Sélection in vivo par phage display dans un modèle de sténose valvulaire aortique chez la souris pour la découverte de nouveaux peptides ciblant la valve aortique

La sténose valvulaire aortique (SVA) est la maladie des valves cardiaques la plus répandue dans les pays développés qui touche les personnes âgées. La SVA est un processus actif caractérisé par des dépôts de lipides, de l’inflammation, de la fibrose et une calcification active des feuillets qui progresse vers un épaississement et durcissement de la valve aortique et une diminution de l’aire de la valve aortique. Nous avons émis l’hypothèse que la pathogénèse de la SVA modifie progressivement l’endothélium de la valve aortique, ce qui engendre l’expression de biomarqueurs spécifiques aux tissus et à la maladie. On rapporte dans cet étude, l’utilisation de la technique de sélection in vivo par phage display d’une librairie de peptides aléatoires afin de trouver de nouveaux peptides candidats qui se lieraient à des biomarqueurs spécifiques à la valve aortique malade d’une souris. Des souris ATX (LDLr-/-;Tg(hApoB+/+)) âgées atteintes de la SVA ont été utilisées pour la sélection in vivo d’une librairie de peptides aléatoires de 7 acides aminés contraints ou linéaires. Après 4 tours de criblage, on a caractérisé 14 phages différents qui ont été séparés en 5 motifs consensus pour la librairie linéaire et 11 phages différents qui représentent 5 différents motifs consensus pour la libraire de peptides contraints. La spécificité de 4 phages candidats de la librairie linéaire et de 5 phages de la librairie contrainte a été étudiée par l’immunomarquage des peptides d’intérêt exprimés par les phages sur les coupes de tissus de la valve aortique malade par rapport aux tissus contrôles du foie, du rein, de la rate, du ventricule et du poumon. Parmi eux, 6 phages représentent des peptides candidats intéressants qui ont besoin d’être testés davantage pour évaluer leur spécificité in vivo à la valve. Bien qu’il reste encore de la validation à effectuer, les peptides candidats spécifiques trouvés peuvent représenter des agents moléculaires d’imagerie utiles ou des transporteurs dans la livraison de drogue qui ciblent la valve aortique malade.

L'étude in vivo de l'impact de la pression pulsée sur les capillaires cérébraux de souris

Plusieurs décennies de recherche ont permis de mieux comprendre les effets de l’athérosclérose sur le système cardiovasculaire, d’améliorer la prévention et de développer des traitements efficaces. Les effets de l’athéroslérose sur le cerveau demeurent toutefois mal compris même si le lien entre le fonctionnement cognitif et la santé du système vasculaire est maintenant bien établi. La venue de nouvelles méthodes d’imagerie telle la microscopie laser à 2-photons (TPLM) permet d’étudier l’impact de certaines maladies sur la microvasculature cérébrale en mesurant le flux sanguin dans des vaisseaux uniques situés dans des régions cérébrales millimétriques sous la surface. Les résultats des études in vitro peuvent dorénavant être corrélés à ceux obtenus in vivo. En premier lieu, ce mémoire revoit la théorie ayant permis le développement de la TPLM qui permet de prendre des mesures hémodynamiques in vivo dans des vaisseaux de très petits calibres tels des capillaires cérébraux de souris. Par la suite, son utilisation est décrite chez des souris anesthésiées afin de comparer les mesures d’hémodynamie cérébrale tels la vitesse des globules rouges, le flux de globules rouges, le flux sanguin cérébral, l’hématocrite sanguin et le diamètre des vaisseaux. Finalement, nous avons comparé les données hémodynamiques entre des souris de 3 mois normales (WT ; n=6) et des souris atteintes d’athérosclérose précoce (ATX ; n=6). Les résultats obtenus sur un nombre total de 209 capillaires (103 pour les souris WT et 106 pour les souris ATX) démontrent que les souris ATX possèdent une vitesse des globules rouges (+40%) plus grande, un flux de globule rouge plus grand (+12%) et un flux capillaire plus élevé (+14%) sans démontrer pour aucun de ces paramètres, une différence statistiquement significative. L’hématocrite moyen (35±4% vs 33±2% ; p=0.71) et le diamètre moyen des vaisseaux (4.88±0.22μm vs 4.86±0.20μm ; p=0.23) étaient également comparables. La vitesse des globules rouges a démontré une faible corrélation avec le diamètre des vaisseaux (r=0.39) et avec le flux de globules rouges/seconde (r=0.59). En conclusion, les travaux menés dans le cadre de ce mémoire de maîtrise permettent d'envisager, grâce aux nouvelles méthodes d’imagerie cérébrale telle la TPLM, une meilleure compréhension des mécanismes hémodynamiques sous-jacents à la microcirculation cérébrale. L’effet d’une pression pulsée augmentée, tel que proposée dans l’athérosclérose reste cependant à démontrer avec cette méthode d’imagerie.

