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6. Chronobiological Aspects of Spontaneous Ultra-Weak Photon Emission in Humans: Ultradian, Circadian and Infradian Rhythms

Author

Volodyaev, Ilya, van Wijk, Eduard, Cifra, Michal, Vladimirov, Yury A, Volodyaev, I ( Ilya ), van Wijk, E ( Eduard ), Cifra, M ( Michal ), Vladimirov, Y A ( Yury A ), Scholkmann, Felix; https://orcid.org/0000-0002-1748-4852, Volodyaev, Ilya, van Wijk, Eduard, Cifra, Michal, Vladimirov, Yury A, Volodyaev, I ( Ilya ), van Wijk, E ( Eduard ), Cifra, M ( Michal ), Vladimirov, Y A ( Yury A ), and Scholkmann, Felix; https://orcid.org/0000-0002-1748-4852

Abstract

In this chapter, the present knowledge of chronobiological rhythms in spontaneous ultra-weak photon emission (i.e. biological autoluminescence) from humans is summarized. The studies available are reviewed and compared to each other. The studies conducted so far show that UPE in humans exhibits ultradian, circadian and infradian rhythms. These rhythms need to be considered when performing UPE measurements in humans and provide unique physiological information. Further research into the chronobiological aspects of UPE in humans is not only relevant for basic physiological research but also has the potential to demonstrate the importance of characterizing the UPE rhythmicity as a method for medical diagnostics.

Published
2023

11. Antisense oligonucleotides for dominantly inherited hearing impairment DFNA9: from cells models to humanized mice.

Author

Aben, F., Verdoodt, D., de Bruijn, S., Oostrik, J., Venselaar, H., Sels, L., De Backer, E., Gommeren, H., Szewczyk, K., Van Camp, G., Ponsaerts, P., Van Rompaey, V., van Wijk, E., and de Vrieze, E.

Subjects
BIOLOGICAL models, CONFERENCES & conventions, NUCLEOTIDES, MICE, ANIMAL experimentation, HEARING disorders, GENETIC mutation
Abstract

The c.151C>T (p.P51S) mutation in COCH is highly prevalent in the Dutch/Belgian population and causes DFNA9 (hearing loss and vestibular dysfunction) in > 1500 individuals. The initial symptoms manifest between the 3rd and 5th decade of life, which leaves ample time for therapeutic intervention. The clear non-haploinsufficiency disease mechanism indicates that blocking or reducing the p.P51S mutant cochlin protein levels may alleviate or prevent the DFNA9 phenotypes. Considering the broad expression of COCH by the fibrocytes of the inner ear, we designed "gapmer" antisense oligonucleotides (ASO) to specifically induce RNase H1-mediated degradation of COCH transcripts containing the c.151C>T mutation. We established several model systems to investigate the molecular efficacy of ASOs targeting the c. 151C>T mutation or low-frequency mutant allele-specific SNPs. Using overexpression models, we identified several ASOs that efficiently induce the degradation of mutant COCH transcripts. By introducing chemical modification to the oligonucleotide bases, we can alter the affinity and selectivity for the mutation transcript. We identified several ASOs with a strong preference for the mutant transcript in overexpression models. To investigate allele-specificity under physiological expression levels, we exposed patient-derived otic progenitor cells (iPCS-OPCs) to different ASOs for 8 days. In parallel, we developed a genetically humanized mouse model for DFNA9 in which human sequence-specific therapeutic strategies can be evaluated. Phenotypic follow-up of mice of all genotypes indicate that the genetic humanization has no adverse effects, and removal of the Cdh23ahl allele is mandatory to observe the late-onset auditory phenotype: the first signs of high-frequency hearing loss emerged at 12 months of age. Studies in iPSC-OPCs indicated that the ASOs identified in overexpression studies also effectively reduce mutant COCH transcript levels in patient-derived cells with physiological expression levels. Unfortunately, variation between replicate wells of OPC differentiation is relatively high, making it difficult to draw conclusions on allele-specificity. We selected a candidate ASO, directed against a rare mutant allele-spe-cific intronic SNP, for subsequent studies in our humanized mouse model. First intracochlear injections will be conducted in May 2024, after which we can collect the first in vivo data on gapmer ASO uptake and efficacy in fibrocytes of the mammalian inner ear. [ABSTRACT FROM AUTHOR]

