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Showing papers by "Utrecht University published in 2000"


Journal ArticleDOI
TL;DR: A short and direct derivation of Hawking radiation as a tunneling process, based on particles in a dynamical geometry, respects conservation laws, but the exact spectrum is not precisely thermal.
Abstract: We present a short and direct derivation of Hawking radiation as a tunneling process, based on particles in a dynamical geometry. The imaginary part of the action for the classically forbidden process is related to the Boltzmann factor for emission at the Hawking temperature. Because the derivation respects conservation laws, the exact spectrum is not precisely thermal. We compare and contrast the problem of spontaneous emission of charged particles from a charged conductor.

1,980 citations


Journal ArticleDOI
TL;DR: In this article, the authors did a multicentre prospective randomised trial to find whether postoperative pelvic radiotherapy improves locoregional control and survival for patients with stage-1 endometrial carcinoma.

1,503 citations


Journal ArticleDOI
08 Dec 2000-Science
TL;DR: Seismic tomography models of the three-dimensional upper mantle velocity structure of the Mediterranean-Carpathian region provide a better understanding of the lithospheric processes governing its geodynamical evolution.
Abstract: Seismic tomography models of the three-dimensional upper mantle velocity structure of the Mediterranean-Carpathian region provide a better understanding of the lithospheric processes governing its geodynamical evolution. Slab detachment, in particular lateral migration of this process along the plate boundary, is a key element in the lithospheric dynamics of the region during the last 20 to 30 million years. It strongly affects arc and trench migration, and causes along-strike variations in vertical motions, stress fields, and magmatism. In a terminal-stage subduction zone, involving collision and suturing, slab detachment is the natural last stage in the gravitational settling of subducted lithosphere.

1,492 citations


Journal ArticleDOI
13 Apr 2000-Nature
TL;DR: It is concluded that AFX-like proteins are involved in cell-cycle regulation and that inactivation of these proteins is an important step in oncogenic transformation.
Abstract: The Forkhead transcription factors AFX, FKHR and FKHR-L1 are orthologues of DAF-16, a Forkhead factor that regulates longevity in Caenorhabditis elegans1,2,3. Here we show that overexpression of these Forkhead transcription factors causes growth suppression in a variety of cell lines, including a Ras-transformed cell line and a cell line lacking the tumour suppressor PTEN. Expression of AFX blocks cell-cycle progression at phase G1, independent of functional retinoblastoma protein (pRb) but dependent on the cell-cycle inhibitor p27kip1. Indeed, AFX transcriptionally activates p27kip1, resulting in increased protein levels. We conclude that AFX-like proteins are involved in cell-cycle regulation and that inactivation of these proteins is an important step in oncogenic transformation.

1,455 citations


Journal ArticleDOI
25 Feb 2000-Science
TL;DR: Transgenic loss-of-function and overexpression models show that the dosage of glial cell line-derived neurotrophic factor (GDNF), produced by Sertoli cells, regulates cell fate decisions of undifferentiated sperMatogonial cells that include the stem cells for spermatogenesis.
Abstract: The molecular control of self-renewal and differentiation of stem cells has remained enigmatic. Transgenic loss-of-function and overexpression models now show that the dosage of glial cell line-derived neurotrophic factor (GDNF), produced by Sertoli cells, regulates cell fate decisions of undifferentiated spermatogonial cells that include the stem cells for spermatogenesis. Gene-targeted mice with one GDNF-null allele show depletion of stem cell reserves, whereas mice overexpressing GDNF show accumulation of undifferentiated spermatogonia. They are unable to respond properly to differentiation signals and undergo apoptosis upon retinoic acid treatment. Nonmetastatic testicular tumors are regularly formed in older GDNF-overexpressing mice. Thus, GDNF contributes to paracrine regulation of spermatogonial self-renewal and differentiation.

