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Rapid technological advances in artificial intelligence (AI), data analytics, big data, the semantic web, the Internet of Things (IoT), and cloud and mobile computing have given rise to a new generation of AI-driven recommendation agents (RAs). These agents continue to evolve and offer potential for use in a variety of application domains. However, extant information systems (IS) research has predominantly focused on user perceptions and evaluations of traditional non-intelligent product-brokering recommendation agents (PRAs), supported by empirical studies on custom-built experimental RAs that heavily rely on explicit user preference elicitations. To address the lack of research in the new generation of intelligent RAs (RAs 2.0), this dissertation aims to study consumer responses to AI-driven RAs using an affordance perspective. Notably, this research is the first in the IS discourse to link RA design artifacts, RA affordances, RA outcomes, and user continuance. It examines how actualized RA affordances influence user engagements with and evaluations of these highly personalized systems, which increasingly focus on user experiences and long-term relationships. This three-essay dissertation, consisting of one theory-building paper and two empirical studies, conceptually defines "RAs 2.0," proposes a comprehensive theoretical framework with testable propositions, and conducts two empirical studies guided by smaller carved-out models to test the validity of the comprehensive framework. The research is expected to enrich the IS literature on RAs and identify potential areas for future research. Moreover, it offers key implications for industry professionals regarding the effective system development of the new generation of intelligent RAs. / Doctor of Philosophy / Rapid technological advances in artificial intelligence (AI), data analytics, big data, the semantic web, the Internet of Things (IoT), and cloud and mobile computing have given rise to a new generation of AI-driven recommendation agents (RAs). These agents continue to evolve and offer potential for use in a variety of application domains. This three-essay dissertation, consisting of one theory-building paper and two empirical studies, conceptually defines "RAs 2.0," proposes a comprehensive theoretical framework with testable propositions, and conducts two empirical studies guided by smaller carved-out models to test the validity of the comprehensive framework. The research is expected to enrich the IS literature on RAs and identify potential areas for future research. Moreover, it offers key implications for industry professionals regarding the effective system development of the new generation of intelligent RAs.

INTRODUÇÃO: as RASopatias, que englobam a síndrome de Noonan e as síndromes relacionadas à síndrome de Noonan (Noonan-like), são doenças monogênicas de herança autossômica dominante causadas por mutações em genes pertencentes a mesma via de sinalização (RAS-MAPK). Caracterizam-se por um envolvimento multissistêmico, no qual a baixa estatura é um sinal cardinal. Os aspectos nutricionais são mais estudados nas síndromes relacionadas à síndrome de Noonan, nas quais uma dificuldade alimentar nos primeiros meses de vida é mais frequente e acentuada, requerendo uma intervenção terapêutica. OBJETIVOS: avaliar o estado nutricional de indivíduos com RASopatias, o consumo de energia e macronutrientes de acordo com a idade e gênero, comparar os dados antropométricos e o consumo alimentar com os dados populacionais e estabelecer uma associação entre o genótipo e o fenótipo dos indivíduos. MÉTODOS: o estado nutricional de 62 indivíduos com Rasopatias, confirmado por estudo molecular, com mediana de idade de 12 anos, foi avaliado a partir da realização de medidas antropométricas (peso, estatura, circunferência do braço e prega tricipital), da análise do consumo alimentar habitual e do nível de atividade física. RESULTADOS: Observou-se um déficit de crescimento de origem pós-natal em 48% dos indivíduos e, na classificação pelo índice de massa corpórea, aproximadamente 80% deles foram classificados como eutróficos ou com baixo peso/ magreza acentuada. Os parâmetros de composição corporal mostraram um comprometimento na circunferência muscular do braço e, nas classificações pela área gordurosa do braço e área muscular do braço, 43,5% apresentavam baixa reserva de gordura e 69% eram desnutridos ou abaixo da média, respectivamente. Ao associar o genótipo ao fenótipo dos indivíduos estudados, os genes SHOC2, RAF1 e KRAS eram os que apresentavam os valores médios mais baixos de estatura e os indivíduos com mutações no gene SHOC2, os menores valores de mediana de índice de massa corpórea Já os indivíduos com mutações no gene BRAF tiveram os maiores valores desta mediana. Houve uma diferença estatisticamente significante no escore-Z da dobra cutânea tricipital e na área gordurosa do braço entre BRAF e SHOC2 e no escore-Z da dobra cutânea tricipital entre