Potentiation of triclabendazole action in vivo against a triclabendazole-resistant isolate of Fasciola hepatica following its co-administration with the metabolic inhibitor, ketoconazole

An in vivo study in the laboratory rat model has been carried out to monitor morphological changes in adult Fasciola hepatica over a 4-day period resulting from co-treatment with triclabendazole (TCBZ) and ketoconazole (KTZ), a cytochrome P450 inhibitor. Rats were infected with the triclabendazole-resistant Oberon isolate of F. hepatica, dosed orally with triclabendazole at a dosage of 10mg/kg live weight and ketoconazole at a dosage of 10mg/kg live weight. Flukes were recovered at 24, 48, 72 and 96 h post-treatment (p.t.) and changes to fluke ultrastructure were assessed using transmission electron microscopy (TEM). Results showed an increase in the severity of changes to the fluke ultrastructure with time p.t. Swelling of the basal infolds and the associated mucopolysaccharide masses became more severe with time. Golgi complexes, if present, were greatly reduced in size and number by 96 h p.t., and sub-tegumental flooding was seen from the 72 h time-period onwards. Some sloughing of the tegumental covering over the spines was observed at 96 h p.t. The results demonstrated that the Oberon isolate is more sensitive to TCBZ action in the presence of KTZ than to TCBZ alone, reinforcing the idea that altered drug metabolism is involved in the resistance mechanism. Moreover, they support the concept that TCBZ+inhibitor combinations (aimed at altering drug pharmacokinetics and potentiating the action of TCBZ) could be used in the treatment of TCBZ-R populations of F. hepatica.

Low cycle fatigue properties of CLAM steel at 823 K

China Low Activation Martensitic (CLAM) steel is considered to be the main candidate material for the first wall components of future fusion reactors in China. In this paper, the low cycle fatigue (LCF) behavior of CLAM steel is studied under fully reversed tension–compression loading at 823 K in air. Total strain amplitude was controlled from 0.14% to 1.8% with a constant strain rate of 2.4×10−3 s−1. The corresponding plastic strain amplitude ranged from 0.023% to 1.613%. The CLAM steel displayed continuous softening to failure at 823 K. The relationship between strain, stress and fatigue life was obtained using the parameters obtained from fatigue tests. The LCF properties of CLAM steel at 823 K followed Coffin–Manson relationship. Furthermore, irregular serration was observed on the stress–strain hysteresis loops of CLAM steel tested with the total strain amplitude of 0.45–1.8%, which was attributed to the dynamic strain aging (DSA) effect. During continuous cyclic deformation, the microstructure and precipitate distribution of CLAM steel changed gradually. Many tempered martensitic laths were decomposed into subgrains, and the size and number of M23C6 carbide and MX carbonitride precipitates decreased with the increase of total strain amplitude. The response cyclic stress promoted the recovery of martensitic lath, while the thermal activation mainly played an important role on the growth of precipitates in CLAM steel at 823 K. In order to have a better understanding of high-temperature LCF behavior, the potential mechanisms controlling stress–strain response, DSA phenomenon and microstructure changes have also been evaluated.

DocLite: A Docker-Based Lightweight Cloud Benchmarking Tool

Existing benchmarking methods are time consuming processes as they typically benchmark the entire Virtual Machine (VM) in order to generate accurate performance data, making them less suitable for real-time analytics. The research in this paper is aimed to surmount the above challenge by presenting DocLite - Docker Container-based Lightweight benchmarking tool. DocLite explores lightweight cloud benchmarking methods for rapidly executing benchmarks in near real-time. DocLite is built on the Docker container technology, which allows a user-defined memory size and number of CPU cores of the VM to be benchmarked. The tool incorporates two benchmarking methods - the first referred to as the native method employs containers to benchmark a small portion of the VM and generate performance ranks, and the second uses historic benchmark data along with the native method as a hybrid to generate VM ranks. The proposed methods are evaluated on three use-cases and are observed to be up to 91 times faster than benchmarking the entire VM. In both methods, small containers provide the same quality of rankings as a large container. The native method generates ranks with over 90% and 86% accuracy for sequential and parallel execution of an application compared against benchmarking the whole VM. The hybrid method did not improve the quality of the rankings significantly.

