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343 results on '"P. A. van der Zwaag"'

5. ATP6V0C variants impair V-ATPase function causing a neurodevelopmental disorder often associated with epilepsy.

Author

Mattison, Kari, Tossing, Gilles, Mulroe, Fred, Simmons, Callum, Butler, Kameryn, Schreiber, Alison, Alsadah, Adnan, Neilson, Derek, Naess, Karin, Wedell, Anna, Wredenberg, Anna, Sorlin, Arthur, McCann, Emma, Burghel, George, Menendez, Beatriz, Hoganson, George, Botto, Lorenzo, Filloux, Francis, Aledo-Serrano, Ángel, Gil-Nagel, Antonio, Tatton-Brown, Katrina, Verbeek, Nienke, van der Zwaag, Bert, Aleck, Kyrieckos, Fazenbaker, Andrew, Balciuniene, Jorune, Dubbs, Holly, Marsh, Eric, Garber, Kathryn, Ek, Jakob, Duno, Morten, Hoei-Hansen, Christina, Deardorff, Matthew, Raca, Gordana, Quindipan, Catherine, van Hirtum-Das, Michele, Breckpot, Jeroen, Hammer, Trine, Møller, Rikke, Whitney, Andrea, Douglas, Andrew, Kharbanda, Mira, Brunetti-Pierri, Nicola, Morleo, Manuela, Nigro, Vincenzo, May, Halie, Tao, James, Sherr, Elliot, Dobyns, William, Baines, Richard, Warwicker, Jim, Parker, J, Banka, Siddharth, Campeau, Philippe, Escayg, Andrew, and Argilli, Emanuela

Subjects
ATP6V0C, V-ATPase, VMA3, epilepsy genetics, neurodevelopmental disorders, Humans, Vacuolar Proton-Translocating ATPases, Saccharomyces cerevisiae, Epilepsy, Adenosine Triphosphate
Abstract

The vacuolar H+-ATPase is an enzymatic complex that functions in an ATP-dependent manner to pump protons across membranes and acidify organelles, thereby creating the proton/pH gradient required for membrane trafficking by several different types of transporters. We describe heterozygous point variants in ATP6V0C, encoding the c-subunit in the membrane bound integral domain of the vacuolar H+-ATPase, in 27 patients with neurodevelopmental abnormalities with or without epilepsy. Corpus callosum hypoplasia and cardiac abnormalities were also present in some patients. In silico modelling suggested that the patient variants interfere with the interactions between the ATP6V0C and ATP6V0A subunits during ATP hydrolysis. Consistent with decreased vacuolar H+-ATPase activity, functional analyses conducted in Saccharomyces cerevisiae revealed reduced LysoSensor fluorescence and reduced growth in media containing varying concentrations of CaCl2. Knockdown of ATP6V0C in Drosophila resulted in increased duration of seizure-like behaviour, and the expression of selected patient variants in Caenorhabditis elegans led to reduced growth, motor dysfunction and reduced lifespan. In summary, this study establishes ATP6V0C as an important disease gene, describes the clinical features of the associated neurodevelopmental disorder and provides insight into disease mechanisms.

Published
2023

7. KidneyNetwork: using kidney-derived gene expression data to predict and prioritize novel genes involved in kidney disease

Author

Boulogne, Floranne, Claus, Laura R., Wiersma, Henry, Oelen, Roy, Schukking, Floor, de Klein, Niek, Li, Shuang, Westra, Harm-Jan, van der Zwaag, Bert, van Reekum, Franka, Sierks, Dana, Schönauer, Ria, Li, Zhigui, Bijlsma, Emilia K., Bos, Willem Jan W., Halbritter, Jan, Knoers, Nine V. A. M., Besse, Whitney, Deelen, Patrick, Franke, Lude, and van Eerde, Albertien M.

