[ES] Durante las últimas décadas, múltiples retos han puesto en riesgo la sostenibilidad medioambiental, económica y social de los sistemas de producción de vacuno lechero (SPL). Esta Tesis Doctoral aborda algunos de los principales retos del sector en materia de sostenibilidad mediante el desarrollo de conceptos, metodologías y estrategias adaptadas a las necesidades particulares de un amplio abanico de SPL en Europa. Las investigaciones se centran en la evaluación de las herramientas de análisis de la sostenibilidad, el análisis de la diversidad de sistemas de producción existentes, así como en la mitigación adaptada de las emisiones de gases de efecto invernadero (GEI) y pérdidas de nitrógeno (N) a escala de granja. Esta Tesis Doctoral presenta un marco cuantitativo que permite un análisis exhaustivo de las herramientas existentes para la determinación de la sostenibilidad a escala de granja. Los resultados muestran como las herramientas evaluadas presentan un mayor número de indicadores asociados con el pilar medioambiental que con el pilar económico y social. En adición, se facilita la identificación de vías para el desarrollo futuro de los modelos, permitiendo una más completa y detallada evaluación de la sostenibilidad. Asimismo, los resultados obtenidos en materia de análisis de la diversidad de SPL, permiten la identificación, descripción y agrupación de las regiones europeas de acuerdo con diferentes tipologías de sistemas productivos. Las 16 tipologías representativas identificadas, combinan las características estructurales, productivas, socioeconómicas y medioambientales de los SPL con la distribución de cultivos forrajeros más relevantes para la producción láctea a escala NUTS2. Al analizar y agrupar la diversidad de sistemas productivos y evaluar su nivel de integración, esta Tesis Doctoral facilita la toma de decisiones basadas en el conocimiento, el diseño y la aplicación de medidas de mitigación de emisiones específicas y adaptadas, así como la promoción de sinergias económicas y sociales positivas. En adición, esta Tesis Doctoral pone de manifiesto la gran influencia de las condiciones climáticas, las características estructurales y las prácticas de manejo sobre las emisiones de N y GEI asociadas a la fermentación entérica, los cultivos, así como a toda la cadena de gestión del estiércol. Al identificar la magnitud y fuentes de emisión de los SPL, se facilita la aplicación de medidas específicas a cada contexto. En términos de mitigación de las emisiones, la reducción de la proteína bruta en la fracción comprada de la dieta es una estrategia eficaz a la hora de mitigar tanto las emisiones de GEI como las pérdidas de N. Además, la implantación de una planta de digestión anaerobia es efectiva a la hora de reducir la intensidad de GEI en todos los SPL evaluados, aumentando únicamente las pérdidas de N en el sistema mediterráneo intensivo. El impacto del incremento de la productividad a través de un mayor uso piensos sobre las pérdidas de N y las emisiones de GEI es variable entre los sistemas examinados. A este respecto, el sistema semi-extensivo centroeuropeo muestra un mayor potencial de reducción de GEI, mientras que el semi-extensivo atlántico obtiene mejores resultados en la reducción de las pérdidas de N. Del mismo modo, el uso de la inyección de purines reduce las pérdidas de N en campo, incrementando las emisiones de GEI en el sistema mediterráneo. La sustitución de urea por nitrato amónico tiene diferentes efectos sobre los GEI y la intensidad de N, observándose un mayor potencial de mitigación en el sistema semi-extensivo atlántico. Por último, las cubiertas rígidas de purines mitigan eficazmente las pérdidas de N durante el almacenamiento, con un impacto mínimo en las emisiones totales de GEI. Así mismo, a lo largo de esta Tesis Doctoral se demuestra como la aplicación cumulativa de medidas de mitigación, deriva en sinergias positivas a la hora de reducir las emisiones globales de la explotación. / [CA] Durant les últimes dècades, múltiples reptes n'han posat en risc la sostenibilitat mediambiental, econòmica i social dels sistemes de producció de boví de llet (SPL). Aquesta Tesi Doctoral aborda alguns dels principals reptes del sector en termes de sostenibilitat mitjançant el desenvolupament de conceptes, metodologies i estratègies adaptades a les necessitats particulars d'un ampli ventall de SPL a Europa. Les investigacions se centren en l'avaluació de les eines per a la seua quantificació, l'anàlisi de la diversitat de sistemes de producció existents, així com en la mitigació adaptada de les emissions de gasos d'efecte d'hivernacle (GEH) i pèrdues de nitrogen (N) a escala de granja. Aquesta Tesi Doctoral presenta un marc quantitatiu que permet una anàlisi exhaustiu de les eines existents per a la determinació de la sostenibilitat a escala de granja. Els resultats obtinguts mostren com les eines avaluades presenten un major nombre