Coccidiosis is a costly parasitic disease to the poultry industry with multiple prevention methods being explored to control its impact. One approach under development is the use of -glucans, which are carbohydrates from cell walls of various plant species. The first study evaluated the feeding effects of algae- derived -glucans on performance and responses of broilers during a coccidiosis challenge. Cobb 500 broilers (n=1280) were fed a control diet, control supplemented with 150 g/MT Algamune (BG), 100 g/MT Algamune ZPC (BGZn), or 0.01% Salinomycin (Sal). On d 15, challenged birds received mixed Eimeria inoculum. Measurements were taken on d 7, 14, 21, and 28, and lesion scores assessed on d 21. The challenge resulted in reduced BW, and higher feed conversion ratio (FCR) was observed in the challenged birds with Sal and BGZn. Escherichia coli (E. coli) is normally commensal to the gastrointestinal tract, but certain serotypes cause disease in domestic poultry. A subsequent study was conducted to evaluate the feeding effects of algae-derived glucan (1,3 -glucan) on performance of broiler chickens during an E. coli challenge. Cobb 500 broilers (n=900) were fed a control diet, control + 25 mg/kg of -glucan, or control + 100 mg/kg of -glucan. On d 0, litter was sprayed with E. coli inoculum. Measurements were taken on d 7, 14, 21, and 28. -glucan supplementation increased BW gain andlowered FCR. The results from these studies offer some insight to the effects of -glucans on poultry and their potential to offset negative effects caused by infectious challenges. / Master of Science

Mathematical modeling of biological systems has improved the knowledge of scientists for many years. In virology, particularly in the study of hepatitis B virus, mathematical models were used to explain interactions between hepatitis B virus and the human host in the absence and presence of interventions such as drug therapy and vaccines. This thesis seeks to explain the role of e-Antigen, a particle produced by hepatitis B virus, in the pathogenesis of hepatitis B infection. To accomplish this goal, I will provide biological background as well as previous modeling work on the role of e-Antigen in hepatitis B virus infection, before finally developing a new model adapted specifically for connecting hepatitis B progression with e-Antigen and drug therapy. I will analyze the model both analytically and numerically, fit it to virus data from humans chronically infected with hepatitis B that undergo drug therapy, and draw conclusions about the relation between drugs, immune activation, and loss of e-Antigen. / Master of Science

Chlorine dioxide (ClO₂) was included in the Spring Hollow Water Treatment Plant (Roanoke County, Virginia) to oxidize manganese and iron, prevent tastes and odors, and avoid the formation of excessive halogenated disinfection by-products. A state-of-the-art, gas:solid ClO₂ generation system manufactured by CDG Technology, Inc. was installed at the plant and is the first full-scale use of this technology in the world. The ClO₂ generator produces a feed stream free of chlorine, chlorite ion (ClO₂⁻), and chlorate ion (ClO₃⁻), resulting in lower by-product concentrations in the treatment system The objectives of this project were to study ClO₂ persistence and by-product concentrations throughout the treatment plant and distribution system and to evaluate granular activated carbon (GAC) columns for removing ClO₂⁻ from the finished water. The ClO₂ dosages applied during this study were relatively low (<0.75 mg/L), and, as a result, ClO₂⁻ concentrations never approached the maximum contaminant level (MCL) (1.0 mg/L). Likewise, the plant effluent ClO₂ concentration never approached the maximum residual disinfectant level (MRDL) (0.80 mg/L), but concentrations as high as 0.15 mg/L reformed in the distribution system by ClO₂⁻ reaction with chlorine. Chlorate ion was monitored despite the fact that no ClO₃⁻ MCL has been proposed, and concentrations were quite low (never greater than 0.10 mg/L) throughout the treatment plant and in the distribution system. The reasons for the low concentrations are that ClO₃⁻ is not produced by the gas-solid generator used at the facility and ClO₂⁻ concentrations in the clearwell prior to chlorination were uniformly low. The average ClO₂⁻ reduction upon passage of treated water through the GAC contactor was approximately 64 percent, but the GAC effectiveness was declining over the six-month study period. Apparently, GAC effectiveness, as shown by others, is short-lived, and if higher ClO₂ dosages are ever applied at the Roanoke County facility, the ClO₂⁻ concentrations will have to be reduced by either ferrous coagulants or reduced-sulfur compounds. Regenerated ClO₂ concentrations in the distribution system were below 0.2 mg/L, but concentrations as low as 0.03 mg/L were found at homes of customers who complained of odors. During this study, twelve complaints were received from eight customers, and each complainant had recently installed new carpeting, which has been shown to contribute volatile organics that react with ClO₂ to produce odors similar to kerosene and cat urine. While meeting the Cl₂ MCL likely will be no problem if the ClO₂ dose at the plant remains below 1.0 mg/L, the problem of offensive odors in the distribution system will likely continue as long as any ClO₂ is in the finished water when chlorine is present. / Master of Science

