NCube/papyrus huggingface dataset:
El portafolio como una estrategia de evaluación de competencias profesionales de los estudiantes en la enseñanza básica en Ecuador

In tertiary education, the paradigm shift, that is one geared towards learning, has brought changes in the teaching of students so that the latter further develop their reflective and self-regulation capabilities. In this line of action, universities in Latin America, including the Pontifical Catholic University of Ecuador (PUCESD) of Santo Domingo, are participating in project Tuning, by gearing professional training towards capacity building, more specifically towards the capacity to innovate and adapt to changes in the work place. This project represents a comprehensive framework to develop curriculum which encourages student participation. In this context, an academic portfolio was established at the PCUE for all students in initial teacher training so as to collect all the proofs related to assessment and evaluation in different courses. However, this tool did not bring the expected results and thus had discouraged the use of the portfolio among students. This project lies in the field of evaluation et aims to determine how instituting a learning portfolio helps to develop competences of those in initial teacher training by encouraging their participation in the construction of their professional competencies and regulation of learning. The methodology used, i.e action research, has allowed to collect data among 10 students preparing for basic education and their professor in science.   Results show that, firstly, the portfolio, as a tool for formative assessment, put in place during and at the end of the learning process, allowed students to determine their level of competency reached through identification of their strengths and weaknesses, and that without the mention of a grade, just on the basis of written feedback.  Secondly, rubrics were highly useful for feedback and the assessment of three professional competencies for which pieces of work were selected. Thirdly, participation and the reflective posture of students were noticed through the report card and self-regulation rubrics.  The learning portfolio proved to be a relevant formative assessment tool for student participation in the reinforcement of their competencies and the regulation of learning by the professor. However, adoption of this type of portfolio by a large number of university professors remains a challenge to be overcome.

Keyphrases: Competency assessment, Initial teacher training, Professional portfolio, Regulation of learning
Approche probabiliste d’adaptation posologique : concrétisation en outil de santé mobile pour l’aide à la décision clinique du trouble du déficit d’attention avec ou sans hyperactivité

The achievement of a better therapeutic effect through an effective dosage adapted to patients’ specific needs remains the ultimate goal of any practitioner.   The prescription of psychostimulant drugs in Attention Deficit Hyperactivity Disorder, largely based on trial and error, reflects this reality. Within this context, pharmacometric approaches based on new computing technologies and embodied in mobile health tools, present themselves as a future solution with high potential.  This thesis deals with the development of a dose adjustment approach of psychostimulants and their combinations in order to select optimal administration regimens, all the while considering the characteristics of the pediatric population and its daily routine. For this, we have introduced therapeutic indicators involving time or blood concentration and combined them in the form of a mathematical function that evaluates administration regimes’ probabilistic performance as modulated by clinical judgment.  By considering three successive levels of dose adjustment (population, group and individual) and taking into account the drug properties and the clinical context, we developed a multi-objective optimization algorithm using a population pharmacokinetic based modeling and simulation approach. This resulted in an a priori selection of the methylphenidate’s total daily dose and its fractioning in terms of doses and administration time, at the population or group level, or a posteriori, at the individual level. Another important contribution of this thesis is reflected in the translational aspect of the included research work. Indeed, a mobile application has been concretized from the algorithms developed, ready to be used in the daily prescription of psychostimulants in order to improve their use.  This research path, ranging from methodological design to clinical valorisation, is further evidence of the growing potential of pharmacometry in the digital and mobile age.

