Apomixis, or asexual seed development, if introduced into crop species, has the potential to greatly improve global food production. Towards this goal, this study focused on uncovering the genetic mechanisms that control the parthenogenesis step within apomixis whereby fertilisation is avoided. In the model apomict, Hieracium praealtum (Asteraceae), parthenogenesis is controlled by the LOSS OF PARTHENOGENESIS (LOP) locus. Previous research showed that in addition to genomic copies of candidate genes at LOP, the genome has at least three other copies referred to as alternative alleles. The main goal of this study was to investigate four candidate genes, Genes B, X, H and Y, at LOP by generating segregation data of the alternative alleles. BAC clones containing alternative allele sequences were identified and Roche 454 pyrosequenced. These sequences were used to design alternative allele specific primers for genotyping two Hieracium praealtum polyhaploid populations (~ 300 plants). Four major conclusions were drawn from this study. First, the alternative alleles were in fact acting like alleles to the LOP alleles of Genes B, X and Y. Second, allelic sequence divergence (ASD) of the LOP alleles of Genes B and X relative to the alternative alleles, indicated a recent and separate evolutionary history. Third and, unexpectedly, recombination was detected at the LOP locus, in contrast to other apomixis loci reported in the literature. Furthermore, Gene B was found to be very closely associated with parthenogenesis in the polyhaploid population indicating that it may be essential to parthenogenesis and therefore requires further investigation. On the other hand, the absence of Genes X, Y and H, due to recombination, had no impact upon parthenogenesis. Fourth, the sequence data suggested that the LOP and alternative alleles originated from a shared common allele ancestor. It is hoped that these findings have made a significant contribution towards the future goal of introducing apomixis into crop species.

In this thesis an analytical design method of the improved broadband passive harmonic filter (IBF) for three phase diode rectifier front-end type adjustable speed drives is presented. The method is based on frequency domain modeling of the rectifier and filter. The success of the method involves accurate representation of the load harmonics. With the harmonics well defined, the harmonic and fundamental frequency equivalent circuits are utilized to analytically calculate the voltages/currents. Thus, the size and the performance of the filter can be optimized. The analytical method is verified via computer simulations and laboratory experiments. Also a performance comparison of various passive harmonic filters for three-phase diode rectifier front-end type adjustable speed drives is provided. The comparison involves the input current total harmonic distortion, input power factor, rectifier voltage regulation, energy efficiency, size, and cost. The parallel/series harmonic resonance problem related issues are addressed and unbalanced operation performance investigated. The comparison is based on analysis and computer simulations and the results are validated by laboratory experiments.

Play is an important contributor to children’s development: it reflects, reinforces, and results in development (Johnson, Christie, Wardle, 2005). However, the tools available to support planning and measurement of play are not sufficiently detailed or focused on children with autism and severe learning difficulties (SLD). Play for children with autism is consistently identified as restrictive and repetitive. Although extensive research examines symbolic play, the content and structure of functional play, which is considered a valuable precursor of symbolic play, is rarely the subject of focused research (Williams, 2003; Lifter, Foster-Sanda, Arzamarski, Briesch, & McClure, 2011). Given the developmental potential that play presents, the aim of this study was to examine the functional play presented by children with autism and SLD, with a view to designing a play framework that enables teachers to support functional play development in the classroom. A pragmatic mixed methods approach was adopted across a three-stage study in three schools. Study 1 provides the background for creating a functional play framework, while Study 2 focuses on the creation of the framework through objective observations of the play activity of a total of 27 children with autism and SLD, as well as interviews with nine classroom teachers. Study 3 was a process of trialling the framework in two schools and collaborating with eight teachers to finalise the functional play framework, in particular by considering its usability. Data collected across the three studies provided a description of functional play that suggests it is more complex than traditionally defined. Four key areas of functional play were identified: interacting with one object; interacting with two (or more) objects; interacting with self; and interacting with the environment. Additionally, 12 subcategories were established as components related to functional play. Teachers reported that they could use the framework to baseline play, set targets and measure play progression for children with autism and SLD. The framework was also identified as a tool that supports classroom management and continuing professional development. The proposed framework facilitates the identification of small increments of progress and extends on other available play frameworks. By developing detailed descriptions of the play that children with autism and SLD present, the framework provides a greater ability to identify precise deficits and, more specifically, to target support in the area of play. Additionally, the collaborative approach with classroom teachers provides diverse viewpoints but also begins to merge the gap between researchers and practitioners in order to ensure a useful resource. Recommendations for further descriptive accounts, greater involvement of classroom professionals in the development of resources and additional trials of the framework are acknowledged.

