934 resultados para Domain of Variability
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The carboxyl-terminal (CT) domain of connexin43 (Cx43) has been implicated in both hormonal and pH-dependent gating of the gap junction channel. An in vitro assay was utilized to determine whether the acidification of cell extracts results in the activation of a protein kinase that can phosphorylate the CT domain. A glutathione S-transferase (GST)-fusion protein was bound to Sephadex beads and used as a target for protein kinase phosphorylation. A protein extract produced from sheep heart was allowed to bind to the fusion protein-coated beads. The bound proteins were washed and then incubated with 32P-ATP. Phosphorylation was assessed after the proteins were resolved by SDS-PAGE. Incubation at pH 7.5 resulted in a minimal amount of phosphorylation while incubation at pH 6.5 resulted in significant phosphorylation reaction. Maximal activity was achieved when both the binding and kinase reactions were performed at pH 6.5. The protein kinase activity was stronger when the incubations were performed with manganese rather than magnesium. Mutants of Cx43 which lack the serines between amino acids 364-374 could not be phosphorylated in the in vitro kinase reaction, indicating that this is a likely target of this reaction. These results indicate that there is a protein kinase activity in cells that becomes more active at lower pH and can phosphorylate Cx43.
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Abnormal production of interferon alpha (IFN-a) has been found in certain autoimmune diseases and can be also observed after prolonged therapy with IFN-a. IFN-a can contribute to the pathogenesis of allograft rejection in bone marrow transplants. Therefore, the development of IFN-a inhibitors as a soluble receptor protein may be valuable for the therapeutic control of these diseases. We have expressed two polypeptides encoding amino acids 93-260 (P1) and 261-410 (P2) of the extracellular domain of subunit 1 of the interferon-a receptor (IFNAR 1-EC) in E. coli. The activities of the recombinant polypeptides and of their respective antibodies were evaluated using antiproliferative and antiviral assays. Expression of P1 and P2 polypeptides was achieved by transformation of cloned plasmid pRSET A into E. coli BL21(DE3)pLysS and by IPTG induction. P1 and P2 were purified by serial sonication steps and by gel filtration chromatography with 8 M urea and refolded by dialysis. Under reducing SDS-PAGE conditions, the molecular weight of P1 and P2 was 22 and 17 kDa, respectively. Polyclonal anti-P1 and anti-P2 antibodies were produced in mice. P1 and P2 and their respective polyclonal antibodies were able to block the antiproliferative activity of 6.25 nM IFN-aB on Daudi cells, but did not block IFN-aB activity at higher concentrations (>6.25 nM). On the other hand, the polypeptides and their respective antibodies did not inhibit the antiviral activity of IFN-aB on Hep 2/c cells challenged with encephalomyocarditis virus.
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The dissertation proposes two control strategies, which include the trajectory planning and vibration suppression, for a kinematic redundant serial-parallel robot machine, with the aim of attaining the satisfactory machining performance. For a given prescribed trajectory of the robot's end-effector in the Cartesian space, a set of trajectories in the robot's joint space are generated based on the best stiffness performance of the robot along the prescribed trajectory. To construct the required system-wide analytical stiffness model for the serial-parallel robot machine, a variant of the virtual joint method (VJM) is proposed in the dissertation. The modified method is an evolution of Gosselin's lumped model that can account for the deformations of a flexible link in more directions. The effectiveness of this VJM variant is validated by comparing the computed stiffness results of a flexible link with the those of a matrix structural analysis (MSA) method. The comparison shows that the numerical results from both methods on an individual flexible beam are almost identical, which, in some sense, provides mutual validation. The most prominent advantage of the presented VJM variant compared with the MSA method is that it can be applied in a flexible structure system with complicated kinematics formed in terms of flexible serial links and joints. Moreover, by combining the VJM variant and the virtual work principle, a systemwide analytical stiffness model can be easily obtained for mechanisms with both