Published
2023
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11. Effect of particle contact on the electrical performance of NTC-epoxy composite thermistors

Author

Deutz, Daniella B., van der Zwaag, Sybrand, and Groen, Pim

Subjects
Physics - Applied Physics, Condensed Matter - Materials Science
Abstract

As demand rises for flexible electronics, traditionally prepared sintered ceramic sensors must be transformed into fully new sensor materials that can bend and flex in use and integration. Negative temperature coefficient of resistance (NTC) ceramic thermistors are preferred temperature sensors for their high accuracy and excellent stability, yet their high stiffness and high temperature fabrication process limits their use in flexible electronics. Here, a low stiffness thermistor based on NTC ceramic particles of micron size embedded in an epoxy polymer matrix is reported. The effect of particle-to-particle contact on electrical performance is studied by arranging the NTC particles in the composite films in one of three ways: 1) Low particle contact, 2) Improved particle contact perpendicular to the electrodes and 3) dispersing high particle contact agglomerated clumps throughout the polymer. At 50 vol.\% of agglomerated NTC particles, the composite films exhibit a $\beta$-value of 2069 K and a resistivity, $\rho$, of 3.3$\cdot 10^5$ $\Omega$m, 4 orders of magnitude lower than a randomly dispersed composite at identical volume. A quantitative analysis shows that attaining a predominantly parallel connectivity of the NTC particles and polymer is a key parameter in determining the electrical performance of the composite film., Comment: Pim Groen aka W.A. Groen, 3 figures, 15 pages double spaced

Published
2019

15. Partial Loss of USP9X Function Leads to a Male Neurodevelopmental and Behavioral Disorder Converging on Transforming Growth Factor β Signaling.

Author

Johnson, Brett V, Kumar, Raman, Oishi, Sabrina, Alexander, Suzy, Kasherman, Maria, Vega, Michelle Sanchez, Ivancevic, Atma, Gardner, Alison, Domingo, Deepti, Corbett, Mark, Parnell, Euan, Yoon, Sehyoun, Oh, Tracey, Lines, Matthew, Lefroy, Henrietta, Kini, Usha, Van Allen, Margot, Grønborg, Sabine, Mercier, Sandra, Küry, Sébastien, Bézieau, Stéphane, Pasquier, Laurent, Raynaud, Martine, Afenjar, Alexandra, Billette de Villemeur, Thierry, Keren, Boris, Désir, Julie, Van Maldergem, Lionel, Marangoni, Martina, Dikow, Nicola, Koolen, David A, VanHasselt, Peter M, Weiss, Marjan, Zwijnenburg, Petra, Sa, Joaquim, Reis, Claudia Falcao, López-Otín, Carlos, Santiago-Fernández, Olaya, Fernández-Jaén, Alberto, Rauch, Anita, Steindl, Katharina, Joset, Pascal, Goldstein, Amy, Madan-Khetarpal, Suneeta, Infante, Elena, Zackai, Elaine, Mcdougall, Carey, Narayanan, Vinodh, Ramsey, Keri, Mercimek-Andrews, Saadet, Pena, Loren, Shashi, Vandana, Undiagnosed Diseases Network, Schoch, Kelly, Sullivan, Jennifer A, Pinto E Vairo, Filippo, Pichurin, Pavel N, Ewing, Sarah A, Barnett, Sarah S, Klee, Eric W, Perry, M Scott, Koenig, Mary Kay, Keegan, Catherine E, Schuette, Jane L, Asher, Stephanie, Perilla-Young, Yezmin, Smith, Laurie D, Rosenfeld, Jill A, Bhoj, Elizabeth, Kaplan, Paige, Li, Dong, Oegema, Renske, van Binsbergen, Ellen, van der Zwaag, Bert, Smeland, Marie Falkenberg, Cutcutache, Ioana, Page, Matthew, Armstrong, Martin, Lin, Angela E, Steeves, Marcie A, Hollander, Nicolette den, Hoffer, Mariëtte JV, Reijnders, Margot RF, Demirdas, Serwet, Koboldt, Daniel C, Bartholomew, Dennis, Mosher, Theresa Mihalic, Hickey, Scott E, Shieh, Christine, Sanchez-Lara, Pedro A, Graham, John M, Tezcan, Kamer, Schaefer, GB, Danylchuk, Noelle R, Asamoah, Alexander, Jackson, Kelly E, Yachelevich, Naomi, Au, Margaret, Pérez-Jurado, Luis A, and Kleefstra, Tjitske

