NCube/papyrus huggingface dataset:
Régulation dépendante du cycle cellulaire de la réparation par excision de nucléotides

Nucleotide excision repair (NER) is a critical pathway in humans for repairing highly genotoxic helix-distorting DNA lesions that strongly block both replication and transcription.  Among these lesions are ultraviolet-induced 6-4 photoproducts (6-4PPs) and cyclobutane pyrimidine dimers (CPDs).  The physiological importance of NER is highlighted by individuals afflicted with Xeroderma pigmentosum (XP), who carry mutations in NER pathway genes and as such exhibit extreme photosensitivity and remarkable predisposition to cutaneous tumorigenesis (1000-fold increase).  On the other hand patients with the variant form of Xeroderma pigmentosum (XPV) are considered proficient in NER, and rather carry germline mutations in the gene encoding DNA polymerase η (polη).  Polη is a specialized translesion DNA polymerase able to accurately bypass certain lesions including CPDs which otherwise completely inhibit the progression of normal replicative polymerases, thereby preventing mutations and allowing the resumption of DNA synthesis.  The main goal of this thesis was to elucidate the potential role in NER of major DNA damage signalling cascades, including that regulated by the ataxia telangiectasia and rad 3-related kinase (ATR). Following UV irradiation, ATR is rapidly activated and phosphorylates hundreds of proteins that regulate cell cycle checkpoints and maintain genomic stability. We postulated that ATR might regulate NER in a cell cycle-specific manner.  However testing this presented a great challenge, as (for technical reasons) traditional NER assays have to date not been adapted for evaluation of repair kinetics during individual phases of the cell cycle.  We therefore developed a novel flow cytometry-based assay for sensitive quantification of 6-4PPs and CPDs repair efficiency during each of G0/G1, S, and G2/M.  With this new assay, we were able to show that inhibition of either ATR or polη results in strong inhibition of NER capacity exclusively during S phase of the cell cycle. This revealed, for the first time, a critical function for these proteins in removal of replication-blocking DNA adducts.  In addition, we demonstrated that active DNA synthesis is required for S phase-specific repair inhibition, reflecting a potential relationship between NER and replication.  Intriguingly, we also showed that among six tumor cell lines, three exhibit total abrogation of NER uniquely during S phase, indicating that many human cancers may be characterized by such a defect.  Our findings therefore could harbour important implications for cancer treatment.  Indeed, NER status of tumors clearly appears to constitute a major determinant in the clinical response to chemotherapeutic drugs such as cisplatin, which inhibit the growth of rapidly proliferating cancer cells through induction of replication-blocking DNA lesions.

Keyphrases: Ultraviolet, ATR, ADN polymerase η, Nucleotide excision repair, DNA damage, Ultraviolet, ATR, DNA polymerase η, Cell cycle
La pronunciación de ELE en los alumnos quebequenses :
dificultades concretas y pautas de corrección

My subject of study is about Spanish as a second language, in French Canadian students, about their difficulties and the correction aid. In a first part, more general, we discuss about teaching pronunciation, the place it has in teaching as a second language. We believe that pronunciation is an aspect in a language that has been left out to emphasize on communication. If a “bad” pronunciation does not interfere in the comprehension or communication, it is not corrected or worked on. We can then find ourselves with students having a very high level in Spanish, but their pronunciation is not as good. We also define what we intend by “better” or “bad” pronunciation, and we also ask ourselves about the pertinence of teaching phonetics. We also interrogate ourselves on the question of the place of pronunciation depending on the didactic methodology, and we analyze the quantity and quality of the pronunciation exercises we find, or not, in scholar manuals, and if they correspond to the demands of the official documents as the Common European Framework of Reference for Languages or the Curricular Plan of Cervantes Institute. In a second part, we ask ourselves about the factors that condition the learning experience of a language, and that is because we believe that no matter the student’s age, there’s always place for amelioration in the pronunciation of a second language. We we’ll also see the French general tendencies in their Spanish pronunciation, and we’ll make a contrastive study on Spanish and French phenomena and then elaborate on French Canadian tendencies, and that is because we believe that they have some sort of vantages in comparison to other French speaking people.  In a third and last part, we propose exercises that tend to help our student’s pronunciation, and to verify the efficiency of those exercises, we will record students that beneficiated of those exercises, and others who did not practice. That study wants to prove that those exercises really help, and that they should be included in the teaching and learning experience. The questionnaire we use is especially dedicated to the [r] phenomenon, because we believe it is a, or the most difficult sound to pronounce in Spanish (simple and multiple vibration forms). Of course, a part of this study will be dedicated to the results analysis.

