A numeric model to simulate solar individual ultraviolet exposure.

Exposure to solar ultraviolet (UV) light is the main causative factor for skin cancer. UV exposure depends on environmental and individual factors. Individual exposure data remain scarce and development of alternative assessment methods is greatly needed. We developed a model simulating human exposure to solar UV. The model predicts the dose and distribution of UV exposure received on the basis of ground irradiation and morphological data. Standard 3D computer graphics techniques were adapted to develop a rendering engine that estimates the solar exposure of a virtual manikin depicted as a triangle mesh surface. The amount of solar energy received by each triangle was calculated, taking into account reflected, direct and diffuse radiation, and shading from other body parts. Dosimetric measurements (n = 54) were conducted in field conditions using a foam manikin as surrogate for an exposed individual. Dosimetric results were compared to the model predictions. The model predicted exposure to solar UV adequately. The symmetric mean absolute percentage error was 13%. Half of the predictions were within 17% range of the measurements. This model provides a tool to assess outdoor occupational and recreational UV exposures, without necessitating time-consuming individual dosimetry, with numerous potential uses in skin cancer prevention and research.

The Selective Phosphodiesterase 4 Inhibitor Roflumilast and Phosphodiesterase 3/4 Inhibitor Pumafentrine Reduce Clinical Score and TNF Expression in Experimental Colitis in Mice.

OBJECTIVE: The specific inhibition of phosphodiesterase (PDE)4 and dual inhibition of PDE3 and PDE4 has been shown to decrease inflammation by suppression of pro-inflammatory cytokine synthesis. We examined the effect of roflumilast, a selective PDE4 inhibitor marketed for severe COPD, and the investigational compound pumafentrine, a dual PDE3/PDE4 inhibitor, in the preventive dextran sodium sulfate (DSS)-induced colitis model. METHODS: The clinical score, colon length, histologic score and colon cytokine production from mice with DSS-induced colitis (3.5% DSS in drinking water for 11 days) receiving either roflumilast (1 or 5 mg/kg body weight/d p.o.) or pumafentrine (1.5 or 5 mg/kg/d p.o.) were determined and compared to vehicle treated control mice. In the pumafentrine-treated animals, splenocytes were analyzed for interferon-γ (IFNγ) production and CD69 expression. RESULTS: Roflumilast treatment resulted in dose-dependent improvements of clinical score (weight loss, stool consistency and bleeding), colon length, and local tumor necrosis factor-α (TNFα) production in the colonic tissue. These findings, however, were not associated with an improvement of the histologic score. Administration of pumafentrine at 5 mg/kg/d alleviated the clinical score, the colon length shortening, and local TNFα production. In vitro stimulated splenocytes after in vivo treatment with pumafentrine showed a significantly lower state of activation and production of IFNγ compared to no treatment in vivo. CONCLUSIONS: These series of experiments document the ameliorating effect of roflumilast and pumafentrine on the clinical score and TNF expression of experimental colitis in mice.

Defining risk thresholds for a 10-year probability of hip fracture model that combines clinical risk factors and quantitative ultrasound: results using the EPISEM cohort.

Using a large prospective cohort of over 12,000 women, we determined 2 thresholds (high risk and low risk of hip fracture) to use in a 10-yr hip fracture probability model that we had previously described, a model combining the heel stiffness index measured by quantitative ultrasound (QUS) and a set of easily determined clinical risk factors (CRFs). The model identified a higher percentage of women with fractures as high risk than a previously reported risk score that combined QUS and CRF. In addition, it categorized women in a way that was quite consistent with the categorization that occurred using dual X-ray absorptiometry (DXA) and the World Health Organization (WHO) classification system; the 2 methods identified similar percentages of women with and without fractures in each of their 3 categories, but the 2 identified only in part the same women. Nevertheless, combining our composite probability model with DXA in a case findings strategy will likely further improve the detection of women at high risk of fragility hip fracture. We conclude that the currently proposed model may be of some use as an alternative to the WHO classification criteria for osteoporosis, at least when access to DXA is limited.

