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101. Abstracts of papers clinical pharmacological meeting

Author

Merkus, F. W. H. M., Gribnau, F. W. J., Thien, Th., Louwerenburg, Hans W., Kingma, J. Herre, van Gilst, Wiek H., Six, A. Jacob, de Graeff, Pieter, Wesseling, Harry, BoeLaert, J. R., Schurgers, M. L., Matthys, E. G., Belpaire, F., Daneels, R. F., de Cre, M. J., Boqaert, M. G., D'Haese, P. C., Verpooten, G. A., Lamberts, L. V., Liang, L., de Broe, M. E., de Meijer, P. H. E. M., Russel, F. G. M., Russel, A. J. M., van Ginneken, C. A. M., van Liedekerke, B. M., Lambert, W. E., Yousouf, M. A., de Roose, J. E., de Leenheer, A. P., Lambert, W., de Bersaques, J., Vanneste, L., de Leenheer, A., de Marie, S., Slaghuis, G., Rozing, P. M., Mattie, H., Poelma, F. G. J., Hilbers, H. W., Jansen, A. C. A., Tukker, J. J., Augusti, Jr, P., Verbeke, N., van Peer, A., Snoeck, E., Heykants, J., Bruynseels, J., Peeters, J., Amery, W., Rogiers, V., Vandenberghe, Y., Comet, M., Callaerts, A., Sonck, W., Guillouzo, A., Vercruysse, A., van Rooy, P., Rombaut, N., vanden Bussche, G., Tan, A. C. I. T. L., Jansen, T. L. Th. A., Termond, E. F. S., Kloppenborg, P. W. C., Thien, Th., Benraad, Th. J., van de Velde, V., Woestenbprghs, R., Hermens, W. A. J. J., Romeijn, S. G., Deurloo, M. J. M., Merkus, F. W. H. M., Musch, G., Massart, D. L., van Hengstum, M., Festen, J., van den Broek, W., Corstens, F., Beurskens, C., Hankel, M., de Smet, M., van Belle, S. J. P., de May, J., Storme, G. A., Kuppen, P. J. K., Schuitemaker, H., Veer, L. J. van't, van Oosterom, A. T., Schrier, P. I., de Bruijn, E. A., de Pooter, C. H., Tjaden, U. R., van Slooten, H., Roelevink, H. P., Smit, E., de Vries, E. G. E., Ijmker, J., Uges, D. R. A., Moors, M., Mertens, K., van Hecken, A., de Lepeleire, I., Verbesselt, R., Tjandra-Maga, T. B., de Schepper, P. J., Guelen, P. J. M., Jansen, T. J., Vrijhof, W. P., de Vos, D., Scharpé, S., Verkerk, R., Lsmeire, N., Zijlstra, I. F., Gribnau, F. W. J., Haaijer-Ruskamp, F. M., Post, D., Reddingius, P. F., Wesseling, H., Wollersheim, H. C. H., van den Meiracker, A. H., Veld, A. J. Man in 't, Admiraal, P., Boomsma, F., Derkx, F., Schalekamp, M. A. D. H., Schoors, D. F., Dupont, A. G., Claessen, F., Reljenga, J., Lenders, J. W. M., Thlen, Th., Laekeman, G., Muylle, L., van Hoydonck, A., Herman, A. G., and Peetermans, M. E.

Published
1988
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105. Dutch Pharmacological Meeting 1984

Author

Timmerman, H., Koeman, J. H., den Tonkelaar, E. H., Merkus, F. W. H. M., Struyker-Boudier, H. A. J., Bolt, G. R., Saxena, P. R., Bos, R. P., Breed, A. S. P. M., Theuws, J. L. G., Henderson, P. Th., de Brauw, L. M., de Bruijn, E. A., van de Velde, C. J. H., Tjaden, U. R., Kothuis, B. J. L., van Oosterom, A. T., Reeuwijk, H. J. E. M., Pinedo, H. M., van der Hoeven, R., Bultsma, T., Linschoten, M. R., Peter, J., Burbach, H., de Kloet, E. Ronald, Castelein, O., Verbeke, N., Leuven, K. U., Conings, L., Doods, H. N., Kalkman, H. O., de Jonge, A., Wilffert, B., Thoolen, M. J. M. C., Timmermans, P. B. M. W. M., van Zwieten, P. A., van Driel, J. B. M., Klaassen, A. B. M., Kuypers, W., Beld, A. J., Rodrigues de Miranda, J. F., Driessen, O., van der Velde, E. A., Engels, F., Oosting, R. S., Nijkamp, F. P., Evelo, C. T. A., Neis, J. M., Peters, J. G. P., ten Broeke, M. A. M., Vulders, C. A. J. M., Franssen, M. J. A. M., van Herwaarden, C. L. A., van de Putte, L. B. A., Gribnau, F. W. J., van der Graaff, M., Vermeulen, N. P. E., Hofman, P. H., Breimer, D. D., 't Hart, B. J., Wilting, J., de Gier, J. J., Hazelhoff, Bernard, de Vries, Jan B., Oijkstra, Durk, Mulder, Theo, Wynberg, Hans, Horn, Alan, van Doorn, R., Leijdekkers, Ch. -M., Anzion, R., Hengstum, M. v., Festen, J., Buijs, W., Broek, W. v. d., Groothedde, R., Corstens, F., van Heuven-Nolsen, P., de Wildt, D. J., Hillen, F. C., van Noordwijk, J., Janssen, Lambert H. M., Jansen, P. A. F., Meyboom, R. H. B., Vree, T. B., Jelinek, J., Schönbaum, E., Lomax, P., de Jong, W., Sandor, P., Cox van Put, J. J., Jongeneelen, F. J., Leijdekkers, Ch. M., Kerklaan, P. R. M., Zoetemelk, C. E. M., Mohn, G. R., Grote, J. J., Kuijpers, W., Kleinbloesem, C. H., van Brummelen, P., van Harten, J., Koopmans, P. P., Kateman, W., Tan, Y., van Ginneken, C. A. M., van Koppen, C. J., van der Beek, E. M., Lammers, J. W. J., Krielaart, M. J., Laban, E., Charbon, G. A., Folgering, H. Th. M., Lenders, J. W. M., Sluiter, H. E., Willemsen, J., Thien, Th., Mooy, J., Schols, M., Baak, M. v., Hooff, M. v., Rahn, K. H., Mulder, Theo B. A., Grol, Cor J., Dijkstra, Durk, Horn, Alan S., Neef, C., Meijer, D. K. F., van Gemert, P. J. L., Roelofs, H. M. J., Osterhuis, B. O, ten Berge, R. J. M., Schellekens, P. T. A., van Boxtel, C. J., Peeters, P. A. M., Raghoebar, M., Tiemessen, H. L. G. H., Raaijmakers, J. A. M., van Rozen, A. J., Terpstra, G. K., Wassink, G. A., Kreukniet, J., Remeyer, L. R., Reeuwijk, H. J. E., Touw, D. J., Rollema, Hans, Mastebroex, Dora, Russel, F. G. M., Wouterse, A. C., Rijk, M. C. M., Salden, H. J. M., De Schaepdryver, A. F., Lefebvre, R. A., Bogaert, M. G., Scheres, H. M. E., Salden, H. J. H., Siero, H. L. M., Slee, P. H. Th. J., van den Berg, L., Huysmans, F. Th. M., Koene, R. A. P., Smits, J. F. M., Nievelstein, H. M. N., Struyker Boudier, H. A. J., Raaijmakers, J. A. H., Huidekoper, H. J., Thljssen, H. H. W., Baars, L. C. M., Mathy, M. J., Veldhoven, C. M. M., AriËns, E. J., Ruland, C. M., de Vos, Cor, de Graaf, Joop, van Aalst, Gerard, Steenbergen, Hans, Hekster, Y. A., Tijhuis, M. W., Nouws, J. F. M., Wollersheim, H., Fennis, J., van 't Laar, A., Wijnands, W. J., van der Gen, A., Jzerman, A. P. I., Aué, G., Dorlas, R., Krajnc, E. I., Loeber, J. G., van Leeuwen, F. X. R., Wester, P. W., Vos, J. G., Vaessen, H. A. M. G., Heijden, C. A. v. d., Canton, J. H., de Klerk, A., Krajc, E. I., Kruizinga, W., van Ommen, B., Rozing, J., van der Heijden, C. A., van der Voet, G. B., de Wolff, F. A., Edelbroek, Peter M., de Reus, Margot J. H., van den Berg, Tjeerd, and de Wolff, Frederik A.

