The use of instructional technology has opened up new avenues in education with broad implications in the foreign or additional language (L2) learning context. One of the research priorities is to explore student perceptions of the use of such modern means in their education which otherwise might not be anticipated. The present study aimed to determine (a) the perceived affordances as well as limitations of the information and communication technology (ICT) pedagogical application in coded corrective feedback (e-feedback) provision on L2 writing, (b) English as a foreign language (EFL) learners’ perspectives on using e-feedback to reduce their local and global mistakes, and (c) the type of self-regulated learning (SRL) behaviours, according to EFL students’ self-reports, electronic feedback and learning logs called forth in cognitive, affective, and metacognitive domains. The participants (n=48) were high-intermediate to advanced EFL learners from four cohorts enrolled on an International English Language Testing System (IELTS) preparation course in a branch of the Institute of Science and Technology in Tehran. Each cohort went through 84 face-to-face tutorial sessions in four months. During this period, they also wrote essays and received e-feedback on 12 IELTS Writing Task 2 prompts with a minimum of drafting work three times for each on an e-learning platform (www.ekbatani.ir) specially designed for this study. The data from all four cohorts were collected over the course of 11 months, using semi-structured interviews, online structured and unstructured learning logs, and an open-ended questionnaire to provide an in-depth picture of student perceptions of this technology mediation. Through a purely qualitative research design, the log, interview, and open-ended questionnaire data were analysed, categorised and coded. The findings represented students’ perceptions of the benefits of the e-feedback and learning logs as (i) offering a motivating and empowering means of providing EFL writing support, (ii) enhancing the thinking and problem-solving processes, (iii) a flexible and fast scaffolding approach for L2 writing improvement, and (iv) encouraging student writers’ active knowledge construction by helping them notice mistakes, focus on writing specifics, overcome the fear of writing, and grow confidence in L2 learning. The self-reported data indicated perceived limitations including (i) the time-consuming nature of the e-feedback processes, (ii) the occasional need for face-to-face discussions, peer feedback addition, providing supplements to e-feedback such as on-demand e-tutorials, and (iii) increased workload for the teacher in proportion to the number of students. Specific writing improvement was perceived to be locally in the use of punctuation signs and grammar, in spelling skills and the scope of vocabulary; and globally in organising ideas, finding ideas in the form of blueprints, and developing ideas into full-length essays. The student perceptions demonstrated that the learner-centred e-feedback environment created different affordances for students’ cognitive, affective, and metacognitive behaviours: (i) cognitively, it assisted the use and development of various learning strategies, enhanced student EFL writing experience, and increased awareness of error patterns in their essays; (ii) affectively, it supported students’ motivational processes, ability to appraise their progress, restore, and sustain positivity, and greater perceived self-efficacy beliefs in their own L2 writing skills; finally, (iii) metacognitive affordances included the ability to rethink and amend their plans as well as seek out support, ability to reflect on the writing processes holistically, ability to self-monitor to remain on course, and ability to devise and implement a plan of action mostly by finding a strategy to deal with mistakes and by taking greater caution in writing their future drafts. Despite arising from a particular contextual framework with the experience of particular cohorts of students, the findings can hopefully be of value to researchers and practitioners in the fields of online language pedagogy, second language acquisition (SLA), EFL writing, and computer-assisted language learning (CALL) with communication uses. The findings can assist language courseware designers, e-feedback platform developers, and L2 writing course administrators to support and enhance their practices and decisions, especially in providing and implementing ICT and SRL initiatives in EFL writing.