1,326 citations


Journal ArticleDOI
04 Feb 2000-Science
TL;DR: Synaptic connectivity does not depend on neurotransmitter secretion, but its maintenance does, and neurotransmitter secretion probably functions to validate already established synaptic connections.
Abstract: Brain function requires precisely orchestrated connectivity between neurons. Establishment of these connections is believed to require signals secreted from outgrowing axons, followed by synapse formation between selected neurons. Deletion of a single protein, Munc18-1, in mice leads to a complete loss of neurotransmitter secretion from synaptic vesicles throughout development. However, this does not prevent normal brain assembly, including formation of layered structures, fiber pathways, and morphologically defined synapses. After assembly is completed, neurons undergo apoptosis, leading to widespread neurodegeneration. Thus, synaptic connectivity does not depend on neurotransmitter secretion, but its maintenance does. Neurotransmitter secretion probably functions to validate already established synaptic connections.

1,302 citations


Journal ArticleDOI
TL;DR: The results quantify the increased fracture risk during oral corticosteroid therapy, with greater effects on the hip and spine than forearm, which has implications for the use of preventative agents against bone loss in patients at highest risk.
Abstract: Treatment with systemic corticosteroids is known to increase the risk of fractures but little is known of the fracture risks associated with inhaled corticosteroids. A retrospective cohort study was conducted using a large UK primary care database (the General Practice Research Database [GPRD]). Inhaled corticosteroid users aged 18 years or older were compared with matched control patients and to a group of noncorticosteroid bronchodilator users. Patients with concomitant use of systemic corticosteroids were excluded. The study comprised 170,818 inhaled corticosteroid users, 108,786 bronchodilator users, and 170,818 control patients. The average age was 45.1 years in the inhaled corticosteroid, 49.3 years in the bronchodilator, and 45.2 years in the control groups. In the inhaled corticosteroid cohort, 54.5% were female. The relative rates (RRs) of nonvertebral, hip, and vertebral fractures during inhaled corticosteroid treatment compared with control were 1.15 (95% CI, 1.10-1.20), 1.22 (95% CI, 1.04-1.43), and 1.51 (95% CI, 1.22-1.85), respectively. No differences were found between the inhaled corticosteroid and bronchodilator groups (nonvertebral fracture RR = 1.00; 95% CI, 0.94-1.06). The rates of nonvertebral fractures among users of budesonide (RR = 0.95; 95% CI, 0.85-1.07) and fluticasone propionate (RR = 1.03; 95% CI, 0.71-1.49) were similar to the rate determined for users of beclomethasone dipropionate. We conclude that users of inhaled corticosteroids have an increased risk of fracture, particularly at the hip and spine. However, this excess risk may be related more to the underlying respiratory disease than to inhaled corticosteroid.

1,259 citations


Journal ArticleDOI
TL;DR: A review on the growth of nanofibers using metallic particles as a catalyst to precipitate the graphitic carbon can be found in this paper, where the authors summarize some of the earlier literature that has contributed greatly to understand the nucleation and growth of carbon carbon and nanotubes and describe in detail recent progress to control the fiber surface structure, texture, and growth into mechanically strong agglomerates.
Abstract: Carbon nanofibers (diameter range, 3–100 nm; length range, 0.1–1000 µm) have been known for a long time as a nuisance that often emerges during catalytic conversion of carbon-containing gases. The recent outburst of interest in these graphitic materials originates from their potential for unique applications as well as their chemical similarity to fullerenes and carbon nanotubes. In this review, we focus on the growth of nanofibers using metallic particles as a catalyst to precipitate the graphitic carbon. First, we summarize some of the earlier literature that has contributed greatly to understand the nucleation and growth of carbon nanofibers and nanotubes. Thereafter, we describe in detail recent progress to control the fiber surface structure, texture, and growth into mechanically strong agglomerates. It is argued that carbon nanofibers are unique high-surface-area materials (˜200 m2/g) that can expose exclusively either basal graphite planes or edge planes. Subsequently, we will present the recently ...

1,253 citations


Journal ArticleDOI
TL;DR: It is reported that withdrawal of cytokine results in upregulation of Bimexpression concomitant with induction of the apoptotic program in lymphocytes, and a mechanism by which cytokines promote lymphocyte survival by inhibition of FKHR-L1, preventing Bim expression is proposed.