Published
1984
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107. Abstracts of papers

Author

Wesseling, H., Veur, E. v. d., Berge, B. S. ten, Donker, A. J. M., May, J. F., Schuurman, F. H., van Schaik, B. A. M., Geyskes, G. G., Petri, H., Böhm, R., Mooy, J., van Kemenade, J., van Baak, M., Rahn, K. H., van Heereveld, H. A. E. M., Wollersheim, H., Thien, Th., Lammers, J. W. J., Folgering, H. Th. M., van Herwaarden, C. L. A., Graafsma, S. J., Snijders, P. J. F., de Miranda, J. F. Rodrigues, de Bruijn, E. A., van Oosterom, A. T., Kuppen, P. J. K., Jol, C., Tjaden, U. R., Trimbos, J. B., Runhaar, E. A., Nooij, H. A., van de Loo, A. A. J., Speth, P. A. J., Linssen, P. C. M., Haanen, C., Leeuwenkamp, O. R., Neyt, J. H., van der Vijgh, W. J. F., Pinedo, H. M., Schellens, J. H. M., Danhof, M., Breimer, D. D., Overdiek, J. W. P. M., Merkus, F. W. H. M., Teeuwen, H. W. A., de Schepper, P., Tjandramaga, T. B., van Rossum, J. M., Tukker, J. J., Blankenstein, M. A., Nortier, J. W. R., Zantvoort, F. A., Wagonvoort, J. H. T., Derkx, F. H. M., Michel, M. F., Wijnands, W. J. A., Baars, A. M., Vree, T. B., van Dalen, R., Termond, E. S. F., Boekema, P., Smits, P., de Abreu, R., Thlen, Th., van 't Laar, A., Böhm, R. O. B., Arends, B. G., van Hooff, H. E. J., van Baak, M. A., Derkx F., Tan-Tjiong H., Wenting G., Manin't Veld A., Schalekamp M., van Harten, J., van Brummelen, P., Danhof, H., Lodewijks, M. Th. M., Jansen, P. A. F., van Ginneken, C. A. M., Gribnau, F. W. J., Lohman, J. J. H. M., Hooymans, P. M., Merkus, F. W. H. H., Mol, M. J. T. M., Stalenhoef, A. F. H., Demacker, P. N. M., van't Laar, A., Raaijmakers, J. A. M., Terpstra, G. K., and Holdrinet, R. S. G.

Published
1986
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108. Abstracts of papers Pharmaceutical and biomedical analysis meeting

Author

Bandhoe, A. U., Paalman, A. C. A., Underberg, W. J. M., Beijnen, J. H., Bekers, O., Otagiri, M., Bult, A., Beuman, Gert, van der Heijden, Jacques, Janss, Jenny, Ceelen, P. R. J., Feenstra-Bielders, G. G. L. M., Groeneveld, D. J., de Boer, D., Rutten, M. J. A., de Jong, E. G., Maes, R. A. A., van Rossum, J. M., de Groot, G., Kopps, R., Savelkoul, T. J. F., van Vloten, P., de Jonag, E. G., van Ooyen, R., Kiffers, J., de Kroon, I. F. I., Langendijk, P. N. J., de Goede, P. N. F. C., De Smet, M., Musch, C., Peeters, A., Buydens, L., Massart, D. L., De Turck, K., Cachet, Th., Hoogmartens, J., Delrue, M., Lannoo, P., Drenth, B. F. H., Beckeringh, F. J., Bosman, J., Feitsma, K. G., van Nijhuisvan Dam, A., Driebergen, R. J., van Gorp, J. A., Ensing, K., Farlam, A., de Jong, G. J., Frel, R. W., Brinkman, U. A. Th., Gerding, T. K., van de Grampel, V. J. M., Niemeijer, N. R., de Zeeuw, R. A., Tepper, P. G., Horn, A. S., Halvax, J. J., Wiese, G., van Bennekom, W. P., Hindriks, Rik, Buydens, Lutgarde, Peeters, Anne, de Smet, Marina, Massart, Luc, Blokland, Aric, Vink, Jan, Keizers, S., de Jong, E. G., Niessen, W. M. A., Verhey, E. R., LaVos, G. F., Tjaden, U. R., van der Greef, J., Ooms, J. A., Haak, G. S. J., Grooten, G., Pattyn, G., Sandra, P., David, F., van Oosterom, A. T., de Bruijn, E. A., Pouwelse, A. V., de Jong, D., Lammers, N. G. F. M., van den Berg, J. H. M., Quintens, I., Roets, E., Reeuwijk, H. J. E. M., Lingeman, H., Keizer, H. J., Rosing, H., Elferink, F., van de Vaart, F. J., Kloeg, P. H. A. M., Sauter, André, Stegehuis, D. S., Reinhoud, N. J., Steijger, O. M., Hilhorst, J. J. L., Holthuis, J. J. M., Underberg-Chitoe, U. K., Meenhorst, P. L., Van den Mooter, G., Hauchecorne, R., Vinckier, C., van der Horst, A., Martens, H. J. M., van der Horst, F. A. L., Post, M. H., van Ginkel, L. A., Zoontjes, P. W., van Blitterswijk, H., Stephany, R. W., van Gijn, R., Bakker, C. H., Koks, C. H. W., Rodenhuis, S., van Opstal, M. A. J., van den Horst, F. A. L., Krabbenborg, P., van Tellingen, O., Woude, H. R. v. d., van Beers, C. J. T., Nooyen, W. J., Varossieau, F. J., Los, G., Nagel, J. D., McVie, J. G., Veen, R. N., Land, J. T. Op 't, Vendrig, D. E. M. M., Teeuwsen, J., Verlaar, F. C. A. M., Trum, T. J. H. M., de Kleijn, J. P., Vervoort, R., Vrieling, M., Maris, F., Hindriks, H., Walhagen, A., Edholm, L. -E., Heeremans, C. E. M., and van der Hoeven, R. A. M.

