24 research outputs found
Delimitation and Coherence of Functional and Administrative Regions
No full textCorvers F., Hensen M. and Bongaerts D. Delimitation and coherence of functional and administrative regions, Regional Studies. The paper tests whether functional regions in the Netherlands show more labour market coherence between the municipalities included in them than the Dutch administrative regions. It turns out that regional disparities are not significantly smaller within functional than within administrative regions with respect to income level, housing prices, employment rate, and unemployment rate. It is argued that the numerous functional delimitations of the labour market that have been made for many countries in other studies are only useful for policy-making if they clearly outperform the administrative delimitations with respect to some relevant indicators of labour market coherence or regional disparities. [image omitted] Corvers F., Hensen M. et Bongaerts D. Delimitation et coherence des regions fonctionnelles et administratives, Regional Studies. Nous verifions si les regions fonctionnelles des Pays-Bas presentent davantage de coherence dans le marche du travail entre les municipalites englobees dans celles-ci que les regions administratives neerlandaises. Il s'avere que les disparites regionales ne sont pas vraiment moindres dans les regions fonctionnelles que dans les regions administratives du point de vue du niveau de revenus, du prix des logements, du taux d'emploi et du taux de chomage. Nous soutenons que les nombreuses delimitations fonctionnelles du marche du travail qui ont ete etablies pour de nombreux pays dans d'autres etudes ne sont utiles pour la prise des decisions politiques que si elles se montrent nettement plus performantes que les delimitations administratives par rapport a certains indicateurs pertinents de la coherence du marche du travail ou des disparites regionales. Regions fonctionnelles Migrations quotidiennes Travel-to-work areas (TTWA - aires fonctionnelles urbaines) Disparites regionales Corvers F., Hensen M. und Bongaerts D. Abgrenzungen und Koharenz von funktionalen und Verwaltungsregionen, Regional Studies. Wir uberprufen, ob die funktionalen Regionen der Niederlande hinsichtlich des Arbeitsmarkts mehr Koharenz zwischen den Gemeinden der einzelnen Regionen aufweisen als zwischen den hollandischen Verwaltungsregionen. Wie sich herausstellt, fallen die regionalen Disparitaten innerhalb der funktionalen Regionen nicht signifikant kleiner aus als innerhalb der Verwaltungsregionen, was das Einkommensniveau, die Hauspreise, das Beschaftigungsniveau und die Arbeitslosenzahlen angeht. Wir argumentieren, dass die zahlreichen funktionalen Abgrenzungen des Arbeitsmarkts, die in anderen Studien fur viele Lander geschaffen wurden, zur politischen Gestaltung nur nutzlich sind, wenn sie den verwaltungstechnischen Abgrenzungen hinsichtlich einiger relevanter Indikatoren fur die Arbeitsmarktkoharenz oder die regionalen Disparitaten klar uberlegen sind. Funktionale Regionen Pendlerverkehr Arbeitsmarktregionen Regionale Disparitaten Corvers F., Hensen M. y Bongaerts D. La delimitacion y coherencia de las regiones funcionales y administrativas, Regional Studies. En este articulo comprobamos si la coherencia del mercado laboral entre las municipalidades de las regiones funcionales de los Paises Bajos es mayor que la coherencia entre las regiones administrativas holandesas. Observamos que las desigualdades regionales no son significativamente menores en las regiones funcionales que en las regiones administrativas con respecto al nivel de ingresos, los precios de la vivienda y las tasas de empleo y desempleo. Sostenemos que las numerosas delimitaciones funcionales del mercado laboral que se han realizado para muchos paises en otros estudios son solo utiles para la elaboracion de politicas si claramente funcionan mejor que las delimitaciones administrativas con respecto a algunos indicadores relevantes de la coherencia del mercado laboral o de las desigualdades regionales. Regiones funcionales Desplazamientos diarios Cuenca de empleo Desigualdades regionalesFunctional regions, Commuting, Travel-to-work areas (TTWA), Regional disparities,
Magnetic manipulation of intracellular signals
No full textIn the context of the MAGNEURON project we have developed magnetic tools to manipulate intracellular proteins involved in intracellular signaling processes. We focused on the manipulation of the subdomain DHPH of ITSN1 in order to control the activity of CDC42.
