The increasing demand for high performance communications systems and signal processing is constantly driving researchers to develop novel devices in both the microwave and optical domains. The possibility of using high temperature superconductors (HTS) as a platform for ultra-fast, ultra-high sensitive optoelectronic and microwave photonic devices has been explored. This report introduces a cryogenic microwave photonic probe station, designed and built to characterize HTS microwave photonic devices. A methodology is presented to design coplanar waveguide transmission lines using HTS. The transmission line is then modified to include a meander line structure to serve the optoelectronic function. The device is characterized in several different operating domains, as an optically tunable microwave resonator, an optically tunable delay line, and finally as a photodetector. A planar HTS weak leak structure is investigated with the measurements of the I-V characteristics. Moreover, this device is proposed as the next generation platform to fabricate ultra-fast and ultra-high sensitive photodetectors using HTS.

High Throughput Screening (HTS) is used in drug discovery to screen large numbers of compounds against a biological target. Data on activity against the target are collected for a representative sample of compounds selected from a large library. The goal of drug discovery is to relate the activity of a compound to its chemical structure, which is quantified by various explanatory variables, and hence to identify further active compounds. Often, this application has a very unbalanced class distribution, with a rare active class. <br /><br /> Classification methods are commonly proposed as solutions to this problem. However, regarding drug discovery, researchers are more interested in ranking compounds by predicted activity than in the classification itself. This feature makes my approach distinct from common classification techniques. <br /><br /> In this thesis, two AIDS data sets from the National Cancer Institute (NCI) are mainly used. Local methods, namely K-nearest neighbours (KNN) and classification and regression trees (CART), perform very well on these data in comparison with linear/logistic regression, neural networks, and Multivariate Adaptive Regression Splines (MARS) models, which assume more smoothness. One reason for the superiority of local methods is the local behaviour of the data. Indeed, I argue that conventional classification criteria such as misclassification rate or deviance tend to select too small a tree or too large a value of <em>k</em> (the number of nearest neighbours). A more local model (bigger tree or smaller <em>k</em>) gives a better performance in terms of drug discovery. <br /><br /> Because off-the-shelf KNN works relatively well, this thesis takes this promising method and makes several novel modifications, which further improve its performance. The choice of <em>k</em> is optimized for each test point to be predicted. The empirically observed superiority of allowing <em>k</em> to vary is investigated. The nature of the problem, ranking of objects rather than estimating the probability of activity, enables the <em>k</em>-varying algorithm to stand out. Similarly, KNN combined with a kernel weight function (weighted KNN) is proposed and demonstrated to be superior to the regular KNN method. <br /><br /> High dimensionality of the explanatory variables is known to cause problems for KNN and many other classifiers. I propose a novel method (subset KNN) of averaging across multiple classifiers based on building classifiers on subspaces (subsets of variables). It improves the performance of KNN for HTS data. When applied to CART, it also performs as well as or even better than the popular methods of bagging and boosting. Part of this improvement is due to the discovery that classifiers based on irrelevant subspaces (unimportant explanatory variables) do little damage when averaged with good classifiers based on relevant subspaces (important variables). This result is particular to the ranking of objects rather than estimating the probability of activity. A theoretical justification is proposed. The thesis also suggests diagnostics for identifying important subsets of variables and hence further reducing the impact of the curse of dimensionality. <br /><br /> In order to have a broader evaluation of these methods, subset KNN and weighted KNN are applied to three other data sets: the NCI AIDS data with Constitutional descriptors, Mutagenicity data with BCUT descriptors and Mutagenicity data with Constitutional descriptors. The <em>k</em>-varying algorithm as a method for unbalanced data is also applied to NCI AIDS data with Constitutional descriptors. As a baseline, the performance of KNN on such data sets is reported. Although different methods are best for the different data sets, some of the proposed methods are always amongst the best. <br /><br /> Finally, methods are described for estimating activity rates and error rates in HTS data. By combining auxiliary information about repeat tests of the same compound, likelihood methods can extract interesting information about the magnitudes of the measurement errors made in the assay process. These estimates can be used to assess model performance, which sheds new light on how various models handle the large random or systematic assay errors often present in HTS data.