Published
1989
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109. Abstracts of papers clinical pharmacological meeting

Author

van den Ouweland, F. A., Eenhoorn, P. C., Tan, Y., Gribnau, F. W. J., van Brupgen, A., de Graeff, P. A., van den Toren, E. W., van Gilst, W. H., Wesseling, H., Lie, K. I., Postula, C. T., Hoefnagels, W. B. L., de Boo, Th., Thien, Th., Boon E. S., Goyskes, C. G., Boor, P., van Schalk, B. A. M., Abma, C., Frijns, T. R. J. A., Wamer, J., Elving, L. D., de Nobel, E., Mattie, H., van Gulpen, C., Lammers, J-W. J., Minette, P., Barnes, P. J., Jongejan, R. C., de Jongste, J. C., Raatgeep, H. C., Bonta, I. L., Kerrebijn, K. F., Mol, M. J., Stalenhoef, A. F., Stuyt, P. M., van 't Laar, A., Ermens, A. A. M., Schoester, M., Lindemans, J., Abels, J., van Baak, M. A., Mooij, J. M. V., Schiffers, P. M. H., Wetzels, J. F. M., v. Berqeyk, J. D., v. Heusden, F. H. J. A., Huysmans, F. Th. M., Hoitsma, A. J., Koene, R. A. P., Jansen, H. M. L., Russel, F. G. M., Wouterse, A. C., van Ginneken, C. A. M., Pol, Y. W. A. v. d., de Vries, E. G. E., Greidanus, J., Mulder, N. H., Sleijfer, D. Th., Willemse, P. H. B., Uges, D. R. A., Smits, P. A. B. M., Louwerenburg, J. W., Kingma, J. H., IJdenberg, F. N., Poelma, F. G. J., Breŝ, R., Tukker, J. J., Remmert, H. P., Olling, M., Slob, W., van der Giesen, W., Rauws, A. G., Runhaar, E. A., Neijt, J. P., Holthuis, J. J. M., de Vos, D., Tukker, J J, Poelma, F G J, Thijssen, H. H. W., Hamulyák, K., Franssen, C., Wollersheim, H., Jansen, R. W. M. M., van Lier, H. J. J., Hoefnagels, W. H. L., Grgen, C., Horan, M-A., Oomerjee, Z. A. R., Breimer, D. D., van Bezooijen, C. F. A., Keizer, H. J., Cleton, F. J., de Bruijn, E. A., Tiaden, U. R., de Boer, A., Stiekema, J. C. J., and Danhof, M.

Published
1988
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111. VET students' integration of knowledge engaged with in schoolbased and workplace-based learning environments in the Netherlands.

Author

Baartman, L. K. J., Kilbrink, N., and de Bruijn, E.

Subjects
EDUCATIONAL relevance, VOCATIONAL education, CAREER education, COLLEGE students, UNIVERSITIES & colleges
Abstract

In vocational education, students learn in different school-based and workplace-based learning environments and engage with different types of knowledge in these environments. Students are expected to integrate these experiences and make meaning of them in relation to their own professional knowledge base. This study focuses both on what types of knowledge students learn in these environments and how they integrate these different types of knowledge. Individual and group interviews were conducted with students, teachers and workplace supervisors in a vocational programme in the Netherlands. Results show that students recognise the importance of vocational knowledge learned in school-based learning environments while they are in the workplace and vice versa, and continuously contextualise knowledge to make it applicable for new circumstances. Also, students learn differently at school due to their experiences in the workplace. [ABSTRACT FROM AUTHOR]

Published
2018
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112. Human neck reflex adaptation towards the frequency content of anterior-posterior torso perturbations

Author

Happee, R., de Bruijn, E., Schouten, A., van der Helm, F., and Forbes, P.

Subjects
Modulation, Posture, Feedback
Abstract

Introduction: Reflex modulation has been extensively reported during posture maintenance in response to task instructions, and to perturbation type, bandwidth and amplitude. For the head-neck system the modulation of the vestibulocollic (VCR) and cervicocollic (CCR) reflexes is essential to maintain upright head posture during unexpected disturbances. Previous studies have estimated that VCR and CCR contribute equally during perturbations in the sagittal plane; however, their modulation with respect to the properties of the disturbance remains unclear. This study seeks to establish how neck reflexes are modulated during perturbations with varying properties and how each reflex contributes to stabilization behavior. We hypothesized that VCR and CCR (a) modulate according to the perturbation bandwidth, (b) are unaffected by the perturbation amplitude and (c) increase when performing a visual acuity task. Methods: Twelve subjects were perturbed via the torso while restrained in a seated position on a motion platform. The anterior-posterior perturbations varied in bandwidth from 0.3 Hz to a maximum frequency of 1.2, 2.0, 4.0 and 8.0 Hz, at three different amplitudes, and with eyes open and closed. Results: Head kinematics and neck muscle EMG demonstrated significant (P < 0.05) changes due to bandwidth, which through modeling and closed loop identification were attributed to modulation of VCR and CCR gains. VCR and CCR demonstrated dominant contributions to stabilization during high (8.0 Hz) and low bandwidth (1.2 and 2.0 Hz) perturbations respectively, and equivalent contributions during mid bandwidth perturbations (4.0 Hz). However both were attenuated when perturbations exceeded the systems natural frequency (~2-3 Hz). Amplitude had an effect only for the lowest amplitude relative to other conditions attributed to thresholding properties of the semicircular canals. With eyes closed reflex gains decreased, attributed to the reduced ability to discriminate self-motion without vision. Conclusions: To maintain head-upright posture adaptations of neck reflexes are observed to occur due to perturbation frequency and visual task conditions but not amplitude. Estimation of reflex contributions demonstrates that previous literature has underestimated the contribution of CCR, particularly during low frequency perturbations.

