NCube/papyrus huggingface dataset:
Copper and nickel catalysis for alkynylation reactions

Alkynes are recognized as versatile building blocks for chemical synthesis as they can participate in an array of transformations. Consequently, expanding the toolbox of efficient and chemoselective methodologies to access internal carbon- and heteroatom-substituted alkynes is of interest. The following thesis describes the development of new copper- and nickel-based catalytic systems to perform alkynylation reactions. The research presented in Chapter 3 describes the first report of a copper-catalyzed Sonogashira-type cross-coupling toward the formation of macrocycles from conformationally unbiased linear precursors. The macrocyclic Sonogashira-type cross-coupling exploited a CuCl/phen/Cs2CO3 catalytic system to generate 17 macrocycles with various ring sizes (10- to 25-membered rings) and functional groups in yields ranging between 38-83 %. Also, the method could be performed at relatively high concentrations (24 mM) without the need for slow addition techniques. The optimized reaction conditions were additionally applied toward the synthesis of a biologically active natural product, (S)-zearalane. The research presented in Chapter 6 describes the first report of a photoredox/nickel dual-catalytic synthesis of aryl- and heteroaryl-substituted alkynyl sulfides. The C(sp)-S bond-forming coupling was achieved between thiols and aromatic bromoalkynes using a 4CzIPN/NiCl2•glyme/pyridine catalytic system under visible-light irradiation at room temperature. Alkynyl sulfides bearing a wide range of electronically and sterically diverse aromatic alkynes and thiols were obtained in good to excellent yields (50-96 %) using an in-house designed visible-light photoreactor in continuous flow. The methodology was also applied toward the synthesis of a macrocycle, a rare example of a photochemical macrocyclization performed in continuous flow. The photochemical dual-catalytic procedure represented the first example of a macrocyclization exploiting photoredox/nickel dual-catalysis. The research presented in Chapter 7 describes the first general method to access all classes of alkynyl sulfides through copper catalysis, including aryl-, alkyl-, silyl-, and heteroatom-substituted alkynyl sulfides. The Cu(MeCN)4PF6/dtbbpy/2,6-lutidine catalyst system gave access to alkynyl sulfides in high yields under ten minutes, and was highly reproducible even on large scale. Furthermore, the methodology efficiently led to a bis(thio-substituted)alkyne, a rare example of an alkyne functional group adorned with two heteroatom substituents.

Keyphrases: copper catalysis, nickel catalysis, photoredox catalysis, macrocyclization, Sonogashira reaction, alkynyl sulfides, continuous flow chemistry
Régulation de l’activité de Dicer par TRBP dans la biogénèse des micro-ARN

Micro-RNAs (miRNA) are small non-coding RNAs that act as post-transcriptional gene regulators. They are part of the RNA-induced silencing complex (RISC) where they serve as guides to target mRNAs by sequence complementarity and inhibit their translation. Together, miRNAs can regulate the translation of virtually every protein in the cell. This confers miRNAs a central role in various cellular processes such as the development of organisms.  To be functional, miRNA must undergo maturation through a highly regulated pathway where they are first transcribed, then cleaved in two steps by endonucleases Drosha and Dicer and, finally, loaded onto the Argonaute protein (AGO) to form the RISC complex. This thesis focuses on the Dicer cleavage step and its regulation by the TRBP cofactor, which is a protein that can simultaneously bind Dicer and its pre-miRNA substrate. The first objective of the thesis is to develop a new protocol for the expression and purification of human Dicer with the intent to improve the yields of existing methods and facilitate its in vitro characterization. We optimized Dicer expression in a human cell expression system that uses an engineered HEK93-6E cell line grown in suspension. Then, we developed a 3-step purification protocol allowing for Dicer purification in a single day. Moreover, these steps were carefully optimized to minimize losses and maximize Dicer stability. The purified Dicer was then analyzed using SEC-MALS and negative-stain EM to confirm that it was a well-folded monomer. Finally, we biochemically characterized Dicer by measuring its binding to a pre-miRNA substrate by EMSA and steady-state kinetic studies. Through these experiments, we calculated new values of kcat and KM that are consistent with a mechanism that involves a conformational change of the Dicer-substrate complex prior to the cleavage step.  The second objective was to characterize the effect of TRBP on Dicer activity. To do this, we first tested different pre-miRNA substrates with Dicer in presence of TRBP and showed that TRBP was both an activator and inhibitor of Dicer. Indeed, TRBP is an activator at low substrate concentration and an inhibitor at higher concentration. Next, we characterized the detailed mechanism of the effect of TRBP by a using a combination of binding and steady-state kinetic experiments. Our final model shows that low TRBP concentration is necessary for activation of Dicer activity at low substrate concentration. Our model suggests that TRBP exerts its activation function without reducing Dicer’s specificity for its substrate. These new results suggest that TRBP evolved to efficiently activate Dicer without modifying the specificity of the reaction.

