Socrate, aujourd'hui. Quelle pertinence ? Quelle utilité ? Que nous enseignerait-il ? De quoi nous libérerait-il ? Où nous mènerait-il ? Répondre à ces questions, indubitablement, c'est refaire le procès de Socrate, donner notre jugement sur ce dernier. Remarquons que, jour après jour, notre monde serait très près de condamner, comme les Athéniens de l'époque, le philosophe. Alors que nous nous imaginerions une distance infinie entre les contempteurs de Socrate et nous, notre parenté en est presque immédiatement démontrée par cette seule opinion. D'ailleurs, notre préoccupation centrale est de bien déterminer ce qui, dans notre monde, encouragerait la mise à mort de Socrate et ce qu'il incarne parfaitement, la philosophie. Notre thèse est là, qu'est-ce qui tue Socrate ? Y répondre éclairera aussi les questions se résumant au bien supposé qu'il peut faire à notre civilisation. Bref, tentons de ne point répéter les mêmes bourdes que certains Athéniens. Il nous faut, impérativement, devenir meilleurs, nous tourner vers le Bien. Nos vies en dépendent. Nous dépendons de Socrate. / Socrates today. What relevance? What use? What would he teach us? What would he free us from? Where would he lead us? To answer these questions, no doubt, is to do over again the trial of Socrates, and to judge the latter ourselves. It is noteworthy that, day after day, our world remains very near condemning the philosopher, as did the Athenians of that time. While we might imagine there may lie an infinite distance between those despisers of Socrates and ourselves, our actual kinship with them is almost immediately brought to the fore by this opinion alone. Our central concern here is, in point of fact, precisely to determine what, in our present world, would indeed encourage the killing of Socrates as well as of what he perfectly embodies, philosophy. There lies our thesis: what is it that kills Socrates? To try to answer this should also help clarify all questions related to what good a Socrates may bring to a civilization such as ours; in a word, then, how not to repeat such blunders as those committed by the Athenians against him. We must imperatively become better, turn to the Good. Our lives depend on it. We depend on Socrates.

En 2005, le comité sur l’immunisation du Québec recommandait de passer du programme de vaccination contre l’hépatite B (HB) des préadolescents à celui des nourrissons lorsqu’un vaccin hexavalent serait disponible. Pour déterminer l’impact d’un tel changement, un bilan épidémiologique de l’HB a été réalisé à partir des cas déclarés au fichier des maladies à déclarations obligatoires. De 2005 à 2009, une vaccination des nourrissons aurait potentiellement pu prévenir 0,0335 (IC 95%: 0.0334-0.0336) cas aigus par 100 000 personnes-années chez les moins de 20 ans. De 2010 à 2013, aucun cas aigu n’a été rapporté dans ce groupe d’âge. Le programme de vaccination actuel des préadolescents est hautement efficace. En 2014, changer ce programme pour une vaccination des nourrissons avec un vaccin hexavalent n’apporterait pas de bénéfice épidémiologique mais permettrait d’augmenter la couverture vaccinale de 8-12%. / In 2005, the Quebec immunization committee recommended to replace the hepatitis B (HB) school-based immunization program by an infant program when an hexavalent vaccine would become available. To estimate the potential impact of such a program change, we summarized the HB epidemiology based on reported cases retrieved from the provincial registry of notifiable diseases. Between 2005 and 2009, 0.0335 (95% CI: 0.0334-0.0336) acute case per 100,000 person-years reported in 0-19 year-olds could have potentially been prevented by an infant immunization program. Between 2010 and 2013, no acute cases were reported in this age group. The current vaccination program is highly effective. In 2014, changing for an infant vaccination program using the hexavalent vaccine can hardly bring additional epidemiological benefit but may increase the vaccine coverage rate by 8-12%.

Using data recorded by the CLEO II detector operating at the Upsilon(4S) resonance at the Cornell Electron Storage Ring, several properties of B mesons are measured using a partially reconstructed tag of the decay mode bar{B0} -> D*+ l- bar{nu}. Using 2.38 fb**{-1} of on-resonance data and the averaged B meson semileptonic branching fraction through inclusive lepton momentum spectrum obtained by previous CLEO analysis, we measure the B0 and B- semileptonic branching fraction to be (10.78 +/- 0.60 +/- 0.69)% and (10.25 +/- 0.57 +/- 0.65)% respectively, which yields the lifetime ratio tau_+/tau_0 = 0.950 +0.117-0.080 +0.091-0.068, assuming the equality of semileptonic partial branching width for bar{B0} and B-. With a larger dataset of 3.1 fb**{-1}, we measured the B0-bar{B0} mixing parameter chi_d to be 0.189 +/- 0.019 +/- 0.006. / Ph. D.

The set of decays known as B⁰ → l⁺l⁻ are exceedingly rare. This thesis details procedures developed to optimize signal extraction and improve the upper limit on the measured branching fraction. When applied to 85 million BB events collected at the Belle experiment in Tsukuba, Japan, the resulting upper limits on branching fractions were 8.8×10⁻⁸ for B⁰ → e⁺e⁻, 1.0×10⁻⁷ for B⁰ → μ⁺μ⁻, and 8.5×10⁻⁸ for B⁰ → e±μ∓" at the 90% confidence level. / Ph. D.