Transtorno do espectro autista (TEA) é um quadro complexo do neurodesenvolvimento associado com elevado prejuízo funcional, onde os pacientes apresentam alterações comportamentais, déficit de comunicação e problemas de sociabilização. A incidência do TEA é muito elevada e vem crescendo constantemente nos últimos anos. Atualmente a prevalência é de 1 em cada 50 crianças nos EUA, sendo os meninos mais afetados que as meninas (4:1). O diagnóstico dos pacientes com TEA é feito clinicamente e ocorre geralmente com a idade de aproximadamente três anos, idade que os sintomas ficam mais evidentes. As causas biológicas e genéticas do autismo vem sendo estudadas em modelos animais e em material biológico humano, como sangue (genéticas) e cérebro post-mortem. Apesar de valiosos, esses modelos não permitem estudos das células neurais humanas em funcionamento. A geração de células neurais funcionais a partir das células previamente reprogramadas mudou esse cenário e abriu portas para gerar modelos celulares e estudar as doenças in vitro. Esse trabalho teve como objetivo modelar o TEA in vitro, a partir de neurônios e astrócitos derivados de células-tronco pluripotentes induzidas obtidas a partir das células-tronco de dente decíduo esfoliado (SHED) de pacientes com transtorno autista. Em nossos resultados observamos que neurônios autistas apresentam uma significativa diminuição na expressão de genes sinápticos quando comparados com neurônios não-autistas (controle). Além disso, ensaios funcionais de eletrofisiologia revelaram que neurônios autistas têm um número menor de picos de estimulação (spikes) por segundo, indicando neurônios possivelmente menos ativos. Em tempo, experimentos de co-cultura de neurônios e astrócitos revelaram que astrócitos autistas podem interferir na maturação e complexidade morfológica dos neurônios controle, e o inverso também foi observado, onde astrócitos de controles podem resgatar o fenótipo de neurônios autistas, sendo que um aumento significativo no nível de marcadores sinápticos, mudanças na morfologia com neurônios de pacientes mais maduros e complexos foi observado quando cultivados sobre astrócitos controles. Nossos dados indicam que os astrócitos influenciam na maturação, na complexidade e funcionalidade dos neurônios, mostrados aqui pela primeira vez para o autismo idiopático. Além disso, com este trabalho podemos afirmar que é possível modelar o autismo idiopático in vitro e estudar formas de resgate fenotípico das células afetadas na patologia visando futuras terapias para esses pacientes. A tecnologia das células reprogramadas e modelagem de doenças abre portas para novas descobertas no campo do autismo / Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by qualitative impairment communication, social interaction and restricted and repetitive patterns of behavior. The prevalence of 1 in every 50 children in The United States has been reported with a tendency to increase in recent years. Patient ASD diagnosis typically occurs by the age of 3 years and affects more boys than girls (4:1). The biological and genetic causes of autism has been studied in animal models, in human biological material such as blood and in post-mortem brain tissues. Although valuable, these models do not allow study of living human neural cells. The generation of functional neural cells from reprogrammed cells previously changed this scenario and opened doors to generate cellular models in vitro and to study diseases as autism. This study aimed to model ASD in vitro to study neurons and astrocytes derived from induced pluripotent stem cells from mesenchymal stem cells from dental pulp (SHED) from patients with idiopathic autism. In our results we found that neurons derived from patients with ASD show a significant decrease in synaptic genes compared with controls. Functional electrophysiology tests were performed and we were able to observe a smaller number of spike per second in neurons derived from patients, indicating that neurons from ASD patients has less activity than control neurons. In our co-culture assay between neurons and astrocytes we observed that astrocytes derived from patients may interfere in the maturation and morphological complexity of neurons derived from controls. On the other hand, when we grow ASD neurons on astrocytes from controls we can observe a significant increase in the level of synaptic markers, changes in morphology where we observe more mature and complex neurons. These data indicate that astrocytes influence in the maturity, complexity and functionality of neurons, data never shown before for ASD patients. With these results we can say that it is possible to model idiopathic autism in vitro. The iPSC technology and disease modeling opens doors to new discoveries and therapies for ASD patients

