With the rise in aging population, about 6.8 million American residents are depen- dent on mobility devices for their day to day activity. More than 40% of these users have di?culty in moving the mobility device on their own. These numbers serve as a motivation on developing a system than can help in manipulation with simple muscle activity and localize the mobility device in the user's home in case of medical emergencies. This research is aimed at creating a user interface of Elec- tromyographic Sensor, attached to the forearm, incorporated with present smart wheelchairs and a simple localization technique using ducial markers. The main outcome of the research is a simulator of the smart wheelchair to analyze the results of my research.

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Since the human immunodeficiency virus (HIV) epidemic in the 1980s, great strides have been made regarding drug therapeutics, which has slowed the progression of HIV to AIDS and decreased the mortality rates in HIV patient populations. Other prevention interventions, such as pre-exposure prophylaxis (PrEP), have also contributed immensely to reducing HIV infections. However, today in many parts of the world, especially in sub-Saharan Africa, HIV is still prevalent. This demonstrates the need to focus on more long-term preventative interventions, such as vaccines. In order to do this, more research has to be conducted on the B cell adaptive immune response to HIV. This thesis research explores how the opportunistic disease tuberculosis, which is present in many HIV-positive patients, affects B cell survival in these HIV patients. Our methods section consists of CD14+ cell isolation and MDM culture experiments that we performed and subsequent planned experiments that we are yet to complete. These experiments include infecting MDM cultures with a double pseudotyped VSVg-NL43 HIV. We will also expose the MDMs to the TB antigen, lipomannan (LM), to represent HIV/TB co-infection in vitro. LM is a toll-like receptor 2 (TLR2) agonist. The MDM cultures will enable us to measure the amount of BAFF and APRIL mRNA produced in the HIV, HIV/LM, and LM MDM cultures using RT-PCR. Using a growth curve, we will observe BAFF and APRIL's effects on the survival of B cells in the different MDM cultures. We hypothesize that the TB antigen will increase B-cell survival through the BAFF system molecules in HIV patients. The results of our research will provide insights on the role TB plays in enhancing the humoral immune response in HIV-1 patients, paving the way for further research on understanding the mechanism responsible for this and consequently creating vaccine and vaccine adjuvant opportunities.

April

Les maladies auto-immunes résultent d’un dysfonctionnement du système immunitaire. L’étiologie de la pathologie reste souvent inconnue, compliquant la conception de traitements adaptés. Ce projet de thèse s’est focalisé sur la molécule « a proliferation inducing ligand » (APRIL), facteur de survie des plasmocytes (PC) produisant les anticorps, dans l’hépatite auto-immune (HAI) et la sclérose en plaques (SEP). Dans l’HAI, une principale caractéristique histologique est la présence d’un infiltrat lymphoplasmocytaire formant une hépatite d’interface dommageable. Dans cette maladie, nous avons d’abord pu mettre en évidence une corrélation positive entre l’expression d’APRIL et l’infiltration des PC dans les espaces portes. In vitro, nous avons observé une survie augmentée des PC du foie en présence d’APRIL. La corticothérapie communément prise par les patients HAI ne cible pas directement les PC. Cependant, nous avons remarqué une réduction simultanée de la densité de PC et de l’expression d’APRIL. Ainsi, cette étude étend le rôle de facteur de survie d’APRIL aux PC du foie dans l’HAI. Les rechutes sont fréquentes après arrêt du traitement, nous indiquant que les cellules pathogènes sont épargnées par la thérapie. Nos résultats montrent que le ciblage d’APRIL pourrait être précieux dans l’HAI. Propre de son rôle sur les PC, APRIL a été ciblée avec succès dans plusieurs maladies auto-immunes. Outre ces succès, un essai clinique visant à bloquer APRIL dans la SEP à malheureusement conduit à une exacerbation inattendue de la maladie. Nous avons été capables de montrer qu’APRIL cible un nouveau type cellulaire dans le système nerveux central, les astrocytes. La fixation d’APRIL à la surface des astrocytes dépend d’un nouveau partenaire de liaison, exprimé par ces derniers, les chondroïtines sulfates protéoglycans. Cette interaction induit la production de la cytokine anti-inflammatoire IL-10, conduisant à l’inhibition de, la prolifération des lymphocytes T auto-réactifs et la sécrétion de cytokines pro-inflammatoires. L’utilisation de souris déficientes pour APRIL dans le modèle standard de la SEP nous a permis de confirmer le rôle neuro-protecteur d’APRIL. Finalement, après injection d’APRIL recombinante dans ce modèle murin, une réduction de la sévérité de la maladie a été observée. Globalement, nous avons identifié APRIL comme une molécule à double rôle dans les maladies auto-immunes. / Autoimmune diseases result from a dysfunction of the immune system. The disease etiology is often unknown, complicating the design of appropriate treatments. This thesis project focused on the molecule “a proliferation inducing ligand” (APRIL), a survival factor for antibody-producing plasma cells (PC), in autoimmune hepatitis (AIH) and multiple sclerosis (MS). In AIH, one main histological feature is the presence of a lymphoplasmacytic infiltration forming a damaging interface hepatitis. In this disease, we first noticed a positive correlation between APRIL expression and PC infiltration in portal spaces. In vitro, we further observed an extended survival of liver PC in the presence of APRIL. The corticosteroid therapy commonly applied to AIH patients does not directly target PC. However, we noticed a concomitant reduction in portal PC density and APRIL expression. Hence, this study is extending the survival role of APRIL to liver PC in AIH. Relapses are frequent after treatment withdrawal, telling us that pathogenic cells are spared by the therapy. Our results indicate that APRIL targeting might also be valuable in AIH. Own to its role on PC, APRIL has been successfully targeted in several autoimmune diseases. Besides successes, a clinical trial aiming at APRIL blockade in MS has unfortunately led to an unexpected disease exacerbation. We have been able to show that APRIL targets a new cell type in the central nervous system, the astrocyte. The APRIL binding to astrocyte surface depends on a new binding partner, expressed by the latter, the chondroitin sulfate proteoglycans. This binding induces the production of the anti-inflammatory cytokine IL-10, leading to the inhibition of, self-reactive T-cell proliferation and pro-inflammatory cytokine secretion. Use of APRIL-deficient mice in the standard model of MS allowed us to confirm the neuroprotective role of APRIL. Finally, after recombinant APRIL injection in this model, a lowered disease severity was observed. Overall, we identified APRIL as a dual role molecule in autoimmune diseases.