Keyphrases: Dicer, miRNA, TRBP, regulation, purification, kinetics
Les relations entre la beauté et l’attribution de compétences : une analyse évolutionniste

Many studies have shown the socio-economic privileges associated with a beautiful face as well as its advantages for all kinds of relationships. Evolutionary theories have tried to understand this phenomenon by showing the link between beauty and health and by demonstrating the role of beauty in competition and cooperation. Social sciences have shown how the link between beauty and competences can be created with three theories: status generalization, stereotype of the association of beauty and goodness, and social reproduction.  However, no study has compared the association between different competences, beauty, and health amongst women and men and according to women and men. With an online survey, it was possible to get rankings for six women and six men according to their beauty, their health, and five competences (intelligence, physical strength, creativity, sociability, and leadership) and to see correlations between those characteristics. Because women more than men attribute a better health to attractive men, results firstly show the role of differences in parental investment between genders and of sexual selection in the attribution of competences to attractive people. Results also show that sociability and leadership are the two competences that are the most correlated to beauty, whatever the gender and the sexual orientation of the respondent are and whatever the gender of the people being evaluated. This shows that people can be attracted to others because they seem good cooperators and able to access higher social statuses, without any presence of sexual attractiveness. This is in agreement with the evolutionary theories of cooperation and attraction to experts. The three above-mentioned social theories propose mechanisms that are in agreement with the evolutionary theories and that allow to explain the social amplification and propagation of those evolutionary phenomenon.

Keyphrases: Beauty, Health, Cooperation, Competition, Competences, Social status
Les céramiques et les réseaux maritimes du fort de Ville-Marie, Montréal, 1642-1688

This thesis examines the transatlantic networks that supplied Montréal’s seventeenth-century foundation site (BjFj-101) also known as the fort of Ville-Marie. By studying the provenances of the coarse earthenware, faience and coarse stoneware found in the site’s 1642-1688 contexts, the thesis aims to understand how the supply and trade of fort Ville-Marie were organised.  The numerous ceramics discovered on New France’s colonial sites are often identified by their production centre. These production centres in France or New France were linked to a particular sea port and the ceramics thus attest to each port city’s commercial influence throughout the French Atlantic. The ceramics from the sealed contexts of Ville-Marie’s fort provide an original database from which we can examine these ports fluvial and maritime networks and their evolution over the course of the 17th century. The site’s various contexts of discovery can be divided into two phases, the first from 1642 to 1674 and the second from 1674 to 1688. These chronological intervals also correspond with differences in the ceramic record and indicate an evolution of Ville-Marie’s fluvio-maritime supply network during its first half-century of existence. The functional and contextual analysis of the ceramics during each interval also reveals the workings and specialisations of several different maritime networks. Our results show the great importance of the Southwestern ports of France, (Bordeaux and La Rochelle), Normandy and also of the more limited influence of other European regions as well as the potters of New France. The origins of these ceramics also shed new light on historical data, especially showing that the city of Bordeaux had a sturdier hold than La Rochelle on the supply lines of 17th-century Montreal.