Keyphrases: ADHD, E-Health, M-Health, Medical application, Methylphenidate, Pharmacometrics, Population-pharmacokinetics, Therapeutic drug monitoring
Évaluation in vivo de l’efficacité thérapeutique, de la résistance et la pharmacocinétique de la colistine sulfate lors du traitement de la diarrhée colibacillaire post sevrage chez le porc

Post-weaning diarrhea (PWD) caused by Escherichia coli is an endemic intestinal infection in pig farms worldwide. This disease is mostly the consequence of the presence and the multiplication in piglet’s gut of an Escherchia pathotype, named enterotoxigenic E. coli (ETEC) and in particular those that express the F4 (K88) fimbrial adhesin (ETEC: F4). The predominant serogroup of E. coli isolated from piglets with PWD worldwide is O149. Several studies have reported a significant resistance rate of O149 ETEC strains against commonly used antibiotics for the treatment of PWD, particularly, aminoglycosides. Thereby, to address therapeutic failures observed in pig farms during PWD treatment, veterinarians in Canada started using, under their responsibilities, the colistin sulfate (CS), an antibiotic not approved for farm animals in Canada. The objectives of this thesis were: to study the pharmacokinetics of CS in vitro and in vivo, to develop a sensitive method for the quantification of CS plasma concentrations in pigs, to determine the therapeutic efficacy of CS in an experimental model of PWD, and to characterize the resistance of E. coli to colistin consecutive to its therapeutic use in pigs. Simulated gastric fluid (SGF) was prepared, and after the addition of CS and pepsin to this solution, the concentrations of CS were followed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). A rapid degradation of CS in the SGF was observed, and the degradation products showed a greater antimicrobial activity compared to the native CS. On the other hand, the experimental challenge of piglets with an ETEC: F4 strain has not increased the CS intestinal absorption in a subclinical model of PWD in pigs. The oral administration of a therapeutic dose of CS at 50,000 IU/kg twice a day for 5 successive days to treat an experimental PWD in pigs, resulted in a significant reduction of fecal ETEC: F4 and total E. coli shedding, and in diarrhea scores but only during the treatment period. However, CS treatment resulted in a slight increase in fecal shedding of CS resistant E. coli and did not prevent weight loss in challenged pigs. In addition, challenge with ETEC: F4 resulted in an increase of CS intestinal absorption in a clinical model of PWD. This study has generated, for the first time, scientific data regarding CS therapeutic efficacy, its pharmacokinetic and the selection of E. coli colistin resistant in an experimental model of PWD in pigs. It also challenged the economic relevance of increasing CS oral doses to accelerate the clinical recovery of pigs. Finally, it indicated that optimal housing conditions were without other predisposing factors, effective as CS in improving clinical symptoms of experimental PWD in pigs.

Keyphrases: E. coli, Colistin sulphate, Post-weaning diarrhea, Pig, Pharmacokinetics
Asthme infantile et polluants du trafic routier

Outdoor air pollution is recognized as an important economic, environmental and sanitary burden. Even though air pollutants are emitted by numerous sources, transportation remains an important source of pollutants, particularly nitrous dioxide (NO2). Road traffic pollutants were linked to health issues, chiefly respiratory problems. This thesis aims to quantify the impact of prolonged exposure to road traffic pollutants on respiratory health for children age between 0 to 12 years old, in Québec.  We developed a birth cohort using medico administrative data and statistical models in order to estimate the association between prolonged exposure to NO2 and onset or exacerbation of childhood asthma. We also used data obtained from transportation, emission and dispersion models to quantified the burden of asthma attributed to road traffic both in 2008 and 2031.  Birth and annual exposure to NO2 are positively linked to childhood asthma onset. Annual NO2 exposure is also associated with the exacerbation of childhood asthma in asthmatic children. In addition of being important the burden associated with transport related air pollution showed important spatial variation in the Montreal region. However the burden associated with road traffic pollution will be reduced in 2031 compared to 2008.  Overall this thesis enables us to quantify the burden associated to NO2 generated by road traffic on respiratory health in children. The results of this research suggest that measures should be taken to reduce the burden of road traffic.

