Brain aminergic systems and autism-associated risk factors in zebrafish

Brain amines are neurotransmitters that modulate important functions in the central nervous system, including behavior and brain development. Several brain disorders are characterized by impairments in aminergic systems, including autism spectrum disorder (ASD). ASD is characterized by impaired social behavior, difficulty in communication and stereotypies. The etiology of ASD is poorly understood, but both environmental and genetic risk factors are known to play a role on it. Valproic acid (VPA), a drug commonly used to treat bipolar disorder, and mutations in the monoamine oxidase a gene are both environmental and genetic risk factors. Zebrafish shares relevant neurochemical aspects with humans and display a wide range of behaviors, which contribute to its appreciation as a model organism in neuroscience. Thus, this study characterized the phenotypes of zebrafish pharmacologically and genetically challenged with ASD risk factors. Additionally, functional aspects of aminergic neurotransmission in the zebrafish brain were studied through the characterization of animals that lacked vesicular monoamine transporter 2 (vmat2, also known as slc18a2) and monoamine oxidase (mao), relevant genes for aminergic vesicular transport and metabolism, respectively. In the first publication of this thesis, larval zebrafish embryonically exposed to VPA showed a reduction in the number of histaminergic neurons and in the levels of histamine when compared to control animals. The histaminergic system of VPA-exposed larvae was also affected by a downregulation of histidine decarboxylase and histamine receptors. Some of these abnormalities persisted until adulthood along with impaired social behavior. This study brings more attention to a possible involvement of the histaminergic system in the outcomes related to ASD. In the second article, the levels of dopamine, noradrenaline, serotonin and histamine of vmat2 mutants were decreased, whereas levels of dopamine and serotonin metabolites were increased, indicating elevated amine turnover. There were also fewer aminergic immunoreactive cells. Further, in mutants notch1a and pax2a were downregulated in brain proliferative zones. This mutant line may be used in the investigation of how amines transport affects brain development and function, and for use in high-throughput and drug screening. In the third article, mao−/− larvae showed a hyperserotonergic phenotype characterized by extracellular serotonin immunoreactivity that was associated with damage in aminergic systems. They also showed weaker responses to visual and acoustic stimuli, abnormal expression of developmental markers and died within 20 days post-fertilization. mao+/- fish were viable and demonstrated impaired social interactions compared with adult mao+/+ siblings. These mutants could be used in investigations aiming to assess the roles of MAOA/B and amines during brain development and to study the behavioral outcomes associated with MAOA/B deficiency. Collectively, the results of the present thesis support zebrafish as a tool to investigate mechanisms underlying ASD. Additionally, it presented two new models to study important aspects of aminergic neurotransmission in zebrafish and its role in brain function and behavior.Aivojen amiinit ovat välittäjäaineita, jotka säätelevät tärkeitä keskushermoston toimintoja, mukaan lukien käyttäytyminen ja aivojen kehitys. Useille aivosairauksille, mukaan