Subjects
Undiagnosed Diseases Network, Animals, Humans, Mice, Ubiquitin Thiolesterase, Transforming Growth Factor beta, Developmental Disabilities, Signal Transduction, Phenotype, Female, Male, Haploinsufficiency, Intellectual Disability, Brain malformation, Deubiquitylating enzyme, Hippocampus, Neurodevelopmental disorder, TGFβ, USP9X, Congenital Structural Anomalies, Genetics, Neurosciences, Pediatric, Mental Health, Behavioral and Social Science, Brain Disorders, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Neurological, TGF beta, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

BackgroundThe X-chromosome gene USP9X encodes a deubiquitylating enzyme that has been associated with neurodevelopmental disorders primarily in female subjects. USP9X escapes X inactivation, and in female subjects de novo heterozygous copy number loss or truncating mutations cause haploinsufficiency culminating in a recognizable syndrome with intellectual disability and signature brain and congenital abnormalities. In contrast, the involvement of USP9X in male neurodevelopmental disorders remains tentative.MethodsWe used clinically recommended guidelines to collect and interrogate the pathogenicity of 44 USP9X variants associated with neurodevelopmental disorders in males. Functional studies in patient-derived cell lines and mice were used to determine mechanisms of pathology.ResultsTwelve missense variants showed strong evidence of pathogenicity. We define a characteristic phenotype of the central nervous system (white matter disturbances, thin corpus callosum, and widened ventricles); global delay with significant alteration of speech, language, and behavior; hypotonia; joint hypermobility; visual system defects; and other common congenital and dysmorphic features. Comparison of in silico and phenotypical features align additional variants of unknown significance with likely pathogenicity. In support of partial loss-of-function mechanisms, using patient-derived cell lines, we show loss of only specific USP9X substrates that regulate neurodevelopmental signaling pathways and a united defect in transforming growth factor β signaling. In addition, we find correlates of the male phenotype in Usp9x brain-specific knockout mice, and further resolve loss of hippocampal-dependent learning and memory.ConclusionsOur data demonstrate the involvement of USP9X variants in a distinctive neurodevelopmental and behavioral syndrome in male subjects and identify plausible mechanisms of pathogenesis centered on disrupted transforming growth factor β signaling and hippocampal function.

Published
2020

18. Rationale and design of the PHOspholamban RElated CArdiomyopathy intervention STudy (i-PHORECAST)

Author

te Rijdt, W. P., Hoorntje, E. T., de Brouwer, R., Oomen, A., Amin, A., van der Heijden, J. F., Karper, J. C., Westenbrink, B. D., Silljé, H. H. W., te Riele, A. S. J. M., Wiesfeld, A. C. P., van Gelder, I. C., Willems, T. P., van der Zwaag, P. A., van Tintelen, J. P., Hillege, J. H., Tan, H. L., van Veldhuisen, D. J., Asselbergs, F. W., de Boer, R. A., Wilde, A. A. M., and van den Berg, M. P.

Published
2022
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24. Enhanced capture of healthcare-related harms and injuries in the 11th revision of the International Classification of Diseases (ICD-11)

Author

Southern, Danielle A, Pincus, Harold A, Romano, Patrick S, Burnand, Bernard, Harrison, James, Forster, Alan J, Moskal, Lori, Quan, Hude, Droesler, Saskia E, Sundararajan, Vijaya, Colin, Cyrille, Gurevich, Yana, Brien, Susan E, Kostanjsek, Nenad, üstün, Bedirhan, Ghali, William A, Ghali, William, Pincus, Harold, Allen, Marilyn, Brien, Susan, Drösler, Saskia, Forster, Alan, Harrison, James E, Munier, William, Pickett, Donna, Romano, Patrick, Spaeth-Rublee, Brigitta, Southern, Danielle, Van der Zwaag, David, Chute, Christopher, Hogan, Eileen, and Cox, Ginger

Subjects
8.1 Organisation and delivery of services, Health and social care services research, Generic health relevance, Good Health and Well Being, Humans, International Classification of Diseases, Patient Safety, Quality Indicators, Health Care, World Health Organization, quality indicators, patient safety, World Health Organization ICD-11 Revision Topic Advisory Group on Quality & Safety, Medical and Health Sciences, Psychology and Cognitive Sciences, Health Policy & Services
Abstract