Keyphrases: Pronunciation, Spanish as a second language, French-Canadian speakers, Quebec, Phoneme [r]
Du bien-être psychologique au travail : fondements théoriques, conceptualisation et instrumentation du construit

Despite growing concern by researchers and practitioners about psychological health at work, the concept of well-being in the workplace is still misunderstood in the scientific community. Indeed, little effort has been made to develop knowledge about psychological well-being at work that is tied to the reality of employees. This thesis aims at developing a conceptualization of psychological well-being at work and a related psychometrically reliable instrumentation. To do so, two studies were carried out. First, an exploratory qualitative study was conducted among 20 French-speaking Canadian workers to identify, using critical incidents they experienced, manifestations of psychological well-being. The manifestations were classified according to a 2-axis model, namely, the reference level at which psychological well-being at work is experienced and the directionality through which it emerges. This model was then compared to existing context-free conceptualizations of psychological well-being; this analysis offered support to the model's convergent and divergent validity. Second, the Index of Psychological Well-Being at Work (IPWBW) was created based on the manifestations identified in the qualitative study, in order to ensure the latter’s content validity. An experimental form of the questionnaire was administered to 1,080 Quebec workers. Exploratory factor analyses revealed an internal structure of 25 items and 5 dimensions, representing a second-order construct. The construct validity of the model was established by analyzing the intercorrelation pattern with various context-free measures of psychological well-being and distress. The results support the convergent validity of the instrument and demonstrate its divergent validity. Finally, the questionnaire shows satisfactory internal consistency. By way of conclusion, the results of the two studies are interpreted in the light of current knowledge on psychological well-being; the limits of the studies are outlined; and avenues for future research are proposed.

Keyphrases: Psychologie positive, Psychological health at work, Psychological well-being at work, Conceptualization, Psychometric instrument, Industrial-organizational psychology, Organizational behavior, Occupational health psychology, Positive psychology
Rebuilding less vulnerable communities : the case of Holy Cross

Resiliency is the capacity to adjust to threats and mitigate or avoid harm; it can be found in hazard-resistant buildings or adaptive social systems (Pelling, 2003). Hence, it  can also be understood as the ability to rebuild a neighbourhood with stronger and more  viable components. Almost four years after Hurricane Katrina, New Orleans is seen as an  open laboratory in which the level of resiliency of its communities can be examined. The  rebuilding status of its neighbourhoods widely differs from one to another. The historic  district of Holy Cross is one of the oldest neighbourhoods in the city; this vulnerable  community is known for its cultural heritage, apparent not only in its unique architecture  but also its social relations. This research investigates the current process of rebuilding a  more sustainable and resilient Holy Cross by assessing the efficiency of stakeholders  involved in the reconstruction of affordable opportunities that work to encourage former  residents to return. It also demonstrates the current efforts to build new sustainable  projects while keeping the patrimonial style of the neighbourhood.