Published
2024

15. Identification of novel biomarkers for pyridoxine-dependent epilepsy using untargeted metabolomics and infrared ion spectroscopy - biochemical insights and clinical implications

Author

Laura A. Tseng, Laura A. Jansen, Karlien L.M. Coene, Jos Oomens, Thomas J. Boltje, van Karnebeek Cd, van Outersterp Re, Leo A. J. Kluijtmans, van Rooij A, Saadet Mercimek-Andrews, Hilal H. Al-Shekaili, Ron A. Wevers, Purva Kulkarni, Levinus A. Bok, Michèl A.A.P. Willemsen, Jona Merx, Marleen C. D. G. Huigen, Broekman S, Struys Ea, Udo F. H. Engelke, Tessa M. A. Peters, Blair R. Leavitt, de Vrieze E, Sidney M. Gospe, Jasmin Mecinović, Jonathan Martens, van Geenen Fa, Giel Berden, Keith Hyland, Floris P. J. T. Rutjes, and van Wijk E

Subjects
Newborn screening, biology, Catabolism, business.industry, Neurotoxicity, Bioinformatics, medicine.disease, biology.organism_classification, Epilepsy, medicine, Biomarker (medicine), Ketosis, business, Pyridoxine-dependent epilepsy, Zebrafish
Abstract

Pyridoxine-dependent epilepsy (PDE-ALDH7A1), also known as antiquitin deficiency, is an inborn error of lysine metabolism that presents with refractory epilepsy in newborns. Bi-allelic ALDH7A1 variants lead to deficiency of α-aminoadipic semialdehyde dehydrogenase, resulting in accumulation of piperideine-6-carboxylate (P6C), and secondary deficiency of the important co-factor pyridoxal-5’-phosphate (PLP, active vitamin B6) through its complexation with P6C. Vitamin B6 supplementation resolves epilepsy in patients, but despite this treatment, intellectual disability may occur. Early diagnosis and treatment, preferably based on newborn screening, potentially optimize long-term clinical outcome. However, the currently known diagnostic PDE-ALDH7A1 biomarkers are incompatible with newborn screening procedures. Using a combination of the innovative analytical methods untargeted metabolomics and infrared ion spectroscopy, we have been able to discover novel biomarkers for PDE-ALDH7A1: 2S,6S-and 2S,6R-oxopropylpiperidine-2-carboxylic acid (2-OPP) and 6-oxopiperidine-2-carboxylic acid (6-oxoPIP). We demonstrate the applicability of 2-OPP as a PDE-ALDH7A1 biomarker in newborn screening. Additionally, we show that 2-OPP accumulates in brain tissue of patients and Aldh7a1 knock-out mice, and induces epilepsy-like behavior in a zebrafish model system. We speculate that 2-OPP may contribute to ongoing neurotoxicity, also in treated PDE-ALDH7A1 patients. As 2-OPP formation appears to increase upon ketosis, we emphasize the importance of avoiding catabolism in PDE-ALDH7A1 patients.

Published
2021
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16. Harmonizing light transmission aggregometry in the Netherlands by implementation of the SSC-ISTH guideline

Author

Munnix, I.C.A., Van Oerle, R., Verhezen, P., Kuijper, P., Hackeng, C.M., Hopman-Kerkhoff, H.I.J., Hudig, F., van de Kerkhof, D., Leyte, A., de Maat, M.P.M., Oude Elferink, R.F.M., Ruinemans-Koerts, J., Schoorl, M., Slomp, J., Soons, H., Stroobants, A., van Wijk, E., Henskens, Y.M.C., Munnix, I.C.A., Van Oerle, R., Verhezen, P., Kuijper, P., Hackeng, C.M., Hopman-Kerkhoff, H.I.J., Hudig, F., van de Kerkhof, D., Leyte, A., de Maat, M.P.M., Oude Elferink, R.F.M., Ruinemans-Koerts, J., Schoorl, M., Slomp, J., Soons, H., Stroobants, A., van Wijk, E., and Henskens, Y.M.C.

