Showing papers by "Utrecht University published in 2010"

The Catalytic Valorization of Lignin for the Production of Renewable Chemicals

Abstract: Biomass is an important feedstock for the renewable production of fuels, chemicals, and energy. As of 2005, over 3% of the total energy consumption in the United States was supplied by biomass, and it recently surpassed hydroelectric energy as the largest domestic source of renewable energy. Similarly, the European Union received 66.1% of its renewable energy from biomass, which thus surpassed the total combined contribution from hydropower, wind power, geothermal energy, and solar power. In addition to energy, the production of chemicals from biomass is also essential; indeed, the only renewable source of liquid transportation fuels is currently obtained from biomass.

elastix : A Toolbox for Intensity-Based Medical Image Registration

Abstract: Medical image registration is an important task in medical image processing. It refers to the process of aligning data sets, possibly from different modalities (e.g., magnetic resonance and computed tomography), different time points (e.g., follow-up scans), and/or different subjects (in case of population studies). A large number of methods for image registration are described in the literature. Unfortunately, there is not one method that works for all applications. We have therefore developed elastix, a publicly available computer program for intensity-based medical image registration. The software consists of a collection of algorithms that are commonly used to solve medical image registration problems. The modular design of elastix allows the user to quickly configure, test, and compare different registration methods for a specific application. The command-line interface enables automated processing of large numbers of data sets, by means of scripting. The usage of elastix for comparing different registration methods is illustrated with three example experiments, in which individual components of the registration method are varied.

Multilevel Analysis : Techniques and Applications, Second Edition

Abstract: This practical introduction helps readers apply multilevel techniques to their research Noted as an accessible introduction, the book also includes advanced extensions, making it useful as both an introduction and as a reference to students, researchers, and methodologists Basic models and examples are discussed in non-technical terms with an emphasis on understanding the methodological and statistical issues involved in using these models The estimation and interpretation of multilevel models is demonstrated using realistic examples from various disciplines For example, readers will find data sets on stress in hospitals, GPA scores, survey responses, street safety, epilepsy, divorce, and sociometric scores, to name a few The data sets are available on the website in SPSS, HLM, MLwiN, LISREL and/or Mplus files Readers are introduced to both the multilevel regression model and multilevel structural models Highlights of the second edition include: Two new chapters—one on multilevel models for ordinal and count data (Ch 7) and another on multilevel survival analysis (Ch 8) Thoroughly updated chapters on multilevel structural equation modeling that reflect the enormous technical progress of the last few years The addition of some simpler examples to help the novice, whilst the more complex examples that combine more than one problem have been retained A new section on multivariate meta-analysis (Ch 11) Expanded discussions of covariance structures across time and analyzing longitudinal data where no trend is expected Expanded chapter on the logistic model for dichotomous data and proportions with new estimation methods An updated website at http://wwwjoophoxnet/ with data sets for all the text examples and up-to-date screen shots and PowerPoint slides for instructors Ideal for introductory courses on multilevel modeling and/or ones that introduce this topic in some detail taught in a variety of disciplines including: psychology, education, sociology, the health sciences, and business The advanced extensions also make this a favorite resource for researchers and methodologists in these disciplines A basic understanding of ANOVA and multiple regression is assumed The section on multilevel structural equation models assumes a basic understanding of SEM

Climate change will affect the Asian water towers.

Abstract: More than 1.4 billion people depend on water from the Indus, Ganges, Brahmaputra, Yangtze, and Yellow rivers. Upstream snow and ice reserves of these basins, important in sustaining seasonal water availability, are likely to be affected substantially by climate change, but to what extent is yet unclear. Here, we show that meltwater is extremely important in the Indus basin and important for the Brahmaputra basin, but plays only a modest role for the Ganges, Yangtze, and Yellow rivers. A huge difference also exists between basins in the extent to which climate change is predicted to affect water availability and food security. The Brahmaputra and Indus basins are most susceptible to reductions of flow, threatening the food security of an estimated 60 million people.

Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia Proposed Modification of the Task Force Criteria

Abstract: Background— In 1994, an International Task Force proposed criteria for the clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) that facilitated recognition and ...

Functional impact of global rare copy number variation in autism spectrum disorders

Abstract: The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.

Amazonia Through Time: Andean Uplift, Climate Change, Landscape Evolution, and Biodiversity

Abstract: The Amazonian rainforest is arguably the most species-rich terrestrial ecosystem in the world, yet the timing of the origin and evolutionary causes of this diversity are a matter of debate. We review the geologic and phylogenetic evidence from Amazonia and compare it with uplift records from the Andes. This uplift and its effect on regional climate fundamentally changed the Amazonian landscape by reconfiguring drainage patterns and creating a vast influx of sediments into the basin. On this “Andean” substrate, a region-wide edaphic mosaic developed that became extremely rich in species, particularly in Western Amazonia. We show that Andean uplift was crucial for the evolution of Amazonian landscapes and ecosystems, and that current biodiversity patterns are rooted deep in the pre-Quaternary.

Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

Abstract: By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P<5x10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.

Treating rheumatoid arthritis to target: recommendations of an international task force

Abstract: Aiming at therapeutic targets has reduced the risk of organ failure in many diseases such as diabetes or hypertension. Such targets have not been defined for rheumatoid arthritis (RA).

Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia

Abstract: Background In 1994, an International Task Force proposed criteria for the clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) that facilitated recognition and interpretation of the frequently nonspecific clinical features of ARVC/D. This enabled confirmatory clinical diagnosis in index cases through exclusion of phenocopies and provided a standard on which clinical research and genetic studies could be based. Structural, histological, electrocardiographic, arrhythmic, and familial features of the disease were incorporated into the criteria, subdivided into major and minor categories according to the specificity of their association with ARVC/D. At that time, clinical experience with ARVC/D was dominated by symptomatic index cases and sudden cardiac death victims–the overt or severe end of the disease spectrum. Consequently, the 1994 criteria were highly specific but lacked sensitivity for early and familial disease. Methods and Results Revision of the diagnostic criteria provides guidance on the role of emerging diagnostic modalities and advances in the genetics of ARVC/D. The criteria have been modified to incorporate new knowledge and technology to improve diagnostic sensitivity, but with the important requisite of maintaining diagnostic specificity. The approach of classifying structural, histological, electrocardiographic, arrhythmic, and genetic features of the disease as major and minor criteria has been maintained. In this modification of the Task Force criteria, quantitative criteria are proposed and abnormalities are defined on the basis of comparison with normal subject data. Conclusions The present modifications of the Task Force Criteria represent a working framework to improve the diagnosis and management of this condition. Clinical Trial Registration clinicaltrials.gov Identifier: NCT00024505.

The construction of next-generation matrices for compartmental epidemic models.

Abstract: The basic reproduction number ℛ0 is arguably the most important quantity in infectious disease epidemiology. The next-generation matrix (NGM) is the natural basis for the definition and calculation...

Critical Evaluation of Nanoparticle Tracking Analysis (NTA) by NanoSight for the Measurement of Nanoparticles and Protein Aggregates

Abstract: Purpose To evaluate the nanoparticle tracking analysis (NTA) technique, compare it with dynamic light scattering (DLS) and test its performance in characterizing drug delivery nanoparticles and protein aggregates.

