Showing papers by "Utrecht University published in 1996"

Probabilistic roadmaps for path planning in high-dimensional configuration spaces

Abstract: A new motion planning method for robots in static workspaces is presented. This method proceeds in two phases: a learning phase and a query phase. In the learning phase, a probabilistic roadmap is constructed and stored as a graph whose nodes correspond to collision-free configurations and whose edges correspond to feasible paths between these configurations. These paths are computed using a simple and fast local planner. In the query phase, any given start and goal configurations of the robot are connected to two nodes of the roadmap; the roadmap is then searched for a path joining these two nodes. The method is general and easy to implement. It can be applied to virtually any type of holonomic robot. It requires selecting certain parameters (e.g., the duration of the learning phase) whose values depend on the scene, that is the robot and its workspace. But these values turn out to be relatively easy to choose, Increased efficiency can also be achieved by tailoring some components of the method (e.g., the local planner) to the considered robots. In this paper the method is applied to planar articulated robots with many degrees of freedom. Experimental results show that path planning can be done in a fraction of a second on a contemporary workstation (/spl ap/150 MIPS), after learning for relatively short periods of time (a few dozen seconds).

AQUA and PROCHECK-NMR: programs for checking the quality of protein structures solved by NMR

Abstract: The AQUA and PROCHECK-NMR programs provide a means of validating the geometry and restraint violations of an ensemble of protein structures solved by solution NMR. The outputs include a detailed breakdown of the restraint violations, a number of plots in PostScript format and summary statistics. These various analyses indicate both the degree of agreement of the model structures with the experimental dat, and the quality of their geometrical properties. They are intended to be of use both to support ongoing NMR structure determination and in the validation of the final results.

B lymphocytes secrete antigen-presenting vesicles.

Abstract: Antigen-presenting cells contain a specialized late endocytic compartment, MIIC (major histocompatibility complex [MHC] class II-enriched compartment), that harbors newly synthesized MHC class II molecules in transit to the plasma membrane. MIICs have a limiting membrane enclosing characteristic internal membrane vesicles. Both the limiting membrane and the internal vesicles contain MHC class II. In this study on B lymphoblastoid cells, we demonstrate by immunoelectron microscopy that the limiting membrane of MIICs can fuse directly with the plasma membrane, resulting in release from the cells of internal MHC class II-containing vesicles. These secreted vesicles, named exosomes, were isolated from the cell culture media by differential centrifugation followed by flotation on sucrose density gradients. The overall surface protein composition of exosomes differed significantly from that of the plasma membrane. Exosome-bound MHC class II was in a compact, peptide-bound conformation. Metabolically labeled MHC class II was released into the extracellular medium with relatively slow kinetics, 10 +/- 4% in 24 h, indicating that direct fusion of MIICs with the plasma membrane is not the major pathway by which MHC class II reaches the plasma membrane. Exosomes derived from both human and murine B lymphocytes induced antigen-specific MHC class II-restricted T cell responses. These data suggest a role for exosomes in antigen presentation in vivo.

The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis.

Abstract: Objective. —Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant disorder. The 3 recognized subtypes include MEN 2A, characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (pheo), and hyperparathyroidism (HPT); MEN 2B, by MTC, pheo, and characteristic stigmata; and familial MTC (FMTC), by the presence of MTC only. The purpose of this study was to establish the relationship between specific mutations and the presence of certain disease features in MEN 2 which could help in clinical decision making. Design. —Correlative survey study of 477 MEN 2 families. Setting. —Eighteen tertiary referral centers worldwide. Patients. —A total of 477 independent MEN 2 families. Main Outcome Measures. —Association between the position and type of germline mutation in the RET proto-oncogene and the presence or absence of MTC, pheo, HPT, and/or other features in a family. Results. —There is a statistically significant association between the presence of any mutation at a specific position (codon 634) and the presence of pheo and HPT. The presence of a specific mutation, CGC at codon 634, has yet to be associated with FMTC. Conversely, mutations at codons 768 and 804 are thus far seen only with FMTC, while codon 918 mutation is MEN 2B-specific. Rare families with both MEN 2 and Hirschsprung disease were found to have MEN 2-specific codon mutations. Patients with Hirschsprung disease presenting with such mutations should be monitored for the possible development of MEN 2 tumors. Conclusions. —This consortium analysis suggests that genotype-phenotype correlations do exist and, if made reliably absolute, could prove useful in the future in clinical management with respect to screening, surveillance, and prophylaxis, as well as provide insight into the genetic effects of particular mutations.