Abstract

Light transmission aggregometry (LTA) is considered the gold standard method for evaluation of platelet function. However, there are a lot of variation in protocols (pre-analytical procedures and agonist concentrations) and results. The aim of our study was to establish a national LTA protocol, to investigate the effect of standardization and to define national reference values for LTA. The SSC guideline was used as base for a national procedure. Almost all recommendations of the SSC were followed e.g. no adjustment of PRP, citrate concentration of 109 mM, 21 needle gauge, fasting, resting time for whole blood and PRP, centrifugation time, speed and agonists concentrations. LTA of healthy volunteers was measured in a total of 16 hospitals with 5 hospitals before and after standardization. Results of more than 120 healthy volunteers (maximum aggregation %) were collected, with participating laboratories using 4 different analyzers with different reagents. Use of low agonist concentrations showed high variation before and after standardization, with the exception of collagen. For most high agonist concentrations (ADP, collagen, ristocetin, epinephrine and arachidonic acid) variability in healthy subjects decreased after standardization. We can conclude that a standardized Dutch protocol for LTA, based on the SSC guideline, does not result in smaller variability in healthy volunteers for all agonist concentrations.

Published
2021

17. Harmonizing light transmission aggregometry in the Netherlands by implementation of the SSC-ISTH guideline

Author

Munnix, I. C.A., Van Oerle, R., Verhezen, P., Kuijper, P., Hackeng, C. M., Hopman-Kerkhoff, H. I.J., Hudig, F., Van De Kerkhof, D., Leyte, A., De Maat, M. P.M., Oude Elferink, R. F.M., Ruinemans-Koerts, J., Schoorl, M., Slomp, J., Soons, H., Stroobants, A., Van Wijk, E., Henskens, Y. M.C., Munnix, I. C.A., Van Oerle, R., Verhezen, P., Kuijper, P., Hackeng, C. M., Hopman-Kerkhoff, H. I.J., Hudig, F., Van De Kerkhof, D., Leyte, A., De Maat, M. P.M., Oude Elferink, R. F.M., Ruinemans-Koerts, J., Schoorl, M., Slomp, J., Soons, H., Stroobants, A., Van Wijk, E., and Henskens, Y. M.C.

Abstract

Light transmission aggregometry (LTA) is considered the gold standard method for evaluation of platelet function. However, there are a lot of variation in protocols (pre-analytical procedures and agonist concentrations) and results. The aim of our study was to establish a national LTA protocol, to investigate the effect of standardization and to define national reference values for LTA. The SSC guideline was used as base for a national procedure. Almost all recommendations of the SSC were followed e.g. no adjustment of PRP, citrate concentration of 109 mM, 21 needle gauge, fasting, resting time for whole blood and PRP, centrifugation time, speed and agonists concentrations. LTA of healthy volunteers was measured in a total of 16 hospitals with 5 hospitals before and after standardization. Results of more than 120 healthy volunteers (maximum aggregation %) were collected, with participating laboratories using 4 different analyzers with different reagents. Use of low agonist concentrations showed high variation before and after standardization, with the exception of collagen. For most high agonist concentrations (ADP, collagen, ristocetin, epinephrine and arachidonic acid) variability in healthy subjects decreased after standardization. We can conclude that a standardized Dutch protocol for LTA, based on the SSC guideline, does not result in smaller variability in healthy volunteers for all agonist concentrations.

Published
2021

20. From cells to cures: hiPSC-derived inner organoids and RNA therapy to resolve genetic hearing loss.

Author

Fousert, E., van den Boogaard, W. M. C., van der Valk, W. H., Lucassen, A. W. A., de Groot, J. C. M. J., van Benthem, P. P. G., Kremer, H., de Vrieze, E., van Wijk, E., and Locher, H.