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs

Abstract: Treatment of rheumatoid arthritis (RA) may differ among rheumatologists and currently, clear and consensual international recommendations on RA treatment are not available. In this paper recommendations for the treatment of RA with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) that also account for strategic algorithms and deal with economic aspects, are described. The recommendations are based on evidence from five systematic literature reviews (SLRs) performed for synthetic DMARDs, biological DMARDs, GCs, treatment strategies and economic issues. The SLR-derived evidence was discussed and summarised as an expert opinion in the course of a Delphi-like process. Levels of evidence, strength of recommendations and levels of agreement were derived. Fifteen recommendations were developed covering an area from general aspects such as remission/low disease activity as treatment aim via the preference for methotrexate monotherapy with or without GCs vis-a-vis combination of synthetic DMARDs to the use of biological agents mainly in patients for whom synthetic DMARDs and tumour necrosis factor inhibitors had failed. Cost effectiveness of the treatments was additionally examined. These recommendations are intended to inform rheumatologists, patients and other stakeholders about a European consensus on the management of RA with DMARDs and GCs as well as strategies to reach optimal outcomes of RA, based on evidence and expert opinion.

Global depletion of groundwater resources

Abstract: [1] In regions with frequent water stress and large aquifer systems groundwater is often used as an additional water source. If groundwater abstraction exceeds the natural groundwater recharge for extensive areas and long times, overexploitation or persistent groundwater depletion occurs. Here we provide a global overview of groundwater depletion (here defined as abstraction in excess of recharge) by assessing groundwater recharge with a global hydrological model and subtracting estimates of groundwater abstraction. Restricting our analysis to sub-humid to arid areas we estimate the total global groundwater depletion to have increased from 126 (±32) km3 a−1 in 1960 to 283 (±40) km3 a−1 in 2000. The latter equals 39 (±10)% of the global yearly groundwater abstraction, 2 (±0.6)% of the global yearly groundwater recharge, 0.8 (±0.1)% of the global yearly continental runoff and 0.4 (±0.06)% of the global yearly evaporation, contributing a considerable amount of 0.8 (±0.1) mm a−1 to current sea-level rise.

Termination of autophagy and reformation of lysosomes regulated by mTOR

Abstract: Autophagy is an evolutionarily conserved process by which cytoplasmic proteins and organelles are catabolized During starvation, the protein TOR (target of rapamycin), a nutrient-responsive kinase, is inhibited, and this induces autophagy In autophagy, double-membrane autophagosomes envelop and sequester intracellular components and then fuse with lysosomes to form autolysosomes, which degrade their contents to regenerate nutrients Current models of autophagy terminate with the degradation of the autophagosome cargo in autolysosomes, but the regulation of autophagy in response to nutrients and the subsequent fate of the autolysosome are poorly understood Here we show that mTOR signalling in rat kidney cells is inhibited during initiation of autophagy, but reactivated by prolonged starvation Reactivation of mTOR is autophagy-dependent and requires the degradation of autolysosomal products Increased mTOR activity attenuates autophagy and generates proto-lysosomal tubules and vesicles that extrude from autolysosomes and ultimately mature into functional lysosomes, thereby restoring the full complement of lysosomes in the cell-a process we identify in multiple animal species Thus, an evolutionarily conserved cycle in autophagy governs nutrient sensing and lysosome homeostasis during starvation