Regulation of the activity of DnaA and its role during the cell cycle of caulobacter crescentus

The initiation of chromosomal replication must be tightly regulated so that the genome is replicated only once per cell cycle. In most bacteria, DnaA binds to the origin of replication and initiates chromosomal replication. DnaA is a dual-function protein that also acts as an important transcription factor that regulates the expression of many genes in bacteria. Thus, understanding how this protein is regulated during the bacterial cell cycle is of major importance. The α-proteobacterium Caulobacter crescentus is an excellent model to study the bacterial cell cycle, mainly because it is possible to isolate synchronized cell cultures and because it initiates the replication of its chromosome once per cell cycle and at a specific time of the cell cycle. This latest feature is of special interest for the major aim of my thesis work, which focused on the temporal and spatial regulation of the activity of the essential DnaA protein in C. crescentus. In Escherichia coli, the Hda protein converts ATP-DnaA into ADP- DnaA by stimulating the ATPase activity of DnaA, to prevent over-initiation of chromosome replication. We propose that there exists a similar mechanism in C. crescentus, which is not only involved in the temporal control of chromosome replication, but also in the control of gene expression. First, we provided evidences indicating that the hydrolysis of the ATP bound to DnaA is essential for the viability of C. crescentus. Our results suggest that ATP-DnaA promotes the initiation of chromosome replication, since we found that cells over-expressing a DnaA protein with a mutated ATPase domain, DnaA(R357A), over-initiated chromosome replication, unlike cells expressing the wild-type DnaA protein at similar levels. By contrast, the DnaA(R357A) protein was less active than DnaA in promoting the transcription of three essential genes, suggesting that these may be more efficiently activated by ADP-DnaA than ATP-DnaA. We propose that the ATP-DnaA to ADP-DnaA switch down-regulates the initiation of DNA replication while activating the transcription of several essential genes involved in subsequent cell cycle events. Second, we studied the role of the HdaA protein, homologous to Hda, in promoting the ATP- DnaA to ADP-DnaA switch in C. crescentus. HdaA is essential for viability and its depletion in the cell leads to an over-replication of the chromosome, indicating that HdaA is a negative regulator of DNA replication. HdaA dynamically co-localizes with the replisome. In this work, we identified DnaN, the β-clamp of the DNA polymerase, as the replisome component that interacts directly with HdaA and that recruits HdaA to the replisome in live C. crescentus cells. We also showed that a mutant HdaA protein that cannot interact or co-localize with DnaN is not functional, indicating that HdaA is probably activated by DnaN. However, we found that another non-functional HdaA protein, mutated in the conserved Arginine finger of its AAA+ domain, was able to localize at the replisome, suggesting that the AAA+ domain of HdaA exerts its essential function after the recruitment of HdaA to the replisome. We propose that HdaA stimulates the ATPase activity of DnaA once DNA replication is ongoing, via its interaction with DnaN and the activity of the two conserved R fingers of DnaA and HdaA. Finally, we created different strains in which HdaA, DnaN or DnaA were over-produced. We observed that the over-production of HdaA seems to lead to a delay in chromosome replication, while the over-production of DnaN had an opposite effect. Our results also indicate that the over-production of DnaA may intensify the over-initiation phenotype of cells depleted for HdaA. We conclude that the dynamic interplay of HdaA and DnaN in the cell contributes to regulating the ATP-DnaA/ADP-DnaA ratio in the cell, to ensure once per cell cycle initiation of chromosomal replication in C. crescentus. Altogether, our work provided important information on the regulation of the activity of DnaA in C. crescentus. Since DnaA, HdaA and DnaN are well-conserved proteins, most of our findings are useful to understand how chromosome replication and gene expression are controlled by DnaA in many other bacterial species. - L'initiation de la réplication des chromosomes doit être précisément régulée de telle sorte que le génome ne soit répliqué qu'une seule fois par cycle cellulaire. Chez la plupart des bactéries, DnaA se lie à l'origine de réplication du chromosome et en initie sa réplication. DnaA est aussi un facteur de transcription qui régule l'expression de nombreux gènes bactériens. De ce fait, il est très important de comprendre comment DnaA est régulée au cours du cycle cellulaire bactérien. L'a-protéobactérie Caulobacter crescentus est un excellent modèle pour étudier le cycle cellulaire bactérien, essentiellement parce qu'il est aisé d'isoler des populations de cellules synchronisées à la même étape du cycle cellulaire et parce que cette bactérie n'initie la réplication de son chromosome qu'une seule fois et à un moment précis de son cycle. Cette dernière caractéristique est particulièrement pertinente pour l'objectif de mon travail doctoral, qui consistait à comprendre comment l'activité de la protéine essentielle DnaA est régulée dans l'espace et dans le temps chez C. crescentus. Chez Escherichia coli, la protéine Hda convertie DnaA-ATP en DnaA-ADP en stimulant l'activité ATPasique de DnaA, ce qui empêche la sur-initiation de la réplication du chromosome. Nous proposons qu'un mécanisme similaire existe chez C. crescentus. Il serait non seulement nécessaire au contrôle de la réplication du chromosome, mais aussi au contrôle de l'expression de certains gènes. Dans un premier temps, nous avons mis en évidence le fait que l'hydrolyse de l'ATP lié à DnaA est un processus essentiel à la viabilité de C. crescentus. Nos résultats suggèrent que DnaA-ATP initie la réplication du chromosome, comme nous avons observé que des cellules qui sur-expriment une protéine DnaA(R357A) mutée sans domaine ATPasique fonctionnel, sur-initie la réplication de leur chromosome, contrairement aux cellules qui sur-expriment la protéine DnaA sauvage à des niveaux équivalents. Au contraire, la protéine DnaA(R357A) était moins active que la protéine DnaA sauvage pour promouvoir la transcription de trois gènes essentiels, ce qui suggère que ces derniers sont peut-être plus efficacement activés par DnaA-ADP que DnaA-ATP. Nous proposons que la conversion de DnaA-ATP en DnaA-ADP réprime l'initiation de la réplication, tandis qu'elle active la transcription de plusieurs gènes impliqués dans des étapes plus tardives du cycle cellulaire. Dans un deuxième temps, nous avons étudié le rôle de la protéine HdaA, homologue à Hda, dans la conversion de DnaA-ATP en DnaA-ADP chez C. crescentus. Cette protéine est essentielle à la viabilité de C. crescentus et sa déplétion donne des cellules qui sur-initient la réplication de leur chromosome, suggérant que HdaA est un répresseur de la réplication du chromosome. HdaA co-localise de manière dynamique avec le réplisome. Lors de mon travail doctoral, nous avons démontré que DnaN, le β-clamp de l'ADN polymérase, est l'élément qui recrute HdaA au réplisome in vivo. Nous avons aussi montré qu'une protéine HdaA mutante qui ne peut pas interagir ou co-localiser avec DnaN, n'est pas fonctionnelle, ce qui suggère que HdaA est activée par DnaN. Nous avons néanmoins aussi isolé une autre protéine HdaA non fonctionnelle, dont une arginine conservée de son domaine AAA+ était mutée, mais qui pouvait toujours co-localiser avec le réplisome, ce qui suggère que le domaine AAA+ de HdaA est nécessaire après le recrutement de HdaA au réplisome. Nous proposons que HdaA stimule l'activité ATPasique de DnaA qu'une fois que la réplication a commencé, grâce à son interaction avec DnaN et aux deux arginines conservées des protéines HdaA et DnaA. Finalement, nous avons construit différentes souches sur-exprimant HdaA, DnaN ou DnaA. Nous avons observé que la sur-production de HdaA retarde la réplication du chromosome, tandis que la sur-production de DnaN a un effet opposé. Nos observations suggèrent aussi que la sur-expression de DnaA dans des cellules déplétées pour HdaA aggrave leur phénotype de sur-initiation. Nous en concluons que HdaA et DnaN collaborent étroitement et de manière dynamique pour réguler le rapport DnaA-ATP/DnaA-ADP dans la cellule, pour s'assurer que la réplication du chromosome ne soit initiée qu'une seule fois par cycle cellulaire chez C. crescentus. Globalement, notre travail a mis en évidence des informations importantes sur la régulation de l'activité de DnaA chez C. crescentus. Comme DnaA, HdaA et DnaN sont des protéines très conservées, la plupart de nos découvertes sont utiles pour mieux comprendre comment la réplication du chromosome bactérien et l'expression des gènes sont contrôlées par DnaA chez de nombreuses autres espèces bactériennes.