Keyphrases: Ville-Marie, Montréal, Bordeaux, La Rochelle, port, Ceramics, Archaeology, Maritime network, Trade network, Harbour, Atlantic sea
Kant and Lévinas on the problem of theodicy

In his article of 1982 “The Useless Suffering” Lévinas writes that his interpretation of the story of Job in the Old Testament is in agreement with the reading offered by Kant in his essay of 1791 on “theodicy.” For the two authors indeed every attempt at showing that a divine justice is at work in the events of the world is doomed to fail, or more precisely: to be contradicted by the facts. The question of theodicy must on the contrary be addressed from a strictly moral point of view. And this question provides a special opportunity to stress the profound differences between Kant’s and Lévinas’ ethics: on the one hand, honesty with oneself, and on the other hand, care for the other.

Keyphrases: Kant, Lévinas, Theodicy, Authenticity, Care for the other
La question de la théodicée chez Kant et Lévinas

In his article of 1982 “The Useless Suffering” Lévinas declares that his interpretation of the story of Job in the Old Testament is in agreement with the reading offered by Kant in his essay of 1791 on “theodicy.” For the two authors indeed every attempt at showing that a divine justice is at work in the events of the world is doomed to fail, or more precisely: to be contradicted by the facts. The question of theodicy must on the contrary be addressed from a strictly moral point of view. And this question provides a special opportunity to stress the profound differences between Kant’s and Lévinas’ ethics: on the one hand, honesty with oneself, and on the other hand, care for the other.

Keyphrases: Lévinas, Kant, Theodicy, Authenticity, Care for the other
Un éclairage sur l’influence des évaluations mutuelles entre enseignants et étudiants en contexte universitaire : vers une conception resocialisante

This article draws on a doctoral thesis problem in which a portrait of research on evaluation in the university context has been achieved. It questions the role played by mutual assessments in relations between university teachers/students in the context of the emergence of modes of governance which give assessment an important regulatory role. Most research, centered on accounting data evaluations, seem to neglect what is negotiated in the interaction between those actors, through their mutual evaluations. We propose a resocializing perspective on assessment to examine particular issues at the heart of their dynamic.

Keyphrases: University teachers/students relationships, Resocializing perspective, Assessment
Le bénéfice des interventions infirmières dans l’accessibilité aux soins de santé : le cas du diabète

Objective The aim of this article is to document the impact of nurse-led primary care prevention programs for diabetic patients on accessibility to care. Method An integrative review of the literature was done by locating articles in the electronic databases CINALH and PubMed. A total of 19 articles were selected and analyzed. Results Nurse-led prevention programs in primary care for diabetic patients has overall positive impacts across the ten accessibility of care dimensions, which are split equally between offer and demand: 1) Approachability; 2) Acceptability; 3) Availability and accommodation; 4) Affordability; 5) Appropriateness, 1) Ability to perceive; 2) Ability to seek; 3) Ability to reach; 4) Ability to pay; and 5) Ability to engage. The nurses taking part in prevention programs in primary care have the potential to improve the accessibility, effectiveness and quality of health care for diabetic patients. Conclusion The front-line nursing workforce can have positive effects on the accessibility of health care for patients with diabetes, such as identifying their healthcare needs, search and find the necessary services for their health condition and use the care and services in a more appropriate way. More robust and accurate research is needed to solidify this knowledge.

Keyphrases: Primary care, Diabetes, Accessibility, Nursing
Formative assessment : revisiting the territory from teacher’s point of view

This research documented the know-how of five elementary-school teachers regarding formative assessment, working from their point of view on the question. Group interviews gave them the opportunity to negotiate their “ways of doing things,” by revisiting and elaborating upon assessment episodes that had been previously identified on classroom videotapes. An interactionist analysis served to describe the territory of formative assessment according to the range of their formal and informal “ways of doing things.”

Keyphrases: Formative assessment, Collaborative research, Primary teachers, Practical knowledge, Ways of doing
Les stratégies des accompagnateurs de l’intégration socioprofessionnelle des enseignants formés à l’étranger : le jeito des despachantes

Given the increasing presence of foreign-trained teachers in Quebec schools and the social issues linked to their socioprofessional integration, the researchers are interested in their experience. However, little attention has been paid to the contribution of the stakeholders of professional and academic communities involved in this process. Individual interviews were conducted with 14 participants from both communities to inform how they work to facilitate the integration of these teachers in their new workplace. Different cultural mediation strategies highlighting the experiential knowledge of these supporters have been identified.