Published
2012

113. Het meten van conceptueel begrip bij hbo-studenten Bedrijfsadministratie: Een exploratief methodologisch onderzoek

Author

Ashley, S., Schaap, H., de Bruijn, E., Interactivity and learning in education, and Afd Educatie

Subjects
Ordered by external client
Abstract

Om complexe problemen in de beroepspraktijk op te lossen hebben studenten in het hoger beroepsonderwijs (hbo) een diep niveau van conceptueel begrip nodig. Een instrument dat conceptueel begrip bij hbo-studenten adequaat kan meten is daarom gewenst. Het doel van dit onderzoek is om een dergelijk instrument te ontwikkelen. In het instrument worden vier oplopende niveaus van begrip beoordeeld op drie criteria. Om dit instrument verder te ontwikkelen zullen 30 vierdejaars hbo-studenten van de Engelstalige cursus International Business and Management Studies participeren. Twee methoden zullen met elkaar vergeleken worden: essays en concept maps. Experts en onderzoekers zullen het niveau van conceptueel begrip zoals geëxpliciteerd in de twee methoden beoordelen.

Published
2012

114. High-throughput target-selected gene inactivation in zebrafish

Author

Kettleborough, R.N., de Bruijn, E., van Eeden, F.J., Cuppen, E., Stemple, D.L., and Hubrecht Institute for Developmental Biology and Stem Cell Research

Abstract

There is an increasing requirement for efficient reverse genetics in the zebrafish, Here we describe a method that takes advantage of conventional mutagenized libraries (identical to ones used in forward screens) and re-sequencing to identify ENU-induced mutations in genes of interest. The efficiency of TILLING (Targeting Induced Local Legions IN Genomes) depends on the rate of mutagenesis in the library being screened, the amount of base pairs screened, and the ability to effectively identify and retrieve mutations on interest. Here we show that by improving the mutagenesis protocol, using in silico methods to predict codon changes for target selection, efficient PCR and re-sequencing, and accurate mutation detection we can vastly improve current TILLING protocols. Importantly it is also possible to use this method for screening for splice and mis-sense mutations, and with even a relatively small library, there is a high chance of identifying mutations across any given gene.

Published
2011

115. Single nucleotide polymorphism (SNP) panels for rapid positional cloning in zebrafish

Author

Clark, M.D., Guryev, V., de Bruijn, E., Nijman, I.J., Tada, M., Wilson, C., Deloukas, P., Postlethwait, J.H., Cuppen, E., Stemple, D.L., and Hubrecht Institute for Developmental Biology and Stem Cell Research

Subjects
ComputingMethodologies_PATTERNRECOGNITION
Abstract

Despite considerable genetic and genomic resources the positional cloning of forward mutations remains a slow and manually intensive task, typically using gel based genotyping and sequential rounds of mapping. We have used the latest genetic resources and genotyping technologies to develop two commercially available SNP panels of thousands of markers that can be used to speed up positional cloning.

Published
2011

116. Classificeren van krachtige leeromgevingen in het (voorbereidend) middelbaar beroepsonderwijs

Author

Koopman, M., De Bruijn, E., and ESoE

Abstract

Dit artikel analyseert de methodologische kwaliteit van een vragenlijst bedoeld om (v)mboopleidingente classificeren op basis van de mate waarin de leeromgeving als krachtig kanworden beschouwd. De vragenlijst is ingezet in twee studies bij respectievelijk 53 mboopleidingen(studie 1) en 15 vmbo- en mbo-opleidingen (studie 2). De betrouwbaarheid vande vragenlijst is bepaald door Crohnbachs alpha’s van de schalen te berekenen. De validiteitvan de vragenlijst is geanalyseerd door te kijken naar gemiddelde schaalscores en spreiding,correlaties tussen schalen, de relatie met de conceptuele onderbouwing, vergelijking vanclassificaties van opleidingen met observatiegegevens en analyse van eventuele verschillentussen de studies. Op basis van de bevindingen kan de conclusie worden getrokken dat demethodologische kwaliteit van de vragenlijst over het geheel genomen redelijk goed is endaarmee goed te gebruiken in onderzoek naar leeromgevingen in het beroepsonderwijs.

Published
2011

121. Identification of Srp9 as a febrile seizure susceptibility gene

Author

Hessel, E.V.S. (Ellen V. S.), de Wit, M. (Marina), Wolterink-Donselaar, I.G. (Inge G.), Karst, H., de Graaff, E. (Esther), Lith, H.A. (H.) van, de Bruijn, E. (Ewart), de Sonnaville, S. (Sophietje), Verbeek, N.E. (Nienke), Lindhout, D. (Dick), de Kovel, C.G.F. (Carolien G. F.), Koeleman, B.P.C. (Bobby), Kempen, M.J.A. (M. J A) van, Brilstra, E. (Eva), Cuppen, E. (Edwin), Loos, M. (Maarten), Spijker, S., Kan, A.A. (Anne A.), Baars, S.E. (Susanne E.), Rijen, P.C. (Peter) van, Gosselaar, P.H. (Peter H.), Groot Koerkamp, M.J.A. (Marian J. A.), Holstege, F.C.P. (Frank), Duijn, C.M. (Cornelia) van, Vergeer, J.M. (Jeanette), Moll, H.A. (Henriette A.), Taubøll, E. (Erik), Heuser, K. (Kjell), Ramakers, G.M.J. (Geert M. J.), Pasterkamp, R.J. (Jeroen), Nieuwenhuizen, O. (Onno) van, Hoogenraad, C.C. (Casper), Kas, M.J.H. (Martien), Graan, P.N.E. (Pierre) de, Hessel, E.V.S. (Ellen V. S.), de Wit, M. (Marina), Wolterink-Donselaar, I.G. (Inge G.), Karst, H., de Graaff, E. (Esther), Lith, H.A. (H.) van, de Bruijn, E. (Ewart), de Sonnaville, S. (Sophietje), Verbeek, N.E. (Nienke), Lindhout, D. (Dick), de Kovel, C.G.F. (Carolien G. F.), Koeleman, B.P.C. (Bobby), Kempen, M.J.A. (M. J A) van, Brilstra, E. (Eva), Cuppen, E. (Edwin), Loos, M. (Maarten), Spijker, S., Kan, A.A. (Anne A.), Baars, S.E. (Susanne E.), Rijen, P.C. (Peter) van, Gosselaar, P.H. (Peter H.), Groot Koerkamp, M.J.A. (Marian J. A.), Holstege, F.C.P. (Frank), Duijn, C.M. (Cornelia) van, Vergeer, J.M. (Jeanette), Moll, H.A. (Henriette A.), Taubøll, E. (Erik), Heuser, K. (Kjell), Ramakers, G.M.J. (Geert M. J.), Pasterkamp, R.J. (Jeroen), Nieuwenhuizen, O. (Onno) van, Hoogenraad, C.C. (Casper), Kas, M.J.H. (Martien), and Graan, P.N.E. (Pierre) de

