Neutrophil recruitment to the site of acute inflammation is a multistep process regulated by specific signaling molecules. The signaling mechanisms that regulate neutrophil-endothelial cell interactions remain incompletely understood. p38 mitogen-activated protein kinase (MAPK) signalling was shown to regulate different steps of neutrophil migration in response to inflammatory stimuli. The mitogen- and stress-activated protein kinase-1 (MSK1) can be activated by either extracellular-signal-regulated kinase (ERK) 1/2 or p38 MAPK. The aim of the present study is to investigate the effects of pharmacological suppression of MSK1 by its specific inhibitor, SB747651A, on various steps of neutrophil recruitment. In vivo studies were conducted using real-time and time-lapsed intravital video microscopy of the cremaster microcirculation to determine the dynamic leukocyte-endothelial cell interactions. Intrascrotal injection of macrophage inflammatory protein-2 (MIP-2, 0.2 μg/mouse) decreased leukocyte rolling velocity which was significantly reversed by pre-treatment with SB747651A (intrascrotal injection of 3 mg/kg). SB747651A pre-treatment enhanced MIP-2-induced increase in neutrophil adhesion and emigration. To better understand the effect of SB747651A on different steps of neutrophil recruitment, we placed a small piece of MIP-2-containing agarose gel on the exposed cremaster muscle and studied directed migration of neutrophils in the postcapillary venule and in the tissue. Superfusion of SB747651A (5 μM) on cremaster muscle subjected to MIP-2 gradient significantly increased rolling velocity and adhesion, but decreased emigration of neutrophils in comparison to superfusion of normal saline III without SB747651A. SB747651A treatment significantly affected transmigration time, detachment time, intravascular crawling and the velocity of migration, but not the directionality of migrating neutrophils in tissue. The expression of intercellular adhesion molecule-1 (ICAM-1) in cultured endothelial cells was up-regulated by co-treatment with SB747651A and MIP-2 but not by MIP-2 alone. Flow cytometry analysis showed that co-treatment of bone marrow neutrophils with SB747651A and MIP-2 significantly decreased macrophage antigen-1 (Mac-1) but not lymphocyte function associated antigen-1 (LFA-1) expression as compared with MIP-2 treatment alone. Collectively, our findings demonstrate that pharmacological suppression of MSK1 by SB747651A affects multiple steps of MIP-2-induced neutrophil recruitment in vivo.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Universiẗat, Diss., 2000--Dortmund. / Dateiformat: PDF.

This dissertation deals with the impact of alcohol advertising, which associates drinking alcohol with many desires and values psychologically appealing to young people. As traditional research on alcohol advertising's impact focused on a direct link between exposure and alcohol consumption, this study breaks the link into several mediating stages. Under the theoretical framework of the Message Interpretation Process (MIP) model, this study involves how college students interpret alcohol advertising, how their desire, wishful thinking and expectancies toward drinking may account for both the impact of exposure to alcohol advertising and reasons for drinking. Specifically, the purpose of the study is to (1) assess the MIP model and (2) explore the impact of anti-alcohol messages on college students' interpretation of alcohol advertising. An experiment was conducted with 94 college students. In the experiment, participants were grouped into three treatment groups: the first was exposed to logic-based anti-alcohol messages followed by alcohol advertisements, the second was exposed to emotion-based anti-alcohol messages followed by alcohol advertisements; and the third group was exposed to alcohol advertising only, as the control group. Results showed support for the MIP model in general. As posited by the model, realism and desirability are both related to identification with characters seen in alcohol advertising, which in turn is related to expectancies toward drinking, which is in turn related to intention to drink. The only two exceptions were the lack of significance for the social norm-identification link and relationships with negative expectancies. Compared with exposure, realism and desirability were better predictors for alcohol advertising's impact. The results also showed impact of logic-based anti-alcohol messages on identification and expectancies as well as impact of emotion-based anti-alcohol messages on desirability and identification. There was no significant difference between the two anti-alcohol groups. This study provides insights on how viewers draw from alcohol advertising to make sense of their own lives. Implications for anti-alcohol campaign are provided. Because negative expectancies toward drinking did not influence the intention to drink, the association between negative outcomes and drinking might not very well. Another association between positive outcomes and non-drinking may work better. Recommendations for future research as well as limitations of this study are discussed.

This diploma thesis addresses the presence and determination of chloramphenicol residues in biological materials. The theoretical part presents the literature retrieval containing information about veterinary medicaments with the banned use in food producing animals and also the sum of the legislative requirements concerning the presence of these substances in foodproducts and raw food materials of animal origin. The comparison was carried out between the existing analytical methods used for the determination of chloramphenicol residues in different biological materials, which are altogether based on the solid phase extraction for the extract cleaning and the new procedures for sample preparations using columns where the sorbent performs on the molecularly imprinted polymers principle.