serial kinematics and parallel kinematics. In the dissertation, a system-wide stiffness model of a kinematic redundant serial-parallel robot machine is constructed based on integration of the VJM variant and the virtual work principle. Numerical results of its stiffness performance are reported. For a kinematic redundant robot, to generate a set of feasible joints' trajectories for a prescribed trajectory of its end-effector, its system-wide stiffness performance is taken as the constraint in the joints trajectory planning in the dissertation. For a prescribed location of the end-effector, the robot permits an infinite number of inverse solutions, which consequently yields infinite kinds of stiffness performance. Therefore, a differential evolution (DE) algorithm in which the positions of redundant joints in the kinematics are taken as input variables was employed to search for the best stiffness performance of the robot. Numerical results of the generated joint trajectories are given for a kinematic redundant serial-parallel robot machine, IWR (Intersector Welding/Cutting Robot), when a particular trajectory of its end-effector has been prescribed. The numerical results show that the joint trajectories generated based on the stiffness optimization are feasible for realization in the control system since they are acceptably smooth. The results imply that the stiffness performance of the robot machine deviates smoothly with respect to the kinematic configuration in the adjacent domain of its best stiffness performance. To suppress the vibration of the robot machine due to varying cutting force during the machining process, this dissertation proposed a feedforward control strategy, which is constructed based on the derived inverse dynamics model of target system. The effectiveness of applying such a feedforward control in the vibration suppression has been validated in a parallel manipulator in the software environment. The experimental study of such a feedforward control has also been included in the dissertation. The difficulties of modelling the actual system due to the unknown components in its dynamics is noticed. As a solution, a back propagation (BP) neural network is proposed for identification of the unknown components of the dynamics model of the target system. To train such a BP neural network, a modified Levenberg-Marquardt algorithm that can utilize an experimental input-output data set of the entire dynamic system is introduced in the dissertation. Validation of the BP neural network and the modified Levenberg- Marquardt algorithm is done, respectively, by a sinusoidal output approximation, a second order system parameters estimation, and a friction model estimation of a parallel manipulator, which represent three different application aspects of this method.
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The MDR1 gene encodes the P-glycoprotein, an efflux transporter with broad substrate specificity. P-glycoprotein has raised great interest in pharmacogenetics because it transports a variety of structurally divergent drugs, including lipid-lowering drugs. The synonymous single-nucleotide polymorphism C3435T and the nonsynonymous single-nucleotide polymorphism G2677T/A in MDR1 have been indicated as potential determinants of variability in drug disposition and efficacy. In order to evaluate the effect of G2677T/A and C3435T MDR1 polymorphisms on serum levels of lipids before and after atorvastatin administration, 69 unrelated hypercholesterolemic individuals from São Paulo city, Brazil, were selected and treated with 10 mg atorvastatin orally once daily for four weeks. MDR1 polymorphisms were analyzed by PCR-RFLP. C3435T and G2677T polymorphisms were found to be linked. The allelic frequencies for C3435T polymorphism were 0.536 and 0.464 for the 3435C and 3435T alleles, respectively, while for G2677T/A polymorphism allele frequencies were 0.580 for the 2677G allele, 0.384 for the 2677T allele and 0.036 for the 2677A allele. There was no significant relation between atorvastatin response and MDR1 polymorphisms (repeated measures ANOVA; P > 0.05). However, haplotype analysis revealed an association between T/T carriers and higher basal serum total (TC) and LDL cholesterol levels (TC: 303 ± 56, LDL-C: 216 ± 57 mg/dl, respectively) compared with non-T/T carriers (TC: 278 ± 28, LDL-C: 189 ± 24 mg/dl; repeated measures ANOVA/Tukey test; P < 0.05). These data indicate that MDR1 polymorphism may have an important contribution to the control of basal serum cholesterol levels in Brazilian hypercholesterolemic individuals of European descent.
