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The quality of GaN template layer plays a very important role in high electron mobility transistors. We proposed a special method in the growth of molecular beam epitaxy to deal with the dilemma between structure and the morphology of GaN. In our study, we used a nitrogen-rich GaN growth condition to deposit the initial varied layer. After that, we changed the N/Ga ratio stepwise to the growth condition of gallium-rich GaN and grew the epitaxy layer right away. In X-ray diffraction analysis, the full width at half-maximum (FWHM) value of rocking curves of GaN(002) was improved relatively to gallium-rich sample from 531.69 arcsecond to 59.43 arcsecond. In atomic force microscopy (AFM) analysis, the root mean square (rms) roughness of sample surface was improved relatively to nitrogen-rich sample from 18.28 nm to 1.62 nm over 5 £gm ¡Ñ 5 £gm area. The Raman scattering shows there is a slightly tilted plane in gradient layer and the gradient layer can also slash the strain force which is caused from Ga-rich GaN epitaxy layer and AlN buffer layer. A series high mobility AlxGa1-xN/GaN heterostructures samples were grown on MOVPE-grown GaN templates substrate by molecular beam epitaxy with different Al concentrations (x = 0.017~0.355). The quality checked by XRD and AFM indicated that the excellent properties agreed with the GaN-template. The highest mobility in this series samples at 8 K is 19593 cm2/Vs with carrier concentration 3.13 ¡Ñ 1012 cm-2 and Al concentration x = 0.017. In our experiments, the carrier density decreases as Al concentration reduces. In the illuminated Hall measurement, there are only few electrons increased following blue LED illumination. It shows that there are only few deep level defects existing near the heterointerface. From temperature-depended Shubnikov-de Haas (SdH) oscillations, the electron effective mass m* in 2DEG are evaluated as 0.213 mo and for x = 0.207 0.227 moand 0.136 respectively. The high mobility AlxGa1-xN/GaN was fabricated to a series of wires by focused ion beam (FIB) equipment, and the width of the active channel is ranged from 900 nm to 50 nm (900 nm, 500 nm, 300 nm, 200 nm, 100 nm, 80 nm and 50 nm) with the channel orientation in [11 0] direction. The largest spin-splitting energy in the series of wires is 2.14 meV. Due to larger spin-splitting energy and quasi-ballistic transportation, the 200 nm wire is the best candidate to be the channel of the quantum-ring interferometer in our case.

Rapid Diagnostic Tests (RDTs) for malaria are restricted to a few biomarkers and antibody-mediated detection. However, the expression of commonly used biomarkers varies geographically and the sensibility of immunodetection can be affected by batch-to-batch differences or limited thermal stability. In this study we aimed to overcome these limitations by identifying a potential biomarker and by developing molecular sensors based on aptamer technology. Using gene expression databases, ribosome profiling analysis, and structural modeling, we find that the High Mobility Group Box 1 protein (HMGB1) of Plasmodium falciparum is highly expressed, structurally stable, and present along all blood-stages of P. falciparum infection. To develop biosensors, we used in vitro evolution techniques to produce DNA aptamers for the recombinantly expressed HMG-box, the conserved domain of HMGB1. An evolutionary approach for evaluating the dynamics of aptamer populations suggested three predominant aptamer motifs. Representatives of the aptamer families were tested for binding parameters to the HMG-box domain using microscale thermophoresis and rapid kinetics. Dissociation constants of the aptamers varied over two orders of magnitude between nano- and micromolar ranges while the aptamer-HMG-box interaction occurred in a few seconds. The specificity of aptamer binding to the HMG-box of P. falciparum compared to its human homolog depended on pH conditions. Altogether, our study proposes HMGB1 as a candidate biomarker and a set of sensing aptamers that can be further developed into rapid diagnostic tests for P. falciparum detection. / Grand Challenges Canada / Revisión por pares

