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Peter molenaar

Susanne N Gröbner, Barbara C Worst, Joachim Weischenfeldt, Ivo Buchhalter, Kortine Kleinheinz, Vasilisa A Rudneva, Pascal D Johann, Gnana Prakash Balasubramanian, Maia Segura-Wang, Sebastian Brabetz, Sebastian Bender, Barbara Hutter, Dominik Sturm, Elke Pfaff, Daniel Hübschmann, Gideon Zipprich, Michael Heinold, Jürgen Eils, Christian Lawerenz, Serap Erkek, Sander Lambo, Sebastian Waszak, Claudia Blattmann, Arndt Borkhardt, Michaela Kuhlen, Angelika Eggert, Simone Fulda, Manfred Gessler, Jenny Wegert, Roland Kappler, Daniel Baumhoer, Stefan Burdach, Renate Kirschner-Schwabe, Udo Kontny, Andreas E Kulozik, Dietmar Lohmann, Simone Hettmer, Cornelia Eckert, Stefan Bielack, Michaela Nathrath, Charlotte Niemeyer, Günther H Richter, Johannes Schulte, Reiner Siebert, Frank Westermann, Jan J Molenaar, Gilles Vassal, Hendrik Witt, Birgit Burkhardt, Christian P Kratz, Olaf Witt, Cornelis M van Tilburg, Christof M Kramm, Gudrun Fleischhack, Uta Dirksen, Stefan Rutkowski, Michael Frühwald, Katja von Hoff, Stephan Wolf, Thomas Klingebiel, Ewa Koscielniak, Pablo Landgraf, Jan Koster, Adam C Resnick, Jinghui Zhang, Yanling Liu, Xin Zhou, Angela J Waanders, Danny A Zwijnenburg, Pichai Raman, Benedikt Brors, Ursula D Weber, Paul A Northcott, Kristian W Pajtler, Marcel Kool, Rosario M Piro, Jan O Korbel, Matthias Schlesner, Roland Eils, David T W Jones, Peter Lichter, Lukas Chavez, Marc Zapatka, Stefan M Pfister
Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers...
February 28, 2018: Nature
Camiel L M de Roij van Zuijdewijn, Isabelle Chapdelaine, Menso J Nubé, Peter J Blankestijn, Michiel L Bots, Constantijn J A M Konings, Ton K Kremer Hovinga, Femke M Molenaar, Neelke C van der Weerd, Muriel P C Grooteman
Background. Available evidence suggests a reduced mortality risk for patients treated with high-volume postdilution hemodiafiltration (HDF) when compared with hemodialysis (HD) patients. As the magnitude of the convection volume depends on treatment-related factors rather than patient-related characteristics, we prospectively investigated whether a high convection volume (defined as ≥22 L/session) is feasible in the majority of patients (>75%). Methods. A multicenter study was performed in adult prevalent dialysis patients...
December 2017: Clinical Kidney Journal
Bob W J Pirok, Stef R A Molenaar, Rianne E van Outersterp, Peter J Schoenmakers
Computer-aided method-development programs require accurate models to describe retention and to make predictions based on a limited number of scouting gradients. The performance of five different retention models for hydrophilic-interaction chromatography (HILIC) is assessed for a wide range of analytes. Gradient-elution equations are presented for each model, using Simpson's Rule to approximate the integral in case no exact solution exists. For most compound classes the adsorption model, i.e. a linear relation between the logarithm of the retention factor and the logarithm of the composition, is found to provide the most robust performance...
December 29, 2017: Journal of Chromatography. A
Chang Liu, Peter C M Molenaar, Jenae M Neiderhiser
By taking advantage of the natural variation in genetic relatedness among identical (monozygotic: MZ) and fraternal (dizygotic: DZ) twins, twin studies are able to estimate genetic and environmental contributions to complex human behaviors. Recently concerns have been raised about the accuracy of twin studies in light of findings of genetic and epigenetic changes in twins. One of the concerns raised is that MZ twins are not 100% genetically and epigenetically similar because they show variations in their genomes and epigenomes leading to inaccurate estimates of heritability...
November 2, 2017: Behavior Genetics
Abhishek Saxena, Jo Stevens, Hakan Cetin, Inga Koneczny, Richard Webster, Konstantinos Lazaridis, Socrates Tzartos, Kathleen Vrolix, Gisela Nogales-Gadea, Barbie Machiels, Peter C Molenaar, Jan Damoiseaux, Marc H De Baets, Katja Simon-Keller, Alexander Marx, Angela Vincent, Mario Losen, Pilar Martinez-Martinez
We report here the sequence and functional characterization of a recombinantly expressed autoantibody (mAb 131) previously isolated from a myasthenia gravis patient by immortalization of thymic B cells using Epstein-Barr virus and TLR9 activation. The antibody is characterized by a high degree of somatic mutations as well as a 6 amino acid insertion within the VHCDR2. The recombinant mAb 131 is specific for the γ-subunit of the fetal AChR to which it bound with sub-nanomolar apparent affinity, and detected the presence of fetal AChR on a number of rhabdomyosarcoma cell lines...
