No description available.

No description available.

A great deal of previous sociological research has examined the social contours of subcultures, focusing either on highly transient subcultures (e.g., among youth) or, conversely, stable institutionalized subcultures (e.g., among professionals). More recent scholarship has examined how leisure subcultures are formed and sustained around a particular interest or activity (e.g., windsurfing). However, little attention has been paid to the role of recreational settings (i.e., specific geographical locales) in the formation of leisure subcultures. Using the Appalachian Trail as a case study, I aim to fill that gap by examining a long-distance hiking subculture. I use ethnographic data collected from long-distance hikers on the Appalachian Trail to carry out the study. My investigation is guided by a subcultural perspective which allows me to identify and understand the sociality and social practices of a long-distance hiking subculture. Consequently, long-distance hikers can be identified and understood through (1) a negative relation to work, (2) a negative or ambivalent relation to class, (3) an association with territory, (4) non-domestic forms of belonging, (5) a range of excessive attributes, and (6) a refusal of the banalities of ordinary life. My qualitative analysis of long-distance hikers’ accounts and interactions permits me to explore how subcultural ideologies and practices are combined with a socially significant place to forge powerful emotional bonds among long-distance hikers and strong attachments to the Appalachian Trail.

Spanning 14 states in the northeast United States, the Appalachian Trail (AT) is a popular destination for outdoor recreation, with thousands of individuals attempting to thru-hike the AT every year. For its scenic views and accessibility from the cities, the AT is experiencing a record number of visitors raising concerns about the sustainability of the trail. Many trail organizations manage the AT to reduce the visitor impact on the outdoors. In this research, I study the role of information and communication technologies in promoting collaboration between these trail agencies and visitors. I identify the need for a formal communication channel between the stakeholders by examining the existing information-sharing practices of hikers and trail managers through social media analysis, interviews, and a design workshop. I present the design of an online discussion platform, the SmarTrail board, and conduct a field usability study with two AT trail clubs to evaluate the platform. Findings from the study reveal that centralized direct communication and streamlined information can support trail management on the AT by promoting collaboration within the trail community. The research paves the path for future research into the design of ICTs for driving nature conservation goals. / Master of Science / The Appalachian Trail (AT) in the northeast of the United States spreads across 14 states. It is accessible from many regional urban centers, offering recreational opportunities to thousands of individuals every year. It is also a popular site for thru-hiking, an endeavor to hike the trail from end to end in a year. Such popularity and accessibility to the trail put pressure on the natural resources, raising concerns about the sustainability of the trail. Management of the trail deals with minimizing the resource impact while preserving the trail experiences of the visitors. Thirty trail clubs maintain separate sections of the AT, and a number of trail organizations work together to manage the trail. The core of this management relies on the collaboration of these trail agencies with each other and the visitors. As communication is central to collaborations in everyday life and for the trail, I explore the practices and possibilities for information sharing and communication on the AT. Digital conservation refers to the technological developments that support and forward nature conservation goals. As the pristine environment of the trails and the AT are not barred from the reach of digital technology, the prevalence of smartphones among visitors presents opportunities for information and communication technologies (ICTs) to support the digital conservation of the trail. In this research, I study digital technology use among hikers and trail managers on the AT, particularly for information sharing. By analyzing comments on Reddit, conducting interviews with the AT trail managers, and organizing a workshop with long-distance hikers, I highlight the need for direct communication between these stakeholders. I present the design of an online discussion board called the SmarTrail platform as a formal communication channel between hikers and trail managers and evaluate it with two trail clubs on the AT. The results from the evaluation offer several use cases of mediated communication, highlighting its need and potential in supporting trail management on the AT. Centralized and formal communication can lead to effective trail management by engaging visitors in trail management, improving volunteer management for the clubs, and enabling knowledge sharing and coordination between the trail agencies. With design considerations for improving human-nature interaction and simplifying the available information for visitors and trail management authorities, this study informs the design of ICTs for trail environments that would forward the digital conservation goals on the AT.

