This thesis is a survey of the field of languages over infinite sequences. There is active research going on in this field, during the last year several new results where published. We investigate the language containment problem for infinite sequences, with focus on complementation of Büchi automata. Our main focus is on the approach with alternating automata by Kupferman&Vardi. The language containment problem has been proved to be in EXPSPACE. We identify some cases when we can avoid the exponential blow-up by taking advantage of properties of the input automaton. Some of the algorithms we explain are also implemented in a Sicstus Prolog library.

Le pâturage, principal mode d’alimentation en zone tropicale, est souvent dévalorisé car il est associé à des performances animales jugées insuffisantes, et peut avoir des effets néfastes sur l’environnement. Même si l’alimentation à l’auge permet de meilleures productions, ce mode de conduite présente également des inconvénients, en termes d’investissements, de rentabilité économique, d’impact des rejets sur l’environnement et de qualité des produits. Une intensification de la conduite au pâturage semble donc une voie d’avenir, mais nécessite une meilleure connaissance de ce mode de conduite et de ses conséquences sur l’alimentation et les performances des animaux. Il apparait également nécessaire de comparer l’élevage au pâturage et à l’auge sur des critères homogènes, en dissociant les composantes de ces modes de conduite.L’objectif de la thèse est d’évaluer et de comparer la conduite au pâturage et la conduite hors sol, en tenant compte également de la distribution ou non de concentré, sur l’alimentation, la croissance, les caractéristiques d’abattage et la consommation d’eau. Dans un premier temps, nous avons étudié au cours d’une expérimentation, les effets de ces deux modes de conduite sur la croissance, les caractéristiques d’abattage et de carcasse de taurillons Créoles abattus à deux âges (précoce vs tardif). Les taurillons à l’auge avaient une croissance plus rapide, des poids de carcasse plus élevés, ainsi que des carcasses plus grasses. Nous avons observé qu’abattre plus tardivement au pâturage (17 et 21 mois vs 14 et 17 mois à l’auge), permettait d’atteindre des poids finaux similaires à ceux obtenus à l’auge et des carcasses de meilleure qualité, plus riche en muscle. Nous avons expliqué la majorité de nos résultats par les effets combinés des modes de conduite et de l’alimentation et avons voulu étudier leurs effets respectifs. Dans un second temps, l’étude des effets du mode de conduite a été faite dans un premier temps, par le biais d’une méta-analyse. Les performances des animaux à l’auge étaient meilleures qu’au pâturage, mais ces effets dépendaient de la stratégie de complémentation. De cette méta-analyse est également apparu le manque d’études auge vs pâturage sur l’alimentation et à ration égale. Afin d’étudier les effets respectifs du mode de conduite et de la stratégie de complémentation, un dispositif analytique avec des taurillons élevés à l’auge et au pâturage complémentés ou non avec du concentré a été mis en place. Dans un premier temps, une étude méthodologique menée grâce à ce dispositif nous a permis d’identifier que la SPIR permettait la meilleure estimation de la dMO, l’OMI et la MODI au pâturage. Les résultats de l’étude analytique ont montré que les animaux au pâturage utilisaient mieux leur alimentation pour leur croît que ceux à l’auge et la stratégie de complémentation influençait davantage ces variables que le mode de conduite. Avec une stratégie de complémentation appropriée, les animaux au pâturage peuvent atteindre des performances similaires à celles obtenues à l’auge. / Grazing, main way of feeding ruminants in the tropics, is often undervalued because it is associated with animal performance deemed insufficient, and may have adverse effects on the environment. Even if stall feeding allows better production, this way of feeding has drawbacks in terms of investment, profitability, impact of emissions on the environment and product quality. Intensification of grazing seems a way forward, but requires a better understanding of this way of feeding and its impact on feeding and animal performance. It also appears necessary to compare grazing and stalls feeding on homogeneous criteria, separating the components of these modes of management.The aim of the thesis is to evaluate and compare stalls and pasture feeding environment, taking into account also the distribution or not of concentrate on feeding, growth, slaughter characteristics and water consumption. At first , we studied in an experiment , the effects of these two feeding systems on growth, slaughter and carcass characteristics of Creoles bulls slaughtered at two ages (early vs. late ). Bulls fed in trough grew faster, had greater carcass weight and fatter carcasses. We observed that a later slaughter of grazing animals (17 and 21 months vs. 14 and 17 months in stalls), allowed to reach final weights similar to those obtained in stalls and carcasses richer in muscle. We explained most of our results by the combined effects of feeding environment and complementation strategy and wanted to study their effects. In a second step, the study of the effects of feeding environment was made in first instance, through a meta-analysis. Stalls fed animals had greater performances than pasture fed ones, but these effects depended on complementation strategy. This meta-analysis also highlighted the lack of knowledge on intake and digestibility at pasture, which is a limitation on attempts to compare with measurements carried out in trough-fed animals. To investigate the relative effects of feeding environment and complementation strategy, we conceived an analytical trial with Creole bulls reared in stalls and at pasture, supplemented or not with concentrate. First of all, this analytical trial was the support of a methodological study, which identified that the NIRS method allows the best estimate of the OMD, OMI and DOMI at pasture. The analytical trial showed that grazing animals had better feed efficiency feed for their growth than stall fed ones and complementation strategy influenced more these variables than feeding environment. With an appropriate strategy for complementation, grazing animals can achieve similar performance to those obtained at the trough.

