Metagenomic sequencing has provided scientists with the ability to investigate microbial populations, termed microbiomes, in environmental and clinical settings. Current approaches to metagenomic research involve the use of next-generation sequencing (NGS) to generate short, precise reads for characterization of microbial compositions. While highly accurate, short reads possess several limitations that restrict their application in metagenomic research. Third generation, long-read sequencing technologies may offer several advantages for metagenomic research. Here, we used simulated datasets, as well as experimental data from murine fecal samples, to compare the relative performance of short and long reads for metagenomic research, and their impact on assessing microbial composition. Long-read data demonstrated increased precision for identification of microbiome constituents and assessing abundance without sacrificing sensitivity. Hierarchical clustering of microbiome similarity from paired short- and long-read datasets obtained from murine fecal samples revealed clustering was driven by read type as opposed to sample type, underscoring the importance of sequence type. These findings led us to use long-read sequencing for elucidating the effects of propionic acid (PPA) on the murine gut microbiome. PPA has been shown to induce physiological changes like those observed in autism spectrum disorder (ASD). Individuals with ASD may suffer from gastrointestinal comorbidities, suggesting an association with the gut microbiome. Murine offspring fed a PPA-rich diet were assessed for microbiota perturbations. Our results demonstrated that a PPA-rich diet alters the gut microbiome of progeny mice, selecting for several bacterial species that have previously been found in greater abundance among people iv with ASD. In our study, changes to microbial abundance were also associated with significant variation in bacterial metabolic pathways related to steroid hormone biosynthesis, amino sugar, and nucleotide sugar metabolism. Taken together, our findings provide empirical evidence supporting the use of long-read sequencing in metagenomic research by elucidating links between PPA exposure and gut microbiome composition.

A healthy gut microbiome is crucial for the development, growth, and health of dairy calves; however, diarrhea in pre-weaned calves is highly prevalent, difficult to treat, and causes detrimental effects to the dairy industry. This study characterized early gut microbiota using longread-based 16S rRNA gene sequencing and investigated its associations with calf diarrhea and colostrum microbiota. The full-length 16S rRNA gene was amplified and sequenced on a Nanopore sequencer. We identified shared bacterial species in colostrum and calf feces, whose abundance in calf feces reduced with age. Diarrheic calves exhibited differing gut diversity before, during, and after diarrhea, and harbored increased bacteria resistant to the Cefotaxime antibiotic. Several bacterial species were associated with age and calf health. Additionally, a machine learning model identified bacteria to predict diarrhea. This study will be useful for the goal of reducing antibiotic use to promote gut health and prevent and treat neonatal calf diarrhea.

I dagens samhälle är det av stor vikt att kunna läsa och skriva då texter finns i olika former överallt, mycket på grund av den tekniska utvecklingen i samhället. Vägen till att "knäcka koden" ser olika ut för barn. I studien har vi valt att fokusera elever med läs- och skrivsvårigheter samt hur tekniken kan fungera som stöd i undervisningen. Syftet med studien är att undersöka hur lärare beskriver sin undervisning i förhållande till läs- och skrivsvårigheter. Vidare är syftet att undersöka hur elever med läs- och skrivsvårigheter upplever sin undervisning. Studien har sin utgångspunkt i den sociokulturella teorin. Empirin till studien är skapad genom semistrukturerade intervjuer med lärare och elever. Materialet har sedan analyserats och presenteras i resultatet. Resultatet av studien indikerar på att undervisning och stödstrukturer inom ASL stödjer elever med läs- och skrivsvårigheter i sin läs- och skrivinlärning genom att de får höra och se sambandet mellan ljud och bokstav. / In today's society it's important to be able to read and write because there are texts everywhere, and also as the technology has made a bigger impact in the society. For some children it can be difficult to learn how to write and read. Because of this we have chosen to focus on pupils with disabilities in the read- and writing process. We also want to see how the technology can support pupils in their learning. The aim of this study is therefore to investigate how teachers describe their teaching in relation to reading and writing disabilities. The study also aims to investigate how pupils with reading and writing disabilities describe their education. The sociocultural theory is the base of this study. The empirics to this study is created by interviews with pupils and teachers. The empirics has been analyzed and presented in the result. The result of this study shows that the method "write to read" supports pupils with writing and reading disabilities in their writing and reading education because the link between letter and sound clarifieds for the pupils.

