TDP-43 est une protéine de liaison aux acides nucléiques qui joue un rôle essentiel dans le métabolisme de l'ARN. À l'état physiologique, un contrôle strict des niveaux d’expression de cette protéine est critique pour la fonction et la survie cellulaire. Une boucle d'autorégulation négative est à la base de ce contrôle du taux intracellulaire de TDP-43. Laquelle a été identifiée comme le constituant principal des inclusions observées chez une majorité des patients atteints de Sclérose Latérale Amyotrophique (SLA) ou de Dégénérescence Lobaire Fronto-Temporale (DLFT). A ce jour, plus de 50 mutations faux-sensdu gène TARDBP/TDP-43 ont été décrites chez des patients DLFT/SLA, démontrant le rôle clé de TDP-43 dans ces pathologies neurodégénératives. Notons cependant que les conséquences fonctionnelles de ces mutations ne sont pas complètement déterminées. Plusieurs études suggèrent qu’une élévation des niveaux d’accumulation de TDP-43 pourraitparticiper aux mécanismes physiopathologiques. La modulation du cycle de production de TDP-43 pourrait donc constituer une nouvelle stratégie thérapeutique. Ce travail de recherche avait donc pour principal objectif d’identifier des modulateurs génétiques de la production de TDP-43 en utilisant un nouveau modèle de drosophile transgénique mimant les principales étapes d’autorégulation de TDP-43. Nous avons ainsi pu montrer que la modulation des niveaux d’expression de la protéine TCERG1 et de plusieurs facteurs d'épissage, parmi lesquels SRSF1, SRSF3 et SF3B1, influe sur les niveaux de production deTDP-43. Nous avons également montré que la présence des mutations DLFT/SLA n’altère pas la capacité de la protéine à s’autoréguler. / TDP-43 is a DNA/RNA binding protein that plays an important role in RNA metabolism. In the physiological state, strict control of its expression levels is critical for cell function and survival. TDP-43 expression is tightly regulated through an autoregulatory negative feedback loop. This protein has been identified as the principal component of the inclusions observed in a majority of patients with Amyotrophic Lateral Sclerosis (ALS) or FrontoTemporal Lobar Degeneration (FTLD). To date, more than 50 missense mutations of the TARDBP / TDP-43 gene have been described in FTLD / ALS patients, demonstrating the key role of TDP-43 in these neurodegenerative pathologies. However, the functional consequences of TDP-43 mutations are not completely determined. Several studies suggest that high accumulation levels of TDP-43 may participate in pathophysiological mechanisms. The modulation of the production cycle of TDP-43 may therefore provide a new therapeutic strategy. The main goal of this research project was to identify genetic modulators of TDP-43 production by using a novel transgenic Drosophila model mimicking main steps of TDP-43 the autoregulatory mechanism. We identified several splicing factors, including SF2, Rbp1 and Sf3b1, as genetic modulators of TDP-43 production. We have also shown that modulation of TCERG1 expression levels affect TDP-43 production levels in flies. Finally, we found that FTLD/ALSlinked TDP-43 mutations do not alter TDP-43’s ability to self-regulate its expression and consequently of the homeostasis of TDP-43 protein levels.

