Using Pareto optimality to explore the topology and dynamics of the human connectome.

Graph theory has provided a key mathematical framework to analyse the architecture of human brain networks. This architecture embodies an inherently complex relationship between connection topology, the spatial arrangement of network elements, and the resulting network cost and functional performance. An exploration of these interacting factors and driving forces may reveal salient network features that are critically important for shaping and constraining the brain's topological organization and its evolvability. Several studies have pointed to an economic balance between network cost and network efficiency with networks organized in an 'economical' small-world favouring high communication efficiency at a low wiring cost. In this study, we define and explore a network morphospace in order to characterize different aspects of communication efficiency in human brain networks. Using a multi-objective evolutionary approach that approximates a Pareto-optimal set within the morphospace, we investigate the capacity of anatomical brain networks to evolve towards topologies that exhibit optimal information processing features while preserving network cost. This approach allows us to investigate network topologies that emerge under specific selection pressures, thus providing some insight into the selectional forces that may have shaped the network architecture of existing human brains.

Selection of internal control genes for real-time quantitative PCR in ovary and uterus of sows across pregnancy

Reproductive traits play a key role in pig production in order to reduce costs and increase economic returns. Among others, gene expression analyses represent a useful approach to study genetic mechanisms underlying reproductive traits in pigs. The application of reverse-transcription quantitative PCR requires the selection of appropriate reference genes, whose expression levels should not be affected by the experimental conditions, especially when comparing gene expression across different physiological stages.

Establishment and characterization of models of chemotherapy resistance in colorectal cancer: Towards a predictive signature of chemoresistance.

Current standard treatments for metastatic colorectal cancer (CRC) are based on combination regimens with one of the two chemotherapeutic drugs, irinotecan or oxaliplatin. However, drug resistance frequently limits the clinical efficacy of these therapies. In order to gain new insights into mechanisms associated with chemoresistance, and departing from three distinct CRC cell models, we generated a panel of human colorectal cancer cell lines with acquired resistance to either oxaliplatin or irinotecan. We characterized the resistant cell line variants with regards to their drug resistance profile and transcriptome, and matched our results with datasets generated from relevant clinical material to derive putative resistance biomarkers. We found that the chemoresistant cell line variants had distinctive irinotecan- or oxaliplatin-specific resistance profiles, with non-reciprocal cross-resistance. Furthermore, we could identify several new, as well as some previously described, drug resistance-associated genes for each resistant cell line variant. Each chemoresistant cell line variant acquired a unique set of changes that may represent distinct functional subtypes of chemotherapy resistance. In addition, and given the potential implications for selection of subsequent treatment, we also performed an exploratory analysis, in relevant patient cohorts, of the predictive value of each of the specific genes identified in our cellular models.

In situ spectroellipsometric study of the nucleation and growth of amorphous silicon

A detailed in situ spectroellipsometric analysis of the nucleation and growth of hydrogenated amorphous silicon (a:Si:H) is presented. Photoelectronic quality a‐Si:H films are deposited by plasma‐enhanced chemical vapor deposition on smooth metal (NiCr alloy) and crystalline silicon (c‐Si) substrates. The deposition of a‐Si:H is analyzed from the first monolayer up to a final thickness of 1.2 μm. In order to perform an improved analysis, real time ellipsometric trajectories are recorded, using fixed preparation conditions, at various photon energies ranging from 2.2 to 3.6 eV. The advantage of using such a spectroscopic experimental procedure is underlined. New insights into the nucleation and growth mechanisms of a‐Si:H are obtained. The nucleation mechanism on metal and c‐Si substrates is very accurately described assuming a columnar microstructural development during the early stage of the growth. Then, as a consequence of the incomplete coalescence of the initial nuclei, a surface roughness at the 10-15 Å scale is identified during the further growth of a‐Si:H on both substrates. The bulk a‐Si:H grows homogeneously beneath the surface roughness. Finally, an increase of the surface roughness is evidenced during the long term growth of a‐Si:H. However, the nature of the substrate influenced the film growth. In particular, the film thickness involved in the nucleation‐coalescence phase is found lower in the case of c‐Si (67±8 Å) as compared to NiCr (118±22 Å). Likewise films deposited on c‐Si present a smaller surface roughness even if thick samples are considered (>1 μm). More generally, the present study illustrates the capability of in situ spectroellipsometry to precisely analyze fundamental processes in thin‐film growth, but also to monitor the preparation of complex structures on a few monolayers scale.

