Rationale and design of a randomized, double-blind, parallel-group study of terutroban 30 mg/day versus aspirin 100 mg/day in stroke patients: the prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) study.

BACKGROUND: Ischemic stroke is the leading cause of mortality worldwide and a major contributor to neurological disability and dementia. Terutroban is a specific TP receptor antagonist with antithrombotic, antivasoconstrictive, and antiatherosclerotic properties, which may be of interest for the secondary prevention of ischemic stroke. This article describes the rationale and design of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic Attack (PERFORM) Study, which aims to demonstrate the superiority of the efficacy of terutroban versus aspirin in secondary prevention of cerebrovascular and cardiovascular events. METHODS AND RESULTS: The PERFORM Study is a multicenter, randomized, double-blind, parallel-group study being carried out in 802 centers in 46 countries. The study population includes patients aged > or =55 years, having suffered an ischemic stroke (< or =3 months) or a transient ischemic attack (< or =8 days). Participants are randomly allocated to terutroban (30 mg/day) or aspirin (100 mg/day). The primary efficacy endpoint is a composite of ischemic stroke (fatal or nonfatal), myocardial infarction (fatal or nonfatal), or other vascular death (excluding hemorrhagic death of any origin). Safety is being evaluated by assessing hemorrhagic events. Follow-up is expected to last for 2-4 years. Assuming a relative risk reduction of 13%, the expected number of primary events is 2,340. To obtain statistical power of 90%, this requires inclusion of at least 18,000 patients in this event-driven trial. The first patient was randomized in February 2006. CONCLUSIONS: The PERFORM Study will explore the benefits and safety of terutroban in secondary cardiovascular prevention after a cerebral ischemic event.

Design, synthesis, and biological and crystallographic evaluation of novel inhibitors of Plasmodium falciparum enoyl-ACP-reductase (PfFabI).

Malaria, a disease of worldwide significance, is responsible for over one million deaths annually. The liver-stage of Plasmodium's life cycle is the first, obligatory, but clinically silent step in malaria infection. The P. falciparum type II fatty acid biosynthesis pathway (PfFAS-II) has been found to be essential for complete liver-stage development and has been regarded as a potential antimalarial target for the development of drugs for malaria prophylaxis and liver-stage eradication. In this paper, new coumarin-based triclosan analogues are reported and their biological profile is explored in terms of inhibitory potency against enzymes of the PfFAS-II pathway. Among the tested compounds, 7 and 8 showed the highest inhibitory potency against Pf enoyl-ACP-reductase (PfFabI), followed by 15 and 3. Finally, we determined the crystal structures of compounds 7 and 11 in complex with PfFabI to identify their mode of binding and to confirm outcomes of docking simulations.

Design of new tools to improve the efficacy of DNA-damaging drugs used in cancer therapy