Context-dependent dual role of SKI8 homologs in mRNA synthesis and turnover.

Eukaryotic mRNA transcription and turnover is controlled by an enzymatic machinery that includes RNA polymerase II and the 3' to 5' exosome. The activity of these protein complexes is modulated by additional factors, such as the nuclear RNA polymerase II-associated factor 1 (Paf1c) and the cytoplasmic Superkiller (SKI) complex, respectively. Their components are conserved across uni- as well as multi-cellular organisms, including yeast, Arabidopsis, and humans. Among them, SKI8 displays multiple facets on top of its cytoplasmic role in the SKI complex. For instance, nuclear yeast ScSKI8 has an additional function in meiotic recombination, whereas nuclear human hSKI8 (unlike ScSKI8) associates with Paf1c. The Arabidopsis SKI8 homolog VERNALIZATION INDEPENDENT 3 (VIP3) has been found in Paf1c as well; however, whether it also has a role in the SKI complex remains obscure so far. We found that transgenic VIP3-GFP, which complements a novel vip3 mutant allele, localizes to both nucleus and cytoplasm. Consistently, biochemical analyses suggest that VIP3-GFP associates with the SKI complex. A role of VIP3 in the turnover of nuclear encoded mRNAs is supported by random-primed RNA sequencing of wild-type and vip3 seedlings, which indicates mRNA stabilization in vip3. Another SKI subunit homolog mutant, ski2, displays a dwarf phenotype similar to vip3. However, unlike vip3, it displays neither early flowering nor flower development phenotypes, suggesting that the latter reflect VIP3's role in Paf1c. Surprisingly then, transgenic ScSKI8 rescued all aspects of the vip3 phenotype, suggesting that the dual role of SKI8 depends on species-specific cellular context.

