MicroRNAs in Ewing's Sarcoma

Les tumeurs de la famille du sarcome d'Ewing (ESFTs) sont les deuxièmes plus fréquentes formes de cancer de l'os chez l'enfant et l'adolescent. Le gène de fusion EWS-FLI1 est associé à 85-90% des ESFTs. Ce cancer a probablement pour origine des cellules souches mésenchymateuses (MSCs). Il a en effet été démontré que les MSCs pédiatriques (hpMSCs) sont particulièrement permissives pour le gène de fusion EWS-FLI1 et que celui-ci induit des gènes de cellules souches embryonnaires. Ceci génère une sous-population de cellules présentant des caractéristiques de cellules souches cancéreuses de sarcome d'Ewing (ESFT CSCs) in vitro. Ces cellules reprogrammées n'ont pas de potentiel tumorigénique et un certain nombre de microARN ne sont pas réprimés ou exprimés comme dans un sarcome d'Ewing primaire et sa sous-population de CSCs. Parmi ces microARN on trouve en particulier les membres de la famille let-7 qui jouent un rôle clé dans le contrôle de l'état de différenciation des cellules et régulent de nombreux oncogènes. De plus, leur répression serait capable de favoriser la tumorigénèse. Tous les membres de la famille des microARNs let-7 ont un régulateur commun, la protéine lin-28, qui exerce notamment son action en bloquant la maturation de ces microARNs. Dans ce travail, il s'agira d'évaluer si la co-expression de EWS-FLI1 et de lin-28 dans des hpMSCs permet de créer une sous-population de cellules présentant les caractéristiques de ESFT CSCs. Nous évaluerons l'effet de lin-28 sur les membres de la famille des let7 dans les hpMSCs et apprécierons le potentiel tumorigénique in vivo des hpMSCs exprimant EWS-FLI1 et lin-28. L'outil « Targetscan » est un logiciel qui permet de prédire les cibles des microARN en analysant leur séquence et en la comparant à l'ARN messager 3' non transcrit. Pour les microARN de la famille des let-7, cet outil identifie des gènes cibles potentiels qui jouent un rôle important dans le sarcome d'Ewing. Nous évaluerons si ces protéines sont en effet régulées de façon let-7 dépendante et les conséquences sur la pathogénèse des ESFTs

Application of Boyd’s periodization and relaxation method in a spectral atmospheric limited-area model, part II : accuracy analysis and detailed study of the operational impact

Spectral limited-area models face a particular challenge at their lateral boundaries: the fields need to be made periodic. Boyd proposed a windowing-based method to improve the periodization and relaxation. In a companion paper, the implementation of this windowing method in the operational semi-implicit semi-Lagrangian spectral HARMONIE system was described and some first reproducibility tests, comparing this method to the old existing one, were presented. The present paper provides an in-depth study of the impact of this method for different configurations of the implementation. This is carried out in three steps in well-controlled experimental setups of increasing complexity. First, different aspects of Boyd’s method are analyzed in an idealized perfect-model test using a representative 1D shallow-water model. Second, the implementation is tested in an adiabatic 3D numerical weather prediction (NWP) model with perfect-model experiments. Finally, the impact of using Boyd’s method in a more operational-like NWP context is investigated as well. The presented tests show that, while the implementation of Boyd’s method is neutral in terms of scores, it is superior to the existing spline method in the case of strong dynamical forcings at the lateral boundaries

Simulating model uncertainty of subgrid-scale processes by sampling model errors at convective scales

Ideally, perturbation schemes in ensemble forecasts should be based on the statistical properties of the model errors. Often, however, the statistical properties of these model errors are unknown. In practice, the perturbations are pragmatically modelled and tuned to maximize the skill of the ensemble forecast. In this paper a general methodology is developed to diagnose the model error, linked to a specific physical process, based on a comparison between a target and a reference model. Here, the reference model is a configuration of the ALADIN (Aire Limitée Adaptation Dynamique Développement International) model with a parameterization of deep convection. This configuration is also run with the deep-convection parameterization scheme switched off, degrading the forecast skill. The model error is then defined as the difference of the energy and mass fluxes between the reference model with scale-aware deep-convection parameterization and the target model without deep-convection parameterization. In the second part of the paper, the diagnosed model-error characteristics are used to stochastically perturb the fluxes of the target model by sampling the model errors from a training period in such a way that the distribution and the vertical and multivariate correlation within a grid column are preserved. By perturbing the fluxes it is guaranteed that the total mass, heat and momentum are conserved. The tests, performed over the period 11–20 April 2009, show that the ensemble system with the stochastic flux perturbations combined with the initial condition perturbations not only outperforms the target ensemble, where deep convection is not parameterized, but for many variables it even performs better than the reference ensemble (with scale-aware deep-convection scheme). The introduction of the stochastic flux perturbations reduces the small-scale erroneous spread while increasing the overall spread, leading to a more skillful ensemble. The impact is largest in the upper troposphere with substantial improvements compared to other state-of-the-art stochastic perturbation schemes. At lower levels the improvements are smaller or neutral, except for temperature where the forecast skill is degraded

The influence of advertising on compulsive buying — The role of persuasion knowledge

