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En physique des particules, les grands accélérateurs permettent de sonder la matière en produisant des collisions de faisceaux à haute énergie. Dans un accélérateur circulaire, l'énergie maximale de collision dépend directement de l'intensité du champ magnétique dipolaire servant à guider les particules le long de leur orbite. Dans le large collisionneur de hadrons installé au CERN, l'énergie de collision maximale est de 14 TeV dans le centre de masse. Réaliser des collisions à plus haute énergies nécessitera alors l'utilisation de matériaux supraconducteurs à haute température critique (HTS). Dans cette perspective, les propriétés électromécaniques des différents conducteurs HTS sont caractérisées et paramétrées à 4.2 K sous des inductions allant jusqu'à 12 T. Dans les aimants supraconducteurs d'accélérateur, le câble doit être à fort ampérage et à haute densité de courant (15 kA-400 A/mm2). Il consistera en plusieurs conducteurs HTS connectés en parallèle. La caractérisation et la modélisation des performances de tels câbles dans leurs futures conditions opérationnelles sont exposées dans cette thèse. / Particle colliders are the main tool for investigating and understanding the fundamental laws of physics. The CERN Large Hadron Collider (LHC), is a circular accelerator which steers and collides two counter-rotating protons beams. It has four collision points where detectors are placed to analyze the products emerging from the collisions. In a synchrotron machine a magnetic flux density is used to guide and focus particles around the orbit. The maximum energy that a circular machine with a given geometry can achieve is limited by the maximum strength of the dipole magnetic flux density. There is therefore an interest in the particle physics community in searching for dipole magnets with higher strength. The LHC has a beam trajectory radius of 4.3 km and a collision center-of-mass energy of 14 TeV. The accelerator employs 1232 large superconducting Nb-Ti dipole magnets operated at a flux density of up to 8.3 T in a bath of superfluid helium at 1.9 K. Energies higher than that achieved with the LHC require magnets made from superconductors with higher upper critical flux density. Nb3Sn is an option for magnets operated up to about 14 T. The level of energies of the type being discussed for a potential energy upgrade of the LHC machine - 33 TeV- would require the use of high temperature superconductors (HTS). Three technical HTS are available today: YBCO, Bi-2212 and Bi-2223. At low temperature YBCO conductors present both irreversible flux density and current density in excess of those measured in Bi-2212 and Bi-2223 conductors. In addition, YBCO can be used as reacted conductor, which makes its use for applications simpler than Bi-2212, which requires heat treatment at high temperature and in oxygen atmosphere after cabling and winding. The level of currents required for application to accelerator magnets, which is above 10 kA at the nominal operating temperature and flux density, excludes the use of single strands. The high current and high current density required can be achieved with cables having several strands connected in parallel. The main objective of my work has been the study of HTS cables for high current/high current density applications, starting from the analysis and selection of suitable conductors, through the characterization of their intrinsic (e.g. critical surface, strain sensitivity and irreversible strain) and extrinsic (e.g. cabling degradation) properties, with the final objective of validating 10 kA-range cables based on HTS material for high flux density magnets. The performance of YBCO and Bi-2223 tapes at 4 K under parallel and perpendicular flux density is measured using purpose built samples