October 31, 2017: Scientific Reports
Shenghua Zong, Carolin Hoffmann, Marina Mané-Damas, Peter Molenaar, Mario Losen, Pilar Martinez-Martinez
Autoimmune diseases are affecting around 7.6-9.4% of the general population. A number of central nervous system disorders, including encephalitis and severe psychiatric disorders, have been demonstrated to associate with specific neuronal surface autoantibodies (NSAbs). It has become clear that specific autoantibodies targeting neuronal surface antigens and ion channels could cause severe mental disturbances. A number of studies have focused or are currently investigating the presence of autoantibodies in specific mental conditions such as schizophrenia and bipolar disorders...
2017: Frontiers in Immunology
Tim van Groningen, Jan Koster, Linda J Valentijn, Danny A Zwijnenburg, Nurdan Akogul, Nancy E Hasselt, Marloes Broekmans, Franciska Haneveld, Natalia E Nowakowska, Johannes Bras, Carel J M van Noesel, Aldo Jongejan, Antoine H van Kampen, Linda Koster, Frank Baas, Lianne van Dijk-Kerkhoven, Margriet Huizer-Smit, Maria C Lecca, Alvin Chan, Arjan Lakeman, Piet Molenaar, Richard Volckmann, Ellen M Westerhout, Mohamed Hamdi, Peter G van Sluis, Marli E Ebus, Jan J Molenaar, Godelieve A Tytgat, Bart A Westerman, Johan van Nes, Rogier Versteeg
Neuroblastoma and other pediatric tumors show a paucity of gene mutations, which has sparked an interest in their epigenetic regulation. Several tumor types include phenotypically divergent cells, resembling cells from different lineage development stages. It has been proposed that super-enhancer-associated transcription factor (TF) networks underlie lineage identity, but the role of these enhancers in intratumoral heterogeneity is unknown. Here we show that most neuroblastomas include two types of tumor cells with divergent gene expression profiles...
August 2017: Nature Genetics
Remco J Molenaar, Robert Js Coelen, Mohammed Khurshed, Eva Roos, Matthan Wa Caan, Myra E van Linde, Mathilde Kouwenhoven, Jos Am Bramer, Judith Vmg Bovée, Ron A Mathôt, Heinz-Josef Klümpen, Hanneke Wm van Laarhoven, Cornelis Jf van Noorden, W Peter Vandertop, Hans Gelderblom, Thomas M van Gulik, Johanna W Wilmink
INTRODUCTION: High-grade chondrosarcoma, high-grade glioma and intrahepatic cholangiocarcinoma are aggressive types of cancer with a dismal outcome. This is due to the lack of effective treatment options, emphasising the need for novel therapies. Mutations in the genes IDH1 and IDH2 (isocitrate dehydrogenase 1 and 2) occur in 60% of chondrosarcoma, 80% of WHO grade II-IV glioma and 20% of intrahepatic cholangiocarcinoma. IDH1/2-mutated cancer cells produce the oncometabolite D-2-hydroxyglutarate (D-2HG) and are metabolically vulnerable to treatment with the oral antidiabetic metformin and the oral antimalarial drug chloroquine...
June 10, 2017: BMJ Open
Weilan Mo, Martin C Michel, Xiang Wen Lee, Alberto J Kaumann, Peter Molenaar
BACKGROUND AND PURPOSE: Mirabegron has been classified as a β3 -adrenoceptor agonist approved for overactive bladder syndrome. We investigated possible cardiac effects of mirabegron in the absence or presence of β-adrenoceptor subtype antagonists. In view of its phenylethanolamine structure, we investigated whether mirabegron has indirect sympathomimetic activity by using neuronal uptake blockers. EXPERIMENTAL APPROACH: Right atrial trabeculae, from non-failing hearts, were paced and contractile force measured at 37°C...
August 2017: British Journal of Pharmacology
Mario Losen, Aran F Labrijn, Vivianne H van Kranen-Mastenbroek, Maarten L Janmaat, Krista G Haanstra, Frank J Beurskens, Tom Vink, Margreet Jonker, Bert A 't Hart, Marina Mané-Damas, Peter C Molenaar, Pilar Martinez-Martinez, Eline van der Esch, Janine Schuurman, Marc H de Baets, Paul W H I Parren
Autoantibodies against ion channels are the cause of numerous neurologic autoimmune disorders. Frequently, such pathogenic autoantibodies have a restricted epitope-specificity. In such cases, competing antibody formats devoid of pathogenic effector functions (blocker antibodies) have the potential to treat disease by displacing autoantibodies from their target. Here, we have used a model of the neuromuscular autoimmune disease myasthenia gravis in rhesus monkeys (Macaca mulatta) to test the therapeutic potential of a new blocker antibody: MG was induced by passive transfer of pathogenic acetylcholine receptor-specific monoclonal antibody IgG1-637...
