The growing applications for IoT devices have caused an increase in the study of low power consuming circuit design to meet the requirement of devices to operate for various months without external power supply. Scaling down the conventional CMOS causes various complications to design due to CMOS properties, therefore various non-conventional CMOS design techniques are being proposed that overcome the limitations. This thesis focuses on some of those emerging and novel low power design technique namely Adiabatic logic and low power devices like Magnetic Tunnel Junction (MTJ) and Carbon Nanotube Field Effect transistor (CNFET). Circuits that are used for large computations (multipliers, encryption engines) that amount to maximum part of power consumption in a whole chip are designed using these novel low power techniques.

Un défi majeur en cancérologie est le traitement des tumeurs mammaires dites triple-négatives (ER-, PR-, HER2-). Elles sont le plus souvent résistantes aux traitements conventionnels et présentent un haut risque de récidive. De plus, l’absence de cibles thérapeutiques ne permet pas le développement de thérapie spécifique. 78% de ces tumeurs expriment faiblement la claudine 1 et sont de très mauvais pronostic. Cette protéine est impliquée dans l'adhérence des cellules entre elles et pourrait jouer un rôle suppresseur de tumeur dans les cancers mammaires. Dans ce contexte, nous étudions si sa réexpression pourrait être une piste de traitement. Au laboratoire, nous avons développé des dérivés de la famille des thiazolidinediones (TZD) qui stimulent l’expression de la claudine 1 et induisent l’apoptose des cellules cancéreuses mammaires. Les objectifs de ma thèse ont consisté 1) à déterminer l’implication de la claudine 1 dans l’effet pro-apoptotique de ces composés 2) à l’étude de leurs mécanismes d’action 3) évaluer si l’expression de la claudine 1 pourrait sensibiliser les cellules cancéreuses triple-négatives aux agents de chimiothérapie. Au cours de cette thèse, nous avons montré que la surexpression de la claudine 1 et le composé Δ2-TGZ induisent l’apoptose des cellules triple-négatives « claudin 1-low » MDA-MB-231 et Hs578T. De plus, la claudine 1 est impliquée dans l’effet pro-apoptotique de la Δ2-TGZ dans les cellules MDA-MB-231. Par ailleurs, nous avons démontré que les dérivés TGZ, la Δ2-TGZ et l’AB186, agissent de manière précoce en modifiant la morphologie des cellules suivie d’une réexpression de la claudine 1 membranaire et d’une inhibition de la migration cellulaire avant même d’induire la mort cellulaire par apoptose. De plus, la surexpression de la claudine 1 inhibe la migration cellulaire associée à la perte des fibres de stress et la formation des jonctions intercellulaires. Nous avons également montré que la réexpression de la claudine 1 sensibilise les cellules MDA-MB-231 à l’agent de chimiothérapie, le 5-FU. L’ensemble des résultats de thèse a permis de mieux comprendre le mécanisme d’action de la Δ2-TGZ et de l’AB186 sur les cellules cancéreuses mammaires mais aussi d’identifier la claudine 1 comme cible potentielle prometteuse dans les cellules triple-négatives « claudin 1-low » / A major challenge in oncology is the treatment of triple-negative breast cancer (ER-, PR-, HER2-) as no targeted therapy are available. These tumors present often a chemotherapy resistance and a higher relapse incidence. 78% of them do not express claudin 1 and display a poor prognosis. Claudin 1 is involved in cell-cell adhesion and may be a tumor suppressor gene in breast cancer. In this context, we study if claudin 1 re-expression could be a possible approach. In the laboratory, we developed derivatives thaziolidinediones (TZD) compounds, which increase claudin 1 expression and lead to apoptosis of breast cancer cells. The goals of my thesis is 1) to characterize the involvement of claudin 1 in their pro-apoptotic effect 2) to study their mechanism of action 3) to determine if claudin 1 could sensitize the TNBC cells to the chemotherapy agents. During my thesis, we showed that claudin 1 overexpression and the compound Δ2-TGZ induce apoptosis of TNBC « claudin 1-low » MDA-MB-231 and Hs578T cells. Claudin 1 is involved in the pro-apoptotic effect of Δ2-TGZ in MDA-MB-231 cells. Then, we demonstrated that Δ2-TGZ and AB186 lead to early action through a modification of cell morphology followed an expression of claudin 1 at the membrane and an inhibition of cell migration before the apoptosis process. In addition, claudin 1 overexpression decreases the cell migration through the loss of stress fibers and the formation of cell junctions. We showed that claudin 1 overexpression potentialize the pro-apoptotic effect of Δ2-TGZ in MDA-MB-231 cells. Finally, we observed that claudin 1 sensitize the MDA-MB-231 cells to 5-FU. In fine, our data allowed a better understanding of Δ2-TGZ and AB186 mechanism of action and identification of claudin 1 as a promising target in TNBC « claudin 1-low »