This is a study that employs error analysis to investigate written production in English, by Swedish upper secondary learners of English, in order to determine which linguistic errors most commonly occur amongst this group, and to compare the results between first-year students and third-year students for a possible indication of which error types continue to occur throughout upper secondary school. The error categories included in this study are grammatical errors and errors as a result of transfer. The variable of gender will also be taken into account, due to the statistics and previous research that show female students tend to achieve higher results in academics. The purpose of the study is to gain a better understanding of how Swedish upper secondary learners acquire English, and to uncover which areas are most challenging for them, in the hopes of highlighting areas within ELT that may need revision. The participants of the study are students attending Swedish upper secondary schools, year 1 and 3. The analyzed data was collected from the Uppsala Learner English Corpus (ULEC), which consists of texts produced by Swedish learners of English attending middle school and upper secondary school.     The results show that certain error categories and types are consistently challenging for both first-year students and third-year students, which provides an indication of which areas in ELT might be lacking. Within the grammatical error category, all groups demonstrated a significant lack of knowledge pertaining to subject-verb agreement, as well as prepositions, which are both to a certain degree attributed to the first language; meaning, they may be the result of transfer. The male students were shown to outperform the female students; however, the female third-year students produced fewer errors than their male counterparts, which suggests a faster progression. The male third-year students were shown to have the same error rate as the male first-year students, which suggests a slower progression. While the third-year students produced fewer errors overall, the error types they struggled the most with are the same error types most commonly occurring in the first-year group, suggesting pedagogical remediation is needed.

This essay aims to investigate theoretically how two currently used coursebooks, What’s Up 9 and Solid Gold 1, in a local area of Southern Sweden, present (introduces and covers) grammar. The overall aim is to investigate how grammar is presented, using the present simple and the present continuous as examples. The findings are also mapped to teaching approaches, as well as SLA (Second Language Acquisition) research, to see what approaches are favoured for teaching grammar in the first decades of the 21st century. In order to investigate the course- books, a qualitative content analysis and conceptual analysis was chosen with the presentation of grammar mapped into different categories, by using concepts for teaching and approaches used in SLA. The results show that the two proposed coursebooks favoured a FoFs (Focus on Forms) approach for presenting grammar. Furthermore, the results show that grammar is pre- sented explicitly and, if the teachers use the structures proposed in the coursebook rigidly, they automatically follow a deductive teaching procedure. When using a FoFs, explicit instructions and taking a deductive teaching approach, it may be regarded as the coursebooks suggest a grammar-translation approach as well. However, when observing other exercises connected to the reading texts in the coursebooks, it was detected that both coursebooks favoured a text- based approach for teaching, where the learners are supposed to learn the structure of different texts. In doing so, the grammatical structures are learned subconsciously and implicitly, which indicates that grammar is, in general, taught implicitly in the coursebooks, but presented (intro- duced and covered) explicitly.

No description available.

This study investigates spelling errors among Swedish students of English. The purpose of this research is to develop a better understanding of the causes of spelling errors and to investigate whether there are any differences between program orientation and gender. The participants are English A students from Swedish high schools in year 1. The data analysed in this study consists of essays written by the participants which have been gathered into the Uppsala Learner English Corpus (ULEC). The results showed that the academic program has a lower error rate when compared to the vocational program and that female students display a lower error frequency than male students. These results reflect the same pattern found by previous studies on achievement between the programs and across gender. However, when comparing all variables, both gender and program, the results demonstrate that academic male students had the lowest error rate of all groups, which could partially be explained by the fact that the academic male students have a higher level of engagement with video- and online games when compared to the other groups. The language processes that the participants found the most challenging were letter omission, letter insertion and letter substitution. These results follow the same pattern highlighted in previous studies on spelling among both native speakers and learners. Finally, the exchange between the vowels <a>, <e> and <i> was found to be a frequent error among the students. Experiencing difficulties with the correct usage of vowels can be explained as a transfer error.

