In this work, the technique of designing and optimizing broadband volume transmission holograms using dichromate gelatin (DCG) is summarized for solar spectrum-splitting application. Spectrum splitting photovoltaic system uses a series of single bandgap PV cells that have different spectral conversion efficiency properties to more fully utilize the solar spectrum. In such a system, one or more high performance optical filters are usually required to split the solar spectrum and efficiently send them to the corresponding PV cells. An ideal spectral filter should have a rectangular shape with sharp transition wavelengths. DCG is a near ideal holographic material for solar applications as it can achieve high refractive index modulation, low absorption and scattering properties and long-term stability to solar exposure after sealing. In this research, a methodology of designing and modeling a transmission DCG hologram using coupled wave analysis for different PV bandgap combinations is described. To achieve a broad diffraction bandwidth and sharp cut-off wavelength, a cascaded structure of multiple thick holograms is described. A search algorithm is also developed to optimize both single and two-layer cascaded holographic spectrum splitters for the best bandgap combinations of two- and three-junction SSPV systems illuminated under the AM1.5 solar spectrum. The power conversion efficiencies of the optimized systems under the AM1.5 solar spectrum are then calculated using the detailed balance method, and shows an improvement compared with tandem structure.

Growth suppression mediated by connexin 37 (Cx37; also known as GJA4) requires interaction between its C-terminus and functional pore-forming domain. Using rat insulinoma cells, we show that Cx37 induces cell death and cell cycle arrest, and slowed cell cycling. Whether differential phosphorylation might regulate intramolecular interactions, and consequently the growth-suppressive phenotype, is unknown. Protein kinase C inhibition increased the open state probability of low-conductance gap junction channels (GJChs) and reduced GJCh closed state probability. Substituting alanine at serine residues 275, 302 and 328 eliminated Cx37-induced cell death, supported proliferation and reduced the GJCh closed state probability. With additional alanine for serine substitutions at residues 285, 319, 321 and 325, Cx37-induced cell death was eliminated and the growth arrest period prolonged, and GJCh closed state probability was restored. With aspartate substitution at these seven sites, apoptosis was induced and the open state probability of large conductance GJChs (and hemichannels) was increased. These data suggest that differential phosphorylation of the C-terminus regulates channel conformation and, thereby, cell cycle progression and cell survival.

Abstract The quantum-mechanical effects typical for single atoms or molecules can be reproduced in micrometer-scale electric devices. In these systems the essential component is a small Josephson junction (JJ) consisting of two superconductors separated by a thin insulator. The quantum phenomena can be controlled in real time by external signals and have a great potential for novel applications. However, their fragility on uncontrolled disturbance caused by typical nearby environments is a drawback for quantum information science, but a virtue for detector technology. Motivated by this we have theoretically studied transistor kind of devices based on single-charge tunneling through small JJs. A common factor of the research is the analysis of the interplay between the coherent Cooper-pair (charge carriers in the superconducting state) tunneling and incoherent environmental processes. In the first work we calculate the current due to incoherent Cooper-pair tunneling through a voltage-biased small JJ in series with large JJs and compare the results with recent experiments. We are able to reproduce the main experimental features and interpret these as traces of energy levels and energy bands of the mesoscopic device. In the second work we analyze a similar circuit (asymmetric single-Cooper-pair transistor) but under the assumption that the Cooper-pair tunneling is mainly coherent. This predicts new resonant transport voltages in the circuit due to higher-order processes. However, no clear traces of most of them are seen in the experiments, and similar discrepancy is present also in the case of the symmetric circuit. We continue to study this problem by modeling the interplay between the coherent and incoherent processes more accurately using a density-matrix approach. By this we are able to demonstrate that in typical conditions most of these resonances are indeed washed out by strong decoherence caused by the environment. We also analyze the contribution of three typical weakly interacting dissipative environments: electromagnetic environment, spurious charge fluctuators in the nearby insulating materials, and quasiparticles. In the last work we model the dynamics of a current-biased JJ perturbed by a smaller JJ using a similar density-matrix approach. We demonstrate that the small JJ can be used also as a detector of the energy-band dynamics in a current biased JJ. The method is also used for modeling the charge transport in the Bloch-oscillating transistor.