d'indicadors associats amb el pilar mediambiental que amb el pilar econòmic i social. A més, aquest treball facilita la identificació de vies per al desenvolupament futur dels models i facilita una avaluació de la sostenibilitat més completa i detallada. Els resultats obtinguts en matèria d'anàlisi de la diversitat de SPL permeten la identificació, descripció i agrupació de les regions europees d'acord amb diferents tipologies de sistemes productius. Les 16 tipologies representatives identificades combinen les característiques estructurals, productives, socioeconòmiques i mediambientals dels SPL amb la distribució de conreus farratgers més rellevants per a la producció làctia a escala NUTS2. En addició, en analitzar i agrupar la diversitat de sistemes productius i avaluar el seu nivell d'integració, aquesta Tesi Doctoral facilita la presa de decisions basada en el coneixement, el disseny i l'aplicació de mesures de mitigació d'emissions específiques i adaptades, així com la promoció de sinergies econòmiques i socials positives. Així mateix, aquesta Tesi Doctoral indica la gran influència de les condicions climàtiques, les característiques estructurals i les pràctiques de maneig sobre les emissions de N i GEH associades a la fermentació entèrica, els conreus, així com tota la cadena de gestió del fem. A més, en identificar la magnitud i fonts d'emissió dels SPL, es facilita l'aplicació de mesures específiques a cada context. En aquest sentit, la reducció de la proteina bruta en la porció comprada de la dieta és una estratègia eficaç per a mitigar tant les emissions de GEH com les de N. A més, la implantació d'una planta de digestió anaeròbia va reduir la intensitat de GEH en totes les SPL avaluades, augmentant únicament les emissions de N en el sistema mediterrani intensiu. L'impacte de l'increment de la productivitat a través d'un major use pinsos sobre les pèrdues de N i les emissions de GEH va variar entre els sistemes d'explotació examinats. Referent a això, el sistema semi-extensiu centreeuropeu va mostrar un major potencial de reducció de GEH, mentre que el semi-extensiu atlàntic va obtindre millors resultats en la reducció de les pèrdues de N. De la mateixa manera, l'ús de la injecció de purins va reduir les emissions de N a nivell de camp, incrementant les emissions de GEH en el sistema mediterrani. La substitució d'urea per nitrat d'amoni va tindre diferents efectes sobre els GEH i la intensitat de N, observant-se un major potencial de mitigació en el sistema semi-extensiu atlàntic. Finalment, les cobertes rígides de purins van reduir eficaçment les pèrdues de N durant l'emmagatzematge amb un impacte mínim en les emissions totals de GEH. Així mateix, al llarg d'aquesta Tesi Doctoral es demostra com l'aplicació cumulativa de mesures de mitigació deriva en sinergies positives a l'hora de reduir les emissions globals de l'explotació. / [EN] During the last decades, multiple challenges have put the environmental, economic, and social sustainability of dairy cattle production systems (DPS) at risk. This Ph.D. Thesis tackles some of the sector's main challenges in terms of sustainability by developing concepts, methodologies, and strategies adapted to the particular needs of a wide range of European DPS. In particular, special emphasis is placed on evaluating the tools for sustainability assessments, the analysis and clustering of the diversity of existing production systems, and the adapted mitigation of greenhouse gas (GHG) emissions and nitrogen (N) losses at the farm scale. This Ph.D. Thesis presents a quantitative framework that comprehensively evaluates whole-farm tools and models. The obtained results show how the models considered incorporate more indicators from the environmental pillar than those related to the economic or social sphere. In addition, this work facilitates the identification of avenues for future model developments, allowing for a more complete and detailed assessment of sustainability. Furthermore, the results obtained allow for the identification, description, and clustering of European regions according to different typologies of production systems. The 16 representative typologies identified combine DPS's structural, productive, socio-economic, and environmental characteristics with the level of overlap with the most relevant fodder crops for dairy production at the NUTS2 scale. Furthermore, by analyzing and clustering the diversity of production systems and assessing their level of integration, this Ph.D. Thesis facilitates knowledge-based decision-making, the design and implementation of targeted and adapted emission mitigation measures, as well as the promotion of positive economic and social synergies. Moreover, this Ph.D. Thesis highlights the strong influence of climatic conditions, structural characteristics, and management practices on N and GHG emissions associated with enteric fermentation, fields, and manure