lukien autismikirjon häiriöt (ASD), on ominaista aminergisten järjestelmien poikkeavuus. Autismikirjon häiriölle on tyypillistä heikentynyt sosiaalinen käyttäytyminen, kommunikaatiovaikeudet ja stereotypiat. Autismin etiologiaa ymmärretään huonosti, mutta sekä ympäristön että geneettisten riskitekijöiden tiedetään vaikuttavan siihen. Valproiinihappo, yleisesti kaksisuuntaisen mielialahäiriön hoitoon käytetty lääke, ja mutaatiot monoamiinioksidaasin geenissä ovat ympäristöllisiä ja geneettisiä riskitekijöitä. Eläinmallit ovat hyödyllisiä työkaluja, joiden avulla voidaan ymmärtää paremmin mekanismeja ja muutoksia liittyvät aminergisiin hermoston kehityshäiriöihin. Niillä voidaan testata uusia lääkkeitä, jotka voivat vaikuttaa näihin tiloihin liittyviin käyttäytymispoikkeavuuksiin. Seeprakalalla on samoja neurokemiallisia ja toiminnallisia ominaisuuksia ihmisten ja muiden nisäkkäiden kanssa. Nämä ja monet käyttäytymistestit mahdollistavat sen käyttämisen neurotieteen malliorganismina. Tämä tutkimus luonnehti seeprakalan fenotyyppejä, jotka oli farmakologisesti ja geneettisesti altistettu ASD-riskitekijöille. Lisäksi seeprakalan aivojen aminergisen neurotransmission toiminnallisia näkökohtia tutkittiin karakterisoimalla eläimiä, joilta puuttui vesikulaarinen monoamiinikuljettaja 2 (vmat2, joka tunnetaan myös nimellä slc18a2) ja monoamiinioksidaasi (mao), aminergisen rakkulakuljetuksen ja aineenvaihdunnan kannalta oleelliset geenit. Tämän opinnäytetyön ensimmäisessä julkaisussa VPA:lle altistetut seeprakalan toukat osoittivat histaminergisten hermosolujen lukumäärän ja histamiinitasojen pienenemistä verrokkieläimiin verrattuna. VPA:lle altistuneiden toukkien histaminergiseen järjestelmään vaikutti myös histidiinidekarboksylaasin ja histamiinireseptorien väheneminen. Jotkut näistä poikkeavuuksista säilyivät aikuisikään asti heikentyneen sosiaalisen käyttäytymisen ohella. Tämä tutkimus osoittaa histaminergisen järjestelmän mahdollisen osuuden ASD:n mekanismeihin. Toisessa artikkelissa vmat2-mutanttien dopamiinin, noradrenaliinin, serotoniinin ja histamiinin tasot laskivat, kun taas dopamiinin ja serotoniinin metaboliittien tasot nousivat verrokkikaloihin verrattuna, mikä viittaa kohonneeseen amiinien vaihduntaan. Aminergisia hermosoluja oli myös vähemmän. Lisäksi mutanteissa notch1a- ja pax2a-geenien ilmentyminen väheni aivojen proliferatiivisilla alueilla. Tämä mutanttikalalinja voi olla hyödyllinen amiinien osuuden selvittämisessä aivojen kehityksessä, ja sitä voidaan käyttää lääkeaineiden seulonnassa. Kolmannessa artikkelissa mao-mutanttikaloilla todettiin hyperserotonerginen fenotyyppi, jota luonnehti solujen ulkopuolinen serotoniini-immunoreaktiviteetti, joka liittyi aminergisten järjestelmien vaurioon. Mutanttikalojen reaktiot näkö- ja kuuloärsykkeille olivat heikentyneet, kehitystä kuvaavien geenien ilmentyminen oli poikkeava, ja kalat menehtyivät noin 20 päivän ikäisinä. Heterotsygootit säilyivät hyväkuntoisina ja niillä oli normaalista poikkeava sosiaalinen käyttäytyminen verrattuna villityypin kaloihin. Tämä mutanttikalalinja sopii amiinien merkityksen selvittämiseen aivojen kehítyksessä ja mao-vajavuuden merkityksen selvittämiseen käyttäytymisessä. Yhteenvetona tulokset tukevat seeprakalan käyttämistä autismikirjoin häiriöiden mekanismien tutkimuksessa. Tutkimuksessa esitettiin kaksi uutta mallia keskeisten aminergisen hermovälityksen mekanismien tutkimiseksi seeprakalalla ja sen merkityksen selvittämiseksi aivojen toiminnassa ja käyttäytymisessä