The mouse nervous system undergoes a vast remodelling of synaptic connections postnatally, resulting in a reduced number of innervating axons to target cells within the first few weeks of life. This extensive loss of connections is known as synapse elimination and it plays a critical role in sculpting and refining neural connectivity throughout the nervous system, resulting in a finely tuned and well-synchronised network of innervation. This process has been well characterised at the mouse neuromuscular junction (NMJ), where synapse elimination takes place postnatally in all skeletal muscles. It has been well studied for the reasons that it is easily accessible for live imaging and post-mortem experimental analysis. Studies utilising this synapse to uncover regulators of synapse elimination have mainly focused on the importance of glial cell lysosomal activity, nerve conduction and target-derived growth factor supply. It is clear that non-axonal cell types play key roles in the success of developmental axon retraction at the NMJ, however the role of glial cells in the regulation of this process has not been fully explored, as lysosomal activity is thought of as a consequence of axon pruning rather than a molecular driver. Previous studies have shown that signals emanating from myelinating glial cells can modulate neurofilament composition and transport within the underlying axons. We know that these changes in neurofilament composition and transport are underway during developmental synapse elimination at the NMJ, so it seems logical to predict that myelinating glial cells may play a role in the regulation of axonal pruning. Myelinating glial cells are found along the entire length of lower motor neurons and form physical interactions with the underlying axons at regions known as paranodes. At the paranode, Neurofascin155 (Nfasc155: expressed by the myelinating glial cell) interacts with a Caspr/contactin complex (expressed by the axon). This site has been proposed as a likely site for axon-glial signalling due to the close apposition of the cell membranes. The main focus of this PhD project was to study the potential role of myelinating glial cells in the success of synapse elimination at the NMJ, using a mouse model of paranodal disruption (Nfasc155-/-). Chapters 3 and 4 show the results of this work. This work has revealed a novel role for glia in the modulation of synapse elimination at the mouse neuromuscular junction, mediated by Nfasc155 in the myelinating Schwann cell. Synapse elimination was profoundly delayed in Nfasc155-/- mice and was found to be associated with a non-canonical role for Nfasc155, as synapse elimination occurred normally in mice lacking the axonal paranodal protein Caspr. Loss of Nfasc155 was sufficient to disrupt axonal proteins contributing to cytoskeletal organisation and trafficking pathways in peripheral nerve of Nfasc155-/- mice and lower levels of neurofilament light (NF-L) protein in maturing motor axon terminals. Synapse elimination was delayed in mice lacking NF-L, suggesting that Nfasc155 influences neuronal remodelling, at least in part, by modifying cytoskeletal dynamics in motor neurons. This work provides the first clear evidence for myelinating Schwann cells acting as drivers of synapse elimination, with Nfasc155 playing a critical role in glial cell-mediated postnatal sculpting of neuronal connectivity in the peripheral nervous system. A small section of the results within this thesis are devoted to the study of axon-glial interactions in a mouse model of childhood motor neuron disease, otherwise known as spinal muscular atrophy (SMA). In SMA, there are reduced levels of the ubiquitously expressed survival motor neuron (SMN) protein. The NMJ is a particularly vulnerable target in SMA, manifesting as a breakdown of neuromuscular connectivity and progressive motor impairment. Recent studies have begun to shed light on the role of non-neuronal cell types in the onset and progression of the disease, presenting SMA as a multi-system disease rather than a purely neuronal disorder. Recent evidence has highlighted that myelinating glial cells are significantly affected in a mouse model of SMA, manifesting as an impaired ability to produce key myelin proteins, resulting in deficient myelination. The final results chapter of this thesis (Chapter 5) is focussed on further exploring the effects that loss of SMN has in Schwann cells including their interactions with underlying axons. This work reveals a disruption to axon-glial interaction, shown by a delay in the development of paranodes, supporting the idea that non-neuronal cell types are also affected in SMA. The results within this thesis reveal a novel role for a glial cell protein, Nfasc155, in the modulation of synapse elimination at the NMJ. Mechanistic insight in to Nfasc155’s role in this process is also uncovered and likely involves axonal cytoskeletal transport systems and the filamentous protein NF-L, which have not previously been implicated in the process of synapse elimination. This work highlights an important role for axon-glial interactions during normal postnatal development of the mouse NMJ. This work also highlights a role for axon-glial interactions in disease states of the NMJ. Using a mouse model of SMA, axon-glial interaction was assessed with the finding of a delay in paranodal maturation due to loss of SMN.