Keyphrases: Public health, Road traffic, Asthma, Air pollution, Burden of disease
The role of amyloid β and Tau in mediating synaptic depression

Alzheimer disease is the most common form of dementia; it is characterized by problems in memory formation, which with time leads to a complete loss of cognitive functions. The peptide amyloid-β (Aβ) and the microtubule-associated protein tau are commonly believed to be responsible for the decline in memory formation. In the early stages of AD, this is thought to happen through a general disruption in synaptic efficiency. The disruptive effects of Aβ on long-term plasticity are well documented; however, little is known about the immediate effects of the peptide on synaptic transmission. My hypothesis is that Aβ does not need a prolonged period to promote changes in synaptic transmission, and that the peptide is able to affect synaptic function even after an acute exposure. In study I, I investigate this hypothesis using an acute exposure of Aβ oligomers to organotypic hippocampal slices. I report that Aβ promotes synaptic depression on hippocampal pyramidal neurons with a fairly rapid kinetic. I also show that the synaptic depression is dependent on the activation of the NMDAR, but independent on the ion flux through the channel. Because it was shown that the activation of the NMDAR leads to phosphorylation of tau, it appears feasible that Aβ modifies neuronal excitability by modulating tau phosphorylation. Since the NMDAR plays a critical role in the induction of long-term plasticity, this cascade of events could contribute to the deficits in plasticity observed during the initial stages of AD. My hypothesis is that Aβ modifies synaptic activity by modulating phosphorylation on tau. To test this hypothesis, I express in hippocampal neurons tau mutants in which phosphorylation on specific sites is blocked. In study II, I report that phosphorylation on tau at the AT8 and AT180 sites regulates the expression of synaptic plasticity as well as the dysfunction in synaptic transmission induced by Aβ oligomers. I also show that phosphorylation at the PHF-1 site is not involved in mediating either effects. Since the AT8 and AT180 sites regulate the interaction of tau protein with the tyrosine kinase Fyn, my results suggested that the interaction between tau and Fyn is important for the expression of synaptic plasticity and the depression mediated by Aβ oligomers. Indeed, I show that inhibiting the activity of Fyn kinase results in a block of LTD and a rescue of synaptic function in presence of Aβ. I conclude that phosphorylation of tau at specific sites is mandatory for the expression of synaptic plasticity, and suggest that Aβ oligomers promote changes of synaptic activity by influencing the stability of the tau-Fyn complex. I therefore propose that disrupting the stability of this complex can be exploited therapeutically to rescue synaptic deficits in the initial stages of AD.

Keyphrases: Fyn, Amyloid β, Tau phosphorylation, Synaptic plasticity, Hippocampus, Alzheimer disease
Effet de l’entraînement des fonctions exécutives sur l’utilisation appropriée de stratégies de mémoire au cours du vieillissement : étude comportementale et électrophysiologique

The main objective of this thesis was to test the efficiency of an executive training program and the transfer effects of this program on other cognitive functions, in particular episodic memory strategies and performance. The present work was based on behavioral and electrophysiological data.  Practice effects of executive tests have been first tested in young and older adults. Two tests have been practiced across ten practice sessions, and the results showed that the executive functions scores increased after practice, more for the older adults than for the younger ones. In order to develop an executive training program requiring several different tests, we have created new executive tests.  The psychometric validity of these tests has been verified and confirmed. These tests have been used for our executive program. Thus, if training effects appeared following this program, they will not be due to the practice of a unique test. Eight sessions of executive stimulation with our new tests have allowed older adults increasing their executive functioning, measured by tests which were different from those employed in the training program (near transfer effects). Other cognitive functions were also improved, as processing speed and episodic memory. For the first time in the literature, far transfer effect have been found memory strategy efficiency and memory performance. More especially, the older adults trained group used more efficient memory strategies (mental imagery or making sentence with the words to be learnt) after the executive training program, and these strategies were more efficient to recall the words. Thus, the memory performance was increased in this group, in comparison the older adults group who did not participate to the training program. At a cerebral level, the executive training seems to decrease the duration of the cerebral activity for the same memory task. However, these results must to be taken with caution and require further analyses to be interpreted correctly. The results of this thesis encourages the development of training programs for executive functions which allows the transfer effects to untrained tasks. These benefits also appear to modify the brain functioning, which implies a longer lasting benefit effect. This work supports the idea that a cognitively stimulating environment is in line with higher cognitive abilities and contributes to successful aging