Orientador: Ricardo Antonio Polanczyk / Resumo: A cana-de-açúcar possui grande destaque no cenário econômico mundial, por ser matéria prima para a produção de açúcar, etanol e uma diversidade de produtos secundários. Esta cultura vem se expandindo para novas áreas agricultáveis do Brasil e consequentemente fatores que limitam a produtividade também se fazem presente. Um dos fatores limitantes são os insetos-pragas. Para cana-de-açúcar estima-se que existam aproximadamente 80 espécies de insetos causando danos. Dentre estas espécies, Sphenophorus levis Vaurie, 1978 (Coleoptera: Curculionidae) é a principal praga de solo, causando perdas significativas na produção. O uso de fungos entomopatogênicos tem se mostrado promissor para o controle deste inseto-praga. Dentre estes fungos, Beauveria bassiana (Hypocreales: Cordycipitaceae) se apresenta como um agente promissor para o controle desta praga; porém é suscetível a fatores abióticos, como radiação UV, que reduzem a sua eficiência em campo. Outro fator limitante ao uso deste agente é a falta de conhecimento em relação compatibilidade com inseticidas químicos. Estas informações são úteis para o uso associado destes dois métodos de controle. Tendo em vista estas problemáticas, o presente estudo teve como objetivo realizar testes de compatibilidade com inseticidas químicos e o encapsulamento de um isolado de B. bassiana para diminuir os efeitos da radiação UV. O encapsulamento do fungo foi realizado pelo método de gelificação iônica, com uma suspensão de alginato de sódio conten... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Sugarcane has great prominence in the economic scenario worldwide, for being raw material to produce sugar, ethanol, and diversity of secondary products. This culture has been expanding to new agricultural areas in Brazil and, consequently, factors limiting productivity are present as well. One of the limiting factors is insect-pests. To estimate the amount of sugarcane in existence, approximately 80 insect species cause damage. Among these species, Sphenophorus levis Vaurie, 1978 (Coleoptera: Curculionidae) is one of the main soil pests, which leads to production losses. The use of entomopathogenic fungi is promising for controlling this pest. Among entomopathogenic fungi, Beauveria bassiana (Hypocreales: Cordycipitaceae), present itself as a promising agent for the control of this pest; however, it may be susceptible to abiotic factors such as UV radiation, which affect its efficiency under field conditions. Another limiting factor to the use of this agent is the lack of knowledge regarding the compatibility with chemical insecticides. This information is useful for the use of both control methods. Given these problems, the present study aimed to encapsulate a B. bassiana isolate to reduce the effects of UV radiation and compatibility with chemical insecticides. The encapsulation of the fungus was performed by the ionic gelation method, with a suspension of silicon alginate, or the fungus in a calcium chloride solution. Pathogenicity test was performed with dry and wet part... (Complete abstract click electronic access below) / Doutor

In this thesis, we consider contextual newsvendor problems where one seeks to determine ordering quantities of perishable products based on the observations of past demands and some features (such as seasonality, weather forecasts, economic indicators, etc.) related to the demand. We propose solving the problems via a single-step optimal decision-tree approach. Unlike the traditional two-step approach that first predicts a demand distribution based on given features and then optimizes the order quantity, our approach seeks to determine a tree-based ordering policy that directly maps given features to optimal order quantities. We show how the optimal policies can be found by solving mixed-integer programming (MIP) problems. The tree structure overcomes the black-box nature of most machine learning algorithms while reaching better performance than simple solutions such as linear regression. In addition to risk-neutral newsvendor problems, we further extend the method to address risk-averse newsvendor problems formulated based on Conditional Value-at-Risk (CVaR). Numerical experiments on synthetic and real-world data suggest that our approach outperforms existing approaches with the same objective function, such as the ERM-based convex optimization model which is referred to as Ban and Rudin's big data newsvendor model, and quantile regression decision trees.

This thesis is concerned with the Resident Scheduling Problem (RSP) in which a good schedule is desired that will meet both departmental requirements and residents' preferences. Three scenarios that represent most situations and account for various departmental requirements and needs are described. Although similar scheduling problems are considered in the literature, no analysis exists that adequately deals with this specific problem. The problem is modeled as a mixed-integer program (MIP) and heuristic solution procedures are developed for the different identified scheduling scenarios. These procedures exploit the network structure of the problem which is an important feature that enhances problem solvability. For the sake of comparison, the problem is also solved exactly via the CPLEX-MIP package. The contribution of this work is important since many hospitals are still utilizing manual techniques in preparing their own schedules, expending considerable effort and time with less scheduling flexibility. / Master of Science