The increasing demand for high performance communications systems and signal processing is constantly driving researchers to develop novel devices in both the microwave and optical domains. The possibility of using high temperature superconductors (HTS) as a platform for ultra-fast, ultra-high sensitive optoelectronic and microwave photonic devices has been explored. This report introduces a cryogenic microwave photonic probe station, designed and built to characterize HTS microwave photonic devices. A methodology is presented to design coplanar waveguide transmission lines using HTS. The transmission line is then modified to include a meander line structure to serve the optoelectronic function. The device is characterized in several different operating domains, as an optically tunable microwave resonator, an optically tunable delay line, and finally as a photodetector. A planar HTS weak leak structure is investigated with the measurements of the I-V characteristics. Moreover, this device is proposed as the next generation platform to fabricate ultra-fast and ultra-high sensitive photodetectors using HTS.

No description available.

Regulators of G-protein signaling (RGS) proteins are a family of proteins that act as GTPase accelerating proteins (GAPs) through their interaction with GΑ subunits, including GΑo, GΑi, and GΑq but not GΑs. This increased rate of hydrolysis of GTP to GDP temporally regulates G-protein coupled receptor (GPCR) signaling. A member of this family, RGS4, has been implicated in several neurological disorders including Parkinson's Disease (PD). A hallmark of PD is the induction of oxidative stress within dopaminergic neurons. In this thesis, we evaluate the role of oxidative stress, including lipid peroxidation products with 4-hydroxy-2-nonenal (4HNE) as a model, in regulating RGS4 activity within neurons. Utilizing transfected RGS4, we evaluated whether RGS4 is readily modified by physiologically relevant concentrations of 4HNE by immuonoprecipitation of RGS4 from 4HNE treated cells. Further examination of recombinant RGS4 by mass spectrometry, revealed that RGS4 is readily modified at several cysteine residues by 4HNE, including C148. Modification at this residue has been shown to be a critical site for allosteric regulation of RGS4. This is confirmed through a malachite green based phosphate generation assay we developed to observe the GAP activity of RGS4 on its native binding partner GΑi. This malachite green based assay was then adapted for high throughput screening. The assay was successfully miniaturized to a 1536-well format. In a screen of 2300 compounds, 4 were identified as hits. The development of this simple and cheap assay can be adapted for usage with a variety of RGS proteins with little work to interrogate other pathways and identify novel RGS modulators. Finally, expansive study of PD has linked oxidative stress to the pathology of both diseases. What has not been discerned is the potential relationship between oxidative stress and the induction of RGS4. In support of the hypothesis, we evaluated the potential relationship between oxidative stress and RGS4 expression. This was accomplished by evaluating two striatal neuron like cell lines, SH-SY5Y and HCN-1A. After treatment with hydrogen peroxide, both cell lines showed increased RGS4 in response to oxidative stress. This response is not however related to mRNA expression, indicating this change is most likely an adjustment of proteasomal regulation of RGS4. This phenomenon may explain the rapid onset of Parkinsonian motor symptoms in reserpine treated animal models of PD, as excess dopamine in the cytoplasm may be rapidly metabolized in reactive products.