Résumé Les tumeurs sont diverses et hétérogènes, mais toutes partagent la capacité de proliférer sans contrôle. Une prolifération dérégulée de cellules couplée à une insensibilité à une réponse apoptotique constitue une condition minimale pour que l'évolution d'une tumeur se produise. Un des traitements les plus utilisés pour traité le cancer à l'heure actuelle sont les chimiothérapies, qui sont fréquemment des composés chimiques qui induisent des dommages dans l'ADN. Les agents anticancéreux sont efficaces seulement quand les cellules tumorales sont plus aisément tuées que le tissu normal environnant. L'efficacité de ces agents est en partie déterminée par leur capacité à induire l'apoptose. Nous avons récemment démontré que la protéine RasGAP est un substrat non conventionnel des caspases parce elle peut induire à la fois des signaux anti et pro-apoptotiques, selon l'ampleur de son clivage par les caspases. A un faible niveau d'activité des caspases, RasGAP est clivé, générant deux fragments (le fragment N et le fragment C). Le fragment N semble être un inhibiteur général de l'apoptose en aval de l'activation des caspases. À des niveaux plus élevés d'activité des caspases, la capacité du fragment N de contrecarrer l'apoptose est supprimée quand il est clivé à nouveau par les caspases. Ce dernier clivage produit deux nouveaux fragments, N 1 et N2, qui contrairement au fragment N sensibilisent efficacement des cellules cancéreuses envers des agents chimiothérapeutiques. Dans cette étude nous avons prouvé qu'un peptide, appelé par la suite TAT-RasGAP317-326, qui est dérivé du fragment N2 de RasGAP et est rendu perméable aux cellules, sensibilise spécifiquement des cellules cancéreuses à trois génotoxines différentes utilisées couramment dans des traitements anticancéreux, et cela dans des modèles in vitro et in vivo. Il est important de noté que ce peptide semble ne pas avoir d'effet sur des cellules non cancéreuses. Nous avons également commencé à caractériser les mécanismes moléculaires expliquant les fonctions de sensibilisation de TAT-RasGAP317-326. Nous avons démontré que le facteur de transcription p53 et une protéine sous son activité transcriptionelle, nommée Puma, sont indispensables pour l'activité de TAT-RasGAP317-326. Nous avons également prouvé que TAT-RasGAP317-326 exige la présence d'une protéine appelée G3BP1, une protéine se liant a RasGAP, pour potentialisé les effets d'agents anticancéreux. Les données obtenues dans cette étude montrent qu'il pourrait être possible d'augmenter l'efficacité des chimiothérapies à l'aide d'un composé capable d'augmenter la sensibilité des tumeurs aux génotoxines et ainsi pourrait permettre de traiter de manière plus efficace des patients sous traitement chimiothérapeutiques. Summary Tumors are diverse and heterogeneous, but all share the ability to proliferate without control. Deregulated cell proliferation coupled with suppressed apoptotic sensitivity constitutes a minimal requirement upon which tumor evolution occurs. One of the most commonly used treatments is chemotherapy, which frequently uses chemical compounds that induce DNA damages. Anticancer agents are effective only when tumors cells are more readily killed than the surrounding normal tissue. The efficacy of these agents is partly determined by their ability to induce apoptosis. We have recently demonstrated that the protein RasGAP is an unconventional caspase substrate because it can induce both anti- and pro-apoptotic signals, depending on the extent of its cleavage by caspases. At low levels of caspase activity, RasGAP is cleaved, generating an N-terminal fragment (fragment N) and a C-terminal fragment (fragment C). Fragment N appears to be a general Mocker of apoptosis downstream of caspase activation. At higher levels of caspase activity, the ability of fragment N to counteract apoptosis is suppressed when it is further cleaved. This latter cleavage event generates two fragments, N1 and N2, which in contrast to fragment N potently sensitizes cancer cells toward DNA-damaging agents induced apoptosis. In the present study we show that a cell permeable peptide derived from the N2 fragment of RasGAP, thereafter called TAT-RasGAP317-326, specifically sensitizes cancer cells to three different genotoxins commonly used in chemotherapy in vitro and in vivo models. Importantly this peptide seems not to have any effect on non cancer cells. We have also started to characterize the molecular mechanisms underlying the sensitizing functions of TAT-RasGAP317-326. We have demonstrated that the p53 transcription factor and a protein under its transcriptional activity, called Puma, are required for the activity of TATRasGAP317-326. We have also showed that TAT-RasGAP317-326 requires the presence of a protein called G3BP1, which have been shown to interact with RasGAP, to increase the effect of the DNA-damaging drug cisplatin. The data obtained in this study showed that it is possible to increase the efficacy of current used chemotherapies with a compound able to increase the efficacy of genotoxins which could be beneficial for patients subjected to chemotherapy.

Characterizing the impact of minor cannula design modification.