Systemic resistance in Arabidopsis induced by biocontrol bacteria is independent of salicylic acid accumulation and pathogenesis-related gene expression.

Abstract: Systemic acquired resistance is a pathogen-inducible defense mechanism in plants. The resistant state is dependent on endogenous accumulation of salicylic acid (SA) and is characterized by the activation of genes encoding pathogenesis-related (PR) proteins. Recently, selected nonpathogenic, root-colonizing biocontrol bacteria have been shown to trigger a systemic resistance response as well. To study the molecular basis underlying this type of systemic resistance, we developed an Arabidopsis-based model system using Fusarium oxysporum f sp raphani and Pseudomonas syringae pv tomato as challenging pathogens. Colonization of the rhizosphere by the biological control strain WCS417r of P. fluorescens resulted in a plant-mediated resistance response that significantly reduced symptoms elicited by both challenging pathogens. Moreover, growth of P. syringae in infected leaves was strongly inhibited in P. fluorescens WCS417r-treated plants. Transgenic Arabidopsis NahG plants, unable to accumulate SA, and wild-type plants were equally responsive to P. fluorescens WCS417r-mediated induction of resistance. Furthermore, P. fluorescens WCS417r-mediated systemic resistance did not coincide with the accumulation of PR mRNAs before challenge inoculation. These results indicate that P. fluorescens WCS417r induces a pathway different from the one that controls classic systemic acquired resistance and that this pathway leads to a form of systemic resistance independent of SA accumulation and PR gene expression.

Ordered accumulation of mutations in HIV protease confers resistance to ritonavir.

Abstract: Analysis of the HIV protease gene from the plasma of HIV-infected patients revealed substitutions at nine different codons selected in response to monotherapy with the protease inhibitor ritonavir. Mutants at valine-82, although insufficient to confer resistance, appeared first in most patients. Significant phenotypic resistance required multiple mutations in HIV protease, which emerged subsequently in an ordered, stepwise fashion. The appearance of resistance mutations was delayed in patients with higher plasma levels of ritonavir. Early mutants retained susceptibility to structurally diverse protease inhibitors, suggesting that dual protease inhibitor therapy might increase the duration of viral suppression.

A simple two-variable model of cardiac excitation

Abstract: We modified the FitzHugh-Nagumo model of an excitable medium so that it describes adequately the dymanics of pulse propagation in the canine myocardium. The modified model is simple enough to be used for intensive 3-dimensional (3D) computations of the whole heart. It simulates the pulse shape and the restitution property of the canine myocardium with good precision.

Schizophrenia after prenatal famine. Further evidence.

Abstract: Background: Suggestive findings of an earlier study that prenatal nutritional deficiency was a determinant of schizophrenia prompted us to undertake a second test of the hypothesis using more precise data on both exposure and outcome. Methods: Among persons born in the cities of western Netherlands during 1944 through 1946, we compared the risk for schizophrenia in those exposed and unexposed during early gestation to the Dutch Hunger Winter of 1944/1945. The frequency of hospitalized patients with schizophrenia at age 24 to 48 years in the exposed and unexposed birth cohorts was ascertained from a national psychiatric registry. Results: The most exposed birth cohort, conceived at the height of the famine, showed a twofold and statistically significant increase in the risk for schizophrenia (relative risk [RR] = 2.0; 95% confidence interval [CI] = 1.2 to 3.4;P Conclusion: Prenatal nutritional deficiency may play a role in the origin of some cases of schizophrenia.

Biexponential diffusion attenuation in various states of brain tissue: implications for diffusion-weighted imaging.

