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Safety and cost control are critical success factors in the realm of drilling. Actual well costs frequently exceed planned costs due to unexpected drilling incidents related to potentially avoidable geohazards. It is estimated that - in the Netherlands on average - around 20% of drilling time is spent recovering from such unexpected incidents. A significant part of this non-productive time (NPT) can be avoided if geohazards are identified upfront. The risk assessment for a well trajectory is largely based on the experience from offset wells: boreholes in the neighbourhood that have been drilled earlier or holes drilled through similar geological settings. Easy access to relevant historic drilling data and the records of geohazards encountered in offset wells is essential for effective de-risking of future drilling programs. Currently operators typically have their own databases containing this type of information. However, their databases are often incomplete and lack data from competitor wells. Obviously, the risk assessment would greatly benefit from access to a complete set of drilling hazard data, whilst making use of "best practices" in data analyses and incident classification. EBN B.V., the Dutch state E&P company with 0.5 million BOE/d equity production, is involved in most of the 40+ wells being drilled annually in the Netherlands. Recognising its major vested interest in improved drilling performance, EBN launched a Joint Industry Project to capture the knowledge of drilling hazards across the Industry. An important tool to classify drilling incidents is the Drilling Incidence Triangle. Based on this new concept, those drilling incidents that have a geological component are selected, analysed and made accessible for the Industry partners. Copyright 2013, Society of Petroleum Engineers.

This paper presents the results from an assessment of high-capacity storage options in the offshore area of The Netherlands. For deep saline formations, available regional geological maps were combined with fault structures derived from seismic data to reveal the compartmentalization of prospective reservoir formations. Adding knowledge concerning these formations from offshore oil and gas activities and concerning the behavior of gas fields located in these formations, resulted in a shortlist of lowest-risk, potential storage locations with a total theoretical capacity of about 1.5 GtCO2. A high-level risk analysis was performed for offshore gas fields. The largest offshore gas fields add another 350 MtCO2. The development of saline formations and gas fields is outlined; while a gas field can be converted from production to storage in 5-6 yrs, it takes at least 7 yrs to develop CO2 storage in a saline formation that has not been accessed before for hydrocarbon production.

Housing systems for captive animals have often been designed on the basis of economic and ergonomic considerations, such as equipment, costs, space, workload, ability to observe the animals and to maintain a certain degree of hygiene, with little or no consideration for animal welfare. Environmental refinement can be defined as any modification in the environment of captive animals that seeks to enhance the physical and psychological well-being of the animals by providing stimuli which meet the animals' species-specific needs. This article provides an overview of environmental factors that influence the well-being of captive animals with specific reference to the needs of the most common laboratory species.It is important to evaluate environmental refinement in terms of the benefit to the animal, by assessing the use of and preference for certain enrichment, the effect on behaviour, and the performance of species-typical behaviour on physiological parameters. It is also necessary to evaluate the impact of refinement on scientific outcome, including whether and how statistical power is affected. Communication and team work between animal welfare scientists, animal research scientists, institutional animal welfare officers, veterinarians and animal ethics committees, animal facility management and personnel, are essential for success. © 2012 Elsevier Ltd.

Hypertension is highly prevalent among renal transplant recipients (RTR) and a risk factor for graft failure and cardiovascular events. Protein intake has been claimed to affect blood pressure (BP) in the general population and may affect renal function. We examined the association of dietary protein with BP and renal function in RTR. We included 625 RTR (age 53 (sd 13) years; 57 % male). Protein intake was assessed with a FFQ, differentiating between animal and plant protein. BP was measured according to a strict protocol. Creatinine clearance and albuminuria were measured as renal parameters. Protein intake was 83 (sd 12) g/d, of which 63 % derived from animal sources. BP was 136 (sd 17) mmHg systolic (SBP) and 83 (sd 11) mmHg diastolic (DBP). Creatinine clearance was 66 (sd 26) ml/min; albuminuria 41 (10-178) mg/24 h. An inverse, though statistically insignificant, association was found between the total protein intake and both SBP (β =-2·22 mmHg per sd, P= 0·07) and DBP (β =-0·48 mmHg per sd, P= 0·5). Protein intake was not associated with creatinine clearance. Although albuminuria was slightly higher in the highest tertile of animal protein intake compared with the lowest tertile (66 v. 33 mg/d, respectively, P= 0·03), linear regression analyses did not reveal significant associations between dietary protein and albuminuria. Protein intake exceeded the current recommendations. Nevertheless, within the range of protein intake in our RTR population, we found no evidence for an association of dietary protein with BP and renal function. Intervention studies focusing on different protein types are warranted to clarify their effect on BP and renal function in RTR. © 2012 The Authors.

Wie aan milieuvervuiling denkt, denkt aan giflozingen, het broeikaseffect of vervuilde lucht, maar schade door lawaai, daar hoor je niet vaak over, en dat terwijl lawaai jaarlijks duizenden gezonde levensjaren kost

Short-chain fatty acids (SCFAs), the end products of fermentation of dietary fibers by the anaerobic intestinal microbiota, have been shown to exert multiple beneficial effects on mammalian energy metabolism. The mechanisms underlying these effects are the subject of intensive research and encompass the complex interplay between diet, gut microbiota, and host energy metabolism. This review summarizes the role of SCFAs in host energy metabolism, starting from the production by the gut microbiota to the uptake by the host and ending with the effects on host metabolism. There are interesting leads on the underlying molecular mechanisms, but there are also many apparently contradictory results . A coherent understanding of the multilevel network in which SCFAs exert their effects is hampered by the lack of quantitative data on actual fluxes of SCFAs and metabolic processes regulated by SCFAs. In this review we address questions that, when answered, will bring us a great step forward in elucidating the role of SCFAs in mammalian energy metabolism. Copyright © 2013 by the American Society for Biochemistry and Molecular Biology, Inc.

