Modulation of angiogenesis during adipose tissue development in murine models of obesity.

peer reviewedDevelopment of vasculature and mRNA expression of 17 pro- or antiangiogenic factors were studied during adipose tissue development in nutritionally induced or genetically determined murine obesity models. Subcutaneous (SC) and gonadal (GON) fat pads were harvested from male C57Bl/6 mice kept on standard chow [standard fat diet (SFD)] or on high-fat diet for 0-15 wk and from male ob/ob mice kept on SFD. Ob/ob mice and C57Bl/6 mice on high-fat diet had significantly larger SC and GON fat pads, accompanied by significantly higher blood content, increased total blood vessel volume, and higher number of proliferating cells. mRNA and protein levels of angiopoietin (Ang)-1 were down-regulated, whereas those of thrombospondin-1 were up-regulated in developing adipose tissue in both obesity models. Ang-1 mRNA levels correlated negatively with adipose tissue weight in the early phase of nutritionally induced obesity as well as in genetically determined obesity. Placental growth factor and Ang-2 expression were increased in SC adipose tissue of ob/ob mice, and thrombospondin-2 was increased in both their SC and GON fat pads. mRNA levels of vascular endothelial growth factor (VEGF)-A isoforms VEGF-B, VEGF-C, VEGF receptor-1, -2, and -3, and neuropilin-1 were not markedly modulated by obesity. This modulation of angiogenic factors during development of adipose tissue supports their important functional role in obesity

De arbeidsmarkt naar opleiding en beroep tot 2018

In deze aanhoudend roerige tijden op de arbeidsmarkt brengt het Researchcentrum voor Onderwijs en Arbeidsmarkt (ROA) de twaalfde uitgave van het rapport De arbeidsmarkt naar opleiding en beroep uit. Hierin wordt een beeld geschetst van de huidige en op de middellange termijn te verwachten arbeidsmarktontwikkelingen. Wij schetsen de arbeidsmarktperspectieven voor de komende vijf jaar (tot 2018) onder andere om de jongeren die nu voor hun studiekeuze staan inzicht te bieden in de verwachte arbeidsmarktsituatie na afstuderen. Deze informatie is van belang voor zowel het geven van voorlichting aan degenen die aan een (vervolg)opleiding willen beginnen als voor werkgevers bij het nemen van strategische beslissingen over hun personeelsbeleid. Het rapport is in het bijzonder bedoeld voor de beleidsontwikkeling van de overheid, de arbeidsbemiddelingssorganisaties, de sociale partners en het onderwijsveld. Het rapport is gebaseerd op gedetailleerde arbeidsmarktinformatie naar sector, beroep en opleiding, zoals deze is opgenomen in het Arbeidsmarktinformatiesysteem (AIS) van het ROA

Heritability of fractional anisotropy in human white matter: a comparison of Human Connectome Project and ENIGMA-DTI data

The degree to which genetic factors influence brain connectivity is beginning to be understood. Large-scale efforts are underway to map the profile of genetic effects in various brain regions. The NIH-funded Human Connectome Project (HCP) is providing data valuable for analyzing the degree of genetic influence underlying brain connectivity revealed by state-of-the-art neuroimaging methods. We calculated the heritability of the fractional anisotropy (FA) measure derived from diffusion tensor imaging (DTI) reconstruction in 481 HCP subjects (194/287 M/F) consisting of 57/60 pairs of mono- and dizygotic twins, and 246 siblings. FA measurements were derived using (Enhancing NeuroImaging Genetics through Meta-Analysis) ENIGMA DTI protocols and heritability estimates were calculated using the SOLAR-Eclipse imaging genetic analysis package. We compared heritability estimates derived from HCP data to those publicly available through the ENIGMA-DTI consortium, which were pooled together from five-family based studies across the US, Europe, and Australia. FA measurements from the HCP cohort for eleven major white matter tracts were highly heritable (h2 = 0.53–0.90, p < 10− 5), and were significantly correlated with the joint-analytical estimates from the ENIGMA cohort on the tract and voxel-wise levels. The similarity in regional heritability suggests that the additive genetic contribution to white matter microstructure is consistent across populations and imaging acquisition parameters. It also suggests that the overarching genetic influence provides an opportunity to define a common genetic search space for future gene-discovery studies. Uniquely, the measurements of additive genetic contribution performed in this study can be repeated using online genetic analysis tools provided by the HCP ConnectomeDB web application

Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter:Comparing meta and megaanalytical approaches for data pooling

