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Dick, Terence. "Functional music and consumer culture (instrumental version)." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape15/PQDD_0008/MQ30210.pdf.
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Mauri, Simone. "Formal and functional properties of grammatical aspect in Ayt Atta Tamazight." Thesis, SOAS, University of London, 2015. http://eprints.soas.ac.uk/23675/.
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The primary aim of this thesis is to provide a description of the aspectual system of Ayt Atta Tamazight (henceforth AAT), a Berber language spoken in south-east Morocco. The thesis focuses on the role of aspect in narration and shows that the association of stativity with perfective marking and the properties of the chainedaorist construction jointly contribute to the observed distribution of verb forms in discourse. Furthermore, my thesis investigates the chained-aorist construction and proposes a novel analysis of it. The close scrutiny of AAT chained-aorist constructions suggests downplaying the role of sequentiality from the centrality previously attributed to it: even data from typically-sequential texts such as main storylines show the limitations of any account of aspect in discourse solely resting on the notion of sequentiality. This work suggests analysing the AAT chained-aorist construction in terms of initial-consecutive clause chaining. The initial-consecutive chaining form is analysed as a narrative device adopted to ensure textual cohesion. The analysis put forward here rests on an investigation of chained-aorist constructions across Berber alongside a cross-linguistic overview of the formal properties of clause chaining: this shows the previously-unreported presence of striking similarities between Berber and a number of other languages, including many affiliated to the Niger-Congo language family. From a typological point of view, this proves that initial-consecutive clause chaining is not as rare as previously thought. The study is also relevant to areal linguistics, since it might point to the existence of a large linguistic area including Moroccan Berber and a number of Berber dialects spoken across the Sahara, as well as languages affiliated to the Niger-Congo family. Another important outcome of this dissertation is a sketch grammar of AAT. This contributes to Berber dialectology by describing a variety spoken in an area littleinvestigated so far. It shows that AAT is similar to related varieties but still presents some specificity which will be of some interest to those scholars of Berber particularly interested in Berber typology and micro-variations.
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Kuram, Kadri. "The organization of functional heads and tense/aspect/mood interpretation in Turkish." Thesis, University of Newcastle upon Tyne, 2015. http://hdl.handle.net/10443/3006.
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This dissertation investigates the IP-related categories and how the verbal domain of Turkish is organized. Within the theory of Universal Grammar, there are three major approaches to the IP domain of languages. The initial distinction is between the Syncretic IP model and the Rich IP model. The former refers to the conception that human language only makes available the heads and phrases required in a specific derivation, and that languages display parametric variation while the latter argues that the human mind comes with a highly articulated and rigid schematic hierarchy where all features of all functional categories are available in every derivation without parametric variation, yet most of them are silent. Additionally, there is an intermediate hypothesis, the Split IP model, where only major categories such as tense, mood and aspect, have dedicated head positions, and the morphological form inserted to each head position specifies its value. The dissertation aims to find out which one of these models is supported by the data in Turkish. I argue that split or syncretic character of the IP in Turkish should be sensitive syntactic operations that can target the functional heads individually. With this in mind, I suggest that a non-finite adjunct clause in Turkish is exceptional in that it lacks any kind of content when it stands alone, and therefore cannot be uttered in isolation. Yet when adjoined to a matrix clause, it is interpreted as having the values of the functional heads in the matrix clause via the mechanism ‘copy’. The data illustrates that although ‘copy’ can target some heads individually, there are two sets of heads that are always copied as a whole. Assuming that ‘copy’ can only single out independent heads, I conclude that Turkish has two syncretic phrases where two morphemes co-head the phrase. Specifically, ability modal and negation form the deontic modality phrase (DmodP) while tense co-heads another phrase with an aspect or modal marker (TAMP).
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Schell, Karyn. "Functional categories and the acquisition of aspect in L2 Spanish : a longitudinal study /." Thesis, Connect to this title online; UW restricted, 2000. http://hdl.handle.net/1773/8407.
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Poursharifi, Pegah. "Immunometabolic aspect of C5L2 and C5aR in adiposity : physical, functional and physiological interactions." Doctoral thesis, Université Laval, 2014. http://hdl.handle.net/20.500.11794/25593.
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L’obésité est maintenant reconnue comme présentant une inflammation chronique et est caractérisée par une augmentation de l’infiltration de macrophages dans le tissu adipeux. Cette infiltration est réflètée par l’activation du système du complément qui agit comme élément déclencheur et précurseur aux autres fonctions immunitaires. Le C5L2 (C5aR-like receptor 2) a récemment été identifié comme récepteur pour la protéine stimulant l’acylation (ASP) ainsi que pour le facteur inflammatoire C5a (capable quant à lui d’aussi se lier au C5aR). Cette thèse porte sur: (i) l’interaction entre C5L2 et C5aR suite à l’activation de ceux-ci par leurs ligands respectifs dans des lignées cellulaires adipocytaires (3T3-L1) et de macrophages (J774), (ii) la contribution du C5aR au métabolisme et à la réponse immunitaire d’adipocytes provenant de modèles murins et (iii) l’association entre C5L2 et C5aR avec des facteurs reliés à l’obésité chez l’humain. Les récepteurs C5L2 et C5aR s’associent entre-eux de façon constitutive en homo- et hétérodimères et l’ajout de ligand à des cultures d’adipocytes 3T3-L1 ou de macrophages J774 augmente cette colocalisation. Autant l’ASP que le C5a ont réussi à induire une réponse fonctionnelle chez des adipocytes primaires. Lorsque des adipocytes primaires provenaient de souris invalidées pour le C5aR, les effets d’un traitement avec C5a étaient perturbés tandis que les effets médiés par un traitement à l’ASP étaient maintenus. De plus, l’addition de C5a bloquait la signalisation et la réponse fonctionnelle causées par un traitement à l’ASP chez les adipocytes primaires provenant de souris C5aRKO et de type sauvage. Finalement, l’expression des gènes C5L2 et C5aR dans le tissu adipeux de femmes obèses morbides était associée avec une adiposité croissante. De façon interessante, les ratios ASP/C5L2 et C5L2/C5aR augmentaient de façon significative avec l’obésité abdominale. Lorsque pris ensemble, l’interaction fonctionelle, physiologique et la proximité physique des récepteurs C5L2 et C5aR chez les adipocytes suggèrent un rôle potentiel de ceux-ci sur l’immunométabolisme du tissu adipeux. De surcroit, cette interaction met en valeur les liens qui existent entre le tissu adipeux et les protéines et récepteurs du complément tout en démontrant comment une réponse excessive au niveau immuno-métabolique pourrait exacerber le développement du niveau d’adiposité chez l’individu.From the convergence of metabolism and immune research has emerged a new research field, termed “Immunometabolism”. Obesity, an immunometabolic disease, is associated with a state of low-grade inflammation and is characterized by increased infiltration of macrophages into adipose tissue. Complement activation can act as an early trigger and precursor of other immune functions. C5aR-like receptor 2 (C5L2) has been identified as a receptor for Acylation Stimulating Protein (ASP) and the inflammatory factor C5a (which can also bind C5aR). This thesis sequentially evaluates (i) ligand-induced C5L2 and C5aR interaction in cultured 3T3-L1 adipocytes and J774 macrophages, (ii) the C5aR contribution in adipocyte metabolic and immune responses in mouse models, (iii) as well as C5L2 and C5aR association with obesity-related factors in humans. The immunometabolic receptors, C5L2 and C5aR, constitutively self-associate into homo-/heterodimers and ligand treatment of 3T3-L1 adipocytes and J774 macrophages increased their colocalization. Both C5a and ASP directly induced primary adipocyte signaling and function. However, in C5aRKO primary adipocytes, C5a effects were disrupted, while stimulatory effects of ASP were mostly maintained. Moreover, addition of C5a completely blocked ASP signaling and activity in both C5aRKO and WT primary adipocytes. Finally, C5L2 and C5aR expression in adipose tissue from morbidly obese women was associated with increased adiposity. Interestingly, ASP/C5L2 and C5L2/C5aR ratio markedly increased with abdominal obesity. Taken together, the closely linked physical, functional and physiological interaction between C5L2 and C5aR in adipocytes suggests a potential role in adipose tissue immunometabolism. This further highlights the important new links between adipose tissue and complement proteins/receptors and demonstrates how excessive immunometabolic responses may exacerbate adiposity.
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Hayashi, Lawrence. "The Relationship Between Visual Event Perception, Dishabituation of Neural Models and Progressive Aspect in English." Thesis, University of Oregon, 1991. http://hdl.handle.net/1794/24567.
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130 pagesProgressive aspect has traditionally been linked to notions of speaker viewpoint on conceptual structure - specifically, whether the speaker perceives an event as bounded or unbounded. The following research examines the cognitive structures of the mental representation that might underlay these conceptual notions, recasting viewpoint in cognitive terms. A cognitive model of information processing is presented, explaining processes of information parsing, message formulation and linguistic encoding as carried out by a functional grammar. In particular, we examine how the grammar uses the habituated or dishabituated states of neural models formed from sensory or memorial inputs in determining progressive or non-progressive message encoding. Hypotheses are tested by experiments based upon a paradigm in which speakers describe visual stimuli while simultaneously watching them on a screen. This online paradigm allows us to approximate the speaker's mental representation, providing text-independent measures to compare against linguistic output.
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Kell, Marilyn Fay, University of Western Sydney, of Arts Education and Social Sciences College, and School of Education and Early Childhood Studies. "Learning by experience: reconstructing the literacy engagement of nine men who self-report literacy difficulties." THESIS_CAESS_EEC_Kell_M.xml, 2005. http://handle.uws.edu.au:8081/1959.7/540.
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This thesis, a qualitative study, examined the literacy practices of nine workers who self-report literacy difficulties. Through a series of interviews it specifically investigated how, in the course of their daily work, their mediated behaviour resulted in development of literacy competence. Through analysis of the workers’ experiences this thesis explored sociocultural themes deriving from Vygotskian traditions such as the central mediational role of psychological tools and signs and the importance of activity taking place in social settings. It took the theoretical position that literacy is an increasingly complex construct that extends beyond functional connotations such as reading, writing and spelling. It focused on the kinds of literacy skills that individuals require in a world characterised by rapid and frequent changes. In doing so this thesis recognised the diverse modalities in literacy performance that emphasise ways of knowing and ways of doing or designing as well as reading, writing, listening, thinking, speaking and comprehending across a range of modalities. This thesis argues that sociocultural concepts are applicable to adult learners. In particular it concludes that adult learners in the course of their jobs demonstrate a repertoire of literacy competence through engagement in meaningful literacy practices. This thesis reports that a significant indicator of the reported broadening in literacy competence is the support structures available in the workplace and in particular the specific characteristics of mentorsDoctor of Philosophy (PhD)
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Jaramillo, Gutierrez Giovanna. "Identification and functional characterization of mosquito genes that affect plasmodium development." Doctoral thesis, Universite Libre de Bruxelles, 2009. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210251.
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Les moustiques anophèles sont les vecteurs du parasite Plasmodium l’agent du paludisme. Le parasite subit des pertes massives pendant son cycle de développement chez l’anophèle, ce qui suggère que les moustiques sont capables de développer une réaction immunitaire efficace contre le parasite. La connaissance de l’immunité et de la résistance des moustiques au genre Plasmodium provient principalement de systèmes de laboratoire qui utilisent des espèces de parasites de rongeurs ou d’oiseaux comme modèles du paludisme humain. Les observations présentées dans cette thèse suggèrent que certains gènes comme Tep1 et LRIM1 sont des médiateurs de réponses antiparsitiques contre différents Plasmodiums dans différents vecteurs. Cependant, le degré d'efficacité avec laquelle un moustique est capable de réduire le nombre de parasites peut être variable surtout entre combinaison de souche de moustique et de souche de parasite différentes, selon que la paire soit hautement compatible ou non.
Doctorat en Sciences
info:eu-repo/semantics/nonPublished
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Lowe, John J. "The syntax and semantics of tense-aspect stem participles in early Ṛgvedic Sanskrit." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:45516bfd-cffb-457a-904c-100695cbd938.
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In this thesis I investigate the syntax and semantics of tense-aspect stem participles in the Ṛgveda, focusing primarily on the data from the earlier books II–VII and IX, seeking to establish a comprehensive and coherent analysis of this category within the linguistic system of Ṛgvedic Sanskrit. In recent literature tense-aspect stem participles are usually treated as semantically equivalent to finite verbs wherever possible, but contradictorily where they differ from finite verbs their adjectival nature is emphasized. I argue that tense-aspect stem participles are a fundamentally verbal formation and can be treated as inflectional verb forms: they are adjectival verbs rather than verbal adjectives. At the same time, however, they constitute an independent sub-category of verb form which is not necessarily semantically dependent on corresponding finite stems. I examine the syntactic and semantic properties of tense-aspect stem participles both in relation to finite verbal forms and their wider syntactic context, formalizing the evidence in the framework of Lexical-Functional Grammar. Consequently I am able to categorize the syntactic and semantic deviations which many participles exhibit in comparison to finite verbal forms. I contend that many such forms cannot be treated synchronically (and sometimes diachronically) as participles, but form distinct synchronic categories. My analysis permits a considerably more refined definition of the category of tense-aspect stem participles, dependent on clear morphological, syntactic and semantic criteria, as opposed to the usual, purely morphological, definition. From a diachronic perspective I argue that the category of tense-aspect stem participles as found in the Ṛgveda more closely reflects an inherited Proto-Indo-European category of tense-aspect stem participles than is usually assumed. I also reconsider theoretical treatments of participial syntax and semantics, and develop a more precise typology of non-finite verb systems which adequately accounts for Sanskrit participles.