RAF1 e SHOC2. O consumo energético e de macronutrientes dos indivíduos foi semelhante à referência de ingestão diária e ao da população brasileira e no nível de atividade física, 65,4% eram sedentários e irregularmente ativos. Encontrou-se somente um indivíduo com dificuldade importante na alimentação, necessitando de gastrostomia. CONCLUSÕES: A baixa estatura é frequente e mais pronunciada nos indivíduos com mutação nos genes SHOC2, RAF1 e KRAS. Diferindo da tendência da população mundial a apresentar uma alta prevalência de obesidade, a grande maioria dos indivíduos com RASopatias apresenta-se eutrófica ou com baixo peso/magreza. Na composição corpórea, há um acometimento do tecido muscular em todos os indivíduos estudados. A diminuição destas medidas não é explicada por uma baixa ingesta alimentar e nem por um aumento nas atividades físicas do grupo. É possível que os fatores genéticos, por um aumento da sinalização da via RAS-MAPK, confiram um perfil mais magro a estes indivíduos, por acometimento não apenas da gordura, mas especialmente da musculatura / INTRODUCTION: RASopathies that include Noonan syndrome and Noonan related disorders (Noonan-like) are monogenic conditions with autosomal dominant inheritance caused by mutations in genes belonging to the same signaling pathway (RAS-MAPK). They are characterized by a multisystemic involvement in which short stature is a cardinal feature. The nutritional aspects are more frequently described in Noonan related disorders, in which feeding difficulties in the first months of life are more frequent and severe, requiring therapeutic intervention. OBJECTIVES: To evaluate the nutritional aspects of individuals with RASopathies, the energy and macronutrients consumption, according to age and sex; to compare the anthropometric data and dietary intake with population references and to establish a genotype-phenotype correlation. METHODS: The nutritional status of 62 individuals with Rasopathies confirmed by DNA analysis, with a median age of 12 years was evaluated by performing anthropometric measurements (weight, height, arm circumference and triceps skinfold thickness), analysis of habitual food intake and physical activity level. RESULTS: There was growth deficiency of postnatal origin in 48% of subjects and in the classification by body mass index, approximately 80% of them were classified as eutrophic or underweight/thinness. The parameters of body composition showed a decreased upper arm muscle circumference and in the classification by the upper arm fat area and upper arm muscle area, 43.5% had low fat reserves and 69% were malnourished or below average, respectively. Genotype-phenotype correlation showed that individuals with mutations in SHOC2, RAF1 and KRAS were those presenting the lowest mean values of stature and individuals with mutations in SHOC2, the lower median values of bone mass index. On the other hand, individuals with mutations in the BRAF had the highest median values. There was a statistically significant difference of the triceps skinfold thickness and upper arm fat area between Z-scores between BRAF and SHOC2 and of the triceps skinfold thickness Z-score between RAF1 and SHOC2. The energy and macronutrient intake of the subjects were similar to the dietary intake reference and the Brazilian population and in the level of physical activity, 65.4% were sedentary and irregularly active. It was found only one individual with significant difficulty in feeding, requiring gastrostomy. CONCLUSIONS: Short stature is common and more pronounced in individuals with mutations in SHOC2, RAF1 and KRAS. Opposed to the trend of the world\'s population of an increased prevalence of obesity, the majority of individuals with RASopathies present as eutrophic or underweight/ thinness. In body composition, there is an involvement of muscle tissue in all studied subjects. The decrease of these measures in the group is explained neither by a lower food intake nor by an increase in physical activity. It is possible that genetic factors, leading to hyperactivation of the RAS/ MAPK signaling, confer a slimmer profile to these individuals, mostly by the muscle involvement and not only by a decrease in fat reserve

INTRODUÇÃO: as RASopatias, que englobam a síndrome de Noonan e as síndromes relacionadas à síndrome de Noonan (Noonan-like), são doenças monogênicas de herança autossômica dominante causadas por mutações em genes pertencentes a mesma via de sinalização (RAS-MAPK). Caracterizam-se por um envolvimento multissistêmico, no qual a baixa estatura é um sinal cardinal. Os aspectos nutricionais são mais estudados nas síndromes relacionadas à síndrome de Noonan, nas quais uma dificuldade alimentar nos primeiros meses de vida é mais frequente e acentuada, requerendo uma intervenção terapêutica. OBJETIVOS: avaliar o estado nutricional de indivíduos com RASopatias, o consumo de energia e macronutrientes de acordo com a idade e gênero, comparar os dados antropométricos e o consumo alimentar com os dados populacionais e