NCube/papyrus huggingface dataset:
Implication du facteur NPM1 et du produit de la translocation NPM-MLF1 dans l’expression génique

Nucleophosmine (NPM1) is one of the most frequent altered proteins in hematopoietic disorders. NPM1 exon 12 mutation characterizes one third of all acute myeloid leukemia and can be fundamental to leukemogenesis. This mutation is characterized by the aberrant sequestration of NPM1 to the cytoplasm, the mutated protein is then called NPMc+. NPM1 can also undergo several translocations leading to the synthesis of fusion proteins including NPM-MLF1. The latter is involved in myeloproliferative disorders and in a lower proportion in acute myeloid leukemia. Little is known about this translocation. NPM1 is a multifunctional protein reported to influence gene regulation. The function(s) of NPM1 in gene regulation remains to be defined. The aim of this doctoral research project was to define how NPM1 regulates transcription and determine whether the NPM-MLF1 translocation could disrupt gene regulation imposed by NPM1. In order to determine new protein interaction partners, we purified NPM1 and NPM-MLF1 complexes in the K562 hematopoietic cell line. In a proteomic analysis performed by tandem immunoaffinity purifications followed by mass spectrometry and immunoprecipitation, we identified multiple nuclear protein partners of NPM1 and NPM-MLF1. Importantly, we found that NPM1 and NPM-MLF1 can interact with the chromatin remodeling complexes NuRD, P/BAF and ISWI. An analysis made by Ampli-Sequencing, indicated that multiple genes dysregulated by the decrease expression of NPM1 were also reported to be abnormally expressed in acute myeloid leukemia cells characterized by the NPMc + mutation. We demonstrate that not only NPM1 but also NPM-MLF1 can be recruited to NPM1 regulated genes and affect the chromatin recruitment of the NuRD complex. The variation in NuRD recruitment imposed by NPM1 knockdown or NPM-MLF1 expression, is associated to the abnormal transcriptional regulation of the target genes. We show here that NPM1 and NPM-MLF1 are involved in both gene repression and activation. In a second part of the project, we investigated the physiological importance of gene regulation imposed by NPM1-NuRD in these cells. Importance of the genetic link between NPM1 and the target gene SPARC was defined. Using the CRISPR-Cas9 methodology, we generated unique K562 clones whereby SPARC expression is abrogated and NPM1 expression is decreased. The decrease of NPM1 expression synergizes with the loss of SPARC expression to induce erythroid differentiation and reduce cell invasion. The results presented provide the first demonstration that NPM1 and NPM-MLF1 translocation can interact with chromatin remodeling complexes, influence their recruitment to target genes and thereby, influence the expression of specific genes. This project provides new information to understanding mechanisms affected in acute myeloid leukemia characterized by NPMc+ mutation or NPM-MLF1 translocation.

Keyphrases: NPM, NPM-MLF1, Chromatin remodeling complexes, Transcriptional regulation, Proteomic, Leukemia
Children’s right to “proper education” in contemporary Iran : a critical legal essay with an ethical and empirical approach towards improving Iranian governance

The research takes place in the current daily life of the educational sphere in Iran. It should be noted that Iran is a non-Western and Islamic state, but nonetheless adhered to the rather Western principles of the International Convention on the Rights of the Child. This research is part of a continuity of research in support of human rights. It offers a path of empowerment to Iranian groups open to democracy, but also to educational movements concerned with the fundamental rights of the person. Divided into four chapters, the hybrid questioning of the thesis leads to a critical interdisciplinary essay benefiting the three disciplines of law, philosophy and empirical study. Facing the international and Iranian legal system from a classical legal view, the philosophical chapter tends to respond to the question of “what could be considered not just the right to education, but the right to a “proper” education based in ethical and philosophical grounds in the sense that it would better suit Iranian culture and social habits than an allegedly “universal” [occidental] classical legal conception?". The empirical chapter, then, looks for the “Iranian social representations of the children’s rights that reveal the gap between the ideal expressed concept of “proper education” and day-to-day life of children?” with an advocative approach. From a philosophical view —more precisely from virtue ethics stand point—the thesis proposes the concept of "right to proper education" as a critical approach to the international and internal positions of the right to education for children. "Proper education" is presented as a moral and legal right for children under the category of developmental rights which serves the right to an open future and the right to maximizing self-fulfillment. It is also a conception of the right to education harmonized with the current Iranian Islamic context. From an empirical standpoint, starting from a typical inductive approach of the Human Rights Advocacy approach and based on more than eighty (80) interviews with children and teachers, the gaps between the official laws and the ways in which they are experienced, mobilized, thought of or denied in the sphere of today Iranian education, are observed and analyzed. Finally, the critical legal essay suggests the Iranian governance to be open to a shift toward a modern contractual authority in educational system to be more compatible with the psycho-emotional needs of children and at the same time to apply the virtue ethics political advice to move toward a liberal form of educational policies that promotes the virtues of autonomy and toleration. These are all crucial information for wise Iranian legislative governance rooted in an Islamic pursuit of virtues as well as the happiness of children.

