Ultra-high-resolution 3D imaging of atherosclerosis in mice with synchrotron differential phase contrast: a proof of concept study.

The goal of this study was to investigate the performance of 3D synchrotron differential phase contrast (DPC) imaging for the visualization of both macroscopic and microscopic aspects of atherosclerosis in the mouse vasculature ex vivo. The hearts and aortas of 2 atherosclerotic and 2 wild-type control mice were scanned with DPC imaging with an isotropic resolution of 15 μm. The coronary artery vessel walls were segmented in the DPC datasets to assess their thickness, and histological staining was performed at the level of atherosclerotic plaques. The DPC imaging allowed for the visualization of complex structures such as the coronary arteries and their branches, the thin fibrous cap of atherosclerotic plaques as well as the chordae tendineae. The coronary vessel wall thickness ranged from 37.4 ± 5.6 μm in proximal coronary arteries to 13.6 ± 3.3 μm in distal branches. No consistent differences in coronary vessel wall thickness were detected between the wild-type and atherosclerotic hearts in this proof-of-concept study, although the standard deviation in the atherosclerotic mice was higher in most segments, consistent with the observation of occasional focal vessel wall thickening. Overall, DPC imaging of the cardiovascular system of the mice allowed for a simultaneous detailed 3D morphological assessment of both large structures and microscopic details.

Improvement of allocentric spatial memory resolution in children from 2 to 4 years of age

Allocentric spatial memory, the memory for locations coded in relation to objects comprising our environment, is a fundamental component of episodic memory and is dependent on the integrity of the hippocampal formation in adulthood. Previous research from different laboratories reported that basic allocentric spatial memory abilities are reliably observed in children after 2 years of age. Based on work performed in monkeys and rats, we had proposed that the functional maturation of direct entorhinal cortex projections to the CA1 field of the hippocampus might underlie the emergence of basic allocentric spatial memory. We also proposed that the protracted development of the dentate gyrus and its projections to the CA3 field of the hippocampus might underlie the development of high-resolution allocentric spatial memory capacities, based on the essential contribution of these structures to the process known as pattern separation. Here, we present an experiment designed to assess the development of spatial pattern separation capacities and its impact on allocentric spatial memory performance in children from 18 to 48 months of age. We found that: (1) allocentric spatial memory performance improved with age, (2) as compared to younger children, a greater number of children older than 36 months advanced to the final stage requiring the highest degree of spatial resolution, and (3) children that failed at different stages exhibited difficulties in discriminating locations that required higher spatial resolution abilities. These results are consistent with the hypothesis that improvements in human spatial memory performance might be linked to improvements in pattern separation capacities.

New features of the layer-by-layer deposition of microcrystalline silicon films revealed by spectroscopic ellipsometry and high resolution transmission electron microscopy

Spectroscopic ellipsometry and high resolution transmission electron microscopy have been used to characterize microcrystalline silicon films. We obtain an excellent agreement between the multilayer model used in the analysis of the optical data and the microscopy measurements. Moreover, thanks to the high resolution achieved in the microscopy measurements and to the improved optical models, two new features of the layer-by-layer deposition of microcrystalline silicon have been detected: i) the microcrystalline films present large crystals extending from the a-Si:H substrate to the film surface, despite the sequential process in the layer-by-layer deposition; and ii) a porous layer exists between the amorphous silicon substrate and the microcrystalline silicon film.

Assessing the use of very high resolution data to predict species distribution in a mountain environment