Wellington County represents a region with an extensive and well developed horse industry. As a result there is significant potential for development in its rural areas. This study reveals important facts regarding the development of equine trail networks in Wellington County. The existing number of horses, horse farms, related facilities, as well as the enormous interest of horse riders and horse industry associations suggest high potential for use of these equine trails. In particular the research points out the current lack of horse trails in the county which has one of the highest horse populations in Ontario. Identification of current trends, demands, and overall situation within the industry has led to an elaboration of a framework for the Wellington County equine trail development. The evaluation of the equine trail potential impacts and contributions to rural communities indicates positive outcomes resulting in sustainable community development. The recommendations drawn from this research further suggest a need to elaborate a General Horse Trail Planning and Construction Guide; establish an Equine Trail Organization; create a Master Plan; continue ongoing development of stakeholder relationships; establish equine trail spatial planning considering private land utilization; and integrate future trail plans into County and Regional Planning.

There is no abstract available for this dissertation. / Department of Educational Studies

Malgré la complexité du processus de transformation, plusieurs systèmes modèles ont été développés dans lesquels les cellules normales se transforment d'une manière progressive par l'introduction d’éléments génétique. Ici, seules les cellules transformées rentrent en apoptose induite par TRAIL. Comme le milieu des cellules sénescentes a déjà été impliqué dans certaines caractéristiques tumorales (la prolifération, l'invasion et d'autres), notre objectif était d'évaluer soneffet potentiel sur l'acquisition de la sensibilité à TRAIL. Lorsque toutes les cellules de ce système de transformation sont incubés avec le milieu conditionné de cellules sénescentes (CMS) la sensibilisation à TRAIL a été observée dans les cellules pré-transformées mais pas dans les cellules immortalisées ou normales. Ainsi, nous avons conclu que les différentes étapes de la transformation fournissent un contexte cellulaire et moléculaire particulier qui agit en synergie avec le CMS afin de promouvoir la sensibilisation à TRAIL. Ces observations mettent l'accent sur le rôle spécifique descellules sénescentes et leur phénotype sécrétoire. Nous avons ensuite étudié les mécanismes activés dans les cellules pré-transformées par le CMS et responsables de leur sensibilisation à TRAIL. Nos résultats suggèrent un rôle clé de l'axe Myc-FLIPL dans la signalisation activée par le CMS. / Despite the complexity of the transformation process, several model systems have been developed in which normal cells are transformed in a step-wise manner by introduction of genetic elements (telomerase, SV40ER viral genes and oncogenes). In this system, only the transformed cells go into TRAIL-induced apoptosis. As senescent-secreted factors have already been involved in promoting some of the tumor characteristics (proliferation, invasion and others), our objective was to assess its potential effect on the acquisition of sensitivity to TRAIL. When all the cells of the transformation system were incubated with conditioned medium of senescent cells (CMS) the sensitization to TRAIL was observed only in the pre-transformed, but never in normal or immortalized cells. Thus, we concluded that the different steps of transformation provide a cellular and molecular context that acts in synergy with the CMS to promote TRAIL sensitivity. These observations emphasize the specific role of senescent cells and their secretory phenotype. We then studied the mechanisms activated inthe pre-transformed cells by the CMS, responsible for their sensitization to TRAIL. Our results suggest a key role of the Myc-FLIPL axis in signaling activated by the CMS.