Le trouble du spectre de l’autisme (TSA) et la déficience intellectuelle (DI) sont des troubles du développement qui affectent un grand nombre de familles partout dans le monde (American Psychiatric Association, 2013). Des études démontrent que les enfants ayant une DI ou un TSA manifestent plus de comportements problématiques que les enfants dans la population en générale. Les agressions physiques et verbales, la destruction de bien, les crises, l’opposition et l’automutilation interfèrent souvent avec les habiletés de l’individu, l’empêchant de bien fonctionner et causant souvent des dommages ou des blessures (Matson et al., 2009; Mazurek et al., 2013; Minshawi et al., 2014). Pour bien cerner l’importance de réduire les comportements problématiques, plusieurs études démontrent les conséquences graves qui peuvent en découler (Caron, Fleury, Godbout et Desranleau, 2005 ; Taylor, Oliver et Murphy, 2011). Ces conséquences peuvent limiter ou mettre à risque l’utilisation optimale de nombreuses ressources découlant de la communauté et réduire la capacité de la personne accompagnée à s’occuper de ses besoins et limitent son potentiel d’intégration sociale et communautaire (Richards, Moss, Nelson et Oliver, 2016). Les interventions comportementales peuvent aider les familles d’enfants ayant un TSA ou une DI qui se retrouvent bien souvent stressées et isolées socialement, s’exposant à des dangers réels, comme faire subir de mauvais traitements physiques à leurs enfants si elles ne reçoivent aucune aide (Bessette Gorlin, McAlpine, Garwick et Wieling, 2016; Chan et Lam, 2016). Cependant, l’accessibilité aux services pour traiter ces difficultés comportementales est souvent limitée à cause des coûts élevés des services privés, de l’isolement géographique, du manque de personnel ou encore des listes d’attente pour les services publics. Parmi les nouveaux moyens technologiques utilisés pour offrir des services précoces aux familles, on retrouve les formations interactives offertes en ligne, simples à utiliser, efficaces et très peu coûteuses (Higbee et al. 2016; Pollard, Higbee, Akers et Brodhead, 2014). Des résultats iii d’études soutiennent qu’il est possible d’impliquer de manière efficace les parents en tant qu’agents de changement dans la réduction des comportements problématiques de leurs enfants par différentes interventions comportementales, directives verbales et écrites, modelage par vidéo et exercices de répétitions (Gerencser, Higbee, Akers et Contreras, 2017; Ilg et al., 2016; Lanovaz, Rapp, Maciw, Dorion et Pelletier, 2016). L’objectif de notre étude était d’examiner les résultats préliminaires d’une formation interactive en ligne développée pour soutenir les parents d’enfants ayant un TSA ou une DI dans la réduction de comportements problématiques. Les objectifs de ce projet pilote portait principalement sur trois variables de réponse : (1) l’identification d’une fonction plausible d’un comportement problématique (2) la sélection d’une intervention fonctionnelle et (3) la satisfaction du parent vis-à-vis de cette formation. Les résultats de ce projet pilote suggèrent une amélioration sur des tâches d’identification de fonctions comportementales plausibles et de sélection d’interventions fonctionnelles ainsi qu’une excellente validité sociale. L’utilisation d’une formation interactive comme ressource aux parents semble être une avenue novatrice et intéressante à explorer. Il serait cependant nécessaire de reproduire l’étude afin de pouvoir valider les résultats / Autism spectrum disorders (ASD) and intellectual disability (ID) are developmental disorders that affect many families around the world (American Psychiatric Association, 2013). Several studies have shown that children with ASD or ID engage in more challenging behavior than children without disability. Aggression, destruction, opposition, and self-injury often interfere with individual skills, preventing those who emit these behavior from functioning adequately in their natural environment and often causing them harm or injury (Matson, Wilkins & Macken, 2008; Mazurek, Kanne & Wodka,2013; Minshawi & al., 2014). Several studies have outlined the serious consequences that can