Keyphrases: Natural hazards, Sustainability, Vulnerability, Resilience, Recovery, Reconstruction, Heritage, Green building, Community, Technologies vertes, Holy Cross, New Orleans
Impact de HOXB4 sur les cellules B

Transplantation of autologous hematopoietic stem cell is increasingly used. However, intensive chemotherapy or radiation therapy protocols can affect stem cells and decrease the number of these cells that can be mobilized for stem cell transplantation. There is therefore a need to create protocols for the expansion of these stem cells to increase their numbers sufficiently to proceed to transplantation. It has been demonstrated that the protein HOXB4 has the ability to expand human and murine hematopoietic stem cells. In the context of autologous transplantation, the bone marrow is often colonized by malignant cells. Our objective was to ensure that the protein HOXB4 expands normal hematopoietic stem cells but not leukemia "stem" cells.  In addition, since previous experiments have shown that in mice transplanted with stem cells overexpressing HOXB4, hematopoietic reconstitution could favour myeloid cells over lymphoid cells, we determined the impact of HOXB4 on the differentiation of normal lymphoid progenitor cells. Toward this goal, we have exposed human and mouse leukemia cells to HOXB4 and compared the proliferation of malignant versus normal B cells. In addition, we have evaluated the impact of HOXB4 on the different stages of B cell differentiation. Our results show that HOXB4 does not favour leukemia cell expansion. In addition, we observed that lymphoid cells overexpressing HOXB4 are slowed in their differentiation process. Also, HOXB4 overexpression decreases the frequency and number of normal lymphoid progenitors. These results demonstrate that HOXB4 protein does not lead to malignant stem cell expansion. In addition, the HOXB4 protein confers a proliferative disadvantage to lymphoid cells.

Keyphrases: CSH, Expansion, CLP, HOXB4, HSC, Expansion, B cells, CLP, HOXB4, Leukemic cells
Développement de méthodes analytiques de séparation des produits de digestion enzymatique des dérivés de cellulose

Cellulose and its derivatives are used in a wide range of applications, including the pharmaceutical industry for the manufacturing of medicines as inactive additives. Various cellulosic derivatives such as carboxymethylcellulose (CMC) and hydroxyethylcellulose (HEC) are readily available for such use. The degree of polymerization and modification differs from one supplier to the other, according to the origin of the cellulose and its process of chemical modification, conferring on them different physico-chemical properties, such as viscosity and solubility. Our interest is to develop an analytical method that can distinguish between different sources of a given CMC or HEC product. The specific objective of this master’s study was to obtain a fingerprint of these complex biopolymers by developing an enzymatic digestion method to produce smaller oligosaccharides that could be separated by simple chromatographic methods. The digestion was studied as a function of various parameters, such as the composition of the hydrolysis solution, the pH, the temperature, the duration of digestion and the substrate/enzyme ratio. A cellulase enzyme from Trichoderma reesei ATCC 26921 was used for the partial digestion of our samples of cellulose. Since these oligosaccharides do not possess a chromophore or fluorophore, they can’t be detected either by absorbance or fluorescence. It was thus necessary to work out the labeling method for oligosaccharides using various agents, such as 8-aminopyrene-1,3,6-trisulfonic acid (APTS), 3-acetylamino-6-aminoacridine (AA-Ac) and  phenylhydrazine (PHN). Finally, the use of capillary electrophoresis and high performance liquid chromatography allowed the separation of the enzymatic digestion products of the cellulose derivatives (CMC and HEC). For each of these analytical separation techniques, several parameters of the separation were studied.

Keyphrases: Capillary electrophoresis, Laser-induced fluorescence, High-performance liquid chromatography, Hydrophilic interaction chromatography, UV detection, Partial digestion, Enzymatic digestion products, 8-aminopyrene-1,3,6-trisulfonic acid, Phenylhydrazine, Cellulose derivatives
L’étude de l’interaction entre les chondrocytes et le collagène modifié par le 4-Hydroxynonénal : implication dans le développement de l’arthrose