Subjects
TREATMENT of hearing disorders, DEAFNESS prevention, CONFERENCES & conventions, RNA, INNER ear, STEM cells, HEARING disorders, CELLS
Abstract

Genetic hearing loss impacts millions worldwide, yet effective treatments remain unavailable, leaving patients reliant on technological aids such as hearing aids or cochlear implants. One major obstacle in therapy development is the lack of representative in vitro models of the human inner ear capable of mimicking genetic inner ear diseases and facilitating treatment validation. In this study, we present a novel approach to address this challenge. We differentiated human induced pluripotent stem cells (hiPSCs) derived from patients with genetic hearing diseases into 3D self-organizing inner ear organoids. Specifically, we focused on two genes associated with significant auditory impairments: USH2A, hereditary deaf-blindness, and COCH, implicated in late-onset genetic hearing loss, the latter presenting a window for intervention. We successfully generated disease-specific inner ear organoids by growing patient hiPSCs through precise modulation with small molecules and growth factors at distinct intervals. With immunohistochemistry we showed the presence of organ-specific cell structures within both USH2A- and COCH-inner ear organoids, including otic vesicles, hair cells and periotic mesenchymal cells. We compared the disease-specific inner ear organoids with healthy inner ear organoids through molecular and structural analyses and confirmed the presence of mutant transcripts in the patient-derived inner ear organoids. Moving beyond characterization, we demonstrate the clinical relevance of the model by countering the disease pheno-type with antisense oligonucleotides (ASOs) in vitro. ASOs can specifically target and modify RNA transcripts and slow down or halt genetic disease progression. We applied ASOs to late-stage disease-specific inner ear organoids via gymnotic delivery and observed its effect on mutant transcript expression through PCR analysis following ASO therapy. This study underscores the potential of human inner ear organoids as a platform for modelling genetic inner ear diseases and evaluating potential therapeutic interventions. Our findings offer promising avenues for increasing treatment options for individuals affected by genetic hearing loss, offering hope for improved outcomes and quality of life. [ABSTRACT FROM AUTHOR]

Published
2024

24. Harmonizing light transmission aggregometry in the Netherlands by implementation of the SSC-ISTH guideline

Author

Munnix, I.C.A., primary, Van Oerle, R., additional, Verhezen, P., additional, Kuijper, P., additional, Hackeng, C.M., additional, Hopman-Kerkhoff, H.I.J., additional, Hudig, F., additional, Van De Kerkhof, D., additional, Leyte, A., additional, De Maat, M.P.M., additional, Oude Elferink, R.F.M., additional, Ruinemans-Koerts, J., additional, Schoorl, M., additional, Slomp, J., additional, Soons, H., additional, Stroobants, A., additional, Van Wijk, E., additional, and Henskens, Y.M.C., additional

Published
2020
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31. De ijzeren verpleegster. Een kwalitatief onderzoek naar de houding van verpleegkundigen tegenover robotisering en de invloed van robotisering op hun baankenmerken

Author

Rosema, V.A.C., van Wijk, E. (Thesis Advisor), Rosema, V.A.C., and van Wijk, E. (Thesis Advisor)

