Understanding the role of CAP proteins in the polarization process of C. elegans

La division cellulaire asymétrique est un processus crucial dans le développement des organismes multicellulaires puisqu’elle permet la génération de la diversité cellulaire. Les cellules qui se divisent de façon asymétrique doivent tout d’abord se polariser et correctement orienter leur fuseau mitotique pour ségréger des déterminants cellulaires en deux entités distinctes. L’embryon du nématode C. elegans est un modèle robuste et largement utilisé pour étudier la division cellulaire asymétrique. Dans cet embryon, le point d'entrée du spermatozoïde détermine l'axe de polarité antéro-postérieur. Suite à la fécondation, le cortex embryonnaire est uniformément contractile et un complexe conservé formé des protéines PAR-3, PAR-6 et PKC-3 (nommé complexe PAR-3 ci-dessous) est localisé sur l'ensemble du cortex. La complétion de la méiose maternelle induit une relaxation corticale au postétieur et un flux cortical vers l’antérieur de l’embryon. Ces contractions corticales asymétriques mènent à la formation d'un domaine antérieur contenant le complexe PAR-3, tandis que le cortex postérieur, dont le complexe PAR-3 s’est délocalisé, est enrichi avec les protéines PAR-2 et PAR-1. Par conséquent, les domaines formés par les protéines PAR définissent un pôle antérieur et un pôle postérieur dans l'embryon suite au remodelage du cytosquelette. Les protéines PAR-4 et PAR-5 restent localisées de façon uniforme dans l'embryon. Curieusement, les protéines PAR exercent une régulation par rétroaction sur la contractilité corticale. Il a été montré qu’une des protéines PAR récemment identifiée, PAR-5, est orthologue à la protéine adaptatrice 14-3-3 et joue un rôle important dans la contractilité corticale. En dépit de son rôle central dans la contractilité corticale et le processus de polarisation cellulaire, le mécanisme par lequel PAR-5 régule la contractilité corticale n’est pas bien compris. Le but de ce projet est de mieux comprendre comment PAR-5 et ses interacteurs contrôlent la régulation des contractions corticales et, de ce fait, la polarité cellulaire. Dans un essai de capture de la protéine GST (GST pull-down), nous avons identifié plusieurs nouveaux interacteurs de PAR-5. Parmi ceux-ci, nous avons trouvé CAP-2 (protéine de coiffage de l'actine), qui a été identifiée dans des éxpériences de capture de 14-3-3 dans trois systèmes modèles différents. CAP-2 est un hétérodimère des protéines CAP, qui sont impliquées dans la régulation de l'actine. Nous avons trouvé que la déplétion des protéines CAP par interférence à l’ARN dans des vers de type sauvage mène à une augmentation létalité embryonnaire, ce qui suggère que ces protéines jouent un rôle important dans le développement embryonnaire. L'imagerie en temps réel d'embryons déplétés pour les protéines CAP montre qu’ils ont une diminution des contractions corticales avec un sillon de pseudoclivage mois stable, suggérant un défaut dans la régulation du cytosquelette d'actine-myosine. Ceci a également été confirmé par la diminution de la vitesse et du nombre de foci de NMY-2::GFP. En outre, ces embryons montrent une légère diminution de la taille du croissant cortical de PAR-2 lors de la phase d’établissement de la polarité. Les embryons déplétés en CAP-2 montrent également un retard dans la progression du cycle cellulaire, mais le lien entre ce phénotype et la régulation des contractions corticales reste à être précisé. La caractérisation des protéines CAP, des régulateurs du remodelage du cytosquelette, permettra d'améliorer notre compréhension des mécanismes qui sous-tendent l'établissement et le maintien de la polarité cellulaire, et donc la division cellulaire asymétrique.