OBJECTIVE: The regulation of cell phenotype and function by the surrounding environment is deeply altered by the oxidative modifications of extracellular matrix (ECM) components that modify their structural and functional properties. This modification may be one cause involved in cartilage degradation in osteoarthritis (OA). Type II collagen (Col II) was reported to be targeted for 4-hydroxynonenal (HNE) binding, a very reactive product of lipid peroxydation. In the present study, we investigated whether HNE-binding to Col II affects OA chondrocytes phenotype and function and then, we determined the protective role of carnosine treatment in preventing these changes. METHODS: Isolated human OA chondrocytes were seeded in control wells and in HNE/Col II adducts-coated plates and incubated afterwards for 48 hours. Adhesion molecules at protein and mRNA levels were determined by Western blotting, flow cytometry and real-time RT-PCR. Commercial kits were used to evaluate cell death, caspase-8 activity and levels of prostaglandin E2 (PGE2), matrix metalloproteinase-13 (MMP-13), MAPK and NF-κB-p65. Col II, cyclooxygenase-2 (COX-2), MAPK and NF-κB-p65 levels were assessed by Western blotting. RESULTS: After 48 hours of incubation, the modification of Col II by 0.2 mM HNE induced strongly the expression of ICAM-1, integrin α1β1, MMP-13 and slightly COX-2 as well as PGE2 release without affecting cell morphology and viability as well as Col II expression. However, the modification of Col II with 2 mM HNE induced shape changes of cells from typical chondrocyte-like polygon shape to round semi-detached, affecting cells viability and inducing caspase-8 activity. It inhibited the expression of ICAM-1, integrin α1β1 and Col II, but in contrast, induced strongly PGE2 release and COX-2 expression. All these effects were prevented by 0.1 mM carnosine treatment, an HNE trapping drug. Carnosine was added to HNE-modified, Col II-coated plates 1h before cell seeding. Upon examination of different signalling pathways involved in these responses, we found that modified Col II with 2 mM HNE inhibited strongly the phosphorylation of ERK1/2 and NF-κB-p65 but induced strongly p38 MAPK. In contrast, the results indicated that MAPK and NF-κB-p65 were activated when cells were incubated with modified Col II by 0.2 mM HNE. CONCLUSION: The interaction between chondrocytes and collagen-bound HNE modulates different signalling pathways via adhesion molecules regulation and consequently leads to the expression of catabolic and inflammatory factors. Carnosine was shown to be an efficient HNE trapping agent able to counteract these effects.

Keyphrases: Chondrocytes, Inflammation, Carnosine, Osteoarthritis, Chondrocyte, Lipid peroxydation, 4-Hydroxynonenal, Type II Collagen, Phenotype, Catabolism, Inflammation, Carnosine
Revue critique des arguments en faveur et à l'encontre de la théorie humienne de la motivation

Although remaining orthodoxy in philosophy of mind, the humean theory of motivation (according to which motivation always comes from a desire, never from a belief alone) has often been critized over the last decades. Here I review the main arguments put forward both to support and reject this theory. On the humean side, I examine the argument from identical beliefs, the direction of fit argument and the argument from theoretical uniformity. On the anti-humean side, the objection that direction of fit caracterizations are circular, the objection from irrational beliefs and the objection according to which there could be mental states with two direction of fit. I conclude that none of these objections should lead us to reject the humean theory, but also that this one finds its main support in theoretical unifomity considerations and not in the direction on fit argument as many think.

Keyphrases: Philosophy, Metaethics, Humean Theory of Motivation, Direction of fit, Theoretical uniformity
La multiculturalité, la communauté et les femmes non-conventionnelles dans The Diviners de Margaret Laurence et O Pioneers! de Willa Cather

Abstract This thesis studies the multicultural stakes at the turn of the twentieth century in North America, the problems occuring in face-to-face communities and the unconventional traits of the feminin protagonists in The Diviners (1974) by Margaret Laurence and O Pioneers! (1913) by Willa Cather. This study aims at highlighting the similarities between the two novels which were written by women writers and narrate the stories of strong and independant women who are living in multicultural communities of the West. This study will also highlight the differences between the period and context in which each novel takes place. Firstly, this thesis will study several problems regarding multiculturality and will analyse the two novels with the help of such concepts as Melting Pot, assimilation and interculturalism. Secondly, this thesis will study several  problems regarding face-to-face community. This section, in an attempt to  deconstruct the ideal of the face-to-face community, will show how frictions and rejections are part of the daily life of the novels’s characters. Lastly, this thesis will study the nonconformism of the two feminine protagonists and will show that in their own way, they deconstruct the feminine stereotypes of their environement and period in order to become emancipated.