The Portuguese Expeditionary Force fought in the trenches of northern France from April 1917 to April 1918. on 9 April 1918 the sledgehammer blow of Operation Georgette fell upon the exhausted Portuguese troops. British accounts of the Portuguese Corps’ participation in combat on the Western Front are terse. Many are dismissive. in fact, Portuguese units experienced heavy combat and successfully held their ground against all attacks. Regarding Georgette, the standard British narrative holds that most of the Portuguese soldiers threw their weapons aside and ran. the account is incontrovertibly false. Most of the Portuguese combat troops held their ground against the German assault. This thesis details the history of the Portuguese Expeditionary Force.

Honours Degree / James April, [hereafter referred to as April] was a member of the ANC's military wing Umkhonto we Sizwe [otherwise referred to as MK. What might have seemed unusual to the court that day, and to many onlookers, was the fact that he was a "Cape Coloured" man espousing his allegiance to the ANC and praising it as" ... the spirit of the African people". April and Basil February Chis close friend and comrade] were among the first non-African people to join MK thereby recognising the common destiny of all black people. In part,to tell April's [and Basil February's] story is to explore from an individual perspective the capacity and ability of people to overcome their socialisation, and to rise above conformity and social restrictions. Most of all, April's story is of an activist whose political involvement led him to realise the inevitability and necessity of armed struggle. Furthermore, it is the story of the commitment of his life to this very armed struggle.

The negative impacts of mass shootings on mental health have been documented within the general trauma literature. Substantial research has also shown the Asian population to be a minority group especially vulnerable to negative psychological outcomes following trauma and stress. Acculturation has been studied extensively as a predictor of psychological outcomes in several minority groups. Furthermore, parental overprotection has also been found to have a negative impact on mental health. The relationship between acculturation and parental overprotection and psychological outcomes following mass shootings in the Asian population, however, has not been studied adequately. The purpose of this study was to examine exposure, acculturation, and parental overprotection as predictors of negative mental health outcomes, and as moderators of the relationship between exposure to trauma and negative outcomes. Results indicate that overprotection predicted higher levels of both posttraumatic stress and anxiety-mood symptoms. Exposure predicted posttraumatic stress but not anxiety-mood symptoms. Acculturation was not found to significantly predict either outcome. Overprotection was found to moderate the relationship between exposure and anxiety-mood symptoms. Implications of these findings are discussed. / Master of Science

April

Le myélome multiple (MM) est une néoplasie B caractérisé par l'accumulation d'un clone plasmocytaire dans la moelle osseuse. Cette pathologie demeure incurable d'où la nécessité d'identifier de nouvelles cibles thérapeutiques. C'est notamment dans cette optique que nous avons initié, au sein du laboratoire, un travail de comparaison des profils d'expression génique des plasmocytes tumoraux purifiés de malades avec ceux de plasmocytes normaux et de lymphocytes B, ce qui permettra l'identification de nouvelles voies importantes pour la biologie du MM et donc de nouvelles cibles thérapeutiques potentielles.<br />Par cette approche, nous avons mis en évidence un rôle essentiel des membres de la famille BAFF/APRIL et de leurs récepteurs (BCMA, BAFF-R et TACI) dans la biologie du MM. Les cellules de MM expriment les récepteurs alors que les ligands sont principalement produits par les cellules de l'environnement médullaire. L'utilisation d'un inhibiteur spécifique de BAFF/APRIL a permis de montrer que ces facteurs de croissance sont importants pour la survie et la prolifération des cellules tumorales. TACI apparaît être le récepteur principal pour médier l'effet de BAFF et APRIL dans le MM. Une forte expression de TACI par les cellules de MM est associée à une signature génique de plasmocytes matures alors que les plasmocytes tumoraux présentant une faibles expression de TACI ont une signature génique de plasmablastes proliférants. Nous avons montré que syndecan-1, un protéoglycane à chaînes héparane sulfate joue un rôle essentiel dans la biologie du MM en permettant l'accumulation de fortes concentrations de facteurs de croissance à la surface des cellules. Nous avons identifié que syndecan-1 joue un rôle de corécepteur pour APRIL et TACI supportant ainsi la croissance des cellules de MM. <br />Ces travaux offrent de nouvelles perspectives thérapeutiques pour le MM et ont débouché sur un essai clinique de phase I/II, au CHU de Montpellier, utilisant un inhibiteur de la voie BAFF/APRIL dans le MM.