The development of Massively Parallel Sequencing (MPS) has enabled more accurate and less time-consuming DNA sequencing. Although MPS technologies are theoretically applicable to all samples and species, the majority of studies on microorganisms have been conducted on those able to be isolated and cultivated in laboratories. In the field of metagenomics, DNA from uncultivated environmental samples is analyzed. Whole genome sequencing of such complex samples poses difficult computational challenges due to the characteristics of metagenomic data, where one major challenge lies in determining the true origin of high similarity reads. In addition, the short-range information acquired from MPS reveals little about how reads from DNA sequencing fit together. Consequently, producing genome drafts from reads generated by MPS remains difficult. Here, the linked-read sequencing technology DB-Seq has been applied to bacterial samples in order to assess its potential in metagenomics. Specifically, its performance in retaining long-range information in de novo whole genome assembly has been tested. The results obtained in this initial study show great potential of DB-Seq in genome assembly, with significantly more contiguous results than conventional methods generate. / Utvecklingen av Massiv Parallel Sekvensering (MPS) har möjliggjort mer korrekt och mindre tidskrävande DNA sekvensering. Trots att MPS teoretiskt sett kan appliceras på alla provtyper och arter, har majoriteten av de studier som utförts på mikroorganismer varit fokuserade på de som kan isoleras och odlas i laboratorium. Inom ämnet metagenomik analyseras DNA från orörda miljöprover. Helgenomssekvensering av sådana prover ger upphov till komplicerade utmaningar för data-analys, där ett av de största problemen är att bestämma ursprunget av snarlika sekvenseringsresultat. Ytterligare komplikationer uppstår på grund av den data som erhålls från MPS, då denna ej ger information om hur sekvenseringsdata bör placeras i förhållande till varandra. Följdaktligen är det svårt att producera hopsatta genom utifrån MPS-data. I detta projekt har "linked-read"-sekvenseringsteknologin DB-Seq applicerats på bakterieprover för att undersöka metodens potential i metagenomik. Specifikt har metodens förmåga att bibehålla information om ursprungspositionen av sekvenseringsdata testats i de novo sammansättning av genom. De erhållna resultaten i denna förstagångsstudie tyder på stor potential för DB-Seq i genomsammansättning, med signifikant mer sammanhängande resultatsekvenser än vad konventionella metoder uppvisar.

No description available.

Arterial blood pressure (BP) undergoes a 24-hour oscillation that peaks in the active day and reaches a nadir at night during sleep in humans. Reduced nocturnal BP fall (also known as non-dipper) is the most common disruption of BP circadian rhythm and is associated with increased risk of untoward cardiovascular events and target organ injury. Up to 75% of diabetic patients are non-dippers. However, the mechanisms underlying diabetes associated non-dipping BP are largely unknown. To address this important question, we generated a novel diabetic db/db-mPer2Luc mouse model (db/db-mPer2Luc) that allows quantitatively measuring of mPER2 protein oscillation by real-time mPer2Luc bioluminescence monitoring in vitro and in vivo. Using this model, we demonstrated that the db/db-mPer2Luc mice have a diminished BP daily rhythm. The phase of the mPER2 daily oscillation is advanced to different extents in explanted peripheral tissues from the db/db-mPer2Luc mice relative to that in the control mice. However, no phase shift is found in the central oscillator, the suprachiasmatic nucleus (SCN). The results indicate that the desynchrony of mPER2 daily oscillation in the peripheral tissues contributes to the loss of BP daily oscillation in diabetes. Extensive research over the past decades has been focused on how the components of food (what we eat) and the amount of food (how much we eat) affect metabolic diseases. Only recently has it become appreciated that the timing of food intake (when we eat), independent of total caloric and macronutrient quality, is also critical for metabolic health. To investigate the potential effect of the timing of food intake on the BP circadian rhythm, we simultaneously monitored the BP and food intake profiles in the diabetic db/db and control mice using radiotelemetry and BioDAQ systems. We found the loss of BP daily rhythm is associated with disrupted food intake rhythm in the db/db mice. In addition, the normal BP daily rhythm is altered in the healthy mice with abnormal feeding pattern, in which the food is available only during the inactive-phase. To explore whether imposing a normal food intake pattern is able to prevent and restore the disruption of BP circadian rhythm, we conducted active-time restricted feeding (ATRF) in the db/db mice. Strikingly, ATRF completely prevents and restorers the disrupted BP daily rhythm in the db/db mice. While multiple mechanisms likely contribute to the protection of ATRF on the BP daily rhythm, we found that ATRF improves the rhythms of energy metabolism, sleep-wake cycle, BP-regulatory hormones and autonomic nervous system (ANS) in the db/db mice. To further investigate the molecular mechanism by which ATRF regulates BP circadian rhythm, we determined the effect of ATRF on the mRNA expressions of core clock genes and clock target genes in the db/db mice. Of particular interest is that we found among all the genes we examined, the mRNA oscillation of Bmal1, a key core clock gene, is disrupted by diabetes and selectively restored by the ATRF in multiple peripheral tissues in the db/db mice. More importantly, we demonstrated that Bmal1 is partially required for ATRF to protect the BP circadian rhythm. In summary, our findings indicate that the desynchrony of peripheral clocks contributes to the abnormal BP circadian pattern in diabetes. Moreover, our studies suggest ATRF as a novel and effective chronotherapy against the disruption of BP circadian rhythm in diabetes.