For the last four decades, Si CMOS technology has been advancing with Moore’s law prediction, working itself down to the sub-20 nm regime. However, fundamental problems and limitations arise with the down-scaling of transistors and thus new innovations needed to be discovered in order to further improve device performance without compromising power consumption and size. Thus, a lot of studies have focused on the development of new CMOS compatible architectures as well as the discovery of new high mobility channel materials that will allow further miniaturization of CMOS transistors and improvement of device performance. Pushing the limits even further, flexible and foldable electronics seem to be the new attractive topic. By being able to make our devices flexible through a CMOS compatible process, one will be able to integrate hundreds of billions of more transistors in a small volumetric space, allowing to increase the performance and speed of our electronics all together with making things thinner, lighter, smaller and even interactive with the human skin. Thus, in this thesis, we introduce for the first time a cost-effective CMOS compatible approach to make high-k/metal gate devices on flexible Germanium (Ge) and Silicon-Germanium (SiGe) platforms. In the first part, we will look at the various approaches in the literature that has been developed to get flexible platforms, as well as we will give a brief overview about epitaxial growth of Si1-xGex films. We will also examine the electrical properties of the Si1-xGex alloys up to Ge (x=1) and discuss how strain affects the band structure diagram, and thus the mobility of the material. We will also review the material growth properties as well as the state-of-the-art results on high mobility metal-oxide semiconductor capacitors (MOSCAPs) using strained SiGe films. Then, we will introduce the flexible process that we have developed, based on a cost-effective “trench-protect-release-reuse” approach, utilizing the industry’s most used bulk Si (100) wafers, and discuss how it has been used for getting flexible and semi-transparent SiGe and Ge platforms. Finally, we examine the electrical characteristics of our materials through the fabrication of high-k/metal gate MOSCAPs with SiGe and Ge as channel material. We present their electrical performance on both non- flexible and flexible platform and discuss further improvement that has to be made in order to get better behaving devices for future MOSFET fabrication.

Myocardial dysfunction is a major consequence of septic shock and contributes to the high mortality of sepsis. High-mobility group box 1 (HMGB1) serves as a late mediator of lethality in sepsis. We have reported that glucan phosphate (GP) attenuates cardiac dysfunction and increases survival in cecal ligation and puncture (CLP)-induced septic mice. In the present study, we examined the effect of GP on HMGB1 translocation from the nucleus to the cytoplasm in the myocardium of septic mice. GP was administered to mice 1 h before induction of CLP. Sham-operated mice served as control. The levels of HMGB1, Toll-like receptor 4 (TLR4), and NF-κB binding activity were examined. In an in vitro study, H9C2 cardiomyoblasts were treated with lipopolysaccharide (LPS) in the presence or absence of GP. H9C2 cells were also transfected with Ad5-IκBα mutant, a super repressor of NF-κB activity, before LPS stimulation. CLP significantly increased the levels of HMGB1, TLR4, and NF-κB binding activity in the myocardium. In contrast, GP administration attenuated CLP-induced HMGB1 translocation from the nucleus to the cytoplasm and reduced CLP-induced increases in TLR4 and NF-κB activity in the myocardium. In vitro studies showed that GP prevented LPS-induced HMGB1 translocation and NF-κB binding activity. Blocking NF-κB binding activity by Ad5-IκBα attenuated LPSinduced HMGB1 translocation. GP administration also reduced the LPS-stimulated interaction of HMGB1 with TLR4. These data suggest that attenuation of HMGB1 translocation by GP is mediated through inhibition of NF-κB activation in CLP-induced sepsis and that activation of NF-κB is required for HMGB1 translocation.

The understanding and study of electron transport in semiconductor systems has been the instigation behind the growth of semiconductor electronics industry which has enabled technological developments that are part of our everyday lives. However, most materials exhibit diffusive electron transport where electrons scatter off disorder (impurities, phonons, defects, etc.) inevitably present in the system, and lose their momentum. Advances in material science have led to the discovery of materials which are essentially disorder-free and exhibit exceptionally high mobilities, enabling transport physics beyond diffusive transport. In this work, we explore non-diffusive transport regimes, namely, the ballistic and hydrodynamic regimes in a high-mobility two-dimensional electron system in a GaAs quantum well in a GaAs/AlGaAs heterostructure. The hydrodynamic regime exhibits collective fluid-like behavior of electrons which leads to the formation of current vortices, attributable to the dominance of electron-electron interactions in this regime. The ballistic regime occurs at low temperatures, where electron-electron interactions are weak, constraining the electrons to scatter predominantly against the device boundaries. To study these non-diffusive regimes, we fabricate mesoscopic devices with multiple point contacts on the heterostructure, and perform variable-temperature (4.1 K to 40 K) zero-field nonlocal resistance measurements at various locations in the device