Abstract: Diffusion-weighted single voxel experiments conducted at b-values up to 1 x 10(4) smm-2 yielded biexponential signal attenuation curves for both normal and ischemic brain. The relative fractions of the rapidly and slowly decaying components (f1, f2) are f1 = 0.80 +/- 0.02, f2 = 0.17 +/- 0.02 in healthy adult rat brain and f1 = 0.90 +/- 0.02, f2 = 0.11 +/- 0.01 in normal neonatal rat brain, whereas the corresponding values for the postmortem situation are f1 = 0.69 +/- 0.02, f2 = 0.33 +/- 0.02. It is demonstrated that the changes in f1 and f2 occur simultaneously to those in the extracellular and intracellular space fractions (fex, f(in)) during: (i) cell swelling after total circulatory arrest, and (ii) the recovery from N-methyl-D-aspartate induced excitotoxic brain edema evoked by MK-801, as measured by changes in the electrical impedance. Possible reasons for the discrepancy between the estimated magnitude components and the physiological values are presented and evaluated. Implications of the biexponential signal attenuation curves for diffusion-weighted imaging experiments are discussed.

Mutations affecting the formation and function of the cardiovascular system in the zebrafish embryo.

Abstract: As part of a large-scale mutagenesis screen of the zebrafish genome, we have identified 58 mutations that affect the formation and function of the cardiovascular system. The cardiovascular system is particularly amenable for screening in the transparent zebrafish embryo because the heart and blood vessels are prominent and their function easily examined. We have classified the mutations affecting the heart into those that affect primarily either morphogenesis or function. Nine mutations clearly disrupt the formation of the heart. cloche deletes the endocardium. In cloche mutants, the myocardial layer forms in the absence of the endocardium but is dysmorphic and exhibits a weak contractility. Two loci, miles apart and bonnie and clyde, play a critical role in the fusion of the bilateral tubular primordia. Three mutations lead to an abnormally large heart and one to the formation of a diminutive, dysmorphic heart. We have found no mutation that deletes the myocardial cells altogether, but one, pandora, appears to eliminate the ventricle selectively. Seven mutations interfere with vascular integrity, as indicated by hemorrhage at particular sites. In terms of cardiac function, one large group exhibits a weak beat. In this group, five loci affect both chambers and seven a specific chamber (the atrium or ventricle). For example, the weak atrium mutation exhibits an atrium that becomes silent but has a normally beating ventricle. Seven mutations affect the rhythm of the heart causing, for example, a slow rate, a fibrillating pattern or an apparent block to conduction. In several other mutants, regurgitation of blood flow from ventricle to atrium is the most prominent abnormality, due either to the absence of valves or to poor coordination between the chambers with regard to the timing of contraction. The mutations identified in this screen point to discrete and critical steps in the formation and function of the heart and vasculature.

LISEM: a single-event physically based hydrological and soil erosion model for drainage basins; I: theory, input and output

Abstract: The Limburg Soil Erosion Model (LISEM) is a physically based model incorporated in a raster geographical information system. This incorporation facilitates easy application in larger catchments, improves the user-friendliness by avoiding conversion routines and allows the use of remotely sensed data. Processes incorporated in this model are rainfall, interception, surface storage in microdepressions, infiltration and vertical movement of water in the soil, overland flow, channel flow, detachment by rainfall and through-fall, detachment by overland flow and transport capacity of the flow. Special attention has been paid to the influence of tractor wheeling, small roads and surface sealing.

Improving structural integrity of cryosections for immunogold labeling.

Abstract: Cryosections of aldehyde-fixed material prepared according to Tokuyasu are a good substrate for immunocytochemistry. However, structural defects occur that limit the resolution of this approach. We found that the step during which sections are thawed and transferred from the cryochamber to the supporting film on an EM grid is most critical for structural preservation. Surface tension of the transfer medium, on which sections are spread during thawing, can easily damage their structure by overstretching. By substituting a mixture of methylcellulose and sucrose for the conventional sucrose transfer medium, we were able to alleviate the problem of overstretching, thus improving greatly the structural integrity of thin cryosections. Also, material extraction from the sections after thawing causes structural damage, particularly when cross-linking is deficient. Incorporation of uranyl acetate in the transfer medium can then further help to maintain the structural integrity of the sections during the immunolabeling procedure. Excellent ultrastructure was featured in sections picked up and dried directly in methylcellulose/uranyl acetate mixtures. Such preparations can provide new insight into subcellular details and is an efficient back-up for immunolabeled sections in respect of their morphology. Cryosections from fresh frozen tissue can be preserved for immunolabeling by using transfer media that contain fixatives. This approach may have advantages if chemical fixation of tissue is thought to induce morphological artifacts or antigen redistribution.

