Études des mécanismes adaptatifs du maintien de l'équilibre orthostatique. Effets d'une fatigue musculaire, d'une douleur expérimentale et d'une perturbation externe.

Le maintien de l'équilibre orthostatique est une activité motrice primordiale parce qu'elle permet de préserver l'autonomie de chaque individu. Les études présentées dans cette thèse traitent comment diverses contraintes influencent les mécanismes de contrôle impliqués lors du maintien de l'équilibre en station debout. Cette thèse a donc pour objectifs de vérifier : (1) Les effets de la fatigue de certains muscles impliqués dans le contrôle du maintien orthostatique. (2) Les effets d'une douleur expérimentale sur les mécanismes de régulation de l'équilibre orthostatique. (3) Les effets d'une perturbation externe pouvant causer une perte d'équilibre.(4) La validité d'un modèle mathématique démontrant l'importance d'une troisième variable nécessaire pour prédire la stabilité en station debout : le temps de développement du moment de force aux chevilles.En conclusion, cette thèse permet d'éclaircir l'implication des mécanismes adaptatifs du système nerveux dans différents contextes.Premièrement, le système nerveux s'adapteraient à la fatigue des triceps suraux en augmentant la fréquence des ajustements posturaux afin d'éviter des déplacements plus excentriques du centre de masse du corps ou en augmentant les propriétés mécaniques des articulations (i.e. la rigidité). Deuxièmement, une stimulation des nocicepteurs altère principalement les processus sensori-moteurs du système de contrôle postural. La détérioration de la stabilité est fonction de la localisation et de l'intensité de la stimulation douloureuse. La perception de la douleur nécessite des ressources attentionnelles qui ne nuisent pas au contrôle du maintien de l'équilibre en station debout. Troisièmement, l'incertitude reliée à l'avènement probable d'une perturbation provoque une altération des processus de contrôle du maintien de l'équilibre dans les situations sans perturbation et avec perturbation. Quatrièmement, le temps de développement du momentde force aux chevilles contraint la capacité d'une personne à retrouver l'équilibre en station debout suite à une déstabilisation vers l'avant. En ajoutant cette variable à un modèle mathématique, celui-ci permet de prédire 73.3 % des chutes et 73.3 % des stabilisations observées expérimentalement

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)

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

Interventions to Promote More Effective Balance-Recovery Reactions in Industrial Settings: New Perspectives on Footwear and Handrails

“Change-in-support” balance-recovery reactions that involve rapid stepping or reaching movements play a critical role in preventing falls. Recent geriatrics studies have led to new interventions to improve ability to execute these reactions effectively. Some of these interventions have the potential to reduce fall risk for younger persons working in industrial settings. In this paper, we review research pertaining to two such interventions: 1) balance-enhancing footwear insoles designed to improve stepping reactions, and 2) proximity-triggered handrail cueing systems designed to improve reach-to-grasp reactions. The insole has a raised ridge around the perimeter that is intended to improve balance control by providing increased stimulation of sensory receptors on the footsole in situations where loss of balance may be imminent. The cueing system uses flashing lights and/or verbal prompts to attract attention to the handrail and ensure that the brain registers its location, thereby facilitating more rapid and accurate grasping of the rail if and when sudden loss of balance occurs. Results to date support the efficacy of both interventions in geriatric populations. There is also some evidence that these interventions may improve balance control in younger persons; however, further research is needed to confirm their efficacy in preventing falls in industrial settings

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

Multiple Mutations in Heterogeneous Miltefosine-Resistant Leishmania major Population as Determined by Whole Genome Sequencing

Leishmania spp. are parasitic protozoa responsible for a spectrum of diseases known as leishmaniasis. There are few drugs available for the treatment of these diseases, and miltefosine is the first oral drug used in treatment of visceral leishmaniasis, a form of the disease that can be lethal if not treated. In this study, we seek to understand the mechanism of action and identify targets of the drug by generating promastigote mutants highly resistant to miltefosine. Two independent mutants were submitted to short read whole genome sequencing. Genome analysis of these mutants has permitted us to identify point mutations in three genes (P-type ATPase, pyridoxal kinase and α-adaptin like protein) that were also present in other independent miltefosine resistant mutants. Some of the new genes identified here could be useful as potential markers for miltefosine resistance in Leishmania. Moreover, our approach has permitted us to highlight that resistance can be highly heterogeneous at the population level with individual clones derived from this population differing both in terms of genotypes but also susceptibility phenotypes. This may have practical applications while studying resistance

Back loading estimation during team handling: Is the use of only motion data sufficient?

Analyzing back loading during team manual handling tasks requires the measurement of external contacts and is thus limited to standardized tasks. This paper evaluates the possibility of estimating L5/S1 joint moments based solely on motion data. Ten subjects constituted five two-person teams and handling tasks were analyzed with four different box configurations. Three prediction methods for estimating L5/S1 joint moments were evaluated by comparing them to a gold standard using force platforms: one used only motion data, another used motion data and the traction/compression force applied to the box and one used motion data and the ground reaction forces of one team member. The three prediction methods were based on a contact model with an optimization-based method. Using only motion data did not allow an accurate estimate due to the traction/compression force applied by each team member, which affected L5/S1 joint moments. Back loading can be estimated using motion data and the measurement of the traction/compression force with relatively small errors, comparable to the uncertainty levels reported in other studies. The traction/compression force can be obtained directly with a force measurement unit built into the object to be moved or indirectly by using force platforms on which one of the two handlers stands during the handling task. The use of the proposed prediction methods allows team manual handling tasks to be analyzed in various realistic contexts, with team members who have different anthropometric measurements and with different box characteristics

Etude des mécanismes adaptatifs du maintien de l'équilibre orthostatique (effets d'une fatigue musculaire, d'une douleur expérimentale et d'une perturbation externe)

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