estabelecer uma associação entre o genótipo e o fenótipo dos indivíduos. MÉTODOS: o estado nutricional de 62 indivíduos com Rasopatias, confirmado por estudo molecular, com mediana de idade de 12 anos, foi avaliado a partir da realização de medidas antropométricas (peso, estatura, circunferência do braço e prega tricipital), da análise do consumo alimentar habitual e do nível de atividade física. RESULTADOS: Observou-se um déficit de crescimento de origem pós-natal em 48% dos indivíduos e, na classificação pelo índice de massa corpórea, aproximadamente 80% deles foram classificados como eutróficos ou com baixo peso/ magreza acentuada. Os parâmetros de composição corporal mostraram um comprometimento na circunferência muscular do braço e, nas classificações pela área gordurosa do braço e área muscular do braço, 43,5% apresentavam baixa reserva de gordura e 69% eram desnutridos ou abaixo da média, respectivamente. Ao associar o genótipo ao fenótipo dos indivíduos estudados, os genes SHOC2, RAF1 e KRAS eram os que apresentavam os valores médios mais baixos de estatura e os indivíduos com mutações no gene SHOC2, os menores valores de mediana de índice de massa corpórea Já os indivíduos com mutações no gene BRAF tiveram os maiores valores desta mediana. Houve uma diferença estatisticamente significante no escore-Z da dobra cutânea tricipital e na área gordurosa do braço entre BRAF e SHOC2 e no escore-Z da dobra cutânea tricipital entre RAF1 e SHOC2. O consumo energético e de macronutrientes dos indivíduos foi semelhante à referência de ingestão diária e ao da população brasileira e no nível de atividade física, 65,4% eram sedentários e irregularmente ativos. Encontrou-se somente um indivíduo com dificuldade importante na alimentação, necessitando de gastrostomia. CONCLUSÕES: A baixa estatura é frequente e mais pronunciada nos indivíduos com mutação nos genes SHOC2, RAF1 e KRAS. Diferindo da tendência da população mundial a apresentar uma alta prevalência de obesidade, a grande maioria dos indivíduos com RASopatias apresenta-se eutrófica ou com baixo peso/magreza. Na composição corpórea, há um acometimento do tecido muscular em todos os indivíduos estudados. A diminuição destas medidas não é explicada por uma baixa ingesta alimentar e nem por um aumento nas atividades físicas do grupo. É possível que os fatores genéticos, por um aumento da sinalização da via RAS-MAPK, confiram um perfil mais magro a estes indivíduos, por acometimento não apenas da gordura, mas especialmente da musculatura / INTRODUCTION: RASopathies that include Noonan syndrome and Noonan related disorders (Noonan-like) are monogenic conditions with autosomal dominant inheritance caused by mutations in genes belonging to the same signaling pathway (RAS-MAPK). They are characterized by a multisystemic involvement in which short stature is a cardinal feature. The nutritional aspects are more frequently described in Noonan related disorders, in which feeding difficulties in the first months of life are more frequent and severe, requiring therapeutic intervention. OBJECTIVES: To evaluate the nutritional aspects of individuals with RASopathies, the energy and macronutrients consumption, according to age and sex; to compare the anthropometric data and dietary intake with population references and to establish a genotype-phenotype correlation. METHODS: The nutritional status of 62 individuals with Rasopathies confirmed by DNA analysis, with a median age of 12 years was evaluated by performing anthropometric measurements (weight, height, arm circumference and triceps skinfold thickness), analysis of habitual food intake and physical activity level. RESULTS: There was growth deficiency of postnatal origin in 48% of subjects and in the classification by body mass index, approximately 80% of them were classified as eutrophic or underweight/thinness. The parameters of body composition showed a decreased upper arm muscle circumference and in the classification by the upper arm fat area and upper arm muscle area, 43.5% had low fat reserves and 69% were malnourished or below average, respectively. Genotype-phenotype correlation showed that individuals with mutations in SHOC2, RAF1 and KRAS were those presenting the lowest mean values of stature and individuals with mutations in SHOC2, the lower median values of bone mass index. On the other hand, individuals with mutations in the BRAF had the highest median values. There was a statistically significant difference of the triceps skinfold thickness and upper arm fat area between Z-scores between BRAF and SHOC2 and of the triceps skinfold thickness Z-score between RAF1 and SHOC2. The energy and macronutrient intake of the subjects were similar to the dietary intake reference and the Brazilian population and in the level of physical activity, 65.4% were sedentary and irregularly active. It was found only one individual with significant difficulty in feeding, requiring gastrostomy. CONCLUSIONS: Short stature is common and more pronounced in individuals with mutations in SHOC2, RAF1 and KRAS. Opposed to the trend of the world\'s population of an increased prevalence of obesity, the majority of individuals with RASopathies present as eutrophic or underweight/ thinness. In body composition, there is an involvement of muscle tissue in all studied subjects. The decrease of these measures in the group is explained neither by a lower food intake nor by an increase in physical activity. It is possible that genetic factors, leading to hyperactivation of the RAS/ MAPK signaling, confer a slimmer profile to these individuals, mostly by the muscle involvement and not only by a decrease in fat reserve