April 20, 2017: Scientific Reports
Thijs de Rooij, Jony van Hilst, Jantien A Vogel, Hjalmar C van Santvoort, Marieke T de Boer, Djamila Boerma, Peter B van den Boezem, Bert A Bonsing, Koop Bosscha, Peter-Paul Coene, Freek Daams, Ronald M van Dam, Marcel G Dijkgraaf, Casper H van Eijck, Sebastiaan Festen, Michael F Gerhards, Bas Groot Koerkamp, Jeroen Hagendoorn, Erwin van der Harst, Ignace H de Hingh, Cees H Dejong, Geert Kazemier, Joost Klaase, Ruben H de Kleine, Cornelis J van Laarhoven, Daan J Lips, Misha D Luyer, I Quintus Molenaar, Vincent B Nieuwenhuijs, Gijs A Patijn, Daphne Roos, Joris J Scheepers, George P van der Schelling, Pascal Steenvoorde, Rutger-Jan Swijnenburg, Jan H Wijsman, Moh'd Abu Hilal, Olivier R Busch, Marc G Besselink
BACKGROUND: Observational cohort studies have suggested that minimally invasive distal pancreatectomy (MIDP) is associated with better short-term outcomes compared with open distal pancreatectomy (ODP), such as less intraoperative blood loss, lower morbidity, shorter length of hospital stay, and reduced total costs. Confounding by indication has probably influenced these findings, given that case-matched studies failed to confirm the superiority of MIDP. This accentuates the need for multicenter randomized controlled trials, which are currently lacking...
April 8, 2017: Trials
Sarah R Langley, Karin Willeit, Athanasios Didangelos, Ljubica Perisic Matic, Philipp Skroblin, Javier Barallobre-Barreiro, Mariette Lengquist, Gregor Rungger, Alexander Kapustin, Ludmilla Kedenko, Chris Molenaar, Ruifang Lu, Temo Barwari, Gonca Suna, Xiaoke Yin, Bernhard Iglseder, Bernhard Paulweber, Peter Willeit, Joseph Shalhoub, Gerard Pasterkamp, Alun H Davies, Claudia Monaco, Ulf Hedin, Catherine M Shanahan, Johann Willeit, Stefan Kiechl, Manuel Mayr
BACKGROUND: The identification of patients with high-risk atherosclerotic plaques prior to the manifestation of clinical events remains challenging. Recent findings question histology- and imaging-based definitions of the "vulnerable plaque," necessitating an improved approach for predicting onset of symptoms. METHODS: We performed a proteomics comparison of the vascular extracellular matrix and associated molecules in human carotid endarterectomy specimens from 6 symptomatic versus 6 asymptomatic patients to identify a protein signature for high-risk atherosclerotic plaques...
April 3, 2017: Journal of Clinical Investigation
Heike Molenaar, Martin Glawe, Robert Boehm, Hans-Peter Piepho
Ornamental plant variety improvement is limited by current phenotyping approaches and neglected use of experimental designs. The present study was conducted to show the benefits of using an experimental design and corresponding analysis in ornamental breeding regarding simulated response to selection in Pelargonium zonale for production-related traits. This required establishment of phenotyping protocols for root formation and stem cutting counts, with which 974 genotypes were assessed in a two-phase experimental design...
2017: Horticulture Research
F Jasmijn Smits, Hjalmar C van Santvoort, Marc G Besselink, Marilot C T Batenburg, Robbert A E Slooff, Djamila Boerma, Olivier R Busch, Peter P L O Coene, Ronald M van Dam, David P J van Dijk, Casper H J van Eijck, Sebastiaan Festen, Erwin van der Harst, Ignace H J T de Hingh, Koert P de Jong, Johanna A M G Tol, Inne H M Borel Rinkes, I Quintus Molenaar
Importance: Postoperative pancreatic fistula is a potentially life-threatening complication after pancreatoduodenectomy. Evidence for best management is lacking. Objective: To evaluate the clinical outcome of patients undergoing catheter drainage compared with relaparotomy as primary treatment for pancreatic fistula after pancreatoduodenectomy. Design, Setting, and Participants: A multicenter, retrospective, propensity-matched cohort study was conducted in 9 centers of the Dutch Pancreatic Cancer Group from January 1, 2005, to September 30, 2013...