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The viscoelastic properties of edible films can provide information at the structural level of the biopolymers used. The objective of this work was to test three simple models of linear viscoelastic theory (Maxwell, Generalized Maxwell with two units in parallel, and Burgers) using the results of stress relaxation tests in edible films of myofibrillar proteins of Nile Tilapia. The films were elaborated according to a casting technique and pre-conditioned at 58% relative humidity and 22ºC for 4 days. The testing sample (15mm x 118mm) was submitted to tests of stress relaxation in an equipment of physical measurements, TA.XT2i. The deformation, imposed to the sample, was 1%, guaranteeing the permanency in the domain of the linear viscoelasticity. The models were fitted to experimental data (stress x time) by nonlinear regression. The Generalized Maxwell model with two units in parallel and the Burgers model represented the relaxation curves of stress satisfactorily. The viscoelastic properties varied in a way that they were less dependent on the thickness of the films.
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Smart home implementation in residential buildings promises to optimize energy usage and save significant amount of energy simply due to a better understanding of user's energy usage profile. Apart from the energy optimisation prospects of this technology, it also aims to guarantee occupants significant amount of comfort and remote control over home appliances both at home locations and at remote places. However, smart home investment just like any other kind of investment requires an adequate measurement and justification of the economic gains it could proffer before its realization. These economic gains could differ for different occupants due to their inherent behaviours and tendencies. Thus it is pertinent to investigate the various behaviours and tendencies of occupants in different domain of interests and to measure the value of the energy savings accrued by smart home implementations in these domains of interest in order to justify such economic gains. This thesis investigates two domains of interests (the rented apartment and owned apartment) for primarily two behavioural tendencies (Finland and Germany) obtained from observation and corroborated by conducted interviews to measure the payback time and Return on Investment (ROI) of their smart home implementations. Also, similar measures are obtained for identified Australian use case. The research finding reveals that building automation for the Finnish behavioural tendencies seems to proffers a better ROI and payback time for smart home implementations.
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Behavioral economics has addressed interesting positive and normative questions underlying the standard rational choice theory. More recently, it suggests that, in a real world of boundedly rational agents, economists could help people to improve the quality of their choices without any harm to autonomy and freedom of choice. This paper aims to scrutinize available arguments for and against current proposals of light paternalistic interventions mainly in the domain of intertemporal choice. It argues that incorporating the notion of bounded rationality in economic analysis and empirical findings of cognitive biases and self-control problems cannot make an indisputable case for paternalism.
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The User Experience (UX) designers are undoubtedly aware of how many UX design methods currently exist and that sometimes it becomes a problem to choose an appropriate one. What are all of methods that designers have in their “arsenal”? When can they use them? This thesis presents the research on the design methods in the contemporary context of User Experience (UX) and Innovations by using a survey approach. The study is limited to cover the domain of consumer mobile services development and provider companies around the world. The study follows 2 clear objectives: (1) to understand what design methods are currently used in that context and to what extent they are used (2) to identify at what stage according to the UX design thinking process for creating innovations they are placed. The study contributes to the research in the field of UX design and Innovations and extends the knowledge in that field together with communities’ (UXPA, SIGCHI, SIGSOFT) members’ cooperation. The research is vital due to lack of information on design practices and their application in the chosen context.
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Since the discovery of West Nile (WN) virus in the Western Hemisphere many surveillance programs have been implemented to monitor the epidemiology and genetic variation of WN virus in North America. This project was based on the WN virus Adult Mosquito Identification and Diagnostic Program conducted at Brock University for Ontario, Canada, during the 2002 and 2003 transmission seasons. There are three sections to this thesis. The first section investigated which mosquito species carry WN virus in Ontario, Canada throughout the 2002-2003 transmission seasons. It was found that from the 2002 data, eight mosquito species were detected with WN virus (Aedes vexans, Anopheles punctipennis, Coquilleltidia perlurbans, Culex salinarius, Cx. pipiens, Cx. resluans, Ochlerolalus Irivillalus and Och. Iriserialus) and 7.19% of the total mosquito pools tested were found to be WN virus positive (129 positive poolsll, 793 total pools tested). In 2003, WN virus was detected in only five mosquito species (Ae. vexans, Cx. salinarius, Och. Iriserialus, Cx. pipiens and Cx. resluans) and 1.42% of the total mosquito pools tested were WN virus positive (101 positive poolsl7,1 01 total pools tested). WN virus positive mosquito pools were detected 3-4 weeks earlier in 2002 compared to 2003 data. The second section investigated the actual infection rate (IR) of clearly identified Cx. pipiens and Cx. resluans from the 2002 outbreak. It was found that significantly more ex. resluans were infected with WN virus compared to ex. pipiens. The third section investigated the degree of variability of the WN virus genome. A 879 nucleotide section of the WN virus genome was amplified from 21 American Crows and 20 adult female mosquitoes from Ontario, Canada, and compared to the homologous region of the original New York 1999 Chilean Flamingo sequence (NY99FL). Seventy-two nucleotides from Ontario WN virus sequences showed variability compared to NY99FL with 10 synapotypic changes. Phylogenetic analysis revealed a close relationship between Ontario and US WN virus sequences.