1,015 citations


Journal ArticleDOI
TL;DR: Exosomes are small membrane vesicles that are secreted by a multitude of cell types as a consequence of fusion of multivesicular late endosomes/lysosomes with the plasma membrane.
Abstract: Exosomes are small membrane vesicles that are secreted by a multitude of cell types as a consequence of fusion of multivesicular late endosomes/lysosomes with the plasma membrane. Depending on their origin, exosomes can play roles in different physiological processes. Maturing reticulocytes externalize obsolete membrane proteins such as the transferrin receptor by means of exosomes, whereas activated platelets release exosomes whose function is not yet known. Exosomes are also secreted by cytotoxic T cells, and these might ensure specific and efficient targeting of cytolytic substances to target cells. Antigen presenting cells, such as B lymphocytes and dendritic cells, secrete MHC class-I- and class-II-carrying exosomes that stimulate T cell proliferation in vitro. In addition, dendritic-cell-derived exosomes, when used as a cell-free vaccine, can eradicate established murine tumors. Although the precise physiological target(s) and functions of exosomes remain largely to be resolved, follicular dendritic cells (accessory cells in the germinal centers of secondary lymphoid organs) have recently been shown to bind B-lymphocyte-derived exosomes at their cell surface, which supports the notion that exosomes play an immunoregulatory role. Finally, since exosomes are derived from multivesicular bodies, their molecular composition might provide clues to the mechanism of protein and lipid sorting in endosomes.

969 citations


Journal ArticleDOI
TL;DR: In this article, a direct correspondence between the classical evolution equations of supergravity and the renormalization group (RG) equations of the dual $4-d$ large $N$ gauge theory was proposed.
Abstract: We propose a direct correspondence between the classical evolution equations of $5-d$ supergravity and the renormalization group (RG) equations of the dual $4-d$ large $N$ gauge theory. Using standard Hamilton-Jacobi theory, we derive first order flow equations for the classical supergravity action $S$, that take the usual form of the Callan-Symanzik equations, including the corrections due to the conformal anomaly. This result gives direct support for the identification of $S$ with the quantum effective action of the gauge theory. In addition we find interesting new relations between the beta-functions and the counterterms that affect the $4-d$ cosmological and Newton constant.

Journal ArticleDOI
TL;DR: This papermarizes recent physicochemical and biological information on polyplexes and aims to provide new insights with respect to thistype of gene delivery system and describes the in vitro and in vivo genetransfection behavior of polyplexe.
Abstract: Gene transfer to humans requires carriers for the plasmid DNA which can efficiently and safely carry the gene into the nucleus of the desired cells. A series of chemically different cationic polymers are currently being investigated for these purposes. Although many cationic polymers indeed condense DNA spontaneously, which is a requirement for gene transfer in most types of cells, the physicochemical and biopharmaceutical behavior of the current generation of polyplexes severely limits an efficient gene transfer in vitro and especially in vivo. This paper summarizes recent physicochemical and biological information on polyplexes and aims to provide new insights with respect to this type of gene delivery system. Firstly, the chemical structure of frequently studied cationic polymers is represented. Secondly, the parameters influencing condensation of DNA by cationic polymers are described. Thirdly, the surface properties, solubility, aggregration behavior, degradation and dissociation of polyplexes are considered. The review ends by describing the in vitro and in vivo gene transfection behavior of polyplexes.

Journal ArticleDOI
Sjef Smeekens1
01 Jun 2000
TL;DR: The role of sugar signaling in seed development and in seed germination is discussed, especially with respect to the various mechanisms by which sugar signaling controls gene expression.
Abstract: Sugars have important signaling functions throughout all stages of the plant's life cycle This review presents our current understanding of the different mechanisms of sugar sensing and sugar-induced signal transduction, including the experimental approaches used In plants separate sensing systems are present for hexose and sucrose Hexokinase-dependent and -independent hexose sensing systems can further be distinguished There has been progress in understanding the signal transduction cascade by analyzing the function of the SNF1 kinase complex and the regulatory PRL1 protein The role of sugar signaling in seed development and in seed germination is discussed, especially with respect to the various mechanisms by which sugar signaling controls gene expression Finally, recent literature on interacting signal transduction cascades is discussed, with particular emphasis on the ethylene and ABA signal transduction pathways