The fabrication of low cost, high efficiency solar cells is imperative in competing with existing energy technologies. Many research groups have explored using III-V materials and thin-film technologies to create high efficiency cells; however, the materials and manufacturing processes are very costly as compared to monocrystalline silicon (Si) solar cells. Since commercial Si solar cells typically have efficiencies in the range of 17-19%, techniques such as surface texturing, depositing a surface-passivating film, and creating multi-junction Si cells are used to improve the efficiency without significantly increasing the manufacturing costs. This research focused on two of these techniques: (1) a tandem junction solar cell comprised of a thin-film perovskite top cell and a wafer-based Si bottom cell, and (2) Si solar cells with single- and double-layer silicon nitride (SiNx) anti-reflection coatings (ARC). The perovskite/Si tandem junction cell was modeled using a Matlab analytical program. The model took in material properties such as doping concentrations, diffusion coefficients, and band gap energy and calculated the photocurrents, voltages, and efficiencies of the cells individually and in the tandem configuration. A planar Si bottom cell, a cell with a SiNx coating, or a nanostructured black silicon (bSi) cell can be modeled in either an n-terminal or series-connected configuration with the perovskite top cell. By optimizing the bottom and top cell parameters, a tandem cell with an efficiency of 31.78% was reached. Next, planar Si solar cells were fabricated, and the effects of single- and double-layer SiNx films deposited on the cells were explored. Silicon nitride was sputtered onto planar Si samples, and the refractive index and thicknesses of the films were measured using ellipsometry. A range of refractive indices can be reached by adjusting the gas flow rate ratios of nitrogen (N2) and argon (Ar) in the system. The refractive index and thickness of the film affect where the minimum of the reflection curve is located. For Si, the optimum refractive index of a single-layer passivation film is 1.85 with a thickness of 80nm so that the minimum reflection is at 600nm, which is where the photon flux is maximized. However, using a double-layer film of SiNx, the Si solar cell performance is further improved due to surface passivation and lowered surface reflectivity. A bottom layer film with a higher refractive index passivates the Si cell and reduces surface reflectivity, while the top layer film with a smaller refractive index further reduces the surface reflectivity. The refractive indices and thicknesses of the double-layer films were varied, and current-voltage (IV) and external quantum efficiency (EQE) measurements were taken. The double-layer films resulted in an absolute value increase in efficiency of up to 1.8%.

By exploiting the versatility of ultracold atoms experiments, a variety of many-body phe- nomena can be studied. Ferromagnetism in a trapped ultracold gas of repulsively interacting fermions is considered within a local-density approximation and beyond, where energetic sig- natures indicate its onset. Transport of a Bose-Einstein condensate is explored experimentally in a tunable double-well potential, and a crossover from hydrodynamic to Josephson transport is observed as the barrier between condensates is raised. To add a degree of freedom for the manipulation of ultracold gases, two schemes for species-specific optical lattices are developed theoretically.

The temperature dependent electrical characteristics of silicon carbide power transistors – 4H-SiC metal semiconductor field-effect transistors (MESFETs) and 4H-SiC bipolar junction transistors (BJTs) have been investigated through simulation and experimental approaches. Junction temperatures and temperature distributions in devices under large power densities have been estimated. The DC and RF performance of 4H-SiC RF Power MESFETs have been studied through two-dimensional electro-thermal simulations using commercial software MEDICI and ISE. The simulated characteristics of the transistors were compared with the measurement results. Performance degradation of transistors under self-heating and high operating temperatures have been analyzed in terms of gate and drain characteristics, power density, high frequency current gain and power gain. 3D thermal simulations have been performed for single and multi-finger MESFETs and the simulated junction temperatures and temperature profiles were compared with the results from electro-thermal simulations. The reduction in drain current caused by self-heating was found to be more prominent for transistors with more fingers and it imposes a limitation on both the output power and the power density (in W/mm) of multi-fingered large area devices. Thermal issues for design of high power multi-fingered SiC MESFETs were also investigated. A couple of useful ways to reduce the self-heating effects were discussed. Trap-induced performance instabilities of the devices were analyzed by carrying out DC, transient, and pulse measurements at room and elevated temperatures. Electrical characteristics of 4H-SiC BJTs have been measured. A reduction in current gain at elevated temperatures was observed. Based on the collector current-voltage diagram measured at three different ambient temperatures the junction temperature was extracted using the assumption that the current gain only depends on the temperature. Temperature measurements have been carried out for SiC BJTs. Thermal images of a device under operation were recorded using an infrared camera. 3D thermal simulations were conducted using FEMLAB. Both the simulations and the measurement showed a significant temperature increase in the vicinity of the device when operated at high power densities, thus causing the decrease of the DC current gain. The junction temperatures obtained from the thermal imaging, simulation and extraction agree well.