OBJECTIVE: Bench evaluation of the hydrodynamic behavior of venous cannulas is a valuable technique for the analysis of their performance during cardiopulmonary bypass (CPB). The aim of this study was to investigate the effect of the internal diameter of the extracorporeal connecting tube of venous cannulas on flow rate (Q), pressure drop (delta P), and cannula resistance (delta P/Q²) values, using a computer assisted test bench.¦METHODS: An in vitro circuit was set up with silicone tubing between the test cannula encased in a movable reservoir, and a static reservoir. The delta P, defined as the difference between the drainage pressure and the preload pressure, was measured using high-fidelity Millar pressure transducers. Q was measured using an ultrasonic flowmeter. Data display and data recording were controlled using virtual instruments in a stepwise fashion.¦RESULTS: The 27 F smartcanula® with a 9 mm connecting tube diameter showed 17% less resistance compared to that with an 8 mm connecting tube diameter. Q values were 7.22±0.1 and 7.81±0.04 L/min for cannulas with 8 mm and 9 mm connecting tube diameters, respectively. The delta P/Q² ratio values were 72% lower for the Medtronic cannula with a 9 mm connecting tube diameter compared to that with an 8 mm connecting tube diameter. Q values for the Medtronic cannula were 3.94±0.23 and 6.58±0.04 L/min with 8 mm and 9 mm connecting tube diameters, respectively. The 27 F smartcanula® showed 13% more flow rate compared to the 28 F Medtronic cannula using the unpaired Student t-test (p<0.0001).¦CONCLUSIONS: Our results demonstrated that Q was increased but delta P and delta P/Q² values were significantly decreased when the connecting tube diameter was increased for venous cannulas. The connecting tube diameter significantly affected the resistance to liquid flow through the cannula. Smartcanulas® outperform Medtronic cannulas.

Evaluation of a piezoelectric system as an alternative to electroencephalogram/ electromyogram recordings in mouse sleep studies.

STUDY OBJECTIVES: Traditionally, sleep studies in mammals are performed using electroencephalogram/electromyogram (EEG/EMG) recordings to determine sleep-wake state. In laboratory animals, this requires surgery and recovery time and causes discomfort to the animal. In this study, we evaluated the performance of an alternative, noninvasive approach utilizing piezoelectric films to determine sleep and wakefulness in mice by simultaneous EEG/EMG recordings. The piezoelectric films detect the animal's movements with high sensitivity and the regularity of the piezo output signal, related to the regular breathing movements characteristic of sleep, serves to automatically determine sleep. Although the system is commercially available (Signal Solutions LLC, Lexington, KY), this is the first statistical validation of various aspects of sleep. DESIGN: EEG/EMG and piezo signals were recorded simultaneously during 48 h. SETTING: Mouse sleep laboratory. PARTICIPANTS: Nine male and nine female CFW outbred mice. INTERVENTIONS: EEG/EMG surgery. MEASUREMENTS AND RESULTS: The results showed a high correspondence between EEG/EMG-determined and piezo-determined total sleep time and the distribution of sleep over a 48-h baseline recording with 18 mice. Moreover, the piezo system was capable of assessing sleep quality (i.e., sleep consolidation) and interesting observations at transitions to and from rapid eye movement sleep were made that could be exploited in the future to also distinguish the two sleep states. CONCLUSIONS: The piezo system proved to be a reliable alternative to electroencephalogram/electromyogram recording in the mouse and will be useful for first-pass, large-scale sleep screens for genetic or pharmacological studies. CITATION: Mang GM, Nicod J, Emmenegger Y, Donohue KD, O'Hara BF, Franken P. Evaluation of a piezoelectric system as an alternative to electroencephalogram/electromyogram recordings in mouse sleep studies.