Journal ArticleDOI
TL;DR: In this article, the results of steady-state and time-resolved luminescence measurements performed on suspensions of nanocrystalline ZnO particles of different sizes and at different temperatures are presented.
Abstract: This report presents the results of steady-state and time-resolved luminescence measurements performed on suspensions of nanocrystalline ZnO particles of different sizes and at different temperatures. In all cases two emission bands are observed. One is an exciton emission band and the second an intense and broad visible emission band, shifted by approximately 1.5 eV with respect to the absorption onset. As the size of the particles increases, the intensity of the visible emission decreases while that of the exciton emission increases. As the temperature decreases, the relative intensity of the exciton emission increases. In accordance with the results presented in a previous paper, we assume that the visible emission is due to a transition of an electron from a level close to the conduction band edge to a deeply trapped hole in the bulk ( ) of the ZnO particle. The temperature dependence and size dependence of the ratio of the visible to exciton luminescence and the kinetics are explained by a model in w...

Journal ArticleDOI
TL;DR: First experimental evidence that protein turnover is a major determinant in AGE accumulation in different collagen types is provided, thereby providing the first reasonable estimates of the half-lives of these collagens.

Journal ArticleDOI
TL;DR: Results confirm the strong effects of job demands and job resources on exhaustion and disengagement respectively, and the mediating role of burnout between the working conditions and life satisfaction.
Abstract: This study, among 109 German nurses, tested a theoretically derived model of burnout and overall life satisfaction. The model discriminates between two conceptually different categories of working conditions, namely job demands and job resources. It was hypothesized that: (1) job demands, such as demanding contacts with patients and time pressure, are most predictive of exhaustion; (2) job resources, such as (poor) rewards and (lack of) participation in decision making, are most predictive of disengagement from work; and (3) job demands and job resources have an indirect impact on nurses' life satisfaction, through the experience of burnout (i.e., exhaustion and disengagement). A model including each of these relationships was tested simultaneously with structural equations modelling. Results confirm the strong effects of job demands and job resources on exhaustion and disengagement respectively, and the mediating role of burnout between the working conditions and life satisfaction. These findings contribute to existing knowledge about antecedents and consequences of occupational burnout, and provide guidelines for interventions aimed at preventing or reducing burnout among nurses.

Journal ArticleDOI
TL;DR: It was concluded that the use of Roundup herbicide does not result in adverse effects on development, reproduction, or endocrine systems in humans and other mammals, and glyphosate is noncarcinogenic.

Journal ArticleDOI
TL;DR: The use of various stabilization approaches has rendered some success in increasing protein stability, but, still, full preservation of the native protein structure remains a major challenge in the formulation of protein-loaded PLGA microparticles.
Abstract: In this review the current knowledge of protein degradation during preparation, storage and release from poly(lactic-co-glycolic acid) (PLGA) microparticles is described, as well as stabilization approaches. Although we have focussed on PLGA microparticles, the degradation processes and mechanisms described here are valid for many other polymeric release systems. Optimized process conditions as well as stabilizing excipients need to be used to counteract several stress factors that compromise the integrity of protein structure during preparation, storage, and release. The use of various stabilization approaches has rendered some success in increasing protein stability, but, still, full preservation of the native protein structure remains a major challenge in the formulation of protein-loaded PLGA microparticles.

Journal ArticleDOI
14 Jan 2000-Science
TL;DR: The real-space dynamics in a model system of colloidal hard spheres was studied by means of time-resolved fluorescence confocal scanning microscopy for direct experimental evidence for the presence of dynamical heterogeneities in a dense liquid.
Abstract: The real-space dynamics in a model system of colloidal hard spheres was studied by means of time-resolved fluorescence confocal scanning microscopy. Direct experimental evidence for the presence of dynamical heterogeneities in a dense liquid was obtained from an analysis of particle trajectories in two-dimensional slices of the bulk sample. These heterogeneities manifest themselves as a non-Gaussian probability distribution of particle displacements and also affect the onset of long-time diffusive behavior.