To control the activity of CDC42 we produced a fusion protein consisting in the DHPH domain of ITSN1, the mCherry fluorescent protein and a nanobody against GFP (aGFPnb).
The manipulations were done either using a magnetic tip or magnetic micropillars done with soft magnetic material (Nickel Iron alloy). Nanoparticles were first injected in the cytoplasm of the cell. After a delay of at least ten minutes, the survival of the cell was controlled and the manipulation could start.
We monitored the fluorescence of the reporter (IRFP-NWASP) and the formation of protrusion/filopodia as markers of a biological response to the manipulation.
We observed protrusion formation as well as NWASP activity when attracting the nanoparticles, but control experiments (Manipulation of particles without ITSN1-mcherry-aGFPnb) also showed increase of fluorescence of the NWASP reporter at the point of attraction of the particles.
In addition, if compared to optogenetic manipulation of the similar ITSN1-DHPH domain, the formation of protrusion was very limited. We concluded that magnetic manipulation of intracellular signals was not efficient to hijack signaling pathways.
We publish here the raw data of some experiments that were produced in the lab.
Each experiment has a README file describing the parameter of the recording and what can be observe on the video</p
De scheiding van Maas en Waal onder verlegging van de uitmonding der Maas naar den Amer
No full textHistorie van overstromingen langs de Maas, de Beerse Maas en de Baardwijkse Overlaat. Verbeteringsplannen van Leemans, Schebbele Nolthenius en C.W. Lely. Uiteindelijke plan en uitvoeringswet. Kosten vande plannen. Uitevoerde werken: riviervan Heleind-Dongemond, normalisering van de Amer, verruiming Heusdens kanaal. Bruggen en veren. Afwateringsvoorzieningen (gemalen, suatiesluizen). Sluiting van de Heerewaardense Overlaat, verhoging van de Waaldijken. Afsluiting van de Maas bij Andel. De Dommel en de Dieze. Bijkomende werken. Deze pdf is samengesteld uit scans van verschillende exemplaren van het rapport. Er is een aparte pdf met de platen 1 t/m5. Plaat 6 is opgenomen in twee versies, als afzonderlijke bladen (zoals uitgegeven) en als één samengestelde kaart van het gehele gebied. Administratieve regelen, Nacalculalatie van de kosten. Waterstanden.Bergsche Maa
Label-free detection of uptake, accumulation, and translocation of diesel exhaust particles in ex vivo perfused human placenta
No full textBackgroundPregnant women and developing fetuses comprise a particularly vulnerable population as multiple studies have shown associations between prenatal air pollution exposure and adverse pregnancy outcomes. However, the mechanisms underlying the observed developmental toxicity are mostly unknown, in particular, if pollution particles can cross the human placenta to reach the fetal circulation.ResultsHere, we investigated the accumulation and translocation of diesel exhaust particles (DEPs), as a model particle for combustion-derived pollution, in human perfused placentae using label-free detection by femtosecond pulsed laser illumination. The results do not reveal a significant particle transfer across term placentae within 6 h of perfusion. However, DEPs accumulate in placental tissue, especially in the syncytiotrophoblast layer that mediates a wealth of essential functions to support and maintain a successful pregnancy. Furthermore, DEPs are found in placental macrophages and fetal endothelial cells, showing that some particles can overcome the syncytiotrophoblasts to reach the fetal capillaries. Few particles are also observed inside fetal microvessels.ConclusionsOverall, we show that DEPs accumulate in key cell types of the placental tissue and can cross the human placenta, although in limited amounts. These findings are crucial for risk assessment and protection of pregnant women and highlight the urgent need for further research on the direct and indirect placenta-mediated developmental toxicity of ambient particulates.This work received fnancial support from the Flemish Scientifc Research Foundation (Grant no 1150920N, G082317N, and 12P6819N) and the Swiss National Science Foundation (Grant no 31003A_179337 and IZSEZ0_193948). The detection equipment was funded by the Interuniversity Attraction Poles Program (P7/05) initiated by the Belgian Science Policy Ofce and the INCALO project (ERC-PoC).