<p>Angiogenesis is the formation of new blood vessels from the pre-existing blood vessels. Blood vessels are composed of endothelial cells and supporting musculature. Angiogenesis is regulated by numerous soluble ligands and by cell-matrix interactions. We have studied the molecular mechanisms in fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor-A (VEGF-A)-induced angiogenesis using immortalized endothelial cell lines in different angiogenesis assays.</p><p>The role of the signaling protein H-Ras in FGF-2-induced <i>in vitro</i> angiogenesis was studied by expressing mutated versions of H-Ras in immortalized mouse brain endothelial cells using a tetracycline-regulated expression system. <i>In vitro</i> angiogenesis was analyzed as the ability of cells to invade a fibrin matrix and form branching structures in response to a combination of FGF-2 and tumor necrosis factor-α (TNF-α). Inhibition of H-Ras through the expression of dominant negative (S17N) H-Ras or pharmacological inactivation of H-Ras with a farnesyl transferase inhibitor, did not inhibit growth factor-induced invasion. In contrast, expression of constitutively active (G12V) H-Ras caused cells to adopt a transformed phenotype which inhibited invasive growth and cells formed solid tumors when injected in nude mice. These studies suggest that H-Ras activity is not required for differentiation but its activity must be tightly regulated as aberrant activity impairs endothelial cell differentiation.</p><p>In order to screen for both known and novel genes that regulate angiogenesis we used large scale microarray analysis. In VEGF-A-stimulated telomerase immortalized human microvascular endothelial cells undergoing invasive growth in fibrin gels, or forming cord-like structures on collagen, we identified several genes that were differentially expressed. Some of these are known to be important for endothelial cell functions and angiogenesis while others have no previous connection with endothelial cell function or were transcripts with no assigned function. Further analysis of these proteins will aid in elucidating the molecular mechanisms underlying endothelial cell differentiation. </p>

<p>Traumatic brain injury (TBI) is a leading cause of death and disability TBI survivors often suffer from severe disturbances of cognition, memory and emotions. Improving the treatment is of great importance, but as of yet no specific neuroprotective treatment has been found. After TBI there are changes in ion homeostasis and protein regulation, causing generation of reactive oxygen species (ROS). Overproduction of ROS can lead to damage cellmembranes, proteins and DNA and secondary cell death. In the present thesis experimental TBI in rats were used to study the effects of the ROS scavengers α-phenyl-N-tert-butyl-nitrone (PBN) and 2-sulfophenyl-N-tert-butyl-nitrone (S-PBN) on morphology, function, intracellular signalling and apoptosis. </p><p>Posttreatment with PBN and S-PBN resulted in attenuation of tissue loss after TBI and S-PBN improved cognitive function evaluated in the Morris water maze (MWM). Pretreatment with PBN protected hippocampal morphology, which correlated to better MWM-performance after TBI.</p><p>To detect ROS-generation in vivo, a method using 4-hydroxybenzoic acid (4-HBA) microdialysis in the injured cortex was refined. 4-HBA reacts with ROS to form 3,4-DHBA, which can be quantified using HPLC, revealing that ROS-formation was increased for 90 minutes after TBI. It was possible to attenuate the formation significantly with PBN and S-PBN treatment. </p><p>The activation of extracellular signal-regulated kinase (ERK) is generally considered beneficial for cell survival. However, persistent ERK activation was found in the injured cortex after TBI, coinciding with apoptosis-like cell death 24 h after injury. Pretreatment with the MEK-inhibitor U0126 and S-PBN significantly decreased ERK activation and reduced apoptosis-like cell death. Posttreatment with U0126 or S-PBN showed robust protection of cortical tissue.</p><p>To conclude: ROS-mediated mechanisms play an important role in secondary cell death following TBI. The observed effects of ROS in intracellular signalling may be important for defining new targets for neuroprotective intervention.</p>