TRAIL (TNF-related apoptosis inducing ligand) est une protéine du système immunitaire appartenant à la famille du TNF (Tumor necrosis factor). L'intérêt de TRAIL en thérapie anti-cancéreuse réside dans sa capacité à induire la mort par apoptose des cellules tumorales, sans exercer de toxicité envers les cellules saines. Le principal frein à l’utilisation de TRAIL est la survenue courante de résistances dans les tumeurs, limitant ainsi son efficacité. Mon travail de thèse a consisté à étudier l’intérêt de l’hyperthermie (ou choc thermique) en tant qu’adjuvant à TRAIL et a décrire ses capacités à contourner les mécanismes de résistance.Dans un premier temps, l’activité et la portée de cette combinaison a été évaluée dans de nombreuses et diverses lignées cellulaires cancéreuses sensibles ou résistantes à TRAIL. Un choc thermique (1h 42°C) permet de sensibiliser efficacement les lignées devenues résistantes à TRAIL et cette association s’est avérée efficace dans toutes les lignées testées.Dans un deuxième temps, mon travail s’est focalisé sur les mécanismes induits par l’hyperthermie, responsables de la sensibilisation et de l’apoptose des cellules. Les analyses des complexes initiateurs de la mort (DISC - Death-inducing signaling complex) ont révélé de nombreuses disparités suivant les conditions thermiques. Les différences majeures impliquent avant tout l’absence de FLIP dans le DISC, celui-ci étant l’inhibiteur principal de la voie, ainsi qu’un retard de la formation du complexe en condition d’hyperthermie. Ceci est associé à l’activation des caspases initiatrices d’une meilleure qualité, une fois la température revenue à la normale.L’absence de FLIP est expliquée par son inactivation due à l’agrégation de cette protéine suite à l’augmentation de la température. Ce phénomène est indépendant d’une quelconque modification post-traductionnelle connue, mais peut être inhibé par la présence de glycérol qui stabilise les protéines dénaturées.L’ensemble de ce travail met en lumière l’intérêt de la combinaison de TRAIL avec une hyperthermie et présente un point de vue nouveau sur les mécanismes expliquant son efficacité. / The TNF-family member TRAIL (TNF-related apoptosis inducing ligand) is a cytokine involved in the immune anti-tumour surveillance. TRAIL is a promising agent currently under investigation for its anti-cancer properties with limited side effects on healthy cells. However, the use of TRAIL in oncology has been limited due to its lack of efficiency, mainly associated with cell resistance to apoptosis. The aim of this project was to study the interest of hyperthermia (or heat shock - HS) as an adjuvant for TRAIL therapy and the mechanisms involved in this sensitization.We have first evaluated the significance of this combination in a large variety of cancer cell lines known to be sensitive or resistant to TRAIL. We could demonstrate that hyperthermia was able to efficiently sensitize resistant cancer cells to TRAIl-induced apoptosis in almost every cell lines tested.We next, focused our work on the molecular mechanisms responsible for the sensitization, during hyperthermia. Analyses of the DISC (Death-Inducing Signaling Complex) revealed a lack of recruitment of FLIP in the DISC, the main inhibitor of the extrinsic pathway, and a delay in the formation of the complex under hyperthermic conditions. Inhibition of FLIP recruitment was associated with enhanced initiator caspases activation when cells were reincubated at 37°C after the HS.The absence of FLIP within the TRAIL DISC was due to its aggregation during HS and was independent of post-translational modifications. Inhibition of FLIP aggregation by glycerol, which stabilizes denaturerated proteins, restored FLIP recruitment within the TRAIL DISC and consequently inhibited TRAIL-induced cell death. Taken together, these results highlight the interest of combining TRAIL with hyperthermia and highlight new mechanisms explaining its efficiency.

L’objectif de cette thèse était d’analyser l’activité en trail et ultra-trail en s’inscrivant dans le paradigme de l’énaction (Varela et al., 1993). Un observatoire multi-sourcing composé de discussions de forum, de récits de courses postés sur les blogs, d’entretiens énactifs et de données en troisième personne caractérisant les accélérations verticales du traileur et de son système de portage a été construit pour mener nos analyses. Les résultats des analyses des discussions de forums ont montré que les traileurs partagent des préoccupations relatives à l’entraînement et la santé. Les résultats des analyses des récits de blogs et des entretiens énactifs ont caractérisé l’activité des traileurs en situation de course, en reportant (a) des gestalts phénoménologiques dont l’agencement temporel a identifié des profils d’activité, (b) des états de vitalité dont la répartition et l’organisation temporelle différaient chez les finisheurs et les abandonneurs et (c) sept étapes-clés impliquées dans les abandons. Les résultats des analyses de l’usage du matériel ont montré que les sensations de ballotement du système de portage reportées par les traileurs étaient confirmées par les données comportementales. Pris dans leur ensemble, ces résultats suggèrent que l’activité des traileurs peut être caractérisée avec différentes sources de données, rendant compte des expériences signifiantes multiples énactés en situation. Ils fournissent des implications pratiques pour le champ de la psychologie du sport et transformatives pour les entreprises souhaitant intégrer les utilisateurs dans leur processus de conception. / Rooted in the enaction paradigm (Varela et al., 1993), the aim of this thesis was to analyse the activity in trail and ultra-trail running. A multi-sourcing observatory was constructed to conduct our analyses. It was composed of forum discussions posted on the community website of the Raidlight brand, races narratives posted on blogs, enactive interviews and third-person data characterising the vertical oscillations of both the runners and their carrying systems. The results of the discussion forums showed that trail runners share common concerns regarding health and training issues. The results of the blog narratives and enactive interviews analyses characterised trail runners’ activity in race situation, by reporting (a) phenomenological gestalts, which temporal layout identified activity profiles, (b) vitality states, which repartition and temporal organisation differed in finishers and withdrawers and (c) seven key-stages involved in withdrawals. The results of analyses of the use of equipment showed that the sensations of bouncing reported by runners were confirmed by the behavioural data. Taken together, these results suggested that trail runners’ activity can be characterised by different data sources, reporting the various meaningful experiences that trail runners enact in situation. They provide practical and transformative implications for the proposition of an intervention model in sport psychology as well as a proposition of a multi-sourcing conception model for companies, which seek to integrate users in their conception processes.