In urban areas, road traffrc noise is a dominant source of environmental noise and a major cause of noise annoyance and disturbed sleep. It has been hypothesized that respondents highly exposed to noise at multiple sides of their dwelling, may be expected to be worse off than respondents with the same exposure at the most exposed side, but also having a quiet side to their dwelling. Previous studies provide support for this hypothesis, however to date only a limited number of studies have investigated this hypothesis. There is a need for strengthening existing evidence, and for further quantification of the effects. Within the EU project QSIDE, the effect of the least exposed facade on annoyance and sleep response is studied in different EU cities in Sweden, Belgium and the Netherlands, including Gothenburg, Stockholm, Antwerp, Gent and Amsterdam. In this paper we discuss the general picture arising from the outcome of these studies. We discuss what the implications may be for new situations (urban planning) and existing high exposure situations (noise abatement measures). The noise environment may be improved by taking into account the exposure levels, and promoting quietness, at the least exposed façade.

Overcoming challenges and innovating success for the production of edible 3D products. A look at the opportunity for the food manufacturing industry to tap into the novel production scheme.

European bridges are today in a state of particular concern with over 50% of European urban bridges being more than 40 years old and thus requiring considerable maintenance or possibly even replacement [1]. This means that interventions in the present infrastructure have to be made while ensuring that mobility continues in a safe and consistent manner. Also the (re-)construction of the bridge has to be completed in a sustainable manner with minimum disturbance to the users and local residents. In order to meet the demand for disturbance friendly construction alternatives, a European benchmark of civil engineering projects was created. Ultimately the solution is the use of a Multi Criteria Decision Model (MCDM) linked with the results of the benchmarking assessment in order to weight the selection criteria for the most advantageous construction alternative possible.

Verkennend onderzoek van TNO en IRAS laat zien dat bewoners langs drukke binnenvaarwegen worden blootgesteld aan roetconcentraties vergelijkbaar met wonen langs een drukke snelweg

Sixty visible range photon signals spontaneously emitted from the dorsal side of both hands of fifteen human subjects are analyzed with the aim of finding their attributes. The signals are of 30 min duration and detected in bins of 50 ms by two synchronized photo multipliers sensitive in the range (290-630 nm). Each signal is a time series of 36,000 elements. The attributes of its signal are determined from the statistical properties of time series. The mean and variance of time series determine the attributes signal strength and intercept (p0) and slope (p1) of the Fano Factor curve. The photon count distribution of the time series determines squeezed state parameters |α|, r, θ and, squeezed state index (SSI), and sum of the squares of residue (SSR). The correlation between simultaneously detected signals determines intercept (c0) and slope (c1) of their correlation curve. The variability of attributes is studied by calculating them in smaller intervals covering the entire signal. The profile of attribute at 12 sites in a subject is more informative and biologically relevant. © 2013 Elsevier B.V. All rights reserved.

This paper presents a general method for finding optimal blocking arrangements of pure-level and mixed-level orthogonal designs of resolution 3. The method requires enumeration of all nonisomorphic 'full designs' that include the treatment factors as well as the blocking factor. For all these designs, generalized word counts expressing the aliasing between main effects and two-factor interactions as well as the aliasing among two-factor interactions are calculated. The same is done for all projections into treatment designs obtained by dropping any possible blocking factor. The generalized word counts of the full design and treatment designs then allow the selection of blocking arrangements that are optimal with respect to five criteria appropriate for blocking resolution-3 orthogonal designs. We provide optimal blocking arrangements for orthogonal pure-level and mixed-level designs of 12, 16, 18, 20, and 27 runs.

Lactose (1,4-0-β-d-galactopyranosyl-d-glucose) is used as a soluble carbon source for the production of cellulases and hemicellulases for - among other purposes - use in biofuel and biorefinery industries. The mechanism how lactose induces cellulase formation in T. reesei is enigmatic, however. Previous results from our laboratory raised the hypothesis that intermediates from the two galactose catabolic pathway may give rise to the accumulation of intracellular oligogalactosides that could act as inducer. Here we have therefore used high-performance anion-exchange chromatography-mass spectrometry to study the intracellular galactoglycome of T. reesei during growth on lactose, in T. reesei mutants impaired in galactose catabolism, and in strains with different cellulase productivities. Lactose, allo-lactose, and lactulose were detected in the highest amounts in all strains, and two trisaccharides (Gal-β-1,6-Gal-β-1,4-Glc/Fru and Gal-β-1,4-Gal-β-1,4-Glc/ Fru) also accumulated to significant levels. Glucose and galactose, as well as four further oligosaccharides (Gal-β-1,3/1,4/1,6-Gal; Gal-β-1,2-Glc) were only detected in minor amounts. In addition, one unknown disaccharide (Hex-β-1,1-Hex) and four trisaccharides were also detected. The accumulation of the unknown hexose disaccharide was shown to correlate with cellulase formation in the improved mutant strains as well as the galactose pathway mutants, and Gal-β-1,4-Gal-β-1,4-Glc/Fru and two other unknown hexose trisaccharides correlated with cellulase production only in the pathway mutants, suggesting that these compounds could be involved in cellulase induction by lactose. The nature of these oligosaccharides, however, suggests their formation by transglycosylation rather than by glycosyltransferases. Based on our results, the obligate nature of both galactose catabolic pathways for this induction must have another biochemical basis than providing substrates for inducer formation. © 2013 Springer-Verlag Berlin Heidelberg.