Learning to Rank Graph-based Application Objects on Heterogeneous Memories

Persistent Memory (PMEM), also known as Non-Volatile Memory (NVM), can deliver higher density and lower cost per bit when compared with DRAM. Its main drawback is that it is typically slower than DRAM. On the other hand, DRAM has scalability problems due to its cost and energy consumption. Soon, PMEM will likely coexist with DRAM in computer systems but the biggest challenge is to know which data to allocate on each type of memory. This paper describes a methodology for identifying and characterizing application objects that have the most influence on the application's performance using Intel Optane DC Persistent Memory. In the first part of our work, we built a tool that automates the profiling and analysis of application objects. In the second part, we build a machine learning model to predict the most critical object within large-scale graph-based applications. Our results show that using isolated features does not bring the same benefit compared to using a carefully chosen set of features. By performing data placement using our predictive model, we can reduce the execution time degradation by 12\% (average) and 30\% (max) when compared to the baseline's approach based on LLC misses indicator

Entrepreneurship, intellectual property and innovation ecosystems

This research aims to determine the relationship between entrepreneurship, intellectual property and innovation ecosystems at a global level. To assess the structural relationships between ecosystems, the unconditional quantile regressions using annual country data are estimated from two perspectives, namely: pooled data and data with fixed effects and time control. The Global Entrepreneurship Index (GEI), the US Chamber International IP Index (IPI) and the Global Innovation Index (GII) are used as a proxy for the entrepreneurship, intellectual property and innovation ecosystem, respectively. The results indicate that the entrepreneurship and intellectual property ecosystems has a causal relationship with the global innovation ecosystem. However, when control of individual and fixed time effects is included, the relationship between ecosystems is confirmed in just a few quantiles. The sterile results require efforts from public, private and other agents to improve the performance of ecosystems, especially to increase the generation of innovative assets. This study looks at ecosystems from a different perspective, and the results are relevant to policymakers looking to improve the ecosystems of entrepreneurship, intellectual property and innovation. The originality of this article lies in bringing together issues that are generally dealt with in theoretical and empirical literature in separate domains. The study of the relationship between ecosystems from global indexes remains a little explored field, despite the various alternative approaches already investigated

Amphibia, Anura, Hylidae, Scinax centralis Pombal and Bastos, 1996: distribution extension, geographic distribution map

This work provides records of Scinax centralis from municipalities of Campo Alegre de Goiás and Orizona, state of Goiás, Brazil. Those records represent, respectively, a southeast range extension of ca. 30 Km east and ca. 60 Km southeast from the previously known locality of Ipameri. All known populations of S. centralis remain restricted to the Paranaíba River basin, and with exception of Orizona, all localities from where the species is known to occur are inside priority areas for conservation of biodiversity in Cerrado and Pantanal

Facial Recognition using Neural Network

Face recognition technology using machine learning and neural networks has become increasingly prevalent in recent years, revolutionizing various fields such as security, law enforcement, and marketing. The development of an AI-based system that can perform face recognition using these technologies has become a significant focus for researchers and developers worldwide. This project aims to create such a system that can recognize and classify faces accurately using machine learning algorithms and neural networks. By leveraging these advanced technologies, the system can learn and improve over time, leading to higher accuracy rates and enhanced performance

Contribuição à análise de interferência e compatibilidade eletromagnética em circuito digital através de simulação numérica

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico, Programa de Pós-Graduação em Engenharia Elétrica, Florianópolis, 2011O presente trabalho tem como objetivo analisar os fenômenos eletromagnéticos que podem causar interferência eletromagnética (IEM) em circuitos digitais, como por exemplo: diafonia e reflexões, bem como abordar os aspectos econômicos causados por problemas de compatibilidade eletromagnética (CEM). Para tanto, foi desenvolvido um circuito digital com o software Proteus e foram realizadas simulações numéricas utilizando os softwares SIwave e Designer. Os resultados foram comparados com dados experimentais.This paper presents the electromagnetic phenomena that can cause electromagnetic interference (EMI) in digital circuits, such as: crosstalk and reflections. Economical aspects caused by electromagnetic compatibility (EMC) issues on the industry are also addressed. A digital circuit was developted using Proteus software and Numerical simulations using the softwares SIwave and Designer were performed and the results were compared to experimental data

Ativos e recursos com especificidade para o desenvolvimento territorial : análise das possibilidades de composição de uma cesta de bens e serviços territoriais no Litoral do Paraná

Orientador: Prof. Dr. Valdir Roque DallabridaDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Humanas, Programa de Pós-Graduação em Desenvolvimento Territorial Sustentável. Defesa : Matinhos, 29/06/2023Inclui referênciasResumo: Entre os enfoques teóricos que dão destaque aos bens ou serviços territoriais que apresentam significativo grau de especificidade, destacam-se as abordagens sobre a Cesta de Bens e Serviços Territoriais (CBST). Tal abordagem trata do processo de uso dos recursos e ativos territoriais, tanto tangíveis quanto intangíveis, aqui compreendidos como elementos constituintes do patrimônio territorial, os quais não dispensam um ambiente socioeconômico-cultural e organizacional ativo. Partindo da compreensão sobre território, patrimônio, governança e desenvolvimento territorial, este trabalho tem o propósito de analisar alguns dos ativos e recursos do Litoral do Paraná que podem vir a contribuir com o desenvolvimento territorial. Assim, partindo da identificação das potencialidades regionais, prospectivamente, propõem-se avaliar bens e serviços com especificidade territorial do Litoral do Paraná, os quais possam oportunizar uma oferta compósita, a exemplo da CBST, ou outras estratégias assemelhadas de valorização e/ou reconhecimento de produtos específicos, por meio da potenciação dos ativos e recursos territoriais, tanto os já ativados, quanto os que ainda não tenham sido reconhecidos.Abstract: Among the theoretical approaches that highlight territorial goods or services that exhibit a significant degree of specificity, the approaches to the Territorial Basket of Goods and Services (TBGS) stand out. This approach deals with the process of using tangible and intangible territorial resources and assets, which are understood here as constituent elements of territorial heritage, requiring an active socio-economic-cultural and organizational environment. Building on the understanding of territory, heritage, territorial governance, and territorial development, this paper aims to analyze some of the assets and resources of the Paraná Coast that can contribute to territorial development. Thus, based on the identification of regional potentialities, it is proposed to prospectively evaluate goods and services with territorial specificity of the Paraná Coast in order to provide a composite offer of products and services (similar to the TBGS), or other similar strategies for valorization and/or recognition of specific products, through the enhancement of territorial assets and resources, both those already activated and those that have not yet been recognized

