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van den Broek, M.J. (author), De Tavernier, D. (author), Hulsman, Paul (author), van der Hoek, D.C. (author), Sanderse, Benjamin (author), van Wingerden, J.W. (author)Near-wake effects of wind turbine models using the free-vortex wake have been studied extensively, but there is a lack of validation for such predictions in the mid to far wake. This paper presents a novel validation study using three free-vortex wake models of increasing complexity: an actuator disc, an actuator disc with rotation, and a...journal article 2023
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Zhang, M. (author), Ganz, Andrea B. (author), Rohde, Susan (author), Lorenz, Linda (author), Rozemuller, Annemieke J.M. (author), Reinders, M.J.T. (author), Hulsman, M. (author), Hoozemans, Jeroen J.M. (author), Holstege, H. (author)INTRODUCTION: Neuropathological substrates associated with neurodegeneration occur in brains of the oldest old. How does this affect cognitive performance?. METHODS: The 100-plus Study is an ongoing longitudinal cohort study of centenarians who self-report to be cognitively healthy; post mortem brain donation is optional. In 85 centenarian...journal article 2023
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van der Lee, S.J. (author), De Rojas, I. (author), Holstege, H. (author), Hulsman, M. (author), Reinders, M.J.T. (author), Tesi, N. (author), van Rooij, Jeroen (author), Zhao, Y. (author), Zhang, X. (author)Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage<br/>genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found...journal article 2022
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Mol, Merel O. (author), van der Lee, S.J. (author), Hulsman, M. (author), Pijnenburg, Yolande A.L. (author), Scheltens, Phillip (author), Seelaar, Harro (author), van Swieten, John C. (author), Kaat, Laura Donker (author), Holstege, H. (author), van Rooij, Jeroen G.J. (author)Background: Many families with clinical early-onset Alzheimer’s disease (EOAD) remain genetically unexplained. A combination of genetic factors is not standardly investigated. In addition to monogenic causes, we evaluated the possible polygenic architecture in a large series of families, to assess if genetic testing of familial EOAD could be...journal article 2022
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Holstege, H. (author), Hulsman, M.J. (author), Charbonnier, Camille (author), Grenier-Boley, Banjamin (author), Quenez, Olivier (author), Grozeva, Detelina (author), van Rooij, Jeroen G.J. (author), Reinders, M.J.T. (author), van der Lee, S.J. (author)Alzheimer’s disease (AD), the leading cause of dementia, has an estimated<br/>heritability of approximately 70%1. The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rare variants2. Here, we compared the gene-based burden of rare damaging variants in exome...journal article 2022
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Zhang, M. (author), Ganz, Andrea B. (author), Rohde, Susan (author), Rozemuller, Annemieke J.M. (author), Bank, Netherlands Brain (author), Reinders, M.J.T. (author), Scheltens, Philip (author), Hulsman, M. (author), Hoozemans, Jeroen J.M. (author), Holstege, H. (author)Introduction: With increasing age, neuropathological substrates associated with Alzheimer's disease (AD) accumulate in brains of cognitively healthy individuals—are they resilient, or resistant to AD-associated neuropathologies?. Methods: In 85 centenarian brains, we correlated NIA (amyloid) stages, Braak (neurofibrillary tangle) stages, and...journal article 2022
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Hulsman, P. (author)Throughout the world, many people have been affected by water related issues in the past, some more extreme than others. In this context, hydrological models have often been used to gain more insight into the situation and to limit negative impacts as much as possible. There are many different types of hydrological models with each their...doctoral thesis 2021
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Tesi, N. (author), van der Lee, S.J. (author), Hulsman, M. (author), Holstege, H. (author), Reinders, M.J.T. (author)Genetic association studies are frequently used to study the genetic basis of numerous human phenotypes. However, the rapid interrogation of how well a certain genomic region associates across traits as well as the interpretation of genetic associations is often complex and requires the integration of multiple sources of annotation, which...journal article 2021
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Tesi, N. (author), van der Lee, S.J. (author), Hulsman, M. (author), Jansen, Iris E. (author), Stringa, N. (author), van Schoor, N.M. (author), Huisman, Martijn (author), Reinders, M.J.T. (author), Holstege, H. (author)Studying the genome of centenarians may give insights into the molecular mechanisms underlying extreme human longevity and the escape of age-related diseases. Here, we set out to construct polygenic risk scores (PRSs) for longevity and to investigate the functions of longevity-associated variants. Using a cohort of centenarians with...journal article 2021