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All pupils have an individual reading development and need different forms of support. The aim of this study is to investigate teachers’ experiences of and ideas about the use of easy-reading books when teaching children to read. Data collection was done through four interviews with active teachers representing three schools in a municipality in southern Sweden. The interviewed teachers’ experiences turned out to agree with previous findings: the teachers were favourably disposed towards easy-reading books and considered them important for learning to read. The teachers also thought that it is essential to aim the teaching at the pupils’ own level so that they will develop in their acquisition of literacy. With the help of easy-reading books, pupils who find it hard to learn to read can also be given a chance to develop.

This thesis treats Daniel Read's music analytically to establish style characteristics. Read's fuging tunes are examined for metric placement and structural occurrence of dissonance, and dissonance as text painting. Read's comments on dissonance are extracted from his tunebook introductions. A historical chapter includes the English origins of the fuging tune and its American heyday. The creative life of Daniel Read is discussed. This thesis contributes to knowledge of Read's role in the development of the New England Psalmody idiom. Specifically, this work illustrates the importance of understanding and analyzing Read's use of dissonance as a style determinant, showing that Read's dissonance treatment is an immediate and central characteristic of his compositional practice.

This thesis introduces three different algorithmical and statistical strategies for the analysis of high-throughput sequencing data. First, we introduce a heuristic method based on enhanced suffix arrays to map short sequences to larger reference genomes. The algorithm builds on the idea of an error-tolerant traversal of the suffix array for the reference genome in conjunction with the concept of matching statistics introduced by Chang and a bitvector based alignment algorithm proposed by Myers. The algorithm supports paired-end and mate-pair alignments and the implementation offers methods for primer detection, primer and poly-A trimming. In our own benchmarks as well as independent bench- marks this tool outcompetes other currently available tools with respect to sensitivity and specificity in simulated and real data sets for a large number of sequencing protocols. Second, we introduce a novel dynamic programming algorithm for the spliced alignment problem. The advantage of this algorithm is its capability to not only detect co-linear splice events, i.e. local splice events on the same genomic strand, but also circular and other non-collinear splice events. This succinct and simple algorithm handles all these cases at the same time with a high accuracy. While it is at par with other state- of-the-art methods for collinear splice events, it outcompetes other tools for many non-collinear splice events. The application of this method to publically available sequencing data led to the identification of a novel isoform of the tumor suppressor gene p53. Since this gene is one of the best studied genes in the human genome, this finding is quite remarkable and suggests that the application of our algorithm could help to identify a plethora of novel isoforms and genes. Third, we present a data adaptive method to call single nucleotide variations (SNVs) from aligned high-throughput sequencing reads. We demonstrate that our method based on empirical log-likelihoods automatically adjusts to the quality of a sequencing experiment and thus renders a \"decision\" on when to call an SNV. In our simulations this method is at par with current state-of-the-art tools. Finally, we present biological results that have been obtained using the special features of the presented alignment algorithm. / Diese Arbeit stellt drei verschiedene algorithmische und statistische Strategien für die Analyse von Hochdurchsatz-Sequenzierungsdaten vor. Zuerst führen wir eine auf enhanced Suffixarrays basierende heuristische Methode ein, die kurze Sequenzen mit grossen Genomen aligniert. Die Methode basiert auf der Idee einer fehlertoleranten Traversierung eines Suffixarrays für Referenzgenome in Verbindung mit dem Konzept der Matching-Statistik von Chang und einem auf Bitvektoren basierenden Alignmentalgorithmus von Myers. Die vorgestellte Methode unterstützt Paired-End und Mate-Pair Alignments, bietet Methoden zur Erkennung von Primersequenzen und zum trimmen von Poly-A-Signalen an. Auch in unabhängigen Benchmarks zeichnet sich das Verfahren durch hohe Sensitivität und Spezifität in simulierten und realen Datensätzen aus. Für eine große Anzahl von Sequenzierungsprotokollen erzielt es bessere Ergebnisse als andere bekannte Short-Read Alignmentprogramme. Zweitens stellen wir einen auf dynamischer Programmierung basierenden Algorithmus für das spliced alignment problem vor. Der Vorteil dieses Algorithmus ist seine Fähigkeit, nicht nur kollineare Spleiß- Ereignisse, d.h. Spleiß-Ereignisse auf dem gleichen genomischen Strang, sondern auch zirkuläre und andere nicht-kollineare Spleiß-Ereignisse zu identifizieren. Das Verfahren zeichnet sich durch eine hohe Genauigkeit aus: während es bei der Erkennung kollinearer Spleiß-Varianten vergleichbare Ergebnisse mit anderen Methoden erzielt, schlägt es die Wettbewerber mit Blick auf Sensitivität und Spezifität bei der Vorhersage nicht-kollinearer Spleißvarianten. Die Anwendung dieses Algorithmus führte zur Identifikation neuer Isoformen. In unserer Publikation berichten wir über eine neue Isoform des Tumorsuppressorgens p53. Da dieses Gen eines der am besten untersuchten Gene des menschlichen Genoms ist, könnte die Anwendung unseres Algorithmus helfen, eine Vielzahl weiterer Isoformen bei weniger prominenten Genen zu identifizieren. Drittens stellen wir ein datenadaptives Modell zur Identifikation von Single Nucleotide Variations (SNVs) vor. In unserer Arbeit zeigen wir, dass sich unser auf empirischen log-likelihoods basierendes Modell automatisch an die Qualität der Sequenzierungsexperimente anpasst und eine \"Entscheidung\" darüber trifft, welche potentiellen Variationen als SNVs zu klassifizieren sind. In unseren Simulationen ist diese Methode auf Augenhöhe mit aktuell eingesetzten Verfahren. Schließlich stellen wir eine Auswahl biologischer Ergebnisse vor, die mit den Besonderheiten der präsentierten Alignmentverfahren in Zusammenhang stehen.