Disturbances in the circadian system are associated with the development of type 2 diabetes mellitus. Here, we studied the direct contribution of the suprachiasmatic nucleus (SCN), the central pacemaker in the circadian system, in the development of insulin resistance. Exclusive bilateral SCN lesions in male C57Bl/6J mice, as verified by immunochemistry, showed a small but significant increase in body weight (+17%), which was accounted for by an increase in fat mass. In contrast, mice with collateral damage to the ventromedial hypothalamus and paraventricular nucleus showed severe obesity and insulin resistance. Mice with exclusive SCN ablation revealed a loss of circadian rhythm in activity, oxygen consumption, and food intake. Hyperinsulinemic-euglycemic clamp analysis 8 weeks after lesioning showed that the glucose infusion rate was significantly lower in SCN lesioned mice compared with sham-operated mice (-63%). Although insulin potently inhibited endogenous glucose production (-84%), this was greatly reduced in SCN lesioned mice (-7%), indicating severe hepatic insulin resistance. Our data show that SCN malfunctioning plays an important role in the disturbance of energy balance and suggest that an absence of central clock activity, in a genetically intact animal, may lead to the development of insulin resistance.

Het beleid voor de biobased economy is inconsistent en richt zich te veel op de vermindering van de CO²-uitstoot. Er zijn belangrijke veranderingen nodig. Zo niet, dan valt het duurzame succes van dit spoor op termijn bitter tegen

Upon analysis of chemically complex food matrices a forest of peaks is likely to be found. Identification of these peaks and concurrent determination of the toxicological relevance upon exposure is very time consuming, expensive and often requires animal studies. Recently, a safety assessment framework based on the Threshold of Toxicological Concern (TTC) was published to assess the safety of chemically complex matrices more efficiently. In this safety assessment framework, the toxicological relevance of exposure to unidentified substances in chemically complex food matrices can be related to the Cramer class III TTC threshold, currently set at 90. μg/day. However, possible additive or synergistic effects of combined exposure is not covered.The current evaluation describes the relevance of combined low dose exposure to unidentified substances in chemically complex food matrices. It is concluded that to some extent cumulative effects at exposure levels for each substance at or below the Cramer class III TTC threshold, being present in a complex mixture including food, might occur. However the health relevance of possible cumulative effects at this dose level is considered to be that low that a need for a correction factor to cover possible cumulative effects is very low to absent. © 2013 Elsevier Ltd.

Turkije verwelkomde afgelopen zomer 388 onderzoekers uit de gehele wereld voor het congres "The power of meat in the 21st Century". Een week lang lag de focus in Izmir op recente ontwikkelingen in de vleeswetenschap en -technologie.

Organic anion-transporting polypeptide 1B1 (OATP1B1) is an important hepatic uptake transporter, of which the polymorphic variant OATP1B1*15 (Asn130Asp and Val174Ala) has been associated with decreased transport activity. Rosuvastatin is an OATP1B1 substrate and often concomitantly prescribed with oral antidiabetics in the clinic. The aim of this study was to investigate possible drug-drug interactions between these drugs at the level of OATP1B1 and OATP1B1*15. We generated human embryonic kidney (HEK)293 cells stably overexpressing OATP1B1 or OATP1B1*15 that showed similar protein expression levels of OATP1B1 and OATP1B1*15 at the cell membrane as measured by liquid chromatography-tandem mass spectrometry. In HEK-OATP1B1*15 cells, the Vmax for OATP1B1-mediated transport of E217b-G (estradiol 17b-D-glucuronide) was decreased

Large scale implementation of CO2 storage can significantly reduce emission of greenhouse gasses into the atmosphere. However, safe and long-term containment of CO2 in storage reservoirs must be ensured. Wellbores in the subsurface present possible leakage pathways for CO2 to the surface and hence wellbore cement reactivity is of major concern. Previous experimental studies of cement reactivity often use high brine to cement ratios which may lead to overestimations of the rate of cement alteration. We aim to study cement reactivity under more realistic CO2 storage conditions. Limited brine is used to represent a wellbore environment with brine mainly present in pore space. The experimental results show a cease or significant reduction of reaction progression after 7 days due to saturation of the fluid. This inhibits further cement dissolution and re-dissolution of secondary calcite. The observed reaction zones are matched by geochemical modeling, showing from core to rim: unreacted cement (zone A), portlandite dissolution and increased porosity (zone B), major calcite and reduced porosity plus minor ferrihydrite precipitation (zone Ci) and minor calcite precipitation (zone Cii). The calibration of the geochemical model aids the development of an accurate reactive transport model for long-term cement alteration and integrity prediction.

Low volatile organophosphorous nerve agents such as VX, will most likely enter the body via the skin. The pharmacokinetics of drugs such as oximes, atropine and diazepam, are not aligned with the variable and persistent toxicokinetics of the agent. Repeated administration of these drugs showed to improve treatment efficacy compared to a single injection treatment. Because of the effectiveness of continuous treatment, it was investigated to what extent a subchronic pretreatment with carbamate (pyridostigmine or physostigmine combined with either procyclidine or scopolamine) would protect against percutaneous VX exposure. Inclusion of scopolamine in the pretreatment prevented seizures in all animals, but none of the pretreatments affected survival time or the onset time of cholinergic signs. These results indicate that percutaneous poisoning with VX requires additional conventional treatment in addition to the current pretreatment regimen. Decontamination of VX-exposed skin is one of the most important countermeasures to mitigate the effects of the exposure. To evaluate the window of opportunity for decontamination, the fielded skin decontaminant Reactive Skin Decontaminant Lotion (RSDL) was tested at different times in hairless guinea pigs percutaneously challenged with 4× LD50 VX in IPA. The results showed that RSDL decontamination at 15 min after exposure could not prevent progressive blood cholinesterase inhibition and therefore would still require additional treatment. A similar decontamination regimen with RSDL at 90 min showed that it still might effectively increase the time window of opportunity for treatment. In conclusion, the delay in absorption presents a window of opportunity for decontamination and treatment. The continuous release of VX from the skin presents a significant challenge for efficacious therapy, which should ideally consist of thorough decontamination and continuous treatment. © 2012 Elsevier Ireland Ltd. All rights reserved.