holders. A complete review of the strain sensitivity of HTS materials is presented, and the measured critical current retention of HTS tapes under torsion is discussed. Expressions that describe the critical current density of HTS conductors as a function of flux density strength, flux density orientation, temperature and strain are introduced. Analytical models that provide the allowable twist and bending radius of YBCO tapes as a function of strain are elaborated and compared with measurements. The accurate expressions are then used to compute the margins of the winding pack of a 19 T dipole made with a YBCO cable. Roebel cables made of YBCO high current strands are characterized at 4.2 K and in flux densities of up to 9.6 These are the first measurements ever performed at 4.2 K and with high currents. The Roebel cables reached critical currents of up to 12 kA with engineering current density in excess of 1.1 kA/mm2 at 7.5 T. These measurements demonstrate the potential of Roebel cables for high flux density magnets. During measurements two out of four Roebel cables were irreversibly damaged. The mechanism of failures is detailed and explained. Finally the performance and current distribution of HTS cables is computed and compared with measurements

Large electrical current transport in the absence of energy losses is thekey factor in commercial applications of high temperature superconductors. This thesis demonstrates an easy and inexpensive bottom-uptechnique to produce self assembled nanorods, segmented nanorodsas well as nanoparticles in YBa2Cu3O7-δ thin films grown by pulsedlaser deposition. The structural and morphological characteristic ofthe pinning landscapes produced are investigated and correlated totheir effects on the superconducting properties of the thin films. In particular two pinning landscapes are investigated: Ba2YNbO6nanorods are grown in YBa2Cu3O7-δ thin films using a Ba2YNbO6doped YBa2Cu3O7-δ pulsed laser deposition targets andBa2(Y/Gd)(Nb/Ta)O6 segmented nanorods together with (Y/Gd)2O3nanoparticles are grown in (Y/Gd)Ba2Cu3O7-δ thin films using aBa2YNbO6 + Gd3TaO7 doped YBa2Cu3O7-δ pulsed laser depositiontargets. The Ba2YNbO6 + YBa2Cu3O7-δ is deeply characterised and the effectsof the deposition parameters are analysed. Ba2YNbO6 is demonstratedto be an interesting novel pinning addition capable to increasethe critical current and to reduce the YBa2Cu3O7-δ critical currentsangular dependencies anisotropy. The Ba2YNbO6 + Gd3TaO7 + YBa2Cu3O7-δ is found to produce anew complex pinning landscape extremely effective. At high fieldsthe synergetic combination of the different defects typology is shownto generate an interesting new feature in the critical current angulardependencies. Chapter 1 is an introduction to superconductivity, the fundamentals ofthe field are briefly presented. In chapter 2 the discussion in focused onpinning in high temperature superconductors. Cuprates and in particularYBa2Cu3O7-δ are presented. The pinning phenomenon andthe practical pinning engineering in thin films is also discussed in thischapter. Chapter 3 describes the thin films preparation methods andthe characterisation techniques used in the research work. Chapter 4and 5 are focused on the Ba2YNbO6 doped YBa2Cu3O7-δ thin films. Chapter 4 is an introduction to Ba2YNbO6 doped YBa2Cu3O7-δ, thepreliminary results obtained on Ba2YNbO6 doped YBa2Cu3O7-δ thin films are shown in this chapter. The crystalline structure, the morphologyand the superconducting properties of thin films depositedadopting different deposition parameters are analysed and discussedin chapter 5. In chapter 6 the new complex pinning landscape ofBa2(Y/Gd)(Nb/Ta)O6 and (Y/Gd)2O3 in (Y/Gd)Ba2Cu3O7-δ is presented. Concluding remarks on the research described in the workends the thesis in a brief final chapter 7.