Pour favoriser la réflexion sur la pratique professionnelle, nous avons proposé à des futurs enseignants en stage d'utiliser un journal de bord au départ de consignes semi-structurées. Notre intention est d'identifier les traces de réflexion dans les journaux de bord et de différencier son utilisation par trois caractéristiques individuelles: l'anxiété, la perception d'efficacité personnelle et le rapport à l'écrit du futur enseignant. Notre thèse développe dans la partie théorique le premier chapitre sur le journal de bord parmi les dispositifs de formation favorisant la réflexion sur la pratique, le deuxième chapitre sur la notion de réflexion sur la pratique et plus particulièrement sur le modèle métacognitif de réflexion de McAlpine et ses collègues (1999, 2001) et le troisième chapitre sur les trois variables individuelles mesurées. La partie empirique développe la méthodologie utilisée, à savoir que cette recherche exploiratoire, visant l'induction d'hypothèses, décrit les trois étapes de la démarche d'analyse de contenus des journaux de bord(recueil, exploitation et transformation des données qualitatives avec traitement quantitatif)en lien avec les questions de recherche et explique la construction et la validation des trois quesitonnaires mesurant les caractéristiques individuelles. Cette partie s'achève par le chapitre des résultats et des discussions. Parmi les 96 futurs enseignants, 45 d'entre eux ont réalisé leur journal de bord. Différents contenus ont été identifiés dont de la réflexion sur la pratique. A partir du modèle de McAlpine et al., nous avons essentiellement trouvé des passages de description de l'action et des passages d'évaluation de l'action. Une typologie des journaux de bord et de la réflexion a été obtenue par une analyse en clusters. Au moyen de corrélations de Kendall, nous avons pu observé une relation positive entre le rapport à l'écrit de l'enseignant et l'appropriation du journal de bord et une relation négative entre la perception d'efficacité personnelle et le composant d'évaluation de l'action. Aucune relation n'a été obtenue avec la variable d'anxiété. POur conclure, de nouvelles hypothèses de recherche ont été formulées ainsi que les apports et les limites de cette recherche.

Three novel mutations (G159D, L29Q and E59D/D75Y) in cardiac troponin C (CTnC) associate their clinical outcomes with a given cardiomyopathy. Current paradigms propose that sarcomeric mutations associated with dilated cardiomyopathy (DCM) decrease the myofilament calcium sensitivity while those associated with hypertrophic (HCM) cardiomyopathy increase it. Therefore, we incorporated the mutant CTnCs into skinned cardiac muscle in order to determine if their effects on the calcium regulation of tension and ATPase activity coincide with the current paradigms and phenotypic outcomes. This required the development of new calculator programs to solve complex ionic equilibria to more accurately buffer and expand the free calcium range of our test solutions. In accordance with the DCM paradigms, our result show that G159D and E59D/D75Y CTnC decrease the myofilament calcium sensitivity and force generating capabilities which would likely increase the rate of muscle relaxation and weaken the contractile force of the myocardium. Alternatively, the lack of myofilament change from L29Q CTnC (associated with HCM) may explain why the only proband is seemingly unaffected. Notably, the changes in the calcium sensitivity of tension (in fibers) do not necessarily occur in the isolated CTnC and vice versa. These counter-intuitive findings are justified through a transition in calcium affinity occurring at the level of cardiac troponin (CTn) and higher, implying that the true effects of these mutations become apparent as the hierarchal level of the myofilament increases. Despite these limitations, the regulated thin filament (RTF) retains its role as the calcium regulatory unit and best indicates a mutation's ability to sensitize (+) or desensitize (-) the muscle to calcium. Since multiple forms of cardiomyopathies exist, the identification of new drugs that sensitize (+) or desensitize (-) the calcium sensitivity could potentially reverse (+ or -) these aberrant changes in myofilament sensitivity. Therefore, we have developed an RTF mediated High Throughput Screening assay to identify compounds in libraries of molecules that can specifically modulate the calcium sensitivity of cardiac contraction. The knowledge gained from these studies will help us and others to uncover new pharmacological agents for the investigation and treatments of cardiomyopathies, hypertension and other forms of cardiovascular diseases.