Tropospheric ozone contributes to the removal of air pollutants from the atmosphere but is itself a pollutant that is harmful to human health and vegetation. Biogenic isoprene emissions are important ozone precursors, and therefore future changes in land use that change isoprene emissions are likely to affect atmospheric ozone concentrations. Here, we use the chemical transport model LOTOS-EUROS (dedicated to the regional modeling of trace gases in Europe) to study a scenario in which 5% of the crop- and grass-land in Europe is converted into poplar plantations to be used for biofuel production. Although this scenario is rather conservative, our simulations project that isoprene emissions are substantially increased by an average of 45% over the simulated domain. As a consequence, ozone peak values are expected to increase by up to 6%, and ozone indicators for damage to human health and vegetation by up to 25% and 40%, respectively. Finally, we show that after the change in land use NOx emission reductions of 15-20% in Europe would be required to restore the ozone levels to current values. Because biomass production is expected to increase throughout Europe in the coming decades, we conclude that careful consideration of the tree types and regions to be used is required to constrain the concomitant air pollution to a minimum. © 2013 Elsevier Ltd.

Previous studies have shown accumulation and an enhanced proinflammatory profile of macrophages in adipose tissue of obese mice, indicating the presence of an interaction between adipocytes and macrophages in this tissue. However, the consequences of this interaction in humans are yet incompletely understood. In this study, we explored the modulating effects of adipocytes on the phenotype of macrophages in humans and studied the possible molecular pathways involved. Adipocyte-conditioned media (ACM) treatment of macrophages for 48 h strongly reduced the LPS-induced IL-12p40 secretion by macrophages, whereas the production of TNF-α and other cytokines remained largely unaffected. This effect was independent of the source of adipocytes. Interestingly, the level of inhibition correlated directly with body mass index (BMI) of the adipocyte donor. Because adipocytes release many different cytokines, adipokines, and lipids, we have separated the protein and lipid fractions of ACM, to obtain insight into the molecular nature of the soluble mediators underlying the observed effect. These experiments revealed that the inhibitory effect resided predominantly in the lipid fraction. Further studies revealed that PGE2 and linoleic and oleic acid were potent inhibitors of IL-12p40 secretion. Interestingly, concentrations of these ACM-derived lipids increased with increase in BMI of the adipocyte donor, suggesting that they could mediate the BMI-dependent effects of ACM. To our knowledge, these results provide first evidence that obesity-related changes in adipose tissue macrophage phenotype could be mediated by adipocyte-derived lipids in humans. Intriguingly, these changes appear to be different from those in murine obesity.

In numerical reservoir simulation practise the orientation of the spatial grid is often dictated by geological features of the reservoir model. As a consequence the trajectory of, in particular, a horizontal or slanted well or a well with a complex geometry, possibly with multilaterals, generally is not aligned to the numerical grid. This situation may lead to significant numerical artefacts, as an irregular inflow profile along the well. Although the total flow rate of the well may be reasonably accurate, a non-smooth profile is unwanted if the simulator is coupled to a dedicated wellbore flow model. Another artefact occurs if the ratio of the vertical to horizontal permeability is small (i. e. kv/kh < 0.001): standard models result in an overestimation of the total flow rate. Well inflow modelling relates the so-called well index, the ratio between well rate times viscosity and the difference between the well pressure and the gridblock pressure, to quantities such as gridblock dimensions and permeability. The origin of the numerical issues is the limitation of the well index estimation as proposed by Peaceman, and generalised by Alvestad for wells not aligned to the grid. We combined simulation results of a semi-analytic model and simulation results from a dedicated numerical simulation to calculate so-called semi-analytical well indices. We demonstrate that by using these semi-analytical well indices in a numerical reservoir simulator the aforementioned issues are resolved. The semi-analytic model that has been used solves the equation for steady state flow in 3D for line sink(s) with variable influx. The variable influx is then exploited to approximate a uniform pressure condition along the wellbore. This modelling approach allows for a complex geometry of the well such as a multilateral. To arrive at a practical implementation of our method we propose to use the standard well index along with a corrective skin factor based on our approach. Correlations for such a corrective skin factor then need to be developed based on a great number of well scenarios, anisotropy ratios and grid aspect ratios. Copyright 2013, Society of Petroleum Engineers.

Developing non-meat food products with an appealing structure is a challenge. In this study, we investigate the possibility to produce thin fibrils as building blocks for texturally interesting meat replacers. The technique applied is electrospinning—a technique which produces thin fibrilswith a high aspect ratio. The spinning of proteins is notoriously difficult and most proteins cannot be spun under food-grade conditions. Only two proteins are known to spin under food-grade conditions. Zein was spun from ethanol, and gelatin from warm water. The current study looks into the possibility of using one of these proteins as a carrier for other proteins. With gelatin it was possible to electrospin a range of globular proteins, showing for the first time electrospinning of globular proteins in a food-grade way. Next steps in the progress towards industrial application are the fixation and alignment of the fibrillar structures and upscaling of the process. Industrial relevance: The demand for high quality protein, that contains all essential amino acids, is growing. One of the challenges of alternative protein sources, such as plant storage protein, green leaf protein or insect protein, is to process it into a structurally appealing product. Fibrillar structure is acknowledged to play an essential role in giving texture and bite to protein products. Techniques for structuring include extrusion or shear cell texturizing. A technique on the nanoscale is not yet available. Such a technique can yield fibrils as building blocks for larger structures and in this way mimics meat. Electrospinning is one of the techniques that could fill that gap.