Nowadays, Species Distribution Models (SDMs) are a widely used tool. Using different statistical approaches these models reconstruct the realized niche of a species using presence data and a set of variables, often topoclimatic. There utilization range is quite large from understanding single species requirements, to the creation of nature reserve based on species hotspots, or modeling of climate change impact, etc... Most of the time these models are using variables at a resolution of 50km x 50km or 1 km x 1 km. However in some cases these models are used with resolutions below the kilometer scale and thus called high resolution models (100 m x 100 m or 25 m x 25 m). Quite recently a new kind of data has emerged enabling precision up to lm x lm and thus allowing very high resolution modeling. However these new variables are very costly and need an important amount of time to be processed. This is especially the case when these variables are used in complex calculation like models projections over large areas. Moreover the importance of very high resolution data in SDMs has not been assessed yet and is not well understood. Some basic knowledge on what drive species presence-absences is still missing. Indeed, it is not clear whether in mountain areas like the Alps coarse topoclimatic gradients are driving species distributions or if fine scale temperature or topography are more important or if their importance can be neglected when balance to competition or stochasticity. In this thesis I investigated the importance of very high resolution data (2-5m) in species distribution models using either very high resolution topographic, climatic or edaphic variables over a 2000m elevation gradient in the Western Swiss Alps. I also investigated more local responses of these variables for a subset of species living in this area at two precise elvation belts. During this thesis I showed that high resolution data necessitates very good datasets (species and variables for the models) to produce satisfactory results. Indeed, in mountain areas, temperature is the most important factor driving species distribution and needs to be modeled at very fine resolution instead of being interpolated over large surface to produce satisfactory results. Despite the instinctive idea that topographic should be very important at high resolution, results are mitigated. However looking at the importance of variables over a large gradient buffers the importance of the variables. Indeed topographic factors have been shown to be highly important at the subalpine level but their importance decrease at lower elevations. Wether at the mountane level edaphic and land use factors are more important high resolution topographic data is more imporatant at the subalpine level. Finally the biggest improvement in the models happens when edaphic variables are added. Indeed, adding soil variables is of high importance and variables like pH are overpassing the usual topographic variables in SDMs in term of importance in the models. To conclude high resolution is very important in modeling but necessitate very good datasets. Only increasing the resolution of the usual topoclimatic predictors is not sufficient and the use of edaphic predictors has been highlighted as fundamental to produce significantly better models. This is of primary importance, especially if these models are used to reconstruct communities or as basis for biodiversity assessments. -- Ces dernières années, l'utilisation des modèles de distribution d'espèces (SDMs) a continuellement augmenté. Ces modèles utilisent différents outils statistiques afin de reconstruire la niche réalisée d'une espèce à l'aide de variables, notamment climatiques ou topographiques, et de données de présence récoltées sur le terrain. Leur utilisation couvre de nombreux domaines allant de l'étude de l'écologie d'une espèce à la reconstruction de communautés ou à l'impact du réchauffement climatique. La plupart du temps, ces modèles utilisent des occur-rences issues des bases de données mondiales à une résolution plutôt large (1 km ou même 50 km). Certaines bases de données permettent cependant de travailler à haute résolution, par conséquent de descendre en dessous de l'échelle du kilomètre et de travailler avec des résolutions de 100 m x 100 m ou de 25 m x 25 m. Récemment, une nouvelle génération de données à très haute résolution est apparue et permet de travailler à l'échelle du mètre. Les variables qui peuvent être générées sur la base de ces nouvelles données sont cependant très coûteuses et nécessitent un temps conséquent quant à leur traitement. En effet, tout calcul statistique complexe, comme des projections de distribution d'espèces sur de larges surfaces, demande des calculateurs puissants et beaucoup de temps. De plus, les facteurs régissant la distribution des espèces à fine échelle sont encore mal connus et l'importance de variables à haute résolution comme la microtopographie ou la température dans les modèles n'est pas certaine. D'autres facteurs comme la compétition ou la stochasticité naturelle pourraient avoir une influence toute aussi forte. C'est dans ce contexte que se situe mon travail de thèse. J'ai cherché à comprendre l'importance de la haute résolution dans les modèles de distribution d'espèces, que ce soit pour la température, la microtopographie ou les variables édaphiques le long d'un important gradient d'altitude dans les Préalpes vaudoises. J'ai également cherché à comprendre l'impact local de certaines variables potentiellement négligées en raison d'effets confondants le long du gradient altitudinal. Durant cette thèse, j'ai pu monter que les variables à haute résolution, qu'elles soient liées à la température ou à la microtopographie, ne permettent qu'une amélioration substantielle des modèles. Afin de distinguer une amélioration conséquente, il est nécessaire de travailler avec des jeux de données plus importants, tant au niveau des espèces que des variables utilisées. Par exemple, les couches climatiques habituellement interpolées doivent être remplacées par des couches de température modélisées à haute résolution sur la base de données de terrain. Le fait de travailler le long d'un gradient de température de 2000m rend naturellement la température très importante au niveau des modèles. L'importance de la microtopographie est négligeable par rapport à la topographie à une résolution de 25m. Cependant, lorsque l'on regarde à une échelle plus locale, la haute résolution est une variable extrêmement importante dans le milieu subalpin. À l'étage montagnard par contre, les variables liées aux sols et à l'utilisation du sol sont très importantes. Finalement, les modèles de distribution d'espèces ont été particulièrement améliorés par l'addition de variables édaphiques, principalement le pH, dont l'importance supplante ou égale les variables topographique lors de leur ajout aux modèles de distribution d'espèces habituels.