management. In terms of emission mitigation, reducing the amount of crude protein in the purchased fraction of the diet is an effective strategy to mitigate both GHG and N emissions. Additionally, implementing an anaerobic digestion plant reduces GHG emissions in all assessed DPS but increases N losses only in the intensive Mediterranean DPS. The impact of increased productivity through larger use of concentrates on N losses and GHG emissions varied depending on the farming systems examined. In this sense, the Central European semi-extensive system shows a higher potential for GHG reduction, while the Atlantic semi-extensive system accounts for better results when lowering the N losses. Similarly, shallow slurry injection effectively decreases N losses at the field level, although it increases GHG emissions in the Mediterranean DPS. Substituting urea with ammonium nitrate has different effects on GHG and N emission intensity, with greater potential for mitigation in the Atlantic semi-extensive system. Lastly, rigid slurry covers effectively reduces N losses during storage with minimal impact on GHG emissions. Furthermore, this Ph.D. Thesis shows how the cumulative application of mitigation measures leads to positive synergies in reducing the overall emissions of the farm. / All studies conducted in the course of this Ph.D. Thesis were funded by the German Federal Ministry of Food and Agriculture (BMEL) through the Federal Office for Agriculture and Food (BLE) within the framework of the project "MilKey" (grant number 2819ERA08A), funded by the joint call 2018 ERA-GAS (grant no. 696356), SusAn (grant no. 696231) and ICT-AGRI 2 (grant no. 618123) on "New technologies, solutions, and systems to reduce greenhouse gas emissions in animal production systems". BC3-Research is supported by the Spanish Government through María de Maeztu excellence accreditation 2018–2022 (Ref. MDM-2017-0714) and María de Maeztu excellence accreditation 2023-2026 (Ref. CEX2021-001201-M, funded by MCIN/AEI/10.13039/501100011033) and by the Basque Government through the BERC 2018–2021 program. Agustin del Prado is financed through the Ramon y Cajal program by the Spanish Ministry of Economy, Industry, and Competitiveness (RYC-2017-22143). / Díaz De Otalora Aguirre, X. (2023). Sustainability Assessment of Key European Dairy Cattle Production Systems: System Identification, Analysis, and Greenhouse Gas and Nitrogen Emission Mitigation [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/196465

Over the past decades, the fast-changing global climate poses a significant challenge to many cities around the world to embrace resilience concepts, whereby a safe-to-fail planning approach replaces traditional fail-safe practices. The change in perspectives has seen an increase in climate-adapted infrastructural projects being integrated with the new urban planning agendas across the world. The investigation conducted was designed to understand the process of how resilience concepts travel between different cities, by investigating the actors who move policy knowledge, their roles in it, as well as the knowledge transfer process mechanism that is responsible for the movement of such policies. The investigation took advantage of a scoping study technique to answer the research questions, using mostly secondary data and an interview to verify the secondary sources. The findings and the discussion provided insights on who is involved in resilience policies and how these policies are transferred from one place to another. The investigation uncovered the influence policy mobilizers has on the movement of policy knowledge, as well as how the mobilization of policy knowledge can both be beneficial or detrimental, depending on the way it was moved or implemented. / Under de senaste decennierna utgör det snabba föränderliga globala klimatet en betydande utmaning för många städer runt om i världen med att anamma motståndskraftskoncept, där en planeringsstrategi med säkerhet att misslyckas ersätter traditionella felsäkra metoder. Förändringen i perspektiv har ökat klimatanpassade infrastrukturprojekten som integrerats med nya stadsplaneringsagendorna över hela världen. Studien genomfördes för att få en förståelse av hur motståndskraftskonceptet färdas mellan olika städer och detta genomfördes genom att undersöka de aktörer som förflyttar politisk kunskap och deras roller i den samt den kunskapsöverföringsmekanism som är ansvarig för rörelsen av sådan politik. Studien utnyttjade en scoping-studieteknik för att få svar på forskningsfrågorna, med mestadels sekundär data och en intervju för att verifiera sekundärkällorna. Resultaten och diskussionen gav insikter om vem som är inblandad i motståndskraft och hur policy överförs från en plats till en annan. Studien avslöjade även inflytande av politiskt mobilisering och kunskap som både kan vara fördelaktig eller skadlig beroende på hur den flyttades eller genomfördes.

