A compound-heterozygous variant occurs when a child inherits a variant from each parent, with these variants occurring at a different position within the same gene and on opposite homologous chromosomes. These inherited variants may result in two nonfunctional versions of the same gene. Compound-heterozygous variants cannot be identified unless a patients' DNA sequence data is phased. Phasing is a computationally demanding process that requires the use of multiple software tools in order to determine which nucleotide was inherited from which parent. First, in Chapter 1, we review the literature to better understand what research has been conducted on the role of compound-heterozygous variants in pediatric cancers and what methods are being used to identify them. In Chapter 2, we develop a pipeline to make it easier for us and other researchers to phase and identify compound-heterozygous variants using VCF files from trios or individuals. We then use this pipeline in Chapter 3 to survey the prevalence of compound-heterozygous variants across 7 pediatric disease types. We show the importance of identifying compound heterozygous and what information would be missed if this variant type was not included in study design. In Chapter 4, we develop a software tool to phase trio data using a combination of Mendelian inheritance logic and an existing phasing software program. We show that our software tool increases the total number of variants that can be phased. Finally, in Chapter 5, we use phased data of three nuclear families, each family having one child with pediatric cancer, to evaluate the potential to use inherited genomic variants to inform diagnostic decisions. The work contained within this dissertation shows the importance of not overlooking compound-heterozygous variants when trying to identify potentially causal genes in pediatric disease. In addition, this work provides software tools that are openly available for other researchers to use; these tools make it easier to phase patient DNA sequence data and to identify compound-heterozygous variants.

Most of the municipalities in Czech republic have old or even disfunctional sewage systems for built up communal areas. General combined sewage systems built earlier are being today replaced by solutions separating rain waters and sewage waters. Municipality Vír has currently only few sewage branches that consequently flow into Svratka river. Aim of this Diploma Thesis is to propose 3 solutions for sewage produced in communal areas of Vír municipality and its consequent disposal in sewage treatment plant. Each of three solutions feature combined gravity-driven and pressure systems of sewage lines as well as water treatment in proposed MTB as well as household and container WTP. Each of three variant is economically weighed with proposed budget.

No description available.

[pt] A termografia infravermelha tem sido usada como uma técnica de avaliação não destrutiva para detectar falhas nos componentes estruturais, desempenhando um papel importante nos programas de inspeção de fabricação, inspeção em serviço e manutenção. Um programa de investigação foi lançado com o objetivo de apresentar combinações de métodos analíticos, experimentais e numéricos para prever e monitorar o início da fadiga e a progressão dos danos à fadiga em equipamentos como vasos de pressão, tanques, tubulações e dutos com mossas ou anomalias complexas. O monitoramento do início e propagação da fadiga nas amostras reais utilizou técnicas de inspeção por infravermelho não destrutivo. Análise termoelástica de tensão (TSA), correlação tridimensional de imagem digital (3D-DIC) e strain gages de fibra óptica Bragg (FBSG) foram utilizados para determinar deformações em locais de fadiga em pontos críticos. Os campos de deformação determinados a partir das medições experimentais e do método de elementos finitos (MEF) foram combinados com a equação de vida-de-fadiga de Coffin-Manson e a regra de dano por fadiga de Miner para prever a vida de fadiga (N). Os resultados das amostras tubulares testadas de 3 m de comprimento contendo mossas de formato complexo foram relatados e analisados completamente. Este trabalho confirmou que os métodos infravermelhos de avaliação rápida de fadiga são ferramentas práticas e eficientes que podem fornecer resultados confiáveis, não destrutivos e rápidos acerca do comportamento à fadiga dos materiais. Uma boa concordância entre as estimativas de vida em fadiga e a vida real de mossas com geometria complexas em dutos só pode ser atingida se medições precisas ou determinações numéricas das deformações circunferenciais que atuam nos pontos de interesse forem acopladas a curvas de fadiga deformação-vida adequadas. Acoplando uma técnica experimental para determinar com precisão a geometria das mossas com uma técnica de análise numérica de deformações fará com que sejam obtidas boas estimativas de deformação das posições críticas que serão combinadas com as curvas de fadiga baseadas na relação deformação-vida. As presentes conclusões podem ser aplicadas a outras estruturas que podem apresentar mossas, como tanques e vasos de pressão. / [en] Infrared thermography has been used as a nondestructive evaluation (NDE) technique to detect flaws in structural components, playing an important role in manufacturing inspection, in-service inspection and maintenance programs. An investigation program was launched with the objective of presenting combinations of analytical, experimental and numerical methods to predict and monitor fatigue initiation and fatigue damage progression in equipment such as pressure vessels, tanks, piping and pipelines with dents or complex-shaped anomalies. The monitoring of fatigue initiation and propagation in the actual specimens used nondestructive inspection techniques such as thermoelastic stress analysis (TSA), three-dimensional digital image correlation (3D-DIC) and fiber optic Bragg strain gages (FBSG) to determine strains at fatigue hot spots locations. Strain fields determined from the experimental measurements and from the finite element method (FEM) were combined with the fatigue Coffin-Manson strain-life equation and the Miner s fatigue damage rule to predict fatigue life (N). Results from tested 3m long tubular (with nominal dimensions: 324mm external diameter and 6.35mm wall thickness) specimens containing complex-shaped dents were reported and fully analyzed. This work confirmed that infrared rapid fatigue assessment methods are practical and efficient tools that can provide a reliable, non-destructive and faster results about the fatigue behavior of materials. Good agreement among fatigue life estimations and actual fatigue lives of complex dent shapes in pipeline specimens can only be achieved if accurate measurements or numerical eterminations of the circumferential strains actuating at the dent hot-spots were coupled with suitable fatigue strain-life curves. Coupling an experimental technique for accurately determining dent shapes to a numerical strain analysis technique will lead to good hot-spot strain estimations to be combined with the strain-life fatigue curves. The present conclusions can be applied to other structures that may present dents such as tanks and pressure vessels.