Acknowledgements
The authors would like to acknowledge all participants of the study. In addition, we owe special thanks to the nurses, midwives, and doctors involved in placenta collection.The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request
Multi-criteria Decision-making for Sustainable Wall Paints and Coatings Using Analytic Hierarchy Process
No full textAbstractTo which extent do potential users of construction products take sustainability into account during their decision-making process? How well could they align themselves in all the legislation frameworks and calculation tools for the sustainable construction products? In accordance with the Environmental Product Declaration (EPD) [1], determining of ecological properties of construction products could be accomplished with applying life cycle assessment (LCA). There is a number of tools and frameworks for evaluating the sustainability of construction products for the European experts, which may be used in such a decision-making process. However, for a non-expert user, this could be quite complex. Therefor, the assumption here is that environmental and human health safety are prior in contrast to the market prices when it comes to choosing a decorative paint or coating. In the framework of herein research, an Analytic Hierarchy/Network Process model was designed involving four major merits of the Analytic Hierarchy Process: Benefits, Opportunities, Costs, and Risks [2]. The model which is based on the major characteristics of a decorative wall paint helps emphasising the best alternative with respect to given priorities: low risk of environmental and human health damage, quality, market price, repairability. The model shows values for all the criteria and alternatives with respect to pairwise comparisons. In a future research step, this model will be validated with a questionnaire survey targeting non-expert users, i.e. average consumers, on the construction market in Germany
Optogenetic control of a GEF of RhoA uncovers a signaling switch from retraction to protrusion
No full textThe ability of a single protein to trigger different functions is an assumed key feature of cell signaling, yet there are very few examples demonstrating it. Here, using an optogenetic tool to control membrane localization of RhoA nucleotide exchange factors (GEFs), we present a case where the same protein can trigger both protrusion and retraction when recruited to the plasma membrane, polarizing the cell in two opposite directions. We show that the basal concentration of the GEF prior to activation predicts the resulting phenotype. A low concentration leads to retraction, whereas a high concentration triggers protrusion. This unexpected protruding behavior arises from the simultaneous activation of Cdc42 by the GEF and sequestration of active RhoA by the GEF PH domain at high concentrations. We propose a minimal model that recapitulates the phenotypic switch, and we use its predictions to control the two phenotypes within selected cells by adjusting the frequency of light pulses. Our work exemplifies a unique case of control of antagonist phenotypes by a single protein that switches its function based on its concentration or dynamics of activity. It raises numerous open questions about the link between signaling protein and function, particularly in contexts where proteins are highly overexpressed, as often observed in cancer
amdSYM, a new dominant recyclable marker cassette for Saccharomyces cerevisiae
No full textDespite the large collection of selectable marker genes available for Saccharomyces cerevisiae, marker availability can still present a hurdle when dozens of genetic manipulations are required. Recyclable markers, counterselectable cassettes that can be removed from the targeted genome after use, are therefore valuable assets in ambitious metabolic engineering programs. In the present work, the new recyclable dominant marker cassette amdSYM, formed by the Ashbya gossypii TEF2 promoter and terminator and a codon-optimized acetamidase gene (Aspergillus nidulans amdS), is presented. The amdSYM cassette confers S. cerevisiae the ability to use acetamide as sole nitrogen source. Direct repeats flanking the amdS gene allow for its efficient recombinative excision. As previously demonstrated in filamentous fungi, loss of the amdS marker cassette from S. cerevisiae can be rapidly selected for by growth in the presence of fluoroacetamide. The amdSYM cassette can be used in different genetic backgrounds and represents the first counterselectable dominant marker gene cassette for use in S. cerevisiae. Furthermore, using astute cassette design, amdSYM excision can be performed without leaving a scar or heterologous sequences in the targeted genome. The present work therefore demonstrates that amdSYM is a useful addition to the genetic engineering toolbox for Saccharomyces laboratory, wild, and industrial strains.BT/BiotechnologyApplied Science
Integration of metabolomics with genomics: Metabolic gene prioritization using metabolomics data and genomic variant (CADD) scores
