Antitumor Effects of Ral-GTPases Downregulation in Glioblastoma

Glioblastoma (GBM) is the most common tumor in the central nervous system in adults. This neoplasia shows a high capacity of growth and spreading to the surrounding brain tissue, hindering its complete surgical resection. Therefore, the finding of new antitumor therapies for GBM treatment is a priority. We have previously described that cyclin D1-CDK4 promotes GBM dissemination through the activation of the small GTPases RalA and RalB. In this paper, we show that RalB GTPase is upregulated in primary GBM cells. We found that the downregulation of Ral GTPases, mainly RalB, prevents the proliferation of primary GBM cells and triggers a senescence-like response. Moreover, downregulation of RalA and RalB reduces the viability of GBM cells growing as tumorspheres, suggesting a possible role of these GTPases in the survival of GBM stem cells. By using mouse subcutaneous xenografts, we have corroborated the role of RalB in GBM growth in vivo. Finally, we have observed that the knockdown of RalB also inhibits cell growth in temozolomide-resistant GBM cells. Overall, our work shows that GBM cells are especially sensitive to Ral-GTPase availability. Therefore, we propose that the inactivation of Ral-GTPases may be a reliable therapeutic approach to prevent GBM progression and recurrence.     

Cytopathological Outcomes of Knocking down Expression of Mitochondrial Complex II Subunits in Dictyostelium discoideum

Mitochondrial Complex II is composed of four core subunits and mutations to any of the subunits result in lowered Complex II activity. Surprisingly, although mutations in any of the subunits can yield similar clinical outcomes, there are distinct differences in the patterns of clinical disease most commonly associated with mutations in different subunits. Thus, mutations to the SdhA subunit most often result in mitochondrial disease phenotypes, whilst mutations to the other subunits SdhB-D more commonly result in tumour formation. The reason the clinical outcomes are so different is unknown. Here, we individually antisense-inhibited three of the Complex II subunits, SdhA, SdhB or SdhC, in the simple model organism Dictyostelium discoideum. Whilst SdhB and SdhC knockdown resulted in growth defects on bacterial lawns, antisense inhibition of SdhA expression resulted in a different pattern of phenotypic defects, including impairments of growth in liquid medium, enhanced intracellular proliferation of the bacterial pathogen Legionella pneumophila and phagocytosis. Knockdown of the individual subunits also produced different abnormalities in mitochondrial function with only SdhA knockdown resulting in broad mitochondrial dysfunction. Furthermore, these defects were shown to be mediated by the chronic activation of the cellular energy sensor AMP-activated protein kinase. Our results are in agreement with a role for loss of function of SdhA but not the other Complex II subunits in impairing mitochondrial oxidative phosphorylation and they suggest a role for AMP-activated protein kinase in mediating the cytopathological outcomes.     

Water retention and gas relative permeability of two industrial concretes

This experimental study aims at identifying the water retention properties of two industrial concretes to be used for long term underground nuclear waste storage structures. Together with water retention, gas transfer properties are identified at varying water saturation level, i.e. relative gas permeability is assessed directly as a function of water saturation level S_w. The influence of the initial de-sorption path and of the subsequent re-saturation are analysed both in terms of water retention and gas transfer properties. Also, the influence of concrete microstructure upon water retention and relative gas permeability is assessed, using porosity measurements, analysis of the BET theory from water retention properties, and MIP. Finally, a single relative gas permeability curve is proposed for each concrete, based on Van Genuchten–Mualem's statistical model, to be used for continuous modelling approaches of concrete structures, both during drying and imbibition.     

Thermodiffusion‐Assisted Pyroelectrics—Enabling Rapid and Stable Heat and Radiation Sensing

Sensors for monitoring temperature, heat flux, and thermal radiation are essential for applications such as electronic skin. While pyroelectric and thermoelectric effects are suitable candidates as functional elements in such devices, both concepts show individual drawbacks in terms of zero equilibrium signals for pyroelectric materials and small or slow response of thermoelectric materials. Here, these drawbacks are overcome by introducing the concept of thermodiffusion‐assisted pyroelectrics, which combines and enhances the performance of pyroelectric and ionic thermoelectric materials. The presented integrated concept provides both rapid initial response upon heating and stable synergistically enhanced signals upon prolonged exposure to heat stimuli. Likewise, incorporation of plasmonic metasurfaces enables the concept to provide both rapid and stable signals for radiation‐induced heating. The performance of the concept and its working mechanism can be explained by ion–electron interactions at the interface between the pyroelectric and ionic thermoelectric materials.     

Segmentation of multiple sclerosis lesions in brain MRI: A review of automated approaches

Automatic segmentation of multiple sclerosis (MS) lesions in brain MRI has been widely investigated in recent years with the goal of helping MS diagnosis and patient follow-up. However, the performance of most of the algorithms still falls far below expert expectations. In this paper, we review the main approaches to automated MS lesion segmentation. The main features of the segmentation algorithms are analysed and the most recent important techniques are classified into different strategies according to their main principle, pointing out their strengths and weaknesses and suggesting new research directions. A qualitative and quantitative comparison of the results of the approaches analysed is also presented. Finally, possible future approaches to MS lesion segmentation are discussed.     