result from these behaviors (Caron, Fleury, Godbout & Desranleau, 2005; Taylor, Oliver & Murphy, 2011). These consequences can limit or put at risk the optimal use of community resources and reduce the persons’ capacity to address their needs and limit their potential for social and community integration (Richards, Moss, Nelson & Oliver, 2016). Behavioral interventions can help families who are often stressed, socially isolated and confronted to risks if they do not receive access to adequate services (Bessette, Gorlin, McAlpine, Garwick & Wieling, 2016; Chan & Lam, 2016). However, accessibility to services to address these behavioral difficulties is often limited due to the high costs of private services, geographic isolation, shortage of staff, or waiting lists for public services. Interactive web training is an easy-to-use, efficient and affordable approach, which can be used to address these issues (Higbee & al., 2016; Pollard, Higbee, Akers & Brodhead, 2014). Research findings suggest that parents can be effectively involved as agents of change and play a meaningful role in the reduction of their children’s challenging behavior when trained adequately using verbal v and written instructions, video modeling and exercises (Gerencser, Higbee, Akers & Contreras, 2017; Ilg & al., 2016; Lanovaz, Rapp, Maciw, Dorion & Pelletier, 2016). The objective of our study was to document the effects of an interactive web training developed to support parents of children with ASD or ID in the reduction of challenging behavior. The objectives of this pilot project focused on three response variables (1) identifying a function of challenging behavior, (2) selecting a functional intervention, and (3) parents’ satisfaction with the training. The results indicated an improvement on behavioral function identification tasks and functional intervention selection tasks as well as an excellent social validity. The use of interactive web training as a resource for parents seems to be an interesting avenue for treatment, but it is necessary to replicate our study in order to validate the results.

Training siblings as change agents for children diagnosed with autism spectrum disorders (ASD) has been shown to be beneficial in teaching a sibling to teach their brother or sister. There are very few interventions, however, that explore the range of effects that targeting particular skills has on sibling interactions. The purpose of this study was to assess the direct and collateral effects of training behavioral teaching techniques to a typically developing sibling. Four experimental conditions were assessed: baseline, sibling teaching toy play, baseline, and sibling teaching social play. Across all conditions, measures of teaching components and siblings' interactions were assessed. Results of the assessment showed that the sibling was an effective change agent and that more favorable interaction and engagement occurred when social play skills were taught. The results of this sibling intervention and guidelines for condition changes are discussed in terms of sibling relationships.

Les Troubles du Spectre Autistique (TSA) forment un groupe hétérogène de troubles neurodéveloppementaux caractérisés par des déficits de l’interaction sociale et de la communication ainsi que la présence de comportements répétitifs et d’intérêts restreints. Les TSA affectent environ un individu sur 68. Ils se manifestent généralement durant les trois premières années de vie mais, pour certains cas, les symptômes sont reconnus plus tard, quand les exigences sociales augmentent. Les études de jumeaux et la récurrence des troubles dans certaines familles démontrent l’importance des facteurs génétiques dans la vulnérabilité aux TSA. Cependant, l’architecture génétique des TSA reste difficile à caractériser car elle est extrêmement hétérogène et il est très compliqué d’identifier, pour chacun des patients, la combinaison d’allèles à risque. Notre laboratoire a identifié la première voie génétique associée aux TSA – la voie NLGN-NRXN-SHANK- qui joue un rôle clé dans la plasticité synaptique. Il existe un nombre de plus en plus grand de gènes associés aux TSA mais peu d’études ont été réalisées sur des cohortes épidémiologiques et dans des populations isolées. L'analyse des données de génotypage et de séquençage d’exome de 357 individus issus des îles Féroé (36 patients, 136 apparentés des patients, 185 témoins) nous a permis de mettre en évidence un nombre plus important de Variations du Nombre