La télomérase est essentielle pour le maintien des télomères. Elle compense le problème de réplication de l’ADN télomérique par l’ajout de séquences d’ADN aux extrémités des chromosomes. Chez l’humain, elle est très active dans les premiers stades du développement (embryon, fœtus). Puis, son activité est réprimée pour devenir indétectable dans la plupart des cellules. Ceci conduit au raccourcissement de l’ADN télomérique, à la déprotection de l’ADN et à un arrêt de division cellulaire, appelé senescence. Par contre, dans 90% des cellules de type cancéreux, elle est suractivée. Elle contribue donc à une capacité continue de la prolifération de ces cellules et à leur immortalisation. Notre organisme d’étude est la levure bourgeonnante, Saccharomyces cerevisiae. En plus de ses nombreux avantages d’utilisation, chez cette levure, la télomérase est exprimée constitutivement, ce qui signifie qu’elle nous rapproche le plus du contexte de cellule cancéreuse. Mon projet de maîtrise vise à étudier un des composants de la télomérase chez la levure S. cerevisiae, c’est-à-dire la sous-unité ARN, appelée Tlc1, et plus particulièrement une sous-partie de cet ARN, formant une jonction à trois branches (« Three Way Junction »). Jusqu’à présent, cette structure a été considérée comme étant non essentielle. Pourtant, cette structure très conservée a été démontrée comme étant essentielle à l’assemblage de la télomérase et à son activité, chez une grande variété d’espèces. Avec ce projet, j’ai tenté de déterminer si cette structure à trois branches a un quelconque rôle à jouer que ce soit dans l’assemblage ou dans l’activité de la télomérase. J’ai exploré cette structure en y réalisant des mutations et en analysant leurs effets sur la croissance cellulaire et sur la longueur des télomères. Parmi tous les mutants, la simple substitution d’un nucléotide spécifique, l’adénine 119, conduit à des télomères plus courts qui demeurent stables au fil des générations et les levures sont viables. De plus, ce raccourcissement est de l’ordre de la centaine de paires de bases lorsque la délétion d’une partie ou de la structure au complet est réalisée. C’est donc un raccourcissement significatif, représentant près d’un tiers de la longueur normale des télomères. Par ailleurs, sur des cellules présentant des télomères anormalement courts, l’ajout de ces mutations de la TWJ de TLC1 crée un phénotype létal. / Abstract : Telomerase is essential for telomere maintenance. It compensates for the End-replication problem by adding DNA sequences to the ends of chromosomes. In humans, telomerase is very active in the early stages of development (embryos, foetus). Later, its activity is repressed, and in most cells its activity becomes undetectable. This leads to telomere shortening, a deprotection of chromosome ends and to an arrest of cellular divisions, a highly regulated process also called cellular senescence. However, in cancer cells of 90% of all subtypes, telomerase is up-regulated. Hence, this enzyme promotes the proliferative capacity of cancer cells and their immortalization. The budding yeast Saccharomyces cerevisiae is our organism of study. In addition to its ease of access, telomerase is constitutively expressed in this yeast, which makes it a useful and inexpensive model of cancer cells. My master’s project aims at studying one of the telomerase components in S. cerevisiae, namely the RNA subunit Tlc1, and more specifically a part of this RNA, forming a Three-Way Junction (TWJ). So far, this structure was considered as non-essential for cell viability. However, this structure is highly conserved among species, and in diverse species it was shown to be crucial for telomerase assembly and activity. My project hence consisted in trying to determine whether or not this structure plays a role in telomerase assembly or activity. The requirements on this structure were explored by creating mutations and by analyzing their effects on cell growth and telomere length. Of all the mutants, a specific nucleotide substitution, Adenine 119 in the TWJ, leads to shortened telomeres, and this shortening is stable during further outgrowth. Furthermore, a telomere shortening of up to 100 base pairs is observed when a part or the complete TWJ structure is deleted. This shortening is quite significant as it represents about one third of the normal length of telomeres. Moreover, expressing these mutants of the TWJ in cells with short telomeres creates a synthetic lethal effect.