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Sapountzaki, Galini G. "Free functional elements of tense, aspect, modality and agreement as possible auxiliaries in Greek sign language." Thesis, University of Bristol, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.424127.
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Dente, Sébastien. "The stakes of circulation in sustainable societies : logistics and functional economy." Thesis, Troyes, 2013. http://www.theses.fr/2013TROY0017/document.
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Les économies circulaires et de fonctionnalité sont souvent présentées comme des stratégies prometteuses quant à leur capacité à résoudre les problèmes environnementaux associés aux systèmes de production et de consommation actuels. Cependant, malgré les consommations d’énergie et émissions croissantes associées à la mondialisation de nos systèmes modernes, la question de la circulation reste peu abordée. Le présent travail s’attache à combler ce manque en analysant les effets de la représentation des activités humaines et des processus de circulation sous le champ de la durabilité. En s’intéressant ainsi au triptyque durabilité/chaîne d’approvisionnement/ économies circulaires et de fonctionnalités, le présent travail montre notamment la barrière à la durabilité que constitue la représentation standardisée de l’espace et du temps associée à la convention économique actuellement dominante. Ainsi, l’approche en circuit fermé de l’économie circulaire et l’approche servicielle de co-production associée à l’économie de fonctionnalité ne s’avèrent être des stratégies efficacement durables que si une approche spécifique des ressources et de la demande y est associée. Ce point a notamment été développé à travers un modèle logistique qui montre par rapport à un scénario logistique de référence une augmentation de 5% des émissions de CO2 liés au transport de marchandises entre régions françaises pour une approche générique de l’économie de fonctionnalité contre une diminution de 3% des émissions dans le cas d’une approche spécifiqueFunctional and circular economies are often presented as promising strategies to address the environmental issues associated with our modern production/consumption systems. Within these systems, the circulation processes themselves are usually poorly addressed, in spite of the increasing energy consumption and emissions associated with logistics under the current trends of globalization. The present thesis aims at filling this gap by analyzing the relationship between the representation of human activities and circulation processes and the issue of sustainability. Dealing with the triptych sustainability/supply chain management/circular and functional economies, the thesis shows that the standardized representation of space and time in the current dominant economic conventions acts as a barrier to the development of truly sustainable circulation processes. It finds that the closing loop approach of the circular economy and the product/service approach of the functional economy require specific definitions and policy measures for resources and demand, so that they can be considered as real sustainable strategies. This necessity to develop specific new approaches was further supported with evidence from a new logistics and freight transportation model for France. The model indicates that a generic approach towards a functional economy would lead to 5% increase of CO2 emissions (associated with French interregional traded tons) while a targeted approach would lead to a 3% reduction in comparison to the reference logistics scenario
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Abeto, Benjamin. "An Application of Systems Engineering to Analyze the Interagency Coordination Aspect of Counter Trafficking and Terrorism." Thesis, Monterey, California: Naval Postgraduate School, 2012. http://hdl.handle.net/10945/7286.
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This thesis utilizes principles of the systems engineering process discussed by Dennis Buede in â The Engineering Design of Systems: Models and Methods (2nd ed.)â (2009). The systems engineering process is used to create a functional architecture to analyze interagency coordination in support of counterterrorism efforts in the United States European Command area of operation. The resulting functional architecture serve as tools for policymakers as they determine the best ways to create a synchronous whole of government approach to defend United States interests.
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Lin, Shang-Chun [Verfasser]. "Aspect of classical density functional theory : crystals and interfaces in hard-disk systems and the problem of constructing functionals using machine learning methods / Shang-Chun Lin." Tübingen : Universitätsbibliothek Tübingen, 2021. http://d-nb.info/1230796320/34.
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Torres, FÃbio Fernandes. "Os domÃnios funcionais do gerÃndio em LÃngua Portuguesa." Universidade Federal do CearÃ, 2014. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=13574.
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CoordenaÃÃo de AperfeÃoamento de Pessoal de NÃvel SuperiorFundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico
Esta tese trata do estudo das construÃÃes gerundivas em LÃngua Portuguesa, a partir de dados provenientes dos sÃculos XVI, XVII, XVIII, XIX e XX, sob o suporte teÃrico do Funcionalismo LinguÃstico Norte-americano, para cumprir trÃs objetivos principais: a) constituir um corpus diacrÃnico, de natureza e caracterÃstica semelhantes, determinado por parÃmetros bem regulares, para se analisar o funcionamento das construÃÃes gerundivas nas variedades do PortuguÃs europeu e brasileiro, em perspectiva sincrÃnica e diacrÃnica, garantindo-se uma amostra equÃnime do material analisado; b) descrever o domÃnio funcional aspecto-temporal do gerÃndio, no qual sÃo codificadas as funÃÃes de tempo, aspecto e modalidade; c) descrever o domÃnio funcional aspecto-circunstancial do gerÃndio, em que sÃo expressas as circunstÃncias associadas a aspecto. Foram encontradas 3.910 ocorrÃncias de gerÃndio, das quais 1.671 estÃo distribuÃdas no domÃnio aspecto-temporal e 2.239 estÃo distribuÃdas no domÃnio aspecto-circunstancial. As construÃÃes gerundivas foram submetidas a tratamento estatÃstico no programa Goldvarx, cuja frequÃncia de uso foi verificada a partir das seguintes categorias: valores semÃntico-sintÃticos, valores circunstanciais, noÃÃes temporais, noÃÃes aspectuais, modalidade, relevo discursivo, sÃculo e variedade do PortuguÃs. Os resultados foram avaliados mediante o PrincÃpio da MarcaÃÃo, proposto por GivÃn (1990, 1991), e revelaram que: no domÃnio funcional aspecto-temporal, o gerÃndio adjetivo e o gerÃndio coordenado apresentam-se como categorias nÃo-marcadas; o gerÃndio independente, o gerÃndio imperativo e o gerÃndio conectivo como categorias intermediÃrias; e o gerÃndio narrativo e o gerÃndio descritivo como categorias marcadas. No domÃnio funcional aspecto-circunstancial, as circunstÃncias de modo, tempo, causa sÃo categorias nÃo-marcadas; as circunstÃncias de consequÃncia, condiÃÃo e finalidade sÃo categorias intermediÃrias; e as circunstÃncias de concessÃo, proporÃÃo, comparaÃÃo e conformidade sÃo circunstÃncias marcadas.
This thesis deals with the study of constructions with gerund in Portuguese, researched from data from XVI, XVII, XVIII, XIX and XX centuries, by the theoretical perspective of North American Functionalism, to get three main purposes: a) to compose a diachronic corpus of similar nature and characteristic, determined by regular parameters in order to analyze the functioning of the constructions with gerund in Brazilian and European Portuguese, in synchronic and diachronic perspective, establishing an equal sample of the material analyzed; b) to describe the tense-aspect functional domain of gerund, in which the functions of tense, aspect and modality are codified; c) to describe the aspect-circumstantial functional domain of the gerund in which the circumstances are associated with the aspect. It was found 3,910 ocurrences of gerund, 1,671 from them are distributed in tense-aspect domain and 2,239 are distributed in circumstantial-aspect domain. The gerund constructions were submitted to statistical analysis in Goldvarx program, whose frequency of use was verified from the following categories: syntactic-semantic values, circumstantial values, tense notions, aspect notions, modality, grounding, century and variety of Portuguese. The results were analyzed by Markedness Principle, proposed by GivÃn (1990, 1991), and they have revealed that: in the tense-aspect functional domain, the adjective gerund and coordinated gerund appear as marked categories; independent gerund, imperative gerund and connective gerund as intermediate categories; and the narrative and descriptive gerund as marked categories. In the circumstantial-aspect functional domain, the circumstances of mood, tense, cause are non- marked categories; the circumstances of consequence, condition and finality are intermediate categories; and the circumstances of concession, proportion, comparison and conformity are marked circumstances.
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Blandin, Stéphanie. "Functional analysis of thioester-containing proteins in immune responses of the mosquito, Anopheles gambiae." Université Louis Pasteur (Strasbourg) (1971-2008), 2004. https://publication-theses.unistra.fr/public/theses_doctorat/2004/BLANDIN_Stephanie_2004.pdf.
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Almeida, Gonçalves Sara de. "Identification of new genes involved in hereditary steroid-resistant nephrotic syndrome using next generation sequencing and in vivo functional characterization in drosophila melanogaster." Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCB030/document.
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Pas de résuméNephrotic syndrome (NS) is a kidney disease characterized by disruption of the glomerular filtration barrier and the massive loss of proteins into the urine. Although in the majority of cases treatment with steroids leads to remission of the disease, in 15-20% of cases the disease is not responsive to this therapy and is classified as steroid-resistant nephrotic syndrome (SRNS). SRNS is a clinical condition with high morbidity leading to progressive renal failure as well as multiple metabolic and cardiovascular complications. Extensive research over the last 20 years has identified more than 40 SRNS causing genes that are crucial for function of the podocyte, a highly specialized kidney epithelial cell. However, the mutated gene is still unknown in about half of the familial cases. We have used exome sequencing to identify new genes mutated in SRNS. In order to prove the pathogenicity of the identified mutations we used the Drosophila model, assessing defects of fly viability and the structure and function of nephrocytes, podocyte like-cells. My thesis work consists of two projects. Firstly, we identified biallelic mutations in a new candidate gene, SGPL1, encoding the sphingosine 1- phosphate lyase, in individuals presenting SRNS with facultative adrenal insufficiency, ichthyosis, neurological defects and immunodeficiency. SGPL1 is the main catabolic enzyme of sphingolipids, irreversibly degrading sphingosine 1-phosphate into phosphoethanolamine and hexadecenal. In flies, these mutations were shown to decrease viability, induce nephrocyte defects and lead to the accumulation of sphingoid bases due to the loss of SGPL1 catabolic activity. Together, these results indicate that the identified SGPL1 mutations are pathogenic and cause a new syndromic form of SRNS. Moreover, in a second project, we defined the contribution of homozygous mutations found in two different genes, ADD3 and KAT2B, to a complex phenotype found in affected individuals from one consanguineous family. These individuals presented with neurological defects, cataracts, mild skeletal defects, cardiomyopathy and SRNS. ADD3 encodes adduciny, an F-actin capping protein that also links the actin cytoskeleton to the spectrin based membrane skeleton, while KAT2B encodes the lysine acetyltransferase 2B, mainly known for acetylation of histones and modulation of transcriptional programs. We found additional nonrelated patients carrying only biallelic ADD3 mutations that presented a partially overlapping syndrome but with no cardiac or renal manifestations. In the Drosophila model we found that both ADD3 and KAT2B mutations impaired fly viability and that the ADD3 mutation also impaired fly motor function. However, only the KAT2B mutation induced functional defects in Drosophila heart and nephrocytes. Altogether, these results suggest that ADD3 mutations are responsible for a neurological phenotype with facultative cataracts and skeletal defects while the KAT2B mutation induces heart and kidney defects. These results highlight the Drosophila as a good in vivo model to test the pathogenicity of the mutations found in SRNS candidate genes
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Lornage, Xavière. "Identification and functional characterization of novel genes implicated in congenital myopathies." Thesis, Strasbourg, 2019. http://www.theses.fr/2019STRAJ067.
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Les myopathies congénitales sont des maladies génétiques sévères caractérisées par une faiblesse musculaire très invalidante de début infantile. Afin d’identifier de nouvelles causes génétiques, nous avons séquencé les exomes de patients myopathes qui ne disposaient pas de diagnostic moléculaire et leur analyse a mis en évidence deux nouveaux gènes de myopathie. MYPN et ACTN2 codent pour deux protéines structurales du sarcomères appelées myopalladine et alphaactinine-2. Afin d’étudier l’impact des mutations sur la fonction de la protéine et sur la physiologie du muscle, des analyses moléculaires et fonctionnelles ont été réalisées en modèles cellulaires et animaux. Les mutations dans MYPN induisent une perte de la protéine, et dans les muscles de souris, l’alpha-actinine-2 mutée conduit à une faiblesse musculaire et génère des défauts structuraux similaires à ceux retrouvés chez les patients. Ces résultats ont un impact direct sur la prise en charge des patients et sur le conseil génétique, sur la compréhension de voies de signalisation fondamentales pour la physiologie musculaire, et mettent en évidence de nouvelles cibles thérapeutiquesCongenital myopathies are severe genetic muscle diseases characterized by a disabling early-onset muscle weakness. In order to identify new genetic causes, we sequenced the exomes of molecularly undiagnosed congenital myopathy patients, and their analysis highlighted two novel myopathy genes. MYPN and ACTN2 encode two structural sarcomeric proteins called myopalladin and alphaactinin-2. To evaluate the impact of the mutations on the protein function and on muscle physiology, molecular and functional analyses were performed in cell and animal models. The MYPN mutations resulted in loss of myopalladin expression, and in mouse muscles, mutated alpha-actinin-2 led to muscle weakness and structural defects similar to those observed in the patient muscles. These results have a direct impact on the disease management of the patients and on genetic counselling, provide a better understanding of the signaling pathways required for muscle physiology, and highlight novel therapeutic targets
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Resnik, Gabriela. "Los Nombres eventivos no deverbales en español." Doctoral thesis, Universitat Pompeu Fabra, 2011. http://hdl.handle.net/10803/22647.