The Planned and the Emergent: An Alternative Model of Learning and Literacy

Within academic institutions, writing centers are uniquely situated, socially rich sites for exploring learning and literacy. I examine the work of the Michigan Tech Writing Center's UN 1002 World Cultures study teams primarily because student participants and Writing Center coaches are actively engaged in structuring their own learning and meaning-making processes. My research reveals that learning is closely linked to identity formation and leading the teams is an important component of the coaches' educational experiences. I argue that supporting this type of learning requires an expanded understanding of literacy and significant changes to how learning environments are conceptualized and developed. This ethnographic study draws on data collected from recordings and observations of one semester of team sessions, my own experiences as a team coach and UN 1002 teaching assistant, and interviews with Center coaches prior to their graduation. I argue that traditional forms of assessment and analysis emerging from individualized instruction models of learning cannot fully account for the dense configurations of social interactions identified in the Center's program. Instead, I view the Center as an open system and employ social theories of learning and literacy to uncover how the negotiation of meaning in one context influences and is influenced by structures and interactions within as well as beyond its boundaries. I focus on the program design, its enaction in practice, and how engagement in this type of writing center work influences coaches' learning trajectories. I conclude that, viewed as participation in a community of practice, the learning theory informing the program design supports identity formation —a key aspect of learning as argued by Etienne Wenger (1998). The findings of this study challenge misconceptions of peer learning both in writing centers and higher education that relegate peer tutoring to the role of support for individualized models of learning. Instead, this dissertation calls for consideration of new designs that incorporate peer learning as an integral component. Designing learning contexts that cultivate and support the formation of new identities is complex, involves a flexible and opportunistic design structure, and requires the availability of multiple forms of participation and connections across contexts.

Understanding the role of CAP proteins in the polarization process of C. elegans

La division cellulaire asymétrique est un processus crucial dans le développement des organismes multicellulaires puisqu’elle permet la génération de la diversité cellulaire. Les cellules qui se divisent de façon asymétrique doivent tout d’abord se polariser et correctement orienter leur fuseau mitotique pour ségréger des déterminants cellulaires en deux entités distinctes. L’embryon du nématode C. elegans est un modèle robuste et largement utilisé pour étudier la division cellulaire asymétrique. Dans cet embryon, le point d'entrée du spermatozoïde détermine l'axe de polarité antéro-postérieur. Suite à la fécondation, le cortex embryonnaire est uniformément contractile et un complexe conservé formé des protéines PAR-3, PAR-6 et PKC-3 (nommé complexe PAR-3 ci-dessous) est localisé sur l'ensemble du cortex. La complétion de la méiose maternelle induit une relaxation corticale au postétieur et un flux cortical vers l’antérieur de l’embryon. Ces contractions corticales asymétriques mènent à la formation d'un domaine antérieur contenant le complexe PAR-3, tandis que le cortex postérieur, dont le complexe PAR-3 s’est délocalisé, est enrichi avec les protéines PAR-2 et PAR-1. Par conséquent, les domaines formés par les protéines PAR définissent un pôle antérieur et un pôle postérieur dans l'embryon suite au remodelage du cytosquelette. Les protéines PAR-4 et PAR-5 restent localisées de façon uniforme dans l'embryon. Curieusement, les protéines PAR exercent une régulation par rétroaction sur la contractilité corticale. Il a été montré qu’une des protéines PAR récemment identifiée, PAR-5, est orthologue à la protéine adaptatrice 14-3-3 et joue un rôle important dans la contractilité corticale. En dépit de son rôle central dans la contractilité corticale et le processus de polarisation cellulaire, le mécanisme par lequel PAR-5 régule la contractilité corticale n’est pas bien compris. Le but de ce projet est de mieux comprendre comment PAR-5 et ses interacteurs contrôlent la régulation des contractions corticales et, de ce fait, la polarité cellulaire. Dans un essai de capture de la protéine GST (GST pull-down), nous avons identifié plusieurs nouveaux interacteurs de PAR-5. Parmi ceux-ci, nous avons trouvé CAP-2 (protéine de coiffage de l'actine), qui a été identifiée dans des éxpériences de capture de 14-3-3 dans trois systèmes modèles différents. CAP-2 est un hétérodimère des protéines CAP, qui sont impliquées dans la régulation de l'actine. Nous avons trouvé que la déplétion des protéines CAP par interférence à l’ARN dans des vers de type sauvage mène à une augmentation létalité embryonnaire, ce qui suggère que ces protéines jouent un rôle important dans le développement embryonnaire. L'imagerie en temps réel d'embryons déplétés pour les protéines CAP montre qu’ils ont une diminution des contractions corticales avec un sillon de pseudoclivage mois stable, suggérant un défaut dans la régulation du cytosquelette d'actine-myosine. Ceci a également été confirmé par la diminution de la vitesse et du nombre de foci de NMY-2::GFP. En outre, ces embryons montrent une légère diminution de la taille du croissant cortical de PAR-2 lors de la phase d’établissement de la polarité. Les embryons déplétés en CAP-2 montrent également un retard dans la progression du cycle cellulaire, mais le lien entre ce phénotype et la régulation des contractions corticales reste à être précisé. La caractérisation des protéines CAP, des régulateurs du remodelage du cytosquelette, permettra d'améliorer notre compréhension des mécanismes qui sous-tendent l'établissement et le maintien de la polarité cellulaire, et donc la division cellulaire asymétrique.