Consistency of the burnout construct across occupations

Abstract: This study assessed the extent to which a recently developed measure of burnout extended the concept of burnout as developed among human service providers to people in other occupations. The study replicated a factor structure derived from a study of aircraft maintenance workers, computer programmers, and administrators with staff in various occupations across two health care settings: a tertiary care hospital (N=3,312) and a residential mental health facility (N=417). Within the larger setting the analysis replicated the factor structure with four occupational groups: clerical/maintenance workers, technical personnel, nurses, and managers. The study found support for the validity of the scale through its consistency with the issues that participants raised in an open-ended questionnaire. Conceptual issues in burnout theory and suggestions for further research are presented.

Nucleocapsid-independent assembly of coronavirus-like particles by co-expression of viral envelope protein genes.

Abstract: Budding of enveloped viruses has been shown to be driven by interactions between a nucleocapsid and a proteolipid membrane. By contrast, we here describe the assembly of viral envelopes independent of a nucleocapsid. Membrane particles containing coronaviral envelope proteins were assembled in and released from animal cells co-expressing these proteins' genes from transfected plasmids. Of the three viral membrane proteins only two were required for particle formation, the membrane glycoprotein (M) and the small envelope protein (E). The spike (S) protein was dispensable but was incorporated when present. Importantly, the nucleocapsid protein (N) was neither required not taken into the particles when present. The E protein, recently recognized to be a structural protein, was shown to be an integral membrane protein. The envelope vesicles were found by immunogold labelling and electron microscopy to form a homogeneous population of spherical particles indistinguishable from authentic coronavirions in size (approximately 100 nm in diameter) and shape. They were less dense than virions and sedimented slightly slower than virions in sucrose velocity gradients. The nucleocapsid-independent formation of apparently bona fide viral envelopes represents a novel mode of virus assembly.

Evaluation and model impacts of alternative boundary-layer height formulations

Abstract: We study bulk formulations for the boundary-layer height which are currently in use for atmospheric modelling. The formulations are based on various forms of the Richardson number, and these are evaluated with Cabauw field data in stable conditions. Results for both a large-eddy simulation model and anE-e turbulence closure model for neutral boundary layers are also utilised. An updated formulation is introduced, which combines the effects of shear in the outer region of the boundary layer with surface friction. The updated formulation has a better performance for neutral boundary layers with upper level stratification. The findings are illustrated with a single-column model for a case with relatively high winds over the tropical ocean including shallow cumulus convection, and for a case with fair weather over land. We also show that for stable conditions, the updated formulation performs better than estimates on the basis of surface friction alone.

Data assimilation and inverse methods in terms of a probabilistic formulation

Abstract: The weak constraint inverse for nonlinear dynamical models is discussed and derived in term of a probabilistic formulation. The well-known result that for Gaussian error statistics the minimum of the weak constraint inverse is equal to the maximum-likelihood estimate is rederived. Then several methods based on ensemble statistics that can be used to find the smoother (as opposed to the filter) solution are introduced and compared to traditional methods. A strong point of the new methods is that they avoid the integration of adjoint equations, which is a complex task for real oceanographic or atmospheric applications. They also avoid iterative searches in a Hilbert space, and error estimates can be obtained without much additional computational effort. The feasibility of the new methods is illustrated in a two-layer quasigeostrophic ocean model.

A Theory of Aspectuality: The Interaction between Temporal and Atemporal Structure

Abstract: Part I. Issues of Compositionality: 1. The plus-principle 2. Aspectual classes and aspectual composition Part II. Noun Phrase Structure: 3. The tools of generalised quantification 4. In search of SQA 5. Numerals and quantifiers: one level up 6. Some problems of prenominal NP structure 7. Determiner structure 8. Some explorative issues Part III. Temporal Structure: 9. Homogeneity 10. Localism and additive structure 11. Event semantics and aspect construal 12. Aspect and perspective 13. Event construal 14. Testing the plus-principle Conclusion Notes References Index.

Reactive oxygen intermediates increase vascular endothelial growth factor expression in vitro and in vivo.