The Small Aircraft Transportation System (SATS) is a partnership among various organizations including NASA, the FAA, US aviation industry, state and local aviation officials, and universities. The program objectives are intend to reduce travel times by providing high-speed, safe travel alternatives by making use of small aircraft and underused small airports throughout the nation. A major component of the SATS program is the Smart Landing Facility (SLF). The SLF is a small airport that has been upgraded to handle SATS traffic. One of the services needed at SLFs is air surveillance of the airspace surrounding it. This thesis researches the different surveillance techniques available for use at the SLFs. The main focuses of this paper are an evaluation of the Traffic Alert and Collision Avoidance System (TCAS) when used as a ground sensor at SLFs and the design of a Position and Identification Reporting Beacon (PIRB). The use of the TCAS ground sensor is modeled in Matlab and the results of that model are discussed. The PIRB is a new system that can be used in conjunction with the Automatic Dependent Surveillance-Broadcast (ADS-B) system or independently to provide position information for all aircraft using GPS based positioning. / Master of Science

Hardwood timber is a substantial economic staple in the eastern U.S., where primary hardwood processors produce more than 10 billion board feet of sawn hardwoods annually. There are over 3,500 sawmills producing hardwood lumber in the Southeastern portion of the United States. Present trends such as increasing labor costs and limited supplies of high quality logs have forced hardwood lumber manufacturers to increase their efforts to maximize the utilization of this raw material. In order to make money in such a competitive business, these sawmills must produce the highest possible grade of lumber from each saw log they process. Of all the primary and secondary processing procedures that are used to transform round wood into a final product, the sawmill edging and trimming operations have the most substantial effect on the grade and, hence, the value of the material produced. Currently, the grading of rough hardwood lumber is done manually by human inspectors according to standardized grading rules developed by the National Hardwood Lumber Association (NHLA, 1994). Standard hardwood edging and trimming operations are less than optimum because of the complexity of the grading rules, the complexity of the decision making processes involved, possible operator fatigue, and the imprecision with which lumber can be sawn by the available equipment. Studies have shown that there is a potential to increase hardwood lumber value by over 20 percent if optimum edging and trimming could be performed in hardwood sawmills. Even a small portion of this percentage would substantially increase the profit of hardwood lumber manufacturers. And this can be achieved just by utilizing some degree of automation. That is, some type of system must be designed that can scan a board to sense important hardwood features, make correct edging and trimming decisions, and then control down stream edgers and trimmers with minimal operator intervention. The most difficult part in the development of this automatic edging and trimming system is to get enough major defect information to make very good edging and trimming decisions. This thesis describes the research that was performed to build a prototype system that can collect images of boards and extract major defect information for making good edging and trimming decisions. The images that are collected include Black/White and laser profile images. Necessary defect information to be extracted for making edging and trimming decisions includes the location and size of large grading defects and areas of the board that are too thin. This thesis talks about the hardware that was used for collecting the needed board images. This includes a discussion of both the Black/White and laser profile imaging systems. The data collection boards that were used for transferring images from these imaging systems to computer memory are also described. This thesis also describes the computer vision algorithms that were developed to extract defect information needed for making improved edging and trimming decisions. Some of the processing steps involved include background extraction, both global and local segmentation, connected component labeling and small area elimination and merging. Processing results obtained of green red oak samples show that both hardware and software of the prototype system seem to work well. However, since the program needed to actually create the edging and trimming solution based on defect information found by the computer vision system was not available it was impossible to quantitatively determine the value improvement to proposed system might offer. / Master of Science