Le prime traduzioni in lingua italiana (1727) ed inglese (1729) di: "Histoires ou contes du temps passé. Avec des moralitez" di Charles Perrault : analisi comparata

Ce travail de recherche a visé deux aspects: celui d'identification et d'analyse des textes et celui de parution des deux premières traductions en langue anglaise et italienne des contes. La recherche s'est développée essentiellement tenant compte de trois notions importantes: dialogue, intertextualité et intercultureLa première étape a donc été de repérer la première traduction en langue italienne et anglaise des contes pour une évaluation du texte qui puisse ainsi permettre de commencer le parcours d'analyse comparée. En ce qui concerne celle anglaise il y avait déjà une date certaine, 1729, et le nom du traducteur: Robert Samber; La version anglaise, ayant paru en 1960 dans une édition partielle sous la direction de Jacques Barchilon et Henry Pettit, était plus facile à repérer; en outre la British Library avait dans son catalogue celle originelle et complète de 1729. Repérer la version italienne a pris plus de temps et a été complexe car on ne connaissait que certaines dates, 1754 et 1752, et aucune autre indication. La première des deux s'avérait inexacte, tandis que la deuxième était celle d'une réédition mais ce n'était pas la date de la première traduction italienne. Traduction que l'on estimait ne plus exister, ou bien perdue. Toutefois, au cours des recherches préliminaires j'ai finalement trouvé une édition en italien des contes de 1727: c'est la plus ancienne connue et, peut-être, c'est bien la première traduction italienne et, de toute façon, à considérer comme la première dans une langue européenne. Les chapitres initiaux se développent autour de l'aspect qui concerne le complexe dialogue interculturel qui a eu lieu et qui a mené, à travers une compliquée mosaïque d'intrigues, au changement de perspective d'un genre dans les différentes cultures: de cunto à conte de fées d'un côté et de conte de fée à fiaba et à fairy taie de l'autre. Les chapitres successifs sont consacrés à la présentation du texte des deux traductions et à l'analyse de celui-ci selon la méthode de la comparaison différentielle. La partie qui concerne plus précisément l'analyse du texte des deux traductions vise à mettre en exergue tous les points de divergence de celui français de l'édition Barbin de 1697, qui est repris ici pour les deux traductions comme le texte fondamental de départ, et a représenté d'un côté l'élément pour une évaluation de l'oeuvre du traducteur et de l'autre a fourni les éléments pour comprendre quel a été l'accueil du texte lui-même dans le nouveau contexte culturel cible. Les points de vue littéraire et linguistique ont été privilégiés dans la recherche, par rapport à celui folkloriste et anthropologique.Avec cette étude on a démontré que, dans les contextes linguistiques et culturels anglais et italien visés, il y a une présence des contes de Perrault. Que cette présence se réalise par l'intermédiaire du travail de traduction qui en a modifié et, parfois, changé la perspective et le plan énonciatif du message selon la nécessité dans laquelle se trouvait le traducteur. Et enfin que chacune des deux traductions peut être considérée comme une ré-énonciation sui generts.Etant donné que les textes des deux traductions ne sont pas faciles à repérer, celui italien de 1727 est à considérer comme une véritable découverte éditoriale, leur parution intégrale constitue non seulement un complément indispensable à la recherche mais aussi une contribution pour leur connaissance et leur étude et approfondissement supplémentaires.

Trials using a crossover design and ambulatory blood pressure recordings to determine the efficacy of antihypertensive agents in individual patients.

The antihypertensive effects of the beta-blocking agent betaxolol and the calcium entry blocker verapamil were compared in a crossover single-blind trial. Seventeen patients with uncomplicated essential hypertension took either betaxolol or a slow-release formulation of verapamil for two consecutive 6-week periods. The sequence of treatment phases was randomly allocated and a 2-week washout period preceded each treatment. The antihypertensive effect of the test drugs was assessed both at the physician's office and during everyday activities using a portable blood pressure recorder. The crossover design of the trial made it possible to evaluate the antihypertensive efficacy of betaxolol and verapamil both in the group as a whole and in the individual patient. The individual patient response to one of these agents was not a reliable indicator of the same patient's response to the alternative agent. Betaxolol brought both office and ambulatory recorded blood pressures under control in a larger fraction of patients than verapamil, although the magnitude of the blood pressure fall in the responders was equal for each drug. These observations stress the need for an individualized approach to the evaluation of antihypertensive therapy. The present results also demonstrate that optimal antihypertensive therapy is still a matter of trial and error. The precise methodology that ought to characterize crossover trials may make it possible to improve the therapeutic approach to hypertensive patients.