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Tesi, N. (author), Hulsman, M. (author), van der Lee, S.J. (author), Jansen, Iris E. (author), Stringa, N. (author), van Schoor, Natasja M. (author), Scheltens, Philip (author), Reinders, M.J.T. (author), Holstege, H. (author)Human longevity is influenced by the genetic risk of age-related diseases. As Alzheimer’s disease (AD) represents a common condition at old age, an interplay between genetic factors affecting AD and longevity is expected. We explored this interplay by studying the prevalence of AD-associated single-nucleotide-polymorphisms (SNPs) in...journal article 2021
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Hulsman, P. (author), Savenije, Hubert (author), Hrachowitz, M. (author)Satellite observations can provide valuable information for a better understanding of hydrological processes and thus serve as valuable tools for model structure development and improvement. While model calibration and evaluation have in recent years started to make increasing use of spatial, mostly remotely sensed information, model...journal article 2021
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Hulsman, P. (author), Savenije, Hubert (author), Hrachowitz, M. (author)Study region: The study area is the river basin upstream of the Kariba dam located in the Zambezi River at the border of Zambia and Zimbabwe. Study focus: During the dry season of 2019 in Sub-Saharan Africa, extremely low water levels occurred in the Zambezi. According to news media, locals perceived this drought as the worst in several...journal article 2021
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Hulsman, P. (author), Hrachowitz, M. (author), Savenije, Hubert (author)In the Luangwa basin in Zambia, long-term total water storage variations were observed with Gravity Recovery and Climate Experiment, but not reproduced by a standard conceptual hydrological model that encapsulates our current understanding of the dominant regional hydrological processes. The objective of this study was to identify potential...journal article 2021
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Tesi, N. (author), Stringa, N. (author), Hadjigeorgiou, Georgios (author), Hulsman, M. (author), van Schoor, Natasja M. (author), Ruiz, A. (author), Jansen, Iris E. (author), Holstege, H. (author), van der Lee, S.J. (author)Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy...journal article 2021
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- van den Akker, E.B. (author), Makrodimitris, S. (author), Hulsman, M. (author), Brugman, Martijn H. (author), Nikolic, Tatjana (author), Bradley, Ted (author), Waisfisz, Quinten (author), Baas, Frank (author), Reinders, M.J.T. (author), Holstege, H. (author) journal article 2020
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Hulsman, P. (author), Winsemius, H.C. (author), Michailovsky, Claire I. (author), Savenije, Hubert (author), Hrachowitz, M. (author)Limited availability of ground measurements in the vast majority of river basins world-wide increases the value of alternative data sources such as satellite observations in hydrological modelling. This study investigates the potential of using remotely sensed river water levels, i.e. altimetry observations, from multiple satellite missions...journal article 2020
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Tesi, N. (author), van der Lee, S.J. (author), Hulsman, M. (author), Jansen, Iris E. (author), Stringa, N. (author), van Schoor, N.M. (author), Scheltens, Philip (author), van der Flier, Wiesje M. (author), Huisman, Martijn (author), Reinders, M.J.T. (author), Holstege, H. (author)Developing Alzheimer’s disease (AD) is influenced by multiple genetic variants that are involved in five major AD-pathways. Per individual, these pathways may differentially contribute to the modification of the AD-risk. The pathways involved in the resilience against AD have thus far been poorly addressed. Here, we investigated to what...journal article 2020
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Wong, Tsz Hang (author), van der Lee, S.J. (author), van Rooij, Jeroen G.J. (author), Meeter, Lieke H.H. (author), Frick, Petra (author), Melhem, Shamiram (author), Seelaar, Harro (author), Ikram, M. Arfan (author), Holstege, H. (author), Hulsman, M. (author)Next-generation sequencing has contributed to our understanding of the genetics of Alzheimer's disease (AD) and has explained a substantial part of the missing heritability of familial AD. We sequenced 19 exomes from 8 Dutch families with a high AD burden and identified EIF2AK3, encoding for protein kinase RNA-like endoplasmic reticulum...journal article 2019
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van der Lee, S.J. (author), Conway, Olivia J. (author), Hansen, Iris (author), Carrasquillo, Minerva M. (author), Kleineidam, Luca (author), van den Akker, E.B. (author), Hulsman, M. (author), Tesi, N. (author), Reinders, M.J.T. (author)The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer’s disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven...journal article 2019
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Tesi, N. (author), van der Lee, S.J. (author), Hulsman, M. (author), Jansen, Iris E. (author), Stringa, N. (author), van Schoor, N.M. (author), Meijers-Heijboer, Hanne (author), Reinders, M.J.T. (author), Holstege, H. (author)The detection of genetic loci associated with Alzheimer’s disease (AD) requires large numbers of cases and controls because variant effect sizes are mostly small. We hypothesized that variant effect sizes should increase when individuals who represent the extreme ends of a disease spectrum are considered, as their genomes are assumed to be...journal article 2019
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