cells was also assessed. The results of these studies establish the first SAR for modulating TPP+ structure to either eliminate, optimize, or maximize uncoupling of mitochondrial OXPHOS, and led to identification of lead molecules for potential applications in the fields of mitochondrial delivery, anti-obesity therapy and anti-cancer therapy.

In the context of the ESA BIOMASS mission in which for the first time, a P-Band SAR sensor isgoing to be mounted into a spaceborne system. With its penetration capability, it will contributeto the measurement of the biomass and carbon content in the Earth’s forests. An autofocusalgorithm is needed for the correction of phase errors introduced by the changing diffraction indexin the ionosphere. Because of the quickly changing nature of the ionosphere, defocusing has to bemeasured and corrected locally over several sections of a SAR capture.In this thesis, a deep introduction into phase errors is made having in mind that the ionosphereis expected to introduce time varying low frequency errors that can be constructed as a series ofquadratic curves. These quadratic phase errors introduce defocusing that is seen as blur and lossof contrast. An algorithm is proposed and tested for measuring this defocusing, while its strengthsand weaknesses are discussed.The idea of measuring defocusing is to try to recover the temporal phase function that introduceddefocusing in the first place. Here a method to recover this temporal phase function is introduced,and a thorough performance assessment of this retrieval is carried out. The variables involved thequality and reliability of this retrieval are studied one by one.

L'objectif de ce travail de thèse a été d'évaluer le potentiel de la technique PolInSAR pour l'extraction des paramètres physiques de la forêt et la transposition de ce type d'analyse aux conditions spatiales. <br /><br />Des travaux antérieurs ont montré que cette technique était efficace pour l'estimation de la hauteur des arbres, qui peut être reliée à la biomasse aérienne par une relation allométrique, à partir de données acquises en bande L. La première partie de ces travaux a porté sur le développement de procédures d'inversions aux fréquences extrêmes du spectre généralement utilisé pour l'étude des surfaces naturelles, la bande X et la bande P, dans le contexte de données acquises par le système aéroporté RAMSES sur des forêts de pins. <br /><br />Ensuite, l'influence des paramètres système qui diffèrent le plus de l'aéroporté au satellitaire, la résolution et le rapport Signal à Bruit, est quantifiée sur la robustesse et la précision de l'inversion en bandes X, L et P afin d'en déterminer les limitations en conditions spatiales.

<p>The technique of ESR-dosimetry and strategies for investigation of new materials as in regard to their applicability as ESR-dosimeters for radiotherapy has been reviewed. As an example six salts of formic and lactic acid has been evaluated. The applicability of the dosimeter has been judged by evaluating the tissue equivalence, radical yield, radical stability, spectral suitability, optimal readout parameters, dose response and sensitivity of the dosimetric system. Dependence of material characteristics and influence parameters has been analysed.</p><p>The reviewed methods have been successfully used for evaluation of the new materials. Lithium formate has been shown to be a good candidate relative to the state of the art dosimeter of alanine. Using optimal readout parameters lithium formate has been shown to be nine times as sensitive but even at moderate settings lithium formate is more sensitive. The results for lithium formate are in accordance to those of previous studies. The signal intensity of sodium formate has also proved to be high but unfortunately the signal fades rapidly.</p><p>Two new methods have been proposed as synthesis of the reviewed methods. The first allows flexible, effective and objective baseline correction of the ESR-spectrum. The second deals with dose response measurement by linear regression of the entire spectrum and was found to be successful in separating the spectral peaks of the induced radicals from the background signal.</p>