Decolorization of Reactive Red 238, Reactive Orange 16, Reactive Black 5 and Reactive Blue 4 was studied in the UV/H2O2 process with H2O2 being produced electrochemically. The experimental results show that decolorization increased considerably when switching on the electrochemical production of H2O2. Complete decolorization (>99%) was achieved for all dyes under the applied experimental conditions, partial mineralization (49–85%) was obtained, which depends on the type of dye. Reactive Red 238 was used to investigate operational parameters and it was found that decolorization was influenced by the applied electrical current of the electrochemical cell and flow rate. Decolorization and mineralization of Reactive Red 238 can be described by pseudo-first order kinetics. It was found that the initial concentration of Reactive Red 238 has a negative influence on the pseudo-first order reaction constant.

Caspase-1 is known to activate the proinflammatory cytokines IL-1β and IL-18. Additionally, it can cleave other substrates, including proteins involved in metabolism. Recently, we showed that caspase-1 deficiency in mice strongly reduces high-fat diet-induced weight gain, at least partly caused by an increased energy production. Increased feces secretion by caspase-1-deficient mice suggests that lipid malabsorption possibly further reduces adipose tissue mass. In this study we investigated whether caspase-1 plays a role in triglyceride-(TG)-rich lipoprotein metabolism using caspase-1-deficient and wild-type mice. Caspase-1 deficiency reduced the postprandial TG response to an oral lipid load, whereas TG-derived fatty acid (FA) uptake by peripheral tissues was not affected, demonstrated by unaltered kinetics of [3H]TG- labeled very low-density lipoprotein (VLDL)-like emulsion particles. An oral gavage of [3H]TG-containing olive oil revealed that caspase-1 deficiency reduced TG absorption and subsequent uptake of TG-derived FA in liver, muscle, and adipose tissue. Similarly, despite an elevated hepatic TG content, caspase-1 deficiency reduced hepatic VLDL-TG production. Intestinal and hepatic gene expression analysis revealed that caspase-1 deficiency did not affect FA oxidation or FA uptake but rather reduced intracellular FA transport, thereby limiting lipid availability for the assembly and secretion of TG-rich lipoproteins. The current study reveals a novel function for caspase-1, or caspase-1-cleaved substrates, in controlling intestinal TG absorption and hepatic TG secretion. Copyright © 2013 by the American Society for Biochemistry and Molecular Biology, Inc.

Introduction: The high complexity and dynamic nature of the regulation of gene expression, protein synthesis, and protein activity pose a challenge to fully understand the cellular machinery. By deciphering the role of important players, including transcription factors, microRNAs, or small molecules, a better understanding of key regulatory processes can be obtained. Various databases contain information on the interactions of regulators with their targets for different organisms, data recently being extended with the results of the ENCODE (Encyclopedia of DNA Elements) project. A systems biology approach integrating our understanding on different regulators is essential in interpreting the regulation of molecular biological processes. Implementation: We developed CyTargetLinker (http://projects.bigcat.unimaas.nl/cytargetlinker) a Cytoscape app, for integrating regulatory interactions in network analysis. Recently we released CyTargetLinker as one of the first apps for Cytoscape 3. It provides a user-friendly and flexible interface to extend biological networks with regulatory interactions, such as microRNA-target, transcription factor-target and/or drug-target. Importantly, CyTargetLinker employs identifier mapping to combine various interaction data resources that use different types of identifiers. Results: Three case studies demonstrate the strength and broad applicability of CyTargetLinker, (i) extending a mouse molecular interaction network, containing genes linked to diabetes mellitus, with validated and predicted microRNAs, (ii) enriching a molecular interaction network, containing DNA repair genes, with ENCODE transcription factor and (iii) building a regulatory meta-network in which a biological process is extended with information on transcription factor, microRNA and drug regulation. Conclusions: CyTargetLinker provides a simple and extensible framework for biologists and bioinformaticians to integrate different regulatory interactions into their network analysis approaches. Visualization options enable biological interpretation of complex regulatory networks in a graphical way. Importantly the incorporation of our tool into the Cytoscape framework allows the application of CyTargetLinker in combination with a wide variety of other apps for state-ofthe- art network analysis. Copyright: © 2013 Kutmon et al.

An inventory of Vanadium emissions for North-West Europe for the year 2005 was made based on an identification of the major sources. The inventory covers Belgium, Germany, Denmark, France, United Kingdom, Luxembourg, Netherlands and the OSPAR region of the North Sea. Vanadium emission were calculated bottom-up using energy use activity data and collected fuel and sector-specific emissions factors, taking into account various emission control measures. The NW European emissions were dominated by combustion of heavy fuel oil and petroleum cokes. Total emissions for 2005 amounted to 1569 tons/yr. The major sources are sea going ships (39%), petroleum refineries (35%) and industry (19%). Emission is strongly concentrated at the densely populated cities with major sea ports. The location of sources at or near the major port cities was confirmed by observational data, as was the downward trend in emissions due to emission control, fuel switches in industry and fuel quality improvement. The results show the positive impact of lower sulphur fuels on other possible health relevant air pollutants such as particle bound Vanadium. The emission inventory can be expanded to the full European domain and can be used to for air quality modeling and particularly for the tracing of source contributions from certain types of fossil fuels (petroleum coke and residual fuel oil). Moreover, it will allow the monitoring of changes in fuel use over time.