Abstract

Hoewel de inzet van robots (zowel bewust als onbewust) kan leiden tot een verandering van het takenpakket van medewerkers (Ter Weel, 2015), heeft het merendeel van de studies naar robots in de zorg aandacht voor ofwel de acceptatie van robots door patiënten of de interactie tussen robots en patiënten (zie voor een overzicht o.a. Broadbent, Stafford & MacDonald, 2009). Een klein aantal studies biedt inzicht in de kijk van verpleegkundigen op robots (Ljungblad, Kotrbova, Jacobsson, Cramer & Niechwiadowicz, 2012; Siino & Hinds, 2005; Van Kemenade, Konijn & Hoorn, 2015). Echter, de bijdrage van robotisering aan het werkproces is nog onvoldoende belicht vanuit het perspectief van het personeel. Toch is het interessant om zicht te verkrijgen in de bijdrage van robotisering aan het werkproces en de invloed hiervan op medewerkers. Dit onderzoek levert daar een bijdrage aan door inzichtelijk te maken wat de houding van verpleegkundigen tegenover robotisering is en welke invloed robotisering volgens hen op hun baankenmerken heeft. Onder robotisering worden die geprogrammeerde middelen verstaan die zowel niet-autonoom als autonoom kunnen worden ingezet om handelingen van verpleegkundigen te ondersteunen of over te nemen. Door het Job Demands-Resources Model (JD-R-model) in dit onderzoek als raamwerk te hanteren, kan ieder baankenmerk worden gecategoriseerd als potentiële bron van werkstress (job demand; werkeis) of energie (job resource; energiebron). De brede definitie van robotisering en de mogelijkheid om het JD-R-model flexibel toe te passen, gaven de mogelijkheid om de centrale concepten (robotisering en baankenmerken) binnen een verkennend onderzoek te bestuderen. Empirische data is verkregen door vijftien semigestructureerde interviews af te nemen onder verpleegkundigen van twee afdelingen van het Universitair Medisch Centrum Utrecht (UMC Utrecht). Dit academische ziekenhuis werkt met niet-autonome robots die bedoeld zijn om handelingen van verpleegkundigen te ondersteu

Published
2017

32. Robotisering in de zorg - Een onderzoek naar de mogelijke gevolgen van robotisering voor de werkbeleving van medewerkers in Verpleeg- Verzorgingshuizen en Thuiszorgorganisaties

Author

Snuverink, S.E., van Wijk, E. (Thesis Advisor), Snuverink, S.E., and van Wijk, E. (Thesis Advisor)

Abstract

In steeds sterkere mate lijkt sprake te zijn van robotisering op de werkvloer, zo ook in de zorgsector. Wat hier de gevolgen van zijn, is echter nog voor een groot deel onbekend. In het huidige onderzoek wordt onderzocht in hoeverre robotisering invloed heeft op de werkbeleving van zorgverleners in Verpleeg-, Verzorgingshuizen en Thuiszorgorganisaties. Werkbeleving is namelijk een voorspeller van veel verschillende werknemers uitkomsten. Het theoretisch model, welke voortkomt uit het theoretisch kader, is gebaseerd op vier verschillende A’s (arbeidsinhoud, arbeidsomstandigheden, arbeidsverhoudingen en arbeidszekerheid) en de Job Characteristics Theory. Het onderzoek is uitgevoerd door middel van een kwalitatieve onderzoeksbenadering, bestaande uit semigestructureerde interviews. Aan het onderzoek deden 14 respondenten mee uit drie verschillende organisaties. Deze respondenten waren ofwel verzorgende/verpleegkundige ofwel projectleider met betrekking tot robotisering. Voor het onderzoek zijn vijf vormen van robotisering bestudeerd, namelijk: tillift, sondevoedings-/medicatiepomp, sensortechnologie, medicijndispenser en beeldzorg. In het onderzoek kwam naar voren dat robotisering een te vooruitstrevende term was voor dit onderzoek, men sprak eerder over technologische hulpmiddelen. Daarnaast kwam naar voren dat de professionele identiteit als erg belangrijk wordt ervaren door de medewerkers. Zij nemen dit mee in hun beoordeling over een technologisch hulpmiddelen. De technologische hulpmiddelen bleken wel degelijk van invloed te zijn op de werkbeleving van de medewerkers. Zo verandert het takenpakket, worden (veelal) ontwikkelingsmogelijkheden op technologisch gebied aangeboden, kunnen technologische hulpmiddelen medewerkers soms fysiek ontlasten, de werkdruk verlagen, veranderen relaties met collega’s, wordt de autonomie vaak vergroot en wordt de werk/privé balans in sommige gevallen beïnvloed. De manier waarop de technologische hulpmiddelen de werkbeleving beïnvloed