Continuous integration, continuous delivery och continuous deployment har blivit väldigt viktiga inom systemutveckling eftersom de hjälper att säkerställa att en programvara håller sig till en viss kvalité samt att den snabbt kan levereras till slutanvändarna. Organisationer som tidigare använde continuous practices i samband med mer traditionella programvaror som till exempel webb-, server- och skrivbordsapplikationer försöker idag även implementera continuous practices i samband med mobila applikationer som till exempel hybrida appar. Bygg- och leveransprocessen för hybrida mobila applikationer består av många steg som ska göras i rätt ordning. När den processen utförs manuellt ökar det risken för att en app inte kommer att hålla en genomgående hög kvalité samt att det kan bli svårt att säkerställa att appen kan levereras vid behov till slutanvändarna. Det kan bero på flera faktorer. En av dessa faktorer är att människor inte är bra på att utföra långa och upprepbara processer och begår därför ofta fel och misstag. Tidigare studier som gjordes inom continuous integration, -delivery och -deployment saknar hur continuous practices kan appliceras till bygg- och leveransprocessen för hybrida mobila applikationer samt hur det kan göras i en organisation där det finns en existerande bygg- och leveransplattform. På grund av det utfördes den här studien med syftet att skapa en IT-artefakt i form av en pipeline som kan minska eller utesluta mänsklig påverkan på bygg- och leveransprocessen för hybrida mobila applikationer. Studien genomfördes med Action Design Research som bestod av tre iterationer och resulterade i en IT-artefakt i form av en pipeline som kunde utföra automatisk bygg och leverans av hybrida mobila applikationer. Förutom IT-artefakten kunde även ett antal designprinciper identifieras som var lämpliga när en pipeline för hybrida appar formades. Studiens resultat visade att med hjälp av continuous practices är det möjligt att automatisera bygg och leverans av hybrida appar samt att det går att implementera en pipeline för hybrida appar i en bygg- och leveransplattform som används för andra typer av programvaror.

No description available.

Styrd borrning är en schaktfri metod för att förlägga ledningar i mark. Examensarbetet har utförts i samarbete med Styrud Ingenjörsfirma AB som uppfattat en okunskap i branschen över prisbilden för styrd borrning. Syftet med arbetet är att utföra en kostnadsanalys för att beskriva hur styrd borrning står sig ekonomiskt mot konventionell schaktning. Arbetet undersöker även vilka faktorer som påverkar en eventuell ekonomisk brytpunkt, vilken i detta arbete definieras som den punkt när en viss metod blir det ekonomiskt gynnsamma alternativet. Studien har utformats för att så objektivt som möjligt belysa ämnet med utgångspunkten att göra metoderna jämförbara analytiskt. För att genomföra en analys har en beräkningsmodell skapats. Målet med modellen och dess utformning är att den enkelt skall gå att bygga vidare på och utvecklas i framtiden samt att användas av projektörer som en fingervisning tidigt i projekteringsstadiet. Från beräkningsmodellen har 70 fiktiva fall studerats. Resultatet visar att styrd borrning är billigare i 73% av fallen. I övriga fall tyder resultatet på att styrd borrning som metod generellt sett inte är så dyrt att övervägning att använda metoden försvinner. Genom resultat och analys dras slutsatsen att styrd borrning i de flesta fall står sig ekonomiskt starkt som alternativ till konventionell schaktning. / Horizontal directional drilling is a trenchless method used to install pipelines underground. This thesis is conducted in collaboration with Styrud Ingenjörsfirma AB, who perceived lacking knowledge within the industry regarding the financial aspects of directional drilling. The purpose of this thesis is to carry out a cost analysis that defines how directional drilling stands financially against traditional excavation. The study also intends to describe which factors that influence a possible economic breakpoint, in this study referring to when a certain method becomes the economically strongest alternative. This thesis has been carried out to as objectively as possible describe the topic focusing on making the methods analytically comparable. To carry out the analysis, an economic model has been created. The model and its design have been created in a manner that makes it easy to develop it in the future and aims to act as a guide for project planners to indicate which method to proceed with. From the economic model, 70 cases have been studied. The result shows that directional drilling is cheaper in 73% of the cases. In the rest of the cases, the result suggests that directional drilling as a method generally is not so expensive that consideration of using the method disappears. Through results and analysis, it is concluded that directional drilling in most cases is a strong alternative to traditional excavation from an economic standpoint.