Le développement d'anticorps thérapeutiques a suscité beaucoup d'intérêt au cours des dernières décennies. Plus de 30 d'entre eux ont été approuvés et sont utilisés pour traiter des patients atteints de cancer. Les récepteurs agonistes de TRAIL (DR4 ou DR5) sont surexprimés par les cellules tumorales et capables de déclencher leur mort. Ils représentent donc des cibles idéales. Malgré des résultats encourageants, la plupart des essais cliniques basés sur des anticorps monoclonaux ciblants DR4 ou DR5 ont été interrompus. Cependant, les connaissances actuelles ouvrent des perspectives thérapeutiques de choix pour l'utilisation de tels anticorps en oncologie. Afin de développer de nouveaux anticorps anti-DR4 et anti-DR5 reconnaissant sélectivement les protéines natives d’intérêt, et doués de propriétés antitumorales, nous avons opté pour une approche d'immunisation génétique basée sur des injections hydrodynamiques d'ADN complémentaire. Cette approche nous a permis d'obtenir des réponses humorales significatives, et après fusions des rates correspondantes, de générer 21 anticorps monoclonaux capables de reconnaître spécifiquement et avec une très grande affinité les récepteurs DR4 ou DR5, sous leurs formes natives. Parmi ces anticorps monoclonaux, deux sont doués de propriétés pro-apoptotiques, et quatre sont capables d'accroitre le potentiel pro-apoptotique du ligand TRAIL. Les propriétés antitumorales de l'anticorps anti-DR4 le plus puissant, l’AcM-C#16, ont également été validées in-vivo dans des modèles de xénogreffes.L'ensemble de ce travail démontre, et ce pour la première fois, que la méthode d'immunisation ADN par injection hydrodynamique peut être utilisée pour générer des anticorps monoclonaux thérapeutiques efficaces ciblant des récepteurs de la superfamille du TNF. Au-delà du système TRAIL, cette approche d'immunisation, peu exploitée, pourrait ouvrir de nouvelles perspectives thérapeutiques en l'adaptant à de nouvelles cibles. / Development of therapeutic antibodies has attracted many interests in recent decades. More than 30 of them have been approved and are used to treat cancer patients. TRAIL agonist receptors (DR4 or DR5) are overexpressed by the tumour cells and are able to trigger their death. Therefore, they represent ideal targets. Despite encouraging results, most clinical trials based on monoclonal antibodies targeting DR4 or DR5 have been discontinued. However, current knowledge opens therapeutic perspectives of choice for the use of such antibodies in oncology. In order to develop new anti-DR4 and anti-DR5 antibodies recognizing selectively the native form of the proteins of interest, and endowed with antitumor properties, we have chosen to perform a genetic immunization approach based on hydrodynamic injections of complementary DNA. This approach allowed us to obtain significant humoral responses, and after fusions of the corresponding spleens, to generate 21 monoclonal antibodies capable of recognizing specifically and with very high affinity DR4 or DR5 receptors, in their native forms. Of these monoclonal antibodies, two are display pro-apoptotic properties, and four are capable of enhancing TRAIL pro-apoptotic potential. The antitumor properties of the most potent anti-DR4 antibody, mAb-C16, have also been validated using in-vivo xenografts models.Altogether this work demonstrates, for the first time, that the DNA immunization hydrodynamic injection method can be used to generate therapeutically effective monoclonal antibodies targeting TNF superfamily receptors. Beyond the TRAIL system, this immunization approach, scarcely exploited, could open new therapeutic perspectives by adapting it to new targets.