Keyphrases: episodic memory, executive training, aging, transfer, strategies, event-related potentials
Rôle de la GTPase ARF1 dans la migration et l’invasion des cellules du cancer du sein

Invasive and metastatic chapacities are fundamental features for tumor malignancy. We have recently shown that the ADP-ribosylation factor 1 (ARF1) is over-expressed in highly invasive breast cancer cell lines and stimulation of the epidermal growth factor receptor (EGFR) may activate this isoform to regulate migration and proliferation. However, the role of this GTPase in regulating cell invasion process and related molecular mechanisms remain unknown. In this thesis, we had as objectives, to define the signaling pathways under the control ARF1 in breast cancer cells and show that the expression and activation of the GTPase is associated with highly invasive phenotype.  Our studies show that the modulation of the expression and activity of ARF1 affect the ability of MDA-MB-231 cells (M. D. Anderson-metastatic breast-231), a highly invasive line, to degrade the extracellular matrix via the activity of the metalloproteinase MMP-9. ARF1 controls the two main structures involved in the invasion, playing on invadopodia maturation and shedding of membrane microvesicles. The molecular mechanisms involve the regulation of RhoA and RhoC activity by ARF1 and the following downtream events associated with and the myosin light chain (MLC) phosphorylation.  Furthermore, we demonstrate that ARF1 also regulates migration by controlling the assembly of focal adhesion complexes in many types of breast cancer cells. ARF1, also prensent in adhesion complexes, regulates the recruitment and activity of key proteins such as paxillin, talin and focal adhesion kinase (FAK) to β1 integrin.  Finally, we report that ARF1 and ARF6 play a major role in the epithelial-mesenchymal transition (EMT). ARF1 is found highly expressed in tumor tissue of the most aggressive and advanced subtypes of breast cancer. Lowered expression of ARF1 in vivo in the MDA-MB-231 cells impars tumor growth in primary tumors and inhibits lung metastasis. We report that upregulation of the ARF in non-invasive cells, MCF7 (Michigan Cancer Foundation-7) induce metastasis nidification. Indeed, we show in MCF7 that ARF1 controls intercellular adhesion via the β-catenin and E-cadherin, promotes Ras (Rat Sarcoma/ Rat Fibrosarcoma virus) oncogene activation, and conrols expression of several epithelial-mesenchymal transition markers such as snail and slug. Moreover, we demonstrate that ARF1 controls invasion, proliferation and even resistance to certain chemo-therapeutic agents, in MCF7 cells.  Overall, our studies identify ARF1, as a molecular switch of tumor progression and suggest that limiting its expression / activity could improve the outcome of breast cancer patients.

Keyphrases: Invasion, Migration, ADP-ribosylation Factor, Epidermal growth factor receptor, Invasion, Migration, Epithelio-mesenchymal transition, Breast cancer
Étude de nouveaux complexes impliquant l'IL-6 et CLCF1