Abstract

Objective: Febrile seizures (FS) are the most common seizure type in young children. Complex FS are a risk factor for mesial temporal lobe epilepsy (mTLE). To identify new FS susceptibility genes we used a forward genetic strategy in mice and subsequently analyzed candidate genes in humans. Methods: We mapped a quantitative trait locus (QTL1) for hyperthermia-induced FS on mouse chromosome 1, containing the signal recognition particle 9 (Srp9) gene. Effects of differential Srp9 expression were assessed in vivo and in vitro. Hippocampal SRP9 expression and genetic association were analyzed in FS and mTLE patients. Results: Srp9 was differentially expressed between parental strains C57BL/6J and A/J. Chromosome substitution strain 1 (CSS1) mice exhibited lower FS susceptibility and Srp9 expression than C57BL/6J mice. In vivo knockdown of brain Srp9 reduced FS susceptibility. Mice with reduced Srp9 expression and FS susceptibility, exhibited reduced hippocampal AMPA and NMDA currents. Downregulation of neuronal Srp9 reduced surface expression of AMPA receptor subunit GluA1. mTLE patients with antecedent FS had higher SRP9 expression than patients without. SRP9 promoter SNP rs12403575(G/A) was genetically associated with FS and mTLE. Interpretation: Our findings identify SRP9 as a novel FS susceptibility gene and indicate that SRP9 conveys its effects through endoplasmic reticulum (ER)-dependent synthesis and trafficking of membrane proteins, such as glutamate receptors. Discovery of this new FS gene and mechanism may provide new leads for early diagnosis and treatment of children with complex FS at risk for mTLE.

Published
2014
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123. Isometric and Dynamic Control of Neck Muscles: Reflexive contributions and muscle synergies

Author

De Bruijn, E. (author) and De Bruijn, E. (author)

Abstract

It is well established that the central nervous system (CNS) stabilizes the head using reflexive feedback and cocontraction. The major reflexive pathways in the neck are through muscle spindles generating the cervicocollic reflex (CCR) and through the vestibular organ generating the vestibulocollic reflex (VCR). The CNS modulates the contribution of the different pathways and the level of cocontraction to change the system dynamics in an effort to optimally withstand motion disturbances. Predetermined groups of muscles, called synergies, are used to generate stabilizing forces, but it is not clear how the CNS modulates the reflexive pathways and how the muscle groups are chosen. To understand the function of the different reflexive pathways and the responses of the different muscles musculoskeletal models are necessary. To date, a neck model with sufficient detail to simulate vertebral injury and reflexive control of individual muscles does not exist. There are a number of reasons why the behavior of the CNS in neck muscle control should be investigated. Cervical dystonia is a movement disorder characterized by involuntary activity of the neck muscles leading to debilitating abnormal postures and twisting movements. Current evidence points towards changes in the neuronal circuitry in the brain, but the underlying pathology remains for the most part unclear. The understanding of normal and aberrant control of muscles is an important key to finding a solution for this disorder. The current treatment involves injecting the dystonic muscles with botulinum toxin. Although this treatment is generally quite successful, it often remains difficult to distinguish dystonic muscles from healthy compensatory activation. Improvements in the protocols to select aberrant muscles in patients would improve the effectiveness of the treatment and could be an asset when treating more difficult cases. Two aims were set out in this thesis. The first was to establish how the CCR and VCR pa, Biomechanical Engineering, Mechanical, Maritime and Materials Engineering

Published
2014

124. Getting more out of less - A quantitative Serological Screening Tool for simultaneous detection of multiple influenza A Hemagglutinin-types in chickens.

Author

Freidl, G.S., de Bruijn, E., van Beek, J., Reimerink, J., de Wit, S.J., Koch, G., Vervelde, L., van der Ham, H.J., Koopmans, M.P.G., Freidl, G.S., de Bruijn, E., van Beek, J., Reimerink, J., de Wit, S.J., Koch, G., Vervelde, L., van der Ham, H.J., and Koopmans, M.P.G.

Abstract

Current avian influenza surveillance in poultry primarily targets subtypes of interest for the veterinary sector (H5, H7). However, as virological and serological evidence suggest, surveillance of additional subtypes is important for public health as well as for the poultry industry. Therefore, we developed a protein microarray enabling simultaneous identification of antibodies directed against different HA-types of influenza A viruses in chickens. The assay successfully discriminated negative from experimentally and naturally infected, seropositive chickens. Sensitivity and specificity depended on the cut-off level used but ranged from 84.4% to 100% and 100%, respectively, for a cut off level of =1:40, showing minimal cross reactivity. As this testing platform is also validated for the use in humans, it constitutes a surveillance tool that can be applied in human-animal interface studies.

Published
2014

127. Highly Efficient ENU Mutagenesis in Zebrafish

Author

de Bruijn, E., Cuppen, E., Feitsma, H., and Hubrecht Institute for Developmental Biology and Stem Cell Research

Subjects
otorhinolaryngologic diseases
Abstract

ENU (N-ethyl-N-nitrosourea) mutagenesis is a widely accepted and proven method to introduce random point mutations in the genome. Because there are no targeted knockout strategies available for zebrafish so far, random mutagenesis is currently the preferred method in both forward and reverse genetic approaches. To obtain high-density mutagenized zebrafish, six consecutive ENU treatments are applied at weekly intervals to adult male zebrafish by bathing them in ENU solution. With this procedure an average germ line mutation load of one mutation every 1.0 x 10(5)-1.5 x 10(5) basepairs is reached routinely in our lab.

Published
2009

132. Wendbaar beroepsonderwijs

Author

den Boer, P.R., Geerligs, J.W.G., Nieuwenhuis, L.F.M., and de Bruijn, E.

Published
2004

133. Active IJburg: The closed building block revised

Author

De Bruijn, E. (author) and De Bruijn, E. (author)

Abstract

Within the research on designed appropriation we concluded that certain aspects or design elements could “trigger” inhabitants to appropriate or actually restrain this. Combining some elements worked better than other, but overall it could be said that renting a property does not encourage possible appropriation. If appropriation has to take place for a dwelling to “work optimal”, the ownership should be privately owned. Low effort mostly combines with low possibilities (for example: the sliding walls flexible housing project by Duinker/vd Torre). In the design project, I wanted to create a certain flexibility in the dwellings. However, climate and structural issues ask for expensive and complex solutions, which are not likely to be applied and/or used in every day practice. Therefore, I “limited” the flexibility to a fixed zone and a service zone, where the service zone allows for flexibility. The fixed zone makes the building stable and strong (prefab concrete load bearing walls with precast plate flooring, whereas the service zone provides flexibility by using a Slimline+floor with a lowered ceiling. In this zone pipes and wires come together to two shafts. In this way, the basic envelope of one dwelling allows for stacking this envelope into row houses, maisonettes or separate maisonettes. By also placing a steel lintel in the prefabricated load bearing walls, openings/passages can be made through the dwellings on horizontal level, allowing for horizontal linking., At Home in the City: Amsterdam, Architecture & Dwelling, Architecture

