Identification des métalloprotéases de la matrice extracellulaire synthétisées et sécrétées par des cellules dérivées de la lignée MDCK, les cellules MSV-MDCK-INV aux propriétés tumorales et invasives

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Antigen Drives Regulatory B10 Cell Development and Function

B cells mediate immune responses via the secretion of antibody and interactions with other immune cell populations through antigen presentation, costimulation, and cytokine secretion. Although B cells are primarily believed to promote immune responses using the mechanisms described above, some unique regulatory B cell populations that negatively influence inflammation have also been described. Among these is a rare interleukin (IL)-10-producing B lymphocyte subset termed “B10 cells.” B cell-derived IL-10 can inhibit various arms of the immune system, including polarization of Th1/Th2 cell subsets, antigen presentation and cytokine production by monocytes and macrophages, and activation of regulatory T cells. Further studies in numerous autoimmune and inflammatory models of disease have confirmed the ability of B10 cells to negatively regulate inflammation in an IL-10-dependent manner. Although IL-10 is indispensable to the effector functions of B10 cells, how this specialized B cell population is selected in vivo to produce IL-10 is unknown. Some studies have demonstrated a link between B cell receptor (BCR)-derived signals and the acquisition of IL-10 competence. Additionally, whether antigen-BCR interactions are required for B cell IL-10 production during homeostasis as well as active immune responses is a matter of debate. Therefore, the goal of this thesis is to determine the importance of antigen-driven signals during B10 cell development in vivo and during B10 cell-mediated immunosuppression.

Chapter 3 of the dissertation explored the BCR repertoire of spleen and peritoneal cavity B10 cells using single-cell sequencing to lay the foundation for studies to understand the full range of antigens that may be involved in B10 cell selection. In both the spleen and peritoneal cavity B10 cells studied, BCR gene utilization was diverse, and the expressed BCR transcripts were largely unmutated. Thus, B10 cells are likely capable of responding to a wide range of foreign and self-antigens in vivo.

Studies in Chapter 4 determined the predominant antigens that drive B cell IL-10 secretion during homeostasis. A novel in vitro B cell expansion system was used to isolate B cells actively expressing IL-10 in vivo and probe the reactivities of their secreted monoclonal antibodies. B10 cells were found to produce polyreactive antibodies that bound multiple self-antigens. Therefore, in the absence of overarching active immune responses, B cell IL-10 is secreted following interactions with self-antigens.

Chapter 5 of this dissertation investigated whether foreign antigens are capable of driving B10 cell expansion and effector activity during an active immune response. In a model of contact-induced hypersensitivity, in vitro B cell expansion was again used to isolate antigen-specific B10 clones, which were required for optimal immunosuppression.

The studies described in this dissertation shed light on the relative contributions of BCR-derived signals during B10 cell development and effector function. Furthermore, these investigations demonstrate that B10 cells respond to both foreign and self-antigens, which has important implications for the potential manipulation of B10 cells for human therapy. Therefore, B10 cells represent a polyreactive B cell population that provides antigen-specific regulation of immune responses via the production of IL-10.

Schéma implicite pour la résolution d'un système hyperbolique d'équations aux dérivées partielles

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Identification des métalloprotéases de la matrice extracellulaire synthétisées et sécrétées par des cellules dérivées de la lignée MDCK, les cellules MSV-MDCK-INV aux propriétés tumorales et invasives

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

What Drives Parental Concerns about their 18-Month-Olds at Familial Risk for Autism Spectrum Disorder?

Thesis (Master's)--University of Washington, 2016-08

Comparative performance analysis of drives for induction motors

The asynchronous polyphase induction motor has been the motor of choice in industrial settings for about the past half century because power electronics can be used to control its output behavior. Before that, the dc motor was widely used because of its easy speed and torque controllability. The two main reasons why this might be are its ruggedness and low cost. The induction motor is a rugged machine because it is brushless and has fewer internal parts that need maintenance or replacement. This makes it low cost in comparison to other motors, such as the dc motor. Because of these facts, the induction motor and drive system have been gaining market share in industry and even in alternative applications such as hybrid electric vehicles and electric vehicles. The subject of this thesis is to ascertain various control algorithms’ advantages and disadvantages and give recommendations for their use under certain conditions and in distinct applications. Four drives will be compared as fairly as possible by comparing their parameter sensitivities, dynamic responses, and steady-state errors. Different switching techniques are used to show that the motor drive is separate from the switching scheme; changing the switching scheme produces entirely different responses for each motor drive.

Understanding what drives informal learning at work: A resource-based view.

The resource-based view identifies a number of factors that may influence employees’ informal learning. In a cross-sectional survey of 113 German employees in the energy sector, we examined a number of potential predictors of informal learning and a more positive informal learning attitude. The results showed that proactive help-seeking and professional self-efficacy were positive predictors of informal learning. Employees who were older, who enjoyed learning, sought help and were self-efficacious learners had a more positive attitude towards formal learning. Employees who had a more positive attitude about informal learning rated organisational learning provisions as less important, potentially due to being proactive help-seekers. Managers rated organisational learning resources as less important than non-managerial employees. However, managers also reported higher professional self-efficacy. These circumstances may also influence their decision-making regarding the need to provide learning resources to others in the workplace.