This thesis presents a novel study on Second Generation High Temperature Superconductors, which covers their electromagnetic characteristics and AC loss analysis. Lorentz Force Electrical Impedance Tomography (LFEIT) is one of the most promising hybrid diagnostic scanners with burgeoning potential for biological imaging, particularly in the detection of cancer and internal haemorrhages. The author tried a novel combination of superconducting magnets together with the LFEIT system. The reason is that superconducting magnets can generate a magnetic field with high intensity and homogeneity, which could significantly enhance the electrical signal induced from a sample, thus improving the Signal-to-Noise Ratio (SNR). The author developed four magnet designs for the LEFIT system using the Finite Element Method (FEM) package, COMSOL Multiphysics, and found that a Superconducting Halbach Array magnet can achieve all the requirements (magnetic field properties, geometry, portability, etc.) for the LFEIT system. The optimization study of the superconducting Halbach Array magnet has been carried out on the FEM platform of COMSOL Multiphysics, with 2D models using H-formulation based on B-dependent critical current density and bulk approximation. Optimization focused on the location of the coils, as well as the geometry and number of coils on the premise of maintaining the total amount of superconducting material used in the design. The optimization results showed that the Halbach Array configuration based superconducting magnet is able to generate a magnetic field with an intensity of over 1 Tesla and improved homogeneity. In order to efficiently predict the optimization performance, mathematical formulas were developed for these optimization parameters to determine the intensity and homogeneity of the magnetic field. The mathematical model for the LFEIT system was built based on the theory of the magneto-acousto-electric effect. Then the basic imaging of the electrical signal was developed using Matlab. The magnetic field properties of the magnet design were imported into the LFEIT model. The LFEIT model simulated two samples located in three different magnetic fields with varying magnetic strength and homogeneity. Even if there are no actual alternating currents involved in the DC superconducting magnets mentioned above, they have power dissipation during normal operation (e.g. magnet ramping) and under different background fields. This problem generally goes under the category of “AC loss”. Therefore, the AC loss characteristics of HTS tapes and coils are still fundamentally important for HTS magnet designs, even if they are normally operating in DC conditions. This thesis starts with the AC loss study of HTS tapes. The investigation and comparison of AC losses on Surround Copper Stabilizer (SCS) Tape and Stabilizer-free (SF) Tape have been carried out, which includes AC loss measurement using the electrical method, as well as the real geometry and multi-layer HTS tape simulation using the 2D H formulation by COMSOL Multiphysics. Hysteresis AC losses in the superconducting layer, and eddy current AC losses in the copper stabilizer, silver overlayer and substrate were concerned in this investigation. The measured AC losses were compared to the AC losses from the simulation, using 3 cases of different AC frequency: 10 Hz, 100 Hz, and 1000 Hz. The frequency dependence of AC losses from Stabilizer free Tape and Copper Stabilizer Tape were compared and analysed. A comprehensive AC loss study of a circular HTS coil has been fulfilled. The AC losses from a circular double pancake coil were measured using the electrical method. A 2D axisymmetric H-formulation model using FEM package COMSOL has been established, which was able to make consistency with the real circular coil used in the experiment. To model a circular HTS coil, a 2D axisymmetric model provided better accuracy than a general 2D model, and was also more efficient than a 3D model. Three scenarios were analysed: (1) AC transport current and DC magnetic field, (2) DC transport current and AC magnetic field, (3) AC transport current and AC magnetic field. The angular dependence analysis on the coil under the magnetic field with the different orientation angle  was carried out for all three scenarios. For scenario (3), the effect of the relative phase difference ∆ between the AC current and the AC field on the total AC loss of the coil was investigated. To summarise, a current/field/angle/phase dependent AC loss (I, B, , ∆) study of circular HTS coil has been carried out, which could potentially benefit the future design and research of HTS AC systems. The AC losses of horizontally parallel HTS tapes have been investigated. The AC losses of the middle and end tape of three parallel tapes have been measured using the electrical method, and compared to those of an individual isolated tape. The effect of the interaction between tapes on AC losses has been analysed, and compared with finite element method (FEM) simulations using the 2D H formulation implemented in COMSOL Multiphysics. The electromagnetic induction around the three parallel tapes was monitored using COMSOL simulation. The electromagnetic induction and AC losses generated by a conventional three turn coil were simulated as well, and then compared to the case of three parallel tapes with the same AC transport current. The analysis demonstrated that HTS parallel tapes could be potentially used in wireless power transfer systems, which could have lower total AC losses than conventional HTS coils. By using FEM simulations, cases of increasing number of parallel tapes was considered, and the normalised ratio between the total average AC losses per tape and the AC losses of an individual single tape have been calculated for different gap distances. A new parameter is proposed, Ns, a turning point the for number of tapes, to divide Stage 1 and Stage 2 for the AC loss study of horizontally parallel tapes. For Stage 1, N < Ns, the total average losses per tape increased with the increasing number of tapes. For Stage 2, N > Ns, the total average losses per tape started to decrease with the increasing number of tapes. The analysis demonstrates that horizontally parallel HTS tapes could be potentially used in superconducting devices like HTS transformers, which could retain or even reduce the total average AC losses per tape with large numbers of parallel tapes.