Internationalization process of TUBOFURO

The central objective of this case study was to formulate the strategy of internationalization of Tubofuro®, discriminating relevant points from its design to its implementation. This is a company located in Leiria, Ortigosa parish, which operates, among others, in the Portuguese PVC pipes industry for which currently the domestic market is clearly insufficient, given the oversupply compared to demand. Being Tubofuro® an exporting company since 2004, the work here developed specifically intended to increase sales to the foreign market, with this representing 45% of total company's business in 2018 increasing of the number of markets through new partners to enable the positioning of Tubofuro® among the main players in each market, particularly in South American markets, North African and European. To achieve the above objectives presented a case study was applied, centred on Tubofuro® company, target of the internationalization strategy. The search carried out for the formulation of the strategy has been supported on a thorough analysis of the external environment and internal characteristics of the company, for which were crossed different types of data, quantitative, qualitative, secondary data and primary data. From this work resulted the development of internationalization and international marketing plan for the next three years, whose objectives are based on entrance and consequent growth in new markets, including the market Chilean, Peruvian, Mexican, Argentine, Algerian and German, as well growth in the presence and turnover in the markets for which Tubofuro® already exports regularly, for example Spain, France, Tunisia and Morocco. Based on the production capacity of Tubofuro® company, which will not suffer any kind of investment for incrementing but only to update, it is expected that the appropriate response capacity for the company is 8 regular markets, and could eventually arise sporadic exports to other markets not interfering with the normal production capacity of the company. The suggestion of the presented markets resulted from the study of the final price based on the one that local customers purchase a product equal or similar to Tubofuro® and the number of potential existing customers in each market. The internationalization model known as Uppsala Model corresponds to the strategy adopted by the company to its internationalization process, taking into account the philosophy of senior management and the risk aversion of them. The sales team Tubofuro® demand for each market, export a full container registering customer feedback, including quality and flow capacity in the market in order to seek a partnership agreement with a local distributor, which allows the Tubofuro® go to step two above mentioned model. The partnership agreement is based on mutual commitment to technical cooperation and trade between the Tubofuro® and partner, in order to increase the performance capacity among local customers. Only if the market presents a greater demand to our supply capacity and be justified by cost / benefit ratio, the entry into this market through a joint venture or subsidiary is that the decision will be taken. Although this is a case study, which means that is adjusted to the concrete case Tubofuro® preventing generalization of findings, we believe that this work can be a useful example for other companies in the internationalization process or the methodology adopted in formulating strategy or the outputs and conclusions drawn.