to map the movement of electrons. The experiments, along with interpretation using kinetic simulations, demarcate hydrodynamic and ballistic regimes and establish the dominant role of electron-electron interactions in the hydrodynamic regime. To further understand the role of electron-electron interactions, we perform nonlocal resistance measurements in the presence of magnetic field in transverse magnetic focusing geometries under variable temperature (0.39 K to 36 K). Using our experimental results and insights from the kinetic simulations, we quantify electron-electron scattering length, while also highlighting the importance of electron-electron interactions even in ballistic transport. At a more fundamental level, we reveal the presence of current vortices in both hydrodynamic and surprisingly, ballistic regimes both in the presence and absence of magnetic field. We demonstrate that even the ballistic regime can manifest negative nonlocal resistances which should not be considered as the hallmark signature of hydrodynamic regime. The work sheds a new light on both hydrodynamic and ballistic transport in high-mobility solid-state systems, highlighting the similarities between these non-diffusive regimes and at the same time providing a way of effectively demarcating them using innovative device design, measurement schemes and one-to-one modeling. The similarities stem from total electron system momentum conservation in both the hydrodynamic and ballistic regimes. The work also presents a sensitive and precise experimental technique for measuring electron-electron scattering length, which is a fundamental quantity in solid-state physics. / Doctor of Philosophy / Electrons are the charged particles that are bound around the nuclei of atoms. But sometimes in a solid material electrons break free away from the nuclei and wander around. They are then the carriers of electric current ubiquitous in our daily lives as in our homes, and in our electronic devices such as smartphones and computers. Often an analogy is made between the flow of electric current in a material and the flow of water in a stream. However, the analogy does not hold well for most materials. In most materials the motion of electrons can be thought of as balls in a pinball machine - their movement hindered and randomized by collisions with the countless defects and impurities present in the material they travel through. However, recently scientists have been able to synthesize ultraclean materials, where electrons can indeed mimic the flow of water under the right conditions. In this aptly-named hydrodynamic regime, electrons predominantly interact with each other and that leads to the formation of current whirlpools or vortices similar to those forming in water. A telling signature of this regime is a negative electrical resistance appearing near the location of the vortex. When the interactions between electrons are weak, such as at very low temperatures, electrons move along straight-line trajectories until they hit and bounce off the device edges, similar to billiard balls. This low-temperature phenomenon is called ballistic transport. In this work we reveal that measurement of negative resistance and formation of current vortices are not unique to the hydrodynamic regime but can occur in the ballistic regime as well. It is indeed counterintuitive that electrons moving like billiards balls can behave similarly to electrons flowing like water. The similarities can be traced back to a fundamental physics conservation law active in both situations, namely momentum conservation. To experimentally realize the tests, we use a very high purity semiconductor material GaAs/AlGaAs and fabricate tiny devices on the material with a cutting-edge design, capable of precisely measuring resistance at various locations along the device to map the movement of electrons. The simulations of the novel physics indeed reveal current vortices of various sizes in the ballistic regime, in agreement with the experimental data showing negative resistance. In another experiment, we apply a magnetic field, making the electrons move in circular paths. If uninterrupted, electrons complete half circles and are collected through an opening in the device, giving resistance peaks in experiments. Due to electron-electron interactions, the electrons on their circular trajectory are interrupted by other electrons which leads to a decay in resistance peaks. This decay is utilized to measure the strength of electron-electron interactions. The work has both fundamental and applied implications. The existence of whirlpools shows that the electron momentum is not lost by collisions, and that in turn means that the conduction of electrical current in these regimes is inherently efficient. This opens up avenues for electronic devices which are faster, more functional and more power efficient than present electronic devices.