Design and methodology of the Swiss Transplant Cohort Study (STCS): a comprehensive prospective nationwide long-term follow-up cohort.

In Switzerland, organ procurement is well organized at the national-level but transplant outcomes have not been systematically monitored so far. Therefore, a novel project, the Swiss Transplant Cohort Study (STCS), was established. The STCS is a prospective multicentre study, designed as a dynamic cohort, which enrolls all solid organ recipients at the national level. The features of the STCS are a flexible patient-case system that allows capturing all transplant scenarios and collection of patient-specific and allograft-specific data. Beyond comprehensive clinical data, specific focus is directed at psychosocial and behavioral factors, infectious disease development, and bio-banking. Between May 2008 and end of 2011, the six Swiss transplant centers recruited 1,677 patients involving 1,721 transplantations, and a total of 1,800 organs implanted in 15 different transplantation scenarios. 10 % of all patients underwent re-transplantation and 3% had a second transplantation, either in the past or during follow-up. 34% of all kidney allografts originated from living donation. Until the end of 2011 we observed 4,385 infection episodes in our patient population. The STCS showed operative capabilities to collect high-quality data and to adequately reflect the complexity of the post-transplantation process. The STCS represents a promising novel project for comparative effectiveness research in transplantation medicine.

Should biomarkers be used to design personalized medicine for the treatment of glioblastoma?

Significant progress has been made in understanding the molecular pathogenesis of gliomas and in predicting general outcome depending on a limited set of clinical parameters and molecular markers. However, methylation of the O⁶-methylguanine DNA methyltransferase (MGMT) gene promoter is the only molecular marker linked to sensitivity of a specific treatment, that is, alkylating agent chemotherapy, and this predictive value may be limited to glioblastoma. Moreover, in the absence of potent alternative drugs, temozolomide chemotherapy should not be withheld from patients with newly diagnosed glioblastoma without MGMT promoter methylation in general practice. In the context of clinical trials, however, irrespective of whether classical cytotoxic drugs, tyrosine kinase inhibitors or antiangiogenic agents are used, tissue should be centrally collected. Appropriate research programs should seek to define enriched patient populations for future trials and ultimately facilitate individualized cancer treatments.

The business model ontology a proposition in a design science approach

The goal of this dissertation is to find and provide the basis for a managerial tool that allows a firm to easily express its business logic. The methodological basis for this work is design science, where the researcher builds an artifact to solve a specific problem. In this case the aim is to provide an ontology that makes it possible to explicit a firm's business model. In other words, the proposed artifact helps a firm to formally describe its value proposition, its customers, the relationship with them, the necessary intra- and inter-firm infrastructure and its profit model. Such an ontology is relevant because until now there is no model that expresses a company's global business logic from a pure business point of view. Previous models essentially take an organizational or process perspective or cover only parts of a firm's business logic. The four main pillars of the ontology, which are inspired by management science and enterprise- and processmodeling, are product, customer interface, infrastructure and finance. The ontology is validated by case studies, a panel of experts and managers. The dissertation also provides a software prototype to capture a company's business model in an information system. The last part of the thesis consists of a demonstration of the value of the ontology in business strategy and Information Systems (IS) alignment. Structure of this thesis: The dissertation is structured in nine parts: Chapter 1 presents the motivations of this research, the research methodology with which the goals shall be achieved and why this dissertation present a contribution to research. Chapter 2 investigates the origins, the term and the concept of business models. It defines what is meant by business models in this dissertation and how they are situated in the context of the firm. In addition this chapter outlines the possible uses of the business model concept. Chapter 3 gives an overview of the research done in the field of business models and enterprise ontologies. Chapter 4 introduces the major contribution of this dissertation: the business model ontology. In this part of the thesis the elements, attributes and relationships of the ontology are explained and described in detail. Chapter 5 presents a case study of the Montreux Jazz Festival which's business model was captured by applying the structure and concepts of the ontology. In fact, it gives an impression of how a business model description based on the ontology looks like. Chapter 6 shows an instantiation of the ontology into a prototype tool: the Business Model Modelling Language BM2L. This is an XML-based description language that allows to capture and describe the business model of a firm and has a large potential for further applications. Chapter 7 is about the evaluation of the business model ontology. The evaluation builds on literature review, a set of interviews with practitioners and case studies. Chapter 8 gives an outlook on possible future research and applications of the business model ontology. The main areas of interest are alignment of business and information technology IT/information systems IS and business model comparison. Finally, chapter 9 presents some conclusions.