Learner beliefs, which contribute to attitude and motivation, may affect language learning. It is therefore valuable to investigate the malleability of learner beliefs, and to determine whether potentially detrimental beliefs can be ameliorated. This study examines how instruction of the principles of Second Language Acquisition (SLA) affects students' beliefs about classroom activities and their beliefs about language learning in general. The 68 first-year German students at Brigham Young University who participated in this study were asked to rate the effectiveness of three activities typical of communicative language teaching: Dialogue activities, Peer Interview activities, and Information-gap activities. They were also asked to respond to 11 statements about language learning, seven of which were taken from the Beliefs About Language Learning Inventory(Horwitz, 1988). Students responded to the survey three times: once during the first week of the semester, again during the fourth week, and again during the eighth week. During the four weeks between the second and third surveys, students in the experimental group received seven treatment lessons based on some of the basic principles of SLA. A Repeated Measures ANCOVA and a Logistical Regression were used to determine the effects of the treatment, time, and a number of demographic variables. Results of this study show that the treatment did not have a significant effect on any of the beliefs that were measured. However, one language learning belief was significantly affected by time. A majority of the students who participated in this study agreed with the statement, “The instructor should teach the class in German.” After three weeks of class instruction, however, they agreed with this statement significantly stronger. The results of this study also show that many of the demographic variables, such as gender and previous language learning experience, had a significant effect on a number of the students' beliefs.

No description available.

In the Manufacturing Industry there is a subset of technologies referred to as Rapid Technologies which are those technologies that create the ability to compress the time to market for new products under development . Of this subset, Additive Fabrication (AF), or more commonly known as Rapid Prototyping (RP), acquires much attention due to its unique and futuristic approach to the production of physical parts directly from 3D CAD data, CT or MRI scans, or data from laser scanning systems by utilizing various techniques to consecutively generate cross-sectional layers of a given thickness upon the previous layer to form 3D objects. While Rapid Prototyping is the most common name for the production technology it is also referred to as Additive Manufacturing, Layer Based Manufacturing, Direct Digital Manufacturing, Free-Form Fabrication, and 3-Dimensional Printing. With over 35 manufacturers of Additive Fabrication equipment in 2006 , the selection of an AF process and material for a specific application can become a significant task, especially for those with little or no technical experience with the technology and to add to this challenge, many of the various processes have multiple material options to select from . This research was carried out in order to design and construct a system that would allow a person, regardless of their level of technical knowledge, to quickly and easily filter through the large number of Additive Fabrication processes and their associated materials in order to find the most appropriate processes and material options to create physical reproductions of any part. The selection methodology used in this paper is a collection of assumptions and rules taken from the author's viewpoint of how, in real world terms, the selection process generally takes place between a consumer and a service provider. The methodology uses those assumptions in conjunction with a set of expert based rules to direct the user to a best set of qualifying processes and materials suited for their application based on as many or as few input fields the user may be able to complete.

This case study research aimed to explore, understand, and compare the experiences of individuals participating in a heterogeneous adult community drama class in Central Sweden. Drawing from classical pragmatism and employing a conceptual framework rooted in sociocultural theory, the study utilized semi-structured interviews, open-questionnaire responses, and participant observations to collect data which was analyzed through reflexive thematic analysis. Key findings indicated that participants generally viewed their engagement in the class positively while also recognizing the challenges and complexities of working within a mixed-language level group. As such, participants identified diverse motivations and preferences which informed their expectations and impressions of participation. As well, Swedish L2 learners of various levels and Swedish L1 speakers identified distinct challenges and opportunities in relation to learning and navigating language within the class context. Despite identified challenges, the high degree of group diversity emerged as a centrally important and beneficial feature of participation by facilitating opportunities to learn and assist one another in a supportive community environment through mediation. Subsequently this paper offers recommendations for transferable contexts to mitigate language-related challenges based on participant accounts and observations. Moreover, this study seeks to contribute to the fields of comparative education and applied drama through its focus on exploring and examining possibilities and consequences of heterogenous group learning among adults and in a community drama class. Consequently, the results of the study may be useful in adult education settings, applied drama contexts, and among policymakers interested in exploring participatory learning approaches, particularly in relation to supporting migrant individuals and migrant integration.