<p>Two studies were conducted to examine the effects of learner-adapted practice on the self-efficacy beliefs, acquisition and retention of a motor task. Through a discovery process all participants learned to perform several keypress patterns, with the goal of completing each sequence as fast and accurate as possible. The first experiment had learners practice the keypress sequences in one of two adaptive schedules, which utilized either a ‘WinSwitch’ or ‘WinRepeat’ task switching algorithm, or follow a pre-determined order of tasks (two yoked-control groups). The purpose of this experiment was to determine if adaptive schedules were effective because they were tailored to a learner’s performance characteristics or due to the nature of the contextual interference employed by the switching algorithm when the 'winning' criterion was satisfied. To examine the psychological factors involved in adaptive practice, the second experiment had all groups practice in a ‘WinSwitch Adaptive’ schedule and manipulated the social-comparative feedback that was provided (positive, negative or control). Together these studies revealed that the effectiveness of adaptive schedules may not necessarily be due to the fact that they are tailored to a learner's performance characteristics. They also suggest that learning is facilitated by a switching algorithm that involves some blocked practice towards the beginning and mostly random practice towards the end of acquisition (WinRepeat schedule). However, providing positive social-comparative feedback can override the negative effects of the opposite schedule (WinSwitch) and result in more effective learning and increases in self-efficacy beliefs. These findings are discussed in reference to contextual interference effects and the self-efficacy framework.</p> / Master of Science in Kinesiology

I det här kandidatarbetet undersöks padelhallar för att hitta potentiella gestaltningslösningar för de utmaningar verksamheterna står inför idag. Vid en statistikundersökning ser man tydligt att antalet utövare har sjunkit kraftigt och att flera hallar runt om i Sverige har behövts stänga igen. Syftet med arbetet är att undersöka huruvida potentiella kulturella verksamheter kan kombineras med dessa hallar för att få ner kostnaderna och skapa ett gynnsamt samarbete. I detta arbete presenteras en analysprocess och en anpassad gestaltningsprocess som visar på hur dessa potentiella kulturella verksamheter både kan identifieras samt implementeras i padelhallar. Genom att undersöka teorier såsom “Low Road and High Road”, “Junkspace” och “The Duck and the Decorated Shed” har arbetet fått en klarare blick över vad padelhallar är, samt vad man behöver tänka på vid en anpassad gestaltning. En detaljerad platsanalys har även gjorts på ett urval padelhallar för att jämföra vilka urbana kontexter de kan befinna sig i, vilka olika konstruktioner de kan ha, vilka planlösningar osv. Utöver detta har även detaljplaner analyserats. Under projektets gång har en av hallarna, lokaliserad i Västra Hamnen, Malmö, hamnat hos en konkursförvaltare, vilket bestämde valet av vilken hall gestaltningen skulle ta form vid. Den slutliga gestaltningen visar på ett konceptuellt förslag över hur lokala kulturella verksamheter kan kombineras med denna hall. / In this thesis, padelhalls are investigated in order to find potential design solutions for the challenges businesses are facing today. A statistical survey clearly shows that the number of practitioners has fallen sharply and that several halls across Sweden have had to close. The purpose of this work is to investigate whether potential cultural activities can be combined with these halls in order to reduce costs and create a favourable collaboration. This work presents an analysis process and an adapted design process that shows how these potential cultural activities can both be identified and implemented in padelhalls. By examining theories such as “Low Road and High Road”, “Junkspace” and “The Duck and the Decorated Shed”, the work has gained a clearer view of what padelhalls are and what needs to be considered when creating an adapted design. A detailed site analysis has also been done on a selection of padelhalls to compare which urban contexts they can be in, which different constructions they can have, which layouts, etc. In addition to this detailed plans have also been analysed. During the course of the project, one of the halls, located in Västra Hamnen, Malmö, ended up with a bankruptcy trustee, which determined the choice of which hall the design would take form at. The final design shows a conceptual proposal for how local cultural activities can be combined with this hall.