The World Health Organization (WHO) plans to submit the 11th revision of the International Classification of Diseases (ICD) to the World Health Assembly in 2018. The WHO is working toward a revised classification system that has an enhanced ability to capture health concepts in a manner that reflects current scientific evidence and that is compatible with contemporary information systems. In this paper, we present recommendations made to the WHO by the ICD revision's Quality and Safety Topic Advisory Group (Q&S TAG) for a new conceptual approach to capturing healthcare-related harms and injuries in ICD-coded data. The Q&S TAG has grouped causes of healthcare-related harm and injuries into four categories that relate to the source of the event: (a) medications and substances, (b) procedures, (c) devices and (d) other aspects of care. Under the proposed multiple coding approach, one of these sources of harm must be coded as part of a cluster of three codes to depict, respectively, a healthcare activity as a 'source' of harm, a 'mode or mechanism' of harm and a consequence of the event summarized by these codes (i.e. injury or harm). Use of this framework depends on the implementation of a new and potentially powerful code-clustering mechanism in ICD-11. This new framework for coding healthcare-related harm has great potential to improve the clinical detail of adverse event descriptions, and the overall quality of coded health data.

Published
2016

25. Cyclic quenching treatment doubles the Charpy V-notch impact energy of a 2.3 GPa maraging steel.

Author

Zhou, Xinlei, Jia, Chunni, Mi, Peng, Zhang, Honglin, Yan, Wei, Wang, Wei, Sun, Mingyue, van der Zwaag, Sybrand, and Rong, Lijian

Subjects
MARTENSITE, AUSTENITE, IMPACT strength, HETEROGENEITY
Abstract

• Impact energy for a 2.3 GPa maraging steel has been improved from 9 to 20 J by Cyclic quenching treatment (CQT), even without strength sacrifice. • CQT has led to the localized Ni partitioning, resulting in the formation of such three substructures as Ni-rich austenite particles, Ni-rich martensite laths and Ni-poor martensite laths. • The improvement of mechanical properties is attributed to the refinement and increased chemical heterogeneity of the martensitic substructure, as well as the TRIP effect facilitated by small austenite grains. A cyclic quenching treatment (CQT) succeeded in turning a 2.3 GPa maraging steel with a Charpy impact energy of 9 J into a new grade with the same strength but a Charpy impact energy of 20 J upon 4 cyclic treatments. The improvement of mechanical properties is attributed to the refinement and increased chemical heterogeneity of the martensitic substructure, rather than the refinement of prior austenite grain (PAG), as well as the Transformation-Induced Plasticity (TRIP) effect facilitated by small austenite grains. The role of local segregation of Ni during CQT in the formation of Ni-rich austenite grains, Ni-rich martensite laths and Ni-poor martensite laths, was investigated and verified by DICTRA simulations. This study highlights the important influence of Ni partitioning behavior during CQT, providing insights into microstructural evolution and mechanical properties. [Display omitted] [ABSTRACT FROM AUTHOR]

Published
2025
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33. Charting the complete elastic properties of inorganic crystalline compounds.

Author

de Jong, Maarten, Chen, Wei, Angsten, Thomas, Jain, Anubhav, Notestine, Randy, Gamst, Anthony, Sluiter, Marcel, Krishna Ande, Chaitanya, van der Zwaag, Sybrand, Plata, Jose J, Toher, Cormac, Curtarolo, Stefano, Ceder, Gerbrand, Persson, Kristin A, and Asta, Mark

Abstract

The elastic constant tensor of an inorganic compound provides a complete description of the response of the material to external stresses in the elastic limit. It thus provides fundamental insight into the nature of the bonding in the material, and it is known to correlate with many mechanical properties. Despite the importance of the elastic constant tensor, it has been measured for a very small fraction of all known inorganic compounds, a situation that limits the ability of materials scientists to develop new materials with targeted mechanical responses. To address this deficiency, we present here the largest database of calculated elastic properties for inorganic compounds to date. The database currently contains full elastic information for 1,181 inorganic compounds, and this number is growing steadily. The methods used to develop the database are described, as are results of tests that establish the accuracy of the data. In addition, we document the database format and describe the different ways it can be accessed and analyzed in efforts related to materials discovery and design.

Published
2015

34. ECG-only explainable deep learning algorithm predicts the risk for malignant ventricular arrhythmia in phospholamban cardiomyopathy.