Algoritmos exatos para fatoração estão limitados a funções Booleanas read-once, onde cada variável aparece uma vez na equação final. No entanto, estes algoritmos apresentam duas restrições principais: (1) eles não consideram funções Booleanas incompletamente especificadas, e (2) eles não são adequados para as funções binate. Para superar o primeiro inconveniente, é proposto um algoritmo que encontra equações read-once para funções Booleanas incompletamente especificadas, sempre que possível, é proposto. Com respeito à segunda limitação, é apresentada uma transformação de domínio que divide variáveis binate existentes em duas variáveis unate independentes. Tal transformação de domínio conduz a funções Booleanas incompletamente especificadas, que podem ser eficientemente fatoradas mediante a aplicação do algoritmo proposto. A combinação das duas contribuições dá resultados ótimos para uma nova classe de funções Booleanas chamada read-polarity-once, onde cada polaridade (positiva ou negativa) de uma variável aparece no máximo uma vez na forma fatorada da expressão Booleana. Resultados experimentais sobre circuitos ISCAS'85 mostrou que funções read-polarity-once são significativamente mais frequentes em circuitos reais quando comparado com a classe de funções read-once, a qual muitos trabalhos já foram dedicados na literatura. / Efficient exact factoring algorithms are limited to read-once functions, in which each variable appears once in the final Boolean equation. However, those algorithms present two main constraints: (1) they do not consider incompletely specified Boolean functions; and (2) they are not suitable for binate functions. To overcome the first drawback, it is proposed an algorithm that finds read-once formulas for incompletely specified Boolean functions, whenever possible. With respect to the second limitation, a domain transformation that splits existing binate variables into two independent unate variables is presented. Such domain transformation leads to incompletely specified Boolean functions, which can be efficiently factored by applying the proposed algorithm. The combination of both contributions gives optimal results for a novel broader class of Boolean functions named as read-polarity-once functions, where each polarity (positive or negative) of a variable appears at most once in the factored form. Experimental results over ISCAS'85 benchmark circuits have shown that read-polarityonce functions are significantly more frequent than read-once functions, for which many works have already been devoted in the literature.