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.

Thesis advisor: Charles Hoffman / Cyclic adenosine monophosphate (cAMP) and the second messengers that modulate several biological processes are regulated by adenylyl cyclase (AC) and cyclic nucleotide phosphodiesterases (PDEs). ACs and PDEs are comprised of superfamilies of enzymes that are viewed as druggable targets due to their many distinct biological roles and tissue-specific distribution. As such, small molecule regulators of ACs and PDEs are important as chemical probes to study the roles of individual ACs or PDEs and as potential therapeutics. In the past, our lab has expressed 15 mammalian PDE genes in S. pombe, replacing the endogenous Cgs2 PDE. High throughput screens for PDE inhibitors identified novel compounds that show relevant biological activity in mammalian cell culture assays. The aim of this thesis is to develop tools to understand the mechanism of interaction between key regulators of the cAMP pathway and small molecules. The current study is comprised of two parts. In the first part of this thesis, I developed a genetic screen that detected alleles whose proteins remain active in the presence of BC54 and was to confirm the effect of the PDE4BT407A mutation using cell-based assays and in vitro enzyme assays. In the second part of this thesis, I developed and carried out HTSs using a PKA-repressed GFP reporter that can identify compounds that reduce PKA activity, which would include PDE activators and AC or GNAS1 inhibitors. To date, I have identified three AC inhibitors that appear to act on several of the ten different mammalian ACs. To our knowledge, this is the first time a large HTS has identified AC inhibitors, where inhibition was assessed inside the cells. The findings in this thesis will be useful in the design of more effective PDE inhibitors and in the development of novel chemical probes for studying cAMP signaling in mammalian cells. / Thesis (PhD) — Boston College, 2016. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

Thesis advisor: Charles Hoffman / Cyclic adenosine monophosphate (cAMP) and the second messengers that modulate several biological processes are regulated by adenylyl cyclase (AC) and cyclic nucleotide phosphodiesterases (PDEs). ACs and PDEs are comprised of superfamilies of enzymes that are viewed as druggable targets due to their many distinct biological roles and tissue-specific distribution. As such, small molecule regulators of ACs and PDEs are important as chemical probes to study the roles of individual ACs or PDEs and as potential therapeutics. In the past, our lab has expressed 15 mammalian PDE genes in S. pombe, replacing the endogenous Cgs2 PDE. High throughput screens for PDE inhibitors identified novel compounds that show relevant biological activity in mammalian cell culture assays. The aim of this thesis is to develop tools to understand the mechanism of interaction between key regulators of the cAMP pathway and small molecules. The current study is comprised of two parts. In the first part of this thesis, I developed a genetic screen that detected alleles whose proteins remain active in the presence of BC54 and was to confirm the effect of the PDE4BT407A mutation using cell-based assays and in vitro enzyme assays. In the second part of this thesis, I developed and carried out HTSs using a PKA-repressed GFP reporter that can identify compounds that reduce PKA activity, which would include PDE activators and AC or GNAS1 inhibitors. To date, I have identified three AC inhibitors that appear to act on several of the ten different mammalian ACs. To our knowledge, this is the first time a large HTS has identified AC inhibitors, where inhibition was assessed inside the cells. The findings in this thesis will be useful in the design of more effective PDE inhibitors and in the development of novel chemical probes for studying cAMP signaling in mammalian cells. / Thesis (PhD) — Boston College, 2016. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

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