Quantitative modelling of transcription factor binding sites

Abstract One of the most important issues in molecular biology is to understand regulatory mechanisms that control gene expression. Gene expression is often regulated by proteins, called transcription factors which bind to short (5 to 20 base pairs),degenerate segments of DNA. Experimental efforts towards understanding the sequence specificity of transcription factors is laborious and expensive, but can be substantially accelerated with the use of computational predictions. This thesis describes the use of algorithms and resources for transcriptionfactor binding site analysis in addressing quantitative modelling, where probabilitic models are built to represent binding properties of a transcription factor and can be used to find new functional binding sites in genomes. Initially, an open-access database(HTPSELEX) was created, holding high quality binding sequences for two eukaryotic families of transcription factors namely CTF/NF1 and LEFT/TCF. The binding sequences were elucidated using a recently described experimental procedure called HTP-SELEX, that allows generation of large number (> 1000) of binding sites using mass sequencing technology. For each HTP-SELEX experiments we also provide accurate primary experimental information about the protein material used, details of the wet lab protocol, an archive of sequencing trace files, and assembled clone sequences of binding sequences. The database also offers reasonably large SELEX libraries obtained with conventional low-throughput protocols.The database is available at http://wwwisrec.isb-sib.ch/htpselex/ and and ftp://ftp.isrec.isb-sib.ch/pub/databases/htpselex. The Expectation-Maximisation(EM) algorithm is one the frequently used methods to estimate probabilistic models to represent the sequence specificity of transcription factors. We present computer simulations in order to estimate the precision of EM estimated models as a function of data set parameters(like length of initial sequences, number of initial sequences, percentage of nonbinding sequences). We observed a remarkable robustness of the EM algorithm with regard to length of training sequences and the degree of contamination. The HTPSELEX database and the benchmarked results of the EM algorithm formed part of the foundation for the subsequent project, where a statistical framework called hidden Markov model has been developed to represent sequence specificity of the transcription factors CTF/NF1 and LEF1/TCF using the HTP-SELEX experiment data. The hidden Markov model framework is capable of both predicting and classifying CTF/NF1 and LEF1/TCF binding sites. A covariance analysis of the binding sites revealed non-independent base preferences at different nucleotide positions, providing insight into the binding mechanism. We next tested the LEF1/TCF model by computing binding scores for a set of LEF1/TCF binding sequences for which relative affinities were determined experimentally using non-linear regression. The predicted and experimentally determined binding affinities were in good correlation.

Simulation of stromatolite growth using diffusion-limited aggregation and a discrete model of biogeochemical exchanges in microbial mat