A aquisição e o desempenho de linguagem humana é um processo pelo qual todas as pessoas passam. No entanto, esse processo não é completamente entendido, o que gera amplo espaço para pesquisa nessa área. Além disso, mesmo após o processo de aquisição da linguagem pela criança estar completo, ainda não há garantia de domínio da língua em suas diferentes modalidades, especialmente de leitura e escrita. Recentemente, em 2016, divulgou-se que 49,3% dos estudantes brasileiros não possuem proficiência de compreensão de leitura plena em português. Isso é particularmente importante ao considerarmos a quantidade de textos disponíveis, mas não acessíveis a pessoas com diferentes tipos de problemas de proficiência na língua. Sob o ponto de vista computacional, há estudos que visam modelar os processos de aquisição da linguagem e medir o nível do falante, leitor ou redator. Em vista disso, neste trabalho propomos uma abordagem computacional independente de idioma para modelar o nível de desenvolvimento linguístico de diferentes tipos de usuários da língua, de crianças e adultos, sendo a nossa proposta fortemente baseada em características linguísticas. Essas características são dependentes de corpora orais transcritos, no segmento de crianças, e de corpora escritos, no segmento de adultos. Para alcançar esse modelo abrangente, são considerados como objetivos a identificação de atributos e valores que diferenciam os níveis de desenvolvimento da linguagem do indivíduo, assim como o desenvolvimento de um modelo capaz de indicá-los. Para a identificação dos atributos, utilizamos métodos baseados em estatística, como o teste de hipóteses e divergência de distribuição. A fim de comprovar a abrangência da abordagem, realizamos experimentos com os corpora que espelham diferentes etapas do desenvolvimento da linguagem humana: (1) etapa de aquisição da linguagem oral de pela criança e (2) etapa pós aquisição, através da percepção de complexidade da linguagem escrita. Como resultados, obtivemos um grande conjunto anotado de dados sobre aquisição e desempenho de linguagem que podem contribuir para outros estudos. Assim como um perfil de atributos para os vários níveis de desenvolvimento. Também destacamos como resultados, os modelos computacionais que identificam textos quanto ao nível de desenvolvimento de linguagem. Em especial, o são resultados do trabalho o modelo de identificação de palavras complexas, que ultrapassou o estado da arte para o corpus estudado, e o modelo de identificação de idade de crianças que ultrapassou os baselines utilizados, incluindo uma medida clássica de desenvolvimento linguístico. / Language acquisition and language performance is a process by which all the people experience. However, this process is not completely understood, which creates room for research in this area. Moreover, even after the acquisition process by a child is completed, there is still no guarantee of language proficiency in different modalities, specially reading and writing. Recently, in 2016, OECD/PIAAC released that 49,3% of Brazilian students do not have written and read proficiency in Portuguese. This is more important when we take into account the large number of available text, but they are not accessible by people with different types of language proficiency issues. In computational point of view, there are some studies which aim to model the language acquisition process and measure the speaker level. For that, we propose an computational approach independent of language to model language development level of different types of language users, children and adults. In that sense our proposal is highly based on linguistics features. Those features dependents of transcript oral corpora from children and adults. To achieve this model, we considered aim to identify attributes and values able to differentiate between leves of development by an individual, as well the desenvolvimento of a model able to indicate them. The attribute identification are based on statistical methods such as hypothesis testing and divergence distribution. Aiming to validate our approach, we performed experiments with the corpora that reflect at different stages of development of human language: (1) oral language acquisition by a child and (2) post-acquisition stage, through the perception of difficulty of written language. With this work, we obtained a large corpus of annotated language acquisition data that can contribute to the acquisition of other studies. We also build an attribute profile of the development levels. From all of our results we highlight the computer models that identify texts and language development level. In particular, the complex word identification model that exceeded the state of the art for the studied corpus, and the children age identifier model, who exceeded the baselines, including a classic measure of language development.