Author

van de Leur, Rutger R., de Brouwer, Remco, Bleijendaal, Hidde, Verstraelen, Tom E., Mahmoud, Belend, Perez-Matos, Ana, Dickhoff, Cathelijne, Schoonderwoerd, Bas A., Germans, Tjeerd, Houweling, Arjan, van der Zwaag, Paul A., Cox, Moniek G.P.J., Peter van Tintelen, J., te Riele, Anneline S.J.M., van den Berg, Maarten P., Wilde, Arthur A.M., Doevendans, Pieter A., de Boer, Rudolf A., and van Es, René

Abstract

Phospholamban (PLN) p.(Arg14del) variant carriers are at risk for development of malignant ventricular arrhythmia (MVA). Accurate risk stratification allows timely implantation of intracardiac defibrillators and is currently performed with a multimodality prediction model. This study aimed to investigate whether an explainable deep learning–based approach allows risk prediction with only electrocardiogram (ECG) data. A total of 679 PLN p.(Arg14del) carriers without MVA at baseline were identified. A deep learning–based variational auto-encoder, trained on 1.1 million ECGs, was used to convert the 12-lead baseline ECG into its FactorECG, a compressed version of the ECG that summarizes it into 32 explainable factors. Prediction models were developed by Cox regression. The deep learning–based ECG-only approach was able to predict MVA with a C statistic of 0.79 (95% CI, 0.76–0.83), comparable to the current prediction model (C statistic, 0.83 [95% CI, 0.79–0.88]; P =.054) and outperforming a model based on conventional ECG parameters (low-voltage ECG and negative T waves; C statistic, 0.65 [95% CI, 0.58–0.73]; P <.001). Clinical simulations showed that a 2-step approach, with ECG-only screening followed by a full workup, resulted in 60% less additional diagnostics while outperforming the multimodal prediction model in all patients. A visualization tool was created to provide interactive visualizations (https://pln.ecgx.ai). Our deep learning–based algorithm based on ECG data only accurately predicts the occurrence of MVA in PLN p.(Arg14del) carriers, enabling more efficient stratification of patients who need additional diagnostic testing and follow-up. [Display omitted] [ABSTRACT FROM AUTHOR]

Published
2024
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35. Mechanistic Behavior of Single-Pass Instruction Sequences

Author

Bergstra, Jan A. and van der Zwaag, Mark B.

Subjects
Computer Science - Programming Languages, Computer Science - Logic in Computer Science, D.1.4, F.3.2, F.3.3
Abstract

Earlier work on program and thread algebra detailed the functional, observable behavior of programs under execution. In this article we add the modeling of unobservable, mechanistic processing, in particular processing due to jump instructions. We model mechanistic processing preceding some further behavior as a delay of that behavior; we borrow a unary delay operator from discrete time process algebra. We define a mechanistic improvement ordering on threads and observe that some threads do not have an optimal implementation., Comment: 12 pages

Published
2008

36. Tuplix Calculus Specifications of Financial Transfer Networks

Author

Bergstra, J. A., Trenite, S. Nolst, and van der Zwaag, M. B.

Subjects
Computer Science - Computational Engineering, Finance, and Science, Computer Science - Logic in Computer Science
Abstract

We study the application of Tuplix Calculus in modular financial budget design. We formalize organizational structure using financial transfer networks. We consider the notion of flux of money over a network, and a way to enforce the matching of influx and outflux for parts of a network. We exploit so-called signed attribute notation to make internal streams visible through encapsulations. Finally, we propose a Tuplix Calculus construct for the definition of data functions.

Published
2008

37. Towards a formalization of budgets

Author

Bergstra, Jan A., Trenité, Sanne Nolst, and van der Zwaag, Mark B.

Subjects
Computer Science - Logic in Computer Science
Abstract

We go into the need for, and the requirements on, a formal theory of budgets. We present a simple algebraic theory of rational budgets, i.e., budgets in which amounts of money are specified by functions on the rational numbers. This theory is based on the tuplix calculus. We go into the importance of using totalized models for the rational numbers. We present a case study on the educational budget of a university department offering master programs.

Published
2008

38. Tuplix Calculus

Author

Bergstra, J. A., Ponse, A., and van der Zwaag, M. B.