Resume : Mieux comprendre les stromatolithes et les tapis microbiens est un sujet important en biogéosciences puisque cela aide à l'étude des premières formes de vie sur Terre, a mieux cerner l'écologie des communautés microbiennes et la contribution des microorganismes a la biominéralisation, et même à poser certains fondements dans les recherches en exobiologie. D'autre part, la modélisation est un outil puissant utilisé dans les sciences naturelles pour appréhender différents phénomènes de façon théorique. Les modèles sont généralement construits sur un système d'équations différentielles et les résultats sont obtenus en résolvant ce système. Les logiciels disponibles pour implémenter les modèles incluent les logiciels mathématiques et les logiciels généraux de simulation. L'objectif principal de cette thèse est de développer des modèles et des logiciels pour aider a comprendre, via la simulation, le fonctionnement des stromatolithes et des tapis microbiens. Ces logiciels ont été développés en C++ en ne partant d'aucun pré-requis de façon a privilégier performance et flexibilité maximales. Cette démarche permet de construire des modèles bien plus spécifiques et plus appropriés aux phénomènes a modéliser. Premièrement, nous avons étudié la croissance et la morphologie des stromatolithes. Nous avons construit un modèle tridimensionnel fondé sur l'agrégation par diffusion limitée. Le modèle a été implémenté en deux applications C++: un moteur de simulation capable d'exécuter un batch de simulations et de produire des fichiers de résultats, et un outil de visualisation qui permet d'analyser les résultats en trois dimensions. Après avoir vérifié que ce modèle peut en effet reproduire la croissance et la morphologie de plusieurs types de stromatolithes, nous avons introduit un processus de sédimentation comme facteur externe. Ceci nous a mené a des résultats intéressants, et permis de soutenir l'hypothèse que la morphologie des stromatolithes pourrait être le résultat de facteurs externes autant que de facteurs internes. Ceci est important car la classification des stromatolithes est généralement fondée sur leur morphologie, imposant que la forme d'un stromatolithe est dépendante de facteurs internes uniquement (c'est-à-dire les tapis microbiens). Les résultats avancés dans ce mémoire contredisent donc ces assertions communément admises. Ensuite, nous avons décidé de mener des recherches plus en profondeur sur les aspects fonctionnels des tapis microbiens. Nous avons construit un modèle bidimensionnel de réaction-diffusion fondé sur la simulation discrète. Ce modèle a été implémenté dans une application C++ qui permet de paramétrer et exécuter des simulations. Nous avons ensuite pu comparer les résultats de simulation avec des données du monde réel et vérifier que le modèle peut en effet imiter le comportement de certains tapis microbiens. Ainsi, nous avons pu émettre et vérifier des hypothèses sur le fonctionnement de certains tapis microbiens pour nous aider à mieux en comprendre certains aspects, comme la dynamique des éléments, en particulier le soufre et l'oxygène. En conclusion, ce travail a abouti à l'écriture de logiciels dédiés à la simulation de tapis microbiens d'un point de vue tant morphologique que fonctionnel, suivant deux approches différentes, l'une holistique, l'autre plus analytique. Ces logiciels sont gratuits et diffusés sous licence GPL (General Public License). Abstract : Better understanding of stromatolites and microbial mats is an important topic in biogeosciences as it helps studying the early forms of life on Earth, provides clues re- garding the ecology of microbial ecosystems and their contribution to biomineralization, and gives basis to a new science, exobiology. On the other hand, modelling is a powerful tool used in natural sciences for the theoretical approach of various phenomena. Models are usually built on a system of differential equations and results are obtained by solving that system. Available software to implement models includes mathematical solvers and general simulation software. The main objective of this thesis is to develop models and software able to help to understand the functioning of stromatolites and microbial mats. Software was developed in C++ from scratch for maximum performance and flexibility. This allows to build models much more specific to a phenomenon rather than general software. First, we studied stromatolite growth and morphology. We built a three-dimensional model based on diffusion-limited aggregation. The model was implemented in two C++ applications: a simulator engine, which can run a batch of simulations and produce result files, and a Visualization tool, which allows results to be analysed in three dimensions. After verifying that our model can indeed reproduce the growth and morphology of several types of stromatolites, we introduced a sedimentation process as an external factor. This lead to interesting results, and allowed to emit the hypothesis that stromatolite morphology may be the result of external factors as much as internal factors. This is important as stromatolite classification is usually based on their morphology, imposing that a stromatolite shape is dependant on internal factors only (i.e. the microbial mat). This statement is contradicted by our findings, Second, we decided to investigate deeper the functioning of microbial mats, We built a two-dimensional reaction-diffusion model based on discrete simulation, The model was implemented in a C++ application that allows setting and running simulations. We could then compare simulation results with real world data and verify that our model can indeed mimic the behaviour of some microbial mats. Thus, we have proposed and verified hypotheses regarding microbial mats functioning in order to help to better understand them, e.g. the cycle of some elements such as oxygen or sulfur. ln conclusion, this PhD provides a simulation software, dealing with two different approaches. This software is free and available under a GPL licence.

Lipoxin A₄ prevents the progression of de novo and established endometriosis in a mouse model by attenuating prostaglandin E₂ production and estrogen signaling.

Endometriosis, a leading cause of pelvic pain and infertility, is characterized by ectopic growth of endometrial-like tissue and affects approximately 176 million women worldwide. The pathophysiology involves inflammatory and angiogenic mediators as well as estrogen-mediated signaling and novel, improved therapeutics targeting these pathways are necessary. The aim of this study was to investigate mechanisms leading to the establishment and progression of endometriosis as well as the effect of local treatment with Lipoxin A4 (LXA₄), an anti-inflammatory and pro-resolving lipid mediator that we have recently characterized as an estrogen receptor agonist. LXA₄ treatment significantly reduced endometriotic lesion size and downregulated the pro-inflammatory cytokines IL-1β and IL-6, as well as the angiogenic factor VEGF. LXA₄ also inhibited COX-2 expression in both endometriotic lesions and peritoneal fluid cells, resulting in attenuated peritoneal fluid Prostaglandin E₂ (PGE₂) levels. Besides its anti-inflammatory effects, LXA₄ differentially regulated the expression and activity of the matrix remodeling enzyme matrix metalloproteinase (MMP)-9 as well as modulating transforming growth factor (TGF)-β isoform expression within endometriotic lesions and in peritoneal fluid cells. We also report for first time that LXA₄ attenuated aromatase expression, estrogen signaling and estrogen-regulated genes implicated in cellular proliferation in a mouse model of disease. These effects were observed both when LXA₄ was administered prior to disease induction and during established disease. Collectively, our findings highlight potential targets for the treatment of endometriosis and suggest a pleotropic effect of LXA₄ on disease progression, by attenuating pro-inflammatory and angiogenic mediators, matrix remodeling enzymes, estrogen metabolism and signaling, as well as downstream proliferative pathways.