Les protéines de liaison à l'ARN (PLA) s'assemblent en complexes cytoplasmiques avec les ARNm pour contrôler la traduction locale des ARNm et le transport axonal. Ces processus sont essentiels au maintien de la survie des neurones et leur déficience est impliquée dans le développement de nombreuses maladies neurodégénératives, telles que la SLA. Il a été montré ultérieurement que la déplétion nucléaire de TDP-43, liée à la SLA, entraîne l'accumulation d'une variante épissée alternativement de la ribonucléoprotéine nucléaire hétérogène A1 (hnRNP A1). Cette isoforme, appelée hnRNP A1B, possède une région désordonnée (RID) et, dans le contexte neuronal, localise dans les neurites et dans le noyau, alors que la hnRNP A1 localise majoritairement dans le noyau. Ceci appui l'hypothèse que la hnRNP A1B peut avoir une fonction cytosolique dans les neurones qui n'est pas partagée avec la hnRNP A1. En outre, les hnRNP A1 et hnRNP A1B sont mutées dans de rares cas de SLA familiale, dont certaines mutations sont spécifiques à la hnRNP A1B. Jusqu'à présent, la littérature se concentre sur l'isoforme hnRNPA1 tandis que peu est répertorié sur la fonction de la hnRNP A1B. Ainsi, cette étude vise à déterminer et caractériser la fonction cytosolique de la hnRNP A1B dans les neurones. Puisque très peu est répertorié sur la hnRNP A1B, il a fallu tout d’abord déterminer des partenaires d’interaction. Ainsi, une immunoprécipitation utilisant un anticorps spécifique à la hnRNP A1B suivi d'une spectrométrie de masse (IP-MS) a été réalisée sur la moelle épinière de souris. Les résultats soulèvent que de nombreux interacteurs de la hnRNP A1B sont associés au trafic intracellulaire dépendant du cytosquelette. Les interactions avec KLC1/KIF5C/Myh9/DyncIHI ont été validées par des tests d'immunoprécipitation et de colocalisation. Aussi, l’impact de certains mutants hnRNP A1B associés à la SLA ont été étudiées au niveau des interactions avec les protéines motrices. Des expériences visant à évaluer comment la hnRNP A1B peut être transportée, ainsi que réguler le transport, sont en cours. Les résultats confirment que la hnRNP A1B peut avoir une fonction cytosolique dans les neurones pour le transport axonal/dendritique de l'ARNm. Des études futures exploreront cette nouvelle fonction dans le contexte de la SLA. / RNA-binding proteins (RBPs) assemble into cytoplasmic complexes with mRNAs to control mRNA local translation and axonal transport. These processes are essential for maintaining neuronal survival and their impairment is implicated in the development of many neurodegenerative diseases, such as ALS. We have discovered that TDP-43 depletion, linked to ALS, drives the accumulation of an alternatively spliced variant of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1). This isoform, termed hnRNP A1B, has an elongated prion-like domain (PrLD) and is present in neuronal processes, while hnRNP A1 is not. This finding supports a hypothesis that hnRNP A1B may have a cytosolic function in neurons that is not shared with hnRNP A1. In addition, hnRNP A1 and hnRNP A1B are mutated in rare cases of familial ALS with some mutations specific to hnRNP A1B. To date, the literature has mostly focused on the hnRNPA1 isoform and little is known about hnRNP A1B function. Thus, this study aims to identify and characterize the cytosolic function of hnRNP A1B in neurons. Since very little is known about hnRNP A1B, it was first necessary to identify interaction partners of the protein. Thus, immunoprecipitation using an antibody specific to hnRNP A1B followed by mass spectrometry (IP-MS) was performed on mouse spinal cord. Our results show that many hnRNP A1B interactors are associated with cytoskeletal-dependent intracellular trafficking. We then proceed to validate the interactions with the motor proteins KLC1/KIF5C/Myh9, by immunoprecipitation and proximity ligation assays. In addition, some hnRNP A1B ALS mutants were studied in the context of these interactions. Experiments to evaluate how hnRNP A1B may be transported, as well as regulate transport are currently underway. Our findings support that hnRNP A1B may have a cytosolic function in neurons in mRNA axonal/dendritic transport. Future studies will explore this novel function in the ALS context.