In this dissertation, we investigate the macroscopic magnetic properties of bulk high-temperature superconductors (HTS) containing an array of artificial holes in view of enhancing their performances. The study involves a numerical modelling part and an experimental characterization part. In each part, novel concepts are highlighted and detailed. In particular, we develop a three-dimensional finite-element method (FEM) for calculating the magnetic field penetration in HTS where a single time-step is used in the case of a linearly varying applied magnetic field, and we probe the magnetic field in the volume of drilled samples with the help of microcoils inserted inside the holes. The thesis starts with an introductory chapter that describes the general concept of high-temperature superconductivity and particularly draws the attention on the interests and on the synthesis of drilled structures. Then, we detail the modelling tools that are used for evaluating the magnetic properties of drilled samples. Three models are taken into account: (1) the numerical Bean model which is a generalization of the Bean model for arbitrary cross sections where the samples are assumed to have an infinite height; (2) a 2D finite element model implemented in the open source solver GetDP for samples with an infinite height and assuming a power law relationship, that is characterized by a critical exponent n, between the electric field, E, and the current density, J; (3) a 3D finite element model with the same equations as those of model (2), but where these are solved in a three-dimensional sample with a finite height. For large values of n, both FEM models use the properties of a slow magnetic diffusion to reduce the number of time steps. In particular, the trapped flux can be calculated with only two time-steps: during the first step, the applied magnetic flux density is increased with a constant sweep rate to a maximum value, it then decreases to zero with the same sweep rate during the second step. The models are first used in simple geometries where they are compared to other available techniques. These are next applied to drilled samples. A systematic numerical study of the influence of the holes on the magnetic properties of the sample is reported. A single hole perturbs the critical current flow over an extended region that is bounded by a discontinuity line, where the direction of the current density changes abruptly. In samples with several holes and a given critical current density, we demonstrate that the trapped magnetic flux is maximized when the centre of each hole is positioned on one of the discontinuity lines produced by the neighbouring holes. For a cylindrical sample, we construct a polar triangular hole pattern that exploits this principle; in such a lattice, the trapped field is 20% higher than in a squared lattice, for which the holes do not lie on discontinuity lines. These results are experimentally validated. Two parallelepipedic samples are drilled with two different hole lattices. The trapped magnetic flux density of these samples is characterized by a Hall probe mapping before and after drilling holes. The sample in which the holes are aligned on the discontinuity lines exhibits the smallest magnetization drop that results from the hole drilling. Then, we resort to a novel experimental technique using microcoils inside the holes to characterize the local magnetic properties in the volume of drilled samples. In a given hole, three different penetration regimes can be observed when the sample is subjected to an AC magnetic field: (i) the shielded regime, where no magnetic flux threads the hole; (ii) the gradual penetration regime, where the amplitude of the magnetic field scales with the applied field; and (iii) the flux concentration regime, where the magnetic field exceeds that of the applied field. A comparison of the measurements with simple models assuming an infinite height shows that the holes may serve as a return path for the demagnetizing field lines. In the case of a pulsed field excitation, that measurement technique also allows us to estimate the trapped magnetic flux density in the volume of the sample and compare it with that on the surfaces. Moreover, the penetration of a magnetic pulse from hole to hole is described in the median plane and on the surface and the differences of penetration speeds are explained. Finally, we investigate the magnetic properties of drilled samples whose holes are filled with a ferromagnetic powder. To this aim, we use experimental techniques (Hall probe mapping techniques, together with measurements of the volume magnetization and of the levitation force between the HTS sample and a permanent magnet) and a numerical model (3D FEM) to characterize the modification of the magnetic properties resulting from the impregnation of the holes with AISI 410 ferromagnetic powder. Numerical results support the experimental observations and give clues to understand the mutual interaction between the HTS sample and the ferromagnetic powder inserted in its holes. In particular, the Hall probe mappings of the distribution of the trapped flux above the non-impregnated and impregnated samples reveal an increase of trapped flux after impregnation that is confirmed by simulations.

No description available.

Dans ce mémoire, nous abordons le problème de la correction d'erreurs systématiques et de la recherche des composés prometteurs (i.e. «hits») dans les procédures de criblage à haut débit (HTS). Nous introduisons une nouvelle approche pour la correction des erreurs systématiques dans les procédures HTS et la comparons à quelques méthodes couramment utilisées. La nouvelle méthode, appelée «well correction» ou correction par puits, procède par une analyse des erreurs systématiques localisées au niveau des puits, à travers toute la procédure de criblage. Cette méthode permet une amélioration des résultats obtenus lors de la sélection des «hits», par des méthodes utilisant un seuil prédéfini. La correction par puits à montré des résultats supérieurs aux méthodes suggérées dans la littérature telles que: correction par soustraction de l'arrière-plan («background correction» : Kevorkov et Makarenkov, 2005a, 2005b); «median-polish» et «B score» (Brideau et al., 2003; Malo et al., 2006). Nous avons également comparé trois méthodes de recherche des «hits» utilisant des approches de groupement (i.e. «clustering»): k-mean; somme des distances inter-cluster moyennes (SASD) et distance moyenne entre clusters (AICD). Ces méthodes proposent des algorithmes différents pour mesurer la distance entre les données provenant du criblage. Les méthodes de groupement utilisant k-means et SASD ont montré des résultats intéressants, mais aucune des méthodes étudiées n'a montré des performances pouvant justifier son utilisation dans tous les cas de figure. Un logiciel, «HTS Corrector», a été développé dans le cadre de ce travail. Il intègre toutes les méthodes étudiées dans ce mémoire. D'autres fonctionnalités auxiliaires, pouvant aider le praticien dans l'analyse des résultats provenant d'une procédure HTS, ont aussi été intégrées. ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Criblage à haut débit, High-throughput Screening, Erreurs systématiques, Correction de données, Méthodes de groupement, Recherche de hits, Normalisation de données.