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El propósito general de esta tesis es demostrar que el denominado aspecto léxico o aktionsart es una propiedad transcategorial, que implica rasgos que pueden asociarse a las raíces léxicas en el SD independientemente de procesos de derivación. Tal es el caso de los nombres eventivos no deverbales en español (fiesta, accidente), objeto principal de análisis del trabajo. La propuesta se enmarca en el modelo de la Morfología Distribuida (Embick & Halle, en prensa) e incluye los siguientes aspectos: una formulación más flexible de la relación entre estructura argumental y eventiva (contra Grimshaw (1990); una explicación de la obligatoriedad de argumento interno con nominalizaciones eventivas en términos de la presencia de v en su estructura funcional (Alexiadou, 2001); la identificación de efectos sintácticos derivados de la eventividad de nombres no deverbales como guerra, dentro y fuera del SD, explicados en términos de una estructura funcional que incluye rasgos o proyecciones específicas; la identificación de clases aspectuales de nombres no deverbales en la línea de Vendler (1967); una explicación de la polisemia en nombres eventivos no deverbales en términos de las características de la estructura funcional que domina la raíz léxica (Borer, 2005); un análisis de los efectos de la presencia de más de un núcleo funcional eventivo en las formas derivadas (llegada, accidentarse) y los núcleos complejos (hacer huelga, dar (una) clase).The general purpose of this thesis is to demonstrate that the so-called lexical aspect or aktionsart is a transcategorial property, involving features that may be associated to lexical roots in the DP in the absence of any derivation process. This is the case of non-deverbal event nouns in Spanish (fiesta, ‘party’; accidente, ‘accident’), our main object of analysis. Our proposal is based on the Distributed Morphology framework (Embick & Halle, to appear) and includes the following topics: a more flexible statement of the relation between argument and event structure (against Grimshaw (1990); an explanation of the obligatoriness of internal argument expression with process nominalizations in terms of the presence of v in its functional structure (Alexiadou, 2001); the identification of syntactic effects derived from the eventive nature of non-deverbal nouns such as guerra (‘war’), inside and outside the DP, accounted for in terms of a functional structure which includes specific features or projections; the identification of aspectual classes of non-deverbal event nouns à la Vendler (1967); an explanation of polysemy in non-deverbal event nouns in terms of the properties of the functional structure dominating the lexical root (Borer, 2005); an analysis of the effects of the presence of more than one eventive functional head in derived forms (llegada, ‘arrival’; accidentarse, ‘to have an accident’) and complex heads (hacer huelga, ‘to go on strike’; dar (una) clase, ‘to teach (a class)’).
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Ochs, Julien. "Développement d'un outil pour l'évaluation fonctionnelle des patients déments : introduction en France du Functional behavior profile et de sa version révisée." Grenoble, 2010. http://www.theses.fr/2010GRENH005.
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Dans le monde, plus de 24 millions de personnes vivent avec une démence. En France, environ 870 000 personnes sont atteintes de la maladie d'Alzheimer ou d'une maladie apparentée, avec près de 220 000 nouveaux cas par an. La pathologie démentielle est la principale cause de dépendance chez la personne âgée. En effet, le déclin des structures cognitives s’accompagne entre autres d'un déclin fonctionnel qui perturbe insidieusement et de plus en plus les activités de la vie quotidienne. En l'absence de traitement curatif de ces pathologies, l'objectif principal des soins apportés aux patients est de maintenir le plus longtemps possible la capacité des personnes à fonctionner de la manière la plus autonome dans leur environnement psycho-social familier. De plus, le nombre et la diversité des pathologies démentielles entraînent souvent une incompréhension de la part de l'entourage en charge du patient. L'aidant qui ne comprend que partiellement les conséquences réelles et la nature des déficits cognitifs en oeuvre chez son proche malade peut parfois ignorer ou sousestimer les déficits existants. Dans ce cadre, l'évaluation psychologique (affective, sociorelationnelle et cognitive) est le premier pas vers la prise en charge des patients. Malheureusement, relativement peu d'outils spécifiques sont disponibles en France pour identifier et mesurer les capacités fonctionnelles des patients. L’objectif de cette thèse était donc d’effectuer le pilotage clinique d’une première étude concernant la traduction française d'un outil hétéro-évaluatif des capacités fonctionnelles des patients déments. Nous avons donc introduit, au sein des consultations gériatriques, une traduction française du Functional Behavior Profile (FBP ; Baum et al. , 1993). Dans un premier temps, nous avons montré que le FBP demeurait un instrument pertinent pour l'évaluation de la démence. De plus, le FBP a permis de renseigner l’équipe pluridisciplinaire sur les capacités résiduelles du patient et sa passation a permis à l’ aidant de réfléchir d'une manière structurée sur les modifications fonctionnelles qui surviennent chez son proche. Dans un second temps, les révisions apportées à l'outil, qui ont donné naissance au FBPr, nous ont permis d’affiner les informations obtenues et d'améliorer la compréhension des items par les aidants. Ces modifications permettent désormais de distinguer la performance des patients pour des tâches simples ou complexes, des tâches routinières et familières, et de savoir si les comportements observés diffèrent des comportements présymptomatiques. Quoi qu'il en soit, ce type d'évaluation, sensible aux effets spécifiques des maladies démentielles, donne des informations plus complètes à l'équipe soignante, tout en mettant l'accent sur ce que les patients sont encore capables de faire au quotidien. Cette base d'information peut ensuite être mise à profit pour discuter avec les aidants familiaux en charge d’un proche dément en promulguant des conseils de prise en charge individualisés et adaptés aux habiletés et déficits de chaque patient, dans le but de maximiser son autonomie en exploitant aux mieux ses ressources résiduelles, et ainsi augmenter ou maintenir son engagement dans les actes de la vie quotidienne. Ce maintient d'activité dans les actes quotidiens, et notamment dans les actes sociaux de la vie quotidienne, peut avoir un impact important et positif sur la qualité de vie des patients souffrant de démence.
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Pineda, Marin Claudia Patricia. "Functional measurement applied to major societal issues in Colombia : drug, sex, violence and forgiveness." Thesis, Toulouse 2, 2018. http://www.theses.fr/2018TOU20061.
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La Colombie est un pays situé dans le nord-ouest de l’Amérique du Sud. La plupart de ses 46 millions d’habitants sont concentrés dans les villes. Selon le Département Administratif National des Statistiques (2017), la répartition de la population s’explique par le déplacement forcé des personnes, causé par le conflit armé qui a duré presque 60 ans (de 1960 à 2015). Dans la présente thèse, quatre problèmes d’un intérêt particulier sont examinés : l’éducation pour prévenir la consommation des drogues, l’éducation sexuelle, la capacité de pardon dans des situations de négligence des soins et la capacité de pardon des actes de violence perpétués contre les femmes dans le contexte du conflit armé colombien. Cette étude a identifié que la volonté de pardon des participants est faible. Cependant, un petit groupe de participants seulement accorde une importance au crime lui-même concernant le pardon, tandis qu’un autre petit groupe, accorde plus d’importance à l’attitude de l’agresseur. Concernant l’éducation des jeunes en vue de prévenir la consommation des drogues, il est important de souligner qu’il existe encore plusieurs sujets tabous en Colombie. Selon les données de l’étude, les points de vue prohibitionniste et autoritaire concernant la consommation des drogues sont les plus partagés. S’agissant de l’éducation sexuelle, la plupart de jeunes en Colombie n’y ont pas accès, bien qu’il s’agisse d’un droit fondamental. De plus, les parents ou les personnes en situation de parentalité semblent être incapables d’éduquer leurs enfants efficacement et assertivement au regard de ce sujetColombia is located in northwestern portion South America. Currently, 46 million people inhabit the country and are mainly concentrated in the cities. According to the National Administrative Department of Statistics (2017), the population distribution is mainly explained by the forced displacement of persons resulting from the Colombian armed conflict that lasted nearly 60 years (from 1960 to 2015). In the present thesis, four problems of particular interest are examined: education for preventing drug use, sexual education, the capacity to forgive in situations of medical negligence, and the capacity to forgive acts of violence perpetrated against women in the context of the Colombian armed conflict. In the first study on the willingness of Colombian adults to forgive, Colombians have difficulties in integrating stimuli at the moment of deciding whether to forgive in a political context, yet it is not easy for them to forgive in a political context compared to other situations such as medical negligence. About the second study, polarization and the invisibility of victims are also common themes with respect to crimes committed against women. The study identified that the willingness to forgive of the participants is low. However, only a small group of participants consider the crime itself upon contemplating forgiveness, while another small group consider the attitude of the aggressor. In regard to the education of young people to prevent drug use, it is important to highlight that many subjects are still taboo in Colombia. As shown by the data, prohibitionist and authoritarian standpoints on drug use are considered to be the most acceptable. In regard to sexual education, the majority of young people in Colombia do not have access to such education despite this being a basic right. Likewise, parents and caretakers are apparently unable to effectively and assertively educate their children on this topic
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Nattarayan, Vasugi. "The functional and therapeutic role of BIN1 and PI3K-C2β in skeletal muscle physiology and pathophysiology." Thesis, Strasbourg, 2019. http://www.theses.fr/2019STRAJ083.
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Les myopathies centronucléaires (CNM) constituent un groupe de troubles congenItaux graves qui affectent les muscles squelettiques et se caractérisent principalement par une faiblesse musculaire, une hypotonie et une détresse respiratoire. L'une des caractéristiques du CNM est la présence de noyaux centraux dans les fibres musculaires, qui s'opposent à sa localisation périphérique normale. La forme la plus grave de la maladie est due aux mutations du gène MTM1, alors que certains des autres gènes couramment mutés sont BIN1 et DNM2. À ce jour, il n’existe aucun traitement pour le CNM. Afin de mieux comprendre le rôle de BIN1 dans les mécanismes pathologiques de la maladie, nous avons créé et caractérisé un nouveau modèle de souris Bin1 (Bin1 cKO) pour la CNM et avons mis en évidence divers défauts structurels et fonctionnels associés à la perte de BIN1 dans les muscles squelettiques. Nous avons fourni une preuve de concept thérapeutique pour CNM liée à BIN1, où la régulation à la baisse de Dnm2 chez des souris Bin1 cKO a sauvé ses phénotypes CNM. Séparément, nous avons montré que l’inhibition de l’activité kinase de PI3K-C2β avait pour résultat le sauvetage des phénotypes CNM de souris Mtm1 KO. De même, nous avons montré une récupération partielle probable des phénotypes CNM de souris Bin1 cKO en inhibant l'activité kinase de PI3K-C2β. Outre les souris Bin1 cKO, nous avons également créé et caractérisé un modèle de souris Bin1 KI, imitant la mutation BIN1 K35N du CNM chez le patientCentronuclear myopathies (CNM) are a group of severe congential disorders that affect the skeletal muscles and are mainly characterized by muscle weakness, hypotonia and respiratory distress. One of the hallmark features of CNM is the presence of central nuclei in the muscle fibers, opposing to its normal peripheral localization. The most severe form of the disease is due to mutations in MTM1 gene, whereas some of the other commonly mutated genes are BIN1 and DNM2. To date, there is no cure available for CNM. To better understand the role of BIN1 in disease pathomechanisms, we have created and characterized a novel Bin1 mouse model (Bin1 cKO) for CNM and have shown various structural and functional defects associated with the BIN1 loss in skeletal muscles. We have provided a therapeutic proof of concept for BIN1 related CNM, where the downregulation of Dnm2 in Bin1 cKO mice rescued its CNM phenotypes. Separately, we have shown that inhibiting the kinase activity of PI3K-C2β results in the rescue of CNM phenotypes of Mtm1 KO mice. Similarly, we have shown a probable partial rescue of CNM phenotypes of Bin1 cKO mice by inhibiting the kinase activity of PI3K-C2β. Apart from Bin1 cKO mice, we have also created and characterized a Bin1 KI mice model, mimicking the BIN1 K35N patient mutation of CNM
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Costa, Renata Cardoso Belo da. "Leishmania infantum extracellular material and human invariant natural killer T cells: a functional study." Doctoral thesis, Sorbonne Paris Cité, 2017. https://hdl.handle.net/10216/107808.