Published
2017

33. Trends in the inter-regional and international research collaboration of the PRC's regions: 2000-2015

Author

Luwel, M., van Wijk, E., van der Wurff, L.J., Wang, L.L., Rafols, Ismael, Molas-Gallart, Jordi, Castro-Martínez, Elena, Woolley, Richard, Mt Economic Research Inst on Innov/Techn, and RS: UNU-MERIT

Subjects
SCIENTIFIC COLLABORATION, PATTERNS, SCIENCE, CHINA
Abstract

The regional structure of the PRC's scientific output is analyzed using publications processed for the Web of Science. Over the period 2000-2015 and measured by the Salton Index of the co-publications the scientific collaboration among the PRC's regions increased only slightly, in stark contrast with the USA' states and during the most recent years the EU member countries. Only for research with other nations, representing about 30% of the total publication output, inter-regional collaboration is on the rise. For the leading PRC's regions the USA is the dominant partner co-authoring about 50% of their publications. Germany and especially Japan seems to lose attractiveness to the advantage of the UK, Australia and neighboring Asian countries.

Published
2016

36. A combination of two truncating mutations in USH2A causes more severe and progressive hearing impairment in Usher syndrome type IIa

Author

Hartel, B.P., Lofgren, M., Huygen, P.L., Guchelaar, I., Lo, A.N.K.N., Sadeghi, A.M., van Wijk, E., Tranebjaerg, L., Kremer, H., Kimberling, W.J., Cremers, C.W.R.J., Moller, C., Pennings, R.J., Hartel, B.P., Lofgren, M., Huygen, P.L., Guchelaar, I., Lo, A.N.K.N., Sadeghi, A.M., van Wijk, E., Tranebjaerg, L., Kremer, H., Kimberling, W.J., Cremers, C.W.R.J., Moller, C., and Pennings, R.J.

Abstract

Contains fulltext : 167662.pdf (publisher's version ) (Closed access), OBJECTIVES: Usher syndrome is an inherited disorder that is characterized by hearing impairment (HI), retinitis pigmentosa, and in some cases vestibular dysfunction. Usher syndrome type IIa is caused by mutations in USH2A. HI in these patients is highly heterogeneous and the present study evaluates the effects of different types of USH2A mutations on the audiometric phenotype. Data from two large centres of expertise on Usher Syndrome in the Netherlands and Sweden were combined in order to create a large combined sample of patients to identify possible genotype-phenotype correlations. DESIGN: A retrospective study on HI in 110 patients (65 Dutch and 45 Swedish) genetically diagnosed with Usher syndrome type IIa. We used methods especially designed for characterizing and testing differences in audiological phenotype between patient subgroups. These methods included Age Related Typical Audiograms (ARTA) and a method to evaluate the difference in the degree of HI developed throughout life between subgroups. RESULTS: Cross-sectional linear regression analysis of last-visit audiograms for the best hearing ear demonstrated a gradual decline of hearing over decades. The congenital level of HI was in the range of 16-33 dB at 0.25-0.5 kHz, and in the range of 51-60 dB at 1-8 kHz. The annual threshold deterioration was in the range of 0.4-0.5 dB/year at 0.25-2 kHz and in the range of 0.7-0.8 dB/year at 4-8 kHz. Patients with two truncating mutations, including homozygotes for the common c.2299delG mutation, developed significantly more severe HI throughout life than patients with one truncating mutation combined with one nontruncating mutation, and patients with two nontruncating mutations. CONCLUSIONS: The results have direct implications for patient counselling in terms of prognosis of hearing and may serve as baseline measures for future (genetic) therapeutic interventions.

Published
2016

37. Observing High Latitudes: extending the core Argo array

Author

van Wijk, E. M., Riser, S., Rintoul, S. R., Speer, K., Klatt, Olaf, Boebel, Olaf, Owens, B., Gascard, J. C., Freeland, H., Wijffels, S., Roemmich, D., and Wong, A.