Background: In this paper, a clone based transcriptome analysis towards the identification of genes related to itaconic acid production in Aspergillus terreus was carried out as an extension of a previously published a clone-based transcriptome analysis from a set of batch fermentation experiments. Also a publically available A. niger transcriptome dataset from cultures similar to those of the A. terreus data set was analyzed to evaluate the specificity of the approach followed for A. terreus. Results: Besides the itaconic acid gene cluster (cis-aconitate decarboxylase, mitochondrial tri-carboxylic acid transporter and major facilitator superfamily transporter) discovered previously, additional genes of interest were identified in the A. terreus transcriptome data correlating to itaconic acid production, including 6 genes encoding enzymes in glycolysis and the pentose phosphate pathway, 4 genes functioning in vitamins synthesis, and a gene encoding a copper transporter. Only three of the 83 low pH specific genes identified from the A. niger dataset corresponded to high itaconicacid / low pH expressed genes identified from the A. terreus data set. However, in all three cases, the regulation of pH dependent gene expression was completely different between the two species. Conclusions: An extended clone based transcriptome analysis using a clone based transcription array to identify genes correlating with itaconic acid production revealed novel genes both in the central metabolism and in other more secondary pathways such as vitamin biosynthesis and Cu2+ transport, providing targets for further metabolic and process engineering to optimize itaconic acid production.

Geomechanical simulations were conducted to study the effects of reservoir depletion on the stability of internal and boundary faults in gas reservoirs overlain by elastic and viscoelastic salt caprocks. The numerical models were of a disk-shaped gas reservoir with idealized geometry; they mimic the structure of a gas field in the northern Netherlands which has experienced induced seismicity during gas production. The geomechanical simulations identified the area of the internal fault most sensitive to fault reactivation as coinciding with the epicenters of the largest seismic events associated with gas production. Depletion-induced shear slip is initiated at the depth of the reservoir, in the fault areas where the vertical fault throw ranges between 0.5 and 1.5 times the reservoir thickness. The extent of reactivated area differs depending on whether the caprock is viscoelastic or elastic: when it is viscoelastic, there is more down-dip shear displacement. High initial horizontal stresses in the rock salt and lower stresses in the elastic side-seal and the reservoir promote unloading of the internal and reservoir-bounding faults even before the reservoir is depleted. Particularly prone to fault reactivation are the fault zones along the interface between the reservoir rock and the salt caprock, which may already be critically stressed before depletion and are likely to be reactivated early during gas production. Stress relaxation and associated geomechanical changes affecting fault stability and ground surface deformation may continue long after production has ceased, due to the viscous behavior of the salt. © 2012 Springer-Verlag Wien.

Since the introduction of low emission zones in Germany in 2008 the question of their efficiency has been debated. In this pilot study, measurement data collected before and after the introduction of the low emission zone in Munich (October 2007 until January 2008 vs. October 2008 until Januar 2009) were analysed on the basis of matched quadruples. Applying previously described methods (Morfeld et al. 2011), continuously measured half-hour fine dust concentration data (PM10) - simultaneously determined at an index station situated inside the low emission zone and a reference station outside of the zone - were contrasted and analysed (difference score method in the two-period case). Meteorological parameters (height of the inversion base, amount of precipitation, wind velocity) as well as baseline data of index and reference stations were taken into account as covariates in regression analyses. The statistical approach was successfully validated in an analysis of simulated data. 26438 quadrupels could be matched for analysis. Averages of PM10 concentration values before (after) introducing the low emission zone were 33.9 μg/m3 (39.0 μg/m3) at 5 index stations and 24.6 μg/m3 (30.5 μg/m3) at 2 reference stations. Taking covariates into account, an additive model estimated the change in concentration associated to the introduction of the low emission zone as +0.017 μg/m3 (0.95-CI: -0.33 μg/m3, +0.37 μg/m3), a multiplicative model estimated the relative effect as -0.5% (0.95-CI: -0.12%, +0.30%). The results of this study differ relevantly from the findings of an earlier investigation by Cyrys et al. (2009) who analyzed the same data. This analysis does not prove the effectiveness of Munich's low emission zone. This study also points out that the methodological approach is crucial for a scientifically reliable evaluation of the efficacy of low emission zones. Strict rules need to be followed in order to prevent from misinterpretations.

Since July 2008, CO2 is injected into a saline aquifer near the town of Ketzin in Germany. For monitoring the CO2-migration close to the injection well, TNO installed a fixed 2D seismic array of 120 meters length in 2009, with 3-component geophones at the surface, 4-component receivers at 50 meters depth and a central vertical array of 4-component receivers. This specific test acquisition set-up was and is being used both for the recording of high-quality active time-lapse seismic data as well as for continuous passive seismic data recording. The latter gave rise to the identification of a large number of surface noise related events and some very weak events possibly originating from the deeper subsurface. The active seismic data acquisition consisted of a conventional repeat survey after 2 years using an accelerated weight drop source, as well as a test with a prototype semi-permanent source located at the site during a period of 3 weeks in which CO2 injection was stopped. In both cases subtle changes at the reservoir level have been observed, though the limitations of the experimental lay-out make it difficult to come up with firm conclusions in terms of CO2 induced pressure and saturation changes. Further analysis of the data is ongoing work.