Published
2013

134. Combined sequence-based and genetic mapping analysis of complex traits in outbred rats

Author

Baud, A., Hermsen, R., Guryev, V., Stridh, P., Graham, D., McBride, M.W., Foroud, T., Calderari, S., Diez, M., Ockinger, J., Beyeen, A.D., Gillett, A., Abdelmagid, N., Guerreiro-Cacais, A.O., Jagodic, M., Tuncel, J., Norin, U., Beattie, E., Huynh, N., Miller, W.H., Koller, D.L., Alam, I., Falak, S., Osborne-Pellegrin, M., Martinez-Membrives, E., Canete, T., Blazquez, G., Vicens-Costa, E., Mont-Cardona, C., Diaz-Moran, S., Tobena, A., Hummel, O., Zelenika, D., Saar, K., Patone, G., Bauerfeind, A., Bihoreau, M.T., Heinig, M., Lee, Y.A., Rintisch, C., Schulz, H., Wheeler, D.A., Worley, K.C., Muzny, D.M., Gibbs, R.A., Lathrop, M., Lansu, N., Toonen, P., Ruzius, F.P., de Bruijn, E., Hauser, H., Adams, D.J., Keane, T., Atanur, S.S., Aitman, T.J., Flicek, P., Malinauskas, T., Jones, E.Y., Ekman, D., Lopez-Aumatell, R., Dominiczak, A.F., Johannesson, M., Holmdahl, R., Olsson, T., Gauguier, D., Hubner, N., Fernandez-Teruel, A., Cuppen, E., Mott, R., Flint, J., Baud, A., Hermsen, R., Guryev, V., Stridh, P., Graham, D., McBride, M.W., Foroud, T., Calderari, S., Diez, M., Ockinger, J., Beyeen, A.D., Gillett, A., Abdelmagid, N., Guerreiro-Cacais, A.O., Jagodic, M., Tuncel, J., Norin, U., Beattie, E., Huynh, N., Miller, W.H., Koller, D.L., Alam, I., Falak, S., Osborne-Pellegrin, M., Martinez-Membrives, E., Canete, T., Blazquez, G., Vicens-Costa, E., Mont-Cardona, C., Diaz-Moran, S., Tobena, A., Hummel, O., Zelenika, D., Saar, K., Patone, G., Bauerfeind, A., Bihoreau, M.T., Heinig, M., Lee, Y.A., Rintisch, C., Schulz, H., Wheeler, D.A., Worley, K.C., Muzny, D.M., Gibbs, R.A., Lathrop, M., Lansu, N., Toonen, P., Ruzius, F.P., de Bruijn, E., Hauser, H., Adams, D.J., Keane, T., Atanur, S.S., Aitman, T.J., Flicek, P., Malinauskas, T., Jones, E.Y., Ekman, D., Lopez-Aumatell, R., Dominiczak, A.F., Johannesson, M., Holmdahl, R., Olsson, T., Gauguier, D., Hubner, N., Fernandez-Teruel, A., Cuppen, E., Mott, R., and Flint, J.

Abstract

Genetic mapping on fully sequenced individuals is transforming understanding of the relationship between molecular variation and variation in complex traits. Here we report a combined sequence and genetic mapping analysis in outbred rats that maps 355 quantitative trait loci for 122 phenotypes. We identify 35 causal genes involved in 31 phenotypes, implicating new genes in models of anxiety, heart disease and multiple sclerosis. The relationship between sequence and genetic variation is unexpectedly complex: at approximately 40% of quantitative trait loci, a single sequence variant cannot account for the phenotypic effect. Using comparable sequence and mapping data from mice, we show that the extent and spatial pattern of variation in inbred rats differ substantially from those of inbred mice and that the genetic variants in orthologous genes rarely contribute to the same phenotype in both species., Genetic mapping on fully sequenced individuals is transforming understanding of the relationship between molecular variation and variation in complex traits. Here we report a combined sequence and genetic mapping analysis in outbred rats that maps 355 quantitative trait loci for 122 phenotypes. We identify 35 causal genes involved in 31 phenotypes, implicating new genes in models of anxiety, heart disease and multiple sclerosis. The relationship between sequence and genetic variation is unexpectedly complex: at approximately 40% of quantitative trait loci, a single sequence variant cannot account for the phenotypic effect. Using comparable sequence and mapping data from mice, we show that the extent and spatial pattern of variation in inbred rats differ substantially from those of inbred mice and that the genetic variants in orthologous genes rarely contribute to the same phenotype in both species.

Published
2013

135. Systematic biases in DNA copy number originate from isolation procedures

Author

van Heesch, S., Mokry, M., Boskova, V., Junker, W., Mehon, R., Toonen, P., de Bruijn, E., Shull, J.D., Aitman, T.J., Cuppen, E., Guryev, V., van Heesch, S., Mokry, M., Boskova, V., Junker, W., Mehon, R., Toonen, P., de Bruijn, E., Shull, J.D., Aitman, T.J., Cuppen, E., and Guryev, V.

Abstract

BACKGROUND: The ability to accurately detect DNA copy number variation in both a sensitive and quantitative manner is important in many research areas. However, genome-wide DNA copy number analyses are complicated by variations in detection signal. RESULTS: While GC content has been used to correct for this, here we show that coverage biases are tissue-specific and independent of the detection method as demonstrated by next-generation sequencing and array CGH. Moreover, we show that DNA isolation stringency affects the degree of equimolar coverage and that the observed biases coincide with chromatin characteristics like gene expression, genomic isochores, and replication timing. CONCLUSION: These results indicate that chromatin organization is a main determinant for differential DNA retrieval. These findings are highly relevant for germline and somatic DNA copy number variation analyses., BACKGROUND: The ability to accurately detect DNA copy number variation in both a sensitive and quantitative manner is important in many research areas. However, genome-wide DNA copy number analyses are complicated by variations in detection signal. RESULTS: While GC content has been used to correct for this, here we show that coverage biases are tissue-specific and independent of the detection method as demonstrated by next-generation sequencing and array CGH. Moreover, we show that DNA isolation stringency affects the degree of equimolar coverage and that the observed biases coincide with chromatin characteristics like gene expression, genomic isochores, and replication timing. CONCLUSION: These results indicate that chromatin organization is a main determinant for differential DNA retrieval. These findings are highly relevant for germline and somatic DNA copy number variation analyses.

Published
2013

136. A systematic genome-wide analysis of zebrafish protein-coding gene function

Author

Kettleborough, R.N., Busch-Nentwich, E.M., Harvey, S.A., Dooley, C.M., de Bruijn, E., van Eeden, F., Sealy, I., White, R.J., Herd, C., Nijman, I.J., Fenyes, F., Mehroke, S., Scahill, C., Gibbons, R., Wali, N., Carruthers, S., Hall, A., Yen, J., Cuppen, E., Stemple, D.L., Kettleborough, R.N., Busch-Nentwich, E.M., Harvey, S.A., Dooley, C.M., de Bruijn, E., van Eeden, F., Sealy, I., White, R.J., Herd, C., Nijman, I.J., Fenyes, F., Mehroke, S., Scahill, C., Gibbons, R., Wali, N., Carruthers, S., Hall, A., Yen, J., Cuppen, E., and Stemple, D.L.