Keyphrases: Supporters, Experiential knowledge, Foreign-trained teachers, Socioprofessional integration, Cultural mediation strategies
Des modes d’interaction au cœur de la mise en œuvre d’une évaluation formative informelle

This research documents the ways in which formative assessment is informally carried out through interactions between teacher and students during classroom activities. Especially, it examined the interactive dynamics involved in its implementation. In order to do so, video sequences of teachers were produced in 10 elementary school classrooms with individual interviews aiming to explicit practices. Results point to different modes of interaction, including confrontation, adjustment, dealing, seduction, humor. They allow us to see that assessment is a privileged time for negotiating the pedagogical contract in the classroom.

Keyphrases: Formative assessment, Modes of interaction, Primary teachers, Socialization, Pedagogical contract
Le mal radical chez Fichte entre Kant et Schelling

In this article, I submit to critical analysis two theses concerning radical evil in Fichte: 1- the thesis according to which his conception would not fundamentally differ from Kant’s position (a thesis defended by A. Soller and M. Ivaldo) and 2- the thesis according to which it is only after the seizure of power by the emperor Napoléon, representing the absolute self-assertion of the free will, that Fichte’s position would have come closer to Kant’s (R. Lauth). I would like to distance myself from both theses by stressing the fact that all through his career Fichte has been the proponent of a conception of radical evil, that he revealingly calls “radiakles Übel,” based on inertia and ignorance.

Keyphrases: Fichte, Kant, Napoléon, Böse/Übel, Ignorance, Paresse, Self-assertion, Laziness
Fichte et la première philosophie de la nature de Schelling

When we reconstruct Fichte's philosophy of nature of the Jena period, we can notice striking similarities between the conception of organism in the Doctrine of Science and Schelling's corresponding developments in his early Naturphilosophie. But even though both thinkers agree to consider organic nature within the framework of transcendental idealism, it is nevertheless possible at this stage to discover slight differences in their interpretation which announce their future disagreement on the status of a philosophy of nature. If, for instance, organism can for both of them be considered as an « analogon » of the absolute, it all depends on how they conceive this analogy: from a practical or from a theoretical point of view.

Keyphrases: Fichte, Schelling, Naturphilosophie, Naturphilosophie, Organism, Transcendental idealism
La phénoménologie de l'expérience morale chez Kant

In his MAN of 1786 Kant exposes his own conception of “phenomenology”, whose task is to trace the a priori principles that structure the phenomenal world. Now I argue that Kant adopts a phenomenological approach in his moral philosophy when in the Grlg of 1785 and in the second Critique he takes as his point of departure the moral judgments of common understanding in order to point out the pure rational principles operating in them. But we can say that another conception of phenomenology is at work in Kant’s moral philosophy, a conception that corresponds this time to Lambert’s definition: a theory of illusion. In fact, the “logic of illusion” of the second Critique has to do indirectly with Hutcheson’s moral feeling, that is: a phenomenon that can be falsely taken for the determining principle of morality. In the end Kant does justice to this phenomenon by reinterpreting it as the feeling of “respect” for the moral law.

Keyphrases: Kant, Hutcheson, Lambert, Phenomenology, Moral feeling, Illusion
L’espace d’une virgule Mendelssohn et Kant sur les preuves de l’existence de dieu

Moses Mendelssohn published his Morning Hours or Lectures on the Existence of God in 1785, that is: four years after the publication of Kant’s Critique of Pure Reason. We know that Kant in his work had explained the fundamental mistake at the origin of the illusion in the “transcendental” proofs of the existence of God: the implicit interrelation between the ontological and the cosmological arguments. However, it seems that Mendelssohn did not take notice of the warning issued by Kant, the alles Zermallmer, since in his lectures he ingenuously falls into the trap and commits the mistake in question.