<p>Disruption of coordinated impulse propagation in the heart as a result of fibrosis or myocardial infarction can create an asynchronous substrate with poor conduction and impaired contractility. This can ultimately lead to cardiac failure and make the heart more vulnerable to life-threatening arrhythmias and sudden cardiac death. The transplantation of exogenous cells into the diseased myocardium, "cardiac cell therapy," has been proposed as a treatment option to improve compromised cardiac function. Clinical trials of stem cell-based cardiac therapy have shown promising results, but also raised concerns about our inability to predict or control the fate of implanted cells and the electrical consequences of their interactions with host cardiomyocytes. Alternatively, genetically engineered somatic cells could be implanted to selectively and safely modify the cardiac electrical substrate, but their unexcitable nature makes them incapable of electrically repairing large conduction defects. The objective of this thesis was thus to develop a methodology to generate actively conducting excitable cells from an unexcitable somatic cell source and to demonstrate their utility for studies of basic electrophysiology and cardiac cell therapy.</p><p>First, based on the principles of cardiac action potential propagation, we applied genetic engineering techniques to convert human unexcitable cells (HEK-293) into an autonomous source of excitable and conducting cells by the stable forced expression of only three genes encoding an inward rectifier potassium (Kir2.1), a fast sodium (Na_v1.5), and a gap junction (Cx43) channel. Systematic pharmacological and electrical pacing studies in these cells revealed the individual contributions of each expressed channel to action potential shape and propagation speed. Conduction slowing and instability of induced arrhythmic activity was shown to be governed by specific mechanisms of I_Na inhibition by TTX, lidocaine, or flecainide. Furthermore, expression of the Na_v1.5 A1924T mutant sodium channel or Ca_v3.3 T-type calcium channel was utilized to study the specific roles of these channels in action potential conduction and demonstrate that genetic modifications of the engineered excitable cells in this platform allow quantitative correlations between single-cell patch clamp data and tissue-level function.</p><p>We further performed proof-of-concept experiments to show that networks of biosynthetic excitable cells can successfully repair large conduction defects within primary excitable tissue cultures. Specifically, genetically engineered excitable cells supported active action potential propagation between neonatal rat ventricular myocytes (NRVMs) separated by at least 2.5 cm in 2-dimensional and 1.3 cm in 3-dimensional cocultures. Using elastic films with micropatterned zig-zag NRVM networks that mimicked the tortuous conduction patterns observed in cardiac fibrosis, we showed that electrical resynchronization of cardiomyocyte activation by application of engineered excitable cells improved transverse conduction by 370% and increased cardiac twitch force amplitude by 64%. This demonstrated that despite being noncontractile, engineered excitable cells could potentially improve both the electrical and mechanical function of diseased myocardial tissue. </p><p>Lastly, we investigated how activation and repolarization gradients at the interface between cardiomyocytes and other excitable cells influence the vulnerability to conduction block. Microscopic optical mapping of action potential propagation was used to quantify dispersion of repolarization (DOR) in micropatterned heterocellular strands in which either well-coupled or poorly-coupled engineered excitable cells with a short action potential duration (APD), seamlessly interfaced with NRVMs that had a significantly longer APD. The resulting electrical gradients originating from the underlying heterogeneity in intercellular coupling and APD dispersion were further manipulated by the application of barium chloride (BaCl2) to selectively prolong APD in the engineered cells. We measured how the parameters of DOR affected the vulnerable time window (VW) of conduction block and found a strong linear correlation between the size of the repolarization gradient and VW. Reduction of DOR by BaCl2 significantly reduced VW and showed that VW correlated directly with dispersion height but not width. Conversely, at larger DOR, VW was inversely correlated with the dispersion width but independent of the dispersion height. In addition, despite their similar APDs, poorly-coupled excitable cells were found to significantly increase the maximum repolarization gradient and VW compared to well-coupled excitable cells, but only at larger DOR.</p><p>In summary, this thesis presents the novel concept of genetically engineering membrane excitability and impulse conduction in previously unexcitable somatic cells. This biosynthetic excitable cell platform is expected to enable studies of ion channel function in a reproducible tissue-level setting, promote the integration of theoretical and experimental studies of action potential propagation, and stimulate the development of novel gene and cell-based therapies for myocardial infarction and cardiac arrhythmias.</p> / Dissertation

High efficiency multi-junction (MJ) solar cells were packaged onto receiver systems. The efficiency change of concentrator cells under continuous high intensity illumination was done. Also, assessment of the receiver design on the overall performance of a Fresnel-type concentration system was investigated. We present on receiver designs including simulation results of their three-dimensional thermal operation and experimental results of tested packaged receivers to understand their efficiency in real world operation. Thermal measurements from solar simulators were obtained and used to calibrate the model in simulations. The best tested efficiency of 36.5% is obtained on a sample A receiver under 260 suns concentration by the XT-30 solar simulator and the corresponding cell operating temperature is ~30.5°C. The optimum copper thickness of a 5 cm by 5 cm simulated alumina receiver design was determined to be 6 mm and the corresponding cell temperature under 1000 suns concentration is ~36°C during operation.

