653 research outputs found
Unravelling the genetic basis of hereditary disorders by high-throughput exome sequencing strategies
No full textThe research presented in this thesis focuses on using Whole Exome Sequencing (WES) to unravel the genetic basis of human hereditary disorders with different inheritance patterns. We set out to apply WES as a diagnostic approach for establishing a molecular diagnosis in a highly heterogeneous group of patients with microcephaly and varied intellectual disability. Additionally, a family with familial glucocorticoid deficiency (FGD) and a cohort of patients with L1 syndrome were studied. In our microcephaly project, we achieved a diagnostic yield of 29% and found mutations in known disease-genes. Our results confirmed that many microcephaly cases are explained by autosomal recessive inheritance. For FGD, trio-exome sequencing revealed a novel homozygous mutation in the NNT gene. We also reviewed the literature for all reported NNT mutations and their clinical presentation. By application of X-exome sequencing in a cohort of 58 patients with L1 syndrome, an X-linked disorder, we identified 5 possible novel candidate genes, among which three independent mutations in DACH2 suggest this gene as the most promising candidate gene for L1 syndrome. Finally, using an in silico composite biological network analysis, we identified molecular pathomechanisms underlying congenital microcephaly (CM) and predicted further CM-candidate genes. Next to known processes, our analysis suggested, telomere biology and tRNA metabolic process as biological functions underlying CM. Supportive evidence for several selected candidate genes demonstrated the potential of our network approach to facilitate gene discovery in genetically heterogeneous disease
Inflammatory biomarker genomics: From discovery to causality
No full textInflammatory biomarkers are a group of proteins circulating in the blood that play key roles in inflammation. The blood levels of these are partially genetically determined, and elevated levels are hallmarks for various types of diseases and sometimes even directly implicated in pathogenesis. In this thesis I aimed to identify previously unknown genetic regions (‘loci’) for well-known inflammatory biomarkers, to understand how they influence molecular levels, and whether they play a causal role in various diseases. After the preface (Chapter 1), I present three large-scale genome-wide association studies (GWASs) that led to the identification of new genetic loci for levels of four inflammatory biomarkers: TNF-α, Interleukin-6, serum albumin and total protein (Chapter 3,4 and 5, respectively). These analyses were supported by a software pipeline that automated data quality checks for these studies (Chapter 2). In Chapter 6, we focussed on disentangling the molecular mechanisms through which genetic determinants influence levels of one of the most widely clinically used inflammatory biomarkers, C-Reactive Protein, followed by an investigation of its involvement in multiple disease classes (Chapter 7). I conclude with a review on GWAS for Coronary Artery Disease (Chapter 8), and argue that we can improve our understanding of the mechanisms by which genetic loci influence traits of interest through the integration with other layers of molecular data, an approach known as systems genetics. This research has increased our biological understanding of genetic determinants of inflammatory biomarkers and provides further leads for investigation of their direct involvement in the pathogenesis of disease
Application of Z-restriction-based Multi-criteria Choice to a Marketing Mix Problem
No full textAbstractIn this paper the method of solving Z-number valued multiobjective linear programming problem proposed in “R.A. Aliev, O.H. Huseynov, R.R. Aliyev, A.V. Alizadeh, The Arithmetic of Z-numbers. Theory and Applications. Singapore: World Scientific, 2015” is applied to solve a marketing mix problem. The method utilizes differential evolution optimization. The obtained results show validity and applicability of the proposed approach
Nutrients and diet quality in gastrointestinal cancers
No full textFindings on the role of foods in the risk of gastrointestinal cancers are not consistent. This thesis studied the role of some essential dietary components that are required for normal development and function, as well as that of balanced and healthy patterns of diet intake, on the risk of gastrointestinal cancers. We show that neither synthetic folic acid nor the blood level folate is associated with an increased risk of colorectal cancer (Chapter 2). However, the results of a large study show that supplementing folic acid and iron at higher levels than provided in the original food may increase the risk for colorectal cancer (Chapter 3). The risk of colorectal cancer also seems not to be increased for pregnant women taking synthetic folic acid according to data from smaller study (Chapter 4). As anticipated, healthy and balanced diet intake patterns are associated with lower risks of gastrointestinal cancers, yet the findings are of insufficient quality to develop dietary recommendations for gastrointestinal cancers prevention (Chapters 5, 6, & 7). Moreover, healthy food intake is inadequate among cancer survivors (Chapter 8). The effect of folic acid and iron, as well as that of a healthy and balanced pattern of food and beverage intake, remain unclear regarding gastrointestinal cancer. Future studies will need to assess the role of inherited features on the effect of essential nutrients in diet and on the healthiest patterns of diet intake needed to prevent gastrointestinal cancer
The Effect of Life Skills Training on Social Health: A Case Study of 15- to 29-Year-Olds in Haji Abad City Mohammad Hassan Sharbatiyan[1], Samereh Alizadeh Khaneghahi[2] Received: 27/06/2017 Accepted: 13/03/2017