Skolans styrdokument påtalar vikten av att vårdnadshavare görs delaktiga i den utredningsprocess som ska bedöma om deras barn ska mottagas i anpassad grundskola.  Forskning visar dock att vårdnadshavare inte alltid inkluderas i processen, utan känner sig maktlösa, frustrerade och exkluderade. Syftet med denna studie är att bidra till ökad kunskap om vårdnadshavares upplevelser av delaktighet kring utredningsprocessen till mottagande i anpassad grundskola för sitt barn. Studiens två frågeställningar fokuserar på hur vårdnadshavare upplever delaktighet i processen både som helhet och de olika delarna, samt vilka faktorer som påverkar vårdnadshavares upplevelser av delaktighet. Studien är en kvalitativ intervjustudie där tio semistrukturerade intervjuer med vårdnadshavare har genomförts, med en fenomenologisk utgångspunkt. Vid analysen har Giorgis modell använts, för att tolka, urskilja och tematisera svaren. Resultatet visar att 60 % av vårdnadshavarna har upplevt delaktighet i processen som helhet, och kring de olika delarna har graden av delaktighet varierat. De påverkansfaktorer som identifierats är förförståelse, maktbalans och beslut, relation, kommunikation, bemötande och samsyn. Slutsatsen är att vårdnadshavares delaktighet inte är självklar, och att det finns mycket kvar att utveckla. En ökad förståelse för vårdnadshavares perspektiv skulle kunna leda till ökad delaktighet och bättre samverkan, något som skulle främja barnets skolgång. / The school´s governing documents points out the importance of guardians being involved in their child´s admission to an adapted primary school. Research shows that guardians are not always included in the process, but feel powerless and exkluded. The purpose of this study is to contribute to increased knowledge about guardian´s experience of participation in the investigation process for their childs´ reception in an adapted primary school. The study´s two questions focus on how guardians experience participation in the process both as a whole and the various parts, as well as which factors influence guardians´ experiences of participation. The study is a qualitative interview study where ten semi-structured interviews with guardians have been conducted, with a phenomenological starting point. In the analysis, Giorgi´s model has been used to interpret, distinguish and thematize the answers. The result show that 60 % of the guardians have experienced participation in the progress as a whole, and different degrees and types of participation have been experienced around the different parts. The influence factors identified are pre-understanding, balance of power and decisions, relationship, communication, treatment and consensus. The conclusion is that guardians´participation is not self-evident, and that there is still much to develop. An increased understanding of the guardian´s perspective could lead to better collaboration, something that promotes the child´s schooling.

Inclusive education is a fundamental part of South African Education with policies and initiatives being designed to provide support for learners with barriers to learning. With autism as a growing global phenomenon, South Africa has the additional challenge of providing learning support for learners with autism. This dissertation focuses on how one specialised preschool provides inclusive opportunities for preschool learners with autism through learning support. This setting is unique as it shares the same physical location as a mainstream preschool. The study focuses upon how the preschool teachers support their learners with autism so that they can be included within the adjoining inclusive environment. The research was conducted through participant observation and supporting interviews over a period of six months. All observations were recorded through field notes and reflections. The research produced a number of key findings. The shared physical environment enabled teachers and learners from both preschool settings to work together on a daily basis. This had a positive effect upon peer acceptance, staff and learner relationships and opportunities for staff to communicate and work collaboratively on a daily basis. The specialised preschool teachers provided learning support through the adaptation of learning environment, curriculum, multi sensory learning and language and communicative means. The main conclusions drawn from this research were the importance of a close working relationship between staff members and learners from both settings; the importance of adapting communication, environment and learning expectations; and lastly, the importance of focusing upon each individual when providing inclusive opportunities. The research recommends having a specialist setting physically close to an inclusive environment as this enables learners with high needs such as autism to build up the skills needed to benefit from being included. In addition, the research recommends staff in mainstream and specialist settings to have regular opportunity to work together collaboratively when developing learning strategies. Finally, the research recommends the publication of a guideline, outlining the nature of autism and recommended strategies to use within the classroom, which would serve as a flexible document for teachers to adapt to support their individual learners. / Inclusive Education / M. Ed. (Inclusive Education)