Abstract

Over the past decade, Argo floats have provided an unprecedented number of profiles of the global oceans (to 2000m depth), far surpassing the number collected historically fromship-based hydrography. The original design of the Argomission specified nominal 3 x 3 degree spacing, with 10 daysampling interval, of the oceans between 60 °N and 60 °S,excluding the high latitudes and marginal seas. The exclusionof the high latitudes was due to the inability of early floats tosample under sea-ice. Technological advances in float designin recent years now give us this capability. Advancements havecome through re-design of hardware (i.e. armoured ice floats),software (ice-avoidance algorithm and open-water test) andcommunications (Iridium), allowing the transmission of storedwinter profiles. Observing circulation in seasonally ice-coveredseas is challenging. To date, most observations have beenmade during ice-free summer periods and consequently thewinter circulation beneath the sea-ice is not well understood.Despite this, Argo has already made a significant contribution tohigh latitude research with successful deployments of floats inthe polar oceans of both hemispheres. As of December 2008,over 100 floats had been deployed above 60 °N and over 200below 60 °S. Approximately 60% of these floats are still active(the failure rate of early floats was high as the ice-capabletechnology was being developed and tested). Mortality rates ofnewer ice floats are now equivalent to those deployed in lessdemanding conditions. In fact, a number of floats deployed inthe Weddell Sea have survived for 7 years (surpassing 225profiles) equal to some of the longest-lived floats deployedglobally. The high latitudes are important deep water massformation regions. The Southern Ocean connects the globalocean basins and regulates the meridional overturningcirculation. The exposed Arctic Ocean will have importantconsequences for ocean and atmospheric circulation, moistureand heat fluxes. Therefore, both polar regions play a critical rolein setting the rate and nature of global climate variabilitythrough their moderation of the earth's heat, freshwater andcarbon budgets. Recent studies have shown that certainregions at high latitudes are warming more rapidly than theglobal average. Some of the most important climate changesignals are seen near ice shelves and within the sea ice zone.In the Arctic, reductions in sea-ice extent and changes infreshwater fluxes, deep water mass properties and convectionhave been observed. Similarly strong reductions in sea-icecoverage are occurring near the Antarctic Peninsula while smallincreases appear in the Ross Sea. At the same time decreasingsalinity on the Ross Sea shelf is thought to be linked toincreased glacial melt. The Argo network has been crucial fordocumenting the recent changes in the open ocean; robust andlarge-scale freshening of the Southern Ocean has beenobserved from Argo and historical hydrographic data. Butsampling at these higher latitudes is less systematic than forthe rest of the globe. Therefore, observations of high latitudeoceans in both hemispheres should be a top priority. Inconsidering sampling strategies for the high latitudes werecommend extending the Argo network beyond 60 °S and60 °N through the deployment of ice-capable floats at thenominal density (3 x 3 degrees). In addition, regional arrays ofacoustically-tracked floats will provide a more focused effort onbasin scales. An established array of sound-sources (RAFOS)and acoustically-tracked floats in the Weddell Sea is alreadyyielding valuable information on ocean circulation and structurebeneath the sea-ice. A similar array should be established tosample the Ross Sea gyre. In the Arctic, an array of lowfrequency (< 100 Hz) sound sources would be required toprovide basin-wide geo-location for profiling floats. Now that wehave come to review the past decade of progress within Argo,we find there is considerable support and justification for theofficial extension of the Argo array into the seasonally icecoveredseas. Sustained, comprehensive observation of thepolar oceans is required to adequately monitor global climatechange signals. This can only be achieved in a broad-scale andcost-effective way by using autonomous platforms like Argoprofiling floats. It is thus imperative that a commitment is madeto enhance and maintain a profiling float array in the highlatitudes. The extension of the core Argo array beyond 60degrees in both hemispheres will ensure that it remains one ofthe most important and truly global components of the oceanobserving system.