Journal ArticleDOI
TL;DR: In this paper, the factorial validity of the Maslach Burnout Inventory-General Survey (MBI-GS) was investigated among employees of a multinational company in the forest industry.
Abstract: The factorial validity of the Maslach Burnout Inventory-General Survey (MBI-GS) was investigated among employees of a multinational company in the forest industry. The present study includes data from Finnish, Swedish and Dutch employees (total N = 9055). The hypothesized three-factor model of the MBI-GS (Exhaustion, Cynicism, Professional Efficacy) was replicated across occupational groups (i.e. managers, clerks, foremen technicians, blue-collar workers) and nations. The fit of this model to the data was superior to alternative one- and two-factor models in all samples under investigation. In addition, the three-factor structure of the MBI-GS proved invariant across all occupational groups. The internal consistencies of the three subscales are satisfactory, except for the cynicism scale in some subsamples. Therefore, it is suggested to exclude one—ambiguous—cynicism item. Finally, some differences in levels of burnout are found between nations and occupational groups that are consistent with earlier findings.


Journal ArticleDOI
TL;DR: Data show that the Corsi Block-Tapping Task can be effectively used to assess visuospatial short-term memory in patients with brain damage, and is selective for the side of the lesion.
Abstract: This article describes a standardized administration and scoring procedure for the widely used Corsi Block-Tapping Task, designed to assess the visual memory span. This method was applied in a group of healthy participants (n = 70) and a group of patients with cerebral lesions (n = 70), that were categorized on the basis of lesion location (left or right hemisphere, bilateral or subcortical). The percentile distribution as well as cutoff points on the basis of the control data are provided. It was found that 20% of the patients perform in the borderline range on this task, and over 8% have an impaired performance ("retarded"). In addition, right hemisphere patients performed worse than left hemisphere patients. These data show that the Corsi Block-Tapping Task can be effectively used to assess visuospatial short-term memory in patients with brain damage, and is selective for the side of the lesion.

Journal ArticleDOI
TL;DR: The results indicated that bite forces achieved with overdentures on dental implants were between those achieved with artificial and natural dentitions, and a significant correlation was found between maximum bite force and chewing efficiency.
Abstract: It has been suggested that the provision of dental implants can improve the oral function of subjects with severely resorbed mandibles, possibly restoring function to the level experienced by satisfied wearers of conventional complete dentures. Nevertheless, a quantitative comparison has never been made and can be drawn from the literature only with difficulty, since studies differ greatly in methodology. To make such a comparison, we measured bite force and chewing efficiency by using identical methods in subjects with overdentures, complete full dentures, and natural dentitions. Our results indicated that bite forces achieved with overdentures on dental implants were between those achieved with artificial and natural dentitions. Chewing efficiency was significantly greater than that of subjects with full dentures (low mandible), but was still lower than that of subjects with full dentures (high mandible) and overdentures on bare roots. Differences in the height of the mandible revealed significant differences in chewing efficiency between the two full-denture groups. Furthermore, subjects with a shortened dental arch exerted bite forces similar to those of subjects with a complete-natural dentition, but their chewing efficiency was limited due to the reduced occlusal area. For all groups combined, a significant correlation was found between maximum bite force and chewing efficiency. Nearly half of the variation in chewing efficiency was explained by bite force alone.

Journal ArticleDOI
11 Oct 2000
TL;DR: In this article, the authors proposed to include spatial information by combining mutual information with a term based on the image gradient of the images to be registered, which not only seeks to align locations of high gradient magnitude, but also aims for a similar orientation of the gradients at these locations.
Abstract: Mutual information has developed into an accurate measure for rigid and affine monomodality and multimodality image registration. The robustness of the measure is questionable, however. A possible reason for this is the absence of spatial information in the measure. The present paper proposes to include spatial information by combining mutual information with a term based on the image gradient of the images to be registered. The gradient term not only seeks to align locations of high gradient magnitude, but also aims for a similar orientation of the gradients at these locations. Results of combining both standard mutual information as well as a normalized measure are presented for rigid registration of three-dimensional clinical images [magnetic resonance (MR), computed tomography (CT), and positron emission tomography (PET)]. The results indicate that the combined measures yield a better registration function does mutual information or normalized mutual information per se. The registration functions are less sensitive to low sampling resolution, do not contain incorrect global maxima that are sometimes found in the mutual information function, and interpolation-induced local minima can be reduced. These characteristics yield the promise of more robust registration measures. The accuracy of the combined measures is similar to that of mutual information-based methods.

