Le nombre de lymphocytes T (LT) présents dans l’organisme est contrôlé de manière étroite et maintenu constant. En réponse à une chute de ce nombre, par exemple suite à une infection, un traitement de chimiothérapie ou lors d’une greffe de moelle osseuse, les LT résiduels ou transférés se divisent activement et repeuplent les compartiments lymphoïdes, rétablissant ainsi un nombre «normal» de cellules immunes périphériques. Ce processus, appelé prolifération homéostatique, est soutenu par l’IL-7 ainsi que les signaux TCR et mène à la génération de LT effecteurs/mémoire. Ces cellules effectrices/mémoire peuvent favoriser le développement d’une réponse anti-tumorale mais sont aussi impliquées dans le développement de maladies auto-immunes et inflammatoires.Des changements métaboliques sont étroitement liés à la différenciation et aux fonctions des LT. De plus, un nombre grandissant de données suggère qu’une modulation du métabolisme permet d’influencer le cours d’une réponse immune. L’AMP-activated protein kinase (AMPK) est un senseurmajeur du stress métabolique qui régule l’homéostasie des mitochondries, la glycolyse et l’équilibre rédox. Si l’AMPK est activée lors de la stimulation du TCR, son implication dans la biologie des LT reste confuse.Au cours de cette thèse, nous avons entrepris une série d’expériences afin d’évaluer le rôle de l’AMPK sur la biologie des LT et plus particulièrement au cours de leur prolifération homéostatique. Grâce à différents modèles in vivo et in vitro, nous avons montré que l’AMPK, bien que dispensable pour les étapes précoces de l’activation du TCR, est requise pour soutenir la viabilité et l’expansion des LT au cours de proliférations de longues durées. L’AMPK promeut l’accumulation de LT effecteurs/ mémoire au cours d’une prolifération homéostatique. En accord avec ces données, la transplantation de LT AMPK-KO dans un hôte allogénique conduit au développement d’une réaction du greffon contre l’hôte de moindre gravité.D’un point de vue métabolique, l’AMPK soutient le potentiel de membrane mitochondrial, permet une plus grande flexibilité métabolique, limite la production de dérivés toxiques de l’oxygène (ROS) et protège les LT contre le stress oxydant. En outre, la neutralisation des ROS par un traitement antioxydant restaure partiellement la prolifération des LT AMPK-KO.Nos données suggèrent qu’en limitant l’accumulation de dégâts mitochondriaux et oxydatifs au cours de cycles de divisions prolongées, l’AMPK soutient la viabilité, la prolifération et les fonctions effectrices des LT. / Doctorat en Sciences / info:eu-repo/semantics/nonPublished

The aim of this thesis is the development and implementation of a controlled testing platform for the Robust Intelligent Sensing and Controls (RISC) Lab at Utah State University (USU). This will be an open source adaptable expandable robotics platform usable for both education and research. This differs from the many other platforms developed in that the entire platform software will be made open source. This open source software will encourage collaboration among other universities and enable researchers to essentially pick up where others have left off without the necessity of replicating months or even years of work. The expected results of this research will create a foundation for diverse robotics investigation at USU as well as enable attempts at novel methods of control, estimation and optimization. This will also contribute a complete software testbed setup to the already vibrant robotics open source research community. This thesis first outlines the platform setup and novel developments therein. The second stage provides an example of how this has been used in education, providing an example curriculum implementing modern control techniques. The third section provides some exploratory research in trajectory control and state estimation of the tip of an inverted pendulum atop a small unmanned aerial vehicle as well as bearing-only cooperative localization experimentation. Finally, a conclusion and future work is discussed.

Indiana University-Purdue University Indianapolis (IUPUI) / Self-driving is simply the capacity of a vehicle to drive itself without human intervention. To accomplish this, the vehicle utilizes mechanical and electronic parts, sensors, actuators and an AI computer. The on-board PC runs advanced programming, which permits the vehicle to see and comprehend its current circumstance dependent on sensor input, limit itself in that climate and plan the ideal course from point A to point B. Independent driving is not an easy task, and to create self-sufficient driving arrangements is an exceptionally significant ability in the present programming designing field. ROS is a robust and versatile communication middle ware (framework) tailored and widely used for robotics applications. This thesis work intends to show how ROS could be used to create independent driving programming by investigating self-governing driving issues, looking at existing arrangements and building up a model vehicle utilizing ROS. The main focus of this thesis is to develop and implement a one-tenth scale of an autonomous RACECAR equipped with Jetson Nano board as the on-board computer, PCA9685 as PWM driver, sensors, and a ROS based software architecture. Finally, by following the methods presented in this thesis, it is conceivable to build an autonomous RACECAR that runs on ROS. By following the means portrayed in this theory of work, it is conceivable to build up a self-governing vehicle.