A high-fat diet disturbs the composition and function of the gut microbiota and generates local gut-associated and also systemic responses. Intestinal mast cells, for their part, secrete mediators which play a role in the orchestration of physiological and immunological functions of the intestine. Probiotic bacteria, again, help to maintain the homeostasis of the gut microbiota by protecting the gut epithelium and regulating the local immune system. In the present study, we explored the effects of two probiotic bacteria, Lactobacillus rhamnosus GG (GG) and Propionibacterium freudenreichii spp. shermanii JS (PJS), on high fat-fed ApoE*3Leiden mice by estimating the mast cell numbers and the immunoreactivity of TNF-α and IL-10 in the intestine, as well as plasma levels of several markers of inflammation and parameters of lipid metabolism. We found that mice that received GG and PJS exhibited significantly lower numbers of intestinal mast cells compared with control mice. PJS lowered intestinal immunoreactivity of TNF-α, while GG increased intestinal IL-10. PJS was also observed to lower the plasma levels of markers of inflammation including vascular cell adhesion molecule 1, and also the amount of gonadal adipose tissue. GG lowered alanine aminotransferase, a marker of hepatocellular activation. Collectively, these data demonstrate that probiotic GG and PJS tend to down-regulate both intestinal and systemic pro-inflammatory changes induced by a high-fat diet in this humanised mouse model. © 2012 The Authors.

Conference abstract of the World Congress on Integrated Care, Singapore, November 7-9, 2013.

Objective. To explore factors that influence intention to participate in hemoglobinopathy (HbP) carrier screening under Dutch subjects at risk, since HbP became more common in The Netherlands. Method. Structured interviews with 301 subjects from Turkish, Moroccan, or Surinamese ethnicity. Results. Half of the participants were familiar with HbP, 27% with carrier screening. Only 55% correctly answered basic knowledge items. After balanced information, 83% percent of subjects express intention to participate in HbP carrier screening. Intention to participate was correlated with (1) anticipated negative feelings, (2) valuing a physician's advice, and (3) beliefs on significance of carrier screening. Risk perception was a significant determinant, while respondents were unaware of HbP as endemic in their country of birth. Respondents preferred screening before pregnancy and at cost < 50. Conclusion. These findings show the importance of informing those at risk by tailored health education. We propose easy access at no costs for those willing to participate in HbP carrier screening. © 2013 Sylvia M. van der Pal et al.

Introduction:β2→1-fructans are dietary fibers. Main objectives of this study were 1) to demonstrate direct signalling of β2→1-fructans on immune cells, 2) to study whether this is mediated by the pattern recognition receptors Toll-like receptors (TLRs) and nucleotide-binding oligomerisation domain-containing proteins (NODs), and 3) to relate the observed effects to the chain length differences in β2→1-fructans.Methods:Four different β2→1-fructan formulations were characterised for their chain length profile. Human peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with β2→1-fructans, and production of IL-1Ra, IL-1β, IL-6, IL-10, IL-12p70, and TNF-α was analysed. Reporter cells for TLRs and NODs were incubated with β2→1-fructans and analysed for NF-κB/AP-1 activation.Results:Cytokine production in human PBMCs was dose- and chain length-dependent. Strikingly, short chain enriched β2→1-fructans induced a regulatory cytokine balance compared to long chain enriched β2→1-fructans as measured by IL-10/IL-12 ratios. Activation of reporter cells showed that signalling was highly dependent on TLRs and their adapter, myeloid differentiation primary response protein 88 (MyD88). In human embryonic kidney reporter cells, TLR2 was prominently activated, while TLR4, 5, 7, 8, and NOD2 were mildly activated.Conclusions:β2→1-fructans possess direct signalling capacity on human immune cells. By activating primarily TLR2, and to a lesser extent TLR4, 5, 7, 8, and NOD2, β2→1-fructan stimulation results in NF-κB/AP-1 activation. Chain length of β2→1-fructans is important for the induced activation pattern and IL-10/IL-12 ratios. © 2013 Vogt et al.

Background: In order to make full use of the opportunities while responsibly managing the risks of working with manufactured nanomaterials (MNM), we need to gain insight into the potential level of exposure to MNM in the industry. Therefore, the goal of this study was to obtain an overview of the potential MNM exposure scenarios within relevant industrial sectors, applied exposure controls, and number of workers potentially exposed to MNM in Dutch industrial sectors producing and applying MNM-enabled end products in the Netherlands. Methods: A survey was conducted in three phases: (i) identification of MNM-enabled end products; (ii) identification of relevant industrial sectors; and (iii) a tiered telephone survey to estimate actual use of the products among 40 sector organizations/knowledge centres (Tier 1), 350 randomly selected companies (Tier 2), and 110 actively searched companies (Tier 3). Results: The most dominant industrial sectors producing or applying MNM-enabled end products (market penetration >5%) are shoe repair shops, automotive, construction, paint, metal, and textile cleaning industry. In the majority of the companies (76%), potential risks related to working with MNM are not a specific point of interest. The total number of workers potentially exposed to MNM during the production or application of MNM-enabled end products was estimated at approximately 3000 workers in the Netherlands. The results of this study will serve as a basis for in-depth exposure and health surveys that are currently planned in the Netherlands. In addition, the results can be used to identify the most relevant sectors for policy makers and future studies focussing on evaluating the risks of occupational exposure to MNM.

The South-Africa Europe Cooperation in Carbon capture and Storage (SAfECCS) project was initiated in 2011. The aim of the project is to support the South African Centre for Carbon Capture and Storage (SACCCS) Roadmap for Carbon Capture and Storage (CCS) in South Africa through assessing the potential for geological storage, the impact of the existing legal framework and the relevance of possible funding streams for the proposed Test Injection Project as well as by undertaking capacity building and knowledge sharing activities.