Chez les eucaryotes pluricellulaires, la différenciation des cellules repose en partie sur l’activation oula répression des gènes. Les profils d’expression génique mis en place vont perdurer d’une générationcellulaire à l’autre. Ce phénomène met en jeu des mécanismes épigénétiques qui remodèlentlocalement la structure de la chromatine. Chez Drosophila melanogaster, les protéines des groupesPolycomb (PcG) et Trithorax (TrxG) participent au maintien du profil d’expression des gènes au coursdu développement. Les protéines PcG maintiennent les gènes réprimés tandis que les protéines TrxGmaintiennent les gènes activés. Une troisième classe de protéines nommée Enhancers of Trithoraxand Polycomb (ETP) module l’activité des PcG et TrxG. Dorsal Switch Protein 1 (DSP1) est uneprotéine HMGB (High Mobility Group B) classée comme une ETP. Par tamisage moléculaire, nousavions montré que la protéine DSP1 était présente au sein de complexes de poids moléculaire de 100kDa à 1 MDa. Le travail de thèse présenté ici a pour but d’identifier les partenaires de la protéineDSP1 dans l’embryon et de mieux connaître les propriétés biochimiques de DSP1. Premièrement, j’aimis en place puis effectué l’immunopurification des complexes contenant DSP1 dans des extraitsprotéiques embryonnaires. Cette approche nous a permis d’identifier 23 partenaires putatifs de laprotéine DSP1. Parmi ces protéines, nous avons identifié la protéine Rm62 qui est une ARN hélicaseà boîte DEAD. Les relations biologiques entre DSP1 et Rm62 ont été précisées. Deuxièmement, j’aidéterminé, par une approche biochimique, de nouvelles caractéristiques physico-chimiques de laprotéine DSP1. / In multicellular organism, the identity of cell is determined by several factors playing on genesexpression. Once established, the gene expression pattern is transmitted to daughter cells through aprocess involving epigenetic mechanisms that locally reshape the structure of chromatin. In Drosophilamelanogaster, the Polycomb (PcG) and trithorax (trxG) group genes are involved in the maintenanceof gene expression profile during development. Inside multimeric complexes, PcG proteins maintaingenes in repressed state whereas TrxG maintain genes active. A third class of proteins, calledEnhancers of Trithorax and Polycomb, regulate PcG and TrxG activities. Dorsal Switch Protein 1(DSP1) is a High Mobility Group B protein acting as an ETP. But DSP1 has not yet been identified inPcG or TrxG complexes. On the basis of gel filtration analysis of protein complexes in embryo nuclearextracts, it appears that the majority of DSP1 is present in complex(es) from 100 kDa to 1MDa. Aimsof present work are the identification of DSP1 protein partners in drosophila embryo and thecharacterization of biochemical properties of DSP1. Firstly, I used immunopurification from drosophilaembryonic nuclear extracts. The proteins purified with DSP1 were characterized through sequencingof peptides from individual protein bands by mass spectrometry. Among identified proteins, wefocused on the DEAD Box RNA helicase, Rm62. The role of interaction between DSP1 and Rm62 hasbeen characterized. Secondly, I have identified a new physicochemical aspect of DSP1 protein.

One of the major challenges in the field of organic semiconductors is to develop molecular design rules and processing routes which optimise the charge carrier mobility, whilst independently controlling the radiative and non-radiative processes. To date there has existed a seeming trade-off between charge carrier mobility and photoluminescence efficiency, which limits the development of some devices such as electrically pumped laser diodes. This thesis investigates fluorescence enhancement strategies for high-mobility polymer semiconductor systems and the mechanisms by which they currently display poor emission properties. Four independent approaches were taken and are detailed as follows. 1. Solubilising chain engineering It is shown that for the high mobility polymer poly(indacenodithiophene-co-benzothiadiazole), the addition of a phenyl- initiated side chain can enhance the solid-state fluorescence quantum yield, exciton lifetime and exciton diffusion length significantly in comparison to that without phenyl-addition. 2. Energy transfer to a highly fluorescent chromophore It is shown that for the high mobility polymer poly(indacenodithiophene-co-benzothiadiazole) efficient energy transfer to a more emissive squaraine dye molecule is possible despite fast non-radiative decay short exciton diffusion lengths. This results in a significant fluorescence enhancement, which in turn facilitates an order of magnitude increase of the efficiency of polymer light emitting diodes made from this material combination. 3. Energy gap engineering The well known Energy Gap Law predicts an increase in the non-radiative rate as the optical bandgap of an organic chromophore decreases in energy. In combination with this, almost all polymer semiconductors reported to date with high charge carrier mobility have low optical bandgaps. Therefore, molecular design principles which act to increase the optical bandgap of polymer semiconductors whilst retaining a high mobility were sought out. One specific system was successfully identified and showed a significant fluorescence enhancement compared to is predecessor poly(indacenodithiophene-co-benzothiadiazole) in both the solution and the solid state. It is found that the Frenkel exciton lifetime in this new system is a factor of four larger which also results in a significantly increased exciton diffusion length. An inter-chain electronic state is also identified and discussed. 4. Hydrogen substitution For some low-bandgap material systems such as erbium chromophores, high energy vibrational modes such as the C-H stretching mode can act as non-radiative pathways. The effect of hydrogen substitution with deuterium and fluorine was therefore investigated in a series of polythiophene derivative families. It was found that in the solid state, fluorescence and exciton lifetime enhancement occurred when the backbone hydrogen atoms were replaced with fluorine. However, evidence is given that this was not owing to the initial hypothesis, and is more likely owing to structural differences which occur in these substituted material systems.