Keyphrases: Kant, Mendelssohn, Ontological/cosmological proof, God, Dogmatic/critical
Traduction française et étude de pré-validation de la batterie d’évaluation des fonctions exécutives NIH-EXAMINER chez l’enfant

Executive functions (EF) allow any goal-oriented action that requires constant adjustment to environmental expectations (Luria, 1973). In childhood, the development of the prefrontal cortex, a region associated with EF, is particularly important. EF have a strong impact on many areas of development. It is therefore essential to properly evaluate FE in clinical neuropsychology. Several tools are currently used without being validated with Francophone children in Quebec or offering a complete FE profile. Some have poor psychometric qualities and are expensive. This study aims to translate the NIH EXAMINER in French and begin its validation process (Kramer et al., 2014). The original version of this battery, available in open access (free of charge), demonstrates excellent psychometric properties and allows to evaluate the majority of FE. Performance on the translated NIH-EXAMINER, on other assessment tools of FE, as well as on tools assessing intellectual reasoning and symptoms associated with ADHD were collected among 17 neurotypical children. The results show good stability in internal consistency, good criterion and construct validity, but are insufficient in contingent validity for self-reported measures of FE in daily life. Further studies with a larger sample size and different clinical groups are needed to pursue the validation process of the French version of the NIH-EXAMINER.

Keyphrases: Validation, Executive functions (EF), Psychometry, Childhood, Cognitive development, Neuropsychological evaluation
L’autoconstitution du sujet connaissant dans l’opus postumum

I argue in this article that there is no break between the CPR and the Opus postumum with respect to the theme of the self-constitution of the knowing subject. To be sure, the exposition of space and time as well as of the categories may seem at first sight quite static in the first edition of the CPR. In fact, if we may say that the CPR contains a genetic philosophy, Kant is primarily concerned with the transcendental genesis of experience and with the genesis of transcendental illusion, and not with the production of the pure forms of knowledge. But the precisions brought by the second edition concerning the pure “elements” of knowledge, namely « self-affection » (Aesthetics) and “epigenesis” (§27 of the Deduction), describe a dynamic that was implicitly present in 1781, as the Reflexionen of the 1770s tend to prove it.

Keyphrases: Kant, Opus postumum, Self-constitution, Epigenesis, Self-affection
Hermann Lotze et la genèse de la philosophie des valeurs

Lotze’s influence on the theory of values of the Baden School of Neo-Kantianism (Windelband, Rickert, Lask) can be reconstructed in two steps : 1- Lotze retains from C. H. Weisse’s speculative theism an enlarged conception of the notions of “spirit” and “idea” in order to distance himself from Hegel’s intellectualism; 2- considering aesthetic judgement as a paradigm for the determination of every value, he insists on the role of the “feeling” of pleasure in Kant’s aesthetics, while rejecting its transcendental background. As part of an “immediate” judgment, the predicate of beauty (based on feeling) is paradigmatic in that it overcomes the traditional limitations of the generic concept, and enables a direct grasp of individuality. It is no wonder that the neo-Kantian School of Baden will later focus on an epistemology of the historical sciences.

Keyphrases: Lotze, Weisse, Windelband, Rickert, Idea, Feeling, Aesthetic judgment
L’instauration d’un ordre juridique juste d’après Fichte (1812-1813)

In this article, I compare tow solutions presented by Fichte to the implementation of a just legal order. In fact, in the space of one year, that is: between the Rechtslehre of 1812 and the Staatslehre of 1813, we observe a radical change in Fichte’s answer to this question. He replaces a practical solution with a theoretical one. If in 1812 the best suited person to proceed to this implementation is the one having the purest “will”, the impediments to the realization of this solution lead Fichte, the following year, to chose rather the person who has the most perfect “understanding” and who, thanks to his/her extensive knowledge of the concrete circumstances in which he/she has to exercise power, rules in the most appropriate manner and is therefore the right person to bring people to accept the legal constraint.

Keyphrases: Fichte, Kant, Just ruler, Will, Understanding