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Les cellules iNKT (de l’anglais invariant Natural Killer T) constituent un sous-type particulier de lymphocytes T caractérisé par un profil de type inné. Ces cellules répondent rapidement à des antigènes lipidiques et glycolipidique présentés par le CD1d, une glycoprotéine exprimée par les différentes cellules présentatrices d'antigène. Suite à l’activation, les cellules iNKT sont capables de produire de grandes quantités de cytokines anti-inflammatoires et pro-inflammatoires et elles sont impliquées dans différentes maladies, telles que l'allergie, l'auto-immunité, le cancer et les infections, parmi lesquelles la leishmaniose. Les parasites protozoaires de les espèces Leishmania sont les agents causaux de la leishmaniose, une maladie tropicale négligée dont la manifestation la plus grave affecte les organes viscéraux et qui peut être mortelle si elle n'est pas traitée. Le succès de l'infection dépend de la capacité du parasite à maitriser la réponse immunitaire de l'hôte. Récemment, quelques groupes, y compris le nôtre, ont observé que les parasites Leishmania libèrent des vésicules extracellulaires (VE). Les VE sont formées par une bicouche membranaire lipidique, contenant des lipides, des protéines et du matériel génétique et elles peuvent transmettre des molécules dérivées des pathogènes aux cellules hôte sans contact direct entre les cellules. Les VE produites par les parasites Leishmania et aussi par d’autres protozoaires ont été associés à des effets pro-parasite car elles favorisent un environnement plus permissif à l'établissement de l'infection. Dans cette thèse, nous avons étudié l'effet du matériel extracellulaire (ME), correspondant aux VE et aux molécules non-associées aux VE, libéré par les promastigotes de L. infantum sur les cellules iNKT. Dans le début de ce travail, il a été observé que le ME de L. infantum empêche l'expansion ex-vivo des cellules iNKT humaines à partir de cellules mononucléaires du sang périphérique. Cela a mis en évidence la communication entre les cellules iNKT et le ME de L. infantum, ce qui a été exploré par la suite. Le ME de L. infantum module la capacité très importante des cellules iNKT à produire des cytokines. En effet, le ME de L. infantum empêche la production des différentes cytokines par les cellules iNKT, comme par exemple IL-4 et IFNγ. De plus, nous avons aussi démontré que le ME de L. infantum compète avec l’α-GalCer, un agoniste très puissant des cellules iNKT, pour la liaison à la molécule CD1d, ce qui justifie l’effet inhibiteur dans l'activation des cellules iNKT. Nous avons aussi montré que les lipides qui sont présents dans chaque fraction du ME de L. infantum ont un rôle très important dans l’inhibition de l'activation et l'expansion des cellules iNKT. Ainsi, le ME de L. infantum, par ces lipides, peut participer à l’altération de l’activation des cellules iNKT dépendante du CD1d. Cela ajoute une nouvelle évidence de la contribution du ME de L. infantum dans la subversion de la réponse immunitaire de l’hôte. La communication entre le ME libéré par un pathogène et les cellules iNKT a été étudié pour la première fois, ce qui a suggéré un mécanisme de modulation de ces cellules qui n’avait jamais été décrit. Ce travail ouvre des perspectives pour l'étude de l'interaction de ME libéré par d'autres pathogènes avec des cellules iNKT. De plus, l'analyse des lipides contenus dans le ME de L. infantum pourra aboutir à la découverte de nouvelles molécules spécifiques pour inhiber les cellules iNKT. Cela apporterait des avantages significatifs dans les approches cliniques ciblant la modulation de l'activation des cellules iNKTThe invariant natural killer T (iNKT) cells constitute a particular subset of T lymphocytes characterized by an innate-like profile. These cells rapidly respond to lipid and glycolipid antigens bound by the glycoprotein CD1d expressed by different antigen presenting cells. Once activated, they release large amounts of anti- and proinflammatory cytokines. Thus, iNKT cells are endowed with a remarkable immunomodulatory potential and they have been implicated in different disorders, such as allergy, autoimmunity, cancer and infection, among which is leishmaniasis. Leishmania spp. are a group of protozoan parasites that includes the causative agents of leishmaniasis. This is a neglected tropical disease in which the most severe form of manifestation affects visceral organs and could be fatal if left untreated. Importantly, the success of Leishmania infection relies on the capacity of the parasite to subvert host immune responses. Recently, a few groups, including ours, observed that Leishmania parasites release extracellular vesicles (EVs). EVs are vesicles formed by a lipid bilayer membrane, containing other lipids, proteins and genetic material on their surface as well as in their lumen. Due to their potential to transmit messages between pathogens and host cells without a direct cell contact, they have been a focus of great interest regarding infection. EVs derived from Leishmania and other protozoan parasites have been associated with pro-parasite effects, by creating a more permissive environment to the establishment of the infection. Herein, we studied the effect of the extracellular material (ExM), which encloses both EVs and vesicle-depleted material, released by L. infantum promastigotes in iNKT cells. In the first steps of this work, it was observed that L. infantum ExM is capable of impairing the expansion of human iNKT cells ex vivo from peripheral blood mononuclear cells. This evidenced the cross-talk between iNKT cells and L. infantum ExM that we explored further. L. infantum ExM also modulates the important capacity of iNKT cells to release cytokines, impairing the production of different cytokines, such as IL-4 and IFNγ by these cells. Furthermore, we also show that L. infantum ExM competes with α-GalCer, a potent iNKT cell agonist, for CD1d binding, which justifies its effect in the impairment of iNKT cell activation. Additionally, we also proved the lipids present in each fraction of L. infantum ExM take an important role in the inhibition of iNKT cell activation and expansion. Thus, L. infantum ExM, through their lipids, is suggested to participate in the impairment of CD1d-mediated activation of iNKT cells, adding a new evidence regarding the contribution of the parasite ExM to subvert host immune responses. To the best of our knowledge, this is the first time that the cross-talk between the ExM released by a microbe and iNKT cells was assessed, shedding light on a mechanism of iNKT cell modulation that remained unexplored so far. This opens new perspectives regarding the study of the interaction of the ExM released by other pathogens with iNKT cells. Moreover, a further analysis of the lipid content of L. infantum ExM might allow the finding of new inhibitory molecules specific to iNKT cells, which can bring significant advantages in clinical approaches targeting the modulation of iNKT cell activation
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Fernandes, Thiago Soares. "Framework para estimar requisitos não funcionais em aplicações móveis." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/117285.
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O desenvolvimento de aplicações móveis é guiado por uma especial atenção aos requisitos não funcionais (do inglês, NFR - Non Functional Requirements), sendo o principal objetivo proporcionar uma boa experiência ao usuário final. Entretanto, a avaliação de NFRs é ainda uma tarefa manual, não estruturada e que consome muito tempo. Esta dissertação apresenta um estudo de várias abordagens relacionadas à avaliação de desempenho (por exemplo, o uso de aplicações de benchmark) e de NFRs no âmbito de sistemas móveis. No entanto, os benchmarks atuais são genéricos, geralmente, voltados para a plataforma de execução e nem sempre instituem um consenso na classificação de dispositivos. Visando uma melhor avaliação de NFRs e uma classificação de dispositivos com base nas necessidades de aplicações reais, este trabalho propõe um framework para gerar benchmarks orientados às necessidades de cada aplicação e, assim, fornecer uma forma eficiente e eficaz para estimar requisitos não funcionais em sistemas móveis. Essa ferramenta é composta por uma biblioteca de testes parametrizáveis, métricas e uma estrutura para geração rápida de benchmarks orientados à aplicação. O framework foi construído utilizando o paradigma de programação orientada a aspectos para coleta das métricas por fornecer uma maior modularidade e separação de interesses, de modo que a sua evolução, através da adição de outras métricas ou testes, seja facilitada. Para validação da proposta, foram realizados experimentos com cinco aplicações Android reais disponíveis na Play Store, sendo que para cada aplicação foi gerado um benchmark específico cujos resultados foram comparados com os obtidos para as aplicações móveis reais. Os resultados são promissores, mostrando que é possível criar aplicações de teste com comportamento semelhante ao de aplicações reais e, assim, classificar dispositivos com base nas necessidades das aplicações, através da análise das métricas presentes no framework. Essas métricas podem, ainda, orientar o desenvolvedor na otimização de suas aplicações ou ainda na escolha de dispositivos com melhor custo benefício para executar seus aplicativos.The mobile application development is guided by a special attention to non-functional requirements (NFRs), where a good experience for the end user is the primary goal. However, NFRs evaluation is still a manual, unstructured and time-consuming task. This thesis presents a study of several approaches related to performance and NFR evaluation within mobile systems. Among these approaches is the use of benchmark applications. Currently available benchmarks are generic, usually focused on the execution platform and do not always establish a consensus on the classification of devices. For a better NFRs assessment and classification of devices based on real application needs, this work proposes a framework for generating application-oriented benchmarks for the early estimation of non-functional requirements in mobile systems. This framework is composed of a configurable test library, a set of metrics and an engine the assembling of the test program. The framework uses aspect-oriented programming to collect the metrics of interest. This approach provides increased modularity and separation of concerns, thus facilitating the improvement of the framework itself, by adding other metrics or testing operations. In order to validate the proposed framework we used five application from the Android Play store. For each application, a specific benchmark is generated and executed in different devices. The results are compared to those of the execution of the actual applications in the same devices. Experimental results are promising, showing that it is possible to create test applications with similar behavior to that of real applications and thus classify devices based on the actual application needs, by analyzing the metrics present in the framework. These metrics can also guide the developer in optimizing her applications or in choosing devices with the best trade-off between cost and performance to run a given application.
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Taylor, John (John Allen). "Aspects of Universality in Function Iteration." Thesis, University of North Texas, 1991. https://digital.library.unt.edu/ark:/67531/metadc278799/.
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Bombonatti, Denise Lazzeri Gastaldo. "PARNAFOA: um processo de análise de requisitos não-funcionais orientado a aspectos." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/3/3141/tde-06122010-105625/.
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Esta tese tem o objetivo de definir um processo para análise de requisitos não-funcionais orientado a aspectos denominado PARNAFOA. Este processo utiliza, de maneira integrada, métodos de tratamento de requisitos não-funcionais, baseados no NFR Framework, e métodos orientados a aspectos. Como resultado principal obtém-se um modelo de casos de uso que incorpora novas funções relacionadas aos requisitos não-funcionais. A aplicação do PARNAFOA foi realizada em cinco sistemas de software, com domínios, características e complexidades diversos. A avaliação da aplicação deste processo mostrou que o tratamento dos requisitos não-funcionais, desde as fases iniciais do desenvolvimento dos sistemas de software, complementa o modelo de casos de uso com funções adicionais ou gera restrições de projeto. Se estes requisitos não forem considerados desde o início, a introdução posterior dessas funções pode causar alterações nos modelos consolidados ou as atividades de projeto podem ser realizadas sem considerar as restrições. As aplicações do PARNAFOA e sua conseqüente melhoria, incorporada após sua avaliação, permitiu torná-lo mais flexível do que sua versal inicial. Aplicações futuras, com outros tipos de requisitos não-funcionais, irão permitir o amadurecimento deste processo.The aim of this thesis is to define an aspect-oriented non-functional requirements analysis process named PARNAFOA. This process applies nonfunctional requirements methods in an integrated manner, based on NFR Framework, and aspect-oriented methods. A use case model that embodies non-functional requirements as new functions is the main result obtained from this process. PARNAFOA application was performed in five software systems, with diverse features, domains and complexities. The evaluation of this process application showed that the treatment of these non-functional requirements, from the early phases of software systems development, complements the use case model with additional new functions or generates project restrictions. If these requirements are not considered from the very beginning, the introduction of these functions at a later phase can generate modifications in consolidated models or project activities, that do not consider these restrictions, can be performed. The PARNAFOA applications and consequent improvement, incorporated after the assessment, allowed it to become more flexible than the initial version. Future applications, with other non-functional requirements types, will provide this process maturity.
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Zea, OBANDO Claudia Yamilet. "Caractérisation et valorisation de microalgues tropicales." Thesis, Lorient, 2015. http://www.theses.fr/2015LORIS385/document.
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La biomasse des microalgues tropicales a des vertus naturelles qui peuvent être utilisées dans une large gamme de bioproduits. Leur valorisation peut permettre une production durable et commercialement viable. En effet, les microalgues tropicales représentent une grande biodiversité et bénéficient de conditions environnementales favorables à une production à grande échelle. Dans ce contexte, cette thèse vise à étudier de nouvelles souches tropicales afin de connaître leur potentiel de valorisation dans le domaine des biotechnologies, et plus particulièrement sur trois aspects : énergie, nutraceutique et antifouling. Ce dernier domaine a été étudié dans le cadre du projet ANR-CD2I « BIOPAINTROP » dont l’objectif est la lutte écoresponsable contre le biofouling. Ces travaux s’orientent vers des applications biotechnologiques, mais aussi vers le développement des nouvelles méthodes de caractérisation de l’activité antifouling. Sur les 50 souches étudiées, certaines ont montré la production de métabolites d'intérêt tels que le glycosylglycerol, des lipides de qualité pour la nutraceutique et la production de biodiesel. La souche Amphidinium sp. (P-43) a conduit à un extrait méthanolique possédant une activité biologique significative. Son efficacité dans la lutte contre le biofilm a été démontrée. De plus, l'étude d'écotoxicologie réalisée laisse présager d'un faible impact environnementalBiomass of tropical microalgae have natural virtues that can be used in a wide range of bioproducts. Their valuation can enable sustainable and commercially viable production. Indeed, tropical microalgae represent a large biodiversity and benefit from favourable environmental conditions for large scale production. In this context, this thesis aims to explore new tropical strains to determine their potential development in the field of biotechnology, particularly in three areas: energy, nutraceutical and antifouling. This field is studied in the project ANR-CD2I "BIOPAINTROP" whose objective is the eco-responsible fight against biofouling. These works target biotechnological applications, but also development of new methods to characterize antifouling activity.Of the 50 strains studied, some have shown interest in the production of metabolites such as glycosyl glycerol, quality nutraceutical and lipids for biodiesel production. The Amphidinium sp. (P-43) stain led to a methanol extract having biological activity of interest. Its efficiency against biofilm was demonstrated. Moreover, the ecotoxicology study has suggested a low environmental impact
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Meehan, Gary. "Aspects of functional programming." Thesis, University of Warwick, 1999. http://wrap.warwick.ac.uk/58566/.