Algoritmos exatos para fatoração estão limitados a funções Booleanas read-once, onde cada variável aparece uma vez na equação final. No entanto, estes algoritmos apresentam duas restrições principais: (1) eles não consideram funções Booleanas incompletamente especificadas, e (2) eles não são adequados para as funções binate. Para superar o primeiro inconveniente, é proposto um algoritmo que encontra equações read-once para funções Booleanas incompletamente especificadas, sempre que possível, é proposto. Com respeito à segunda limitação, é apresentada uma transformação de domínio que divide variáveis binate existentes em duas variáveis unate independentes. Tal transformação de domínio conduz a funções Booleanas incompletamente especificadas, que podem ser eficientemente fatoradas mediante a aplicação do algoritmo proposto. A combinação das duas contribuições dá resultados ótimos para uma nova classe de funções Booleanas chamada read-polarity-once, onde cada polaridade (positiva ou negativa) de uma variável aparece no máximo uma vez na forma fatorada da expressão Booleana. Resultados experimentais sobre circuitos ISCAS'85 mostrou que funções read-polarity-once são significativamente mais frequentes em circuitos reais quando comparado com a classe de funções read-once, a qual muitos trabalhos já foram dedicados na literatura. / Efficient exact factoring algorithms are limited to read-once functions, in which each variable appears once in the final Boolean equation. However, those algorithms present two main constraints: (1) they do not consider incompletely specified Boolean functions; and (2) they are not suitable for binate functions. To overcome the first drawback, it is proposed an algorithm that finds read-once formulas for incompletely specified Boolean functions, whenever possible. With respect to the second limitation, a domain transformation that splits existing binate variables into two independent unate variables is presented. Such domain transformation leads to incompletely specified Boolean functions, which can be efficiently factored by applying the proposed algorithm. The combination of both contributions gives optimal results for a novel broader class of Boolean functions named as read-polarity-once functions, where each polarity (positive or negative) of a variable appears at most once in the factored form. Experimental results over ISCAS'85 benchmark circuits have shown that read-polarityonce functions are significantly more frequent than read-once functions, for which many works have already been devoted in the literature.

Algoritmos exatos para fatoração estão limitados a funções Booleanas read-once, onde cada variável aparece uma vez na equação final. No entanto, estes algoritmos apresentam duas restrições principais: (1) eles não consideram funções Booleanas incompletamente especificadas, e (2) eles não são adequados para as funções binate. Para superar o primeiro inconveniente, é proposto um algoritmo que encontra equações read-once para funções Booleanas incompletamente especificadas, sempre que possível, é proposto. Com respeito à segunda limitação, é apresentada uma transformação de domínio que divide variáveis binate existentes em duas variáveis unate independentes. Tal transformação de domínio conduz a funções Booleanas incompletamente especificadas, que podem ser eficientemente fatoradas mediante a aplicação do algoritmo proposto. A combinação das duas contribuições dá resultados ótimos para uma nova classe de funções Booleanas chamada read-polarity-once, onde cada polaridade (positiva ou negativa) de uma variável aparece no máximo uma vez na forma fatorada da expressão Booleana. Resultados experimentais sobre circuitos ISCAS'85 mostrou que funções read-polarity-once são significativamente mais frequentes em circuitos reais quando comparado com a classe de funções read-once, a qual muitos trabalhos já foram dedicados na literatura. / Efficient exact factoring algorithms are limited to read-once functions, in which each variable appears once in the final Boolean equation. However, those algorithms present two main constraints: (1) they do not consider incompletely specified Boolean functions; and (2) they are not suitable for binate functions. To overcome the first drawback, it is proposed an algorithm that finds read-once formulas for incompletely specified Boolean functions, whenever possible. With respect to the second limitation, a domain transformation that splits existing binate variables into two independent unate variables is presented. Such domain transformation leads to incompletely specified Boolean functions, which can be efficiently factored by applying the proposed algorithm. The combination of both contributions gives optimal results for a novel broader class of Boolean functions named as read-polarity-once functions, where each polarity (positive or negative) of a variable appears at most once in the factored form. Experimental results over ISCAS'85 benchmark circuits have shown that read-polarityonce functions are significantly more frequent than read-once functions, for which many works have already been devoted in the literature.