Partant du constat que, trop souvent, les théoriciens de la guerre juste se contentent uniquement de présenter et d'appliquer une liste de critères afin de juger une guerre particulière sans exposer les raisons justifiant cette liste, il est important, pour défendre une théorie plus forte de la guerre juste, d'exposer plus clairement l'enquête métaéthique soutenant les critères que cette théorie présente. Dans le présent mémoire, nous entendons procéder d’abord à l’examen des justifications classiques des critères de la guerre juste et interroger les critiques qu’on leur oppose de même que les théories philosophiques modernes appuyant le concept de la guerre juste. Puis, nous entendons démontrer qu’en adoptant une méthode cohérentiste et contextualiste, les théoriciens pourront se doter des outils nécessaires pour soutenir une théorie de la guerre juste, laquelle sera apte à justifier efficacement ces mêmes critères et résister aux principales théories rivales.

La leucémie lymphoïde chronique (LLC) est le type de leucémie le plus répandu chez les adultes des pays occidentaux. Elle provient notamment de la prolifération accrue des cellules B malignes matures qui s'accumulent progressivement dans les ganglions lymphatiques, la moelle osseuse, la rate et la circulation sanguine. L'évolution clinique de la LLC est très variable. Il a été montré, par notre groupe et répliqué par d'autres, qu'une expression tumorale élevée de la glycosyltransférase UGT2B17 identifie un sous-groupe de patients LLC avec une survie sans traitement et une survie globale réduites. L'expression élevée d'UGT2B17 favorise la prolifération des cellules B leucémiques, suggérant un rôle de cette enzyme dans ce processus, médié entre autres par son activité en inactivant des molécules comme la molécule anti-apoptotique prostaglandine E₂. De plus, l'expression élevée d'UGT2B17 est associée à une réponse réduite aux traitements de chimiothérapie à base de fludarabine et est associée à la résistance aux thérapies ciblées telle que l'ibrutinib. L'ibrutinib cible la tyrosine kinase de Bruton (BTK) de la voie de pro-survie du récepteur à l'antigène des cellules B (BCR). La voie du BCR est reconnue comme étant une voie de pro-survie contribuant largement à la progression de la maladie et elle constitue une cible thérapeutique en LLC. Au cours de mon programme de maîtrise, nous avons testé l'hypothèse que l'UGT2B17 influence le signalosome du BCR. Notre étude de l'expression génique des cellules B leucémiques révèle un enrichissement des effecteurs de la voie du BCR associé à l'expression élevée d'UGT2B17, dont BTK et d'autres effecteurs proximaux de cette voie, suggérant un lien entre UGT2B17 et cette voie de signalisation. L'une de ces protéines, ZAP70, constitue un marqueur de mauvais pronostic connu pour amplifier la signalisation du BCR. L'expression de *ZAP70* est associée à celle d'*UGT2B17* dans plusieurs cohortes de patients LLC. La co-expression élevée de ces deux gènes permet d'identifier un sous-groupe de patients avec le risque le plus élevé de survie globale réduite en comparaison avec l'expression de chacun d'entre eux, suggérant un effet additif. Dans les modèles cellulaires de LLC, la manipulation génétique de l'expression de ces deux gènes démontre une influence sur la prolifération cellulaire. De plus, l'inhibition de *ZAP70* compromet la prolifération des cellules B induite par l'UGT2B17, suggérant que l'effet de UGT2B17 pourrait être médié, du moins en partie, par ZAP70. Les travaux montrent également pour la première fois que la protéine UGT2B17 forme un complexe protéique avec plusieurs kinases du signalosome BCR, incluant