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This thesis explores the application of functional programming in new areas and its implementation using new technologies. We show how functional languages can be used to implement solutions to problems in fuzzy logic using a number of languages: Haskell, Ginger and Aladin. A compiler for the weakly-typed, lazy language Ginger is developed using Java byte-code as its target code. This is used as the inspiration for an implementation of Aladin, a simple functional language which has two novel features: its primitives are designed to be written in any language, and evaluation is controlled by declaring the strictness of all functions. Efficient denotational and operational semantics are given for this machine and an implementation is devel- oped using these semantics. We then show that by using the advantages of Aladin (simplicity and strictness control) we can employ partial evaluation to achieve con- siderable speed-ups in the running times of Aladin programs.
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Dorgans, Kevin. "Ultrastructural, molecular and functional heterogeneities of cerebellar granule cell presynaptic terminals." Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAJ083/document.
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Le cervelet est une structure cérébrale impliquée dans la régulation motrice. Dans le cortex cerebelleux, les informations sensorimotrices sont transmises par les cellules en grain. Mon travail de thèse démontre que les connections synaptiques de ces neurones ont des propriétés hétérogènes. D’une synapse à l’autre, j’ai pu observer des variations d’ultrastructure, de composition moléculaire et de fonctionnement au cours de trains de potentiels d’action à haute fréquence. Plus particulièrement, j’ai caractérisé les propriétés de « plasticité à court terme » des synapses unitaires des cellules en grain : 1) Elles sont très différentes d’une synapse à l’autre et peuvent être classées en différentes sous-catégories. 2) Certaines catégories de fonctionnement synaptique reposent sur l’expression de molécules telles que la Synapsine2. 3) La réponse d’un neurone post-synaptique à de hautes fréquences de stimulation dépend de la nature de la synapse activéeCerebellum is a brain structure involved in motor regulation and motor learning. In the cerebellar cortex, sensorimotor information is transmitted by granule cells. During my PhD, I demonstrated that the properties of individual granule cell synaptic connections are highly heterogeneous. From one synapse to another, I observed ultrastructural, molecular and functional variability at unitary contacts. More precisely, I assessed the properties of short term plasticity at individual synapses during high frequency trains of stimulation :1) Short term plasticities are highly heterogeneous from one synapse to another and can be classified in sub-categories.2) Some categories of short-term plasticity profiles relie on the expression of molecules such as Synapsin2.3) The response of post-synaptic neuron to high-frequency inputs is dependent on the nature of the activated synaptic contact
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Costa, Renata Cardoso Belo da. "Leishmania infantum extracellular material and human invariant natural killer T cells : a functional study." Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCB022/document.
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Les cellules iNKT (de l’anglais invariant Natural Killer T) constituent un sous-type particulier de lymphocytes T caractérisé par un profil de type inné. Ces cellules répondent rapidement à des antigènes lipidiques et glycolipidique présentés par le CD1d, une glycoprotéine exprimée par les différentes cellules présentatrices d'antigène. Suite à l’activation, les cellules iNKT sont capables de produire de grandes quantités de cytokines anti-inflammatoires et pro-inflammatoires et elles sont impliquées dans différentes maladies, telles que l'allergie, l'auto-immunité, le cancer et les infections, parmi lesquelles la leishmaniose. Les parasites protozoaires de les espèces Leishmania sont les agents causaux de la leishmaniose, une maladie tropicale négligée dont la manifestation la plus grave affecte les organes viscéraux et qui peut être mortelle si elle n'est pas traitée. Le succès de l'infection dépend de la capacité du parasite à maitriser la réponse immunitaire de l'hôte. Récemment, quelques groupes, y compris le nôtre, ont observé que les parasites Leishmania libèrent des vésicules extracellulaires (VE). Les VE sont formées par une bicouche membranaire lipidique, contenant des lipides, des protéines et du matériel génétique et elles peuvent transmettre des molécules dérivées des pathogènes aux cellules hôte sans contact direct entre les cellules. Les VE produites par les parasites Leishmania et aussi par d’autres protozoaires ont été associés à des effets pro-parasite car elles favorisent un environnement plus permissif à l'établissement de l'infection. Dans cette thèse, nous avons étudié l'effet du matériel extracellulaire (ME), correspondant aux VE et aux molécules non-associées aux VE, libéré par les promastigotes de L. infantum sur les cellules iNKT. Dans le début de ce travail, il a été observé que le ME de L. infantum empêche l'expansion ex-vivo des cellules iNKT humaines à partir de cellules mononucléaires du sang périphérique. Cela a mis en évidence la communication entre les cellules iNKT et le ME de L. infantum, ce qui a été exploré par la suite. Le ME de L. infantum module la capacité très importante des cellules iNKT à produire des cytokines. En effet, le ME de L. infantum empêche la production des différentes cytokines par les cellules iNKT, comme par exemple IL-4 et IFNγ. De plus, nous avons aussi démontré que le ME de L. infantum compète avec l’α-GalCer, un agoniste très puissant des cellules iNKT, pour la liaison à la molécule CD1d, ce qui justifie l’effet inhibiteur dans l'activation des cellules iNKT. Nous avons aussi montré que les lipides qui sont présents dans chaque fraction du ME de L. infantum ont un rôle très important dans l’inhibition de l'activation et l'expansion des cellules iNKT. Ainsi, le ME de L. infantum, par ces lipides, peut participer à l’altération de l’activation des cellules iNKT dépendante du CD1d. Cela ajoute une nouvelle évidence de la contribution du ME de L. infantum dans la subversion de la réponse immunitaire de l’hôte. La communication entre le ME libéré par un pathogène et les cellules iNKT a été étudié pour la première fois, ce qui a suggéré un mécanisme de modulation de ces cellules qui n’avait jamais été décrit. Ce travail ouvre des perspectives pour l'étude de l'interaction de ME libéré par d'autres pathogènes avec des cellules iNKT. De plus, l'analyse des lipides contenus dans le ME de L. infantum pourra aboutir à la découverte de nouvelles molécules spécifiques pour inhiber les cellules iNKT. Cela apporterait des avantages significatifs dans les approches cliniques ciblant la modulation de l'activation des cellules iNKTThe invariant natural killer T (iNKT) cells constitute a particular subset of T lymphocytes characterized by an innate-like profile. These cells rapidly respond to lipid and glycolipid antigens bound by the glycoprotein CD1d expressed by different antigen presenting cells. Once activated, they release large amounts of anti- and proinflammatory cytokines. Thus, iNKT cells are endowed with a remarkable immunomodulatory potential and they have been implicated in different disorders, such as allergy, autoimmunity, cancer and infection, among which is leishmaniasis. Leishmania spp. are a group of protozoan parasites that includes the causative agents of leishmaniasis. This is a neglected tropical disease in which the most severe form of manifestation affects visceral organs and could be fatal if left untreated. Importantly, the success of Leishmania infection relies on the capacity of the parasite to subvert host immune responses. Recently, a few groups, including ours, observed that Leishmania parasites release extracellular vesicles (EVs). EVs are vesicles formed by a lipid bilayer membrane, containing other lipids, proteins and genetic material on their surface as well as in their lumen. Due to their potential to transmit messages between pathogens and host cells without a direct cell contact, they have been a focus of great interest regarding infection. EVs derived from Leishmania and other protozoan parasites have been associated with pro-parasite effects, by creating a more permissive environment to the establishment of the infection. Herein, we studied the effect of the extracellular material (ExM), which encloses both EVs and vesicle-depleted material, released by L. infantum promastigotes in iNKT cells. In the first steps of this work, it was observed that L. infantum ExM is capable of impairing the expansion of human iNKT cells ex vivo from peripheral blood mononuclear cells. This evidenced the cross-talk between iNKT cells and L. infantum ExM that we explored further. L. infantum ExM also modulates the important capacity of iNKT cells to release cytokines, impairing the production of different cytokines, such as IL-4 and IFNγ by these cells. Furthermore, we also show that L. infantum ExM competes with α-GalCer, a potent iNKT cell agonist, for CD1d binding, which justifies its effect in the impairment of iNKT cell activation. Additionally, we also proved the lipids present in each fraction of L. infantum ExM take an important role in the inhibition of iNKT cell activation and expansion. Thus, L. infantum ExM, through their lipids, is suggested to participate in the impairment of CD1d-mediated activation of iNKT cells, adding a new evidence regarding the contribution of the parasite ExM to subvert host immune responses. To the best of our knowledge, this is the first time that the cross-talk between the ExM released by a microbe and iNKT cells was assessed, shedding light on a mechanism of iNKT cell modulation that remained unexplored so far. This opens new perspectives regarding the study of the interaction of the ExM released by other pathogens with iNKT cells. Moreover, a further analysis of the lipid content of L. infantum ExM might allow the finding of new inhibitory molecules specific to iNKT cells, which can bring significant advantages in clinical approaches targeting the modulation of iNKT cell activation
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Freitas, Edison Pignaton de. "Metodologia orientada a aspectos para a especificação de sistemas tempo-real embarcados distribuídos." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2007. http://hdl.handle.net/10183/10268.
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Sistemas de tempo-real embarcados distribuídos se caracterizam pela complexidade e especificidade de seus projetos. Tanto a complexidade quanto a especificidade apresentam forte influência dos diversos requisitos ligados às restrições advindas das três características que distinguem tais sistemas, i.e. presença de fortes restrições temporais, restrições de sistemas embarcados e distribuição de processamento. Estes requisitos, chamados de requisitos não-funcionais, afetam diversas partes do sistema de maneira não uniforme, tornando-se por esta razão difícil o seu gerenciamento. Metodologias orientadas a objetos não apresentam mecanismos específicos para tratar tais requisitos, o que implica na aplicação de um significativo esforço ao se realizar o reuso ou a manutenção de componentes afetados por requisitos de natureza nãofuncional. Novas tecnologias têm surgido com o objetivo de contornar este problema, notadamente a orientação a aspectos. Este paradigma propõe a separação no tratamento dos requisitos não-funcionais contribuindo com a modularização do sistema. Esta dissertação propõe a aplicação de orientação a aspectos para a especificação de sistemas tempo-real embarcados distribuídos. Para isto realizou-se a adaptação de uma metodologia de desenvolvimento de sistemas orientada a aspectos, a FRIDA (From RequIrements to Design using Aspects), contextualizando-a para o domínio de interesse. A utilização desta metodologia provê suporte ao mapeamento de requisitos em elementos de projeto de modo a promover a rastreabilidade entre as fases de análise e projeto. Na fase de projeto é proposta a utilização de aspectos em conjunto com elementos do perfil RT-UML para o tratamento dos requisitos identificados e especificados na fase de análise.Distributed real-time embedded systems generally have complex and very specific projects. Those characteristics are influenced by several requirements that have relation with constraints about the time, embedded and distribution restrictions. Those requirements, called non-functional requirements, can affect the whole system in a nonuniform way, what makes it difficult to handle with this kind of requirement. Objectoriented methodologies do not present specific mechanisms to handle those requirements, what imply in a significant effort to perform reuse and maintainability tasks in those components affected by non-functional requirements. New technologies are emerging to fulfill this gap, noteworthy the aspect orientation. This paradigm proposes the separation in handling functional and non-functional requirements, giving a contribution to the system modularity. This dissertation proposes the use of aspect orientation to specify distributed realtime embedded systems. To support this proposal, it was performed an adaptation of an aspect-oriented method called FRIDA (From RequIrements to Design using Aspects). The use of this method supports the mapping of requirements in design model elements, in order to promote traceability between analysis and design phases. The presented approach proposes the use of RT-UML together with aspect oriented elements in design phase aiming to improve the handling of those requirements specified in the analysis phase.
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Raess, Matthieu. "Deciphering the functional and molecular differences between MTM1 and MTMR2 to better understand two neuromuscular diseases." Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAJ088.
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MTM1 et MTMR2 sont 2 phosphatases de phosphoinositides appartenant à la famille des myotubularines, conservée pendant l’évolution. Bien qu’étant très similaires, des mutations dans MTM1 entraînent la sévère myopathie XLCNM alors que les mutations dans MTMR2 entraînent la neuropathie CMT4B. On ne comprend pas encore les bases moléculaires de cette spécificité de tissu, et il n’existe aucun traitement spécifique pour ces maladies. J’ai tout d’abord caractérisé l’activité des 2 isoformes endogènes de MTMR2, nommés MTMR2-L et MTMR2-S. J’ai démontré que la différence fonctionnelle entre MTM1 et MTMR2 s’explique principalement par l’extension N-terminale de MTMR2, et que l’isoforme MTMR2-S dépourvu de cette extension entraîne les mêmes phénotypes que MTM1. Ensuite, grâce à l’injection d’AAV dans les souris Mtm1 KO, j’ai démontré que l’expression exogène des isoformes de MTMR2, et surtout de MTMR2-S, améliore grandement l’atrophie musculaire, la force musculaire et les marqueurs histologiques de ces souris myopathiques. Ces résultats révèlent une première base moléculaire expliquant les spécificités fonctionnelles de MTM1 et MTMR2, et montrent que MTMR2 est une cible thérapeutique potentielle pour la myopathie XLCNMMTM1 and MTMR2 are 2 phosphatases of phosphoinositides that belong to the myotubularin family conserved through evolution. Despite their high level of similarity, mutations in MTM1 lead to the severe XLCNM myopathy while mutations in MTMR2 lead to the CMT4B neuropathy. The molecular bases for the surprising tissue-specific functions of these ubiquitously expressed proteins was unclear. Moreover, there is no specific therapy for these diseases.I first characterized the activity of the two naturally occurring isoforms of MTMR2, that we named MTMR2-L (long) and MTMR2-S (short). I found that the functional differences between MTM1 and MTMR2 reside mostly in the N-terminal extension of MTMR2-L, and that the endogenous MTMR2-S isoform lacking this N-terminal extension behaves similarly as MTM1. Then, using the myopathic Mtm1 KO mouse and AAV-mediated expression, I showed that exogenous expression of MTMR2 isoforms, and specifically of MTMR2-S, strongly improved the muscle atrophy, muscle force and the histological hallmarks of the myopathic mice. These data reveal a first molecular basis for the functional specificities of MTM1 and MTMR2, and highlight MTMR2 as a therapeutic target for XLCNM myopathy
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Chan, G. K. L. "Aspects of density functional theory." Thesis, University of Cambridge, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.597413.