Severe Hypoglycemia and Risks of Vascular Events and Death

Abstract: Background Severe hypoglycemia may increase the risk of a poor outcome in patients with type 2 diabetes assigned to an intensive glucose-lowering intervention. We analyzed data from a large study of intensive glucose lowering to explore the relationship between severe hypoglycemia and adverse clinical outcomes. Methods We examined the associations between severe hypoglycemia and the risks of macrovascular or microvascular events and death among 11,140 patients with type 2 diabetes, using Cox proportional-hazards models with adjustment for covariates measured at baseline and after randomization. Results During a median follow-up period of 5 years, 231 patients (2.1%) had at least one severe hypoglycemic episode; 150 had been assigned to intensive glucose control (2.7% of the 5571 patients in that group), and 81 had been assigned to standard glucose control (1.5% of the 5569 patients in that group). The median times from the onset of severe hypoglycemia to the first major macrovascular event, the first major microvascular event, and death were 1.56 years (interquartile range, 0.84 to 2.41), 0.99 years (interquartile range, 0.40 to 2.17), and 1.05 years (interquartile range, 0.34 to 2.41), respectively. During follow-up, severe hypoglycemia was associated with a significant increase in the adjusted risks of major macrovascular events (hazard ratio, 2.88; 95% confidence interval [CI], 2.01 to 4.12), major microvascular events (hazard ratio, 1.81; 95% CI, 1.19 to 2.74), death from a cardiovascular cause (hazard ratio, 2.68; 95% CI, 1.72 to 4.19), and death from any cause (hazard ratio, 2.69; 95% CI, 1.97 to 3.67) (P<0.001 for all comparisons). Similar associations were apparent for a range of nonvascular outcomes, including respiratory, digestive, and skin conditions (P<0.01 for all comparisons). No relationship was found between repeated episodes of severe hypoglycemia and vascular outcomes or death. Conclusions Severe hypoglycemia was strongly associated with increased risks of a range of adverse clinical outcomes. It is possible that severe hypoglycemia contributes to adverse outcomes, but these analyses indicate that hypoglycemia is just as likely to be a marker of vulnerability to such events. (Funded by Servier and the National Health and Medical Research Council of Australia; ClinicalTrials.gov number, NCT00145925.)

A step-up approach or open necrosectomy for necrotizing pancreatitis

Abstract: Background Necrotizing pancreatitis with infected necrotic tissue is associated with a high rate of complications and death. Standard treatment is open necrosectomy. The outcome may be improved by a minimally invasive step-up approach. Methods In this multicenter study, we randomly assigned 88 patients with necrotizing pancreatitis and suspected or confirmed infected necrotic tissue to undergo primary open necrosectomy or a step-up approach to treatment. The step-up approach consisted of percutaneous drainage followed, if necessary, by minimally invasive retroperitoneal necrosectomy. The primary end point was a composite of major complications (new-onset multiple-organ failure or multiple systemic complications, perforation of a visceral organ or enterocutaneous fistula, or bleeding) or death. Results The primary end point occurred in 31 of 45 patients (69%) assigned to open necrosectomy and in 17 of 43 patients (40%) assigned to the step-up approach (risk ratio with the step-up approach, 0.57; 95% confidence interval, 0.38 to 0.87; P = 0.006). Of the patients assigned to the step-up approach, 35% were treated with percutaneous drainage only. New-onset multiple-organ failure occurred less often in patients assigned to the step-up approach than in those assigned to open necrosectomy (12% vs. 40%, P = 0.002). The rate of death did not differ significantly between groups (19% vs. 16%, P = 0.70). Patients assigned to the step-up approach had a lower rate of incisional hernias (7% vs. 24%, P = 0.03) and new-onset diabetes (16% vs. 38%, P = 0.02). Conclusions A minimally invasive step-up approach, as compared with open necrosectomy, reduced the rate of the composite end point of major complications or death among patients with necrotizing pancreatitis and infected necrotic tissue. (Current Controlled Trials number, ISRCTN13975868.)

The HADDOCK web server for data-driven biomolecular docking

Abstract: Computational docking is the prediction or modeling of the three-dimensional structure of a biomolecular complex, starting from the structures of the individual molecules in their free, unbound form. HADDOCK is a popular docking program that takes a data-driven approach to docking, with support for a wide range of experimental data. Here we present the HADDOCK web server protocol, facilitating the modeling of biomolecular complexes for a wide community. The main web interface is user-friendly, requiring only the structures of the individual components and a list of interacting residues as input. Additional web interfaces allow the more advanced user to exploit the full range of experimental data supported by HADDOCK and to customize the docking process. The HADDOCK server has access to the resources of a dedicated cluster and of the e-NMR GRID infrastructure. Therefore, a typical docking run takes only a few minutes to prepare and a few hours to complete.

