Nanoscale Stiffness Distribution in Bone Metastasis

Nanomechanical heterogeneity is expected to have an effect on elasticity, injury and bone remodelling. In normal bone, we have two types of cells (osteoclasts and osteoblasts) working together to maintain existing bone. Bone cancers can produce factors that make the osteoclasts work harder. This means that more bone is destroyed than rebuilt, and leads to weakening of the affected bone. We report here the first demonstration of the nanoscale stiffness distribution in bone metastases before and after treatment of animals with the bisphosphonate Risedronate, a drug which is currently used for the treatment of bone metastases in patients with advanced cancers. The strategy used here is applicable to a wide class of biological tissues and may serve as a new reflection for biologically inspired scaffolds technologies

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Analytical development methodology in SFC and coupling strategies in on-line SFE-SFC-MS

Si les systèmes utilisant des fluides supercritiques pour l’extraction ou la séparation de molécules continuent de s’implanter dans nos laboratoires, des études sont encore nécessaires afin de lever les derniers freins à l’utilisation de ces approches. Le développement d’instruments et de phases stationnaires dédiés aide cependant dans ce sens, permettant un regain d’intérêt pour la chromatographie en phase supercritique (SFC) notamment ces dernières années. Utilisant toutes deux du CO₂ supercritique comme principal éluant, l'extraction par fluide supercritique (SFE) et la SFC couplées en ligne offrent une approche de choix afin de répondre à des problématiques comme le gain de productivité et la diminution des erreurs humaines. De plus, le couplage à la spectrométrie de masse (MS) offre une solution analytique très complète.L’objectif de cette thèse en partenariat avec le constructeur Shimadzu est donc d’étudier le potentiel de colonnes dédiées à l’analyse de petites molécules par fluides supercritiques et de mieux comprendre les avantages et inconvénients de leur instrument de SFE-SFC en ligne. Une étude des colonnes proposées par Shimadzu a d’abord été réalisée grâce à des relations quantitatives structure-rétention (QSRR), afin de comprendre les différentes interactions impliquées dans la rétention des composés. Les colonnes ont ensuite été utilisées pour l’analyse de divers composés d’intérêt (produits pharmaceutiques et produits naturels) permettant ainsi de proposer un jeu de colonnes réduit, de sélectivités orthogonales permettant de démarrer efficacement le développement de méthodes SFC. La SFC-MS a ensuite été utilisée pour l’identification et la quantification de triglycérides provenant d’huiles végétales d’origines variées, permettant de comparer les similarités entre les divers échantillons. Enfin, la SFE-SFC-MS en ligne a été mise en œuvre pour l’extraction et l’analyse de molécules apolaires (triglycérides) et polaires (flavonolignanes) provenant de graines de Chardon-Marie (Silybum marianum). Cette dernière approche a permis d’étudier l’impact du mode de transfert entre la SFE et la SFC sur la qualité chromatographique de la méthode en ligne.If systems using supercritical fluids for the extraction or separation of molecules continue to implant in laboratories, studies are still necessary to remove the last barriers to the use of these approaches. However, the development of dedicated systems and consumables is favourable, allowing a renewed interest in supercritical fluid chromatography (SFC), especially in recent years. As they both employ supercritical CO₂ as the major eluent, supercritical fluid extraction (SFE) and SFC hyphenated on-line offer an excellent solution to address issues such as productivity gain and human error reduction. Furthermore, hyphenation with mass spectrometry (MS) offers a most powerful analytical solution.The objective of this thesis in partnership with the manufacturer Shimadzu is to study the potential of columns dedicated to the analysis of small molecules with supercritical fluids and to understand the advantages and disadvantages of their on-line SFE-SFC system. A study of Shimadzu stationary phases was first carried out thanks to quantitative structure-retention relationships (QSRRs), in order to understand the different interactions involved in compounds retention. The columns were then used to analyse various pharmaceutical and natural compounds allowing to propose an orthogonal set of columns to facilitate method development. SFC-MS was then applied to identify and quantify triglycerides from vegetable oils of various origins, allowing to compare the similarities between these samples. Finally, on-line SFE-SFC-MS was used for the extraction and analysis of non-polar (triglycerides) and polar molecules (flavonolignans) from milk thistle (Silybum marianum) seeds. This last approach allowed to examine the impact of the transfer mode between SFE and SFC on the chromatographic quality of the on-line method