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The first part of our work, we describe investigations into the formal and conceptual aspects of density functional theory. These have been in four main areas. The first, is the theory of the derivative discontinuity, where we extended the theory to density matrix functionals, and carried out calculations of the effects of the discontinuity. Our second investigation concerned a new channel concept, namely, the shape and local chemical potentials. These describe the electron donating or accepting power of a density fragment. We demonstrated in simple model systems, that chemical features such as shell structure, or atoms in molecules, could be characterised as regions of constant shape chemical potential. Our third investigation concerned the homogeneous scaling of the Kohn-Sham kinetic energy. We disproved certain existing relations in the literature; we then went on to derive simple bounds on the kinetic energy, and to numerically calculate the approximate scaling of the kinetic energy in atomic systems. Our fourth investigation concerned an improved Lieb-Oxford bound for the exchange-correlation energy. By improving the numerical optimisation in the last part of the proof, we were able to tighten the bound. The second part of our work focused on the search for new energy functionals, and procedures for developing new functionals. Our efforts have been in two areas. The first was an investigation of the correlation functional of Hartree-Fock-Kohn-Sham theory. We observed the deficiencies of current functionals in the reproduction of the correlation potential, and attempted to correct this by fitting a functional to best reproduce numerical correlation potentials. In doing so, we observed the highly non-local nature of correlation in Hartree-Fock-Kohn-Sham theory, and the important effect of the derivative discontinuity on the energy. The second investigation attempted an exhaustive study of the Generalised Gradient Approximation (GCA), within a well-defined ab initio model. We developed a rigorous fitting methodology, and constructed well-converged fits to conclusively explore the limits of the accuracy of the GCA. A large number of observations were made concerning the choice of functional basis, the importance of additional gradient corrections, and the role of exact exchange. We also applied our fitting methodology to the construction of approximate Kohn-Sham kinetic energy functionals, with some success.
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Shirbate, Rajshree. "Functional aspects of gastropod mucus." Thesis, Durham University, 1987. http://etheses.dur.ac.uk/7099/.
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The gross anatomy and histochemical properties of the mucus-producing glands of three prosobranchs from different habitats (Littorina littorea, Bithynia tentaculata and Pomatias elegans), and a pulmonate slug (Limax pseudoflavus) were investigated. A supra-pedal gland was present in Pomatias and Limax that secreted mucoprotein and acid mucopolysaccharide in the former and neutral mucopolysaccharide in the latter. All species examined except Pomatias possessed glandular areas at the leading edge of the foot secreting a mucoprotein, and widely distributed glands on the ventral surface of the foot secreting a variety of mucosubstances, The ventral secretory cells of Pomatias, which contained protein and both neutral and acid mucopolysaccharides, were confined to a band either side of a deep medial pedal furrow. The secretory cells on the exposed dorsal surface of all four species contained a variety of mucosubstances and protein. However, a neutral mucopolysaccharide component was found to be absent in the dorsal body mucus of Limax. In the prosobranchs examined, specialized cells of the opercular groove and disc produced mucopolysaccharide and at least two differently staining proteins. In Pomatias and Bithynia the dorsal mantle epithelium possessed no secretory cells whereas that of Littorina possessed cells secreting mucopolysaccharide. At the mantle edge of Pomatias and Littorina two types of glands produced a variety of mucosubstances but at that of Bithynia one cell type produced mainly protein. The hypobranchial gland of Pomatias contained no specialised cell types but that of Bithynia and Littorina possessed cells secreting mainly protein and acid mucopolysaccharide respectively. The mode and mechanism of discharge of the mucus-producing gland cells of these gastropods and functional aspects of the distribution of cell types and their mucus are discussed. It is suggested that the pedal mucus of Limax is especially suitable for the gastropod creeping system. Many areas of the body surface of Limax and the foot of Pomatias, Bithynia and Littorina are capable of producing both fluid (neutral or weakly acid) and viscous (acid) mucus. It is postulated that such an arrangement allows for both adhesion and lubrication at different times.
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Gemmill, John Douglas. "Functional aspects of thrombolytic therapy." Thesis, University of Edinburgh, 1993. http://hdl.handle.net/1842/19783.
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The benefits of thrombolytic therapy in acute myocardial infarction are established, yet there remain important questions, including the safe interval for effective readministration of the streptokinase-containing thrombolytic agents, and how to expedite the administration of therapy and the restoration of coronary patency. The work in this thesis addresses some aspects of these questions. The administration of thrombolytic agents by bolus injection has practical attractions. The pharmacokinetic properties of streptokinase (SK) and anistreplase in their standard administration regimens are compared, and demonstrate the significantly earlier, higher plasma concentrations and longer half-life achieved by bolus administration of anistreplase. Domiciliary administraiton reduces the delay to therapy. The feasibility of this approach was assessed comparing general practitioners' assessment of 139 patients, with and without electrocardiographs, with the coronary care unit diagnosis and the prescription of thrombolytic therapy. Domiciliary assessment is insufficiently reliable to recommend routine use of thrombolytic therapy at home at the present time. The significance of antibodies to SK-containing thrombolytic agents is largely unknown. Pretreatmet SK resistance titre and anti-SK IgG concentrations were measured in 128 patients with acute myocardial infarction treated with SK or anistreplase. A significant minor negative influence of SK resistance titre on coronary patency was observed. The haemodynamic responses to these agents were observed in detail, and blood pressure falls found to be usually short-lived and not require specific intervention. An association was sought between hypotensive episodes and markers of immunological resistance, markers of thrombin activity, and plasma viscosity. No relationship was found, refuting their implication in the hypotensive mechanism. The time course of the development of changes in SK resistance titre and anti-SK IgG concentration were documented in detail in the same patients over 30 months. Both indices peaked at 2 weeks following therapy, and declined slowly, with 50 & 58% of the population returning to within two standard deviations of pretreatment levels within 2 years. The functional sequelae of these antibody responses were studied in vitro using a pooled clot lysis assay. These data demonstrated near complete inhibition of lysis up to 9 months, with 75% recovery at 30 months.
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Tescari, Neto Aquiles 1983. "AdvPs de aspecto habitual como modalizadores inerentes : um estudo translinguistico." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/268920.
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Orientador: Sonia Maria Lazzarini CyrinoDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Estudos da Linguagem
Made available in DSpace on 2018-08-10T16:06:14Z (GMT). No. of bitstreams: 1 TescariNeto_Aquiles_M.pdf: 1050741 bytes, checksum: ce0a61b21caa2d194b6fc32fc095c6e2 (MD5) Previous issue date: 2008
Resumo: O estudo da modalização na literatura lingüística tem excluído do grupo dos advérbios modalizadores os que indicam aspecto habitual (como ¿normalmente¿ e ¿geralmente¿, em português; ¿usually¿ e ¿generally¿, em inglês; ¿tongchang¿, em chinês; ¿sinithos¿, em grego; etc.). Esta dissertação propõe, ao assumir a Teoria dos Especificadores Funcionais, uma abordagem formal de sintaxe adverbial (Cinque, 1999, 2004), que advérbios habituais constituem, nas línguas do mundo, um subgrupo de modalizadores de descomprometimento do falante, como os epistêmicos (¿provavelmente¿), os irrealis (¿talvez¿) e os aléticos de possibilidade (¿possivelmente¿), considerados os representantes dos AdvPs modais. AdvPs habituais, a exemplo dos outros AdvPs modalizadores, tornam a proposição indeterminada em relação a seu estatuto factual (definição de modalidade proposta em Narrog (2005)). Com base na agramaticalidade de sentenças envolvendo, no espaço IP, advérbios habituais e advérbios modalizadores tradicionais, propomos que os advérbios de aspecto habitual são modalizadores inerentes, por reagirem à presença dos outros modalizadores. Para tanto, formulamos a Condição (¿tau¿), que bloquearia as sentenças com itens funcionais de mesmo traço em um XP funcional (CP, IP ou DP estendidos). Evidência adicional para o reconhecimento dos advérbios habituais como modalizadores vem do comportamento também modalizador do núcleo de aspecto habitual, em línguas que o expressam morfofonologicamente, como o grego, o coreano e o basco. Nesse sentido, não apenas os adverbiais aspectuais habituais são modalizadores; o aspecto habitual como um todo instanciaria modalização
Abstract: The study of modality available in general Linguistics literature has excluded from the group of modal adverbs those which indicate habitual aspect, such as ¿normalmente¿ and ¿geralmente¿, in Portuguese; ¿usually¿ and ¿generally¿, in English; ¿tongchang¿, in Chinese; ¿sinithos¿ in Modern Greek, etc. By acknowledging the Funtional-Specifiers Theory, a formal approach to adverbial Syntax (Cinque, 1999, 2004), this thesis proposes the idea that habitual aspect adverbs are indeed modal ones, such as the epistemic (¿probably¿), irrealis (¿perhaps¿) and alethic of possibility (¿possibly¿) adverbs, usually considered as the representatives of modal AdvP classes. Habitual adverbs, as the traditional modal adverbs, make the proposition undetermined with respect to its factual status (Narrog (2005)¿s definition of modality). Based on the ungrammaticality of sentences which have habitual adverbs and traditional modal ones in the extended-IP space, we will propose that habitual aspect AdvPs are inherent modals: they cannot co-occur with another modal adverb, as a consequence of ¿_ (tau) Condition¿, which we have formulated to account for the ungrammatical sentences which have more than one functional item (Spec or Head) in the same functional XP domain (extended CP, IP or DP). Additional evidence for the modal status of habitual aspect adverbs comes from the moda behavior of the habitual aspect head in some languages which express morphophonologically the habitual aspect, such as Modern Greek, Korean and Basque. In this sense, Habitual Aspect as a whole, no only habitual aspect adverbs, would express modality in the languages of the world
Mestrado
Linguistica
Mestre em Linguística
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Taylor, Andrew. "Functional aspects of optic nerve regeneration." University of Western Australia. School of Animal Biology, 2006. http://theses.library.uwa.edu.au/adt-WU2006.0095.
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[Truncated abstract] Formation and consolidation of the retinotectal projection during optic nerve regeneration has been associated with two major interlinked processes. Initially, retinal ganglion cell (RGC) axons are guided by molecular guidance cues, such as the Eph receptor tyrosine kinases and their ligands, the ephrins, to their approximately correct location and form a coarse topographic map in the optic tecum. Such axon guidance occurs in the absence of neural activity and is considered to be activity-independent. The second process involves glutamatergic excitation, whereby correctly located connections are strengthened by correlated neural activity, whilst removing inappropriately located ones thereby sharpening the topography.The second process is considered to be activitydependent. Here, a number of experiments were undertaken to further examine the interrelationships of activity-dependent and independent processes with respect to functional outcomes. Two models of optic nerve regeneration were studied. In goldfish, following optic nerve crush, regeneration is successful. … In goldfish, guidance along the medio-lateral tectal axis may occur through preordering of axons prior to entering the tectum via the appropriate medial and lateral brachium, with EphA/ephrin-A then guiding axons over the rostral-caudal axis establishing gross topography. The increase in involvement of NMDA-mediated transmission during the period of activity-dependent refinement consolidated the role of this receptor in synapse plasticity. However what triggers NMDA-mediated activity to increase is still largely unresolved, although as the factors governing receptor trafficking during development and synaptic plasticity become better understood, these can be applied to the period of plasticity associated with regenerating axons. And finally, as GABAergic inhibition appears to suppress activity-dependent refinement, means of overcoming this inhibition through 4 such methods as visual training or pharmacological intervention may have significance for mammalian regeneration.
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Stephenson, Sally Louise. "Functional aspects of renal microvillar peptidases." Thesis, University of Leeds, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.232948.
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Andersson, Michael R. "Functional aspects of inorganic phosphate transport." Doctoral thesis, Linnéuniversitetet, Institutionen för naturvetenskap, NV, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-18651.