Abstract Background and aims The growing concern over compulsive buying (CB) among consumers has led to vast amount of research examining the antecedents of this maladaptive behaviour. The focus of previous research was, however, mainly on examining the internal, psychological factors contributing to CB. The current research, on the other hand, sheds light on one of the external triggers which can possibly stimulate CB, namely advertising. Methods An online survey has been conducted to identify the attitudes and scepticism towards advertising as well as ad avoidance and persuasion knowledge among a sample of 582 Belgian consumers. Furthermore, all participants were screened with regard to compulsive buying tendencies. Results This research provides evidence that positive attitudes towards advertising can lead to CB. An important factor in this relation is persuasion knowledge. Conclusions The study results lead to the conclusion that people higher in persuasion knowledge dispose less positive attitudes towards advertising which can subsequently prevent them from engaging in CB. Moreover high scores on scepticism towards advertising and ad avoidance among Belgian consumers in our sample point to a need for advertisers to modify their practices in order to gain more trust from consumers. This study also shows that advertising in particular attracts and seems to affect an already disadvantaged group of people — namely compulsive buyers

Predicting small-scale, short-lived downbursts : case study with the NWP limited-area ALARO model for the Pukkelpop thunderstorm

The authors consider a thunderstorm event in 2011 during a music festival in Belgium that produced a short-lived downburst of a diameter of less than 100 m. This is far too small to be resolved by the kilometric resolutions of today's operational numerical weather prediction models. Operational forecast models will not run at hectometric resolutions in the foreseeable future. The storm caused five casualties and raised strong societal questions regarding the predictability of such a traumatic weather event.In this paper it is investigated whether the downdrafts of a parameterization scheme of deep convection can be used as proxies for the unresolved downbursts. To this end the operational model ALARO [a version of the Action de Recherche Petite Echelle Grande Echelle-Aire Limitee Adaptation Dynamique Developpement International (ARPEGE-ALADIN) operational limited area model with a revised and modular structure of the physical parameterizations] of the Royal Meteorological Institute of Belgium is used. While the model in its operational configuration at the time of the event did not give a clear hint of a downburst event, it has been found that (i) the use of unsaturated downdrafts and (ii) some adaptations of the features of this downdraft parameterization scheme, specifically the sensitivity to the entrainment and friction, can make the downdrafts sensitive enough to the surrounding resolved-scale conditions to make them useful as indicators of the possibility of such downbursts

Jean-François Geleyn, professeur à l'université de Gand

Jean-François Geleyn had a strong link with Belgium through the activities of the ALADIN consortium. When Ghent university started a postgraduate program on meteorology and numerical weather prediction in 2007 he became a guest professor and one of the main driving forces of the creation of this academic program. Later the curriculum of this program was extented to include climate modeling. Many experts at the Royal Meteorological Institute of Belgium followed his courses. Recently, the activities at Ghent university formed the basis for the creation of the Atmospheric Physics Unit within the Department of Physics and Astronomy

The European Central Bank: Decision Rules and Macroeconomic Performance.

In this paper we analyze the effects of different decision rules in the ECB on monetary stability. We consider a model where asymmetric shocks and divergent propagation of shocks on output and inflation are potential causes of tensions within the ECB concerning the conduct of monetary (interest rate) policy. Given divergence of desired interest rates (due to the asymmetries) we analyze the effect of different voting procedures within the Governing Council of the ECB. Welfare implications are discussed.

Generalization and application of the flux-conservative thermodynamic equations in the AROME model of the ALADIN system

General yet compact equations are presented to express the thermodynamic impact of physical parameterizations in a NWP or climate model. By expressing the equations in a flux-conservative formulation, the conservation of mass and energy by the physics parameterizations is a built-in feature of the system. Moreover, the centralization of all thermodynamic calculations guarantees a consistent thermodynamical treatment of the different processes. The generality of this physics-dynamics interface is illustrated by applying it in the AROME NWP model. The physics-dynamics interface of this model currently makes some approximations, which typically consist of neglecting some terms in the total energy budget, such as the transport of heat by falling precipitation, or the effect of diffusive moisture transport. Although these terms are usually quite small, omitting them from the energy budget breaks the constraint of energy conservation. The presented set of equations provides the opportunity to get rid of these approximations, in order to arrive at a consistent and energy-conservative model. A verification in an operational setting shows that the impact on monthly-averaged, domain-wide meteorological scores is quite neutral. However, under specific circumstances, the supposedly small terms may turn out not to be entirely negligible. A detailed study of a case with heavy precipitation shows that the heat transport by precipitation contributes to the formation of a region of relatively cold air near the surface, the so-called cold pool. Given the importance of this cold pool mechanism in the life cycle of convective events, it is advisable not to neglect phenomena that may enhance it

IMPs: an RNA-binding protein family that provides a link between stem cell maintenance in normal development and cancer.

IMPs, also known as insulin-like growth factor 2 (IGF2) messenger RNA (mRNA)-binding proteins (IGF2BPs), are highly conserved oncofetal RNA-binding proteins (RBPs) that regulate RNA processing at several levels, including localization, translation, and stability. Three mammalian IMP paralogs (IMP1-3) have been identified that are expressed in most organs during embryogenesis, where they are believed to play an important role in cell migration, metabolism, and stem cell renewal. Whereas some IMP2 expression is retained in several adult mouse organs, IMP1 and IMP3 are either absent or expressed at very low levels in most tissues after birth. However, all three paralogs can be re-expressed upon malignant transformation and are found in a broad range of cancer types where their expression often correlates with poor prognosis. IMPs appear to resume their physiological functions in malignant cells, which not only contribute to tumor progression but participate in the establishment and maintenance of tumor cell hierarchies. This review summarizes our current understanding of the functions of IMPs during normal development and focuses on a series of recent observations that have provided new insight into how their physiological functions enable IMPs to play a potentially key role in cancer stem cell maintenance and tumor growth