Ce mémoire présente et discute d’une problématique importante qui s’inscrit dans un contexte actuel, autant sur le plan international que local, puisqu’elle touche 1 enfant sur 68 (CDC, 2010). On parle ici du trouble du spectre de l’autisme (TSA). Plus spécifiquement, cette recherche se concentre sur les jeunes adultes autistes, qui du jour au lendemain, se retrouvent face à une interruption de services. Elle suggère qu’une adaptation adéquate de l’environnement soit davantage explorée en vue d’offrir des centres de jour adaptés à cette clientèle. La question de recherche est la suivante : Quels sont les éléments du design intérieur qui peuvent améliorer la qualité de vie des adultes autistes? Il est essentiel de s’y attarder, puisque les personnes TSA sont entre autres caractérisées par leur hypersensibilité et leur hyposensibilité face à l’environnement. Bien que le sujet de l’autisme soit richement documenté par le domaine des sciences médicales, il est apparu qu’il l’est moins par celui de l’aménagement. La stratégie méthodologique de cette recherche repose sur des analyses de précédents, des observations participantes ainsi que la tenue d’entretiens semi-dirigés auprès de parents d’enfants autistes. Cette étude vise simultanément l’amélioration de la compréhension de la pratique émergente du design comme moyen d’intervention ainsi que l’identification des facteurs (éclairages, couleurs, matériaux, division de l’espace, etc.) pouvant améliorer le bien-être des adultes autistes. Sur la base des données collectées, il a été remarqué qu’effectivement, plusieurs moyens peuvent être entrepris pour concevoir des environnements améliorant le bien-être de ces adultes. Les résultats extraits du terrain mènent à des propositions d’aménagement claires : rendre l’abstrait le plus concret possible, aménager des zones de retrait social, offrir une variété d’ambiances, et finalement, offrir un encadrement sécuritaire. / This thesis presents and discusses an important issue that is part of a current context, both international and local level, since it affects 1 child in 68 (CDC, 2010). We are talking about the Autism spectrum disorder (ASD). More specifically, this research focuses on young autistic adults who suddenly find themselves facing a lack of services. It suggests that an adequate adaptation of the environment should be explored in order to provide adapted day Centers to this clientele. The question of the research is the following: What are the elements of interior design that can improve the quality of life of autistic adults? It is essential to linger over it, since ASD people are characterized by hypersensitivity and hyposensitivity to the environment. Even if the subject of autism is richly documented by medical science, it appeared that it is less studied by the interior architecture domain. The methodological strategy of this research is based on analysis of precedents, participant observation and the conducting semi-structured interviews with parents of autistic people. This study aims simultaneously to improve the understanding of the emerging practice of design as an intervention and the identification of factors (lightings, colors, materials, spatial organization) that could improve the wellbeing of autistics adults. Based on the data collected, it was noticed that, indeed, several means can be undertaken to design environments improving the well-being of adults. The results extracted from the field study lead us to clear layout proposals: making the abstract as concrete as possible, develop areas of social withdrawal, offer a variety of atmospheres, and finally provide a safe environment.