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Inorganic phosphate is an essential nutrient for all organisms. It is required for many cellular components as nucleic acids and phospholipids, and as energy-carrying compounds such as ATP. Thus, a regulated uptake of this pivotal nutrient is of outermost importance. Depending of the availability of phosphate in the surroundings the yeast Saccharomyces cerevisiae make use of two different systems for transporting phosphate into the interior of the cell: a low-affinity system that is active during surplus phosphate conditions and a high-affinity system that is active when the availability becomes limited. This thesis focuses on the high-affinity system, which is comprised of the Pho84 and Pho89 transporters. Of the two transporters, Pho84 is the predominant one, responsible for almost all phosphate uptake during low phosphate conditions, and the contribution of Pho89 is of minor importance. Hence Pho84 is by far the most well characterized phosphate transporter. Even though much is known about phosphate transporters in yeast little in known about how phosphate is transported. The work in this thesis aims to broaden the knowledge about the transport mechanism by the means of site-directed mutagenesis and functional characterization. Also the similarity of Pho84 to glucose sensors and the potential role of conserved residues in phosphate signaling are investigated. By the use of a high-affinity system deletion strain (∆Pho84 ∆Pho89), we also managed to investigate the functional importance of well conserved residues in Pho89. In summary: the work presented in this thesis has contributed to increase the knowledge about transport mechanisms in phosphate transporters.
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Naoumenko, Paul. "Designing non-functional aspects with components." Nice, 2010. http://www.theses.fr/2010NICE4073.
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In this thesis we are considering programming models for large-scale and distributed applications that are deployed in dynamic ever-changing environments, like the Grid. To maintain their function with minimal involvement of human operators, those applications have to be instrumented with self-adaptive capabilities. We ground our research on the autonomic computing paradigm, which proposes to design applications as compositions of autonomic elements. Those are software entities exposing two parts: a business part, and a management part, with managers in charge of supervising the business part by reacting to environmental changes. Managers have the possibility to implement complex management strategies: additionnaly to the supervision of the business part, they can contact managers from other autonomic elements involved in the application, and collaborate with them in order to elaborate adequate reactions. Strategies of managers can be dynamically updated. We propose to design distributed autonomic applications using a component-oriented model: the GCM (Grid Component Model). GCM components are distributed by essence and the model features as a part of its specification separation of concerns (GCM components have a business part and a management part), hierarchical structure, and dynamic reconfiguration. Our contribution is twofold. First, we extend the management part (called the membrane) of GCM components, giving the possibility to include managers that correspond to the vision of autonomic computing. Thanks to newly introduced architectural elements, the managers are able to supervise the business part of GCM components. They can also contact managers of other components of the application and collaborate with them. A GCM component with self-adaptive capabilities should be easy to produce: we suggest a development process that allows to design and implement the management part separately from the business part, and then integrate both parts inside one unified software entity. We modify the ADL (architecture description language) used to statically describeGCMcomponent assemblies according to the new development process. Second, we include the previously presnted extensions in the reference implementation of the GCMDans cette thèse nous considérons des modèles de programmation pour des applications à grande échelle, distribuées et déployées dans des contextes en constant changement, comme la grille de calcul. Pour maintenir leur fonctionnalité tout en minimisant les interventions humaines, ces applications doivent être équipées de capacités auto-adaptatives. Notre recherche a pour base le paradigme de l'"Autonomic Computing", qui conçoit les applications auto-adaptables comme des compositions d'éléments autonomes. Ce sont des entités logicielles qui sont constituées de deux parties: une partie métier (ou fonctionnelle), et une partie contrôle, composée d'entités de contrôle (ou "managers") qui supervisent la partie métier et maintiennent sa fonctionnalité en réagissant aux changements de l'environnement. Les managers peuvent implémenter des stratégies de contrôle complexes: en plus de contrôler la partie métier, ils peuvent communiquer avec des managers d'autres éléments autonomes de l'application et collaborer afin d'élaborer les stratégies adéquates. Les stratégies des managers peuvent être mises à jour dynamiquement. Nous proposons de concevoir des applications autonomes distribuées en utilisant un modèle à composants: GCM (pour Grid Component Model). Les composants GCM sont distribués par nature et le modèle inclut dans sa spécification la séparation des aspects (les composants GCM ont une partie métier et une partie de contrôle), une structure hiérarchique et la reconfiguration dynamique. Notre contribution peut être résumée en deux points. Premièrement, nous étendons la partie de contrôle (également appelée la membrane) des composants GCM, en donnant la possibilité d'y inclure des managers qui correspondent à la vision de l'Autonomic Computing. Grâce à l'introduction de nouveaux éléments architecturaux, les managers ont la capacité de superviser la partie métier des composants GCM. Ils peuvent également entrer en contact avec des managers d'autres composants faisant partie de la même application. Un composant GCM devrait être facile à produire: nous proposons un processus de développement qui permet de concevoir et développer la partie non-fonctionnelle séparément de la partie métier, puis d'intégrer ces deux parties dans une entité logicielle unifiée. On apporte des modifications au langage de description architectural (ADL), utilisé pour décrire un assemblage GCM statique. Deuxièmement, nous avons inclus les extensions introduites précédemment dans l'implémentation de référence du GCM
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Meulemans, Laetitia. "Caractérisation fonctionnelle de variations splicéogéniques à l'origine d'anomalies d'épissage en phase dans des gènes de prédisposition aux cancers : implications en génétique médicale Skipping nonsense to maintain function : the paradigm of BRCA2 Exon 12 Functional characterization of MSH2 variants resulting into in-frame splicing alterations." Thesis, Normandie, 2021. http://www.theses.fr/2021NORMR008.
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Aujourd’hui, le défi majeur en génétique médicale est l’interprétation clinique des variations détectées dans le génome des patients. Dans un contexte de maladie monogénique, l’identification de la variation pathogène permet d’optimiser la prise en charge des patients et de leurs apparentés. Les variations non-sens ainsi que celles localisées au niveau des sites canoniques d’épissage (IVS±1/2) sont généralement considérées causales. Toutefois, il est possible que certaines d’entre elles induisent des anomalies d’épissage en phase permettant potentiellement la production d’une protéine fonctionnelle. Afin de tester cette hypothèse, nous avons choisi comme modèles d’étude deux gènes majeurs de prédisposition aux cancers : BRCA2, pour le syndrome sein-ovaire et MSH2, pour le syndrome de Lynch. Des approches expérimentales complémentaires ont été mises à profit afin de caractériser l’impact de ce type de variations non seulement au niveau de l’épissage mais également au niveau de la protéine. Notre étude portant sur des variations de BRCA2 a démontré que certaines variations IVS±1/2 et non-sens (i) induisent un saut en phase de l’exon 12 du fait de l’altération de sites d’épissage ou d’éléments de régulation et (ii) sont de ce fait responsables du maintien de l’activité BRCA2, tout en étant hypomorphes. Ces travaux montrent, pour la première fois dans un gène de prédisposition au cancer, que certaines variations présumées nulles peuvent contourner la perte totale de fonction du fait de leur impact sur l’épissage. Nos données remettent ainsi en question le caractère pathogène de ces variations. Dans le cadre de notre étude portant sur des variations IVS±1/2 de MSH2, nous avons caractérisé trois biotypes d’anomalies d’épissage en phase : (i) des sauts d’exon, (ii) des délétions de portions exoniques et (iii) des rétentions introniques, avec pour conséquence au niveau protéique des délétions ou insertions de plus ou moins grande taille dans différents domaines fonctionnels. Toutes les isoformes protéiques MSH2 résultant de ces variations splicéogéniques se sont avérées inactives, confirmant ainsi leur caractère pathogène. L’ensemble de ces travaux souligne l’importance d’exercer une certaine prudence dans l’interprétation des variations considérées a priori pathogènes mais susceptibles de générer des anomalies d’épissage en phase. Dans ce contexte, la combinaison d’approches expérimentales complémentaires pour appréhender l’impact biologique au niveau de l’ARN et de la protéine est essentielle pour une interprétation fiable de ce type de variations. Ces données mettent également en exergue la problématique de l’interprétation clinique des variations hypomorphes dans les gènes de prédisposition aux cancersToday, the major challenge in medical genetics is the clinical interpretation of nucleotide variants detected in a patient’s genome. In the context of a monogenic disease, the identification of the pathogenic variant allows the optimization of the medical care of patients and their relatives. Nonsense variations as well as those located at the canonical splice sites (IVS±1/2) are generally considered pathogenic. However, it is possible that a fraction of them induce in-frame splicing anomalies that can potentially result in the production of a functional protein. To test this hypothesis, we used as model systems two major cancer-predisposition genes: BRCA2, implicated in hereditary breast and ovarian cancer syndrome and MSH2, involved in Lynch syndrome. We took advantage of complementary experimental approaches to characterize the impact of this type of variants not only in RNA splicing but also at the protein level. Our study on BRCA2 demonstrated that a subset of IVS±1/2 and nonsense variants (i) induce in-frame skipping of exon 12 via the modification of splice sites or of splicing regulatory elements and (ii) are able to maintain BRCA2 activity though being hypomorphic. These data provide the first evidence, in a cancer-predisposition gene, that certain presumed null variants can bypass total loss of function due to their impact on splicing. Thus our findings call into question the pathogenic nature of these variants. In our study on MSH2 IVS±1/2 variants, we characterized three biotypes of in-frame splicing defects responsible for deletions or insertions at the protein level in different MSH2 functional domains: (i) exon skipping, (ii) deletions of exonic portions and (iii) intron retentions. All the MSH2 protein isoforms resulting from these spliceogenic variants were found to be inactive, thus confirming their pathogenic classification. Altogether, our findings highlight the need to exercise caution in the interpretation of putative pathogenic variants susceptible to induce in-frame splicing modifications. In this context, the combination of complementary experimental approaches assessing the biological impact at the RNA and protein level is essential for a reliable interpretation of this type of variants. Furthermore, our results stress the problem of the clinical interpretation of hypomorphic variants in cancer-predisposition genes
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Falcão, Pedro Alonso Amaral. "Aspectos da teoria de funções modais." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/8/8133/tde-11042013-104549/.
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Apresentamos alguns aspectos da teoria de funções modais, que é o correlato modal da teoria de funções de verdade. Enquanto as fórmulas da lógica proposicional clássica expressam funções de verdade, as fórmulas da lógica proposicional modal (S5) expressam funções modais. Generalizamos alguns dos teoremas da teoria de funções de verdade para o caso modal; em particular, exibimos provas da completude funcional de alguns conjuntos de funções modais e definimos uma (nova) noção de reduto vero-funcional de funções modais, bem como a composição de funções modais em termos destes redutos.We present some aspects of the theory of modal functions, which is the modal correlate of the theory of truth-functions. While the formulas of classical propositional logic express truth-functions, the formulas of modal propositional logic (S5) express modal functions. We generalize some theorems of the theory of truth-functions to the modal case; in particular, we show the functional completeness of some sets of modal functions and define a (new) notion of truth-functional reduct of modal functions, as well as the composition of modal functions in terms of such reducts.
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Yu, Mengyao. "Exploitation des données issues d'études d'association pangénomiques pour caractériser les voies biologiques associées au risque génétique du prolapsus de la valve mitrale GWAS-driven gene-set analyses, genetic and functional follow-up suggest GLIS1 as a susceptibility gene for mitral valve prolapse Up-dated genome-wide association study and functional annotation reveal new risk loci for mitral valve prolapse." Thesis, Sorbonne Paris Cité, 2019. https://wo.app.u-paris.fr/cgi-bin/WebObjects/TheseWeb.woa/wa/show?t=2203&f=17890.
