Magnetoelectricity in the ferrimagnetic Cu2OSeO3: symmetry analysis and Raman scattering study

sublattices ferrimagnet Cu2OSeO3 with a cubic symmetry and a linear magnetoelectric effect. There is no spectroscopic evidence for structural lattice distortions below T-C=60 K, which are expected due to magnetoelectric coupling. Using symmetry arguments we explain this observation by considering a special type of ferrimagnetic ground state which does not generate a spontaneous electric polarization. Interestingly, Raman scattering shows a strong increase of electric polarization of media through a dynamic magnetoelectric effect as a remarkable enhancement of the scattering intensity below T-C. New lines of purely magnetic origin have been detected in the magnetically ordered state. A part of them are attributed as scattering on exchange magnons. Using this observation and further symmetry considerations we argue for strong Dzyaloshinskii-Moriya interaction existing in the Cu2OSeO3. (c) 2010 American Institute of Physics. [doi:10.1063/1.3455808]

Optimization of HS-SPME/GC-MS analysis and its use in the profiling of illicit ecstasy tablets (Part 1)

A headspace solid-phase microextraction procedure (HS-SPME) was developed for the profiling of traces present in 3,4-methylenedioxymethylampethamine (MDMA). Traces were first extracted using HS-SPME and then analyzed by gas chromatography-mass spectroscopy (GC-MS). The HS-SPME conditions were optimized using varying conditions. Optimal results were obtained when 40 mg of crushed MDMA sample was heated at 80 °C for 15 min, followed by extraction at 80 °C for 15 min with a polydimethylsiloxane/divinylbenzene coated fibre. A total of 31 compounds were identified as traces related to MDMA synthesis, namely precursors, intermediates or by-products. In addition some fatty acids used as tabletting materials and caffeine used as adulterant, were also detected. The use of a restricted set of 10 target compounds was also proposed for developing a screening tool for clustering samples having close profile. 114 seizures were analyzed using an SPME auto-sampler (MultiPurpose Samples MPS2), purchased from Gerstel GMBH & Co. (Germany), and coupled to GC-MS. The data was handled using various pre-treatment methods, followed by the study of similarities between sample pairs based on the Pearson correlation. The results show that HS-SPME, coupled with the suitable statistical method is a powerful tool for distinguishing specimens coming from the same seizure and specimens coming from different seizures. This information can be used by law enforcement personnel to visualize the ecstasy distribution network as well as the clandestine tablet manufacturing.

Decision curve analysis revisited: overall net benefit, relationships to ROC curve analysis, and application to case-control studies.

ABSTRACT: BACKGROUND: Decision curve analysis has been introduced as a method to evaluate prediction models in terms of their clinical consequences if used for a binary classification of subjects into a group who should and into a group who should not be treated. The key concept for this type of evaluation is the "net benefit", a concept borrowed from utility theory. METHODS: We recall the foundations of decision curve analysis and discuss some new aspects. First, we stress the formal distinction between the net benefit for the treated and for the untreated and define the concept of the "overall net benefit". Next, we revisit the important distinction between the concept of accuracy, as typically assessed using the Youden index and a receiver operating characteristic (ROC) analysis, and the concept of utility of a prediction model, as assessed using decision curve analysis. Finally, we provide an explicit implementation of decision curve analysis to be applied in the context of case-control studies. RESULTS: We show that the overall net benefit, which combines the net benefit for the treated and the untreated, is a natural alternative to the benefit achieved by a model, being invariant with respect to the coding of the outcome, and conveying a more comprehensive picture of the situation. Further, within the framework of decision curve analysis, we illustrate the important difference between the accuracy and the utility of a model, demonstrating how poor an accurate model may be in terms of its net benefit. Eventually, we expose that the application of decision curve analysis to case-control studies, where an accurate estimate of the true prevalence of a disease cannot be obtained from the data, is achieved with a few modifications to the original calculation procedure. CONCLUSIONS: We present several interrelated extensions to decision curve analysis that will both facilitate its interpretation and broaden its potential area of application.