Purpose: Despite the importance of skin exposure, studies of skin symptoms in relation to exposure and respiratory symptoms are rare. The goals of this study were to describe exposure-response relationships for skin symptoms, and to investigate associations between skin and respiratory symptoms in bakery and auto body shop workers. Methods: Data from previous studies of bakery and auto body shop workers were analyzed. Average exposure estimates for wheat allergen and isocyanates were used. Generalized linear models were constructed to describe the relationships between exposure and skin symptoms, as well as between skin and respiratory symptoms. Results: Data from 723 bakery and 473 auto body shop workers were analyzed. In total, 5.3 % of bakery and 6.1 % of auto body shop workers were female; subjects' mean age was 39 and 38 years, respectively. Exposure-response relationships were observed in auto body shop workers for itchy or dry skin (PR 1.55, 95 % CI 1.2-2.0) and work-related itchy skin (PR 1.97, 95 % CI 1.2-3.3). A possible exposure-response relationship for work-related itchy skin in bakery workers did not reach statistical significance. In both groups, reporting skin symptoms was strongly and significantly associated with reporting respiratory symptoms, both work-related and non-work-related. Conclusions: Exposure-response relationships were observed for skin symptoms in auto body shop workers. The lack of significant exposure-response associations in bakery workers should be interpreted cautiously. Workers who reported skin symptoms were up to four times more likely to report respiratory symptoms. Improved awareness of both skin and respiratory outcomes in exposed workers is needed. © 2012 The Author(s).

The human gut contains a diverse microbiota with large potential to influence health. Given the difficulty to access the main sites of the gut, in vitro models have been developed to dynamically monitor microbial processes at the site of metabolic activity. These models range from simple batch fermentations to complex multi-compartmental continuous systems. The latter include different models, focussing on similar but each also on distinct digestive parameters. The most intensively used include the three-stage continuous culture system, SHIME®, EnteroMix, Lacroix model and TIM-2. Especially after inclusion of surface-attached mucosal microbes (M-SHIME), such models have been shown representative of the in vivo situation in terms of microbial composition and activity. They have even been shown to maintain the interpersonal variation among different human fecal inocula. Novel developments, such as the incorporation of host cells, will further broaden the potential of in vitro models to unravel the importance of gut microbes for human health and disease. © 2013 Elsevier Ltd. All rights reserved.

Assessing the impact of climate change and anthropogenic activity on Florida coastal areas requires a thorough understanding of natural climate variability. The available instrumental record, however, is too short and too limited to capture the full range of natural variability. In order to provide additional data on the natural state of the climate system and to evaluate the influence of human impact, we reconstructed climatic and environmental changes of the past 300 years. Pre- (before 1900 ad) and post-human impact conditions were compared in Rookery Bay, a subtropical, southern Florida estuary and its bordering wetland system. Biomarkers from terrestrial and aquatic environments were used to reconstruct temperature, runoff, and aquatic productivity. Pre-anthropogenic conditions before 1750 ad indicate a relatively large contribution of mangrove-derived organic matter, locally decreasing at the end of this period. After 1750 ad follows a relatively stable period in which biomarker concentrations indicate relatively low levels of runoff and aquatic production. Enhanced anthropogenic activities, such as land clearance and hydrological alterations, end this period of stability by altering the hydrological conditions. This leads to a more dynamic system which is more sensitive to disturbances of vegetation and drainage, as evidenced by peak terrestrial biomarker fluxes during the twentieth century. These episodes of enhanced runoff resulted in eutrophication and algal blooms in Rookery Bay. Natural climate phenomena, such as a positive AMO phase and hurricane activity, might have added to ongoing processes during the twentieth century. © 2012 Coastal and Estuarine Research Federation.

We report here the first case of indigenous tularemia detected inTheNetherlands, a nonendemic country, since 1953.Whole genome DNAsequence analysis assigned the isolate BD11-00177 to the genomic group B.FTNF002-00,which previously has been exclusively reported from Spain, France, Italy, Switzerland, and Germany. The patient had not been abroad for years, which implies that this is an indigenous infection. The current case might predict an upcoming distribution of Francisella tularensis holarctica genomic group B.FTNF002-00 in Europe.

Objectives: Algorithm-based exposure assessments based on patterns in questionnaire responses and professional judgment can readily apply transparent exposure decision rules to thousands of jobs quickly. However, we need to better understand how algorithms compare to a one-by-one job review by an exposure assessor. We compared algorithm-based estimates of diesel exhaust exposure to those of three independent raters within the New England Bladder Cancer Study, a population-based case-control study, and identified conditions under which disparities occurred in the assessments of the algorithm and the raters.Methods: Occupational diesel exhaust exposure was assessed previously using an algorithm and a single rater for all 14 983 jobs reported by 2631 study participants during personal interviews conducted from 2001 to 2004. Two additional raters independently assessed a random subset of 324 jobs that were selected based on strata defined by the cross-tabulations of the algorithm and the first rater's probability assessments for each job, oversampling their disagreements. The algorithm and each rater assessed the probability, intensity and frequency of occupational diesel exhaust exposure, as well as a confidence rating for each metric. Agreement among the raters, their aggregate rating (average of the three raters' ratings) and the algorithm were evaluated using proportion of agreement, kappa and weighted kappa (κw). Agreement analyses on the subset used inverse probability weighting to extrapolate the subset to estimate agreement for all jobs. Classification and Regression Tree (CART) models were used to identify patterns in questionnaire responses that predicted disparities in exposure status (i.e., unexposed versus exposed) between the first rater and the algorithm-based estimates.Results: For the probability, intensity and frequency exposure metrics, moderate to moderately high agreement was observed among raters (κw = 0.50-0.76) and between the algorithm and the individual raters (κw = 0.58-0.81). For these metrics, the algorithm estimates had consistently higher agreement with the aggregate rating (κw = 0.82) than with the individual raters. For all metrics, the agreement between the algorithm and the aggregate ratings was highest for the unexposed category (90-93%) and was poor to moderate for the exposed categories (9-64%). Lower agreement was observed for jobs with a start year