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The world of work with Western society appears to be undergoing a major change. The literature has described this phenomenon as a change from an industrialbased economy to a knowledge-based economy. This change will represent a complete transformation of the world of work; some suggest that everything we have come to accept and know as normal will change. Our present society seems to be in a period of transition. It is a time with many challenges and problems, many of which cannot be solved with thinking patterns from an old industrial-based economy. A fundamental shift in thinking patterns consistent with a new emerging world of work must take place. This change in thinking represents a fundmental shift from traditional and linear ways of seeing the world (worldview), to more holistic ways of seeing the world. In this investigation the word paradigm was used to define how people see their world. A paradigm shift is defined as a change in how a person sees their world: a change from an old to new or different way of viewing the world. Those individuals who are the first to shift their paradigm are called paradigm pioneers. These individuals do not only shift their ways of seeing the world, but they also begin to act and behave in ways consistent with the new paradigm. Thus far the research literature has adequately described the concepts of paradigms and paradigm shifts. However, little is known regarding how people actually and eventually make a shift. As it will be important for each individual to make a personal paradigm shift, then it will be extremely valuable to learn more about the process itself. The purpose of this investigation was to explore these issues in more detail and specifically, describe the experience of paradigm shifts and explore the experience of paradigm pioneers. A qualitative research methodology involving in-depth interviews was used to investigate the experiences of four participants identified as paradigm pioneers. It is interesting to note that the participants in this study did not describe an allencompassing paradigm shift. In fact, each participant, defined a paradigm shift in several different ways. They did relate several examples of paradigm shifts. However, even among these examples, there was a high degree of variability. The findings of this investigation centered upon the participants' experience as pioneers. Each pioneer shared many of the same qualities, the first quality of which described how these pioneers dealt with change. I called this a change-sense quality. The pioneers viewed change in an open and positive manner, and were also aware of change taking place in their world. Finally, they displayed an understanding of change, and a bias to take positive action in the face it. The participants also shared an inner quality. The four pioneers demonstrated a personal purpose and vision, and were selfdirected individuals. They also had an innate curiosity which translated into a love of learning. They also displayed a quality where relationships with others were highly valued. Relationships were important to the pioneers because they played a support role to help them deal with the challenges of being a pioneer. Pioneers also valued relationships because, they relied on others to make change happen. The above mentioned qualities enabled pioneers to be effective in a changing world of work. The findings from this investigation have many implications for research and practice. First, the concept of paradigms and paradigm shifts must be further researched. A great deal more must be learned in order to better understand the kind of shift individuals must make to be effective in the new world of work. Second, the qualities displayed by pioneers are important for all members of the world of work to develop. The qualities shared by pioneers appeared to represent an enduring set of traits that can possibly help individuals deal more positively with uncertainty and rapid change taking place in today's North American world of work.