Leadership and Pedagogical Interaction as Predictors of Learning Outcomes in Physical Education

This research aims to understand the relative contribution of leadership styles and teacher-student and student-student pedagogical interaction concerning learning performance and academic achievement in Physical Education. A quantitative methodology was implemented, comprising a sample of 447 students attending a school grouping located in the coastal region of central Portugal. In order to verify the nature, the strength and the direction of the relations among the variables, correlation and multiple regression analyses were used. For this, scales already validated and used in other researches were applied. The results show that the learning performance and the academic achievement are significantly associated with teacher leadership styles and teacher-student and student-student pedagogical interaction. A stronger association was obtained with leadership styles, especially the democratic one. It should be mentioned that these factors provide a higher relative contribution to the learning performance than to the academic achievement. The analysis conducted highlights the importance of the democratic teacher leadership style and of the pedagogical interaction established within the classroom towards the improvement of students’ ability to understand the gains and the effort made in learning.

The complexity in the implementation process of empowerment-based chronic kidney care: a case study

Background: This study is part of an interactive improvement intervention aimed to facilitate empowerment-based chronic kidney care using data from persons with CKD and their family members. There are many challenges to implementing empowerment-based care, and it is therefore necessary to study the implementation process. The aim of this study was to generate knowledge regarding the implementation process of an improvement intervention of empowerment for those who require chronic kidney care. Methods: A prospective single qualitative case study was chosen to follow the process of the implementation over a two year period. Twelve health care professionals were selected based on their various role(s) in the implementation of the improvement intervention. Data collection comprised of digitally recorded project group meetings, field notes of the meetings, and individual interviews before and after the improvement project. These multiple data were analyzed using qualitative latent content analysis. Results: Two facilitator themes emerged: Moving spirit and Encouragement. The healthcare professionals described a willingness to individualize care and to increase their professional development in the field of chronic kidney care. The implementation process was strongly reinforced by both the researchers working interactively with the staff, and the project group. One theme emerged as a barrier: the Limitations of the organization. Changes in the organization hindered the implementation of the intervention throughout the study period, and the lack of interplay in the organization most impeded the process. Conclusions: The findings indicated the complexity of maintaining a sustainable and lasting implementation over a period of two years. Implementing empowerment-based care was found to be facilitated by the cooperation between all involved healthcare professionals. Furthermore, long-term improvement interventions need strong encouragement from all levels of the organization to maintain engagement, even when it is initiated by the health care professionals themselves.

A study of costs in higher institutions of learning

This is a questionnaire devised by the author that was sent state colleges as well as colleges in the Southeast concerned the inventory of the institution, sources and amounts of income, expenditures for 1912-24, types of schools, departments and courses at the institution and general information. Graphs was designed with the answers supplied by the institution.

Benthic nematode assemblage composition and diversity during a natural recovery process of Zostera noltii seagrass beds,

In 2008, the stable seagrass beds of the Mira estuary (SW Portugal) disappeared completely; however, during 2009, they have begun to present early symptoms of natural recovery, characterised by a strongly heterogeneous distribution. This study was designed to investigate the spatial and temporal variability patterns of species composition, densities and trophic composition of the benthic nematode assemblages in this early recovery process, at two sampling sites with three stations each and at five sampling occasions. Because of the erratic and highly patchy seagrass recovery and the high environmental similarity of the two sampling sites, we expected within-site variability in nematode assemblages to exceed between-site variability. However, contrary to that expectation, whilst nematode genus composition was broadly similar between sites, nematode densities differed significantly between sites, and this between-site variability exceeded within-site variability. This may be linked to differences in the Zostera recovery patterns between both sites. In addition, no clear temporal patterns of nematode density, trophic composition and diversity were evident.

The Selection Process of Applications to the Portuguese Innovation Incentive System: Who Gets Financial Support?