Enhanced cerebral expression of MCT1 and MCT2 in a rat ischemia model occurs in activated microglial cells.

Monocarboxylate transporters (MCTs) are essential for the use of lactate, an energy substrate known to be overproduced in brain during an ischemic episode. The expression of MCT1 and MCT2 was investigated at 48 h of reperfusion from focal ischemia induced by unilateral extradural compression in Wistar rats. Increased MCT1 mRNA expression was detected in the injured cortex and hippocampus of compressed animals compared to sham controls. In the contralateral, uncompressed hemisphere, increases in MCT1 mRNA level in the cortex and MCT2 mRNA level in the hippocampus were noted. Interestingly, strong MCT1 and MCT2 protein expression was found in peri-lesional macrophages/microglia and in an isolectin B4+/S100beta+ cell population in the corpus callosum. In vitro, MCT1 and MCT2 protein expression was observed in the N11 microglial cell line, whereas an enhancement of MCT1 expression by tumor necrosis factor-alpha (TNF-alpha) was shown in these cells. Modulation of MCT expression in microglia suggests that these transporters may help sustain microglial functions during recovery from focal brain ischemia. Overall, our study indicates that changes in MCT expression around and also away from the ischemic area, both at the mRNA and protein levels, are a part of the metabolic adaptations taking place in the brain after ischemia.

A New Look at Emotional Intelligence: A Dual-Process Framework

In this article, the author provides a framework to guide¦research in emotional intelligence. Studies conducted up¦to the present bear on a conception of emotional intelligence¦as pertaining to the domain of consciousness and¦investigate the construct with a correlational approach.¦As an alternative, the author explores processes underlying¦emotional intelligence, introducing the distinction¦between conscious and automatic processing as a potential¦source of variability in emotionally intelligent¦behavior. Empirical literature is reviewed to support the¦central hypothesis that individual differences in emotional¦intelligence may be best understood by considering¦the way individuals automatically process emotional¦stimuli. Providing directions for research, the author¦encourages the integration of experimental investigation¦of processes underlying emotional intelligence with¦correlational analysis of individual differences and¦fosters the exploration of the automaticity component¦of emotional intelligence.

Integration in strategic alliances : a conceptual framework of IT use in marketing as NPD key factor

En una economia basada en el coneixement, la innovació del producte es considera un factor clau a l'hora de determinar la competitivitat, la productivitat i el creixement d'una companyia. No obstant això, l'experiència de les companyies demostra la necessitat d'un nou model de gestió de la innovació del producte: una gestió basada en el màrqueting, en què la cooperació i l'ús intensiu de les tecnologies de la informació i de la comunicació (TIC) són especialment importants. En els darrers anys, la bibliografia sobre màrqueting ha analitzat el paper de la cooperació en l'èxit del procés d'innovació. No obstant això, fins ara pocs treballs han estudiat el paper que té l'ús de les TIC en el màrqueting en l'èxit del desenvolupament de nous productes (NPD, New Product Development en anglès). És una omissió curiosa, tenint en compte que el nou entorn competitiu és definit per una economia i una societat basades principalment en l'ús intensiu de les TIC i del coneixement. L'objectiu d'aquest treball és investigar el paper que l'ús de les TIC en el màrqueting té en el procés de desenvolupament de nous productes, com a element que reforça la integració d'agents al projecte, afavorint l'establiment de relacions dirigides a la cooperació i l'adquisició d'intel·ligència de mercat útil en el procés de desenvolupament de nous productes. L'estudi d'una mostra de 2.038 companyies de tots els sectors de l'activitat econòmica a Catalunya ens permet contrastar hipòtesis inicials i establir un perfil de companyia innovadora basat en les importants relacions que hi ha entre la innovació, l'ús de TIC en el màrqueting i la integració. Sobresurten dues idees en la nostra anàlisi. En primer lloc, l'ús intensiu de les TIC en el màrqueting fa que la companyia sigui més innovadora, ja que percep que el seu ús ajuda a superar barreres a la innovació i accelera els processos, que es tornen més eficients. En segon lloc, incrementant l'ús de les TIC en el màrqueting es fa augmentar la predisposició de la companyia a integrar agents particulars en l'entorn de negoci en el desenvolupament del procés d'innovació i a col·laborar-hi, de manera que es millora el grau d'adaptació del nou producte a les demandes del mercat.