Les champignons sont des microorganismes essentiellement connus en écosystèmes aériens, s'étant diversifiés en milieu continental. A partir d'analyses d'horloges moléculaires, nous avons émis l'hypothèse d'une diversification des champignons dans les océans. Par ailleurs, de nombreux auteurs considèrent les écosystèmes hydrothermaux marins profonds comme le Berceau de la Vie : nous avons donc choisi d'étudier ces milieux, très peu exploités en terme de diversité fongique, dans l'espoir de retrouver des champignons ayant conservé des caractères ancestraux de ce Règne. Des analyses de diversité (établies après la création d'une base de données moléculaires dédiée), par PCR indépendantes de la culture (amplification du gène codant l'ARNr18S), ont révélé des organismes se branchant à la base de la phylogénie des champignons (phylum Chytridiomycota), en accord avec notre hypothèse de travail, couplée à une forte diversité spécifique fongique (phyla Chytridiomycota, Basidiomycota, et Ascomycota). Des souches isolées de ces écosystèmes en laboratoire ont également permis de détecter de nombreuses nouvelles espèces de champignons (phylum Ascomycota). Ces 2 approches combinées nous ont ainsi permis de révéler une diversité insoupçonnée dans ces milieux. Des hypothèses évolutives sur la diversification des champignons en milieu marin ont ainsi pu être proposées. Le second objectif de notre travail était de connaître les rôles de ces organismes au sein de ces écosystèmes. Pour cela, nous avons choisi une approche métagénomique originale : l'échantillon choisi sur la base de la fréquence du gène codant l'ARNr18S et des études de diversité, a été pyroséquencé (GS FLX ; 454 Life Sciences, ROCHE). L'échantillon testé contenait un seul phylotype fongique, constituant une branche profonde des champignons (phylum Chytridiomycota). Six ng d'ADN extraits ont été pyroséquencés en 3 runs indépendants : 168.909 contigs (longueur moyenne : 352 pb) ont été assemblés à partir de 1.441.839 séquences individuelles. Deux approches ont alors été choisies. La première consistait à analyser les contigs générés, afin d'extraire les fragments de gènes fongiques et de reconstruire leur métabolisme hypothétique. Des hypothèses de fonctionnement métabolique des champignons dans ces milieux, établies sur la base de recherche d'homologies dans les bases de données (BLASTX, ORF finder, KOG,...) ont pu être établies. La seconde approche, basée cette fois sur l'étude des séquences non assemblées, consistait à reconstruire les voies métaboliques du métagénome (BLASTX, mgRAST, ASGARD), et reconstituer la composition taxonomique de notre échantillon (MEGAN). Les résultats de l'analyse métagénomique présentés dans cette thèse, nous ont permis d'émettre des hypothèses sur les modes de vie des champignons en écosystème hydrothermal et nous ont également permis de reconstruire avec succès les métabolismes bactériens dominants dans l'écosystème. Les limites de cette analyse, ainsi que les nombreuses perspectives qu'offrent ce travail sont également développées.

Στην παρούσα διδακτορική διατριβή επιχειρείται μία αντιμετώπιση του προβλήματος της μοντελοποίησης πολυμερών σε πολλαπλές κλίμακες μήκους και χρόνου μέσα από την ανάπτυξη και εφαρμογή νέων αλγορίθμων που, σε συνδυασμό με τους ήδη υπάρχοντες, μπορούν να προσφέρουν μια καθαρή εικόνα για τους δεσπόζοντες μηχανισμούς που καθορίζουν την συμπεριφορά του συστήματος καθώς και να παράσχουν έγκυρες προβλέψεις για τις ιδιότητες δομής, ισορροπίας και διαπερατότητας/φραγής των πολυμερών. / -