No full textThe Effect of Life Skills Training on Social Health: A Case Study of 15- to 29-Year-Olds in Haji Abad City Mohammad Hassan Sharbatiyan[1], Samereh Alizadeh Khaneghahi[2] Received: 27/06/2017 Accepted: 13/03/2017 Abstract The aim of this research is to investigate the effect of life skills on social health regarding theoretical foundations by Keyes (social health) and the Bandura social learning theory (life skills). The sample size was 368 persons who were selected through simple random sampling using a standardized questionnaire. The results have been analysed using the SPSS 22 software. T-Tests, Pearson correlation, regression and path analysis have been used to analyse the relationships between variables. The results indicate that the rate of youth social health was medium to high. Findings show a direct relationship between the dimensions of life skills and social health in the studied population. Also social health of youth is significant different depending on marital status, but not on gender. The regression results also indicate that among factors influencing health, the communication skill variable, beta=0.93, has the greatest direct impact on social health in the studied population. The findings of path analysis show that only the critical-creative thinking variable has a direct and indirect effect, other variables only have a direct effect on the participants. Results also indicate that measures of communication skill, rate of self-consciousness, decision making, excitement and creative thinking can explain up to 90 percent of the dependent variable. Keywords: Youth, Haji Abad, Social Health, Life Skills [1]. Corresponding Author Faculty Member at Department of Sociology. Payame NoorUniversity (PNU). (Corresponding Author). [email protected] [2]. Master of Social Science research, MazandaranUniversity. [email protected]
Bioinformatics of genomic association mapping
No full textIn this thesis we present an overview of bioinformatics-based approaches for genomic association mapping, with emphasis on human quantitative traits and their contribution to complex diseases. We aim to provide a comprehensive walk-through of the classic steps of genomic association mapping illustrating the application and development of bioinformatics tools along the way. We start with a classic heritability study, continue with providing novel tools for genome-wide association studies (GWASs) of complex traits, and end with an integrated post-GWAS pipeline for translating GWAS findings of any human trait or disease to biological knowledge. Using this A-to-Z approach, we emphasize the importance of following the consecutive steps of genomic association mapping. To show how bioinformatics tools can facilitate and support analysis of high-throughput biological data, in Chapters 2, 3, 5, 6, and 7 we applied a number of already available tools, whereas in Chapters 3, 4, and 7 we developed novel bioinformatics tools supporting appropriate analysis of “big data” for genomic association mapping. Our in-house developed and extensively documented bioinformatics tools are freely available to the scientific community for further use. Furthermore, and as a running example of genomic association mapping of a typical human complex trait, we strictly adhered to serum levels of C-reactive protein (CRP). Using appropriate bioinformatics-based tools, either already available or our in-house developed ones, we succeeded to gain in knowledge of biological mechanisms controlling serum levels of CRP as well as its (causal) contribution to the pathophysiology of human diseases
Statistical approaches to explore clinical heterogeneity in psychosis
No full textPsychotische stoornissen tonen een zeer heterogeen klinisch beeld; iets wat vaak over het hoofd wordt gezien. Doel van dit proefschrift is om inzicht te krijgen in de heterogeniteit, stabiliteit en familiaire kwetsbaarheid van mensen met een psychose en hun broers/zussen. Om deze heterogeniteit en stabiliteit aan te tonen werd gebruikt gemaakt van classical clustering, linear, generalized linear mixed effects en group-based trajectory modeling (GBTM). Wat betref heterogeniteit, lieten we zien dat Duda en Hart de geschikte index is om cluster te identificeren. Daarmee bevestigden wij eerder studie over cognitieve subtypes vanuit het GROUP-project. Vervolgens toonden we de waarde van deze subtypes aan in de loop van de stoornis met behulp van GBTM. Stabiliteit bleek een belangrijk kenmerk bij cognitie te zijn, maar niet bij negatieve symptomen. Familiaire kwetsbaarheid kwam tot uiting in cognitie ( siblings presteerden tussen controles en patiënten), in somatische comorbiditeit (risico voor siblings lag ook tussen beide) en in psychotische belevingen (meer aanwezig bij siblings dan bij controles). Binnen dit proefschrift werd een aantal verschillende predictoren geïdentificeerd. Het cognitieve profiel van de patiënten voorspelden de cognitie van siblings. Bovendien bleek de Theory of Mind bij siblings een voorspeller voor psychotische belevingen, drie jaar later. Negatieve symptomen voorspelden functioneren in de tijd. Bij multimorbiditeit bleek familiaire kwetsbaarheid de belangrijkste voorspeller. Tenslotte was migratie de belangrijkste risicofactor voor duur van de onbehandelde psychose. Concluderend, heterogeniteit bij psychosen is een klinisch relevant concept. Subtypering van patiënten opent nieuwe wegen naar inzicht en behandeling van mensen met een psychose
Knowledge Type Identification in API Documentation
No full text<p>This release contains the source code and instruction on how to obtain the dataset to reproduce the results presented in the following paper</p>
<pre><code>@inproceedings{FMM19,
title={On Using Machine Learning to Identify Knowledge in API Reference Documentation},
author={Fucci, Davide and M. Alizadeh B., Alireza and Maalej, Walid},
booktitle={27th ACM Joint European Software Engineering Conference and Symposium on the Foundations of Software Engineering},
pages={103--112},
year={2019},
doi={10.1145/3338906.3338943}
organization={IEEE}
}
</code></pre>
Osteoarthritis and Hemochromatosis: A genetic epidemiologic study
No full textOsteoarthritis (OA) refers to a heterogeneous group of distinct diseases which express a
common radiographic and clinical phenotype at diarthrodial joints.It is the leading cause of
pain and disability in the elderly with a prevalence of 75 percent in the population aged 70
years. There is a substantial genetic component in the etiology of osteoarthritis. It is
expected that genetic heterogeneity, the extent of which is unknown yet, contributes to a
spectrum of osteoarthritis related phenotypes. Linkage as well as candidate gene studies are
being performed to identify the genes involved.The overall aim of our research project is
to identify genes that contribute to osteoarthritis. The aim of the present thesis was to
understand the relation between hemochromatosis and osteoarthritis. As a part of this project,
candidate osteoarthritis genes were analysed. These include the gene encoding the alpha
domain of collagen type IX (COL9A1) and the HFE gene involved in hereditary
hemochromatosis, a disorder that coincides with arthropathy. This thesis, therefore, brings
together two related complex diseases, that share related phenotypes and possibly some of the
underlying genetic components
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