Analyse fonctionnelle de la polycystine-1 et de son domaine intracellulaire dans le développement de la polykystose rénale autosomique dominante

La polykystose rénale autosomique dominante (PKRAD) est la maladie génétique rénale la plus commune touchant 1/500 personnes. Elle se caractérise principalement par la formation de kystes rénaux dans tous les segments du néphron, entraînant l’insuffisance rénale, et par des manifestations extrarénales kystiques (foie, pancréas, rate) et non-kystiques (anomalies cardiaques, vasculaires et cérébrales). Deux gènes, PKD1 et PKD2, sont responsables de 85 et 15% des cas respectivement. Ces gènes encodent les polycystine-1 (PC-1) et -2 (PC-2) qui forment un complexe à la membrane plasmique et ciliaire des cellules épithéliales rénales. PC-1 est une protéine transmembranaire de 4302 acides aminés possédant un court domaine intracellulaire incluant un motif coiled-coil impliqué dans l’interaction entre PC-1 et PC-2 in-vitro. L’importance du coiled-coil est démontrée par des mutations affectant spécifiquement ce motif chez des patients PKRAD. Le mécanisme pathogénétique responsable de la PKRAD est indéterminé. Chez la souris, la PKRAD se développe suite à l’ablation (Pkd1-/-) ou lors de la surexpression (SBPkd1TAG) de Pkd1, ce qui suggère un effet de dosage. Des anomalies ciliaires sont aussi souvent associées à PKRAD. Mon objectif était de déterminer in-vivo le mécanisme pathogénétique de la polycystine-1 dans le développement des symptômes PKRAD rénaux et extrarénaux et plus spécifiquement, le rôle du motif coiled-coil dans le mécanisme de kystogenèse. Pour ce faire, nous avons généré deux constructions, Pkd1 sauvage (Pkd1TAG) et Pkd1 tronquée de son motif coiled-coil (Pkd1ΔCoiled-coil), par recombinaison homologue à partir du BAC-Pkd1 sauvage comprenant la séquence murine entière de Pkd1. Trois lignées de souris Pkd1TAG générées par microinjection démontrent un niveau d’expression de Pkd1 qui corrèle avec le nombre de copie du transgène (2, 5 et 15 copies). Les souris Pkd1TAG reproduisent la PKRAD en développant des kystes rénaux dans toutes les parties du néphron et des cils primaires plus longs que les contrôles non transgéniques. Les analyses physiologiques supportent que les souris Pkd1TAG développent une insuffisance rénale et démontrent une augmentation du volume urinaire de même qu’une diminution de l’osmolalité, de la créatinine et des protéines urinaires. De plus, les souris Pkd1TAG développent des kystes hépatiques, des anomalies cardiaques associées à des dépôts de calcium et des anévrismes cérébraux. La sévérité du phénotype augmente avec l’expression de Pkd1 appuyant l’hypothèse d’un mécanisme de dosage. Nous avons aussi déterminé que l’expression du transgène Pkd1TAG complémente le phénotype létal-embryonnaire des souris Pkd1-/-. D’autre part, nous avons générés 4 lignées de souris Pkd1ΔCoiled-coil (2 et 15 copies du transgène) dont le nombre de copies corrèle avec le niveau d’expression du transgène. Ces souris Pkd1ΔCoiled-coil, contrairement aux Pkd1TAG de même âge, ne développent pas de kystes et possèdent des cils primaires de longueur normale. Afin d’évaluer le rôle du motif coiled-coil en absence de polycystine-1 endogène, nous avons croisé les souris Pkd1ΔCoiled-coil avec les souris Pkd1-/-. Contrairement aux souris Pkd1-/- qui meurent in-utéro, les souris Pkd1ΔCoiled-coil; Pkd1-/- survivent ~10 à 14 jours après la naissance. Elles démontrent des kystes rénaux et pancréatiques sévères, un retard de croissance et des anomalies pulmonaires. Tous les segments du néphron sont affectés. Mon projet démontre que la surexpression de Pkd1 est un mécanisme pathogénique de la PKRAD tant au niveau rénal qu’extrarénal. De plus, il démontre que le motif coiled-coil est un élément déterminant dans la kystogenèse/PKRAD in-vivo.

La configuration spatiale et la hiérarchie urbaine en Colombie

Ce mémoire présente les résultats d'une recherche portant sur cinq villes colombiennes sélectionnées selon leur taille et le nombre d’emplois par secteur économique, d’après les données des recensements du Département Administratif National des Statistiques (DANE) qui s’étalent entre 1985 et 2005. La méthode d'analyse adoptée est de type descriptif et met l'accent sur des facteurs de taille et de nombre d’habitants afin d’évaluer la hiérarchie entre les villes entre 1985 et 2005, et de comprendre, pour la même période, la spécialisation des cinq villes à travers leurs données d’emplois respectives. Cette méthode est complétée par l’utilisation des outils d’évaluation régionale et urbaine pour comprendre le processus de polarisation en Colombie. L’économie colombienne est dominée par les villes de grande taille ou les régions métropolitaines qui constituent les plus grands marchés (économies d'agglomération). Cependant, ces zones (Bogota, Medellin, Cali, Barranquilla et Bucaramanga) ne sont pas intégrées. Par conséquent, la prédominance de ces centres s’est considérablement réduite.