Detailed analysis and follow-up studies of a high-throughput screening for indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors.

Indoleamine 2,3-dioxygenase 1 (IDO1) is a key regulator of immune responses and therefore an important therapeutic target for the treatment of diseases that involve pathological immune escape, such as cancer. Here, we describe a robust and sensitive high-throughput screen (HTS) for IDO1 inhibitors using the Prestwick Chemical Library of 1200 FDA-approved drugs and the Maybridge HitFinder Collection of 14,000 small molecules. Of the 60 hits selected for follow-up studies, 14 displayed IC50 values below 20 μM under the secondary assay conditions, and 4 showed an activity in cellular tests. In view of the high attrition rate we used both experimental and computational techniques to identify and to characterize compounds inhibiting IDO1 through unspecific inhibition mechanisms such as chemical reactivity, redox cycling, or aggregation. One specific IDO1 inhibitor scaffold, the imidazole antifungal agents, was chosen for rational structure-based lead optimization, which led to more soluble and smaller compounds with micromolar activity.

Four essays on economic geography, trade and development

RESUME Cette thèse se situe à la frontière de la recherche en économie du développement et du commerce international et vise à intégrer les apports de l'économie géographique. Le premier chapitre s'intéresse aux effets de création et de détournement de commerce au sein des accords régionaux entre pays en développement et combine une approche gravitaire et une estimation non paramétrique des effets de commerce. Cette analyse confirme un effet de commerce non monotone pour six accords régionaux couvrant l'Afrique, l'Amérique Latine et l'Asie (AFTA, CAN, CACM, CEDEAO, MERCO SUR et SADC) sur la période 1960-1996. Les accords signés dans les années 90 (AFTA, CAN, MERCOSUR et SADC) semblent avoir induis une amélioration du bien-être de leurs membres mais avec un impact variable sur le reste du monde, tandis que les accords plus anciens (CEDEAO et CACM) semblent montrer que les effets de commerce et de bien-être se réduisent pour finir par s'annuler à mesure que le nombre d'années de participation des Etats membres augmente. Le deuxième chapitre pose la question de l'impact de la géographie sur les échanges Sud-Sud. Ce chapitre innove par rapport aux méthodes classiques d'estimation en dérivant une équation de commerce à partir de l'hypothèse d'Armington et en intégrant une fonction de coût de transport qui prend en compte la spécificité des pays de l'UEMOA. Les estimations donnent des effets convaincants quant au rôle de l'enclavement et des infrastructures: deux pays enclavés de l'UEMOA commercent 92% moins que deux autres pays quelconques, tandis que traverser un pays de transit au sein de l'espace UEMOA augmente de 6% les coûts de transport, et que bitumer toutes les routes inter-Etat de l'Union induirait trois fois plus de commerce intra-UEMOA. Le chapitre 3 s'intéresse à la persistance des différences de développement au sein des accords régionaux entre pays en développement. Il montre que la géographie différenciée des pays du Sud membres d'un accord induit un impact asymétrique de celui-ci sur ses membres. Il s'agit d'un modèle stylisé de trois pays dont deux ayant conclu un accord régional. Les résultats obtenus par simulation montrent qu'une meilleure dotation en infrastructure d'un membre de l'accord régional lui permet d'attirer une plus grande part industrielle à mesure que les coûts de transport au sein de l'accord régional sont baissés, ce qui conduit à un développement inégal entre les membres. Si les niveaux d'infrastructure domestique de transport sont harmonisés au sein des pays membres de l'accord d'intégration, leurs parts industrielles peuvent converger au détriment des pays restés hors de l'union. Le chapitre 4 s'intéresse à des questions d'économie urbaine en étudiant comment l'interaction entre rendements croissants et coûts de transport détermine la localisation des activités et des travailleurs au sein d'un pays ou d'une région. Le modèle développé reproduit un fait stylisé observé à l'intérieur des centres métropolitains des USA: sur une période longue (1850-1990), on observe une spécialisation croissante des centres urbains et de leurs périphéries associée à une évolution croissante puis décroissante de la population des centres urbains par rapport à leurs périphéries. Ce résultat peut se transférer dans un contexte en développement avec une zone centrale et une zone périphérique: à mesure que l'accessibilité des régions s'améliore, ces régions se spécialiseront et la région principale, d'abord plus importante (en termes de nombre de travailleurs) va finir par se réduire à une taille identique à celle de la région périphérique.