The goal of this thesis is three-fold: to examine complementation in Balinese from typological, syntactic, and cognitive perspectives. This thesis contributes to typological studies of complementation by providing a descriptive account of the distinguishing syntactic properties of four types of Balinese clausal complements: sentence-like (s-like), Subject Control (SC), Object Control (OC), and Raising complements. The data presented in this thesis demonstrate the clausal complement in Balinese can be differentiated through the kinds of elements that can be admitted within the complements: the type of complementizer, aspectual auxiliaries, modals, temporal specifications, and overt subjects. The theoretical aspect of this thesis is the application of Minimalist theory to account for the syntactic structure of Balinese monoclausal and biclausal constructions. This thesis also addresses a theoretical problem related to the syntactic structure of complementation within Generative syntax: finiteness. The presence of modals, aspectual auxiliaries, and the temporal specification of the complement do not signify finiteness in Balinese. Instead, finiteness in Balinese is marked by the licensing of overt subjects in the clausal complement, following the argument made by Kurniawan & Davies (2015), based on the evidence provided through the comparison of control complements and their subjunctive sentence-like complement counterparts. The cognitive processing of Balinese complementation is investigated through two sentence processing experiments with the goals of understanding how ambiguous Crossed Control Construction (CCC) sentences are processed in comparison to the processing of unambiguous Subject Control (SC) sentences and Raising sentences. The self-paced reading experiment focuses on the comparison of reading times for the verbs in these three types of sentences when the animacy of the subject is manipulated (i.e. animate or inanimate clause-initial DP). The results suggest that CCC sentences are processed differently than the SC and Raising sentences. The second experiment aims at investigating the effect of discourse context on the interpretation of the ambiguous CCC sentences. The results show the influence of context that primes subject control interpretation on the processing of Balinese SC and CC sentences.

abstract: Prior to the first successful allogeneic organ transplantation in 1954, virtually every attempt at transplanting organs in humans had resulted in death, and understanding the role of the immune mechanisms that induced graft rejection served as one of the biggest obstacles impeding its success. While the eventual achievement of organ transplantation is touted as one of the most important success stories in modern medicine, there still remains a physiological need for immunosuppression in order to make organ transplantation work. One such solution in the field of experimental regenerative medicine is interspecies blastocyst complementation, a means of growing patient-specific human organs within animals. To address the progression of immune-related constraints on organ transplantation, the first part of this thesis contains a historical analysis tracing early transplant motivations and the events that led to the discoveries broadly related to tolerance, rejection, and compatibility. Despite the advancement of those concepts over time, this early history shows that immunosuppression was one of the earliest limiting barriers to successful organ transplantation, and remains one of the most significant technical challenges. Then, the second part of this thesis determines the extent at which interspecies blastocyst complementation could satisfy modern technical limitations of organ transplantation. Demonstrated in 2010, this process involves using human progenitor cells derived from induced pluripotent stem cells (iPSCs) to manipulate an animal blastocyst genetically modified to lack one or more functional genes responsible for the development of the intended organ. Instead of directly modulating the immune response, the use of iPSCs with interspecies blastocyst complementation could theoretically eliminate the need for immunosuppression entirely based on the establishment of tolerance and elimination of rejection, while also satisfying the logistical demands imposed by the national organ shortage. Although the technology will require some further refinement, it remains a promising solution to eliminate the requirement of immunosuppression after an organ transplant. / Dissertation/Thesis / Masters Thesis Biology 2020