Very high-resolution digital elevation models: are multi-scale-derived variables ecologically relevant?

1. Digital elevation models (DEMs) are often used in landscape ecology to retrieve elevation or first derivative terrain attributes such as slope or aspect in the context of species distribution modelling. However, DEM-derived variables are scale-dependent and, given the increasing availability of very high-resolution (VHR) DEMs, their ecological relevancemust be assessed for different spatial resolutions. 2. In a study area located in the Swiss Western Alps, we computed VHR DEMs-derived variables related to morphometry, hydrology and solar radiation. Based on an original spatial resolution of 0.5 m, we generated DEM-derived variables at 1, 2 and 4 mspatial resolutions, applying a Gaussian Pyramid. Their associations with local climatic factors, measured by sensors (direct and ambient air temperature, air humidity and soil moisture) as well as ecological indicators derived fromspecies composition, were assessed with multivariate generalized linearmodels (GLM) andmixed models (GLMM). 3. Specific VHR DEM-derived variables showed significant associations with climatic factors. In addition to slope, aspect and curvature, the underused wetness and ruggedness indices modelledmeasured ambient humidity and soilmoisture, respectively. Remarkably, spatial resolution of VHR DEM-derived variables had a significant influence on models' strength, with coefficients of determination decreasing with coarser resolutions or showing a local optimumwith a 2 mresolution, depending on the variable considered. 4. These results support the relevance of using multi-scale DEM variables to provide surrogates for important climatic variables such as humidity, moisture and temperature, offering suitable alternatives to direct measurements for evolutionary ecology studies at a local scale.

Europeanisation and Conflict Resolution: The Case of Cyprus

This paper investigates the example of Cyprus as a case study for the Europeanisation of conflict resolution. The argument advanced is that the European Union (EU) impacts the positions of the parts of the conflict (here, Greek Cypriots, Turkish Cypriots and Turkey) but not always towards the resolution of the dispute and compliance with EU conditionality. Conformity with EU conditionality depends on its credibility, which is decreased by the internalisation of the conflict into the EU. In this context, this work contributes to the discussion on Europeanisation and the aptitude of the EU in conflict resolution as well as the role of the EU in the Cyprus conflict during the post-accession years.

Predicting richness and composition in mountain insect communities at high resolution: a new test of the SESAM framework

Aim The aim of this study was to test different modelling approaches, including a new framework, for predicting the spatial distribution of richness and composition of two insect groups. Location The western Swiss Alps. Methods We compared two community modelling approaches: the classical method of stacking binary prediction obtained fromindividual species distribution models (binary stacked species distribution models, bS-SDMs), and various implementations of a recent framework (spatially explicit species assemblage modelling, SESAM) based on four steps that integrate the different drivers of the assembly process in a unique modelling procedure. We used: (1) five methods to create bS-SDM predictions; (2) two approaches for predicting species richness, by summing individual SDM probabilities or by modelling the number of species (i.e. richness) directly; and (3) five different biotic rules based either on ranking probabilities from SDMs or on community co-occurrence patterns. Combining these various options resulted in 47 implementations for each taxon. Results Species richness of the two taxonomic groups was predicted with good accuracy overall, and in most cases bS-SDM did not produce a biased prediction exceeding the actual number of species in each unit. In the prediction of community composition bS-SDM often also yielded the best evaluation score. In the case of poor performance of bS-SDM (i.e. when bS-SDM overestimated the prediction of richness) the SESAM framework improved predictions of species composition. Main conclusions Our results differed from previous findings using community-level models. First, we show that overprediction of richness by bS-SDM is not a general rule, thus highlighting the relevance of producing good individual SDMs to capture the ecological filters that are important for the assembly process. Second, we confirm the potential of SESAM when richness is overpredicted by bS-SDM; limiting the number of species for each unit and applying biotic rules (here using the ranking of SDM probabilities) can improve predictions of species composition

Imaging the time-integrated cerebral metabolic activity with subcellular resolution through nanometer-scale detection of biosynthetic products deriving from (13)C-glucose.