Several researches aimed to study new interactions that take place between the different subunits of cytokines and related receptors. The general goal of this thesis is to study the formation of new complexes involving the soluble receptor EBI3 and the cytokine CLCF1, determine their signaling pathways, and examine the impact of these interactions on the induction of new biological functions.  EBI3 is a soluble receptor participating in the formation of three composite cytokines: IL-27 (EBI3/p28), IL-35 (EBI3/p35), and IL-39 (EBI3/p19). These cytokines belong to the IL-12 family. IL-27 is a pleiotropic cytokine that exerts both pro-inflammatory functions characterized by the differentiation of Th1 cells, and anti-inflammatory functions associated with the inhibition of Th17 cells differentiation and the production of GM-CSF. IL-35 is known to induce an immunosuppressive effects while IL-39 has recently been identified to induce inflammation in mice with lupus. Since EBI3 doesn’t form a covalent complexes with p28, p35 and p19 subunits, we wanted to know if the effects of EBI3 could go through the formation of a different compound than that of IL-27, IL-35 and IL-39. We have shown that EBI3 induces a trans-signaling pathway by forming a complex with IL-6. Both IL-6/sIL-6Rα and EBI3/IL-6 complexes share similar pro-inflammatory effects. Indeed, both cytokines activate gp130 chain, induce phosphorylation of STAT3, and increase the expression of chemiokines by human endothelial cells.  CLCF1 belongs to the IL-6 family of monomeric cytokines. CLCF1 is efficiently secreted in the presence of CLF, a soluble cytokine receptor. Mutations in the genes coding for CLCF1 or CLF cause the cold-induced sweating syndrome also called "Crisponi" or "CISS". The interaction between CNTF, a cytokine which may have similar protective effects as CLCF1 at the central nervous system, and apolipoprotein E was observed in vitro (1). We hypothesized that CLCF1 could also form a complex with apoE. We demonstrated that CLCF1 binds with different apoE isoforms, namely, apoE2, apoE3, and apoE4. ApoE is a protein involved in lipid transport and is located primarily on the surface of chylomicrons, VLDL, and a fraction of HDL. We observed that CLCF1 interacts with lipoproteins in the presence and absence of apoE. The impact of CLCF1 interaction with apoE or lipoproteins was examined on cells expressing the chain CNTFRα.

Keyphrases: EBI3, IL-6, IL-6Rα soluble, Inflammation, ApoE, CLCF1, EBI3, IL-6, soluble IL-6Rα, Trans-signaling, Inflammation, Endothelial cells, ApoE, CLCF1, Lipoproteins
Rôles combinés des cytokines IL-2, IL-15 et IL-21 dans le développement et le maintien des lymphocytes T CD8+ mémoires

Over the course of an infection, antigenic signals trigger a specific CD8+ T cells (LTn CD8+) response. Upon antigen recognition, LTn CD8+ are activated and undergo a massive proliferation wave. This leads them to differentiate into effector cells (LTe CD8+) in charge of pathogen elimination. While most effector T cells die after the infection is resolved, a small part of this population persists and differentiates into memory T cells (LTm CD8+). These cells provide long term protection to the organism against the initial infectious agent. It is thus crucial to have a better understanding of all mechanisms governing the development and the maintenance of LTm CD8+. Several studies have already shown that some members of the "C-dependent cytokines family (IL-2, IL-7, IL-15 and IL-21) individually regulate LTe and LTm CD8+ development. However, we believe that these cytokines have a far greater impact on the homeostasis of LTe and LTm CD8+ than the current literature suggests. Indeed, we hypothesized that "C-dependant cytokines act in synergy to promote the development of LTe and LTm CD8+. To assess their effect, we first studied the combined impact of IL-2 and IL-15 signals on the generation of LTe and LTm CD8+ during an LCMV Armstrong infection in mice. In this same experimental model, we also studied the effect of a deficiency in IL-2, IL-15 and IL-21 signals on the development of LTe and LTm CD8+. Our results show that these three cytokines cooperate to support the expansion and differentiation of LTe CD8+. More accurately, IL-2, IL-15 and IL-21 are essential for the homeostasis of a particular LTe CD8+ subset : Short- Lived Effector Cells (SLECs). We also demonstrated that all three cytokines are required to generate a maximal number of LTm CD8+. In addition, differentiation and maintenance of the memory effector population (TEM) are substantially reduced in the combined absence of IL-2, IL-15 and IL-21 signals. These results are the first to our knowledge to highlight redundant and synergistic functions of three "C-dependent cytokines as promoters of the development and maintenance of LTe and LTm CD8+.

Keyphrases: Lymphocytes T CD8 mémoires, cytokines gamma c, Migration, redondance, Virus, CD8+ T lymphocytes, synergy, redundancy, differentiation, maintenance, secondary infection, migration