L-asparaginase (L-ASNase) é uma enzima com propriedades interessantes para a indústria médica, farmacêutica e de alimentos, que tem recebido atenção especial, inclusive no Brasil, por fazer parte do protocolo de tratamento de distúrbios linfoproliferativos, como a leucemia linfoblástica aguda (LLA). No mercado desde a década de 1970, as enzimas de origem bacteriana enfrentam algumas limitações por provocarem reações adversas graves em quase 80% dos pacientes em tratamento. Nesse contexto, L-ASNases provenientes de leveduras se destacam como alternativa, por serem mais próximas às congêneres humanas. A Antártica ainda é um ambiente pouco explorado, com grande diversidade de microrganismos com potencial para a produção de moléculas biológicas de interesse industrial. Nesse contexto, 150 leveduras isoladas de amostras de sedimento marinho coletadas na Península Antártica como parte do projeto MICROSFERA (PROANTAR/CNPq) foram avaliadas para a produção de L-ASNase. A triagem resultou em 9 isolados produtores, dos quais 7 pertencem ao gênero Leucosporidium. A linhagem L. muscorum CRM 1648 foi a que produziu mais enzima (540 U.L-1), com maior produtividade (5,6 U.L-1.h-1) e, por isso, foi alvo deste estudo. A análise univariada de fontes de carbono e nitrogênio indicou maior crescimento desse microrganismo e produção de L-ASNase em meio CD com extrato de levedura, prolina e sacarose. Ureia, cloreto de amônio e sulfato de amônio resultaram em baixa ou nenhuma produção da enzima, sugerindo que a metabolização de fontes de nitrogênio por essa linhagem está sob a influência do fenômeno de repressão catabólica pelo nitrogênio (RCN). Dois delineamentos experimentais do tipo fatorial completo resultaram em um aumento de 10 vezes na produção e produtividade da enzima (4582,5 U.L-1 e 63,6 U.L-1.h-1, respectivamente). A análise univariada da concentração inicial de inóculo (X0), pH inicial do meio, temperatura e adição de água do mar mostrou que a melhor condição para a produção foi: pH = 5,5 ou 6,5, cultivo a 15°C com adição de água do mar (25-50% m/v). A variável X0 não foi significativa nas concentrações avaliadas. Cultivos em biorreator (batelada) foram conduzidos em quatro diferentes níveis de oxigênio dissolvido (OD): (1) OD não controlado e abaixo de 20%, (2) OD não controlado e acima de 20%, (3) OD controlado em 80% e (4) OD controlado em 20%. Os resultados mostraram que OD é fator limitante para o crescimento de L. muscorum CRM 1648 e produção de L-ASNase por essa levedura e deve ser mantido acima de 35% para maior produção da enzima.Neste trabalho, a composição do meio e condições de cultivo foram estabelecidas para favorecer a produção de uma nova L-ASNase livre de atividade glutaminásica por levedura adaptada ao frio, abrindo espaço para novos estudos acerca de seu potencial antileucêmico e possível uso como alternativa às enzimas já existentes no mercado no tratamento de LLA. / L-asparaginase (L-ASNase) is an enzyme with interesting properties for medical, pharmaceutical and food industry, which has received special consideration, especially in Brazil, for being part of lymphoproliferative disorders treatment, such as acute lymphoblastic leukemia (ALL). Bacterial enzymes are on the market since the 1970s and face some limitations related to theirserious adverse reactions that reach almost 80% of all patients in treatment. In this context, L-ASNases from yeasts are highlighted as important alternative to bacterial enzymes, due to the closerphylogeny to human congeners. Antarctic environment has much to be explored, with a vast diversity of microorganisms with potential to produce biomolecules with industrial interest. A total of 150 yeasts isolated from Antarctic marine sediments as part of MICROSFERA project (PROANTAR/CNPq) were evaluated for L-ASNase production. The screening resulted in 9 producers, 7 species from the genus Leucosporidium. L. muscorum CRM 1648 was the strain that yielded the highest L-ASNase activity (540 U.L-1) and volumetric productivity (5.6 U.L-1.h-1). Carbon and Nitrogen sources were evaluated by a method of one-factor at a time (OFAT). From the gather results, sucrose, yeast extract and proline resulted in a maximal growth and highest enzyme production.The absence or low production of L-ASNase in medium with urea, ammonium chloride and ammonium sulfate suggests the presence of nitrogen catabolic repression (NCR). Carbon and nitrogen concentration were evaluated by full factorial design and yielded about ten times higher enzyme and volumetric productivity (4582.5 U.L-1 and 63.6 U.L-1.h-1, respectively). Initial inoculum concentration (X0), initial pH, temperature and concentration of seawater in the culture were evaluated by OFAT analysis and the best condition for L-ASNase production was: pH = 5.5 or 6.5, at 15 °C with addition of seawater (25-50 wt%). X0 was not considered a significant variable. Bioreactor assays (in batch regime) were performed in four different dissolved oxygen (DO) levels: (1) without DO control (DO remained under 20%), (2) without DO control (DO remained above 20%), (3) DO controlled at 80%, and (4) DO controlled at 20%.The results showed that DO is a key factor for growth of L. muscorum CRM 1648 and production of L-ASNase by this yeast and should be maintained above 35% for higher production of this enzyme.At this work, the medium and culture conditions were established to support the production of a novel glutaminase-free L-ASNase by a cold adapted yeast, opening a new path for further studies regarding its antileukemic potential and possible use as an alternative for ALL treatment.