Published
2009

38. Responsive regulation at the Dutch food and commodity authority: an empirical assessment of assumptions underlying the theory

Author

Mascini, Peter, van Wijk, E (Eelco), Mobility, culture and social in equality (ASSR, FMG), and Sociology

Abstract

Responsive regulation usually boils down to the assumption that enforcers should not shift to coercing before it has become clear that persuading does not work. This presupposes that it is possible to determine what the correct enforcement style is, that enforcers can apply the most suitable style, and that enforcers control the negative unintended consequences of their conduct. We have studied the applicability of these presuppositions at the Dutch Food and Consumer Product Safety Authority by way of observations, interviews, and a survey. The applicability of all three presuppositions has proven problematic; enforcement agents apply different styles in comparable cases; they are impeded in applying the most appropriate style; and they do not control the perverse consequences of their conduct because regulatees tend to perceive it as more coercive than intended by inspectors. Our findings are not unique to this inspectorate and hence raise questions about the applicability of the theory of responsive regulation.

Published
2009

44. The mitotic spindle protein SPAG5/Astrin connects to the Usher protein network postmitotically

Author

Kersten, F.F.J., van Wijk, E., Hetterschijt, E.C.G.M., Baub, K., Peters, T.A., Aslayan, M.G., Van der Zwaag, B., Keunen, J.E.E., Roepman, R., Kremer, J.M.J., Kersten, F.F.J., van Wijk, E., Hetterschijt, E.C.G.M., Baub, K., Peters, T.A., Aslayan, M.G., Van der Zwaag, B., Keunen, J.E.E., Roepman, R., and Kremer, J.M.J.

Abstract

Contains fulltext : 109883.pdf (publisher's version ) (Open Access), Background Mutations in the gene for Usher syndrome 2A (USH2A) are causative for non-syndromic retinitis pigmentosa and Usher syndrome, a condition that is the most common cause of combined deaf-blindness. To gain insight into the molecular pathology underlying USH2A-associated retinal degeneration, we aimed to identify interacting proteins of USH2A isoform B (USH2AisoB) in the retina. Results We identified the centrosomal and microtubule-associated protein sperm-associated antigen (SPAG)5 in the retina. SPAG5 was also found to interact with another previously described USH2AisoB interaction partner: the centrosomal ninein-like protein NINLisoB. Using In situ hybridization, we found that Spag5 was widely expressed during murine embryonic development, with prominent signals in the eye, cochlea, brain, kidney and liver. SPAG5 expression in adult human tissues was detected by quantitativ Conclusions Based on these results and on the suggested roles for USH proteins in vesicle transport and providing structural support to both the inner ear and the retina, we hypothesize that SPAG5, USH2AisoB and NINLisoB may function together in microtubule-based cytoplasmic trafficking of proteins that are essential for cilium formation, maintenance and/or function.

Published
2012

45. Organisatie commitment van medewerkers buiten het primaire proces

Author

Groot, J.M., van Wijk, E. (Thesis Advisor), Groot, J.M., and van Wijk, E. (Thesis Advisor)

Abstract

De identiteit van medewerkers kan grote invloed hebben op de mate waarin zij zich commiteren aan de organisatie waar ze werken. Hun identiteit kan bepalend zijn op gebieden als waar aan ze zich commiteren en op welke manier zij zich commiteren. Maar waar aan commiteren medewerkers zich als ze niet in het primaire proces zitten, maar ondersteunende werkzaamheden verrichten?

Published
2010

46. Obsering High Latitudes: extending the core Argo array

Author

van Wijk, E., Wijffels, S., Riser, S., Rintoul, S., Speer, K., Klatt, Olaf, Boebel, Olaf, Owens, B., Gascard, C., Freeland, F., Roemmich, D., Wong, A., van Wijk, E., Wijffels, S., Riser, S., Rintoul, S., Speer, K., Klatt, Olaf, Boebel, Olaf, Owens, B., Gascard, C., Freeland, F., Roemmich, D., and Wong, A.

Published
2009

47. Jubileum Volkshuisvesting 25 jaar

Author

Schutte, Y. and Van Wijk, E.

Subjects
volkshuisvesting, stadsvernieuwing
Abstract

Dit is een publicatie van de afstudeerrichting Volkshuisvesting & Stadsvernieuwing van de Faculteit der Bouwkunde van de Technische Universiteit Delft Uitgave naar aanleiding van het 2S-jarig jubileum van de afstudeerrichting gehouden op 24 oktober 1997

Published
1997

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