Indiana University-Purdue University Indianapolis (IUPUI) / Type 1 diabetes (T1D) is a multifactorial disease involving genetic and environmental factors. One of the factors implicated in disease pathogenesis is early life viral infection. A typical immune response to viral infection includes production of type 1 interferons (IFN), such as IFN-α, which can induce stress in the pancreatic β-cells. Reactive oxygen species (ROS) accumulation occurs after exposure to other inflammatory cytokines, causing oxidative stress that may be linked to T1D pathogenesis. Therefore, we hypothesized that IFN-α may also elicit β-cell ROS accumulation. Our in vivo and in vitro experiments with human islets showed rapid and heterogenous ROS accumulation with IFN-α. Although T1D is characterized by autoimmune destruction of β-cells, some cells survive this persistent attack. We hypothesized that survival/ death of β-cells could be attributed to the ability to effectively mitigate ROS accumulation. One mechanism to mitigate ROS is autophagy, which degrades and recycles cellular components to promote cellular homeostasis. We observed an impairment in autophagy in β-cells of donors with T1D as well as in islets of diabetic non-obese diabetic (NOD) mouse model of autoimmune diabetes. Autophagic flux was also impaired in diabetic NOD mouse islets, further confirming impairment of autophagy. Interestingly, we observed an induction of autophagy after acute treatment with IFN-α both in vitro and in vivo, suggesting compensatory upregulation of autophagy to restore homeostasis. Similarly, we observed an increase in autophagosomes and telolysosomes in β-cells of normoglycemic autoantibody positive organ donors compared to nondiabetic organ donors. Together, these data implicate a defect in the final degradation step of autophagy involving lysosomes. Therefore, we analyzed the activity and expression of lysosomal cysteine protease Cathepsin H (CTSH, a T1D susceptibility locus), and found both to be increased in islets of pre-diabetic NOD mice. Together, these data support compensatory hyperactivation of lysosomal enzymes prior to overt diabetes, potentially to rid the cell of ROS and degradation-resistant oxidized proteins and lipids. We also observed that C57Bl/6J mice lacking a key autophagy enzyme, ATG7, in their β-cells, spontaneously developed hyperglycemia. Collectively, these data highlight the importance of -phagic degradation process in the pathogenesis of T1D. / 2022-12-28

ROS is a set of computer operating system framework designed for robot software development, and Red Door, a lightweight software firewall that serves the ROS, is intended to strengthen its security. ROS has many flaws in security, such as clear text transmission of data, no authentication mechanism, etc. Red Door can achieve identity verification and access control policy with a small performance loss, all without modifying the ROS source code, to ensure the availability and authentication of ROS applications to the greatest extent.

No description available.

Oxidative stress (OS) occurs when DNA repair mechanisms are overcome by the amount of single and double strand DNA breaks caused by an accumulation of reactive oxygen species (ROS). Genomic instability (GI) by microsatellite instability (MSI) accumulation is characterized by changes in DNA single tandem repeats (STR) as a direct result of ROS. Deregulation of DNA repair and tumor suppressor pathways have been described as causes of tumor progression and metastasis. Studies in mammals have focused on GI and the implications of increased mutation frequency due to accumulation of MSI leading to development of diseases, including infertility and cancer. Ovarian cancer is a deadly disease displaying the highest mortality rate among gynecological cancers. Hereditary ovarian cancer displays GI that can be established early in primordial germinal cells (PCGs) development and migration across the genital ridge, where PGCs are exposed to ROS damage. The hypothesis of this study was ROS-induced GI is marked by the accumulation of MSI on repetitive sequences of DNA that override DNA repair, tumor suppressor and redox homeostasis pathways. In this study, we induced ROS in human ovarian cell lines by hydrogen peroxide (H2O2) exposure, as well as evaluated mouse PGCs to determine whether MSI occurs in specific regions of human and mouse genomes. Our results show that MSI was present in specific markers after ROS-induced damage in human ovarian cells and in mouse Sod1 knockout PGCs during cell migration, both of which accumulate specific mutations caused by free radical damage. Ovarian tumor cells and mouse PGCs showed an increase of MSI in 12 human and 5 mouse repetitive markers that are located near important genes related to DNA repair, tumor suppression, cell proliferation, apoptosis and differentiation. This could be a signal that leads to tumor initiation, formation and progression in adult ovarian cells due to improper DNA repair and tumor suppression mechanisms or in disruption of PGC migration that determines germinal cell pool selection during early embryonic development due to absence of cell antioxidant mechanisms. Therefore, these specific unstable STRs are novel biomarkers that could be useful in early diagnostics, prognosis, and successful therapy of ovarian tumorigenesis.