High efficiency multi-junction (MJ) solar cells were packaged onto receiver systems. The efficiency change of concentrator cells under continuous high intensity illumination was done. Also, assessment of the receiver design on the overall performance of a Fresnel-type concentration system was investigated. We present on receiver designs including simulation results of their three-dimensional thermal operation and experimental results of tested packaged receivers to understand their efficiency in real world operation. Thermal measurements from solar simulators were obtained and used to calibrate the model in simulations. The best tested efficiency of 36.5% is obtained on a sample A receiver under 260 suns concentration by the XT-30 solar simulator and the corresponding cell operating temperature is ~30.5°C. The optimum copper thickness of a 5 cm by 5 cm simulated alumina receiver design was determined to be 6 mm and the corresponding cell temperature under 1000 suns concentration is ~36°C during operation.

<p>Cardiac arrhythmias triggered by both reentrant and focal sources are closely correlated with regions of tissue characterized by significant structural heterogeneity. Experimental and modeling studies of electrical activity in the heart have shown that local microscopic heterogeneities which average out at the macroscale in healthy tissue play a much more important role in diseased and aging cardiac tissue which have low levels of coupling and abnormal or reduced membrane excitability. However, it is still largely unknown how various combinations of microheterogeneity in the intracellular and interstitial spaces affect wavefront propagation in these critical regimes. </p> <p>This thesis uses biophysically realistic 1-D and 2-D computer models to investigate how heterogeneity in the interstitial and intracellular spaces influence both the initiation of ectopic beats and the escape of multiple ectopic beats from a poorly coupled region of tissue into surrounding well-coupled tissue. An approximate discrete monodomain model that incorporates local heterogeneity in both the interstitial and intracellular spaces was developed to represent the tissue domain. </p> <p>The results showed that increasing the effective interstitial resistivity in poorly coupled fibers alters the distribution of electrical load at the microscale and causes propagation to become more like that observed in continuous fibers. In poorly coupled domains, this nearly continuous state is modulated by cell length and is characterized by decreased gap junction delay, sustained conduction velocity, increased sodium current, reduced maximum upstroke velocity, and increased safety factor. In inhomogeneous fibers with adjacent well-coupled and poorly coupled regions, locally increasing the effective interstitial resistivity in the poorly coupled region reduces the size of the focal source needed to generate an ectopic beat, reduces dispersion of repolarization, and delays the onset of conduction block that is caused by source-load mismatch at the boundary between well-coupled and poorly-coupled regions. In 2-D tissue models, local increases in effective interstitial resistivity as well as microstructural variations in cell arrangement at the boundary between poorly coupled and well-coupled regions of tissue modulate the distribution of maximum sodium current which facilitates the unidirectional escape of focal beats. Variations in the distribution of sodium current as a function of cell length and width lead to directional differences in the response to increased effective interstitial resistivity. Propagation in critical regimes such as the ectopic substrate is very sensitive to source-load interactions and local increases in maximum sodium current caused by microheterogeneity in both intracellular and interstitial structure.</p> / Dissertation

Angiography is an invasive procedure since contrast medium is injected into circulatory system of patients and the mostly preferred technique is X-ray angiography. For diagnosis, treatment planning, and risk assessment purposes, interventional radiologists utilize visual inspection to determine connectivity relations between vessels. This situation leads angiography to be more invasive, since it requires additional injection of contrast medium and X-ray dose. This thesis work presents a 3-D vascular connectivity tracking toolkit for automated extraction of vascular networks in 3-D medical images. The proposed method automatically extracts the vascular network connected to a user-defined point in a user-defined direction, and requires no further user interaction. The toolkit prevents additional injection of contrast agent and X-ray dose, saves time for the interventional radiologist. While the algorithm is applicable on all 3-D angiography images, performance of the method is observed on 3-D catheter angiography image of cerebrovascular structures. The algorithm iteratively tracks gravity centers of vascular branches in the user-defined direction, preserving connection to the user-defined point. Curvy branches are tracked even if they have discontinuous portions. Since this tracking method does not depend on lumen diameter and intensity differences, branches with stenoses and branches having large intensity difference can be successfully tracked. Skeletonization and junction detection methods are described, which are used to detect the sub branches, indirectly connected to the point. These methods are capable of handling bifurcations, trifurcations, and junctions having more branches. However, false junctions occurring due to superposition of vessels are not eliminated.