Subjects
Computer Science - Logic in Computer Science, Computer Science - Computational Engineering, Finance, and Science
Abstract

We introduce a calculus for tuplices, which are expressions that generalize matrices and vectors. Tuplices have an underlying data type for quantities that are taken from a zero-totalized field. We start with the core tuplix calculus CTC for entries and tests, which are combined using conjunctive composition. We define a standard model and prove that CTC is relatively complete with respect to it. The core calculus is extended with operators for choice, information hiding, scalar multiplication, clearing and encapsulation. We provide two examples of applications; one on incremental financial budgeting, and one on modular financial budget design., Comment: 22 pages

Published
2007

42. Combining Nickel- and Zinc-Porphyrin Sites via Covalent Organic Frameworks for Electrochemical CO2Reduction

Author

Veldhuizen, Hugo, Abdinejad, Maryam, Gilissen, Pieter J., Albertsma, Jelco, Burdyny, Thomas, Tichelaar, Frans D., van der Zwaag, Sybrand, and van der Veen, Monique A.

Abstract

Covalent organic frameworks (COFs) are ideal platforms to spatially control the integration of multiple molecular motifs throughout a single nanoporous framework. Despite this design flexibility, COFs are typically synthesized using only two monomers. One bears the functional motif for the envisioned application, while the other is used as an inert connecting building block. Integrating more than one functional motif extends the functionality of COFs immensely, which is particularly useful for multistep reactions such as electrochemical reduction of CO2. In this systematic study, we synthesized five Ni(II)- and Zn(II)-porphyrin-based COFs, including two pure component COFs (Ni100and Zn100) and three mixed Ni/Zn-COFs (Ni75/Zn25, Ni50/Zn50, and Ni25/Zn75). Among these, the Ni50/Zn50-COF exhibited the highest catalytic performance for the electroreduction of CO2to CO and formate at −0.6 V vs RHE, as was observed in an H-cell. The catalytic performance of the COF catalysts was further extended to a zero-gap membrane electrode assembly (MEA) operation where, utilizing Ni50/Zn50, CH4was detected along with CO and formate at a high current density of 150 mA cm–2. In contrast, under these conditions predominantly H2and CO were detected at Ni100and Zn100respectively, indicating a clear synergistic effect between the Ni- and Zn-porphyrin units.

Published
2024
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46. Author Correction: The phospholamban p.(Arg14del) pathogenic variant leads to cardiomyopathy with heart failure and is unresponsive to standard heart failure therapy

Author

Eijgenraam, Tim R., Boukens, Bastiaan J., Boogerd, Cornelis J., Schouten, E. Marloes, van de Kolk, Cees W. A., Stege, Nienke M., te Rijdt, Wouter P., Hoorntje, Edgar T., van der Zwaag, Paul A., van Rooij, Eva, van Tintelen, J. Peter, van den Berg, Maarten P., van der Meer, Peter, van der Velden, Jolanda, Silljé, Herman H. W., and de Boer, Rudolf A.

Published
2020
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47. The phospholamban p.(Arg14del) pathogenic variant leads to cardiomyopathy with heart failure and is unresponsive to standard heart failure therapy

Author

Eijgenraam, Tim R., Boukens, Bastiaan J., Boogerd, Cornelis J., Schouten, E. Marloes, van de Kolk, Cees W. A., Stege, Nienke M., te Rijdt, Wouter P., Hoorntje, Edgar T., van der Zwaag, Paul A., van Rooij, Eva, van Tintelen, J. Peter, van den Berg, Maarten P., van der Meer, Peter, van der Velden, Jolanda, Silljé, Herman H. W., and de Boer, Rudolf A.

Published
2020
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50. Lack of evidence for a causal role of CALR3 in monogenic cardiomyopathy

Author

Verhagen, Judith M. A., Veldman, Job H., van der Zwaag, Paul A., von der Thüsen, Jan H., Brosens, Erwin, Christiaans, Imke, Dooijes, Dennis, Helderman-van den Enden, Apollonia T. J. M., Lekanne Deprez, Ronald H., Michels, Michelle, van Mil, Anneke M., Oldenburg, Rogier A., van der Smagt, Jasper J., van den Wijngaard, Arthur, Wessels, Marja W., Hofstra, Robert M. W., van Slegtenhorst, Marjon A., Jongbloed, Jan D. H., and van de Laar, Ingrid M. B. H.

Published
2018
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