No full textThe integration of metabolomics data with sequencing data is a key step towards improving the diagnostic process for finding the disease-causing genetic variant(s) in patients suspected of having an inborn error of metabolism (IEM). The measured metabolite levels could provide additional phenotypical evidence to elucidate the degree of pathogenicity for variants found in genes associated with metabolic processes. We present a computational approach, called Reafect, that calculates for each reaction in a metabolic pathway a score indicating whether that reaction is deficient or not. When calculating this score, Reafect takes multiple factors into account: the magnitude and sign of alterations in the metabolite levels, the reaction distances between metabolites and reactions in the pathway, and the biochemical directionality of the reactions. We applied Reafect to untargeted metabolomics data of 72 patient samples with a known IEM and found that in 81% of the cases the correct deficient enzyme was ranked within the top 5% of all considered enzyme deficiencies. Next, we integrated Reafect with Combined Annotation Dependent Depletion (CADD) scores (a measure for gene variant deleteriousness) and ranked the metabolic genes of 27 IEM patients. We observed that this integrated approach significantly improved the prioritization of the genes containing the disease-causing variant when compared with the two approaches individually. For 15/27 IEM patients the correct affected gene was ranked within the top 0.25% of the set of potentially affected genes. Together, our findings suggest that metabolomics data improves the identification of affected genes in patients suffering from IEM.Pattern Recognition and Bioinformatic
Using out-of-batch reference populations to improve untargeted metabolomics for screening inborn errors of metabolism
No full textUntargeted metabolomics is an emerging technology in the laboratory diagnosis of inborn errors of metabolism (IEM). Analysis of a large number of reference samples is crucial for correcting variations in metabolite concentrations that result from factors, such as diet, age, and gender in order to judge whether metabolite levels are abnormal. However, a large number of reference samples requires the use of out-of-batch samples, which is hampered by the semi-quantitative nature of untargeted metabolomics data, i.e., technical variations between batches. Methods to merge and accurately normalize data from multiple batches are urgently needed. Based on six metrics, we compared the existing normalization methods on their ability to reduce the batch effects from nine independently processed batches. Many of those showed marginal performances, which motivated us to develop Metchalizer, a normalization method that uses 10 stable isotope-labeled internal standards and a mixed effect model. In addition, we propose a regression model with age and sex as covariates fitted on reference samples that were obtained from all nine batches. Metchalizer applied on log-transformed data showed the most promising performance on batch effect removal, as well as in the detection of 195 known biomarkers across 49 IEM patient samples and performed at least similar to an approach utilizing 15 within-batch reference samples. Furthermore, our regression model indicates that 6.5–37% of the considered features showed significant age-dependent variations. Our comprehensive comparison of normalization methods showed that our Log-Metchalizer approach enables the use out-of-batch reference samples to establish clinically-relevant reference values for metabolite concentrations. These findings open the possibilities to use large scale out-of-batch reference samples in a clinical setting, increasing the throughput and detection accuracy.Pattern Recognition and Bioinformatic
Clustering and dynamics of cytochrome bd-I complexes in the Escherichia coli plasma membrane in vivo.
No full textThe cytochrome bd-I complex of Escherichia coli is a respiratory terminal oxidase and an integral component of the cytoplasmic membrane. As with other respiratory components, the organization and dynamics of this complex in living membranes is unknown. We set out to visualize the distribution and dynamics of this complex in vivo. By exchanging cydB for cydB-gfpgcn4 on the E. coli chromosome, we produced a strain (YTL01) that expresses functional GFP-tagged cytochrome bd-I terminal oxidase complexes under wild-type genetic control. We imaged live YTL01 cells using video-rate epifluorescence and total internal reflection fluorescence (TIRF) microscopy in combination with fluorescence recovery after photobleaching (FRAP) and saw mobile spots of GFP fluorescence in plasma membranes. Numbers of GFP molecules per spot were quantified by step-wise photobleaching giving a broad distribution with a mean of approximately 76, indicating that cytochrome bd-I is concentrated in mobile patches in the E. coli plasma membrane. We hypothesize that respiration occurs in mobile membrane patches which we call 'respirazones'