Torque vibration model of axial-flux surface-mounted permanent magnet synchronous machine

In order that the radius and thus ununiform structure of the teeth and otherelectrical and magnetic parts of the machine may be taken into consideration the calculation of an axial flux permanent magnet machine is, conventionally, doneby means of 3D FEM-methods. This calculation procedure, however, requires a lotof time and computer recourses. This study proves that also analytical methods can be applied to perform the calculation successfully. The procedure of the analytical calculation can be summarized into following steps: first the magnet is divided into slices, which makes the calculation for each section individually, and then the parts are submitted to calculation of the final results. It is obvious that using this method can save a lot of designing and calculating time. Thecalculation program is designed to model the magnetic and electrical circuits of surface mounted axial flux permanent magnet synchronous machines in such a way, that it takes into account possible magnetic saturation of the iron parts. Theresult of the calculation is the torque of the motor including the vibrations. The motor geometry and the materials and either the torque or pole angle are defined and the motor can be fed with an arbitrary shape and amplitude of three-phase currents. There are no limits for the size and number of the pole pairs nor for many other factors. The calculation steps and the number of different sections of the magnet are selectable, but the calculation time is strongly depending on this. The results are compared to the measurements of real prototypes. The permanent magnet creates part of the flux in the magnetic circuit. The form and amplitude of the flux density in the air-gap depends on the geometry and material of the magnetic circuit, on the length of the air-gap and remanence flux density of the magnet. Slotting is taken into account by using the Carter factor in the slot opening area. The calculation is simple and fast if the shape of the magnetis a square and has no skew in relation to the stator slots. With a more complicated magnet shape the calculation has to be done in several sections. It is clear that according to the increasing number of sections also the result will become more accurate. In a radial flux motor all sections of the magnets create force with a same radius. In the case of an axial flux motor, each radial section creates force with a different radius and the torque is the sum of these. The magnetic circuit of the motor, consisting of the stator iron, rotor iron, air-gap, magnet and the slot, is modelled with a reluctance net, which considers the saturation of the iron. This means, that several iterations, in which the permeability is updated, has to be done in order to get final results. The motor torque is calculated using the instantaneous linkage flux and stator currents. Flux linkage is called the part of the flux that is created by the permanent magnets and the stator currents passing through the coils in stator teeth. The angle between this flux and the phase currents define the torque created by the magnetic circuit. Due to the winding structure of the stator and in order to limit the leakage flux the slot openings of the stator are normally not made of ferromagnetic material even though, in some cases, semimagnetic slot wedges are used. In the slot opening faces the flux enters the iron almost normally (tangentially with respect to the rotor flux) creating tangential forces in the rotor. This phenomenon iscalled cogging. The flux in the slot opening area on the different sides of theopening and in the different slot openings is not equal and so these forces do not compensate each other. In the calculation it is assumed that the flux entering the left side of the opening is the component left from the geometrical centre of the slot. This torque component together with the torque component calculated using the Lorenz force make the total torque of the motor. It is easy to assume that when all the magnet edges, where the derivative component of the magnet flux density is at its highest, enter the slot openings at the same time, this will have as a result a considerable cogging torque. To reduce the cogging torquethe magnet edges can be shaped so that they are not parallel to the stator slots, which is the common way to solve the problem. In doing so, the edge may be spread along the whole slot pitch and thus also the high derivative component willbe spread to occur equally along the rotation. Besides forming the magnets theymay also be placed somewhat asymmetric on the rotor surface. The asymmetric distribution can be made in many different ways. All the magnets may have a different deflection of the symmetrical centre point or they can be for example shiftedin pairs. There are some factors that limit the deflection. The first is that the magnets cannot overlap. The magnet shape and the relative width compared to the pole define the deflection in this case. The other factor is that a shifting of the poles limits the maximum torque of the motor. If the edges of adjacent magnets are very close to each other the leakage flux from one pole to the other increases reducing thus the air-gap magnetization. The asymmetric model needs some assumptions and simplifications in order to limit the size of the model and calculation time. The reluctance net is made for symmetric distribution. If the magnets are distributed asymmetrically the flux in the different pole pairs will not be exactly the same. Therefore, the assumption that the flux flows from the edges of the model to the next pole pairs, in the calculation model from one edgeto the other, is not correct. If it were wished for that this fact should be considered in multi-pole pair machines, this would mean that all the poles, in other words the whole machine, should be modelled in reluctance net. The error resulting from this wrong assumption is, nevertheless, irrelevant.