Maximal compactness, min- imal Hausdor ness and reversibility of frames and a study on automorphism group of frames

One can do research in pointfree topology in two ways. The rst is the contravariant way where research is done in the category Frm but the ultimate objective is to obtain results in Loc. The other way is the covariant way to carry out research in the category Loc itself directly. According to Johnstone [23], \frame theory is lattice theory applied to topology whereas locale theory is topology itself". The most part of this thesis is written according to the rst view. In this thesis, we make an attempt to study about 1. the frame counterparts of maximal compactness, minimal Hausdor - ness and reversibility, 2. the automorphism groups of a nite frame and its relation with the subgroups of the permutation group on the generator set of the frame

Rätten till min egen identitet? : En etisk studie om barns sociala status, rättigheter och möjlighetertill identitetsskapande i vår samtid

Syftet med studien är att i utvalt material, FN:s deklaration om de mänskliga rättigheterna, FN:s barnkonvention samt Parliament of the World´s Religions dokument om global etik (DTGE), lokalisera en formulerad värdegrund rörande individens möjlighet till identitetsut-veckling, avsedd att tillämpas globalt i vår samtid. Jag har som ambition att försöka räta ut en del frågetecken rörande vilka rättigheter och möjligheter individen har enligt dokumenten till sin egen identitetsformering. Dessutom undersöker jag om materialets värdegrund kan kopp-las till problematiken om hur individens rätt till identitetsformering påverkar dennes formule-rade rätt till religionsfrihet och religioner. Studien är en litteraturstudie och metoden jag använt är en kombination av innehållsanalys och idéanalys som bearbetar material i form av litteratur och dokument rörande identitetsut-veckling. Materialet analyseras med hjälp av teoretiska redskap hämtade från tre författares olika synsätt på identitetsformering samt kringliggande problematik i ämnet. Då min studie även är av komparativ art har jag selekterat analysverktygen liksom primärkäl-lorna, efter tanken att med olika teoretikers perspektiv bemöta och besvara mina breda fråge-ställningar. Resultaten av analysen visar att alla människor inte har getts möjligheten till egen identitetsformering. Vilka av materialets värderingar angående individuell rätt till identitets-formering som kan kopplas till religionsfrihet eller religioner, var betydligt svårare att utröna, då dokumenten är mycket försiktiga i sin formulering rörande olika religioners inverkan på individens identitetsformeringsmöjligheter.

Mio i folksagan och karnevalen : En tolkning och narratologisk studie av Astrid Lindgrens verk Mio, min Mio

The purpose of the study is, based on a narratological perspective, to analyze and interpret the novel written by Astrid Lindgren: Mio, min Mio. It is based on the legacy of the folktale tradition, which is also the basis for carnival concept according to Bachtin. The study is based on a narrative model of Gérard Genette. Mio, min Mio is told as a first person narrator and can be interpreted as Bo tells it to himself. It is a frame story in which the outer story is the reality, while the inner story is the structure of the folktale where Mio embarks on a predetermined mission to fight against evil. Carnival concept involves a timed up-and-down-turn that is sanctioned and controlled, this fits well with this story seen from this interpretation. In the fantasy world everything has an idealized counterpart and Bo is, via Mio, in this world for a limited time. Children in our society are powerless, but are allowed to be mighty in children's literature. The story gets a subversive effect as it shows that adult standards are not absolute. Even if Bo turns back to his foster parents, he goes through this inner battle processing his thoughts and feelings. The love Bo will experience in imagination gives him the power to manage his real situation.

Relationship of upper-limb and thoracic muscle strength to 6-min walk distance in COPD patients

Study objectives: This study was developed to investigate the influence of thoracic and upperlimb muscle function on 6-min walk distance (6MWD) in patients with COPD.Design: A prospective, cross-sectional study.Setting: the pulmonary rehabilitation center of a university hospital.Patients: Thirty-eight patients with mild to very severe COPD were evaluated.Measurements and results: Pulmonary function and baseline dyspnea index (BDI) were assessed, handgrip strength, maximal inspiratory pressure (Pimax), and 6MWD were measured, and the one-repetition maximum (1RM) was determined for each of four exercises (bench press, lat pull down, leg extension, and leg press) performed on gymnasium equipment. Quality of life was assessed using the St. George Respiratory Questionnaire (SGRQ). We found statistically significant positive correlations between 6MWD and body weight (r = 0.32; p < 0.05), BDI (r = 0.50; p < 0.01), FEV, (r = 0.33; p < 0.05), PImax (r = 0.53; p < 0.01), and all values of 1RM. A statistically significant negative correlation was observed between 6MWD and dyspnea at the end of the 6-min walk test (r = -0.29; p < 0.05), as well as between 6MWD and the SGRQ activity domain (r = -0.45; p < 0.01) and impact domain (r = -0.34; p < 0.05) and total score (r = -0.40; p < 0.01). Multiple regression analysis selected body weight, BDI, Pimax, and lat pull down IRM as predictive factors for 6MWD (R-2 = 0.589).Conclusions: the results of this study showed the importance of the skeletal musculature of the thorax and upper limbs in submaximal exercise tolerance and could open new perspectives for training programs designed to improve functional activity in COPD patients.