The discovery of stem and progenitor cells capable of ongoing neurogenesis in the adult mammalian brain has raised hope that we will one day be able to harness their intrinsic regenerative capacity following injury. Development of such therapeutic strategies relies on a comprehensive understanding of the underlying regulation of the neurogenic process. To this end, I show, in this thesis, that cultured post-natal hippocampal neural progenitor cells (NPCs) express a specific repertoire of connexins (Cx), a family of channel forming proteins critical for communication prior to the development of functional chemical synapses. I show that this pattern of Cx expression, specifically Cx43 and Cx45, is modulated by interaction with the extracellular matrix component laminin providing evidence of extracellular matrix-cell interaction in the regulation of intrinsic Cx expression and function in postnatal NPCs. In adult brain, I show, for the first time, that Cx45 localizes to all cell types of the neuronal lineage with the exception of the type 3 doublecortin (DCX)-positive NPCs. Using a loss of function approach, I show that this expression is required for the normal proliferation of type 1 nestin and glial fibrillary acidic protein-positive stem like NPCs but not for the differentiation or survival of their progeny in the adult hippocampus. With respect to exogenous pharmacological cues that influence hippocampal neurogenesis, this thesis also demonstrates that chronic treatment with a sub-set of selective serotonin reuptake inhibitor antidepressants, fluoxetine and escitalopram, increases the proliferation but not the survival of adult NPCs in healthy, non-depressed mice. Further, standard post-operative analgesia with the opiate buprenorphine inhibits the proliferation of DCX-positive adult NPCs and increases the survival of their progeny. Finally, over the course of the research for this thesis, it became clear that exposing research animals to even very subtle environmental changes can influence the basal neurogenic process. Ultimately this work further highlights the exquisite sensitivity of the regulation of what is already recognized to be a highly dynamic process and provides important insight into the neurogenic process that can be used to inform future therapeutic development and application.

A novel approach to the design of multi-junction solar cells on silicon substrates for 1-sun applications is described. Models for device simulation including porous silicon layers are presented. A silicon bottom subcell is formed by diffusion of dopants into a silicon wafer. The top of the wafer is porosified to create a compliant layer, and a III-V buffer layer is then grown epitaxially, followed by middle and top subcells. Due to the resistivity of the porous material, these designs are best suited to high efficiency 1-sun applications. Numerical simulations of a multi-junction solar cell incorporating a porous silicon compliant membrane indicate an efficiency of 30.7% under AM1.5G, 1-sun for low threading dislocation densities (TDD), decreasing to 23.7% for a TDD of 10^7 cm^-2.

At the author’s request, the abstract has been removed due to the confidential nature of the thesis. It will be added once the embargo period has passed.