BTK, SYK, BTK, ZAP70, LYN et LCK . Ces données suggèrent qu'UGT2B17 pourrait influencer la prolifération des cellules leucémiques par un mécanisme impliquant des interactions protéine-protéine (IPP). Enfin, nos travaux montrent que la double inhibition de SYK et JAK1/3 par le cerdulatinib, s'est avérée plus efficace pour contrer l'effet pro-prolifératif d'UGT2B17 comparativement à l'inhibition de BTK avec l'ibrutinib. Ces observations suggèrent une vulnérabilité thérapeutique chez les patients LLC à haut risque surexprimant UGT2B17. Nos découvertes supportent un rôle pro-oncogénique pour l'UGT2B17 en LLC en tant que nouveau constituant du signalosome BCR. / RChronic lymphocytic leukemia (CLL) is the most common type of leukemia among adults in Western countries. It comes in particular from the increased proliferation of mature malignant B cells which gradually accumulate in the lymph nodes, bone marrow, spleen and blood circulation. The clinical course of CLL is very variable. It has been shown, by our group and replicated by others, that high tumor expression of the glycosyltransferase UGT2B17 identifies a subgroup of CLL patients with reduced treatment-free survival and overall survival. The high expression of UGT2B17 promotes the proliferation of leukemic B cells, suggesting a role for this enzyme in the disease, mediated among other things by its activity in inactivating molecules such as the anti-apoptotic molecule prostaglandin E2. Furthermore, high expression of UGT2B17 is associated with reduced response to fludarabine-based chemotherapy treatments and is associated with resistance to targeted therapies such as ibrutinib. Ibrutinib targets Bruton's tyrosine kinase (BTK) of the B-cell antigen receptor (BCR) pro-survival pathway. The BCR pathway is recognized as a pro-survival pathway contributing largely to disease progression and constitutes a therapeutic target in CLL. During my master program, we tested the hypothesis that UGT2B17 influences the BCR signalosome. Our study of gene expression in leukemic B cells reveals an enrichment of BCR pathway effectors associated with elevated UGT2B17 expression, including BTK and other proximal effectors of this pathway, suggesting a link between UGT2B17 and this signaling pathway. One of these proteins, ZAP70, is a poor prognosis marker known to amplify BCR signaling. ZAP70 expression is associated with that of UGT2B17 in several cohorts of CLL patients. The high co-expression of these two genes allows the identification of a subgroup of patients with the highest risk of reduced overall survival compared to the expression of each of them, suggesting an additive effect. In cellular models of CLL, genetic manipulation of the expression of these two genes demonstrates an influence on B cell proliferation. Furthermore, inhibition of ZAP70 impairs UGT2B17-induced B cell proliferation, suggesting that the effect of UGT2B17 may be mediated, at least in part, by ZAP70. The work also shows for the first time that the UGT2B17 protein forms a protein complex with several BCR signalosome kinases, including BTK, SYK, BTK, ZAP70, LYN and LCK. These datasuggest that UGT2B17 may influence leukemia cell proliferation through a mechanisminvolving protein-protein interactions (PPIs). Finally, our work shows that the dual inhibition of SYK and JAK1/3 by cerdulatinib provedto be more effective in countering the pro-proliferative effect of UGT2B17 compared to theinhibition of BTK with ibrutinib. These observations suggest therapeutic vulnerability inhigh-risk CLL patients overexpressing UGT2B17. Our findings support a pro-oncogenic rolefor UGT2B17 in CLL as a novel constituent of the BCR signalosome.

