161 research outputs found
Numeriek model voor de bepaling van het zandtransport onder invloed van golven
No full textEr zijn door o.a. Vetlinga en Schepers proeven gedaan in een laboratoriumgoot ter bepaling van zandtransport in de voortplantingsrichting van golven onder invloed van die golven. Doel van deze proeven is om neer inzicht te krijgen in de opwoeling van het bcdemmateriaal aan de bcdem en op die manier in het zandtransportmechanisme . In al die proeven is als bcdemmateriaal zand van verschillende dianeter gebruikt. Aangezien het verschijnsel aan de bcdem zeer gecompliceerd is, is uitgegaan van een benadering via een rechtstreekse bepaling van het zandtransport. Bij de proeven van Schepers, die tevens een aantal proeven deed met fijn zand, D50 = 125 um, bleek dat dit zand anders reageerde op de golfbeweging dan het wat grovere zand door Vellinga en Schepers gebruikt. Omdat daar in eerste instantie geen sluitende verklaring voor was te vinden is een aanzet gemaakt tot een cornputerberekening. Aan de hand van een geschematiseerde aanpak van het opwoelingsmechanisme en het neerslaan van dit zand is het effect van de valsnelheid te onderzoeken. In eerste instantie is, het probleem simpel gehouden om duidelijk te herkennen wat een variatie in de valsnelheid voor gevolgen heeft. Omdat ook het faseverschil tussen de top van de lste harmonische en de top van de resulterende 2de hanronische een rol speelt, is dit aan de hand van berekeningen nagegaan. Bij enkele berekeningen is een eenparige stroom toegevoegd. Hoewel dUidelijk was dat het effect hiervan niet zou overeenkomen met de proeven van Schepers op dit gebied, was het als indicatie voor proeven met wat grotere eenparige stroming waardevol.Hydraulic EngineeringCivil Engineering and Geoscience
Decoding the genetic puzzle of inherited cardiac arrhythmias : insights from molecular autopsy, genetic profiling and iPSC-derived cardiomyocyte modelling
No full textAbstract: Inherited cardiac arrhythmias (ICA) encompass a group of cardiac diseases with common characteristics such as low prevalence, reduced penetrance and variable phenotypical expression including electrocardiogram abnormalities, syncopes, ventricular fibrillations and increased risk for sudden cardiac death (SCD). Approximately 70 genes contribute to ICAs, demonstrating substantial genetic overlap. Despite advancements in next-generation sequencing (NGS), many cases remain genetically unsolved due to complex inheritance patterns and variants of uncertain significance (VUS) in known genes. Functional analyses can provide the ultimate proof to reclassify a VUS but as this is labour intensive and expensive and not routinely done in a diagnostic setting. A case of SCD was investigated using NGS gene panels. We detected two VUS in the KCNQ1 and DSG2 genes. An in vitro functional analysis of the KCNQ1 variant did not show any effect on the potassium current. Segregation analysis revealed that the DSG2 variant was de novo, upscaling its classification to likely pathogenic. In only 30% of Brugada Syndrome (BrS) patients a genetic cause is identified. We analyzed 350 patients and found (likely) pathogenic variants in 9%. These patients showed more severe clinical features. Utilizing the Shanghai scoring system for definite BrS diagnosis increased yield to 18%. 31% of all the patients carried a VUS but such VUS do not contribute to more informative genetic counselling for the patient. Induced pluripotent stem cells (iPSCs) emerged as a valuable human cellular model. iPSCs, derived from Brugada syndrome patients with a specific SCN5A mutation, displayed pluripotency and validated through molecular assays. Despite sharing the same Belgian SCN5A founder mutation, patients exhibited diverse clinical phenotypes. Differentiated into cardiomyocytes, patient iPSC-CMs showed variations in SCN5A transcripts but similar total expression, sodium current, and action potential characteristics compared to controls. Notably, statistical analysis challenges arose from significant variability between iPSC clones and individuals. The use of a CRISPR-generated isogenic control underscores the promising utility as a strategy for studying mutations in Brugada syndrome. With enhanced molecular techniques for investigating the genetic landscape of ICAs, it has become clear that the effect of genetic variants is not always easy to interpret and functional analysis is needed. For this purpose, novel study models such as iPSC-CMs can play an important role as they represent the disease-relevant cell type with full cardiomyocyte-specific molecular machinery, can be patient-specific and isogenic lines can be generated. In this way, also more complex interactions can be studied in a relevant cell model
Fish, founders and fluorescent indicators : progress of inherited cardiac arrhythmia genomics in the new sequencing era
No full textAbstract: Inherited Cardiac Arrhythmia (ICA) syndromes are a group of rare genetic disorders characterised by an increased risk for potentially lethal ventricular arrhythmias, which occur in structurally (seemingly) normal myocardium. While recent technological advances in DNA sequencing have improved in the diagnostic yield in ICA, they have also led to an increased identification of variants of uncertain significance (VUS). Functional characterisation plays a crucial role in variant annotation. Nevertheless, sufficiently high-throughput ICA disease models are still lacking. We set out to fill this gap by generating a zebrafish assay for cardiac arrhythmia, with co-expression of the Ace2N-mNeon genetically encoded voltage indicator and R-GECO genetically encoded calcium indicator in the heart. Our zebrafish cardiac arrhythmia assay was able to detect electrophysiological