June 1, 2017: JAMA Surgery
Peter C M Molenaar
Equivalences of two classes of dynamic models for weakly stationary multivariate time series are discussed: dynamic factor models and autoregressive models. It is shown that exploratory dynamic factor models can be rotated, yielding an infinite set of equivalent solutions for any observed series. It also is shown that dynamic factor models with lagged factor loadings are not equivalent to the currently popular state-space models, and that restriction of attention to the latter type of models may yield invalid results...
March 2017: Multivariate Behavioral Research
Lu Ou, Sy-Miin Chow, Linying Ji, Peter C M Molenaar
The autoregressive latent trajectory (ALT) model synthesizes the autoregressive model and the latent growth curve model. The ALT model is flexible enough to produce a variety of discrepant model-implied change trajectories. While some researchers consider this a virtue, others have cautioned that this may confound interpretations of the model's parameters. In this article, we show that some-but not all-of these interpretational difficulties may be clarified mathematically and tested explicitly via likelihood ratio tests (LRTs) imposed on the initial conditions of the model...
March 2017: Multivariate Behavioral Research
Inga Koneczny, Jo A A Stevens, Anna De Rosa, Saif Huda, Maartje G Huijbers, Abhishek Saxena, Michelangelo Maestri, Konstantinos Lazaridis, Paraskevi Zisimopoulou, Socrates Tzartos, Jan Verschuuren, Silvère M van der Maarel, Philip van Damme, Marc H De Baets, Peter C Molenaar, Angela Vincent, Roberta Ricciardi, Pilar Martinez-Martinez, Mario Losen
Autoimmunity mediated by IgG4 subclass autoantibodies is an expanding field of research. Due to their structural characteristics a key feature of IgG4 antibodies is the ability to exchange Fab-arms with other, unrelated, IgG4 molecules, making the IgG4 molecule potentially monovalent for the specific antigen. However, whether those disease-associated antigen-specific IgG4 are mono- or divalent for their antigens is unknown. Myasthenia gravis (MG) with antibodies to muscle specific kinase (MuSK-MG) is a well-recognized disease in which the predominant pathogenic IgG4 antibody binds to extracellular epitopes on MuSK at the neuromuscular junction; this inhibits a pathway that clusters the acetylcholine (neurotransmitter) receptors and leads to failure of neuromuscular transmission...
February 2017: Journal of Autoimmunity
Alejandro M Gomez, Jo A A Stevens, Marina Mané-Damas, Peter Molenaar, Hans Duimel, Fons Verheyen, Judith Cossins, David Beeson, Marc H De Baets, Mario Losen, Pilar Martinez-Martinez
Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies that target proteins at the neuromuscular junction, primarily the acetylcholine receptor (AChR) and the muscle-specific kinase. Because downstream of kinase 7 (Dok-7) is essential for the full activation of muscle-specific kinase and consequently for dense clustering of AChRs, we hypothesized that reduced levels of Dok-7 increase the susceptibility to passive transfer MG. To test this hypothesis, Dok-7 expression was reduced by transfecting shRNA-coding plasmids into the tibialis anterior muscle of adult rats by in vivo electroporation...
October 2016: American Journal of Pathology
Melissa C Kilby, Peter C M Molenaar, Semyon M Slobounov, Karl M Newell
The experiment was setup to investigate the control of human quiet standing through the manipulation of augmented visual information feedback of selective properties of the motion of two primary variables in postural control: center of pressure (COP) and center of mass (COM). Five properties of feedback information were contrasted to a no feedback dual-task (watching a movie) control condition to determine the impact of visual real-time feedback on the coordination of the joint motions in postural control in both static and dynamic one-leg standing postures...
January 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
Arja Gerritsen, Thijs de Rooij, Marcel G Dijkgraaf, Olivier R Busch, Jacques J Bergman, Dirk T Ubbink, Peter van Duijvendijk, G Willemien Erkelens, Mariël Klos, Philip M Kruyt, Dirk Jan Bac, Camiel Rosman, Adriaan C Tan, I Quintus Molenaar, Jan F Monkelbaan, Elisabeth M Mathus-Vliegent, Marc G Besselink
OBJECTIVES: Electromagnetic (EM)-guided bedside placement of nasoenteral feeding tubes by nurses may improve efficiency and reduce patient discomfort and costs compared with endoscopic placement by gastroenterologists. However, evidence supporting this task shift from gastroenterologists to nurses is limited. We aimed to compare the effectiveness of EM-guided and endoscopic nasoenteral feeding tube placement. METHODS: We performed a multicenter randomized controlled non-inferiority trial in 154 adult patients who required nasoenteral feeding and were admitted to gastrointestinal surgical wards in five Dutch hospitals...
August 2016: American Journal of Gastroenterology
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