Journal ArticleDOI
TL;DR: For example, the authors of the paper as discussed by the authors presented the results of a study at the Netherlands Institute of Terrestrial Ecology (ZG Heteren) and the University of Utrecht (UTHeteren).
Abstract: Assistant professor in the Department of Biology at Western Washington University, Bellingham, Washington 98225-9160 10: Professor at the Laboratoire d'Ecologie de Sols Tropicaux, ORSTOM/Universite Paris VI, 32 Avenue Henri Varagnat, 93143 Bondy, France 11: Senior scientist at the Centre for Terrestrial Ecology, Netherlands Institute of Ecology, 6666 ZG Heteren, Netherlands Utrecht, Netherlands 12: Professor at the Department of Environmental Studies, University of Utrecht, Utrecht, Netherlands 13: Professor at the Institute of Soil Biology, Academy of Sciences of the Czech Republic, Na sadkach 7, 370 05 Ceske Budejovice, Czech Republic 14: Professor at the Department of Environmental Science, Policy,and Management, University of California, Berkeley, California 94720-3110 15: Professor at the Center for Microbial Ecology, Michigan State University, 540 Plant and Soil Science Building, East Lansing, Michigan 48824-1325 16: Professor at the Department of Animal Ecology, Justus Liebig University of Giessen, Heinrich-Buff-Ring 26-32 (IFZ), D-35392 Giessen, Germany 2: Professor at the Queen Mary and Westfield College, School of Biological Sciences, University of London, London E1 4NS, United Kingdom 3: Research professor and the director of the Centre for Agri-Environmental Research, Department of Agriculture, University of Reading, Earley Gate, Reading RG6 6AT, United Kingdom 4: Professor of Soil Biology and Biological Soil Quality and director of the Department of Environmental Sciences, Wageningen University, 6700 EC Wageningen, Netherlands 5: Professor at the Centre for Biodiversity and Bioresources, School of Biological Sciences, Macquarie University, Sydney, New South Wales 2109, Australia 6: Chair, SCOPE Committee on Soil and Sediment Biodiversity and Ecosystem Functioning, and professor and director, Natural Resource Ecology Laboratory, Colorado State University, Fort Collins, Colorado 80523 7: Scientist at Landcare Research, Lincoln, New Zealand 8: Research professor in the Institute of Ecology at the University of Georgia, 102 Ecology Annex, Athens, Georgia 30602-2360 9: Professor at the Department of Soil Science and Agricultural Engineering, University of Zimbabwe, Mount Pleasant, Harare, Zimbabwe

Journal ArticleDOI
TL;DR: It now appears clear that the polar-aromatic residues Trp and Tyr have a specific affinity for a region near the lipid carbonyls, whereas positively charged residues extend into the lipid phosphate region.

Journal ArticleDOI
TL;DR: In this article, an integrated wetland research framework suggests that a combination of economic valuation, integrated modelling, stakeholder analysis, and multi-criteria evaluation can provide complementary insights into sustainable and welfare-optimising wetland management and policy.

Journal ArticleDOI
TL;DR: High levels of factor XI are a risk factor for deep venous thrombosis, with a doubling of the risk at levels that are present in 10 percent of the population.
Abstract: Background Factor XI, a component of the intrinsic pathway of coagulation, contributes to the generation of thrombin, which is involved in both the formation of fibrin and protection against fibrinolysis. A deficiency of factor XI is associated with bleeding, but a role of high factor XI levels in thrombosis has not been investigated. Methods We determined factor XI antigen levels in the patients enrolled in the Leiden Thrombophilia Study, a large population-based, case–control study (with a total of 474 patients and 474 controls) designed to estimate the contributions of genetic and acquired factors to the risk of deep venous thrombosis. Odds ratios were calculated as a measure of relative risk. Results The age- and sex-adjusted odds ratio for deep venous thrombosis in subjects who had factor XI levels above the 90th percentile, as compared with those who had factor XI levels at or below that value, was 2.2 (95 percent confidence interval, 1.5 to 3.2). There was a dose–response relation between the facto...

Journal ArticleDOI
TL;DR: Comparing the QL of a wide range of chronic disease patients found that patients who were older, female, had a low level of education, were not living with a partner, and had at least one comorbid condition, in general, reported the poorest level of QL.