Abstract

Since the publication of the human reference genome, the identities of specific genes associated with human diseases are being discovered at a rapid rate. A central problem is that the biological activity of these genes is often unclear. Detailed investigations in model vertebrate organisms, typically mice, have been essential for understanding the activities of many orthologues of these disease-associated genes. Although gene-targeting approaches and phenotype analysis have led to a detailed understanding of nearly 6,000 protein-coding genes, this number falls considerably short of the more than 22,000 mouse protein-coding genes. Similarly, in zebrafish genetics, one-by-one gene studies using positional cloning, insertional mutagenesis, antisense morpholino oligonucleotides, targeted re-sequencing, and zinc finger and TAL endonucleases have made substantial contributions to our understanding of the biological activity of vertebrate genes, but again the number of genes studied falls well short of the more than 26,000 zebrafish protein-coding genes. Importantly, for both mice and zebrafish, none of these strategies are particularly suited to the rapid generation of knockouts in thousands of genes and the assessment of their biological activity. Here we describe an active project that aims to identify and phenotype the disruptive mutations in every zebrafish protein-coding gene, using a well-annotated zebrafish reference genome sequence, high-throughput sequencing and efficient chemical mutagenesis. So far we have identified potentially disruptive mutations in more than 38% of all known zebrafish protein-coding genes. We have developed a multi-allelic phenotyping scheme to efficiently assess the effects of each allele during embryogenesis and have analysed the phenotypic consequences of over 1,000 alleles. All mutant alleles and data are available to the community and our phenotyping scheme is adaptable to phenotypic analysis beyond embryogenesis., Since the publication of the human reference genome, the identities of specific genes associated with human diseases are being discovered at a rapid rate. A central problem is that the biological activity of these genes is often unclear. Detailed investigations in model vertebrate organisms, typically mice, have been essential for understanding the activities of many orthologues of these disease-associated genes. Although gene-targeting approaches and phenotype analysis have led to a detailed understanding of nearly 6,000 protein-coding genes, this number falls considerably short of the more than 22,000 mouse protein-coding genes. Similarly, in zebrafish genetics, one-by-one gene studies using positional cloning, insertional mutagenesis, antisense morpholino oligonucleotides, targeted re-sequencing, and zinc finger and TAL endonucleases have made substantial contributions to our understanding of the biological activity of vertebrate genes, but again the number of genes studied falls well short of the more than 26,000 zebrafish protein-coding genes. Importantly, for both mice and zebrafish, none of these strategies are particularly suited to the rapid generation of knockouts in thousands of genes and the assessment of their biological activity. Here we describe an active project that aims to identify and phenotype the disruptive mutations in every zebrafish protein-coding gene, using a well-annotated zebrafish reference genome sequence, high-throughput sequencing and efficient chemical mutagenesis. So far we have identified potentially disruptive mutations in more than 38% of all known zebrafish protein-coding genes. We have developed a multi-allelic phenotyping scheme to efficiently assess the effects of each allele during embryogenesis and have analysed the phenotypic consequences of over 1,000 alleles. All mutant alleles and data are available to the community and our phenotyping scheme is adaptable to phenotypic analysis beyond embryogenesis.

Published
2013

138. Primary colorectal cancers and their subsequent hepatic metastases are genetically different: implications for selection of patients for targeted treatment

Author

Vermaat, J.S., Nijman, I.J., Koudijs, M.J., Gerritse, F.L., Scherer, S.J., Mokry, M., Roessingh, W.M., Lansu, N., de Bruijn, E., van Hillegersberg, R., van Diest, P.J., Cuppen, E., Voest, E.E., Vermaat, J.S., Nijman, I.J., Koudijs, M.J., Gerritse, F.L., Scherer, S.J., Mokry, M., Roessingh, W.M., Lansu, N., de Bruijn, E., van Hillegersberg, R., van Diest, P.J., Cuppen, E., and Voest, E.E.

Abstract

PURPOSE: In the era of DNA-guided personalized cancer treatment, it is essential to conduct predictive analysis on the tissue that matters. Here, we analyzed genetic differences between primary colorectal adenocarcinomas (CRC) and their respective hepatic metastasis. EXPERIMENTAL DESIGN: The primary CRC and the subsequent hepatic metastasis of 21 patients with CRC were analyzed using targeted deep-sequencing of DNA isolated from formalin-fixed, paraffin-embedded archived material. RESULTS: We have interrogated the genetic constitution of a designed "Cancer Mini-Genome" consisting of all exons of 1,264 genes associated with pathways relevant to cancer. In total, 6,696 known and 1,305 novel variations were identified in 1,174 and 667 genes, respectively, including 817 variants that potentially altered protein function. On average, 83 (SD = 69) potentially function-impairing variations were gained in the metastasis and 70 (SD = 48) variations were lost, showing that the primary tumor and hepatic metastasis are genetically significantly different. Besides novel and known variations in genes such as KRAS, BRAF, KDR, FLT1, PTEN, and PI3KCA, aberrations in the up/downstream genes of EGFR/PI3K/VEGF-pathways and other pathways (mTOR, TGFbeta, etc.) were also detected, potentially influencing therapeutic responsiveness. Chemotherapy between removal of the primary tumor and the metastasis (N = 11) did not further increase the amount of genetic variation. CONCLUSION: Our study indicates that the genetic characteristics of the hepatic metastases are different from those of the primary CRC tumor. As a consequence, the choice of treatment in studies investigating targeted therapies should ideally be based on the genetic properties of the metastasis rather than on those of the primary tumor., PURPOSE: In the era of DNA-guided personalized cancer treatment, it is essential to conduct predictive analysis on the tissue that matters. Here, we analyzed genetic differences between primary colorectal adenocarcinomas (CRC) and their respective hepatic metastasis. EXPERIMENTAL DESIGN: The primary CRC and the subsequent hepatic metastasis of 21 patients with CRC were analyzed using targeted deep-sequencing of DNA isolated from formalin-fixed, paraffin-embedded archived material. RESULTS: We have interrogated the genetic constitution of a designed "Cancer Mini-Genome" consisting of all exons of 1,264 genes associated with pathways relevant to cancer. In total, 6,696 known and 1,305 novel variations were identified in 1,174 and 667 genes, respectively, including 817 variants that potentially altered protein function. On average, 83 (SD = 69) potentially function-impairing variations were gained in the metastasis and 70 (SD = 48) variations were lost, showing that the primary tumor and hepatic metastasis are genetically significantly different. Besides novel and known variations in genes such as KRAS, BRAF, KDR, FLT1, PTEN, and PI3KCA, aberrations in the up/downstream genes of EGFR/PI3K/VEGF-pathways and other pathways (mTOR, TGFbeta, etc.) were also detected, potentially influencing therapeutic responsiveness. Chemotherapy between removal of the primary tumor and the metastasis (N = 11) did not further increase the amount of genetic variation. CONCLUSION: Our study indicates that the genetic characteristics of the hepatic metastases are different from those of the primary CRC tumor. As a consequence, the choice of treatment in studies investigating targeted therapies should ideally be based on the genetic properties of the metastasis rather than on those of the primary tumor.