Combining datasets across independent studies can boost statistical power by increasing the numbers of observations and can achieve more accurate estimates of effect sizes. This is especially important for genetic studies where a large number of observations are required to obtain sufficient power to detect and replicate genetic effects. There is a need to develop and evaluate methods for joint-analytical analyses of rich datasets collected in imaging genetics studies. The ENIGMA-DTI consortium is developing and evaluating approaches for obtaining pooled estimates of heritability through meta-and mega-genetic analytical approaches, to estimate the general additive genetic contributions to the intersubject variance in fractional anisotropy (FA) measured from diffusion tensor imaging (DTI). We used the ENIGMA-DTI data harmonization protocol for uniform processing of DTI data from multiple sites. We evaluated this protocol in five family-based cohorts providing data from a total of 2248 children and adults (ages: 9-85) collected with various imaging protocols. We used the imaging genetics analysis tool, SOLAR-Eclipse, to combine twin and family data from Dutch, Australian and Mexican-American cohorts into one large "mega-family". We showed that heritability estimates may vary from one cohort to another. We used two meta-analytical (the sample-size and standard-error weighted) approaches and a mega-genetic analysis to calculate heritability estimates across-population. We performed leave-one-out analysis of the joint estimates of heritability, removing a different cohort each time to understand the estimate variability. Overall, meta- and mega-genetic analyses of heritability produced robust estimates of heritability

Experimental study of direct contact condensation of steam in turbulent duct flow

This thesis deals with an experimental study on direct injection of steam into a crossflow of water. The main goals are to identify the main parameters that influence direct steam injection in liquids and to quantitatively access their impact on the interaction of the condensation and the liquid cross-flow both in the proximity of the injection nozzle and in the far-field single-phase flow. The experiments are carried out in a pressurized flow loop consisting of a measurement section with a square inner geometry of dimensions 30 x 30 mm2 . The measurement section is optical accessible near the steam injection point and also includes a hydraulic development section with a length of 1200 mm (40Dh). To verify whether the flow is fully developed after passing the hydraulic development section, velocity measurements, using PIV 1 are performed in the centre plane of the duct parallel to the main direction of the flow. For two Reynolds lltunhers, profiles of the mean axial and lateral velocity components as well as distributions of the higher order statistics are measured and compared with DNS and LES results at corresponding Reynolds numbers. The agreement between the measured and numerical profiles is satisfactory, apart from some deviations of the experimental profiles in the near-wall wall regions due to measurement inaccuracies. The experimentally observed dependency of the Reynolds stress gradient on the Reynolds number is in close agreement with the trend estimated from Prandtl's law of friction for fully developed pipe flow. This indicates that the duct flow has reached its fully developed state at a distance of 43Dh from the inlet of the hydraulic development section. If any streamwise variations in the flow properties are present, they are expected to be small and would remain undetected due to the limited height of the observed domain. The condensation of steam in the liquid cross-flow has been investigated in the proximity of the steam injection point by means of high speed photography at various steam mass fluxes, liquid cross-flow rates and approaching liquid temperatures. The high-speed recordings clearly reveal an intermittent character of steam pocket growth and collapse/condensation. Pocket length typically grows linearly until it reaches a maximum penetration depth. Subsequent disappearance of the pocket occurs either via detachment and collapse or via instantaneous break-up. The initial steam pocket shape predominantly resembles that of a truncated sphere while in later stages of growth either a spherical or ellipsoidal shape is observed, depending on the steam mass flux and temperature of approaching liquid. The main effect of the liquid crossflow is a significant reduction of the steam pockets' maximum length and growth time. Heat transfer coefficients between water and steam have been determined, based on the smoothed steam pocket interfacial area. The measured trends show an increase of the heat transfer coefficient with increasing liquid cross-flow rate. A new correlation to predict the Nusselt number of intermittent steam condensation is presented, using a characteristic steam plume length, as the physically relevant length scale. The effect of cross-flow is incorporated in the Nusselt correlation via an extra Reynolds number based on the liquid cross-flow rate. A model for topology history prediction has been developed to facilitate interpretation of measurement results and to increase our predictive capacity of intermittent steam condensation. With a correction factor on the input value of the heat transfer coefficient, both the steam pockets' growth time and its maximum penetration depth, are predicted reasonably well. The growth of a steam pocket in intermittent condensation regimes is found to be controlled by fluid inertia and injected momentum of steam, while drag is negligible. Velocity measurements in the region upstream the steam injection point have been carried out to investigate the far-field single-phase jet that is induced by the condensation of steam and deflected by the liquid cross-flow. The injected steam mass flux, liquid cross-flow rate and the liquid approach temperature are varied to study their influence on the jet centreline, velocity distributions and turbulence properties. The measured velocity fields show that the ratio of injected steam momentum and cross-flow momentum is largely governing the flow field, while effects of the liquid approach temperature are found to be minor. Jet center lines trajectories, based on the loci of maximum velocity magnitude in the jet appear to collapse onto a single curve if scaled with the product of the nozzle diameter and the effective velocity ratio. This collapse of centerlines is similar to that observed in non-condensing jets in cross-flow. A power-law correlation is proposed to describe the position of the collapsed centreline trajectories for the condensing jet in cross-flow. A similarity analysis has been applied to the lateral distributions of the mean streamwise velocity component by evaluating the velocity components, measured in cartesian coordinates, in a rotated frame of axes. Lateral distributions of the jets' mean velocity excess, scaled with the maximum excess, at successive streamwise coordinates collapse onto a single curve when the spanwise coordinate is scaled with the jets' half-width. In addition, the centerline velocity excess appears to be inversely proportional to the streamwise coordinate whereas the jets' half-width is found to increase linearly in that direction. This demonstrates that the jet flow displays self-similarity properties which resemble those of a free turbulent jet. turbulence intensity profiles have been investigated in the rotated frame, for two momentum flux ratios. The distributions along the spanwise axis show that the streamwise and lateral turbulent fluctuations exhibit maximum values at the centreline of the jet and that they rapidly decrease in spanwise direction to the normal turbulence level of the cross-flow. turbulence intensities appear to increase with increasing momentum flux ratio. Finally, scaling laws are proposed for the centreline decay of the streamwise and lateral RMS-fluctuations