Conceptualisation et emploi du passé composé et de l'imparfait en français langue étrangère (L3) au Sri Lanka : l'impact du singhalais langue maternelle (L1) et de l'anglais langue seconde (L2)

Résumé: Notre étude chevauche deux domaines de recherche quasi indissociables : ceux de la linguistique et de la didactique des langues. Comme l'indique le sujet, elle examine la conceptualisation et l'emploi de deux notions aspecto-temporelles du français (le passé composé et l'imparfait), sous l'impact des connaissances grammaticales déjà acquises sur deux autres langues : le singhalais et l'anglais. Notre recherche relève des domaines de la psycholinguistique, de la linguistique acquisitionnelle et de la linguistique comparative. Toutefois, dans le cadre de cette étude, nous examinons ces notions grammaticales françaises et leurs équivalents présumés dans les deux autres langues comme étant des concepts relevant des langues à statuts sociaux spécifiques [à savoir, langue maternelle (L1), langue seconde (L2) et langue étrangère (L3)], dans un contexte particulier d'enseignement/apprentissage et d'acquisition de langue [à savoir, le contexte d'enseignement/apprentissage et d'acquisition du français langue étrangère (FLE) au Sri Lanka]. En ce sens, notre étude est également liée aux domaines de la sociolinguistique et de la didactique des langues, notamment, étrangères. Ce qui pourrait probablement distinguer cette recherche des autres, c'est qu'elle aborde certaines questions linguistiques et didactiques peu étudiées jusqu'ici. Entre autres, l'influence de deux langues sur l'enseignement/apprentissage d'une L3, l'enseignement/apprentissage des langues dans des contextes exolingues et le rôle des transferts dans la conceptualisation des notions grammaticales. Pourtant, lorsque nous avons choisi le contexte d'apprentissage du FLE au Sri Lanka comme terrain de recherche, nous avons également visé d'autres objectifs : examiner les systèmes verbaux de trois langues dont l'imbrication n'a pas encore été objet d'étude ; examiner le système verbal aspecto-temporel peu explicité du singhalais à la lumière des descriptions linguistiques occidentales ; vérifier certains préjugés concernant les liens de proximité et de distance entre les trois langues choisies et étudier les causes de ces préjugés. Notre corpus provient de plusieurs classes de FLE au Sri Lanka. Le public observé était constitué d'adolescents ou d'adultes bilingues ayant le singhalais en L1 et l'anglais en L2. Les cours choisis se distinguaient les uns des autres par plusieurs critères, mais travaillaient tous sur les notions du passé composé et de l'imparfait. A la conclusion de notre étude, nous avons constaté qu'un nombre important de nos hypothèses initiales se sont avérées véridiques. A titre d'exemples, les transferts entre les langues premières et la langue cible sont récurrents et non négligeables chez l'écrasante majorité des apprenants exolingues observés, et parfois, même chez leurs enseignants; si ces apprenants recourent à ces langues pour étayer leur apprentissage, ni leurs enseignants ni leurs manuels provenant de l'étranger ne les guident dans ce travail; les transferts ayant l'anglais pour origine l'emportent considérablement sur ceux provenant du singhalais. De même, suite à l'analyse contrastive des trois systèmes verbaux aspecto-temporels et à l'analyse du corpus, nous avons également eu un résultat imprévu : contrairement à une représentation répandue chez les apprenants singhalais, il existe des points convergents entre leur L1 et le français ; du moins, au niveau de l'emploi de certains temps du passé. Un fait dont on était jusqu'ici ignorants mais dont on peut sûrement profiter dans les cours de FLE au Sri Lanka. Suite à ces observations et à la fin de notre thèse, nous avons fait quelques recommandations didactiques afin d'améliorer les conditions d'enseignement/apprentissage des langues étrangères, au Sri Lanka et ailleurs. Abstract: Our research is related to the fields of both linguistics and didactics, two research areas which are almost inseparable. As the title