Разработана экономическая модель формирования инвестиций в попериодный горизонт до 15,30,50 лет и требуемой ставке дохода с применением функции «формирования фонда возмещения» определены равномерные периодические платежи, необходимые для получения итогового объема инвестиций в будущем. / An economic model has been developed for the formation of investments in a period horizon of up to 15,30,50 years and the required rate of return using the function of "formation of the compensation fund" determined uniform periodic payments necessary to obtain the final volume of investments in the future.

No description available.

Abstract Predicting Location and Training Effectiveness (PLATE) Erik Bruenner Physical activity and exercise have been shown to have an enormous impact on many areas of human health and can reduce the risk of many chronic diseases. In order to better understand how exercise may affect the body, current kinesiology studies are designed to track human movements over large intervals of time. Procedures used in these studies provide a way for researchers to quantify an individual’s activity level over time, along with tracking various types of activities that individuals may engage in. Movement data of research subjects is often collected through various sensors, such as accelerometers. Data from these specialized sensors may be fed into a deep learning model which can accurately predict what movements a person is making based on aggregated sensor data. However, in order for prediction models to produce accurate classifications of activities, they must be ‘trained’. Training occurs through the process of supervised learning on large amounts of data where movements are already known. These training data sets are also known as ‘validation’ data or ‘ground truth’. Currently, generation of these ground truth sets is very labor-intensive. To generate these labeled data sets, research assistants must analyze many hours of video footage with research subjects. These research assistants painstakingly categorize each video, second by second, with a description of the activity the subject was engaging in. Using only labeled video, the PLATE project facilitates the generation of ground truth data by developing an artificial intelligence (AI) that predicts video quality labels, along with labels that denote the physical location that these activities occurred in. The PLATE project builds on previous work by a former graduate student, Roxanne Miller. Miller developed a classification system to categorize subject activities into groups such as ‘Stand’, ‘Sit’, ‘Walk’, ‘Run’, etc. The PLATE project focuses instead on development of AI to generate ground truth training in order to accurately detect and identify the quality of video data, and the location of the video data. In the context of the PLATE project, video quality refers to whether or not a test subject is visible in the frame. Location classifications include categorizing ‘indoors’, ‘outdoors’, and ‘traveling’. More specifically, indoor categories are further identified as ‘house’, ‘office’, ‘school’, ‘store’ or ‘commercial’ space. Outdoor locations are further classified as ‘commercial space’, ‘park/greenspace’, ‘residential’ or ‘neighborhood’. The nature of our location classification problem lends itself particularly well to a hierarchical classification approach, where general indoor, outdoor, or travel categories are predicted, then separate models predict the subclassifications of these categories. The PLATE project uses three convolutional neural networks in its hierarchical location prediction pipeline, and one convolutional neural network to predict if video frames are high or low quality. Results from the PLATE project demonstrate that quality can be predicted with an accuracy of 96%, general location with an accuracy of 75%, and specific locations with an accuracy of 31%. The findings and model produced by the PLATE project are utilized in the PathML project as part of a ground truth prediction software for activity monitoring studies. PathML is a project funded by the NIH as part of a Small Business Research Initiative. Cal Poly partnered with Sentimetrix Inc, a data analytics/machine learning company, to build a methodology for automated labeling of human physical activity. The partnership aims to utilize this methodology to develop a software tool that performs automatic labeling and facilitates the subsequent human inspection. Phase I (proof of concept) of the project took place from September 2021 to August 2022, Phase II (final software production) is pending. This thesis is part of the research that took place during Phase I lifetime, and continues to support Phase II development.