Keyphrases: Children’s right, “Proper education”, Virtue ethics, Human Rights Advocacy, Interdisciplinary and critical essay, Iranian educational system, Iranian-Islamic legislative governance
Youth employment incentives : activation policy in Denmark, France and the United Kingdom (2008-2016)

Youth (15 to 29-year-olds) are vulnerable to economic shocks, and the ability to enter the labour market has significant effects on their long-term wellbeing. Consequently, the 2007-08 financial crisis had the potential to affect youth gravely, which is why welfare states adopted a series of policy initiatives to help youth in the post-crisis. Although countries adopted policies, traditional data such as labour market policy expenditures do not reveal increased spending consistent with higher unemployment levels. Research also shows welfare states have favoured policies that reinforce incentives to join the labour market and help individuals market their skills over more expensive policies that invest in human capital since the financial crisis. These analyses support the argument welfare states are converging around low-cost policies. These pressures notwithstanding, the adoption of similar policies is unusual because the needs between countries remain diverse. For that reason, and despite the factors inhibiting change, countries should not be adopting the same policies to respond to high youth unemployment. This dissertation investigates this complex policy environment by using a typology of activation incentives to compare policy instrument mixes between governments. Process-tracing is then used to determine how welfare states modified their youth employment policies since the financial crisis.  First, qualitative data is used to identify the different policy mixes adopted in each case. Second, the policymaking process is analyzed using process-tracing methods. Research findings indicate all three cases, Denmark, France, and the United Kingdom, adopted new youth policies after the financial crisis. In addition to funding policies that continue typical logics found in each country, evidence shows each case adopted policies that deviate from established logics. These results are explained using three theoretical frameworks to identify mechanisms for change: policy learning, power resources and historical institutionalism. For each case, the dissertation outlines how these factors interacted to affect the policymaking process. This research contributes to welfare state literature by going beyond existing quantitative analysis to provide an in-depth account of youth activation policies and the policymaking process in the post-crisis.

Keyphrases: activation, comparative welfare state, youth, transition policy, labour market policy, institutional change
Les réseaux de trafic de drogue à Genève, Suisse : application des outils d'analyse de réseaux sociaux

This Masters project focuses on the application of social network analysis (SNA) methods on drug trafficking network cases in Geneva, Switzerland. Two general objectives guide the research. The first is to expand empirical knowledge on the use of SNA techniques in police investigations; the second is to offer practical recommendations in order to optimize police interventions in drug trafficking cases. Two drug networks are analyzed, a cocaine-trafficking network (LITOS) and a heroin-trafficking network (VRAN), both of which were investigated by the main drug squad of the Geneva cantonal police. Specific objectives include evaluating the structure of these two networks, identifying key players, and measuring network dismantlement potential. Actor and tie attributes are also examined, including the importance of ethnic, familial and intimate ties.   Results show that both networks adopt scale-free properties, and are centralized around traffickers of the network core. Both networks also tend to form cliques that are dominated by core actors, themselves often linked by familial and intimate ties. In both networks, the most central actors are also the main brokers. However, the LITOS network also has a broker positioned more strategically, and who’s position seemed to have protected him from being arrested. Regarding network dismantlement, analyses show that both networks can be completely fragmented, isolating all remaining actors. When comparing these results with the arrests actually carried out by the police, it seems that investigators in the LITOS case managed to dismantle this cocaine network almost entirely, and arrested most of the key players. In the VRAN case, the arrests made did have a considerable impact on network fragmentation, but dismantlement wasn’t complete, as investigators failed to apprehend some of the most important traffickers. Furthermore, the two cases studied suggest that a comparative advantage may be present for certain ethnic minorities in drug trafficking enterprises, and reveal the importance of family and intimate ties between traffickers as regards to network structure and functioning. From these results and their interpretation, this study closes with five practical recommendations for drug-trafficking network investigations.