abnormalities induced by drugs and genetic models of ICA generated at our lab. These consisted of a long QT syndrome model, induced by a knock-in mutation in the cacna1c gene and a catecholaminergic polymorphic ventricular tachycardia (CPVT) model, due to a homozygous knockout of the casq2 gene. The use of light sheet imaging also enabled us to generate three-dimensional maps of the cardiac action potential characteristics of the entire heart in zebrafish embryos. Additionally, we optimized the process of the generation of zebrafish knock-in mutants through CRISPR-Cas9 gene editing. By combining minimally invasive early genotyping with the Zebrafish Embryo Genotyper device with next-generation sequencing, we were able to achieve an almost seventeen-fold improvement in editing efficiency. Lastly, we performed clinical and functional assessments of variants in known arrhythmia genes to clarify the remaining issues in ICA genetics. We explored a novel hypothesis of autosomal dominant CPVT for a heterozygous c.738-2A>G splice site variant in CASQ2. We assessed a cohort of (c.4813+3_4813+6dupGGGT) SCN5A founder mutation carriers for clinical signs of a complex genetic architecture in Brugada syndrome. Additionally, we demonstrated the role of the disease model in the functional assessment of the allelic effect of a recurrent KCNQ1 c.1124_1127delTTCA p.(Ile375Argfs*43) variant. With increased identification of VUS and the confounding contributions of poly- and oligogenic factors, as well as variable allelic effects of established pathogenic variants, the field of ICA genetics research remains complex and challenging. Future studies in promising disease models, such as zebrafish, as well as clinical and molecular investigations in cohorts of patients carrying the same pathogenic variant, will likely aid in clarifying some of the remaining questions
Fishing for genes : a disease transgressing approach to unravel the genetic basis of thoracic aortic aneurysm
No full text
Genetics of vascular disease: Marfan syndrome and aortic disease
No full textMarfan syndrome is an autosomal dominant, multisystemic disorder, presenting with skeletal, ocular, and cardiovascular symptoms. This connective tissue disease is caused by mutations in FBN1, encoding fibrillin-1, which is an important extracellular matrix protein. Marfan syndrome shows significant clinical overlap with Loeys–Dietz syndrome, which is caused by genetic defects in components of the transforming growth factor-beta pathway: TGFBR1, TGFBR2, TGFB2, TGFB3, SMAD2, and SMAD3. Overlapping clinical features between Marfan syndrome and Loeys–Dietz syndrome include aortic root aneurysm, arachnodactyly, scoliosis, and pectus deformity.</p
Genetic diseases of the aorta: chromosomal and inherited diseases
No full textGenetic diseases of the aorta account for significant cardiovascular morbidity and mortality worldwide. The most common inherited aortic diseases are thoracic aortic aneurysm and dissection, aortic coarctation, and arterial stenosis. These clinical entities can occur either as part of a syndrome or as isolated diseases. Over recent years, an increasing number of disease-causing genes affecting the aorta have been identified, leading to the demarcation of several genetic syndromes related to aortic disease.</p
Vertical-axis wind turbine aerodynamics
No full textThis chapter highlights the main aerodynamic phenomena and challenges of vertical-axis wind turbines. First, an introduction is provided on the VAWT history and (dis-)advantages. The basics of VAWT aerodynamics and the various rotor simplifications/representations are presented. Further, the state-of-the art aerodynamic modeling techniques, specifically for VAWTs, are discussed. Since VAWTs are inherently unsteady, the main unsteady phenomena that play a crucial role in VAWT aerodynamics are summarized. Finally, wake aerodynamics and the importance of airfoil design for VAWTs are highlighted.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Wind Energ
Entrepreneurial intention-action gap in family firms: bifurcation bias and the board of directors as an economizing mechanism
No full textThis study investigates under which conditions entrepreneurial intentions will transform into entrepreneurial actions in a family firm context. Although entrepreneurial intentions are often a good predictor for entrepreneurial activity, intentions will not always lead to the expected action. We aim to explain this intention-behavior gap in family firms by investigating the moderating role of bifurcation bias, defined as the de facto asymmetric treatment of family vs. nonfamily assets. Our results support the argument that bifurcation bias in family firms hinders the smooth transition of entrepreneurial intentions into entrepreneurial actions. Nevertheless, results also support the notion that the appointment of outside directors in the board could serve as an economizing mechanism for bifurcation biased family firms to transform entrepreneurial intentions into entrepreneurial actions.Schepers, J (corresponding author), Hasselt Univ, Res Ctr Entrepreneurship & Family Firms RCEF, Agoralaan,Bldg D, B-3590 Diepenbeek, Belgium.
[email protected]
The Augmented Movement Platform For Embodied Learning (AMPEL): development and reliability
No full textThere was an error in the affiliations of the co-authors Dr. Thomas Vervust and Prof. Peter Feys. Their correct affiliations are given in this correctionMoumdjian, L (corresponding author),
.Univ Ghent, IPEM Inst Psychoacoust & Elect Mus, Fac Arts & Philosophy, B-9000 Ghent, Belgium.
UMSC Hasselt, Pelt, Belgium.
Hasselt Univ, Fac Rehabil Sci, REVAL Rehabil Res Ctr, B-3500 Hasselt, Belgium.
[email protected]
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