Il y a deux choses. On a souvent de la difficulté à l’admettre. Ce sont deux manières de connaître, ce à quoi on résiste déjà ; mais ce sont plus encore deux manières d’être au monde et de se lier à lui en étant pour ou contre lui. La différence entre l’esprit et le corps, le dedans et le dehors, apparaît maintenant comme étant la différence entre le monde et son image, entre la réalité connue immédiatement, réalité sensible, affective, vécue, et le réel connu médiatement : connaissances symboliques, quantitatives, manières qu’a l’intelligence d’indexer un réel extérieur à partir d’un sensible immédiat. Or, ne plus reconnaître de réalité qu’en une connaissance objective, ce serait substituer l’image du réel au réel, se fermer à notre propre réalité, et donc à la vie, puisque nous sommes vie. Le travail de la raison consisterait à analyser, à découper, contrôler, dominer. Or, si ce savoir objectif, savoir de la raison, a sa praxis, le savoir subjectif aurait la sienne propre. À ces deux savoirs correspondent deux praxis, deux éthiques inscrites nécessairement dans la structure même du vivant. Ce n’est point ce que, dans la littérature contemporaine anglophone — du moins en philosophie analytique —, on semble disposé à reconnaître. On y dépeint plutôt la connaissance subjective comme étant une forme de connaissance primitive, « folklorique ». Les présentes recherches ont donc dû s’attarder à mettre en lumière l’incompréhension dont souffre le dualisme épistémique dans la philosophie de l’esprit qui répond au goût du jour, laissant surtout en friche la tâche d’élucider plus longuement le sens du dualisme éthique en tant que tel, quoique celui-ci se trouve néanmoins exposé dans le dernier chapitre du travail.

No / Earlier it has been shown that human proliferating/undifferentiated basal keratinocytes hold the full capacity for autocrine catecholamine synthesis/degradation and express b2-adrenoceptors (b2-AR). In this report, we show that human melanocytes also express all of the mRNA and enzymes for autocrine synthesis of norepinephrine but fail to produce epinephrine. So far, it was established that human melanocytes express b1-AR which are induced by norepinephrine yielding the inosine triphosphate diacylglycerol signal. The presence of catecholamine synthesis and the b2-AR signal escaped definition at that time. Using RT-PCR, immunofluorescence and radioligand binding with the b2-AR antagonist (-)-[3H]CGP 12177, we show here that human melanocytes express functional b2-AR (4230 receptors per cell) with a Bmax at 129.3 and a KD of 3.19 nM but lack b1-AR expression. 2-AR stimulation with epinephrine 10-6 M and salbutamol 10-6¿10-5 M yielded a strong cyclic adenosine monophospate (cAMP) response in association with upregulated melanin production. Taken together these results indicate that the biosynthesis and release of epinephrine (10-6 M) by surrounding keratinocytes can provide the cAMP response leading to melanogenesis in melanocytes via the b2-AR signal. Moreover, the discovery of this catecholaminergic cAMP response in melanocytes adds a new source for this important second messenger in melanogenesis.

No / Streptococcus agalactiae is a major human and animal pathogen, most notable as a cause of life-threatening disease in neonates. S. agalactiae is also called the Group B Streptococcus in reference to the diagnostically significant Lancefield Group B typing antigen. Although the structure of this complex carbohydrate antigen has been solved, little is known of its biosynthesis beyond the identification of a relevant locus in sequenced S. agalactiae genomes. Analysis of the sugar linkages present in the Group B carbohydrate (GBC) structure has allowed us to deduce the minimum enzymology required to complete its biosynthesis. Most of the enzymes required to complete this biosynthesis can be identified within the putative biosynthetic locus. Surprisingly, however, three crucial N-acetylglucosamine transferases and enzymes required for activated precursor synthesis are not apparently located in this locus. A model for GBC biosynthesis wherein the complete polymer is assembled at the cytoplasmic face of the plasma membrane before translocation to the cell surface is proposed. These analyses also suggest that GBC is the major teichoic acid-like polymer in the cell wall of S. agalactiae, whereas lipoteichoic acid is the dominant poly(glycerophosphate) antigen. Genomic analysis has allowed us to predict the pathway leading to the biosynthesis of GBC of S. agalactiae.