Abstract: Elevated vascular endothelial growth factor (VEGF) levels are required for ocular and tumor angiogenesis in animal models. Ischemic hypoxia is strongly correlated with increased VEGF expression in these systems and is considered a physiologically relevant stimulus. Because ischemic hypoxia is often followed by reperfusion and reactive oxygen intermediate (ROI) generation, we examined the potential role of ROI in the control of VEGF gene expression. Human retinal pigment epithelial cells exposed to superoxide or hydrogen peroxide rapidly increased VEGF mRNA levels. Superoxide-associated mRNA increases were dose dependent, blocked by antioxidants, and associated with elevated VEGF protein levels in conditioned media. Increases in VEGF mRNA levels were also observed in cultured human melanoma and rat glioblastoma cells with superoxide or hydrogen peroxide. Cycloheximide prevented the ROI-associated increases in VEGF mRNA. Transcriptional inhibition with actinomycin D revealed an inducible increase in VEGF mRNA half-life, but nuclear run-on experiments showed no increase in VEGF transcriptional rate. Reoxygenation of human retinal pigment epithelial cells in vitro and ocular reperfusion in vivo increased retinal VEGF mRNA levels. Antioxidants prevented the reperfusion-associated VEGF mRNA increases in retina. We conclude that ROIs increase VEGF gene expression in vitro and during the reperfusion of ischemic retina in vivo. The ROI-associated increases are mediated largely through increases in VEGF mRNA stability.

A plasmocyte selective monoclonal antibody (B-B4) recognizes syndecan-1.

Abstract: We developed a new monoclonal antibody. B-B4, which specifically identifies human plasma cells. It strongly reacts with all multiple myeloma cell lines and with malignant plasma cells of all tumour samples of the multiple myeloma patients tested. B-B4 does not react with any peripheral blood, bone marrow or tonsil cells. Cloning of the B-B4 antigen reveals that the monoclonal antibody recognizes syndecan-1. It appears that the monoclonal antibody B-B4 is a suitable marker for human plasmocyte identification among haemopoietic cells and a useful probe for the diagnosis of haematological malignancies. Furthermore, this monoclonal antibody can be used for depletions prior to CD34 grafting.

Assimilation of Geosat Altimeter Data for the Agulhas Current Using the Ensemble Kalman Filter with a Quasigeostrophic Model

Abstract: The ring-shedding process in the Agulhas Current is studied using the ensemble Kalman filter to assimilate Geosat altimeter data into a two-layer quasigeostrophic ocean model. The properties of the ensemble Kalman filter are further explored with focus on the analysis scheme and the use of gridded data. The Geosat data consist of 10 fields of gridded sea surface height anomalies separated 10 days apart that are added to a climatic mean field. This corresponds to a huge number of data values, and a data reduction scheme must be applied to increase the efficiency of the analysis procedure. Further, it is illustrated how one can resolve the rank problem occurring when a too large dataset or a small ensemble is used.

Studies on identity development in adolescence: An overview of research and some new data

Abstract: The fundamental developmental hypothesis of the identity status model is that as adolescents become older they undergo progressive developmental shifts in identity status: from diffusion to foreclosure or moratorium, from foreclosure to moratorium, and from moratorium to identity achievement. In Study I we give an overview of identity status studies carried out during the period 1966–1993 and show that progressive developmental trends (PDTs) are found in most of these studies. However, they usually involve progressive developmental trends in one of the higher or lower statuses (PDT 1), while only a small minority involve systematic progressive developmental trends, i.e., in at least three statuses (PDT≥3). It is easier to show progressive developmental trends with separate measures for commitment and exploration than with identity status classification. Study II reports on our own research into relational identity, measured with a new instrument: the Utrecht-Groningen Identity Development Scale (U-GIDS). Application of the U-GIDS allows the construction of four statuses: diffusion, moratorium, closed commitment and achieving commitment. For these four statuses progressive developmental trends were found for relational identity in both one of the higher and one of the lower statuses. The four statuses of our model display exactly the same connection with psychological well-being as the statuses of Marcia's model. The high commitment statuses show the highest level of psychological well-being, followed by the diffusions, while the moratoriums are the least happy. This result offers a new perspective on moratorium as a high identity status. Finally it was found that the differences in psychological well-being among the statuses become greater as adolescents become older.