Public policies to support entrepreneurship and innovation play a vital role when firms have difficulties in accessing external finance. However, some authors have found evidence of long-term inefficiency in subsidized firms (Bernini and Pelligrini, 2011; Cerqua and Pelligrini, 2014) and ineffectiveness of public funds (Jorge and Suárez, 2011). The aim of the paper is to assess the effectiveness in the selection process of applications to public financial support for stimulating innovation. Using a binary choice model, we investigate which factors influence the probability of obtaining public support for an innovative investment. The explanatory variables are connected to firm profile, the characteristics of the project and the macroeconomic environment. The analysis is based on the case study of the Portuguese Innovation.Incentive System (PIIS) and on the applications managed by the Alentejo Regional Operational Program in the period 2007 – 2013. The results show that the selection process is more focused on the expected impact of the project than on the firm’s past performance. Factors that influence the credit risk and the decision to grant a bank loan do not seem to influence the government evaluator regarding the funding of some projects. Past activities in R&D do not significantly affect the probability of having an application approved under the PIIS, whereas an increase in the number of patents and the number of skilled jobs are both relevant factors. Nevertheless, some evidence of firms’ short-term inefficiency was found, in that receiving public financial support is linked to a smaller increase in productivity compared to non-approved firm applications. At the macroeconomic level, periods with a higher cost of capital in financial markets are linked to a greater probability of getting an application for public support approved, which could be associated with the effectiveness of public support in correcting market failings.

The Pleasure of Learning

The evolution, from an education centered in teaching to a perspective of learning, constitutes a change of paradigm as stated by the author in this article - who invites us to use the pleasure of learning as a facilitator for the construction of the senses. The author underlines that education must advance from the non-critical repetition of content to the generation of pleasant learning, and that the search for alternatives for an education that overcomes the traditional paradigm leads to the need to promote an authentic learning pleasure.

Unlocking the Potential of Women in the Rural Development Process of Republic of Srpska: The Role of Extension Service

In Bosnia Herzegovina the development of clear policy objectives and endorsement of a long-term, coherent and mutual agricultural and rural development policy have also been affected by structural problems: a lack of reliable information on population and other relevant issues, the absence of an adequate land registry system and cadastre. Moreover in BiH the agricultural and rural sectors are characterized by many factors that have typically affected transition countries such as land fragmentation, lack of agricultural mechanization and outdated production technologies, and rural aging, high unemployment and out-migration. In such a framework the condition and role of women in rural areas suffered for the lack of gender disaggregated data and a consequent poor information that lead to the exclusion of gender related questions in the agenda of public institutions and to the absence of targeted policy interventions. The aim of the research is to investigate the role and condition of women in the rural development process of Republic of Srpska and to analyze the capacity of extension services to stimulate their empowerment. Specific research questions include the status of women in the rural areas of Republic of Srpska, the role of government in fostering the empowerment of rural women, and the role of the extension service in supporting rural women. The methodology - inspired by the case study method developed by R. Yin - is designed along the three specific research questions that are used as building blocks. Each of the three research questions is investigated with a combination of methodological tools - including surveys, experts interviews and focus groups - aimed to overcome the lack of data and knowledge that characterize the research objectives.

At the intersection of Behavioural Economics, Nudging and Regulation: Rethinking the process of nudge design for regulation

Alongside the developments in behavioural economics, the concept of nudge was introduced as an intervention able to guide individual behaviour towards better choices without using coercion or incentives. While behavioural teams were created inside governmental units and regulatory authorities, nudging emerged in regulatory discourse, being increasingly regarded as a regulatory instrument that could overcome the disadvantages of other tools. This thesis analyses the viability of incorporating nudges into regulation. In particular, it investigates the implications for regulators of bringing iterative experimental testing – a widespread nudge design methodology outside regulation – into their own design practices. Nudges outside regulation are routinely designed using experiments of all kinds. This thesis intends to answer whether design premises rooted in iterative experimentation are still valid in the regulatory space, an arena that nudging entered into and that is distinct from the one where it originally emerged. The design and provision of nudges using the premises of iterative experimental testing is possible, but at a cost and burden for regulatory nudge designers. Therefore, the thesis evaluates how this burden can be reduced, in particular how nudges can be feasibly designed and provided through regulation or, put differently, how to more efficiently design and provide nudging as a regulatory tool.

Shaping the future of learning using the student voice: we’re listening but are we hearing clearly?