No description available.

Plague bacteria (Yersinia pestis) are transmitted to susceptible mammals by fleas. At least 25 flea species found in North America have been identified as plague vectors. The most efficient flea vector is the Oriental rat flea Xenopsylla cheopis, while the cat flea Ctenocephalides felis is a poor vector. The factors that determine vector competence of different fleas are not known. The main obstacles that the bacteria must overcome in the flea gut are also unknown. Fleas' molecular responses to Y. pestis invading could be a determining factor to control the bacterial survival and growth. Good and poor vectors might have different gene expression patterns when they are infected with Y. pestis. To investigate this hypothesis, we constructed cDNA libraries of infected fleas (X. cheopis and C. felis) using Suppression Subtractive Hybridization at 1 and 2 days post-infection. The infection approaches were either hemocoel injection or oral infection. We measured expression of several of the genes using quantitative real-time PCR. The results indicated that changes in gene expression were modest. We observed that the route of infection (oral vs. hemocoel injection) had a strong effect on the genes that were upregulated, with hemocoel injection inducing more obvious immune-related genes than oral infection. We also saw that infected X. cheopis has different gene expression patterns than infected C. felis. Several of the genes from both species are predicted to be involved in production and removal of reactive oxygen species (ROS). Consistent with this observation, the levels of peroxide in X. cheopis midguts was higher following oral infection with Y. pestis, than in uninfected fleas, and Y. pestis grew differently in antioxidant-fed fleas, demonstrating that ROS production could be an important defense in fleas early after infection

Reactive oxygen species (ROS) such as H2O2 can damage cellular components and are formed as a byproduct of mitochondrial oxidative metabolism. Studies using the nematode C. elegans have found that increasing ROS during development or early adulthood can extend lifespan, while increasing ROS during later adulthood normally decreases lifespan. NADPH provides the reducing power for several cellular antioxidants and is synthesized in a two-step reaction from NAD+ with the first step being catalyzed by NAD kinase (NADK). In this study, it questioned the effects of knocking down C. elegans cytoplasmic NADK, nadk-1 globally or in a neuron or intestine-specific manner starting from early development on oxygen consumption and ROS levels. It was hypothesized that knocking down the cytoplasmic NADK in C. elegans alters NADP+/NADPH ratios. This led to the prediction that ROS and O2 consumption levels would be decreased, and thioredoxin reductase activity levels will be increased in global and tissue-specific knockdowns. Three different strains of nematodes were used for this study: N2 wild type, intestinal RNAi sensitive strain VP303, and neuronal RNAi sensitive strain TU3401. The nadk-1 RNAi was introduced to the nematodes through their food source. To measure ROS levels, nematodes were treated with a tert-butylhydroperoxide insult to induce ROS generation, along with H2DCFDA dye to fluoresce when oxidized by ROS, pipetted into a 96-well plate, and ran through a microplate reader. For the oxygen consumption measurements, the nematodes were run through a Clark O2 electrode. Finally, Thioredoxin Reductase activity levels were measured using an assay kit that would inhibit testing groups thioredoxin reductase to only measure glutathione reductase levels and subtract it from uninhibited testing groups. The nematodes were pipetted into a 96-well plate and ran through a microplate reader. All experiments were normalized to average protein levels of C. elegans and analyzed using a t-test. Whole body knockdown of nadk-1 to decrease cytoplasmic NADPH levels decreased oxygen consumption and tert-butyl hydroperoxide-stimulated ROS levels, which was phenocopied by intestine-specific or neuron-specific knockdown. Thioredoxin reductase measurements following nadk-1 knockdown showed a trend toward increased activity. These results establish that nadk-1 does have antioxidant properties but does not extend lifespan as is the case of other NADPH generating enzyme knockdowns. .