Keyphrases: Multiculturality, Community, Feminin emancipation, Colonialism, West expansion
Modification d'acides biliaires à l'aide de polymères pour en moduler les propriétés d'agrégation

Amphiphilic polymers are very useful in biomedical and pharmaceutical applications.  To improve the biocompatibility of such polymers, we chose to use natural compounds such as bile acids as the starting material in the synthesis of the polymers. New anionic polymers have been prepared by atom transfer radical polymerization.  Poly(acrylic acid) arms of various lengths have been grafted onto a bile acid core.  The molecular architecture has been confirmed by 1H NMR spectroscopy and by mass spectrometry.  The star polymers obtained from modified bile acid can aggregate in water, even though the hydroxyl groups were replaced by bulkier chains.  The ester linkages between the polymers and the bile acid core are prone to hydrolysis in aqueous solutions. In order to improve the stability of the polymers in aqueous solutions and to introduce neutral and biocompatible hydrophilic arms, ethylene oxide has been polymerized onto a cholic acid core by anionic polymerization.  The ether linkages formed between the hydroxyl groups of the bile acid and the poly(ethylene glycol) are more stable than the ester linkages formed with the poly(acrylic acid) polymers.  The reaction conditions for the anionic polymerization have been optimized and provided well-defined polymers with narrow molecular weight distributions.  The new polymers formed spherical aggregates as shown by transmission electron microscopy with samples prepared by the freeze-fracture technique.  Their morphology is different from those of the cylindrical aggregates formed by bile salts. With the optimized method for anionic polymerization, allyl glycidyl ether was grafted onto a derivative of cholic acid, followed by thiolation, a radical addition, of the allyl groups to introduce amine or carboxylic acid groups to the polymer chains.  This radical addition had an efficiency of more than 90%.  The resulting polymers were water-soluble and were found to aggregate above a certain critical concentration.  It is particularly interesting to observe thermosensitivity of the star polymers bearing amine groups.  The thermosensitivity of such polymers can be further tuned by partial acetylation of the amine groups, yielding polymers with cloud points in the temperature range from 15 to 48°C.

Keyphrases: Bile acids, Star polymers, Living polymerization, Amphiphilic polymers, Aggregation, Thermosensitivity
La vulnérabilité face aux risques environnementaux à Kigali (Rwanda) : enjeux et facteurs

The purpose of this research is to make an inventory of knowledge produced on environmental risks and vulnerability and apply this knowledge to the Kigali city (Rwanda). After presenting different approaches, we used the analytical framework that is part of the approach of J. C. Thouret and R. D’Ercole (1996). This approach is articulated around three dimensions: issues, factors of vulnerability and social responses. Through the implementation of relevant elements of these three dimensions in the case of Kigali city, conducted through a qualitative analysis focusing on the analysis of documents and the interpretation of semi-directed interviews, here are the main results we have obtained: the analysis of the issues has revealed that the Kigali city is facing damages, including the loss of human lives, demolition of houses, contamination of rivers, proliferation of diseases, and disruption of basic needs (drinking water, power and transportation)  due to riks. This situation is explained by the combination of several factors including the hilly terrain, the granite soil, heavy rains, the centrifugal character of the river system, under-sizing of spillways and the inadequate sewerage system. Others factors exacerbate the vulnerability, including the demographic explosion due to an unconscious and spontaneous urbanization in flood areas, the silting of river beds, the legal vacuum, fragmentary policies and dysfunctional stakeholders involved in risks management. This situation would probably have been improved if social responses were effective. However, on one side, low risk perception among residents affected by the risks, accelerates the vulnerability and on the other side, the significant intervention of CIB is not accompanied by complementary actions of public institutions and international agencies as well.

Keyphrases: Vulnerability, Environmental risks, Issues, Damages, Factors, Actors, Social responses, Kigali, Kigali, Rwanda, Rwanda