Predictive analysis and mapping of indoor radon concentrations in a complex environment using kernel estimation: an application to Switzerland.

PURPOSE: The aim of this study was to develop models based on kernel regression and probability estimation in order to predict and map IRC in Switzerland by taking into account all of the following: architectural factors, spatial relationships between the measurements, as well as geological information. METHODS: We looked at about 240,000 IRC measurements carried out in about 150,000 houses. As predictor variables we included: building type, foundation type, year of construction, detector type, geographical coordinates, altitude, temperature and lithology into the kernel estimation models. We developed predictive maps as well as a map of the local probability to exceed 300 Bq/m(3). Additionally, we developed a map of a confidence index in order to estimate the reliability of the probability map. RESULTS: Our models were able to explain 28% of the variations of IRC data. All variables added information to the model. The model estimation revealed a bandwidth for each variable, making it possible to characterize the influence of each variable on the IRC estimation. Furthermore, we assessed the mapping characteristics of kernel estimation overall as well as by municipality. Overall, our model reproduces spatial IRC patterns which were already obtained earlier. On the municipal level, we could show that our model accounts well for IRC trends within municipal boundaries. Finally, we found that different building characteristics result in different IRC maps. Maps corresponding to detached houses with concrete foundations indicate systematically smaller IRC than maps corresponding to farms with earth foundation. CONCLUSIONS: IRC mapping based on kernel estimation is a powerful tool to predict and analyze IRC on a large-scale as well as on a local level. This approach enables to develop tailor-made maps for different architectural elements and measurement conditions and to account at the same time for geological information and spatial relations between IRC measurements.

The knock-out of ARP3a gene affects F-actin cytoskeleton organization altering cellular tip growth, morphology and development in moss Physcomitrella patens.

The seven subunit Arp2/3 complex is a highly conserved nucleation factor of actin microfilaments. We have isolated the genomic sequence encoding a putative Arp3a protein of the moss Physcomitrella patens. The disruption of this ARP3A gene by allele replacement has generated loss-of-function mutants displaying a complex developmental phenotype. The loss-of function of ARP3A gene results in shortened, almost cubic chloronemal cells displaying affected tip growth and lacking differentiation to caulonemal cells. In moss arp3a mutants, buds differentiate directly from chloronemata to form stunted leafy shoots having differentiated leaves similar to wild type. Yet, rhizoids never differentiate from stem epidermal cells. To characterize the F-actin organization in the arp3a-mutated cells, we disrupted ARP3A gene in the previously described HGT1 strain expressing conditionally the GFP-talin marker. In vivo observation of the F-actin cytoskeleton during P. patens development demonstrated that loss-of-function of Arp3a is associated with the disappearance of specific F-actin cortical structures associated with the establishment of localized cellular growth domains. Finally, we show that constitutive expression of the P. patens Arp3a and its Arabidopsis thaliana orthologs efficiently complement the mutated phenotype indicating a high degree of evolutionary conservation of the Arp3 function in land plants.

Combining digital elevation model analysis and run-out modeling to characterize hazard posed by a potentially unstable rock slope at Turtle Mountain, Alberta, Canada

Turtle Mountain in Alberta, Canada has become an important field laboratory for testing different techniques related to the characterization and monitoring of large slope mass movements as the stability of large portions of the eastern face of the mountain is still questionable. In order to better quantify the volumes potentially unstable and the most probable failure mechanisms and potential consequences, structural analysis and runout modeling were preformed. The structural features of the eastern face were investigated using a high resolution digital elevation model (HRDEM). According to displacement datasets and structural observations, potential failure mechanisms affecting different portions of the mountain have been assessed. The volumes of the different potentially unstable blocks have been calculated using the Sloping Local Base Level (SLBL) method. Based on the volume estimation, two and three dimensional dynamic runout analyses have been performed. Calibration of this analysis is based on the experience from the adjacent Frank Slide and other similar rock avalanches. The results will be used to improve the contingency plans within the hazard area.