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Le Syndrome Néphrotique à Lésions Glomérulaires Minimes (SNLGM) et la glomérulonéphrite extra membraneuse (GEM) sont deux podocytopathies primitives d'origine immunitaire associant des altérations immunes et des atteintes podocytaires à l'origine d'un syndrome néphrotique. Cependant, bien que l'origine dysimmunitaire soit confortée par de nombreux arguments cliniques, les mécanismes impliqués restent obscurs. Initialement identifié dans les lymphocytes T (LT) de patients en phase de poussée de SNLGM, le gène c-mip est également exprimé dans les podocytes de patients atteints de SNLGM et de GEM, alors qu'il est physiologiquement réprimé. Ainsi, les objectifs de ce travail étaient : 1) appréhender le rôle de c-mip dans le LT d'une part à travers l'étude d'un modèle murin transgénique (Tg), et 2) comprendre la fonction de c-mip au niveau du podocyte grâce au modèle expérimental de GEM humaine induit chez le rat.Le modèle murin Tg Lck-cmip surexprime spécifiquement c-mip dans les LT matures périphériques. Cette surexpression est à l'origine d'un phénotype lymphocytaire altéré marqué par une accumulation de LT naïf, et une inhibition de la synthèse de cytokines de type TH1 et TH2, après une activation T spécifique ex vivo. Cette régulation négative est associée à une accumulation des formes inactives des kinases de la famille des Src et un blocage du recrutement des lipids rafts nécessaire à la formation de la synapse immunologique. Ces résultats suggèrent donc que c-mip est un régulateur négatif de l'activation T impliqué dans la signalisation proximale lymphocytaire et pourrait être impliqué dans l'hyporéactivité lymphocytaire observée chez les patients atteints de SNLGM actif.L'étude de la néphrite de Heymann passive, un modèle expérimental de GEM humaine, montre que l'induction podocytaire de c-mip coïncide avec l'apparition de la protéinurie. Cette surexpression est associée d'une part, à une diminution des taux de synaptopodine qui engendre une diminution de l'activité RhoA, à l'origine d'une désorganisation du cytosquelette podocytaire, et d'autre part à une induction de DAPK (death-associated protein kinase) et ILK (Integrin Linked Kinase) impliquées dans des phénomènes pro-apoptotiques. La cyclosporine A en inhibant l'expression de c-mip restaure les taux de DAPK et ILK ainsi que l'activité RhoA. Ainsi dans le podocyte, c-mip semble impliquer dans les troubles de la signalisation podocytaire aboutissant à une protéinurie néphrotique.C-mip semble donc jouer un rôle crucial dans les perturbations podocytaires et lymphocytaires observées chez les patients atteints de podocytopathies primitives et représente à ce titre une cible thérapeutique.Mots clefs :C-mip, Syndrome Néphrotique à Lésions Glomérulaires Minimes, Glomerulonéphrite Extra Membraneuse, signalisation proximale, lymphocyte T, podocyte, cytosquelette / Minimal Change Nephrotic Syndrome (MCNS) and Membranous Nephropathy (MN) are two primitive immune podocytopathies associating immune alterations and podocyte damage ultimately leading to proteinuria. Although the immune origin of the disease is corroborated by numerous clinical data, the mechanisms involved are still unknown. In previous works by the team, the c-mip protein was found expressed in T lymphocytes (TL) from patients with MCNS relapse, and in podocytes from MCNS and MN patients, while it is physiologically repressed. The aims of the present work were: firstly, to investigate the rôle of c-mip in TL by the study of Lck-cmip transgenic mice (Tg); secondly, to understand c-mip function in podocyte using a rat experimental model of human MN (Heymann nephritis).Transgenic mice overexpressed specifically c-mip in peripheral mature TL. This expression led to an altered TL phenotype characterized by accumulation of naïve LT associated with inhibition of TH1's and TH2's cytokines, after T-specific activation ex vivo. This negative regulation was correlated with an increase in the inactive forms of Src kinases and a blockage of the lipid raft clustering required for immunological synapse formation. These results suggest that (i) c-mip is a negative regulator of the proximal signaling events associated with TL activation involved in proximal signaling and (ii) it could be involved in the TL hyporeactivity described in SNLGM patients.In the study based on passive Heymann Nephritis, the experimental model of MN, the results highlight a correlation between podocyte expression of c-mip and proteinuria. This expression is associated, on the one hand, with a decrease in synaptopodin levels, which generate a decrease of RhoA activity resulting in podocyte cytoskeleton disorganization, and on the other hand with DAPK (Death Associated Protein Kinase) and ILK (Integrin Linked Kinase) induction, known to be involved in pro-apoptotic mechanisms. Cyclosporin A inhibited c-mip expression and restored the basal levels of DAPK, ILK and Rhoa activity. These results suggest that in podocyte, c-mip could be involved in proximal signaling alterations leading to nephrotic proteinuria.In conclusion, c-mip could play a crucial rôle in both the lymphocyte and podocyte alterations observed in patients suffering from primitive podocytopathies, strongly suggesting its potential as a therapeutic target in these disorders.Key words :C-mip, MCNS, MN, proximal signaling, Src kinase, T lymphocyte, podocyte, cytoskeleton