Forage de données pour la détection d'un état de blocage de l'apprenant dans le cadre du système tutoriel intelligent QED-Tutrix

L’état de blocage est le moment où un apprenant, en pleine résolution de problème sur un système tutoriel intelligent, a besoin d’une intervention tutorielle pour poursuivre sa résolution. Dans ce mémoire, des modèles probabilistes seront développés pour détecter les états de blocage d’un apprenant qui résout un problème sur le système tutoriel intelligent en mathématiques QED-Tutrix. La méthodologie inclut deux expérimentations avec une version modifiée de QED-Tutrix pour recueillir des séquences d’actions associées à un état de blocage ou de non-blocage. Dans ces ensembles de données, des états de blocage ont été observés à partir des fréquences d’actions et des distributions de sous-séquences. Quatre modèles probabilistes ont été développés en tout : le modèle de processus de fréquence d’actions, le modèle bayésien en sous-séquences d’actions, le modèle du réseau de neurones convolutif et le modèle hybride. Ce dernier surpasse les autres avec un score F1 de 80,4 % pour la classification des états de blocage sur l’ensemble d’entraînement et 77,3 % sur l’ensemble test. L’application de cette recherche mène directement à l’amélioration de la machine à états de QED-Tutrix dans son interaction avec l’apprenant. Elle aboutit aussi sur une deuxième phase de travaux de recherche durant laquelle le développement d’interventions tutorielles ciblées est approché. Puisqu’il est possible d’identifier les moments de blocage de l’apprenant avec une bonne précision, il faut à présent concevoir des algorithmes pouvant comprendre le contexte du blocage et pouvant intervenir en conséquence. En ce qui concerne l’amélioration des performances des modèles, l’incorporation de l’historique des blocages dans les modèles probabilistes est à considérer en plus d’une considération du contexte mathématique.----------ABSTRACT: A blocking state is a cognitive state in which a student cannot make any progress toward finding a solution to a problem. In this research, we present the development of probabilistic models to detect a blocking state while solving a Canadian high school-level problem in Euclidean geometry on an intelligent tutoring system. Our methodology includes an experimentation with a modified version of QED-Tutrix, an intelligent tutoring system, which was used to gather labelled datasets composed of sequences of mouse and keyboard actions. We observed blocking states in this dataset from subsequence distributions and frequency of states. Using a probabilistic framework, we developed four predicting models: an actionfrequency model, a subsequence-detection model, a 1D convolutional neural network model and an hybrid model. The hybrid model outperforms the others with a F1 score of 80.4 % on classification of blocking state on training set. It performs 77.3 % on test set. The applications of this research lead to an upgrade of QED-Tutrix internal finite-state machine for its interactions with the learner. Also, this research opens a second research stage, in which targeted tutorial interventions in QED-Tutrix can be developed. This can be achieved with an algorithm that understands the context of intervention and that is able to help precisely the learner. In order to get better performances from the current models, the history of the previous blocking states needs to be incorporated. Moreover, the mathematical concepts used by the learner can be integrated

Postural stability is altered by the stimulation of pain but not warm receptors in humans

BACKGROUND: It is now recognized that large diameter myelinated afferents provide the primary source of lower limb proprioceptive information for maintaining an upright standing position. Small diameter afferents transmitting noxious stimuli, however, can also influence motor behaviors. Despite the possible influence of pain on motor behaviors, the effects of pain on the postural control system have not been well documented. METHODS: Two cutaneous heat stimulations (experiment 1: non-noxious 40 degrees C; experiment 2: noxious 45 degrees C) were applied bilaterally on the calves of the subject with two thermal grills to stimulate A delta and C warm receptors and nociceptors in order to examine their effects on postural stability. The non-noxious stimulation induced a gentle sensation of warmth and the noxious stimulation induced a perception of heat pain (visual analogue scores of 0 and 46 mm, respectively). For both experiments, ten healthy young adults were tested with and without heat stimulations of the lower limbs while standing upright on a force platform with eyes open, eyes closed and eyes closed with tendon co-vibration of tibialis anterior and triceps surae muscles. The center of pressure displacements were analyzed to examine how both stimulations affected the regulation of quiet standing and if the effects were exacerbated when vision was removed or ankle proprioception perturbed. RESULTS: The stimulation of the warm receptors (40 degrees C) did not induce any postural deterioration. With pain (45 degrees C), subjects showed a significant increase in standard deviation, range and mean velocity of postural oscillations as well as standard deviation of the center of pressure velocity. The effects of heat pain were exacerbated when subjects had both their eyes closed and ankle tendons vibrated (increased standard deviation of the center of pressure velocity and mean velocity of the center of pressure). CONCLUSIONS: A non-noxious stimulation (40 degrees C) of the small diameter afferents is not a sufficiently intense sensory stimulation to alter the control of posture. A painful stimulation (45 degrees C) of the skin thermoreceptors, however, yielded a deterioration of the postural control system. The observed deteriorating effects of the combined stimulation of nociceptors and Ia afferents (when ankle tendons were vibrated) could result from the convergence of these afferents at the spinal level. This could certainly lead to the hypothesis that individuals suffering from lower limb pain present alterations of the postural control mechanisms; especially populations already at risk of falling (for example, frail elderly) or populations suffering from concomitant lower limb pain and sensory deficits (for example, diabetic polyneuropathy)

Rat endopeptidase-24.18 α subunit is secreted into the culture medium as a zymogen when expressed by COS-1 cells