The impact of harvesting on a formerly endangered tropical bird: insights from life-history theory

1. Life-history theory assumes that trade-offs exist between an individual's life-history components, such that an increased allocation of a resource to one fitness trait might be expected to result in a cost for a conflicting fitness trait. Recent evidence from experimental manipulations of wild individuals supports this assumption. 2. The management of many bird populations involves harvesting for both commercial and conservation purposes. One frequently harvested life-history stage is the egg, but the consequences of repeated egg harvesting for the individual and the long-term dynamics of the population remain poorly understood. 3. We used a well-documented restored population of the Mauritius kestrel Falco punctatus as a model system to explore the consequences of egg harvesting (and associated management practices) for an individual within the context of life-history theory. 4. Our analysis indicated that management practices enhanced both the size and number of clutches laid by managed females, and improved mid-life male and female adult survival relative to unmanaged adult kestrels. 5. Although management resulted in an increased effort in egg production, it reduced parental effort during incubation and the rearing of offspring, which could account for these observed changes. 6. Synthesis and applications. This study demonstrates how a commonly applied harvesting strategy, when examined within the context of life-history theory, can identify improvements in particular fitness traits that might alleviate some of the perceived negative impact of harvesting on the long-term dynamics of a managed population.

Scaling up classification rule induction through parallel processing

The fast increase in the size and number of databases demands data mining approaches that are scalable to large amounts of data. This has led to the exploration of parallel computing technologies in order to perform data mining tasks concurrently using several processors. Parallelization seems to be a natural and cost-effective way to scale up data mining technologies. One of the most important of these data mining technologies is the classification of newly recorded data. This paper surveys advances in parallelization in the field of classification rule induction.

Differential effects of two fermentable carbohydrates on central appetite regulation and body composition

BACKGROUND: Obesity is rising at an alarming rate globally. Different fermentable carbohydrates have been shown to reduce obesity. The aim of the present study was to investigate if two different fermentable carbohydrates (inulin and b-glucan) exert similar effects on body composition and central appetite regulation in high fat fed mice. METHODOLOGY/PRINCIPAL FINDINGS: Thirty six C57BL/6 male mice were randomized and maintained for 8 weeks on a high fat diet containing 0% (w/w) fermentable carbohydrate, 10% (w/w) inulin or 10% (w/w) b-glucan individually. Fecal and cecal microbial changes were measured using fluorescent in situ hybridization, fecal metabolic profiling was obtained by proton nuclear magnetic resonance (1H NMR), colonic short chain fatty acids were measured by gas chromatography, body composition and hypothalamic neuronal activation were measured using magnetic resonance imaging (MRI) and manganese enhanced MRI (MEMRI), respectively, PYY (peptide YY) concentration was determined by radioimmunoassay, adipocyte cell size and number were also measured. Both inulin and b-glucan fed groups revealed significantly lower cumulative body weight gain compared with high fat controls. Energy intake was significantly lower in b-glucan than inulin fed mice, with the latter having the greatest effect on total adipose tissue content. Both groups also showed an increase in the numbers of Bifidobacterium and Lactobacillus-Enterococcus in cecal contents as well as feces. b- glucan appeared to have marked effects on suppressing MEMRI associated neuronal signals in the arcuate nucleus, ventromedial hypothalamus, paraventricular nucleus, periventricular nucleus and the nucleus of the tractus solitarius, suggesting a satiated state. CONCLUSIONS/SIGNIFICANCE: Although both fermentable carbohydrates are protective against increased body weight gain, the lower body fat content induced by inulin may be metabolically advantageous. b-glucan appears to suppress neuronal activity in the hypothalamic appetite centers. Differential effects of fermentable carbohydrates open new possibilities for nutritionally targeting appetite regulation and body composition.

Suppression of gliadins results in altered protein body morphology in wheat

Wheat gluten proteins, gliadins and glutenins, are of great importance in determining the unique biomechanical properties of wheat. Studies have therefore been carried out to determine their pathways and mechanisms of synthesis, folding, and deposition in protein bodies. In the present work, a set of transgenic wheat lines has been studied with strongly suppressed levels of γ-gliadins and/or all groups of gliadins, using light and fluorescence microscopy combined with immunodetection using specific antibodies for γ-gliadins and HMW glutenin subunits. These lines represent a unique material to study the formation and fusion of protein bodies in developing seeds of wheat. Higher amounts of HMW subunits were present in most of the transgenic lines but only the lines with suppression of all gliadins showed differences in the formation and fusion of the protein bodies. Large rounded protein bodies were found in the wild-type lines and the transgenic lines with reduced levels of γ-gliadins, while the lines with all gliadins down-regulated had protein bodies of irregular shape and irregular formation. The size and number of inclusions, which have been reported to contain triticins, were also higher in the protein bodies in the lines with all the gliadins down-regulated. Changes in the protein composition and PB morphology reported in the transgenic lines with all gliadins down-regulated did not result in marked changes in the total protein content or instability of the different fractions.