The transtheoretical model in weight management: Validation of the Processes of Change Questionnaire

Objective: The processes of change implied in weight management remain unclear. The present study aimed to identify these processes by validating a questionnaire designed to assess processes of change (the P-Weight) in line with the transtheoretical model. The relationship of processes of change with stages of change and other external variables is also examined. Methods: Participants were 723 people from community and clinical settings in Barcelona. Their mean age was 32.07 (SD = 14.55) years; most of them were women (75.0%), and their mean BMI was 26.47 (SD = 8.52) kg/m2. They all completed the P-Weight and the stages of change questionnaire (SWeight), both applied to weight management, as well as two subscales from the Eating Disorders Inventory-2 and Eating Attitudes Test-40 questionnaires about the concern with dieting. Results: A 34-item version of the PWeight was obtained by means of a refinement process. The principal components analysis applied to half of the sample identified four processes of change. A confirmatory factor analysis was then carried out with the other half of the sample, revealing that the model of four freely correlated first-order factors showed the best fit (GFI = 0.988, AGFI = 0.986, NFI = 0.986, and SRMR = 0.0559). Corrected item-total correlations (0.322-0.865) and Cronbach"s alpha coefficients (0.781-0.960) were adequate. The relationship between the P-Weight and the S-Weight and the concern with dieting measures from other questionnaires supported the validity of the scale. Conclusion: The study identified processes of change involved in weight management and reports the adequate psychometric properties of the P-Weight. It also reveals the relationship between processes and stages of change and other external variables.

A diet enriched with cocoa prevents IgE synthesis in a rat allergy model

Previous studies in young rats reported the impact of cocoa intake on healthy immune status and allow suggesting it may have a role in the prevention of some immune-mediated diseases. The aim of this study was to ascertain the effect of a cocoa diet in a model of allergy in young rats. Three-week-old Brown Norway rats were immunized by i.p. injection of ovalbumin (OVA) with alum as adjuvant and Bordetella pertussis toxin. During the next 4 weeks rats received either a cocoa diet (containing 0.2% polyphenols, w/w) or a standard diet. Animals fed a standard diet showed high concentrations of anti-OVA IgG1, IgG2a, IgG2b and high anti-OVA IgE titres, which is the antibody involved in allergic response. In contrast, animals fed a cocoa diet showed significantly lower concentrations of anti-OVA IgG1 and IgG2a antibodies. Interestingly, the cocoa diet prevented anti-OVA IgE synthesis and decreased total serum IgE concentration. Analysis of cytokine production in lymph node cells at the end of the study revealed that, in this compartment, the cocoa diet decreased the tumor necrosis factor (TNF) - alpha and the interleukin (IL) -10 secretion but not IL-4 production. In conclusion, a cocoa-enriched diet in young rats produces an immunomodulatory effect that prevents anti-allergen IgE synthesis, suggesting a potential role for cocoa flavonoids in the prevention or treatment of allergic diseases.

Examining the virulence of Candida albicans transcription factor mutants using Galleria mellonella and mouse infection models.

The aim of the present study was to identify Candida albicans transcription factors (TFs) involved in virulence. Although mice are considered the gold-standard model to study fungal virulence, mini-host infection models have been increasingly used. Here, barcoded TF mutants were first screened in mice by pools of strains and fungal burdens (FBs) quantified in kidneys. Mutants of unannotated genes which generated a kidney FB significantly different from that of wild-type were selected and individually examined in Galleria mellonella. In addition, mutants that could not be detected in mice were also tested in G. mellonella. Only 25% of these mutants displayed matching phenotypes in both hosts, highlighting a significant discrepancy between the two models. To address the basis of this difference (pool or host effects), a set of 19 mutants tested in G. mellonella were also injected individually into mice. Matching FB phenotypes were observed in 50% of the cases, highlighting the bias due to host effects. In contrast, 33.4% concordance was observed between pool and single strain infections in mice, thereby highlighting the bias introduced by the "pool effect." After filtering the results obtained from the two infection models, mutants for MBF1 and ZCF6 were selected. Independent marker-free mutants were subsequently tested in both hosts to validate previous results. The MBF1 mutant showed impaired infection in both models, while the ZCF6 mutant was only significant in mice infections. The two mutants showed no obvious in vitro phenotypes compared with the wild-type, indicating that these genes might be specifically involved in in vivo adapt.