Parkinson’s disease is an incurable neurodegenerative disease characterized by motor deficits, owing to dopaminergic denervation in the nigrostriatal pathway. The abnormal formation of hallmark Lewy bodies underlies the disease process. The pre-synaptic protein alpha- synuclein (⍺-syn) has prion-like properties arising from its propensity to propagate, seed misfolding, and self-aggregate. Pathogenesis is postulated to arise in olfactory and enteric regions, exploiting connected neuronal pathways to ultimately propagate to the substantia nigra pars compacta. There is little known about the earliest stages of ⍺-syn aggregation and its prion-like propagation mechanisms. Bimolecular fluorescence complementation of ⍺-syn aggregates has allowed us to directly visualize aggregation in transgenic mice and mice transduced with an adeno-associated virus vector. Although our transgenic mice expressed BiSyn in a mosaic fashion that limited utility, we were successful in transducing neurons in the mouse striatum. This work has validated the AAV2/9-CMV-BiSyn approach as groundwork for future systematic studies.

The present contribution examines object complement clauses from the perspective of constituent-order typology. In particular, it provides the first principled empirical investigation of the position of object clauses relative to the matrix verb. Based on a stratified sample of 100 languages, we establish that there is an overall cross-linguistic preference for postverbal complements, due largely to the heterogeneous ordering patterns in OV-languages. Importantly, however, we also show that the position of complement clauses correlates with aspects of their structural organization: Preverbal complement clauses are significantly more likely to be coded by morphosyntactically “downgraded” structures than postverbal complements. Given that previous research has found a parallel correlation between structural downgrading and the semantics of the complement-taking predicate (Givón 1980. The binding hierarchy and the typology of complements. Studies in Language 4. 333–377, Cristofaro 2003. Subordination. Oxford: Oxford University Press), one needs to analyze how positional, structural and semantic factors interact with one another. Our data suggest that the correlation between clause order and morphosyntactic structure holds independently of semantic considerations: All predicate classes distinguished in the present study increase their likelihood of taking downgraded complements if they are preceded by the complement clause. We thus propose that, in addition to the well-known “binding hierarchy”, a second correlation needs to be recognized in the typology of complementation: the co-variation of linear order and morphosyntactic structure.

No description available.

Comment le plan d’organisation d’un organisme est-il mis en place est une question centrale de la biologie du développement. Les séquençages complets de plusieurs génomes de métazoaires ont montré qu’un nombre restreint de molécules régulatrices soutiennent la diversité des plans d’organisation des animaux, suggérant que ces molécules sont utilisées de manière répétée dans des contextes différents. Cela soulève la question de la diversité d’action : comment ces molécules acquièrent-elle une diversité fonctionnelle ? De plus, la plupart des molécules régulatrices partagent des motifs (fonctionnels/structuraux) communs, soulevant la question de la spécificité : comment des molécules partageant des propriétés biochimiques similaires contrôlent-elles des programmes développementaux spécifiques ?Mon équipe d’accueil s’intéresse à ces questions en utilisant les facteurs de transcription Hox de la Drosophile comme paradigme d’étude.Durant ma thèse, j’ai développé trois lignes de recherches : (1) J’ai adapté la technique de complémentation bi-moléculaire de fluorescence (BiFC) de visualisation des interactions protéines-protéines à l’embryon de drosophile en développement.(2) J’ai employé la BiFC pour disséquer la formation des complexes Hox-protéines PBC. Mes résultats remettent en question le paradigme établit : (a) en soulignant la multiplicité des modes d’interaction Hox-PBC existants, (b) en démontrant que cette diversité peut être source de spécificité d’action.(3) La BiFC a ensuite été exploitée dans un crible par approche gènes candidats pour identifier de nouveaux partenaires des protéines Hox. / My current laboratory aims to tackle the issue of specificity and diversity of regulatory molecules, taking the Drosophila Hox transcription factors as a paradigm for the analysis. During my PhD, I developed three connected research lines.Project 1: Visualization of protein interactions in living Drosophila embryos by the BiFC assayOur results establish the general suitability of BiFC for revealing and studying protein interactions in their physiological context during the rapid course of Drosophila embryonic development.Project 2: Investigation of Hox/PBC complex formation in vivo using BiFC Our findings challenge the current paradigm of Hox/Pbx complex assembly: (a) highlighting the existence of alternative modes of Pbx recruitment, (b) demonstrating that unique Hox-PBC interaction modes can provide specific regulatory function in absence of DNA-binding selectivity.To achieve this project BiFC was also performed with vertebrate Hox proteins in chicken embryos.Project 3: Realization of a candidate interaction screen based on BiFC to identify novel Hox protein partners in vivo(a) We have revealed that Hox proteins establish specific interactions with different subunits of the general mediator complex. These results constituted one of the rare studies making a direct link between the Hox regulators and components of the basal transcriptional machinery, in a physiological context.(b) We have discovered that Hox proteins can interact with importin proteins. This result allows us to assess the importance of controlling the nuclear localization of Hox proteins for controlling their regulatory activities during embryogenesis.