Horses are prone to potentially lethal endotoxemia due to their surrounding fecal containing environment and their predisposition to colic. Their gastrointestinal tract and feces naturally contain gram-negative bacteria. These bacteria express lipopolysaccharide (LPS) on their cell membranes, which is recognized by Toll-like receptor 4 (TLR4). In cases where epithelial barriers are compromised or breached LPS has the potential to enter circulation and cause the inflammatory symptoms seen with endotoxemia. The objective of this study was to determine TLR4 presence and functionality on equine B cells. TLR4 expression on B lymphocytes has been studied in mouse, human and many other mammals, but has not been well characterized in the horse. Humans are highly sensitive to LPS but their B cells express non-functional TLR4. Mice in contrast are highly tolerant of LPS yet their B cells express functional TLR4. Studies in horse have perhaps been limited by the limited array of antibody markers available for use in horse. Anti-human CD21 has previously been shown to mark equine B lymphocytes. We show rat anti-mouse CD45R(B220) mAbs also accurately labels equine B lymphocytes. To investigate TLR4 expression in horses 12 Thoroughbred geldings, ages 5-10, were used for blood collection. By using the density gradient, Lympholyte, lymphocytes were separated from peripheral blood and incubated with or without LPS. B lymphocyte proliferation, TLR4 expression and mRNA changes were examined before or after culture in the presence or absence of LPS. We demonstrate TLR4 is expressed on equine B lymphocytes through the use of a mouse anti-human TLR4 antibody, clone 76B357.1, not previously used in horse. We demonstrated equine B cells fail to proliferate under LPS challenge as opposed to highly proliferative mouse B lymphocytes. However, transcriptional changes were observed in the equine cells within the TLR4 pathway upon treatment with LPS. / Master of Science

Decays of B mesons to three-body charmless final states probe the properties of the weak interaction through their dependence on the complex quark couplings in the CKM matrix. They also test dynamical models for hadronic B decays. Based on a sample of 772 million BB pairs collected by the Belle experiment, we present a study of direct CP violation in the decay of charged B to three charged pions. / Ph. D.

Geometric trimming of a surface involves removal of unwanted portions of the surface and providing a new mathematical description for the trimmed patch. This entails creating a new geometry for the trimmed patch, which closely approximates the corresponding portion on the original patch. The procedure is shown to involve obtaining data points on the B-spline surface that lie within the region specified by the parameter values for the trimming curve and describing a new surface which interpolates this new set of data points. This research looks at optimizing the procedure described above by basing the choice of parameter values for the trimming curve, at points where curvature optima occur over the surface. A visualization tool kit has been developed using OpenGL, as a means to discern the difference between the two surfaces. In order to quantify and aid in minimizing the error (difference) in approximating the original surface with the trimmed patch, an error measurement tool developed in MATLAB has been employed. / Master of Science

Most of the work accomplished on surface blending is based on visual trimming. In the process of visual trimming, the unwanted portion of a surface is only hidden but not removed. Geometric trimming provides a complete mathematical description of the wanted portion of the trimming surface, and generates a new mathematical surface or sets of surface patches. The new surface is intended to resemble closely the corresponding portion of the original surface. A robust procedure is developed to geometrically trim the intersecting surfaces and blend the trimmed surface patches into one new surface. This research generates a filleting algorithm for surface blending of an aircraft fuselage shape and a wing shape at a closed trimming intersection curve, and verifies the properties of the newly created surface. In order to distinguish how well the new surface approximates the original, an error comparison tool developed in MATLAB has been employed. / Master of Science

published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

Gene therapy has shown potential in alleviating a wide range of diseases, ranging from viral infections to autosomal diseases. One of the obstacles to gene therapy reaching its full potential is the inadequacy of methods to deliver therapeutic nucleic sequences. Current delivery of gene therapy entails use of viral and non-viral vectors. Viral vectors are however associated with drawbacks such as potential toxicity, high cost and labour-intensive production. Thus non-viral delivery alternatives are being developed in an attempt to overcome difficulties associated with nucleic acid delivery for gene therapy. Virus-like particles are potentially very useful delivery vehicles as their production is simple and cost effective, the particle surface is amenable to modification and the capsid interior can be altered to accommodate a variety of cargoes. One such particle is the recombinant HBV capsid, which comprises a single species of protein and is tolerant of amino acid substitutions on the surface exposed immunodominant loops. This study aimed to enhance the vector-like properties of the HBV virus-like particle by including amino acid substitutions on the particle surface. These substituted residues in turn provided a conjugation site for tropic and immuno evasive moieties. It was found that lysine substitutions resulted in poor conjugation to the capsid surface, whereas substituted cysteine residues resulted in almost all protein-moiety conjugates forming. In order to introduce lysine and cysteine substitutions, a novel method of cloning into the HBV was generated. In doing so, complicated procedures associated with cloning into the immunodominant loop of the HBV capsid have been alleviated. Ligands containing galactose were utilised on the surface of both the HBV capsid and liposomes to confer hepatotropism. The presence of the galactose moieties on the surface of the HBV capsid prevented indiscriminate cellular uptake in cultured cells, however did not improve hepatotropism. Galactose ligands on the surface of liposomes did improve transfection efficiency, however they required a short linker distance between liposome surface and galactose group. The inclusion of galactose in liposome formulations also provided a means to deliver siRNA to the liver of transgenic HBV mice. It is believed that with alterations to the ligand structure, it is possible to provide HBV capsids with hepatotropism in future experimentation. This study demonstrated that the exposed external surface of the HBV capsid is amenable to convenient conjugation, which potentially facilitates immune evasion and conferring of defined tropism.