Oligonucleotide-polyethylenimine complexes targeting retinal cells: structural analysis and application to anti-TGFbeta-2 therapy.

PURPOSE: The aim of this study was to characterize oligonucleotide-polyethylenimine (ODN/PEI) complex preparation for potential transfection of retinal cells in vitro and in vivo. METHODS: The effect of medium preparation [HEPES-buffered saline (HBS), water] on particle size and morphology was evaluated. Cultured Lewis rat retinal Müller glial (RMG) cells were transfected using fluorescein isothiocyanate (FITC)-ODN/PEI complexes specifically directed at transforming growth factor beta (TGFbeta)-2. Efficacy of transfection was evaluated using confocal microscopy, and regulation of gene expression was assayed using quantitative real-time RT-PCR and ELISA assay. One, 24, and 72 h after injection of FITC-ODN/PEI complexes into the vitreous of rat eyes, their distribution was analyzed on eye sections. RESULTS: Complexes prepared in HBS were smaller than complexes prepared in pure water and presented a core-shell structure. These particles showed a high cellular internalization efficacy, along with a significant and specific down-regulation of TGFbeta-2 expression and production in RMG cells, correlating with specific inhibition of cell growth at 72 h. In vivo, complexes efficiently transfect retinal cells and follow a transretinal migration at 24 h. After 72 h, ODN seems to preferentially target RMG cells without inducing any detectable toxicity. CONCLUSIONS: Specific down-regulation of TGFbeta-2 expression using ODN/PEI complexes may have potential interest for the treatment of retinal diseases associated with glial proliferation.

Meta-analysis and imputation refines the association of 15q25 with smoking quantity.

Smoking is a leading global cause of disease and mortality. We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (P = 9.45 x 10(-19)) that includes CHRNA5, CHRNA3 and CHRNB4, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a fivefold increase in marker density over HapMap2 (ref. 2) as an imputation reference panel. Our fine-mapping approach identified a SNP showing the highest significance, rs55853698, located within the promoter region of CHRNA5. Conditional analysis also identified a secondary locus (rs6495308) in CHRNA3.

Raman spectroscopy and microspectroscopy of reactive dyes on cotton fibres: analysis and detection limits

A collaborative study on Raman spectroscopy and microspectrophotometry (MSP) was carried out by members of the ENFSI (European Network of Forensic Science Institutes) European Fibres Group (EFG) on different dyed cotton fabrics. The detection limits of the two methods were tested on two cotton sets with a dye concentration ranging from 0.5 to 0.005% (w/w). This survey shows that it is possible to detect the presence of dye in fibres with concentrations below that detectable by the traditional methods of light microscopy and microspectrophotometry (MSP). The MSP detection limit for the dyes used in this study was found to be a concentration of 0.5% (w/w). At this concentration, the fibres appear colourless with light microscopy. Raman spectroscopy clearly shows a higher potential to detect concentrations of dyes as low as 0.05% for the yellow dye RY145 and 0.005% for the blue dye RB221. This detection limit was found to depend both on the chemical composition of the dye itself and on the analytical conditions, particularly the laser wavelength. Furthermore, analysis of binary mixtures of dyes showed that while the minor dye was detected at 1.5% (w/w) (30% of the total dye concentration) using microspectrophotometry, it was detected at a level as low as 0.05% (w/w) (10% of the total dye concentration) using Raman spectroscopy. This work also highlights the importance of a flexible Raman instrument equipped with several lasers at different wavelengths for the analysis of dyed fibres. The operator and the set up of the analytical conditions are also of prime importance in order to obtain high quality spectra. Changing the laser wavelength is important to detect different dyes in a mixture.