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Underlying intergroup perceptions include processes of social projection (perceiving personal traitslbeliefs in others, see Krueger 1998) and meta-stereotyping (thinking about other groups' perceptions of one's own group, see Vorauer et aI., 1998). Two studies were conducted to investigate social projection and meta-stereotypes in the domain of White-Black racial relations. Study 1, a correlational study, examined the social projection of prejudice and 'prejudiced' meta-stereotypes among Whites. Results revealed that (a) Whites socially projected their intergroup attitudes onto other Whites (and Blacks) [i.e., Whites higher in prejudice against Blacks believed a large percentage of Whites (Blacks) are prejudiced against Blacks (Whites), whereas Whites low in prejudice believed a smaller percentage of Whites (Blacks) are prejudiced]; (b) Whites held the meta:..stereotype that their group (Whites) is viewed by Blacks to be prejudiced; and (c) prejudiced meta-stereotypes may be formed through the social projection of intergroup attitudes (result of path-model tests). Further, several correlates of social projection and meta-stereotypes were identified, including the finding that feeling negatively stereotyped by an outgroup predicted outgroup avoidance through heightened intergroup anxiety. Study 2 replicated and extended these findings, investigating the social projection of ingroup favouritism and meta- and other-stereotypes about ingroup favouritism. These processes were examined experimentally using an anticipated intergroup contact paradigm. The goal was to understand the experimental conditions under which people would display the strongest social projection of intergroup attitudes, and when experimentally induced meta-stereotypes (vs. other-stereotypes; beliefs about the group 11 preferences of one's outgroup) would be most damaging to intergroup contact. White participants were randomly assigned to one of six conditions and received (alleged) feedback from a previously completed computer-based test. Depending on condition, this information suggested that: (a) the participant favoured Whites over Blacks; (b) previous White participants favoured Whites over Blacks; (c) the participant's Black partner favoured Blacks over Whites; (d) previous Black participants favoured Blacks over Whites; (e) the participant's Black partner viewed the participant to favour Whites over Blacks; or (£) Black participants previously participating viewed Whites to favour Whites over Blacks. In a defensive reaction, Whites exhibited enhanced social projection of personal intergroup attitudes onto their ingroup under experimental manipulations characterized by self-concept threat (i.e., when the computer revealed that the participant favoured the ingroup or was viewed to favour the ingroup). Manipulated meta- and otherstereotype information that introduced intergroup contact threat, on the other hand, each exerted a strong negative impact on intergroup contact expectations (e.g., anxiety). Personal meta-stereotype manipulations (i.e., when the participant was informed that her/ his partner thinks s/he favours the ingroup) exerted an especially negative impact on intergroup behaviour, evidenced by increased avoidance of the upcoming interracial interaction. In contrast, personal self-stereotype manipulations (i.e., computer revealed that one favoured the ingroup) ironically improved upcoming intergroup contact expectations and intentions, likely due to an attempt to reduce the discomfort of holding negative intergroup attitudes. Implications and directions for future research are considered.
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The Arabidopsis NPRI protein regulates systemic acquired resistance dependent on salicylic acid. Analyses by plant two-hybrid analysis in vivo and pull-down assays in vitro showed that the BTB/POZ domain of NPRI at the N-terminus serves as an autoinhibitory domain to negate the function of the transactivation domain at the C-terminus through direct binding of these two domains. I t was also shown that the binding of the BTB/POZ domain to the C-terminus of NPRI was abolished by SA treatment, suggesting that SA could interfere directly with this binding. By gel filtration, it was demonstrated that SA affects the conformation of full-length NPRl , confirming the role of NPRI as an SA receptor. Gel filtration analysis also indicated that NPRI could be converted from an oligomer to a dimer with SA treatment. Furthermore, one N-terminal deletion ~513 has been shown to act as a metal-binding protein and its two Cys-521 and Cys-529 are important for binding to Ni 2 + by pull-down assays.