Coexistence of Quiescent and Active Adult Stem Cells in Mammals

Abstract: Adult stem cells are crucial for physiological tissue renewal and regeneration after injury. Prevailing models assume the existence of a single quiescent population of stem cells residing in a specialized niche of a given tissue. Emerging evidence indicates that both quiescent (out of cell cycle and in a lower metabolic state) and active (in cell cycle and not able to retain DNA labels) stem cell subpopulations may coexist in several tissues, in separate yet adjoining locations. Here, we summarize these findings and propose that quiescent and active stem cell populations have separate but cooperative functional roles.

Definition of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage as an Outcome Event in Clinical Trials and Observational Studies Proposal of a Multidisciplinary Research Group

Abstract: Background and Purpose—In clinical trials and observational studies there is considerable inconsistency in the use of definitions to describe delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage. A major cause for this inconsistency is the combining of radiographic evidence of vasospasm with clinical features of cerebral ischemia, although multiple factors may contribute to DCI. The second issue is the variability and overlap of terms used to describe each phenomenon. This makes comparisons among studies difficult. Methods—An international ad hoc panel of experts involved in subarachnoid hemorrhage research developed and proposed a definition of DCI to be used as an outcome measure in clinical trials and observational studies. We used a consensus-building approach. Results—It is proposed that in observational studies and clinical trials aiming to investigate strategies to prevent DCI, the 2 main outcome measures should be: (1) cerebral infarction identified on CT or MRI or proven at au...

Identification of Functional Elements and Regulatory Circuits by Drosophila modENCODE

Abstract: To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.

Spin Transfer Torques in MnSi at Ultralow Current Densities

Abstract: Spin manipulation using electric currents is one of the most promising directions in the field of spintronics. We used neutron scattering to observe the influence of an electric current on the magnetic structure in a bulk material. In the skyrmion lattice of manganese silicon, where the spins form a lattice of magnetic vortices similar to the vortex lattice in type II superconductors, we observe the rotation of the diffraction pattern in response to currents that are over five orders of magnitude smaller than those typically applied in experimental studies on current-driven magnetization dynamics in nanostructures. We attribute our observations to an extremely efficient coupling of inhomogeneous spin currents to topologically stable knots in spin structures.

Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database

Abstract: Objectives To determine the causes and predictors of mortality in systemic sclerosis (SSc). Methods Patients with SSc (n=5860) fulfilling the American College of Rheumatology criteria and prospectively followed in the EULAR Scleroderma Trials and Research (EUSTAR) cohort were analysed. EUSTAR centres completed a structured questionnaire on cause of death and comorbidities. Kaplan-Meier and Cox proportional hazards models were used to analyse survival in SSc subgroups and to identify predictors of mortality. Results Questionnaires were obtained on 234 of 284 fatalities. 55% of deaths were attributed directly to SSc and 41% to non-SSc causes; in 4% the cause of death was not assigned. Of the SSc-related deaths, 35% were attributed to pulmonary fibrosis, 26% to pulmonary arterial hypertension (PAH) and 26% to cardiac causes (mainly heart failure and arrhythmias). Among the non-SSc-related causes, infections (33%) and malignancies (31%) were followed by cardiovascular causes (29%). Of the non-SSc-related fatalities, 25% died of causes in which SSc-related complications may have participated (pneumonia, sepsis and gastrointestinal haemorrhage). Independent risk factors for mortality and their HR were: proteinuria (HR 3.34), the presence of PAH based on echocardiography (HR 2.02), pulmonary restriction (forced vital capacity below 80% of normal, HR 1.64), dyspnoea above New York Heart Association class II (HR 1.61), diffusing capacity of the lung (HR 1.20 per 10% decrease), patient age at onset of Raynaud's phenomenon (HR 1.30 per 10 years) and the modified Rodnan skin score (HR 1.20 per 10 score points). Conclusion Disease-related causes, in particular pulmonary fibrosis, PAH and cardiac causes, accounted for the majority of deaths in SSc.