Experimental and analytical study of intermittency in direct contact condensation of steam in a cross-flow of water

The topology of a condensing steam jet, at low steam mass fluxes, injected in a cross-flow of water has been investigatedexperimentally for various conditions (system pressure around 3 bar). The intermittent character of the steam pocket growthand collapse clearly appeared from the high speed recordings. The typical pocket size grows almost linear until it reaches amaximum penetration depth. Pocket disappearance occurs either via partial detachment and collapse or instantaneous break-upof the entire pocket. The main effect of the liquid cross-flow is an increased heat transfer coefficient for otherwise identicalprocess conditions. This results in a notable reduction of both growth time and maximum penetration depth. A model has beendeveloped and presented to facilitate interpretation of measurement results and to increase our predictive capacity of unstabledirect steam injection. Comparison of model predictions and experimental findings shows that the steam pocket growth timeand its maximum penetration depth are generally well-predicted. The chugging regime occurring at the lowest watertemperature is atypical and has nonzero waiting times. The growth of a steam pocket in unstable condensation regimes is foundto be controlled by fluid inertia and momentum of the injected steam, while drag is negligible

Turbulent stresses in a direct contact condensation jet in cross-flow in a duct with implications for particle break-up

An experimental study has been conducted to investigate the turbulent mixing and heating caused by a (superheated) steam jet injected into a turbulent cross-flow of water in a square channel. The velocity field in the mid plane of the channel has been measured by means of particle image velocimetry for several different values of the ratio of the momentum fluxes of steam and water and various bulk temperatures of the approaching water flow. Condensation is rapid and the single phase jet created is strong, turbulent and with a self-similar velocity profile. The focus of the present paper is an analysis of the three components of the Reynolds stress tensor in a curvilinear coordinate system aligned with the curved centerline of the single-phase jet downstream of the condensation region. It is found that both measured diagonal components of the Reynolds stress tensor exhibit a maximum value at the jet centerline. Scaling laws for the decay of the turbulence intensities along the centerline have been formulated. Moreover, consequences for the break-up of particles in this flow are discussed and compared with the case of a steam jet injected into a stagnant fluid

Physiology-based regularization of the electrocardiographic inverse problem

The inverse problem of electrocardiography aims at noninvasively reconstructing electrical activity of the heart from recorded body-surface electrocardiograms. A crucial step is regularization, which deals with ill-posedness of the problem by imposing constraints on the possible solutions. We developed a regularization method that includes electrophysiological input. Body-surface potentials are recorded and a computed tomography scan is performed to obtain the torso–heart geometry. Propagating waveforms originating from several positions at the heart are simulated and used to generate a set of basis vectors representing spatial distributions of potentials on the heart surface. The real heart-surface potentials are then reconstructed from the recorded body-surface potentials by finding a sparse representation in terms of this basis. This method, which we named ‘physiology-based regularization’ (PBR), was compared to traditional Tikhonov regularization and validated using in vivo recordings in dogs. PBR recovered details of heart-surface electrograms that were lost with traditional regularization, attained higher correlation coefficients and led to improved estimation of recovery times. The best results were obtained by including approximate knowledge about the beat origin in the PBR basis