Perfil y grado de dependencia de personas de la tercera edad y sobrecarga de sus cuidadores

OBJETIVO: Analisar o perfil e o grau de dependência de idosos usuários de um Centro de Internação Domiciliar, bem como o perfil e a sobrecarga em seus cuidadores. MÉTODOS: Estudo exploratório e descritivo composto por amostra de 31 idosos e 31 cuidadores. A coleta de dados foi realizada por meio de entrevista no domicílio, com aplicação de questionário semiestruturado, contendo variáveis sóciodemográficas. Para avaliação do grau de dependência dos idosos, foram utilizados o Índice de Katz e Escala de Lawton e a sobrecarga dos cuidadores foi mensurada com base na Escala Zarit Burden Interview. RESULTADOS: Foi revelado percentual elevado de idosos com dependência total para atividades básicas e instrumentais da vida diária, sendo a variável estatisticamente significativa em relação à sobrecarga dos cuidadores e a percepção sobre seu estado de saúde. CONCLUSÃO: A análise das variáveis estudadas pode contribuir para o delineamento de propostas de intervenção baseada nas reais necessidades do grupo estudado.OBJECTIVE: To analyze the profile and degree of dependency of elderly users of a home care center, as well as the profile and burden their caregivers. METHODS: Exploratory and descriptive study with a sample consisting of 31 elderly and 31 caregivers. Data collection was conducted through interviews at home, using a semi-structured questionnaire containing sociodemographic variables. To assess the degree of dependency of the elderly, the Katz Index and Lawton Scale were used, and the burden of caregivers was measured using the Zarit Burden Interview Scale. RESULTS: A high percentage of elderly patients were identified with total dependence for basic and instrumental activities of daily living, with a statistically significant variable in relation to caregiver burden and perception of their health status. CONCLUSION: The analysis of variables can contribute to the design of intervention proposals based on the real needs of the group studied

A nova quesitação no tribunal do júri com o advento da lei 11.689/2008

Com a implementação da Lei 11.689/2008, a sistemática do Tribunal do Júri sofreu diversas alterações. A formulação de um quesito no Júri corresponde a uma pergunta. Compreende-se o questionário como o conjunto de perguntas formuladas pelo Juiz Presidente do Tribunal acerca do fato imputado ao réu o qual deverá ser respondido pelo Conselho de Sentença. Neste prisma, diante das alterações sofridas no referido instituto, discutir-se-á se a nova sistemática adotada no que tange a quesitação é mais benéfica ao acusado. A abordagem do trabalho se baseará em um estudo comparativo entre o antigo rito do Tribunal do Júri e o novo procedimento a partir da implementação da referida Lei. O comparativo torna-se indispensável, visto que a problemática suscitada é um dos últimos atos do julgamento em plenário. A pesquisa terá como foco os aspectos históricos e contemporâneos do júri para evidenciar sua origem, mudanças e as conseqüências destas na atualidade. O estudo se concentrará em livros doutrinários e artigos publicados que tratam diretamente do tema. Desse modo, a intenção da pesquisa é nortear o leitor para que este não se perca ao longo da dissertação, para ao fim, proporcionar um entendimento lógico do que se buscará durante o estudo, isto é, chegar a uma conclusão suficientemente lastreada acerca das conseqüências, benefícios e prejuízos do novo questionário no Tribunal Popular