Pour favoriser la réflexion sur la pratique professionnelle, nous avons proposé à des futurs enseignants en stage d'utiliser un journal de bord au départ de consignes semi-structurées. Notre intention est d'identifier les traces de réflexion dans les journaux de bord et de différencier son utilisation par trois caractéristiques individuelles: l'anxiété, la perception d'efficacité personnelle et le rapport à l'écrit du futur enseignant. Notre thèse développe dans la partie théorique le premier chapitre sur le journal de bord parmi les dispositifs de formation favorisant la réflexion sur la pratique, le deuxième chapitre sur la notion de réflexion sur la pratique et plus particulièrement sur le modèle métacognitif de réflexion de McAlpine et ses collègues (1999, 2001) et le troisième chapitre sur les trois variables individuelles mesurées. La partie empirique développe la méthodologie utilisée, à savoir que cette recherche exploiratoire, visant l'induction d'hypothèses, décrit les trois étapes de la démarche d'analyse de contenus des journaux de bord(recueil, exploitation et transformation des données qualitatives avec traitement quantitatif)en lien avec les questions de recherche et explique la construction et la validation des trois quesitonnaires mesurant les caractéristiques individuelles. Cette partie s'achève par le chapitre des résultats et des discussions. Parmi les 96 futurs enseignants, 45 d'entre eux ont réalisé leur journal de bord. Différents contenus ont été identifiés dont de la réflexion sur la pratique. A partir du modèle de McAlpine et al., nous avons essentiellement trouvé des passages de description de l'action et des passages d'évaluation de l'action. Une typologie des journaux de bord et de la réflexion a été obtenue par une analyse en clusters. Au moyen de corrélations de Kendall, nous avons pu observé une relation positive entre le rapport à l'écrit de l'enseignant et l'appropriation du journal de bord et une relation négative entre la perception d'efficacité personnelle et le composant d'évaluation de l'action. Aucune relation n'a été obtenue avec la variable d'anxiété. POur conclure, de nouvelles hypothèses de recherche ont été formulées ainsi que les apports et les limites de cette recherche.

Angiogenesis is the formation of new blood vessels from the pre-existing blood vessels. Blood vessels are composed of endothelial cells and supporting musculature. Angiogenesis is regulated by numerous soluble ligands and by cell-matrix interactions. We have studied the molecular mechanisms in fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor-A (VEGF-A)-induced angiogenesis using immortalized endothelial cell lines in different angiogenesis assays. The role of the signaling protein H-Ras in FGF-2-induced in vitro angiogenesis was studied by expressing mutated versions of H-Ras in immortalized mouse brain endothelial cells using a tetracycline-regulated expression system. In vitro angiogenesis was analyzed as the ability of cells to invade a fibrin matrix and form branching structures in response to a combination of FGF-2 and tumor necrosis factor-α (TNF-α). Inhibition of H-Ras through the expression of dominant negative (S17N) H-Ras or pharmacological inactivation of H-Ras with a farnesyl transferase inhibitor, did not inhibit growth factor-induced invasion. In contrast, expression of constitutively active (G12V) H-Ras caused cells to adopt a transformed phenotype which inhibited invasive growth and cells formed solid tumors when injected in nude mice. These studies suggest that H-Ras activity is not required for differentiation but its activity must be tightly regulated as aberrant activity impairs endothelial cell differentiation. In order to screen for both known and novel genes that regulate angiogenesis we used large scale microarray analysis. In VEGF-A-stimulated telomerase immortalized human microvascular endothelial cells undergoing invasive growth in fibrin gels, or forming cord-like structures on collagen, we identified several genes that were differentially expressed. Some of these are known to be important for endothelial cell functions and angiogenesis while others have no previous connection with endothelial cell function or were transcripts with no assigned function. Further analysis of these proteins will aid in elucidating the molecular mechanisms underlying endothelial cell differentiation.

Traumatic brain injury (TBI) is a leading cause of death and disability TBI survivors often suffer from severe disturbances of cognition, memory and emotions. Improving the treatment is of great importance, but as of yet no specific neuroprotective treatment has been found. After TBI there are changes in ion homeostasis and protein regulation, causing generation of reactive oxygen species (ROS). Overproduction of ROS can lead to damage cellmembranes, proteins and DNA and secondary cell death. In the present thesis experimental TBI in rats were used to study the effects of the ROS scavengers α-phenyl-N-tert-butyl-nitrone (PBN) and 2-sulfophenyl-N-tert-butyl-nitrone (S-PBN) on morphology, function, intracellular signalling and apoptosis. Posttreatment with PBN and S-PBN resulted in attenuation of tissue loss after TBI and S-PBN improved cognitive function evaluated in the Morris water maze (MWM). Pretreatment with PBN protected hippocampal morphology, which correlated to better MWM-performance after TBI. To detect ROS-generation in vivo, a method using 4-hydroxybenzoic acid (4-HBA) microdialysis in the injured cortex was refined. 4-HBA reacts with ROS to form 3,4-DHBA, which can be quantified using HPLC, revealing that ROS-formation was increased for 90 minutes after TBI. It was possible to attenuate the formation significantly with PBN and S-PBN treatment. The activation of extracellular signal-regulated kinase (ERK) is generally considered beneficial for cell survival. However, persistent ERK activation was found in the injured cortex after TBI, coinciding with apoptosis-like cell death 24 h after injury. Pretreatment with the MEK-inhibitor U0126 and S-PBN significantly decreased ERK activation and reduced apoptosis-like cell death. Posttreatment with U0126 or S-PBN showed robust protection of cortical tissue. To conclude: ROS-mediated mechanisms play an important role in secondary cell death following TBI. The observed effects of ROS in intracellular signalling may be important for defining new targets for neuroprotective intervention.