Nesta tese, são obtidas taxas de convergência a zero, do risco de estimação obtido com regressão não-paramétrica via ondaletas, quando há erros correlacionados. Quatro métodos de regressão não-paramétrica via ondaletas, com delineamento desigualmente espaçado são estudados na presença de erros correlacionados, oriundos de processos estocásticos. São apresentadas condições sobre os erros e adaptações aos procedimentos necessárias à obtenção de taxas de convergência quase minimax, para os estimadores. Sempre que possível são obtidas taxas de convergência para os estimadores no domínio da função, sob condições bastante gerais a respeito da função a ser estimada, do delineamento e da correlação dos erros. Mediante estudos de simulação, são avaliados os comportamentos de alguns métodos propostos quando aplicados a amostras finitas. Em geral sugere-se usar um dos procedimentos estudados, porém aplicando-se limiares por níveis. Como a estimação da variância dos coecientes de detalhes pode ser problemática em alguns casos, também se propõe um procedimento iterativo semi-paramétrico geral para métodos que utilizam ondaletas, na presença de erros em séries temporais. / In this thesis, rates of convergence to zero are obtained for the estimation risk, for non-parametric regression using wavelets, when the errors are correlated. Four non-parametric regression methods using wavelets, with un-equally spaced design are studied in the presence of correlated errors, that come from stochastic processes. Conditions on the errors and adaptations to the procedures are presented, so that the estimators achieve quasi-minimax rates of convergence. Whenever is possible, rates of convergence are obtained for the estimators in the domain of the function, under mild conditions on the function to be estimated, on the design and on the error correlation. Through simulation studies, the behavior of some of the proposed methods is evaluated, when used on finite samples. Generally, it is suggested to use one of the studied methods, however applying thresholds by level. Since the estimation of the detail coecients can be dicult in some cases, it is also proposed a general semi-parametric iterative procedure, for wavelet methods in the presence of time-series errors.

La drépanocytose est une hémoglobinopathie génétique ayant pour conséquences une anémie hémolytique chronique et sévère et des crises vaso-occlusives itératives. Cette pathologie s’accompagne également d’une intolérance à l’effort et d’altérations de la fonction et du tissu musculaire. Récemment, nous avons pu montrer, par une étude contrôlée et randomisée, l’innocuité et les bénéfices fonctionnels d’un programme d’entrainement en endurance, d’intensité modérée, chez des patients drépanocytaires. L’objectif de ce travail doctoral a été d’évaluer les effets de ce programme d’entrainement sur les caractéristiques musculaires de quarante patients drépanocytaires homozygotes. L’analyse des biopsies musculaires rapporte des adaptations tissulaires chez les patients entrainés, illustrées par une augmentation de la surface des myocytes, une amélioration de leur capacité oxydative, une augmentation du nombre de microvaisseaux sans modification de leur tortuosité, laissant supposer une meilleure oxygénation musculaire. L’excellente tolérance de ce mode d’entrainement semble reposer sur une plus faible mobilisation des voies anaérobies comme en témoigne la stabilité des activités enzymatiques associées à la glycolyse lactique et l’absence de modification du contenu musculaire des protéines impliquées dans la régulation du pH. Par ailleurs, cet entrainement n’a pas engendré de dégradation tissulaire notable. Ainsi, cet entrainement a non seulement apporté des bénéfices fonctionnels, mais également réduit les dysfonctionnements tissulaires musculaires. Cette thérapie par l’exercice peut donc être considéré comme une stratégie adjuvante prometteuse pour les patients drépanocytaires. / Sickle cell disease is a genetic hemoglobinopathy resulting in chronic and severe hemolytic anemia and iterative vaso-occlusive crisis. This pathology is also accompanied by exercise intolerance and alterations in muscle function and tissue. Recently, we demonstrated, through a randomized controlled study, the safety and functional benefits of a moderate-intensity endurance exercise training program in sickle cell disease patients. The objective of this doctoral work was to evaluate the effects of this training program on the muscle characteristics of forty homozygous sickle cell disease patients. The analysis of muscle biopsies reported tissue adaptations in trained patients, illustrated by an increase in the surface area of myocytes, an improvement in their oxidative capacity, an increase in the number of microvessels without modification of their tortuosity, suggesting a better muscle oxygenation. The excellent tolerance of this training mode seems to be based on a lower mobilization of the anaerobic pathways, as shown by the stability of the enzymatic activities associated with lactic glycolysis and the lack of any modification of the muscle protein content involved in pH regulation. Moreover, this training did not result in any significant tissue degradation. Thus, this training provided functional benefits, but also reduced muscle tissue dysfunctions. This exercise therapy can therefore be considered a promising adjuvant strategy for sickle cell disease patients.