Cette thèse décrit la fabrication de systèmes hybrides basés sur le semi-conducteur InAs et leur étude par spectroscopie STM et la mesure de jonctions Josephson. Dans une première expérience, je montre que des nanocristaux (NC) de plomb (Pb) supraconducteurs de haute qualité peuvent être réalisés sur la surface (110) d'InAs. Lorsque la taille latérale des NC est inférieure à la longueur d'onde de Fermi du gaz d'électrons bidimensionnel accumulé à la surface de InAs, les NC ne sont que faiblement couplés à ce gaz électronique et se retrouvent donc dans le régime de blocage de Coulomb. Ce phénomène a permis la première étude de l'effet de parité supraconducteur par spectroscopie STM, que nous avons utilisée pour vérifier la validité de la limite d'Anderson. Dans une seconde expérience, je montre que des NC de Bismuth (Bi) de haute qualité peuvent également être réalisés sur la surface (110) d'InAs. Contrairement aux NC de Pb, une couche de mouillage de Bi sépare les NC de la surface InAs, conduisant à un fort couplage entre les NC de Bi et le substrat. A partir de la spectroscopie STM, nous avons identifié des états de bord sur le plan (111) des NC avec une symétrie C3. En supposant que le bismuth est un isolant topologique de second ordre comme suggéré théoriquement, les états de bords observés peuvent être interprétés naturellement comme les états de charnière prédits dans cette dernière théorie de bande topologique. / This thesis describes the fabrication of hybrid systems based on the narrow-gap semiconductor InAs and their study through STM spectroscopy and measure of the Josephson characteristics. In the first experiment, I show that high quality superconducting Lead (Pb) nanocrystals can be grown on the (110) surface of InAs. When the lateral size of the Pb nanocrystals is smaller than the Fermi wavelength of the two-dimensional electron gas accumulated at the surface of InAs, the nanocrystals are only weakly coupled to this electron gas and, consequently, are found in the regime of Coulomb blockade. This phenomenon enabled the first study of the superconducting parity effect through STM spectroscopy, which we employed to check the validity of the Anderson limit. In the second experiment, I show that high quality Bismuth (Bi) nanocrystals can also be grown on the (110) surface of InAs. In contrast to Pb nanocrystals, a wetting layer of Bi separates the nanocrystals from the InAs surface, leading to a strong coupling between the Bi nanocrystals and the substrate. From STM spectroscopy, we have identified edge-states on the (111) plane of the nanocrystals with C3 symmetry. Assuming that Bismuth is a 2nd order topological insulator as suggested theoretically, the observed edge-states can be interpreted naturally as the hinge-states predicted in this last topological band-theory. Finally, I will present the methods that I developed for the fabrication of hybrid Josephson junctions on bulk InAs and InAs/GaSb heterostructures, together with preliminary measurements of Josephson characteristics.

Magnetic sensors are deployed in many applications such as automotive, consumer electronics, navigation and data storage devices. Their market’s growth is driven by demands of higher performance; primarily to assist in the advancement of the Internet of Things (IoT) and smart systems. Challenging obstacles of miniaturization and power consumptions must be overcome. A leading sensor that has the potential to accelerate the development is the magnetic tunnel junction (MTJ) devices. Corrosion causes catastrophic consequences for industries. Preventive measures could save up to 35% of annual corrosion-related costs. An advanced corrosion sensing technique is developed based on iron nanowires. The iron nanowires are magnets which lose their magnetization when corroded. Their magnetization loss is monitored using sensitive MTJ sensor. Combined, the nanowires and the MTJ sensor realize a highly integrated sensor concept that enables corrosion sensing with an ultra-low power consumption of less than 1 nW, a sensitivity of 0.1 %/min, a response time of 30 minutes and an area of 128 μm2. Surgical tool development is accelerating in the healthcare sector. Cardiac catheterization specifically is a minimally invasive surgery that relies heavily on x-ray imaging and contrast dyes. A flexible tri-axis MTJ sensor is developed to help minimizing the need for x-ray imaging during the procedure. The flexible sensor can bend to a diameter of 500 μm without compromising the performance and can endure over 1000 bending cycles without fatigue. Three flexible sensors are mounted onto the tip of a 3 mm cardiac catheter, realizing a novel sensor-on-tube (SOT) tri-axis sensor concept. The sensor has a high sensitivity of 9 Ω/° and an MR ratio of 29%. It weighs 16 μg only, adds 5 μm to the catheter’s diameter and a total size 300 μm2. The prototype system estimated the heading angle with an RMS error value of 7° and tracked the orientation of the sensor with an acceptable accuracy. However, the sensor has a misalignment issue caused by the manual placement of the sensors. A high precision tool is needed for the assembly, and any further misplacement -within a reasonable margin of error- could be corrected by calibration algorithms.