Most dam break studies require complex numerical simulations and advanced knowledge in hydraulics. A number of programs are available to perform these simulations and the choice regarding the software to be used must be done within the resources available and the complexity of the problem to be addressed. It remains that this choice is also influenced by the experience and by the knowledge of the analyst. This study reports the simulations results of a comparative study performed for three (3) cases of varying complexity with the software NWS FLDWAV and HEC RAS. Thus, the rupture of a dam in a rectangular channel with uniform characteristics showed that both of the software allows obtaining almost identical results. The other two cases associated with the historical failure of Teton Dam (Idaho, United States) and the combined failure of Drummond and Rock Forest dams (Québec, Canada) showed significant differences in dam breach flow rates and maximum tailwater levels. A comparative analysis of the results leads to recommendations intended for users of these softwares.

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Oncogenes drive cancer by hijacking normal cellular functions involved in proliferation and survival. Suppression of the driving oncogene is highly effective for promoting tumor regression, a phenomenon termed "oncogenic addiction." By using unbiased genetic tools to functionally probe oncogenic addiction, we can identify cancer dependencies and characterize aspects of oncogenic signaling.

Temporary Concrete Traffic Barriers (TCTBs) are essential in order to protect the traveling public and highway construction crews from accidents due to driver misfortune or negligence. In order for TCTBs to be installed, however, they must be successfully crash tested. Barrier height and drainage open space are key characteristics that influence this crash test rating. This is because an increase in height will insure that a vehicle will not over-top the barrier and a decrease in drainage open space will result in greater barrier mass, which will in turn resist larger impact forces. The factors that increase the crash worthiness of a barrier, however, lead to poor hydraulic performance. This then becomes a concern if barriers are placed in areas where they may adversely impact the local floodplain elevation. The objective of this research is the development of a hydraulic rating curve that describes the relationship between upstream energy head and the flow rate passing the barrier. To accomplish this objective, a three parameter model with three unknown coefficient terms was utilized. The model was then fit to experimentally obtained data, and a rating curve was developed. In addition, the effects of downstream submergence and clogging of the drainage opening, with respect to the rating curve, was also analyzed. Finally, a method for using this information in the hydraulic modeling software HEC-RAS was developed. / text

A key cardiovascular signaling molecule involved in both physiologic and pathologic regulation of cardiomyocytes is the small molecular weight G-protein, Ras. Differential effects of Ras are mediated by multiple effector molecules, including the RalGEFs which activate Ral. Studies performed in cardiomyocytes have indicated a role for Ral in cardiac hypertrophic signaling and the RalGEF family member, Rgl2, was shown to specifically interact with Ras in the heart. Therefore, I hypothesized that Rgl2 was an important Ras effector that would regulate cardiomyocyte signaling. To elucidate the potential importance of Rgl2 in regulating cardiomyocyte signaling, a gain-of-function approach was utilized in which NRVMs were infected with an adenovirus to increase Rgl2 expression. Using this approach, I found that Rgl2 increased Ral-GTP levels, Ras-GTP levels, and PI3-kinase-Akt signaling, but decreased ERK phosphorylation. Overall, my results suggest a model in which Rgl2 disrupts Ras-Raf and Ras-RasGAP interaction to decrease ERK phosphorylation and increase Ras-GTP, respectively. Furthermore, Rgl2-induced Ral activation promotes the enhanced PI3- kinase-Akt signaling. The physiologic consequence of Rgl2 signaling is difficult to predict, but the increase in PI3-kinase-Akt signaling would be expected to promote cardiomyocyte survival and enhance cardiac function, both of which are characteristic of physiologic hypertrophy.