H HARP (heparin-affin regulatory peptide), γνωστή και ως πλειοτροπίνη (PTN), είναι ένας 18 kDa αυξητικός παράγοντας, ο οποίος έχει υψηλή συγγένεια για την ηπαρίνη. Η HARP έχει πολλαπλές βιολογικές δράσεις, όπως συμμετέχει στη ρύθμιση του κυτταρικού πολλαπλασιασμού, στη μετανάστευση και τη διαφοροποίηση. Επιπλέον η έκφραση της σχετίζεται με την φυσιολογική και καρκινική αγγειογένεση in vitro και in vivo. Στην παρούσα εργασία μελετήθηκε η έκφραση της HARP και των υποδοχέων της, ALK και RPTPβ/ζ, στις διάφορες ημέρες ανάπτυξης της CAM εμβρύου όρνιθας. Επίσης, μελετήθηκε η μείωση της έκφρασης της ενδογενούς HARP, με πλασμίδιο που φέρει την αντινοηματική αλληλουχία (AS-HARP), στην αγγειογένεση in vivo, στη φωσφορυλίωση των Εrk1,2 και στη λεμφαγγειογένεση της CAM εμβρύου όρνιθας. Ανάλυση κατά Western και RT-PCR στις διάφορες ημέρες ανάπτυξης του εμβρύου έδειξε ότι η έκφραση της HARP συμβαδίζει με τη δημιουργία νέων αγγείων στη CAM, ενώ η έκφραση των υποδοχέων της HARP στην CAM φαίνεται να είναι αυξημένη στα πρώτα στάδια ανάπτυξης του ιστού. Επίσης, η μείωση της έκφρασης της HARP μετά τη χορήγηση του πλασμιδίου AS-HARP, μείωσε τα επίπεδα της πρωτεΐνης, το μήκος των αγγείων και τη φωσφορυλίωση των Erk1/2 στο in vivo μοντέλο της CAM εμβρύου όρνιθας. Αντίθετα, η μείωση της έκφρασης της HARP μετά τη χορήγηση του πλασμιδίου AS-HARP, δεν επηρέασε τη λεμφαγγειογένεση της CAM εμβρύου όρνιθας. Σαν τελικό συμπέρασμα προκύπτει ότι η έκφραση της ενδογενούς HARP στην CAM εμβρύου όρνιθας είναι σημαντική για τη φυσιολογική αγγειογένεση in vivo. / Heparin-affin regulatory peptide (HARP), also known as pleiotrophin or heparin-binding growth-associated molecule, is an 18 kDa growth factor that has a high affinity for heparin. HARP is involved in the control of cellular proliferation, migration and differentiation. Moreover, there is a strong correlation between HARP expression and tumor growth and angiogenesis. In the present work, we studied the expression of HARP and its receptors, ALK and RPTPβ/ζ, during development of the chicken embryo chorioallantoic membrane (CAM), in relation to angiogenesis. By western blot analysis and RT-PCR, it was shown that HARP, ALK and RPTPβ/ζ expression increased at days of on-going angiogenesis and decreased at later time points. Transfection of CAMs with an anti-sense HARP gene construct led to a significant decrease in HARP amounts compared to vector control transfected CAMs, a significant decrease in the length of CAM blood vessels, and a decrease in the phosphorylation of Erk1/2. Contrary, transfection of CAMs with the anti-sense HARP gene construct had no influence in lymphangiogenesis of the chicken embryo chorioallantoic membrane (CAM). These data suggest that endogenous HARP is involved in angiogenesis in vivo.

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