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The goal of the four studies that comprised this dissertation was to examine how spirituality/religiosity (SIR), as both an institutional and personal phenomenon, developed over time, and how its institutional (i.e., religious activity involvement) and personal (i.e., sense of connection with the sacred) components were uniquely linked with psychosocial adjustment. In Study 1, the differential longitudinal correlates of religious service attendance, as compared to involvement in other clubs, were evaluated with a sample of adolescents (n=1050) who completed a survey in grades 9, 11 and 12. Religious attendance and involvement in non-religious clubs were uniquely associated with positive adjustment in terms of lower substance use and better academic marks, particularly when involvement was sustained over time. In Study 2, the direction of effects was tested for the association between religious versus non-religious activities and both substance use and academic marks. Participants (n= 3993) were surveyed in grades 9 through 12. Higher religious attendance (but not non-religious club involvement) in one grade predicted lower levels of substance use in the next grade. Higher levels of nonreligious club involvement (but not religious service attendance) in one grade predicted higher academic achievement in the next grade, and higher academic achievement in one grade predicted more frequent non-religious club involvement in the next grade. The results suggest that different assets may be fostered in religious as compared to nonreligious activities, and, specifically, religious activity involvement may be important for the avoidance of substance use. The goal of Study 3 was to assess the unique associations between the institutional versus personal dimensions of SIR and a wide range of domains of psychosocial adjustment (namely, intrapersonal well-being, substance use, risk attitudes, parental relationship quality, academic orientation, and club involvement), and to examine the direction of effects in these associations. Participants (n=756) completed a survey in grades 11 and 12. Personal and institutional dimensions of SIR were differentially associated with adjustment, but it may only be in the domain of risk-taking (Le., risk attitudes, substance use) that SIR may predict positive adjustment over time. Finally, in Study 4, the goal was to examine how institutional and personal aspects of SIR developed within individual adolescents. Configurations of mUltiple dimensions of spirituality/religiosity were identified across 2 time points with an empirical classification procedure (cluster analysis), and sample- and individual-level development in these configurations were assessed. A five cluster-solution was optimal at both grades. Clusters were identified as aspirituallirreligious, disconnected wonderers, high institutional and personal, primarily personal, and meditators. With the exception of the high institutional and personal cluster, the cluster structures were stable over time. There also was significant intraindividual stability in all clusters over time; however, a significant proportion of individuals classified as high institutional and personal in Grade 11 moved into the primarily personal cluster in Grade 12. This program of research represented an important step towards addressing some of the limitations within the body of literature; namely, the uniqueness of religious activity involvement as a structured club, the differential link between institutional versus personal SIR and psychosocial adjustment, the direction of effects in the associations between institutional versus personal SIR and adjustment, and the way in which different dimensions of SIR may be configured and develop within individual adolescents over time.
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Human Class I phosphatidylinositol transfer proteins (PITPs) exists in two forms: PITPα and PITPβ. PITPs are believed to be lipid transfer proteins based on their capacity to transfer either phosphatidylinositol (PI) or phosphatidylcholine (PC) between membrane compartments in vitro. In Drosophila, the PITP domain is found to be part of a multi-domain protein named retinal degeneration B (RdgBα). The PITP domain of RdgBα shares 40 % sequence identity with PITPα and has been shown to possess PI and PC binding and transfer activity. The detailed molecular mechanism of ligand transfer by the human PITPs and the Drosophila PITP domain remains to be fully established. Here, we investigated the membrane interactions of these proteins using dual polarization interferometry (DPI). DPI is a technique that measures protein binding affinity to a flat immobilized lipid bilayer. In addition, we also measured how quickly these proteins transfer their ligands to lipid vesicles using a fluorescence resonance energy transfer (FRET)-based assay. DPI investigations suggest that PITPβ had a two-fold higher affinity for membranes compared to PITPα. This was reflected by a four-fold faster ligand transfer rate for PITPβ in comparison to PITPα as determined by the FRET assay. Interestingly, DPI analysis also demonstrated that PI-bound human PITPs have lower membrane affinity compared to PC-bound PITPs. In addition, the FRET studies demonstrated the significance of membrane curvature in the ligand transfer rate of PITPs. The ligand transfer rate was higher when the accepting vesicles were highly curved. Furthermore, when the accepting vesicles contained phosphatidic acid (PA) which have smaller head groups, the transfer rate increased. In contrast, when the accepting vesicles contained phosphoinositides which have larger head groups, the transfer rate was diminished. However, PI, the favorite ligand of PITPs, or the presence of anionic lipids did not appear to influence the ligand transfer rate of PITPs. Both DPI and FRET examinations revealed that the PITP domain of RdgBα was able to bind to membranes. However, the RdgBα PITP domain appears to be a poor binder and transporter of PC.
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Affiliation: Faculté de Médecine Vétérinaire, Université de Montréal