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Le prolapsus de la valve mitrale (MVP) est une valvulopathie fréquente qui touche près de 1 personne sur 40 dans la population générale. Il s'agit de la première indication de réparation et / ou de remplacement de la valve. De nombreux gènes comme FLNA, DCHS1 pour les formes familiales et TNS1 et LMCD1 pour les formes sporadiques ont récemment été décrit comme associés au MVP. Cependant, les défauts génétiques touchant ces gènes n'expliquent pas tous les cas du MVP. De plus, les mécanismes biologiques expliquant la susceptibilité génétique au MVP, notamment pour les formes sporadiques les plus fréquentes restent mal compris. Dans cette thèse, mon objectif était 1) de caractériser globalement les mécanismes biologiques impliqués dans le risque génétique du MVP dans le contexte des études d'association pangénomique (GWAS), et 2) d'améliorer la résolution du génotypage par l'imputation génétique et par l'addition d'une nouvelle étude cas témoins, (UKBioBank) afin de permettre la découverte de nouveaux loci de prédisposition. Dans la première partie, j'ai appliqué des outils d'enrichissement de voies biologiques ou sets de gènes (i-GSEA4GWAS, DEPICT) aux données GWAS. J'ai pu montrer que les gènes présents autour des loci GWAS sont impliqués dans l'organisation des filaments d'actine, l'organisation du cytosquelette et le développement cardiaque. Nous avons également décrits de nombreux régulateurs de la transcription impliqués le développement, la prolifération cellulaire et la migration, comme le gène GLIS1 qui joue un rôle dans les transitions morphologiques cellulaires (EndoMT, MET). Afin de confirmer le rôle de GLIS1 dans l'association avec le MVP, j'ai réalisé une analyse génétique dans UKBiobank et, en combinaison avec les données françaises, l'association a atteint le seuil de significativité génomique. Des expériences d'immunohistochimie ont indiqué que Glis1, la protéine orthologue de la souris est exprimée au cours du développement embryonnaire principalement dans les noyaux des cellules endothéliales et interstitielles des valves mitrales. D'autre part, l'inactivation de Glis1 à l'aide d'oligonucléotides de type Morpholinos ont été l'origine d'une régurgitation atrio-ventriculaire chez le poisson zèbre. Dans la deuxième partie, j'ai généré des données de génotypage plus dense à l'aide d'une imputation basée sur Haplotype Reference Consortium (HRC) et TOPMed. J'ai d'abord comparé la précision d'imputation entre les données utilisant les différents panels et constaté qu'aucun panel n'atteignait une précision optimale pour les variants rares (MAF <0,01) dans nos échantillons. La précision d'imputation s'améliorait pour les variants fréquents (MAF> 0,05), en particulier pour les cohortes dont le génotypage étaient réalisé avec des puces identiques. J'ai pu ainsi cartographier avec plus de précision les loci déjà confirmés (ex. Chr 2 autour de TNS1). J'ai également identifié 6 nouveaux loci associés au MVP prometteurs. Les nouveaux variants associés sont tous fréquents. L'annotation fonctionnelle fine à l'aide de données publiques a indiqué leurs rôles potentiels dans la régulation transcriptionnelle de plusieurs gènes candidats (ex. PDGFD et ACTN4). En résumé, mes travaux de thèse ont apporté des résultats génétiques originaux mettant en lumière de nouveaux mécanismes biologiques en rapport avec la biologie et le développement de la valve. Ces travaux ont fait appel à de nombreuses stratégies génétiques d'association et d'enrichissement, d'imputation haute densité et d'annotations fonctionnelles. Mes travaux ont également été renforcés par des validations dans des modèles animaux en collaboration. Il sera nécessaire toutefois de confirmer par réplication, et potentiellement par des expériences biologiques, les résultats nouveaux issus des travaux d'imputation haute densité afin de déclarer ces nouveaux gènes de prédispositions au MVPMitral valve prolapse (MVP) is a common heart valve disease affecting nearly 1 in 40 individuals in the general population. It is the first indication for valve repair and/or replacement and moreover, a risk factor for mitral regurgitation, an established cause of endocarditis and sudden death. MVP is characterized by excess extracellular matrix secretion and cellular disorganization which leads to bulky valves that are unable to coapt correctly during ventricular systole. Even though several genes including FLNA, DCHS1 TNS1, and LMCD1 were reported to be associated with MVP, these explain partially its heritability. However, understanding the biological mechanisms underlying the genetic susceptibility to MVP is necessary to characterize its triggering mechanisms. In this thesis, I aimed 1) to characterize globally the biological mechanisms involved in the genetic risk for MVP in the context of genome-wide association studies (GWAS), and 2) improve the genotyping resolution using genetic imputation, which allowed the discovery of additional risk genes for MVP. In the first part of my study, I applied pathway enrichment tools (i-GSEA4GWAS, DEPICT) to the GWAS data. I was able to show that genes at risk loci are involved in biological functions relevant to actin filament organization, cytoskeleton biology, and cardiac development. The enrichment for positive regulation of transcription, cell proliferation, and migration motivated the follow-up of GLIS1, a transcription factor that regulates Hedgehog signalling. I followed up the association with MVP in a dataset of cases and controls from the UK Biobank and, in combination with previously available data, I found a genome-wide significant association with MVP (OR=1.22, P=4.36 ×10-10). Through collaborative efforts, immunohistochemistry experiments in mouse indicated that Glis1 is expressed during embryonic development predominantly in nuclei of endothelial and interstitial cells of mitral valves, while Glis1 knockdown using morpholinos caused atrioventricular regurgitation in zebrafish. In the second part of my work, I generated larger genotyping datasets using a imputation based on Haplotyp Refernece Consortium and TOPMed, two large and highly dense imputation panels that were recently made available. I first compared the imputation accuracy between data using HRC and TopMED and found that both panels have low imputation accuracy for rare allele (MAF<0.01). However, the imputation accuracy increased with the input sample size for common variants (MAF>0.05), especially when genotyping platforms were harmonised. I was able to fine map established loci (e.g Chr 2) and also able to identify six novel and promising associated loci. All new loci are driven by common variants that I confirmed as high profile regulatory variants through an extensive computationally-based functional annotations at promising loci that pointed at several candidate genes for valve biology and development (e.g PDGFD and ACTN4). In summary, my PhD work applied up-to-data high throughput genetic association methods and functional enrichment and annotation to GWAS data. My results provide novel insights into the genetics, molecular and cellular basis of valve disease. Further genetic confirmation through replication, but also through biological experiments are expected to consolidate these statistically and computationally supported results
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Belkhiria, Chama. "Exploration et analyse de la relation cerveau-muscles squelettiques lors de la préparation et de l’exécution motrice." Thesis, Paris 10, 2016. http://www.theses.fr/2016PA100191.
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Les travaux de cette thèse s’inscrivent à la frontière des neurosciences et de la physiologie musculaire. Trois études se sont articulées de la préparation et l’exécution motrice. La première étude (A) a relié l'activité cérébrale à l'activité musculaire lors de la préparation motrice. Les résultats ont montré que des régions, telles que le cortex moteur primaire et l’aire motrice supplémentaire sont impliquées dans l'activité du muscle fléchisseur (FDS) alors que d’autres régions, telles que les ganglions de la base, les aires fronto-pariétales et le cervelet, sont impliquées dans l'activité du muscle extenseur (EDC). L’étude (B) a exploré le rôle du réseau cérébro-cérébelleux et du réseau striatal lors de l’exécution d’une tâche cognitive et motivationnelle. Les données ont révélé que la partie antérieure du lobule VI droit était activée par l'exécution motrice tandis que sa partie postérieure était spécifiquement activée par les encouragements verbaux. Les mesures de l’interaction psychophysiologique ont permis de faire immerger une boucle de connectivité fermée et formée par le cortex cérébral, le cervelet et les noyaux rouges. La troisième étude (C) concerne l’effet de la consigne réalisée lors de l’exécution motrice sur les paramètres neuromusculaires de FDS et EDC. Les résultats ont montré que la Force Maximale Volontaire, la Pente Maximale de Montée de Force et l’éléctromyographie associée étaient plus élevées (p < 0.05) avec la consigne accompagnée d’encouragement verbalThe present work fits on the border of neurosciences and muscular physiology. Three studies explored the brain and muscle activities following motor preparation and execution. The first study (A) linked brain and muscle activity during motor preparation. The results revealed that regions (e.g primary motor cortex and supplementary motor area) are involved in the activity of the flexor muscle (FDS) while other regions (e.g basal ganglia, fronto-parietal areas and cerebellum) are involved in the activity of the extensor muscle (EDC). The study (B) explored the role of cerebro-cerebellar and striatal networks during the execution period of cognitive and motivational task. The data showed that the anterior part of the right lobule VI was activated by the motor task, while its posterior part was specifically activated by verbal encouragement. Measurements of psychophysiological interaction revealed a closed connectivity loop formed by the cerebral cortex, the cerebellum and the red nuclei. The third study (C) concerned the effect of instruction on neuromuscular parameters of FDS and EDC muscles during motor execution. The results showed that the Maximum Voluntary Force, the Maximum Rate of Force Development and the associated electromyographic signal are the highest (p < 0.05) with cognitive, motivational and verbal encouragement condition
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Sluijmer, Alexander Victor. "The postmenopausal ovary functional and morphological aspects /." [Maastricht : Maastricht : Universiteit Maastricht] ; University Library, Maastricht University [Host], 1999. http://arno.unimaas.nl/show.cgi?fid=6841.
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Enberg, Ulla. "Functional and diagnostic aspects on adrenocortical adenoma /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-150-0/.
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Robson, Catherine Ruth. "Aspects of ocular structural and functional assessment." Thesis, Cardiff University, 2006. http://orca.cf.ac.uk/55449/.
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This thesis is a continuation of previous work within the Research Group and comprises an investigation of two perimetry-related topics; firstly, the role of ocular media properties on the visual field derived by Short Wavelength Automated Perimetry (SWAP); and, secondly, the perimetric assessment of patients with epilepsy treated with vigabatrin and the potential of alternative (imaging) techniques to overcome the subjective limitations of perimetry. The influence of ocular media adsorption and intra-ocular straylight on the visual field indices Mean Sensitivity, Mean Deviation, Pattern Standard Deviation and Short-term fluctuation derived by white-on-white (W-W) perimetry and by SWAP was investigated in 35 normal individuals. Approximately 62% of the variance for W-W perimetry was explained by the assessment of logMAR visual acuity in conjunction with a low contrast chart. However, no relationship was evident for SWAP. This suggests that ocular media properties are a component of the between-individual variability in SWAP but that their contribution is masked by other sources of variability. The prevalence of visual field loss associated with vigabatrin, (VAVFL), was investigated for 80 individuals with long-term exposure to vigabatrin (Mean duration 8.6 years SD3.5 and mean cumulative dose 7.6kg SD4.4). The prevalence was 62.5%; risk factors for VAVFL were treatment duration (p=0.001) and male gender (p=0.04). The ability of Optical Coherence Tomography (OCT) and confocal Scanning Laser Ophthalmoscopy (cSLO) to detect retinal damage in 21 patients exposed to VGB and 43 control patients (16 exposed to carbamazepine monotherapy, 7 exposed to sodium valproate monotherapy and 20 normals) was investigated. In patients with VAVFL, RNFL was attenuated but macular thickness was normal compared to the remaining individuals in the cohort.
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Sjöberg, Inga. "The vagina : morphological, functional and ecological aspects." Doctoral thesis, Umeå universitet, Obstetrik och gynekologi, 1991. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-100564.
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The vagina is one organ of the body which has not been studied exhaustively. Moreover, most of the studies found in the contemporary literature have been performed on women affected by a variety of genital diseases. In the present study the vaginal epithelium was examined with a histological method, morphometry, whereby cyclical changes related to hormonal variation during the menstrual cycle were demonstrated. Determination of the quantity of estrogen receptors in the vaginal epithelium on two occasions during the menstrual cycle revealed a significantly greater number in the follicular than in the luteal phase. The results of these studies indicate the presence of a menstrual variation in the vaginal epithelium comparable to that in the endometrium. Phenoxymethylpenicillin (pcV) was used as a marker substance to study the dynamics of the transport mechanisms into the vagina. PcV was found to accumulate in the vaginal fluid and high concentrations persisted for a long period of time. In hysterectomized women, the appearance of pcV in the vaginal fluid followed the same pattern. Consequently, the substance is transported through the vaginal wall and need not enter with the secretions from the internal genitalia. The greatest concentration of pcV was in the distal portion of the vagina, possibly due to the specific internal circulation of fluid within the vagina. Bacterial vaginosis as an example of an ‘ecological disease’ has been studied with regard to the formation of endotoxin, a constituent of the cell wall of Gram- negative bacteria. Large amounts of endotoxin were found and the clinical implication of this finding has been pointed out. Furthermore, the influence of pcV on the vaginal microbial flora of healthy women has been investigated. A change from a situation with predominance of lactobacilli to the appearance of Gram-negative rods was observed. In one of the women the lactobacilli disappeared completely and were replaced by E. coliand high levels of endotoxin in the vaginal fluid were found. This study demonstrates the complexity of the ecological balance of the vaginal microbial flora and illustrates the difficulty of defining a ‘normal’ vaginal condition. Is there any unquestionable state of ‘normality’ even in a healthy woman free from symptoms of genital disease?S. 1-22: sammanfattning, s. 25-64: 6 uppsatser
digitalisering@umu
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Xu, Hao. "Functional aspects of modified nucleosides in tRNA." Doctoral thesis, Umeå universitet, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet), 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-109491.
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Transfer ribonucleic acids (tRNAs) are extensively modified, especially their anticodon loops. Modifications at position 34 (wobble base) and 37 in these loops affect the tRNAs’ decoding ability, while modifications outside the anticodon loops, e.g. m1A58 of tRNAMeti, may be crucial for tRNA structure or stability. A number of gene products are required for the formation of modified nucleosides, e.g. at least 26 proteins (including Elongator complex) are needed for U34 modifications in yeast, and methyl transferase activity of the Trm6/61p complex is needed to form m1A58. The aim of the studies which this thesis is based upon was to investigate the functional aspects of tRNA modifications and regulation of the modifying enzymes’ activity. First, the hypothesis that ncm5U34, mcm5U34, or mcm5s2U34 modifications may be essential for reading frame maintenance was investigated. The results show that mcm5 and s2 group of mcm5s2U play a vital role in reading frame maintenance. Subsequent experiments showed that the +1 frameshifting event at Lys AAA codon occurs via peptidyl-tRNA slippage due to a slow entry of the hypomodified tRNA-Lys. Moreover, the hypothesis that Elp1p N-terminal truncation may regulate Elongator activity was investigated. Cleavage of Elp1p was found to occur between residue 203 (Lys) and 204 (Ala) and to depend on the vacuolar protease Prb1p. However, including trichloroacetic acid (TCA) during protein extraction abolished the appearance of truncated Elp1p, showing that its truncation is a preparation artifact. Finally, in glioma cell line C6, PKCα was found to interact with TRM61. RNA silencing of TRM6/61 causes a growth defect that can be partially suppressed by tRNAMeti overexpression. PKCα overexpression reduces the nuclear level of TRM61, likely resulting in reduced level of TRM6/61 complex in the nucleus. Furthermore, lower expression of PKCα in the highly aggressive GBM (relative to its expression in less aggressive Grade II/III glioblastomas) is accompanied by increased expression of TRM6/61 mRNAs and tRNAMeti, highlighting the clinical relevance of the studies.
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Covernton, Patrick John O'Neill. "Functional aspects of neuronal nicotinic receptor diversity." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.321967.
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Lerchner, Walter. "Regulation and functional aspects of Xenopus Brachyury." Thesis, Open University, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300013.
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