de Copies (CNVs), un coefficient de consanguinité supérieur, un plus grand nombre de mutations homozygotes et délétères ainsi qu’un Polygenic Risk Score (ASD-PRS) supérieur chez les patients TSA comparés aux individus témoins. Notre analyse confirme le rôle de plusieurs loci associés aux TSA (NRXN1, ADNP, délétion 22q11) et a permis d’identifier de nouvelles mutations tronquant la protéine (GRIK2, ROBO1, NINL et IMMP2L) ou récessives (KIRREL3 et CNTNAP2) affectant des gènes déjà associés aux TSA. Nous avons également mis en évidence trois nouveaux gènes candidats jouant un rôle important dans la plasticité synaptique (RIMS4, KALRN et PLA2G4A) à travers la présence de mutations de novo délétères chez des patients sans déficience intellectuelle. Au total, nous avons pu identifier une cause génétique expliquant les TSA pour 11% des patients et au moins une mutation fortement délétère dans des gènes candidats chez 39% des patients. Aucune cause génétique n'a pu être trouvée chez 50% des patients. En résumé, notre étude permet de mieux comprendre l’architecture génétique des TSA dans les populations isolées en soulignant à la fois l'impact des variants communs et des variants rares mais également en révélant le rôle de nouveaux gènes pour les TSA. Ces gènes codent pour des protéines essentielles pour le neurodéveloppement et l’identification de ces facteurs impliqués dans la formation et l'entretien des synapses pourrait ainsi fournir de nouvelles pistes afin de mieux comprendre les bases biologiques des TSA et de découvrir de nouvelles stratégies thérapeutiques. Il est cependant nécessaire de comprendre plus avant l'impact de la combinaison de différentes mutations sur la fonction neuronale afin de mieux caractériser l’architecture génétique des TSA. / Autism Spectrum Disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders characterized by deficits in social interaction and communication as well as the presence of repetitive behaviors and restricted interests. ASD affects approximately one in 68 individuals. They usually occur during the first three years of life but, in some cases, symptoms are recognized later, when social demands increase. There is a strong genetic component to ASD, as indicated by the recurrence risk in families and twin studies. However, the genetic architecture of ASD remains largely unknown because of its extreme heterogeneity. It is very challenging to identify, for each patient, the combination of risk alleles. Our laboratory identified the first genetic pathway associated with ASD – the NLGN-NRXN-SHANK pathway – playing a key role in synaptogenesis during development. There are an increasing number of genes associated with ASDs but few studies have been conducted on epidemiological cohorts and isolated populations. Here, we investigated 357 individuals from the Faroe Islands including 36 patients with ASD, 136 of their relatives and 185 non-ASD controls. Data from SNP array and whole exome sequencing revealed that patients had a higher burden of copy-number variants, higher inbreeding status, higher load of homozygous deleterious mutations, and a higher ASD polygenic risk score compared to controls. We confirmed the role of several ASD-associated loci (NRXN1, ADNP, 22q11 deletion) and identified new truncating (GRIK2, ROBO1, NINL and IMMP2L) or recessive variants (KIRREL3 and CNTNAP2) affecting genes already associated with ASD. We have also identified three novel candidate genes playing key roles in synaptic plasticity (RIMS4, KALRN and PLA2G4A) carrying deleterious de novo mutations in patients without intellectual disability. Overall, for 11% of individuals with ASD, a known genetic cause was identified, for 39% at least one strongly deleterious mutation was identified in a compelling candidate gene and for 50% no obvious genetic cause was detected. In summary, our study provides a better understanding of the genetic architecture of ASD in isolated populations by highlighting both the impact of common and rare variants but also by revealing the role of new genes for ASD. These genes code for proteins that are essential for neurodevelopment. The identification of these factors involved in synapse formation and maintenance could provide new leads to better understand the biological basis of ASD and find novel therapeutic strategies. However, it is necessary to further understand the combined impact of different mutations on neuronal function in order to better characterize the genetic architecture of ASD.