shows, the thesis examines the issue of conceptualizing and using of two grammatical (aspectual and temporal) concepts of the French language (le passé composé and l'imparfait), under the influence of previously acquired grammatical knowledge of two other languages: Sinhalese and English. Thus, our research is linked to the domains of psycholinguistics, acquisitional linguistics and comparative linguistics. However, within the framework of this study, we will consider the above-mentioned two French grammatical concepts and their presumed equivalents in the other two languages as concepts belonging to three languages with specific social status [i.e. first language (L1), second language (L2) and foreign language (L3)], taught/learnt/acquired in a particular language teaching/learning context [the context of teaching/learning of French as a foreign language (FFL) in Sri Lanka]. In that sense, our study is also associated with the fields of sociolinguistics and language teaching, especially foreign language teaching. What could probably make this study outstanding is that it studies certain linguistic and didactic issues which have not yet been studied. For example, it examines, among other issues, the following: the influence of two languages (i.e. mother tongue -L1 & second language -L2) on the teaching/learning process of a third language (i.e. foreign language- L3); foreign language teaching and learning in an exolingual context (where the target language is not spoken outside the classroom); the role of language transfers in the process of grammatical notion conceptualization. However, in selecting the FFL teaching/learning context in Sri Lanka as our field of research, we had further objectives in mind : i.e. 1) studying the verb systems of three languages whose combination has never been studied before ; 2) studying the aspectual-temporal formation of the Sinhalese verb system (which is hardly taught explicitly) in the light of the linguistic descriptions of dominant European languages; 3) verifying certain preconceived ideas regarding the proximity and the distance between the three chosen languages, and 4) studying the causes for these preconceptions. Our corpus is obtained from a number of FFL classes in Sri Lanka. The observed student groups consisted of bilingual adolescents and adults whose first language (L1) was Sinhalese and the second language (L2) was English. The observed classes differed in many ways but in each of those classes, a common factor was that the students had been learning some aspect of the two grammatical concepts, le passé composé and l'imparfait. Having completed our study, we now see that a considerable number of our initial hypotheses are proven correct. For example, in the exolingual French language teaching/learning context in Sri Lanka where we carried out our research, language transfers between the first and target languages were recurrent and numerous in the work of the greater majority of the observed language learners, and even their teachers; these transfers were so frequent that they could hardly be ignored during the teaching/learning process ; although learners turned to their first languages to facilitate the learning process of a new language, neither their teachers, nor their text books helped them in this task; the transfers originating from English were far too numerous than those originating from Sinhalese; however, contrary to the popular belief among many Sinhalese learners of French, the contrastive analysis of the three aspectual-temporal verb systems and the study of our corpus helped us in proving that there are common linguistic features between the Sinhalese and the French languages ; at least, when it comes to using some of their past tenses. This is a fact which had been ignored up to now but which could probably be used to improve French teaching/learning in Sri Lanka. Taking all observations into account, we made some pedagogical recommendations in the concluding part of our thesis with the view of improving foreign language teaching/learning in Sri Lanka, and elsewhere.