On estime que 10%-20% de la population mondiale est infectée chaque année par des virus influenza A (IAV) saisonniers, causant 250 à 500 000 morts. De plus ces virus présentent des risques de pandémie, et sont à ce titre un problème de santé publique majeur. Le cycle viral est dépendant de la capacité du virus à manipuler le protéome cellulaire. Par ailleurs, le système ubiquitine-protéasome (SUP) cellulaire est impliqué dans de nombreux processus de régulation cellulaires par l'induction de la dégradation de protéines, ou par la modification de leur activation ou de leur localisation sub-cellulaire. Le SUP est une cible privilégiée des virus lors de l'infection. Des études récentes indiquent qu'un réseau d'interactions entre les protéines virales des IAV et les protéines du SUP pourrait contribuer à la réplication virale et l’échappement du virus face au système immunitaire. Cependant ces interactions restent encore mal connues. Nous avons construit une banque contenant 570 facteurs du SUP, ce qui représente environ 60% des facteurs SUP humains connus. Puis nous avons mis au point une méthodologie permettant de réaliser un crible comparatif des interactions entre cette banque SUP et cinq PB2 provenant de souches de virus influenza A de virulence différentes chez l’homme : deux souches saisonnières circulant actuellement dans la population humaine (H1N1pdm09 et H3N2), deux souches hautement pathogènes chez l’homme (H7N9 et H1N1-1918) et une souche de laboratoire (H1N1-WSN). Cette première phase de cartographie a permis de sélectionner 42 facteurs du SUP interagissant avec au moins une des protéines PB2 étudiées. Par ailleurs, l’analyse des similarités de profils d’interaction PB2/UPS des souches étudiées a permis de mettre en évidence une corrélation avec le temps de circulation de chaque souche dans la population humaine. Nous avons ensuite caractérisé le rôle fonctionnel des partenaires de PB2 dans le cycle viral par des expériences de déplétion transitoire de l’expression des facteurs cellulaires par siARN, et validé 36 des 42 facteurs testés. La très grande quantité de facteurs identifiés impliqués dans le cycle viral démontre la qualité de la méthodologie développée pour l’identification de ces interacteurs. Parmi ces facteurs, nous avons étudié plus en détail le rôle de trois deubiquitinases (DUBs) dans l’infection. Nous avons montré que les DUBs sont impliquées dans les phases précoces et tardives du cycle viral. De plus, avec des collègues de Hong Kong nous avons mis en évidence que la DUB OTUB1 est impliquée dans la réponse cellulaire à l’infection produisant des cytokines, et probablement dans l’assemblage des nouveaux virions. Nous avons identifié que la DUB OTUD6A est également impliquée dans les phases tardives du cycle viral. A l’inverse PAN2 qui fait partie des complexes de poly-d’adénylation est impliqué dans les phases précoces. Nous poursuivons nos études afin d’élucider le rôle de ces DUBs dans l’infection par IAV. / An estimated 10%-20% of the world's population is affected each year by seasonal epidemic influenza, causing about 250,000 to 500,000 fatal cases. The pandemic risk reinforces the trait of influenza A virus (IAV) infection as a public health issue. The virus life cycle critically relies on its ability to manipulate the host proteome. Besides, the ubiquitin-proteasome system (UPS) is involved in many regulatory processes in mammalian cells by inducing protein degradation, mediating protein activation or shaping their sub-cellular localisation. Therefore, UPS is a prime target hijacked by viruses. Recent evidence indicates that an intricate regulatory network involving viral proteins and the cellular UPS is likely to contribute to viral replication and immune evasion of influenza A viruses. However, usurpation of the host UPS by IAV is far from being comprehensively deciphered. To gain better understanding, we assessed the interplay between the human UPS and the PB2 subunit of the influenza A virus polymerase through a global proteomic profiling approach. For that purpose, an UPS-dedicated library of 590 human cDNAs, comprising 63% of the whole human UPS, was constituted and characterised. In an initial screen, UPS factors were challenged using a high-throughput split luciferase assay for interaction with the PB2 protein from 5 influenza A strains of different pathogenicity in human. A total of 80 UPS factors emerged as potential PB2 partners, of which 42 were validated as high-confidence PB2 partners for at least one of the strains. Further comparison of interaction profiles of the 5 PB2 with the UPS by hierarchical clustering revealed an interaction dendrogram fitting with the circulation time in the human population.Functional importance of interactors was tested by siRNA-mediated knock down experiments using luciferase tagged recombinant IAV viruses. Depletion of 36 out of the 42 tested UPS factors showed an effect on the infection with all or a subset of IAV strains, underlying the strong functional output of the developed methodology. Among these factors three deubiquitinases (DUBs) were further studied to decipher their involvement in IAV viral cycle. We have shown that they are involved in early and late stage of the infection and began to draw their function in viral cycle. We demonstrated with our colleagues in Hong-Kong that OTUB1 is involved in the host cytokine response and most probably in virus assembly. OTUD6A was also shown to be implicated in late stages of the infection but we still don't know its exact role. Contrariwise, the inactive DUB PAN2, which is part of poly-deadenylation complexes, is implicated in early phase of IAV infection, but surprisingly apparently not through viral mRNA regulation. More work is on-going to precise by which mechanisms these DUBs are implicated in IAV infection.