Novel European free-living, non-diazotrophic Bradyrhizobium isolates from contrasting soils that lack nodulation and nitrogen fixation genes - a genome comparison

The slow-growing genus Bradyrhizobium is biologically important in soils, with different representatives found to perform a range of biochemical functions including photosynthesis, induction of root nodules and symbiotic nitrogen fixation and denitrification. Consequently, the role of the genus in soil ecology and biogeochemical transformations is of agricultural and environmental significance. Some isolates of Bradyrhizobium have been shown to be non-symbiotic and do not possess the ability to form nodules. Here we present the genome and gene annotations of two such free-living Bradyrhizobium isolates, named G22 and BF49, from soils with differing long-term management regimes (grassland and bare fallow respectively) in addition to carbon metabolism analysis. These Bradyrhizobium isolates are the first to be isolated and sequenced from European soil and are the first free-living Bradyrhizobium isolates, lacking both nodulation and nitrogen fixation genes, to have their genomes sequenced and assembled from cultured samples. The G22 and BF49 genomes are distinctly different with respect to size and number of genes; the grassland isolate also contains a plasmid. There are also a number of functional differences between these isolates and other published genomes, suggesting that this ubiquitous genus is extremely heterogeneous and has roles within the community not including symbiotic nitrogen fixation.

Guides of the Falu Mine : Perceptions of Differences and Similarities onDomestic and International Visitors

Industrial heritage tourism has been in focus for many academic studies and tourism is an alternative developmental tool for mines and contributes to their economic success. This thesis is about the Falu Mine in Dalarna, Sweden, which has World Heritage status since 2001 and is one of the biggest attractions in the region. Its history and cultural importance are reasons for the importance of preserving the heritage. The Falu Mine is under the management of the Great Copper Mountain Trust and one of their ambitions is to ensure the continuous popularity among domestic and international visitors. In order to gain a better understanding of the visitors and to find strategies to improve performance, a visitor survey has been conducted in the summer of 2011. It is the authors believe that the guides of the Falu Mine have the best available insight and that their perceptions help to add to the understanding about the visitors. Therefore, this thesis aims to explore the perceptions of the guides about their visitors, to investigate how the perceptions correspond to the statistical results and to study if there are any differences between domestic and international visitors. The mixed methods approach will increase the depth and accuracy of the results, by linking qualitative with quantitative data. The results show that differences between domestic and international visitors exist, both proven by interviews with the guides and the visitor survey. These differences occur in the factors, such as level of education of the visitors, group size and number of children in the group, knowledge of the visitors prior to and after the visit, sources of information and the fulfillment of the visitor expectations. The perceptions emphasize how these differences impact the guided tours. The guides of the Falu Mine have to be aware of those differences in order to adjust the tour accordingly, as well as the management of the Falu Mine can use this knowledge in order to identify strategies for improving performance.

Assessing the maturity levei of an organization in its adoption of collaboration technologies

Nowadays there are many information technologies that can make a significant difference to support collaborative efforts in the workspace. The role of IT is to support group collaboration by empowering team members with the right capabilities. One way to assess capabilities is through a maturity model. This paper proposes a first version of the Collaboration-Technology Maturity model (CTMM), aiming to serve as a strategic instrument for IT managers to control and manage the adoption of Collaboration Technologies (CITs) among their organizations. Our contribution is both theoretical and practical as we propose a descriptive maturity model. Nevertheless, it is also an application method and assessment instruments. We also completed an empirical evaluation by conducting 89 assessments at Latin American companies of all sizes and industries. This extensive field exercise allowed us to not only evaluate the usefulness of the model and instruments but also investigate CIT adoption patterns in Latin America in an attempt to collect historical data to further evolve CTMM into a comparative model. Responses were used to provide conclusions on CIT adoption in Latin America with respect to three specific backgrounds: the country of origin (region), size (in number of employees) and industry type. The implications of our findings are discussed for practitioners and researchers.

Natural rubber latex used as drug delivery system in guided bone regeneration (GBR)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Ultramorphology of the Digestive Tract of Paratrechina longicornis (Hymenoptera, Formicidae)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Realized evolvability: quantifying phenotypic evolution in a Drosophila clade

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)