Ecological restoration of solar park plant communities and the effect of solar panels

The construction of solar parks leads to soil degradation and the destruction of vegetation. Solar panels change the microclimate affecting plant survival and vegetation development. The increasing solar energy production requires solutions for ecological restoration from the beginning of electricity production. We compared three methods to restore Mediterranean dry grasslands as a target community not affecting solar energy production: seed material transfer, sowing of the target species Brachypodium retusum and an increase in soil organic matter by compost addition. The experiment was set up in a solar park located in South-Eastern France, both outside and below solar panels (SP). After four years, seed material transfer was the best method to initiate plant succession towards the reference community. SP hampered restoration success and strongly reduced plant species richness, in particular of species from the reference community. B. retusum survival decreased by 50% and phytometabolic indices revealed a light stress under SP. However, the species still maintained growth similar to plants outside SP suggesting shade tolerance. Long-term monitoring is required to evaluate whether communities better adapted to light reduction under panels need to be taken into account for successful restoration

Precondition Coverage in Software Testing

Preconditions indicate when it is permitted to use a given function. However, it is not always the case that both outcomes of a precondition are observed during testing. A precondition that is always false makes a function unusable, a precondition that is always true may turn out to be actually an invariant. In model-based testing, preconditions describes when a transition may be executed from a given state. If no outgoing transition is enabled in a given state because all preconditions of all outgoing transitions are false, the test model may be flawed. Experiments show a low test coverage of preconditions in the Scala library. We also investigate preconditions in Modbat models for model-based testing, in that case, a certain number of test cases is needed to produce sufficient coverage, but remaining cases of low coverage indeed point to legitimate flaws in test models or code.QC 20170109</p

Effects of solar park construction and solar panels on soil quality, microclimate, CO 2 effluxes, and vegetation under a Mediterranean climate

International audienceSolar energy is increasingly used to produce electricity in Europe, but the environmental impact of constructing and running solar parks (SP) is not yet well studied. Solar park construction requires partial vegetation removal and soil leveling. Additionally, solar panels may alter soil microclimate and functioning. In our study of three French Mediterranean solar parks, we analyzed:(1) effects of solar park construction on soil quality by comparing solar park soils with those of semi-natural land cover types (pinewood and shrubland) and abandoned croplands (former vineyards); and (2) the effect of solar panels on soil microclimate, CO2 effluxes, and vegetation. We measured 21 soil properties of physical, chemical, and microbiological soil quality in one solar park and its surroundings to calculate integrated indicators of soil quality. We surveyed soil temperature and moisture, CO2 effluxes, and vegetation below and outside solar panels of three solar parks. Soil aggregate stability was reduced by SP construction resulting in a degradation of soil physical quality. Soil chemical quality and a general indicator of soil quality were lower in anthropogenic (SP and abandoned vineyards) than in semi-natural (pinewood and shrubland) land cover types. However, differences between abandoned vineyards representing the preconstruction land cover type and solar parks were not significant. Solar panels reduced the soil temperature by 10% and soil CO2 effluxes by 50% but did not affect early successional plant communities. Long-term monitoring is needed to evaluate the effects of solar panels on vegetation

Model-based Testing of Stateful APIs with Modbat

Modbat makes testing easier by providing a user-friendly modeling language to describe the behavior of systems, from such a model, test cases are generated and executed. Modbat's domain-specific language is based on Scala, its features include probabilistic and non-deterministic transitions, component models with inheritance, and exceptions. We demonstrate the versatility of Modbat by finding a confirmed defect in the currently latest version of Java, and by testing SAT solvers.QC 20170109</p

On the link between emotion, attention and content in virtual immersive environments

International audienceWhile immersive media have been shown to generate more intense emotions, saliency information has been shown to be a key component for the assessment of their quality, owing to the various portions of the sphere (viewports) a user can attend. In this article, we investigate the tri-partite connection between user attention, user emotion and visual content in immersive environments. To do so, we present a new dataset enabling the analysis of different types of saliency, both lowlevel and high-level, in connection with the user's state in 360 • videos. Head and gaze movements are recorded along with self-reports and continuous physiological measurements of emotions. We then study how the accuracy of saliency estimators in predicting user attention depends on user-reported and physiologically-sensed emotional perceptions. Our results show that high-level saliency better predicts user attention for higher levels of arousal. We discuss how this work serves as a first step to understand and predict user attention and intents in immersive interactive environments