Published
2012

139. Genetic basis of transcriptome differences between the founder strains of the rat HXB/BXH recombinant inbred panel

Author

Simonis, M., Atanur, S.S., Linsen, S., Guryev, V., Ruzius, F.P., Game, L., Lansu, N., de Bruijn, E., van Heesch, S., Jones, S.J., Pravenec, M., Aitman, T.J., Cuppen, E., Simonis, M., Atanur, S.S., Linsen, S., Guryev, V., Ruzius, F.P., Game, L., Lansu, N., de Bruijn, E., van Heesch, S., Jones, S.J., Pravenec, M., Aitman, T.J., and Cuppen, E.

Abstract

BACKGROUND: With the advent of next generation sequencing it has become possible to detect genomic variation on a large scale. However, predicting which genomic variants are damaging to gene function remains a challenge, as knowledge of the effects of genomic variation on gene expression is still limited. Recombinant inbred panels are powerful tools to study the cis and trans effects of genetic variation on molecular phenotypes such as gene expression. RESULTS: We generated a comprehensive inventory of genomic differences between the two founder strains of the rat HXB/BXH recombinant inbred panel: SHR/OlaIpcv and BN-Lx/Cub. We identified 3.2 million single nucleotide variants, 425,924 small insertions and deletions, 907 copy number changes and 1,094 large structural genetic variants. RNA-sequencing analyses on liver tissue of the two strains identified 532 differentially expressed genes and 40 alterations in transcript structure. We identified both coding and non-coding variants that correlate with differential expression and alternative splicing. Furthermore, structural variants, in particular gene duplications, show a strong correlation with transcriptome alterations. CONCLUSIONS: We show that the panel is a good model for assessing the genetic basis of phenotypic heterogeneity and for providing insights into possible underlying molecular mechanisms. Our results reveal a high diversity and complexity underlying quantitative and qualitative transcriptional differences., BACKGROUND: With the advent of next generation sequencing it has become possible to detect genomic variation on a large scale. However, predicting which genomic variants are damaging to gene function remains a challenge, as knowledge of the effects of genomic variation on gene expression is still limited. Recombinant inbred panels are powerful tools to study the cis and trans effects of genetic variation on molecular phenotypes such as gene expression. RESULTS: We generated a comprehensive inventory of genomic differences between the two founder strains of the rat HXB/BXH recombinant inbred panel: SHR/OlaIpcv and BN-Lx/Cub. We identified 3.2 million single nucleotide variants, 425,924 small insertions and deletions, 907 copy number changes and 1,094 large structural genetic variants. RNA-sequencing analyses on liver tissue of the two strains identified 532 differentially expressed genes and 40 alterations in transcript structure. We identified both coding and non-coding variants that correlate with differential expression and alternative splicing. Furthermore, structural variants, in particular gene duplications, show a strong correlation with transcriptome alterations. CONCLUSIONS: We show that the panel is a good model for assessing the genetic basis of phenotypic heterogeneity and for providing insights into possible underlying molecular mechanisms. Our results reveal a high diversity and complexity underlying quantitative and qualitative transcriptional differences.

Published
2012

147. Evaluation of the Diurnal Cycle in the Atmospheric Boundary Layer Over Land as Represented by a Variety of Single-Column Models : The Second GABLS Experiment

Author

Svensson, Gunilla, Holtslag, A. A. M., Kumar, V., Mauritsen, T., Steeneveld, G. J., Angevine, W. M., Bazile, E., Beljaars, A., de Bruijn, E. I. F., Cheng, A., Conangla, L., Cuxart, J., Ek, M., Falk, M. J., Freedman, F., Kitagawa, H., Larson, V. E., Lock, A., Mailhot, J., Masson, V., Park, S., Pleim, J., Söderberg, S., Weng, W., Zampieri, M., Svensson, Gunilla, Holtslag, A. A. M., Kumar, V., Mauritsen, T., Steeneveld, G. J., Angevine, W. M., Bazile, E., Beljaars, A., de Bruijn, E. I. F., Cheng, A., Conangla, L., Cuxart, J., Ek, M., Falk, M. J., Freedman, F., Kitagawa, H., Larson, V. E., Lock, A., Mailhot, J., Masson, V., Park, S., Pleim, J., Söderberg, S., Weng, W., and Zampieri, M.

Abstract

We present the main results from the second model intercomparison within the GEWEX (Global Energy and Water cycle EXperiment) Atmospheric Boundary Layer Study (GABLS). The target is to examine the diurnal cycle over land in today's numerical weather prediction and climate models for operational and research purposes. The set-up of the case is based on observations taken during the Cooperative Atmosphere-Surface Exchange Study-1999 (CASES-99), which was held in Kansas, USA in the early autumn with a strong diurnal cycle with no clouds present. The models are forced with a constant geostrophic wind, prescribed surface temperature and large-scale divergence. Results from 30 different model simulations and one large-eddy simulation (LES) are analyzed and compared with observations. Even though the surface temperature is prescribed, the models give variable near-surface air temperatures. This, in turn, gives rise to differences in low-level stability affecting the turbulence and the turbulent heat fluxes. The increase in modelled upward sensible heat flux during the morning transition is typically too weak and the growth of the convective boundary layer before noon is too slow. This is related to weak modelled near-surface winds during the morning hours. The agreement between the models, the LES and observations is the best during the late afternoon. From this intercomparison study, we find that modelling the diurnal cycle is still a big challenge. For the convective part of the diurnal cycle, some of the first-order schemes perform somewhat better while the turbulent kinetic energy (TKE) schemes tend to be slightly better during nighttime conditions. Finer vertical resolution tends to improve results to some extent, but is certainly not the solution to all the deficiencies identified., authorCount :25

Published
2011
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149. Het lerend vermogen van leerwerkgemeenschappen

Author

Interactivity and learning in education, Teacher learning and expertise throughout the professional career, Afd Educatie, Schaap, H., Volkhoven, H., Swierts, K., de Bruijn, E., Interactivity and learning in education, Teacher learning and expertise throughout the professional career, Afd Educatie, Schaap, H., Volkhoven, H., Swierts, K., and de Bruijn, E.

Published
2011

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