UNDERSTANDING CHASSIS INPUTS FROM THE REAR SUSPENSION OF A SNOWMOBILE

Today’s snowmobile industry faces great challenges in the field of noise & vibration. The area of main concern is the pass-by noise restriction defined by the Society of Automotive Engineers (SAE) test standard J192, with a maximum sound pressure level of 78 dB(A) being required by many states and national parks. To continue meet or beat this requirement without effecting machine performance, a deeper understanding of the sound transfer paths is required. This thesis examines the transfer paths created by the tunnel, rear suspension, drive shaft, and rubber composite track, with the primary source being suspension input through the ground. Using a combination of field experiments and analytical modeling, perspective was gained on which suspension and drive elements create the primary transfer paths. With further understanding of these paths, industry can tailor and fine-tune the approaches taken in to control overall noise output.

Organisational cognitive neuroscience drives theoretical progress, or: the curious case of the straw man murder

In this critical essay, we respond to Lindebaum’s (2016) argument that neuroscientific methodologies and data have been accepted prematurely in proposing novel management theory. We acknowledge that building new management theories requires firm foundations. We also find his distinction between demand and supply side forces helpful as an analytical framework identifying the momentum for the contemporary production of management theory. Nevertheless, some of the arguments Lindebaum (2016) puts forward, on closer inspection, can be contested, especially those related to the supply side of organizational cognitive neuroscience (OCN) research: fMRI data, motherhood statements and ethical concerns. We put forward a more positive case for OCN methodologies and data, as well as clarifying exactly what OCN really means, and its consequences for the development of strong management theory.

Unified control system for three-phase electric drives operating in magnetic saturation region

The research project aims to study and develop control techniques for a generalized three-phase and multi-phase electric drive able to efficiently manage most of the drive types available for traction application. The generalized approach is expanded to both linear and non- linear machines in magnetic saturation region starting from experimental flux characterization and applying the general inductance definition. The algorithm is able to manage fragmented drives powered from different batteries or energy sources and will be able to ensure operability even in case of faults in parts of the system. The algorithm was tested using model-in-the-loop in software environment and then applied on experimental test benches with collaboration of an external company.

Multi-phase electric drives for mobility

Multi-phase electrical drives are potential candidates for the employment in innovative electric vehicle powertrains, in response to the request for high efficiency and reliability of this type of application. In addition to the multi-phase technology, in the last decades also, multilevel technology has been developed. These two technologies are somewhat complementary since both allow increasing the power rating of the system without increasing the current and voltage ratings of the single power switches of the inverter. In this thesis, some different topics concerning the inverter, the motor and the fault diagnosis of an electric vehicle powertrain are addressed. In particular, the attention is focused on multi-phase and multilevel technologies and their potential advantages with respect to traditional technologies. First of all, the mathematical models of two multi-phase machines, a five-phase induction machine and an asymmetrical six-phase permanent magnet synchronous machines are developed using the Vector Space Decomposition approach. Then, a new modulation technique for multi-phase multilevel T-type inverters, which solves the voltage balancing problem of the DC-link capacitors, ensuring flexible management of the capacitor voltages, is developed. The technique is based on the proper selection of the zero-sequence component of the modulating signals. Subsequently, a diagnostic technique for detecting the state of health of the rotor magnets in a six-phase permanent magnet synchronous machine is established. The technique is based on analysing the electromotive force induced in the stator windings by the rotor magnets. Furthermore, an innovative algorithm able to extend the linear modulation region for five-phase inverters, taking advantage of the multiple degrees of freedom available in multi-phase systems is presented. Finally, the mathematical model of an eighteen-phase squirrel cage induction motor is defined. This activity aims to develop a motor drive able to change the number of poles of the machine during the machine operation.

Imatinib Restores Vasp Activity And Its Interaction With Zyxin In Bcr-abl Leukemic Cells.

Vasodilator-stimulated phosphoprotein (VASP) and Zyxin are interacting proteins involved in cellular adhesion and motility. PKA phosphorylates VASP at serine 157, regulating VASP cellular functions. VASP interacts with ABL and is a substrate of the BCR-ABL oncoprotein. The presence of BCR-ABL protein drives oncogenesis in patients with chronic myeloid leukemia (CML) due to a constitutive activation of tyrosine kinase activity. However, the function of VASP and Zyxin in BCR-ABL pathway and the role of VASP in CML cells remain unknown. In vitro experiments using K562 cells showed the involvement of VASP in BCR-ABL signaling. VASP and Zyxin inhibition decreased the expression of anti-apoptotic proteins, BCL2 and BCL-XL. Imatinib induced an increase in phosphorylation at Ser157 of VASP and decreased VASP and BCR-ABL interaction. VASP did not interact with Zyxin in K562 cells; however, after Imatinib treatment, this interaction was restored. Corroborating our data, we demonstrated the absence of phosphorylation at Ser157 in VASP in the bone marrow of CML patients, in contrast to healthy donors. Phosphorylation of VASP on Ser157 was restored in Imatinib responsive patients though not in the resistant patients. Therefore, we herein identified a possible role of VASP in CML pathogenesis, through the regulation of BCR-ABL effector proteins or the absence of phosphorylation at Ser157 in VASP.