Enrollment in post-secondary education for individuals with autism spectrum disorder (ASD) is increasing; however, students with ASD are less likely to complete a degree than students with other disabilities. Classroom performance requires attending to course-related information while filtering distractions. These attentional functions are critical for academic achievement. However, ASD is associated with pervasive impairments in attentional filtering. The present study used visual search, a task in which individuals with ASD excel, to investigate filtering of irrelevant social and non-social auditory information in college students with and without ASD. Results of the present study suggest a filtering deficit for individuals with ASD and indicate that this filtering impairment is present for both social and non-social information. Importantly, these deficits are present on a task in which individuals with ASD excel. Our findings suggest that irrelevant social and non-social sounds may adversely affect performance in college-aged students with high-functioning ASD and highlight the importance of minimizing competing background noise for these students.

Orientador: Vera Lúcia Messias Fialho Capellini / Resumo: Atualmente no Brasil, a inclusão escolar nas classes comuns de educação básica está sendo assegurada por meio de políticas públicas que estão sendo desenvolvidas, no entanto, ainda há outros fatores que impedem todos os alunos de participarem ativa e criticamente da sociedade. Mostrando-se favorável a esse processo de inclusão, a Pedagogia Waldorf baseia-se em princípios de valorização das potencialidades do ser humano, propondo uma educação integral que visa o atendimento às necessidades de cada indivíduo. Dentre os alunos Público-Alvo da Educação Especial (PAEE), que estão sendo inclusos nas escolas regulares, há os com Transtorno do Espectro Autista (TEA), que devido à possíveis déficits no aspecto da comunicação, precisam de instrumentos que possam auxiliar no processo de aquisição da linguagem escrita. Dentro dessa temática, a presente pesquisa teve como objetivo geral descrever e analisar o processo inicial de alfabetização e letramento, considerando uma classe comum com um aluno diagnosticado com TEA, desenvolvido em contexto de Pedagogia Waldorf. Os objetivos específicos foram: a) descrever o efeito do desenvolvimento da habilidade consciência fonológica no processo de alfabetização e letramento desses alunos; b) avaliar a aplicabilidade de materiais produzidos e adequados/adaptados pela pesquisadora, para alunos com TEA; e c) ao final do estudo, como produto educacional, criar uma história social, em formato de livro ilustrado, paradidático, para crianças em fase ini... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Currently in Brazil, school inclusion in common basic education classes is being ensured through public policies that are being developed, however, there are still other factors that prevent all students from participating actively and critically in society. Showing itself favorable to this inclusion process, Waldorf Education is based on principles of valuing the potential of the human being, proposing a comprehensive education that aims to meet the needs of each individual. Among the Target Public of Special Education (PAEE) students, who are being included in regular schools, there are those with Autistic Spectrum Disorder (ASD), who due to possible deficits in the aspect of communication, need instruments that can assist in the process acquisition of written language. Within this theme, the present research aimed to describe and analyze the initial process of literacy and literacy, considering a common class with a student diagnosed with ASD, developed in the context of Waldorf Education. The specific objectives were: a) to describe the effect of the development of the phonological awareness skill in the literacy and literacy process of these students; b) evaluate the applicability of materials produced and adapted / adapted by the researcher, for students with ASD; and c) at the end of the study, as an educational product, create a social history, in the format of an illustrated, paradidactic book, for children in the initial phase of literacy. The research methodology w... (Complete abstract click electronic access below) / Mestre

Students with Autism Spectrum Disorder (ASD) often require academic support to participate in the inclusive classroom. SRSD writing interventions have proven to be effective on this population. As there is a gap in the literature regarding the effectiveness of SRSD writing interventions on high-school students with ASD, this study employed a single-case design (SCD) to investigate the implementation of PLEASE paragraph-writing on two high-school students with high-functioning ASD. Response to intervention was assessed with pretest and posttest measures and with progress monitoring across intervention sessions. Data analysis included Percentage of Non-Overlapping Data (PNDs) and visual inspection of the line. Results indicated that PLEASE was very effective in improving the student’s writing and planning skills regarding theme development and organization, and draft-writing and self-monitoring respectively. Results of this study are discussed in relation to existing literature on SRSD, writing interventions, and ASD. Implications for educators and professionals working with high-school students identified with ASD and writing difficulties are discussed. / Graduate