Superconductivity Centennial Conference 2011- EUCAS–ISEC–ICMC (18-23 Sep 2011, The Hague, The Netherlands)

Rapeseed is the world's third most important oil plant (the second seminal). It is the most cultivation and most important oil plant in Czech Republic. Winter rapeseed reaches about 85% of the harvest area of oilseeds in the country. The desiccation of oilseed crop is sphere of agricultural engineering, which is still worth discussing. The main problems are how to use the product, what dose and which dates to choose to desiccate. The results of this thesis could help to partially clarify this complex issue. The aim of the thesis is to observe the effect of different terms oilseed rape desiccation by glyphosate on yield and seed quality. Small-plot experiments to investigate the influence of the term desiccation of winter rapeseed were established in the years 2013/2014 and 2014/2015 on the lands of the experimental station of the Czech Agricultural University, Faculty of Agronomy Food and Natural Resources at the Červený Újezd. In the first experimental year 2013/2014 was founded five variants in three replications (including undesiccated control). In the year 2014/2015 was founded seven variants in four replicates (including undesiccated controls). In the first experimental year was the first term desiccation 16. 6. 2014, the second year 8. 6. 2015. Subsequent periods of desiccation were a week apart. The variety of winter rapeseed used for the experiments was a hybrid variety Rohan. The desiccating agent was used Dominator active substance glyphosate. The dose of 4 l / ha + 200 l H2O. For all samples, both experimental, years yield was determined, the weight of a thousand seeds and oiliness. For desiccated variants were carried out pre-harvest analysis for the determination of solids in pods. Further, all harvested samples taken for laboratory germination test (Determination of germination) ISTA according to the methodology. The results of the experiment sprouting were statistically analyzed using ANOVA analysis of variance. Differences between mean values were evaluated by Tukey test, the computer program SAS at a significance level of p = 0.05. Effect of desiccation term influences of winter oilseed rape seed quality in terms of weight and thousands of seeds in terms of oil content. Too early desiccation (46 to 39 days before harvest) HTS reduced by 7-17% and the oil content of 2-4% of the overall average. Oiliness of the observed characters minimum interference term desiccation. Desiccation in the optimum date (17 days before harvest) increased oiliness of 1-6%. Influence term desiccation oilseed rape also greatly influences seed yield. Too early desiccation (46 to 39 days before harvest) reduced the yield by 11-14%. Undesiccated control in both years achieved the highest yields, increase yield by 5-12%. Desiccation in the optimum date (17 days before harvest) increased the yield of attempts by 5-6%. The term desiccation of winter rapeseed, also significantly affects the vitality of seeds, where very reduces energy germinating seedlings in the first days. The term desiccation, however, does not affect overall seed germination. Too early desiccation (46 to 39 days before harvest) EK2 decreased by 12-40%, EK3 decreased by 4-24%, 3-4% EK4 and extended MGT of 7-15%. In the first experimental year was the most vital option undesiccated control (EK2 = 50.4% = 91.3% EK3, EK4 = 97.9%). In the second experimental year was the most vital seeds of the optimal term desiccation, (Sixth term, 17 days before harvest) = 68.9% EK2, EK3 = 98.2%, EK4 = 100%. Seed samples of 2014/15 had a higher overall vitality of seeds, than samples from 2013/14, the overall vitality is probably worse given year old and transsilaged seed. The results of the two-year experiment that term desiccation affects the quality of seeds, the yield of seeds and vitality of seeds. Pre-analysis was determined optimum solids content in siliques desiccated samples to values of 40-50%. Like most technology seems to desiccation in the optimum date (17 days before harvest) and agro technology without desiccated vegetation. As the least appropriate technology seems very early desiccation (46 to 30 days before harvest). The first scientific hypothesis: Premature desiccation reduces seed yield, oil content and HTS. Yes, the hypothesis was confirmed. The second scientific hypothesis: Desiccation made in the correct term do not affect the quality of the seeds (oiliness and HTS). Yes, the hypothesis was confirmed.