Glucose is the primary source of energy for the brain but also an important source of building blocks for proteins, lipids, and nucleic acids. Little is known about the use of glucose for biosynthesis in tissues at the cellular level. We demonstrate that local cerebral metabolic activity can be mapped in mouse brain tissue by quantitatively imaging the biosynthetic products deriving from [U-(13)C]glucose metabolism using a combination of in situ electron microscopy and secondary ion mass-spectroscopy (NanoSIMS). Images of the (13)C-label incorporated into cerebral ultrastructure with ca. 100nm resolution allowed us to determine the timescale on which the metabolic products of glucose are incorporated into different cells, their sub-compartments and organelles. These were mapped in astrocytes and neurons in the different layers of the motor cortex. We see evidence for high metabolic activity in neurons via the nucleus (13)C enrichment. We observe that in all the major cell compartments, such as e.g. nucleus and Golgi apparatus, neurons incorporate substantially higher concentrations of (13)C-label than astrocytes.

Identification of new transformation products during enzymatic treatment of tetracycline and erythromycin antibiotics at laboratory scale by an on-line turbulent flow liquid-chromatography coupled to a high resolution mass spectrometer LTQ-Orbitrap

This work describes the formation of transformation products (TPs) by the enzymatic degradation at laboratory scale of two highly consumed antibiotics: tetracycline (Tc) and erythromycin (ERY). The analysis of the samples was carried out by a fast and simple method based on the novel configuration of the on-line turbulent flow system coupled to a hybrid linear ion trap – high resolution mass spectrometer. The method was optimized and validated for the complete analysis of ERY, Tc and their transformation products within 10 min without any other sample manipulation. Furthermore, the applicability of the on-line procedure was evaluated for 25 additional antibiotics, covering a wide range of chemical classes in different environmental waters with satisfactory quality parameters. Degradation rates obtained for Tc by laccase enzyme and ERY by EreB esterase enzyme without the presence of mediators were ∼78% and ∼50%, respectively. Concerning the identification of TPs, three suspected compounds for Tc and five of ERY have been proposed. In the case of Tc, the tentative molecular formulas with errors mass within 2 ppm have been based on the hypothesis of dehydroxylation, (bi)demethylation and oxidation of the rings A and C as major reactions. In contrast, the major TP detected for ERY has been identified as the “dehydration ERY-A”, with the same molecular formula of its parent compound. In addition, the evaluation of the antibiotic activity of the samples along the enzymatic treatments showed a decrease around 100% in both cases

Can chest high-resolution computed tomography findings diagnose pulmonary alveolar microlithiasis?

AbstractObjective:The present study was aimed at retrospectively reviewing high-resolution computed tomography (HRCT) findings in patients with pulmonary alveolar microlithiasis in order to evaluate the frequency of tomographic findings and their distribution in the lung parenchyma.Materials and Methods:Thirteen patients (9 females and 4 males; age, 9 to 59 years; mean age, 34.5 years) were included in the present study. The HRCT images were independently evaluated by two observers whose decisions were made by consensus. The inclusion criterion was the presence of abnormalities typical of pulmonary alveolar microlithiasis at HRCT, which precludes lung biopsy. However, in 6 cases lung biopsy was performed.Results:Ground-glass opacities and small parenchymal nodules were the predominant tomographic findings, present in 100% of cases, followed by small subpleural nodules (92.3%), subpleural cysts (84.6%), subpleural linear calcifications (69.2%), crazy-paving pattern (69.2%), fissure nodularity (53.8%), calcification along interlobular septa (46.2%) and dense consolidation (46.2%).Conclusion:As regards distribution of the lesions, there was preferential involvement of the lower third of the lungs. No predominance of distribution in axial and anteroposterior directions was observed.

Identification of metabolites and thermal transformation products of quinolones in raw cow milk by liquid chromatography coupled to high resolution mass spectrometry

The presence of residues of antibiotics, metabolites, and thermal transformation products (TPs), produced during thermal treatment to eliminate pathogenic microorganisms in milk, could represent a risk for people. Cow"s milk samples spiked with enrofloxacin (ENR), ciprofloxacin (CIP), difloxacin (DIF), and sarafloxacin (SAR) and milk samples from cows medicated with ENR were submitted to several thermal treatments. The milk samples were analyzed by liquid chromatography-mass spectrometry (LC-MS) to find and identify TPs and metabolites. In this work, 27 TPs of 4 quinolones and 24 metabolites of ENR were found. Some of these compounds had been reported previously, but others were characterized for the first time, including lactose-conjugated CIP, the formamidation reaction for CIP and SAR, and hydroxylation or ketone formation to produce three different isomers for all quinolones studied.