Keyphrases: Social network analysis, Drug trafficking, Police data, Network dismantlement, Crime analysis
Changements comportementaux et neuro-anatomiques suite à un entrainement aérobie chez les individus atteints de la maladie de Parkinson

Parkinson’s disease (PD) is the second most common neurodegenerative disease in Canada and other industrialized countries. The pathology is characterized by motor symptoms such as resting tremor, muscle rigidity, difficulty in initiating voluntary gestures and slowness in the execution of movements (i.e. bradykinesia). Non-motor symptoms, such as cognitive impairment, sleep disorders and others are commonly encountered. To date, physical activity has been an interesting complement to existing pharmacological and neurosurgical treatments to relieve the symptoms of PD. However, despite the knowledge gained so far about the impact of physical exercise in patients with the disease, it is possible to note that many questions remain unanswered or unclear. This work is part of a larger research project that aims to fill some of theses gaps. More specifically, the main objective of this thesis is to evaluate the effects of an aerobic training in a population with PD on walking parameters, upper limb mobility and anatomical brain structures. A second objective is to observe the relationships existing between these three components, and with other parameters such as the improvement of aerobic capacities, the executive functions and the learning capacities of a new motor skill. 20 healthy adults and 19 persons with PD participated in a 3-month stationary recumbent bicycle training program, with 3 sessions per week during which the duration (20 to 40 minutes) and intensity (60 to 80%) were increased gradually. Several measures such as walking pattern, upper limb function, executive functions, learning of a new motor skill, aerobic capacities (VO2 peak), motor symptoms of PD and magnetic resonance imaging were acquired before and after the exercise program. The results showed that a 3-month training on stationary bike is beneficial for people with PD. Indeed, this type of exercise can increase the cadence and walking speed. It is also possible III to reduce the antagonist force, in addition to improve the propagation of this neuromuscular signal, generally improving the mobility of the upper limb. Finally, an aerobic exercise of 3 months can also increase the volume of certain brain structures, such as globus pallidus. This research project is among the first to demonstrate the effectiveness of a stationary bicycle aerobic exercise program to improve gait parameters and upper limb function in persons with PD. This study is also the first to investigate the effects of exercise on the brain structures of these patients and to try to understand the mechanisms that underlie improvements in motor and non-motor symptoms following a moderate to high intensity exercise program. We believe that the results obtained will help physical activity specialists to provide a more tailored and varied exercise prescription for people living with Parkinson’s disease.

Keyphrases: Parkinson's disease, Aerobic exercise, Walking pattern, Executive functions, Upper limb, Neuroimaging
Rôle de l’attention lors de la recherche visuelle : mesures électrophysiologiques

The overarching thesis was to understand better the relationship between the deployment of visual spatial attention and the eventual response during visual search. We combined mental chronometry with electrophysiological measures, allowing us to track the temporal sequence of events and bisect processing into sub-phases. The two first studies used the N2pc, an event-related potential (ERP) component, as an electrophysiological marker of visual attention to laterally presented stimuli using a pop-out (i.e., the target stands out) visual search task. The N2pc is characterised by an enhanced negativity emerging around 200 ms after the display onset at posterior sites contralateral to the attended visual field. In Study 1, we first evaluated the relationship between the N2pc component and the moment of response. Electrophysiological data were split according to the response time (RT) median. The N2pc was larger for both fast compared with slow trials and participants, suggesting that a more efficient deployment of attention (larger N2pc) sped up downstream processing (shorter RTs). In Study 2, processing from the deployment of attention to the response was elucidated by examining N2pc onset relative to the response instead of to the display onset. We pioneered the use of the RLpcN (response-locked contralateral negativity), composed of the N2pc and the SPCN (a component following the N2pc and reflecting processing of task-relevant stimuli in visual short-term memory). Importantly, more time passed between RLpcN onset and the response for longer RTs, reflecting more processing time following the onset of visual spatial attention. We then used this component to study difficult search (Study 3), where the target was not easily located, using experimental manipulations designed to modulate the RLpcN. We showed that when there were more items present in the visual field or response selection was more difficult, there was a longer duration between RLpcN onset and the response, demonstrating that it is possible to observe activity associated with specific processes during difficult visual search. In summary, we provide evidence that (1) a more efficient deployment of attention speeds up downstream processing, (2) processing determining RTs occurs, in majority, following the deployment of attention, and (3) it is possible to identify electrophysiological markers of target and response selection during difficult search. Together, the results of these experiments go beyond typical electrophysiological experiments of visual search, which use pop-out targets, and elucidate the time course of processing during more complex search.