AbstractEndopeptidase-24.18 (EC 3.4.24.18, E-24.18) is an oligomeric Zn-ectoenzyme. The α and β submits have been cloned from both rat and mouse kidneys. The primary structure of these subunits revealed that they both contain the consensus Zn binding site and that they are members of the astacin family. Analysis of the hydropathy plot also suggested that they are anchored by a C-terminal hydrophobic domain. In order to verify the mode of anchoring of the rat E-24.18 α subunit and to test the functionality of the astacin-like domain in the α subunit when expressed alone, COS-1 cells were transfected with a cloned cDNA for rat α subunit. Despite the presence of its putative transmembrane domain, the α subunit was not anchored in the plasma membrane but rather secreted as a dimer into the culture medium. When the enzymatic activity of the secreted recombinant protein was tested in the azocasein degradation assay, the α subunit was found to be inactive. Activity could, however, be revealed after mild trypsin digestion. This activity was abolished by replacing the Glu-157 in the active site by Val. Taken together our results suggest that the α subunit of Endopeptidase-24.18 contains a latent astacin-like Zn metallopeptidase activity which could be secreted as a soluble enzyme by kidney and intestine

Genome-wide gene expression profiling analysis of Leishmania major and Leishmania infantum developmental stages reveals substantial differences between the two species

<p>Abstract</p> <p>Background</p> <p><it>Leishmania </it>parasites cause a diverse spectrum of diseases in humans ranging from spontaneously healing skin lesions (e.g., <it>L. major</it>) to life-threatening visceral diseases (e.g., <it>L. infantum</it>). The high conservation in gene content and genome organization between <it>Leishmania major </it>and <it>Leishmania infantum </it>contrasts their distinct pathophysiologies, suggesting that highly regulated hierarchical and temporal changes in gene expression may be involved.</p> <p>Results</p> <p>We used a multispecies DNA oligonucleotide microarray to compare whole-genome expression patterns of promastigote (sandfly vector) and amastigote (mammalian macrophages) developmental stages between <it>L. major </it>and <it>L. infantum</it>. Seven per cent of the total <it>L. infantum </it>genome and 9.3% of the <it>L. major </it>genome were differentially expressed at the RNA level throughout development. The main variations were found in genes involved in metabolism, cellular organization and biogenesis, transport and genes encoding unknown function. Remarkably, this comparative global interspecies analysis demonstrated that only 10–12% of the differentially expressed genes were common to <it>L. major </it>and <it>L. infantum</it>. Differentially expressed genes are randomly distributed across chromosomes further supporting a posttranscriptional control, which is likely to involve a variety of 3'UTR elements.</p> <p>Conclusion</p> <p>This study highlighted substantial differences in gene expression patterns between <it>L. major </it>and <it>L. infantum</it>. These important species-specific differences in stage-regulated gene expression may contribute to the disease tropism that distinguishes <it>L. major </it>from <it>L. infantum.</it></p

Perturbation of the postural control system induced by muscular fatigue.

In this experiment, we induced muscular fatigue of ankle plantar-flexors to examine how it deteriorates the regulation of bipedal quiet upright standing. Postural stability was assessed in conditions with and without vision over 60 s period to examine not only classical postural variables (time- and frequency-domain analyses), but also structural variables (stabilogram-diffusion analysis). Muscular fatigue was induced with repeated plantar-flexion of both legs. With muscular fatigue, subjects exhibited an increased postural sway (faster center of pressure (CP) velocity, and greater CP mean and median frequency) and a decreased long-term scaling exponent compared with the control conditions. The fatigue conditions, however, did not modify the range of oscillations and the variability of the postural oscillations around the mean position of CP. The effects of muscular fatigue were similar with eyes open and eyes closed. These results suggest that fatigue did induce some changes in the control mode of postural stability, but the detection/action capabilities of the sensorimotor system remained partly efficient when the ankle plantar-flexors were fatigued. Furthermore, the decreased long-term scaling exponent observed with fatigue suggests that the control of upright stance operates in a less stochastic and more antipersistent manner when fatigue is present (i.e. past and future behaviors were more negatively correlated and thus more tightly regulated). Altogether, the present results suggest that, compared with the no-fatigue conditions, fatigue places higher demands on the postural control system by increasing the frequency of actions needed to regulate the upright stance

Gene amplification and point mutations in pyrimidine metabolic genes in 5-fluorouracil resistant Leishmania infantum.

The human protozoan parasites Leishmania are prototrophic for pyrimidines with the ability of both de novo biosynthesis and uptake of pyrimidines.Five independent L. infantum mutants were selected for resistance to the pyrimidine analogue 5-fluorouracil (5-FU) in the hope to better understand the metabolism of pyrimidine in Leishmania. Analysis of the 5-FU mutants by comparative genomic hybridization and whole genome sequencing revealed in selected mutants the amplification of DHFR-TS and a deletion of part of chromosome 10. Point mutations in uracil phosphorybosyl transferase (UPRT), thymidine kinase (TK) and uridine phosphorylase (UP) were also observed in three individual resistant mutants. Transfection experiments confirmed that these point mutations were responsible for 5-FU resistance. Transport studies revealed that one resistant mutant was defective for uracil and 5-FU import.This study provided further insights in pyrimidine metabolism in Leishmania and confirmed that multiple mutations can co-exist and lead to resistance in Leishmania

Resistance levels to 5-FU and MTX in <i>L. infantum</i> 263 WT and 5-FU resistant mutants.

*<p>Rev = revertant strain cultured without drug pressure over 30 passages;</p>**<p>(p<0,005).</p