High mobility group box 1 (HMGB-1) protein is a non-histone chromosomal protein. As a DNA binding protein, HMGB-1 is involved in the maintenance of nucleosome structure, regulation of gene transcription and it is active in DNA recombination and repair. It has been known that HMGB-1 is a late mediator of endotoxemia and sepsis. HMGB-1 is released from activated macrophages, induces the release of other proinflammatory mediators, and mediates cell death when overexpressed. We speculated that the course of sepsis maybe different without the involvement of HMGB-1. The aims of this study are to investigate the role of HMGB-1 in mediating sepsis and to observe the effects by using RNAi to affect the production of HMGB-1. Lipopolysaccharide (LPS) was used to simulate sepsis in culture as well as stimulate the release of HMGB-1 from RAW 264.7 cells. Levels of HMGB-1 in the culture medium were subsequently measured by Western blot. Other proinflammatory cytokines (TNF-£\, IL-6 and TGF-£]) were measured by ELISA. HMGB-1 could not be detected in the culture medium in the absence of LPS stimuli, but after 0.5 £gg/ml LPS treatment HMGB-1 release could be detected. HMGB-1 the amount of released from LPS activated RAW 264.7 cells was in a time- and dose-dependent manner. The present study demonstrated that RNAi in the treatment of LPS-stimulated RAW264.7 cells resulted in the blockade of HMGB-1 and decreased LPS-induced inflammatory response. The results demonstrated that HMGB-1 plays a pivotal role in macrophage inflammatory responses by modulating the production of inflammatory mediators.

In the eukaryotic nucleus, an immense length of DNA is compactly packaged to generate an ordered three-dimensional hierarchical structure called chromatin (van Holde, 1988; Wolffe, A.P, 1998). This organization forms a template for various DNA transaction processes like replication, transcription, recombination etc. The different stages of organization of the chromatin finally results in the 10,000-fold compaction observed in the metaphase chromosome. The problem of how the fibres of chromatin are folded has interested biologists and biochemists for decades. It has long been recognized that the Histones play a major part in this folding. However, the distinctly different roles of the Histones H2A, H2B, H3 and H4 on one hand and the lysine rich Histones such as Histone H1 and its cognates on the other, were not understood until after the discovery of the nucleosomes in the early 1970s. Some of the early insights into the structure of chromatin came through the digestion of nuclear chromatin with calcium-dependent endonucleases like micrococcal nuclease. A repeating kinetic intermediate of about 200 bp of DNA with Histones was obtained (Simpson, 1978). Based on repeating pattern of micrococcal nuclease digested chromatin and structural studies, Kornberg (1974) proposed that chromatin is composed of a flexible chain of repeating units of 100 A0 diameter. These units were termed as "nucleosomes" (Oudet et al, 1975). It then became clear that the Histones H2A, H2B, H3 and H4 were constituents of the nucleosome core particle whereas the lysine rich Histone H1 was somehow associated with the linker DNA between core particles. Hence, the formers are called core Histones and the latter as linker Histones. On further digestion of nucleosome, a nucleosome core was obtained in which wrapping of 146 bp of DNA about the Histone octamer to form the core particle provided the first level of folding. Electron microscopy and X-ray diffraction techniques suggested that this particle is a disk, 57 A0 thick and 110 A0 in diameter, and that the DNA is wound around the Histone core (Finch et al, 1977), But this cannot account for the many thousand-fold condensation of the DNA in the eukaryotic nucleus. The "string of beads" structure observed obviously could not satisfy the compaction requirement. It soon became evident that there exists some level of higher order folding of the chromatin fiber. In a classical paper, Finch and Klug (1976), showed that the extended nucleosomal filaments condense into irregular fibers of about 30 nm diameter in the presence of low concentrations of Mg 2+. Based on the data from earlier structural studies, these authors proposed a solenoid model in which nucleosomes were wrapped into a regular helix with a pitch of about 11nm. Later, it was observed that the formation of well defined fibers requires the presence of lysine rich Histones such as Histone H1.