Effects of gender on stroke rates, critical speed and velocity of a 30-min swim in young swimmers

Our objective was to analyze the effect of gender on the relationship between stroke rates corresponding to critical speed (SRCS) and maximal speed of 30 min (SRS30) in young swimmers. Twenty two males (GM1) (Age = 15.4 ± 2.1 yr., Body mass = 63.7 ± 12.9 kg, Stature = 1.73 ± 0.09 m) and fourteen female (GF) swimmers (Age = 15.1 ± 1.6 yr., Body mass = 58.3 ± 8.8 kg, Stature = 1.65 ± 0.06 m) were studied. A subset of males (GM2) was matched to the GF by their velocity for a 30 min swim (S30). The critical speed (CS) was determined through the slope of the linear regression line between the distances (200 and 400 m) and participant's respective times. CS was significantly higher than S30 in males (GM1 - 1.25 and 1.16 and GM2 - 1.21 and 1.12 m·s-1) and females (GF - 1.15 and 1.11 m·s-1). There was no significant difference between SRCS and SRS30 in males (GM1 - 34.16 and 32.32 and GM2 - 34.67 and 32.46 cycle·s-1, respectively) and females (GF - 34.18 and 33.67 cycle·s-1-1, respectively). There was a significant correlation between CS and S30 (GM1 - r = 0.89, GF - r = 0.94 and GM2 - r = 0.90) and between SRCS and SRS30 (GM1 - r = 0.89, GF - r = 0.80 and GM2 - r = 0.88). Thus, the relationship between SRCS and SRS30 is not influenced by gender, in swimmers with similar and different aerobic capacity levels. ©Journal of Sports Science and Medicine (2007).

Test-retest reliability of a 3-min isokinetic all-out test using two different cadences

Objectives: To investigate the test-retest reliability of mechanical parameters derived from a 3-min isokinetic all-out test, performed at 60 and 100 rpm. Reliability and validity of the peak oxygen uptake derived from 3-min isokinetic all-out test were also tested. Design: 14 healthy male subjects completed an incremental ramp testing and four randomized 3-min isokinetic all-out test (two at 60 rpm and two at 100 rpm). Methods: The absolute and relative reliability of the following parameters were analyzed: peak power, mean power, end power, fatigue index, work performed above end power and peak oxygen uptake. Results: No difference was found between each two sets of data, although there were between-cadence differences for peak power, mean power, end power, and fatigue index. Higher intra-class correlation (ICC) and lower coefficient of variation (CV) were found for end power (ICC = 0.91 and 0.95; CV = 5.6 and 5.7%) and mean power (ICC = 0.97 and 0.98; CV = 2.4 and 3.1%), than for peak power (ICC = 0.81 and 0.84; CV = 8.7 and 10%) and work performed above end power (ICC = 0.79 and 0.84; CV = 7.9 and 10.6%; values reported for 60 rpm and 100 rpm, respectively). High reliability scores were also observed for peak oxygen uptake at both cadences (60 rpm, CV = 3.2%; 100 rpm, CV = 2.3%,) with no difference with the incremental ramp testing peak oxygen uptake. Conclusions: The power profile and peak oxygen uptake of a 3-min isokinetic all-out test are both highly reliable, whether the test is performed at 60 or 100 rpm. Besides, peak oxygen uptake and work performed above end power were not affected by the change in cadence while peak power, mean power, end power, and fatigue index were. © 2013.

Preoperative 6-min walking distance does not predict pulmonary complications in upper abdominal surgery

Background and objective: Field exercise tests have been increasingly used for pulmonary risk assessment. The 6-min walking distance (6MWD) is a field test commonly employed in clinical practice; however, there is limited evidence supporting its use as a risk assessment method in abdominal surgery. The aim was to assess if the 6MWD can predict the development of post-operative pulmonary complications (PPCs) in patients having upper abdominal surgery (UAS). Methods: This prospective cohort study included 137 consecutive subjects undergoing elective UAS. Subjects performed the 6MWD on the day prior to surgery, and their performance were compared with predicted values of 6MWD (p6MWD) using a previously validated formula. PPCs (including pneumonia, tracheobronchitis, atelectasis with clinical repercussions, bronchospasm and acute respiratory failure) were assessed daily by a pulmonologist blinded to the 6MWD results. 6MWD and p6MWD were compared between subjects who developed PPC (PPC group) and those who did not (no PPC group) using Student's t-test. Results: Ten subjects experienced PPC (7.2%) and no significant difference was observed between the 6MWD obtained in the PPC group and no PPC group (466.0 +/- 97.0 m vs 485.3 +/- 107.1 m; P = 0.57, respectively). There was also no significant difference observed between groups for the p6MWD (100.7 +/- 29.1% vs 90.6 -/+ 20.9%; P > 0.05). Conclusions: The results of the present study suggest that the 6-min walking test is not a useful tool to identify subjects with increased risk of developing PPC following UAS.