Student voice data is a key factor as Manchester Metropolitan University strives to continually improve institutional technology enhanced learning (TEL) infrastructure. A bi-annual Institutional Student Survey enables students to communicate their experience of learning, teaching and assessment on programmes and specific units studied. Each cycle of the survey contains approximately 40–50,000 free text comments from students pertaining to what they appreciate and what they would like to see improved. A detailed thematic analysis of this data has identified 18 themes, arranged into six categories relating to the ‘Best’ aspects of courses, and 25 themes, arranged in seven categories in relation to aspects of courses considered to be ‘in need of improvement’. This student data was then used as a basis for semi-structured interviews with staff. Anecdotally, evidence suggested that student expectations and staff expectations around TEL and the virtual learning environment (VLE) differed. On-going evaluation of this work has highlighted a disconnect. In significant instances, academic colleagues seemingly misinterpret the student voice analysis and consequently struggle to respond effectively. In response to the analysis, the learning technologist's role has been to re-interpret the analysis and redevelop TEL staff development and training activities. The changes implemented have focused on: contextualising resources in VLE; making lectures more interactive; enriching the curriculum with audio–visual resources; and setting expectations around communications.

Supporting Scientific Research Through Machine and Deep Learning: Fluorescence Microscopy and Operational Intelligence Use Cases

Although the debate of what data science is has a long history and has not reached a complete consensus yet, Data Science can be summarized as the process of learning from data. Guided by the above vision, this thesis presents two independent data science projects developed in the scope of multidisciplinary applied research. The first part analyzes fluorescence microscopy images typically produced in life science experiments, where the objective is to count how many marked neuronal cells are present in each image. Aiming to automate the task for supporting research in the area, we propose a neural network architecture tuned specifically for this use case, cell ResUnet (c-ResUnet), and discuss the impact of alternative training strategies in overcoming particular challenges of our data. The approach provides good results in terms of both detection and counting, showing performance comparable to the interpretation of human operators. As a meaningful addition, we release the pre-trained model and the Fluorescent Neuronal Cells dataset collecting pixel-level annotations of where neuronal cells are located. In this way, we hope to help future research in the area and foster innovative methodologies for tackling similar problems. The second part deals with the problem of distributed data management in the context of LHC experiments, with a focus on supporting ATLAS operations concerning data transfer failures. In particular, we analyze error messages produced by failed transfers and propose a Machine Learning pipeline that leverages the word2vec language model and K-means clustering. This provides groups of similar errors that are presented to human operators as suggestions of potential issues to investigate. The approach is demonstrated on one full day of data, showing promising ability in understanding the message content and providing meaningful groupings, in line with previously reported incidents by human operators.

FORMAÇÕES DISCURSIVAS E PROCESSOS IDENTIFICATÓRIOS NA AQUISIÇÃO DE LÍNGUAS

This paper discusses theoretical results of the research project Linguistic Identity and Identification: A Study of Functions of Second Language in Enunciating Subject Constitution. Non-cognitive factors that have a crucial incidence in the degree of success and ways of accomplishment of second language acquisition process are focused. A transdisciplinary perspective is adopted, mobilising categories from Discourse Analysis and Psychoanalysis. The most relevant ones are: discursive formation, intradiscourse, interdiscourse, forgetting n° 1, forgetting n° 2 (Pêcheux, 1982), identity, identification (Freud, 1966; Lacan, 1977; Nasio, 1995). Revuz s views (1991) are discussed. Her main claim is that during the process of learning a foreign language, the foundations of psychical structure, and consequently first language, are required. After examining how nomination and predication processes work in first and second languages, components of identity and identification processes are focused on, in an attempt to show how second language acquisition strategies depend on them. It is stated that methodological affairs of language teaching, learner s explicit motivation and the like are subordinated to the comprehension of deeper non-cognitive factors that determine the accomplishment of the second language acquisition process. It is also pointed out that those factors are to be approached, questioning the bipolar biological-social conception of subjectivity in the study of language acquisition and use and including in the analysis symbolic and significant dimensions of the discourse constitution process.