A aquisição e o desempenho de linguagem humana é um processo pelo qual todas as pessoas passam. No entanto, esse processo não é completamente entendido, o que gera amplo espaço para pesquisa nessa área. Além disso, mesmo após o processo de aquisição da linguagem pela criança estar completo, ainda não há garantia de domínio da língua em suas diferentes modalidades, especialmente de leitura e escrita. Recentemente, em 2016, divulgou-se que 49,3% dos estudantes brasileiros não possuem proficiência de compreensão de leitura plena em português. Isso é particularmente importante ao considerarmos a quantidade de textos disponíveis, mas não acessíveis a pessoas com diferentes tipos de problemas de proficiência na língua. Sob o ponto de vista computacional, há estudos que visam modelar os processos de aquisição da linguagem e medir o nível do falante, leitor ou redator. Em vista disso, neste trabalho propomos uma abordagem computacional independente de idioma para modelar o nível de desenvolvimento linguístico de diferentes tipos de usuários da língua, de crianças e adultos, sendo a nossa proposta fortemente baseada em características linguísticas. Essas características são dependentes de corpora orais transcritos, no segmento de crianças, e de corpora escritos, no segmento de adultos. Para alcançar esse modelo abrangente, são considerados como objetivos a identificação de atributos e valores que diferenciam os níveis de desenvolvimento da linguagem do indivíduo, assim como o desenvolvimento de um modelo capaz de indicá-los. Para a identificação dos atributos, utilizamos métodos baseados em estatística, como o teste de hipóteses e divergência de distribuição. A fim de comprovar a abrangência da abordagem, realizamos experimentos com os corpora que espelham diferentes etapas do desenvolvimento da linguagem humana: (1) etapa de aquisição da linguagem oral de pela criança e (2) etapa pós aquisição, através da percepção de complexidade da linguagem escrita. Como resultados, obtivemos um grande conjunto anotado de dados sobre aquisição e desempenho de linguagem que podem contribuir para outros estudos. Assim como um perfil de atributos para os vários níveis de desenvolvimento. Também destacamos como resultados, os modelos computacionais que identificam textos quanto ao nível de desenvolvimento de linguagem. Em especial, o são resultados do trabalho o modelo de identificação de palavras complexas, que ultrapassou o estado da arte para o corpus estudado, e o modelo de identificação de idade de crianças que ultrapassou os baselines utilizados, incluindo uma medida clássica de desenvolvimento linguístico. / Language acquisition and language performance is a process by which all the people experience. However, this process is not completely understood, which creates room for research in this area. Moreover, even after the acquisition process by a child is completed, there is still no guarantee of language proficiency in different modalities, specially reading and writing. Recently, in 2016, OECD/PIAAC released that 49,3% of Brazilian students do not have written and read proficiency in Portuguese. This is more important when we take into account the large number of available text, but they are not accessible by people with different types of language proficiency issues. In computational point of view, there are some studies which aim to model the language acquisition process and measure the speaker level. For that, we propose an computational approach independent of language to model language development level of different types of language users, children and adults. In that sense our proposal is highly based on linguistics features. Those features dependents of transcript oral corpora from children and adults. To achieve this model, we considered aim to identify attributes and values able to differentiate between leves of development by an individual, as well the desenvolvimento of a model able to indicate them. The attribute identification are based on statistical methods such as hypothesis testing and divergence distribution. Aiming to validate our approach, we performed experiments with the corpora that reflect at different stages of development of human language: (1) oral language acquisition by a child and (2) post-acquisition stage, through the perception of difficulty of written language. With this work, we obtained a large corpus of annotated language acquisition data that can contribute to the acquisition of other studies. We also build an attribute profile of the development levels. From all of our results we highlight the computer models that identify texts and language development level. In particular, the complex word identification model that exceeded the state of the art for the studied corpus, and the children age identifier model, who exceeded the baselines, including a classic measure of language development.