Subspace Procrustes Analysis

Procrustes analysis (PA) has been a popular technique to align and build 2-D statistical models of shapes. Given a set of 2-D shapes PA is applied to remove rigid transformations. Later, a non-rigid 2-D model is computed by modeling the residual (e.g., PCA). Although PA has been widely used, it has several limitations for modeling 2-D shapes: occluded landmarks and missing data can result in local minima solutions, and there is no guarantee that the 2-D shapes provide a uniform sampling of the 3-D space of rotations for the object. To address previous issues, this paper proposes subspace PA (SPA). Given several instances of a 3-D object, SPA computes the mean and a 2-D subspace that can model rigid and non-rigid deformations of the 3-D object. We propose a discrete (DSPA) and continuous (CSPA) formulation for SPA, assuming that 3-D samples of an object are provided. DSPA extends the traditional PA, and produces unbiased 2-D models by uniformly sampling different views of the 3-D object. CSPA provides a continuous approach to uniformly sample the space of 3-D rotations, being more efficient in space and time. We illustrate the benefits of SPA in two different applications. First, SPA is used to learn 2-D face and body models from 3-D datasets. Experiments on the FaceWarehouse and CMU motion capture (MoCap) datasets show the benefits of our 2-D models against the state-of-the-art PA approaches and conventional 3-D models. Second, SPA learns an unbiased 2-D model from CMU MoCap dataset and it is used to estimate the human pose on the Leeds Sports dataset.     

Synthesis of probabilistic models for quality-of-service software engineering

An increasingly used method for the engineering of software systems with strict quality-of-service (QoS) requirements involves the synthesis and verification of probabilistic models for many alternative architectures and instantiations of system parameters. Using manual trial-and-error or simple heuristics for this task often produces suboptimal models, while the exhaustive synthesis of all possible models is typically intractable. The EvoChecker search-based software engineering approach presented in our paper addresses these limitations by employing evolutionary algorithms to automate the model synthesis process and to significantly improve its outcome. EvoChecker can be used to synthesise the Pareto-optimal set of probabilistic models associated with the QoS requirements of a system under design, and to support the selection of a suitable system architecture and configuration. EvoChecker can also be used at runtime, to drive the efficient reconfiguration of a self-adaptive software system. We evaluate EvoChecker on several variants of three systems from different application domains, and show its effectiveness and applicability.     

Reorientation patterns in central-place foraging: internal clocks and klinokinesis

We study central-place foraging patterns of Aphaenogaster senilis ants at a population level by video framing individual ant trajectories in a circular arena with a nest connected to its centre. The ants naturally leave and enter the nest and forage generating non-trivial movement patterns around the nest. Our data analysis indicated that the trajectories observed can be classified into two strategies: the risk-averse strategy, which involves wandering around the nest without departing far from it and the risk-prone strategy, which involves long exploration paths with periodic returns to the central region, nearby the nest. We found that both risk-prone and risk-averse strategies exhibit qualitatively the same reorientation patterns, with the time between consecutive reorientations covering a wide range of scales, and fitting a stretched exponential function. Nevertheless, differences in the temporal scales and the time variability of such reorientation events differ, together with other aspects of motion, such as average speed and turns. Our results give experimental evidence that the internal mechanisms driving reorientations in ants tend to favour frequently long relocations, as theory predicts for efficient exploration in patchy landscapes, but ants engaged in central-place foraging can modulate such behaviour to control distances from the nest. Previous works on the species support the idea that risk-prone and risk-averse strategies may reflect actual differences between individuals age and experience; these factors (age and experience) should be then relevant in modulating the internal reorientation clocks. To support the validity of our findings, we develop a random-walk model combining stretched exponential reorientation clocks with klinokinesis that fits the time length and the travelled distance distributions of the observed trajectories.     

The effect of the research setting on the emotional and sensory profiling under blind,expected, and informed conditions: A study on premium and private label yogurt products

Although sensory and emotional evaluation of food products mostly occurs in a controlled laboratory environment, it is often criticized as it may not reflect a realistic situation for consumers. Moreover, products are mainly blind evaluated by participants, whereas external factors such as brand are often considered as key drivers of food choice. This study aims to examine the role of research setting (central location test versus home-use test) and brand information on the overall acceptance, and sensory and emotional profiling of 5 strawberry-flavored yogurts. Thereby, private label and premium brands are compared under 3 conditions: blind, expected, and informed (brand information). A total of 99 adult subjects participated in 3 sessions over 3 consecutive weeks. Results showed that overall liking for 2 yogurt samples was higher in the laboratory environment under the informed evaluation condition, whereas no effect of research setting was found under the blind and expected conditions. Although emotional profiles of the products differed depending on the research setting, this was less the case for the sensory profiles. Furthermore, brand information clearly affected the sensory perception of certain attributes but had less influence on overall liking and emotional profiling. These results indicate that both scientists and food companies should consider the effect of the chosen methodology on ecological validity when conducting sensory research with consumers because the laboratory context could lead to a more positive evaluation compared with a home-use test.