Hans W. Loewald: a importância da realidade na constituição do sujeito e na clínica psicanalítica

Enfatiza-se a importância da realidade e da experiência atual na constituição do sujeito, por meio da apresentação das ideias de Hans W. Loewald e do exame de sua concepção original de realidade. A natureza relacional das pulsões, a ideia do novo objeto na relação analítica, a noção de invenção da realidade, o conceito de sublimação e a forma de compreender o simbolismo estão entre as formulações mais importantes de Loewald acerca do papel do ambiente na constituição do sujeito. Suas formulações também permitem a compreensão da inserção do sujeito na realidade social contemporânea.

The frequency of CD127(low) expressing CD4(+)CD25(high) T regulatory cells is inversely correlated with human T lymphotrophic virus type-1 (HTLV-1) proviral load in HTLV-1-infection and HTLV-1-associated myelopathy/tropical spastic paraparesis

Background: CD4(+)CD25(high) regulatory T (T(Reg)) cells modulate antigen-specific T cell responses, and can suppress anti-viral immunity. In HTLV-1 infection, a selective decrease in the function of T(Reg) cell mediated HTLV-1-tax inhibition of FOXP3 expression has been described. The purpose of this study was to assess the frequency and phenotype of T(Reg) cells in HTLV-1 asymptomatic carriers and in HTLV-1-associated neurological disease (HAM/TSP) patients, and to correlate with measures of T cell activation. Results: We were able to confirm that HTLV-1 drives activation, spontaneous IFN gamma production, and proliferation of CD4+ T cells. We also observed a significantly lower proportion of CTLA-4(+) T(Reg) cells (CD4(+)CD25(high) T cells) in subjects with HAM/TSP patients compared to healthy controls. Ki-67 expression was negatively correlated to the frequency of CTLA-4(+) T(Reg) cells in HAM/TSP only, although Ki-67 expression was inversely correlated with the percentage of CD127(low) T(Reg) cells in healthy control subjects. Finally, the proportion of CD127(low) T(Reg) cells correlated inversely with HTLV-1 proviral load. Conclusion: Taken together, the results suggest that T(Reg) cells may be subverted in HAM/TSP patients, which could explain the marked cellular activation, spontaneous cytokine production, and proliferation of CD4(+) T cells, in particular those expressing the CD25(high)CD127(low) phenotype. T(Reg) cells represent a potential target for therapeutic intervention for patients with HTLV-1-related neurological diseases.

Functional characterization of the sciarid BhC4-1 core promoter in transgenic Drosophila

Background: Core promoters are cis-regulatory modules to which bind the basal transcriptional machinery and which participate in the regulation of transcription initiation. Although core promoters have not been extensively investigated through functional assays in a chromosomal context, the available data suggested that the response of a given core promoter might vary depending on the promoter context. Previous studies suggest that a (-57/+40) fragment constitutes the core promoter of the BhC4-1 gene which is located in DNA puff C4 of the sciarid fly Bradysia hygida. Here we tested this (-57/+40) fragment in distinct regulatory contexts in order to verify if promoter context affects its core promoter activity. Results: Consistent with the activity of a core promoter, we showed that in the absence of upstream regulatory sequences the (-57/+40) fragment drives low levels of reporter gene mRNA expression throughout development in transgenic Drosophila. By assaying the (-57/+40) fragment in two distinct regulatory contexts, either downstream of the previously characterized Fbp1 enhancer or downstream of the UAS element, we showed that the BhC4-1 core promoter drives regulated transcription in both the germline and in various tissues throughout development. Furthermore, the use of the BhC4-1 core promoter in a UAS construct significantly reduced salivary gland ectopic expression in third instar larvae, which was previously described to occur in the context of the GAL4/UAS system. Conclusions: Our results from functional analysis in transgenic Drosophila show that the BhC4-1 core promoter drives gene expression regardless of the promoter context that was assayed. New insights into the functioning of the GAL4/UAS system in Drosophila were obtained, indicating that the presence of the SV40 sequence in the 3' UTR of a UAS construct does not preclude expression in the germline. Furthermore, our analysis indicated that ectopic salivary gland expression in the GAL4/UAS system does not depend only on sequences present in the GAL4 construct, but can also be affected by the core promoter sequences in the UAS construct. In this context, we propose that the sciarid BhC4-1 core promoter constitutes a valuable core promoter which can be employed in functional assays in insects.