A aquisição e o desempenho de linguagem humana é um processo pelo qual todas as pessoas passam. No entanto, esse processo não é completamente entendido, o que gera amplo espaço para pesquisa nessa área. Além disso, mesmo após o processo de aquisição da linguagem pela criança estar completo, ainda não há garantia de domínio da língua em suas diferentes modalidades, especialmente de leitura e escrita. Recentemente, em 2016, divulgou-se que 49,3% dos estudantes brasileiros não possuem proficiência de compreensão de leitura plena em português. Isso é particularmente importante ao considerarmos a quantidade de textos disponíveis, mas não acessíveis a pessoas com diferentes tipos de problemas de proficiência na língua. Sob o ponto de vista computacional, há estudos que visam modelar os processos de aquisição da linguagem e medir o nível do falante, leitor ou redator. Em vista disso, neste trabalho propomos uma abordagem computacional independente de idioma para modelar o nível de desenvolvimento linguístico de diferentes tipos de usuários da língua, de crianças e adultos, sendo a nossa proposta fortemente baseada em características linguísticas. Essas características são dependentes de corpora orais transcritos, no segmento de crianças, e de corpora escritos, no segmento de adultos. Para alcançar esse modelo abrangente, são considerados como objetivos a identificação de atributos e valores que diferenciam os níveis de desenvolvimento da linguagem do indivíduo, assim como o desenvolvimento de um modelo capaz de indicá-los. Para a identificação dos atributos, utilizamos métodos baseados em estatística, como o teste de hipóteses e divergência de distribuição. A fim de comprovar a abrangência da abordagem, realizamos experimentos com os corpora que espelham diferentes etapas do desenvolvimento da linguagem humana: (1) etapa de aquisição da linguagem oral de pela criança e (2) etapa pós aquisição, através da percepção de complexidade da linguagem escrita. Como resultados, obtivemos um grande conjunto anotado de dados sobre aquisição e desempenho de linguagem que podem contribuir para outros estudos. Assim como um perfil de atributos para os vários níveis de desenvolvimento. Também destacamos como resultados, os modelos computacionais que identificam textos quanto ao nível de desenvolvimento de linguagem. Em especial, o são resultados do trabalho o modelo de identificação de palavras complexas, que ultrapassou o estado da arte para o corpus estudado, e o modelo de identificação de idade de crianças que ultrapassou os baselines utilizados, incluindo uma medida clássica de desenvolvimento linguístico. / Language acquisition and language performance is a process by which all the people experience. However, this process is not completely understood, which creates room for research in this area. Moreover, even after the acquisition process by a child is completed, there is still no guarantee of language proficiency in different modalities, specially reading and writing. Recently, in 2016, OECD/PIAAC released that 49,3% of Brazilian students do not have written and read proficiency in Portuguese. This is more important when we take into account the large number of available text, but they are not accessible by people with different types of language proficiency issues. In computational point of view, there are some studies which aim to model the language acquisition process and measure the speaker level. For that, we propose an computational approach independent of language to model language development level of different types of language users, children and adults. In that sense our proposal is highly based on linguistics features. Those features dependents of transcript oral corpora from children and adults. To achieve this model, we considered aim to identify attributes and values able to differentiate between leves of development by an individual, as well the desenvolvimento of a model able to indicate them. The attribute identification are based on statistical methods such as hypothesis testing and divergence distribution. Aiming to validate our approach, we performed experiments with the corpora that reflect at different stages of development of human language: (1) oral language acquisition by a child and (2) post-acquisition stage, through the perception of difficulty of written language. With this work, we obtained a large corpus of annotated language acquisition data that can contribute to the acquisition of other studies. We also build an attribute profile of the development levels. From all of our results we highlight the computer models that identify texts and language development level. In particular, the complex word identification model that exceeded the state of the art for the studied corpus, and the children age identifier model, who exceeded the baselines, including a classic measure of language development.

This thesis is about comparison between C# and Java in implementation of a university desktop application. In .Net world the prominent IDE is MS Visual studio and DB is MS SQL server. In Java domain we have several IDEs and techniques to approach the problem. The knowledge to choose between these techniques to use is as much as important if a programmer can gain it, he can apply it in many other software engineering domains like a personal management system, library system, etc.     Therefore the importance of a descriptive and applied experience is showing itself up. This thesis has started with a discussion to choose NetBeans IDE and application definition, and use case modeling then it goes through comparison and implementation part. The comparison will go in depth for each use case in this project in its implementation in C# and Java and see which techniques are used. This includes comparison between these two apps in Software quality factors.

The focus of this thesis was to use active noise control (ANC) to globally minimize the tonal and broadband noise radiating from a diesel generator enclosure. The major goal of this research was to show that minimizing the noise within the enclosure can lead to an overall sound pressure level (SPL) reduction of radiated noise. The target levels for overall SPL reduction were at least 2 dBA. The control algorithms used in this research were based on a filtered-x LMS adaptive algorithm, which minimizes energy density (ED). Both feedforward and feedback control approaches were investigated. The noise spectrum produced by the diesel generator enclosure includes tonal and broadband components. The target range for control was from 0 to 300 Hz. Tonal frequencies at exterior locations were often reduced by 20 to 30 dB using feedforward control. With feedback control, tones were reduced 5 to 10 dB. Broadband control results were obtained at an exterior location using a feedforward control configuration. This control was achieved for frequencies between 100 and 600 Hz and levels were reduced by up to 5 dB. Some broadband control was achieved using feedback control, but this was limited to regions at the error sensor. An overall SPL reduction of 1.9 dBA outside the enclosure was achieved near the power terminal side of the enclosure. This was accomplished using tonal and broadband feedforward control. Experimental results show that control source placement, as well as error and reference sensor location, is key to global noise reduction.