Keyphrases: N2pc, SPCN, RLpcN, Electrophysiology, Visual spatial attention, Event-related potential, Visual short-term memory
Le rôle adaptatif de la tristesse dans le deuil d’un parent chez l’endeuillé adulte

Normal, or resilient, grief has often been neglected in the literature, overshadowed by the greater number of studies on pathological grief. This fact, congruent with the trend towards a culture of medicalization, can explain the normalization of the idea of grief as uselessly painful, or even harmful, a nuisance to productivity and functioning. On the other hand, there has been a growing interest in the processes of normal grief in recent years, the idea that resilient grief is more common than pathological grief having only been recently supported by empirical research (Bonanno, 2009). However, the function and nature of grief-related emotions, which are often seen as symptoms, still isn’t clear. Sadness, contrarily to common knowledge, seems to be a healthy characteristic of resilient grief, and could have an adaptive function, whereas distress and depression would evoke the protest and despair phases of the separation between the child and her attachment figure. Thus, these three affective experiences would be qualitatively, and not only quantitatively, distinct. This thesis aims to present, in its first part, a theoretical model of both resilient and pathological grief, elaborating on the function and place of sadness, distress and depression. These two types of grief are presented as the extremes of a continuum, in between which any number of variations could exist. Sadness, in this model, is depicted as a useful emotion that plays a part in the acceptation of loss and in the creation of a meaning. In its second, empirical part, the subjective experience of sadness in resilient grieving adults who lost a parent is observed. Semi-structured interviews were conducted with six participants, and the results were analyzed using Interpretative Phenomenological Analysis (IPA). Results show that sadness was experienced as tolerable, adaptive, and making sense, even if it was painful. As grief is never an isolated experience in life, circumstances and concurrent events, and variations in mentalization abilities, can explain the presence of other emotions or of somatic symptoms. Sadness, however, seems to be an essential ingredient of resilient grief, where the person remains functional, but is sad only by shorts bursts, coming in waves. The clinical and diagnostic implications of these results and of the theoretical model presented in this thesis are discussed.

Keyphrases: Tristesse adaptative, Resilient grief, Pathological grief, Grief, Sadness, Adaptive sadness, Function of sadness, Distress, Depression, Emotions, Emotion regulation, Mentalization, Interpretative phenomenological analysis
L'impact des variables sémantiques sur le traitement des mots

Over the past decade, research has shown that word processing is influenced by the orthographic, lexical, and semantic features of words. High values of semantic variables, such as conceptual familiarity, imageability, concreteness and sensory experience, are usually associated with faster and more accurate word processing as, for instance, measured with a written lexical decision task. However, norms for crucial semantic variables, such as conceptual familiarity, and another new variable of modality specific perceptual strength, are not available for a large set of French words. This thesis presents norms for conceptual familiarity, visual and auditory perceptual strength for 3,596 French words. We collected these norms from approximately 300 healthy participants, all French-Canadian native speakers, between 18 and 35 years of age. Descriptive statistics and correlational analyses were conducted on these norms and on other known subjective variables (age of acquisition, imageability, concreteness) and objective variables (number of letters, objective frequency). Correlation analyzes revealed the semantic nature of our variables. More specifically, values of visual and auditory perceptual strength have shown a strong relationship with semantic variables. This highlights the importance of the role of perceptual experience in the conceptual representation of words. We then demonstrated the usefulness of these new norms of conceptual familiarity and perceptual strength by evaluating their impact on latencies in a written lexical decision task. Using stepwise regression models, conceptual familiarity and perceptual strength demonstrated independent contribution to latencies, beyond the contribution of other well-known psycholinguistic variables, such as word length, frequency, imageability, age of acquisition and concreteness. The databases developed in these studies are a meaningful contribution to future studies that will shed further light on the interaction between the linguistic, semantic and perceptual systems. These studies will help researchers to select French stimuli with specific psycholinguistic characteristics for experiments in which conceptual familiarity and perceptual strength must be taken into account. These norms will also have a broad area of use, such as research in human health sciences and the creation of teaching materials and language assessment tests.

Keyphrases: Norms, Psycholinguistic variables, Semantics, Conceptual familiarity, Visual and auditory perceptual strength, Lexical decision, Regression, Sensory experience, Conceptual representation, Perceptual experience