中文裡有一種特別的結構，稱為動賓複合詞(Verb-object compound)。根 據李與湯普森(Li & Thompson)觀察：從歷史的觀點來看，這種動賓複合 詞是從動賓詞組衍生得來。在本論文中，嘗試以貝克(Baker,1988)的併入 理論(Incorporation Theory)來證明他們的這個觀察。我們認為有一名為 「名詞併入」(Noun Incorporation)的句法移位律對動賓詞組產生作用。 在經過此規律作用後，動詞和它的直接賓語便在句法層次上結合成一帶動 詞性的複雜結構，此外，我們在此理論中，我們主張應加入一條構詞結合 律。此律在名詞併入後作用，把名詞併入後新產生的句法性複雜結構變換 成一構詞單位，即複合詞。這樣的解釋方式不只具有「解釋充份性」 (explanatory adequacy)，而且從歷史的觀點來看此一名詞併入現象，上 述方式也可以妥善地解決一個爭議已久有關動賓複合詞是否可以離合的問 題，以及有關雙重分類的動賓複合詞所造成的難題。藉著這樣的分析，我 們討論了八類動賓結構。這八類恰好形成一個漸次變化。其大抵反映出動 賓結構從詞組變成複合詞的詞彙化過程。至於此八類之間的句法變異，我 們發現其「分類差異」(status variation)與及物性變異(transitivity variation)是一些規律互相競爭(competition)與互補(complementation) 的結果。此現象在謝(Hsieh,1989)的交互作用理論(Interaction Theory) 中早已被指出。而此理論在解釋句法變異上的完善，更證明了我們先前利 用名詞併入方式分析動賓結構是正確的。 / In Mandarin Chinese, there is a special construction called verb-object compounds. It has been observed by Li & Thompson (1981) that the verb-object compounds are derived historically from verb-object phrases. In this thesis, we attempt to verify this observation by means of the Incorporation Theory by Baker (1988). We argue that a syntactic rule, noun incorporation, applies to verb-object phrases and combines the verb and its direct object together to form a syntactic verbal complex. A morphological merging rule is added into the Theory, and applies immediately after the former rule to transform the newly created syntactic construct into a morphological one, a compound. Such and approach not only achieves the explanatory adequacy, but also resolves the long-standing controversies on the expandability of verb-object compounds and the paradox of verb-object compounds with dual status, if we keep a historical view on the process of the noun incorporation. Based on this analysis, the eight types of verb-object constructions form a continuum which roughly reflects a lexicalization process from verb-object phrases to verb-object compounds. As for the syntactic variation--status variation and transitivity variation--among different types verb-object consrtuctions, it is found to be a result of the competition and complementation among some rules, a fact evidenced in Hsieh's (1989) Interaction theory. the success of the interaction account further justifies our incorporation analysis on verb-object construcitons.