Data-division-specific robustness and power of randomization tests for ABAB designs

This study deals with the statistical properties of a randomization test applied to an ABAB design in cases where the desirable random assignment of the points of change in phase is not possible. In order to obtain information about each possible data division we carried out a conditional Monte Carlo simulation with 100,000 samples for each systematically chosen triplet. Robustness and power are studied under several experimental conditions: different autocorrelation levels and different effect sizes, as well as different phase lengths determined by the points of change. Type I error rates were distorted by the presence of autocorrelation for the majority of data divisions. Satisfactory Type II error rates were obtained only for large treatment effects. The relationship between the lengths of the four phases appeared to be an important factor for the robustness and the power of the randomization test.

Spermiogenesis and spermatozoon of the liver fluke Mediogonimus jourdanei (Microphalloidea: Prosthogonimidae), a parasite of Myodes glareolus (Rodentia: Cricetidae)

Spermatological characters of the liver fluke Mediogonimus jourdanei Mas-Coma et Rocamora, 1978 were studied by means of transmission and scanning electron microscopy. Spermiogenesis begins with the formation of the differentiation zone containing two centrioles associated with striated rootlets and an intercentriolar body. These two centrioles originate two free flagella that undergo a 90 degrees rotation before fusing with the median cytoplasmic process. Both nuclear and mitochondrial migrations toward the median cytoplasmic process occur before the proximodistal fusion of flagella. Finally, the constriction of the ring of arched membranes gives rise to the young spermatozoon. The mature sperm of M. jourdanei measures about 260 microm and presents two axonemes of different lengths with the typical pattern of the Trepaxonemata, two bundles of parallel cortical microtubules, one mitochondrion, a nucleus and granules of glycogen. An analysis of all the microphalloidean species studied to date emphasised some differences in certain characters found in Maritrema linguilla Jägerskiöld, 1908 and Ganeo tigrinum Mehra et Negi, 1928 in comparison to those in the remaining microphalloideans. The presence and variability of such ultrastructural characters according to family, superfamily or order have led several authors to propose their use in the analysis of trematode relationships and phylogeny. Therefore, apart from producing new data on the family Prosthogonimidae, the present study also compares the spermatological organization of M jourdanei with other available ultrastructural studies focusing on the Microphalloidea.

Taxogenomics of the order Chlamydiales.

Bacterial classification is a long-standing problem for taxonomists and species definition itself is constantly debated among specialists. The classification of strict intracellular bacteria such as members of the order Chlamydiales mainly relies on DNA- or protein-based phylogenetic reconstructions because these organisms exhibit few phenotypic differences and are difficult to culture. The availability of full genome sequences allows the comparison of the performance of conserved protein sequences to reconstruct Chlamydiales phylogeny. This approach permits the identification of markers that maximize the phylogenetic signal and the robustness of the inferred tree. In this study, a set of 424 core proteins was identified and concatenated to reconstruct a reference species tree. Although individual protein trees present variable topologies, we detected only few cases of incongruence with the reference species tree, which were due to horizontal gene transfers. Detailed analysis of the phylogenetic information of individual protein sequences (i) showed that phylogenies based on single randomly chosen core proteins are not reliable and (ii) led to the identification of twenty taxonomically highly reliable proteins, allowing the reconstruction of a robust tree close to the reference species tree. We recommend using these protein sequences to precisely classify newly discovered isolates at the family, genus and species levels.

Mood disorders in eating disorder patients: Prevalence and chronology of ONSET.

OBJECTIVES: In a clinical population, we estimated the frequency of mood disorders among 271 patients suffering from Anorexia Nervosa (AN) and Bulimia Nervosa (BN) in comparison to a control group matched for age and gender. METHOD: The frequency of mood disorders was measured using the Mini International Neuropsychiatric Interview (MINI), DSM-IV version. RESULTS: Mood disorders were more frequent among eating disorder (ED) patients than among controls, with a global prevalence of the order of 80% for each ED group. The majority of the mood disorders comorbid with ED were depressive disorders (MDD and dysthymia). The relative chronology of onset of these disorders was equivocal, because mood disorders in some cases preceded and in others followed the onset of the eating disorders. LIMITATIONS: Our sample was characterized by patients with severe ED and high comorbidities, and thus do not represent the entire population of AN or BN. This also may have resulted in an overestimation of prevalence. CONCLUSION: Mood disorders appear significantly more frequently in patients seeking care for ED than in controls. These results have implications for the assessment and treatment of ED patients, and for the aetio-pathogenesis of these disorders.

Establishing the Stages and Processes of Change for Weight Loss by Consensus of Experts

The present study aimed to establish, by a consensus of experts, the stages and processes of change for weight management in overweight and obese people. The first step involved developing two questionnaires aimed at assessing stages and processes of change for weight loss in overweight and obese people. The processes-ofchange questionnaire consisted of 12 subscales, and contained 107 items. A three-round Delphi study was carried out through a website, where participants were asked to give their opinion about the representativeness and clarity of the scale items. The stages-of-change questionnaire consisted of five items and was presented in the final round of the study. A team of 66 experts in the obesity field from 29 countries participated in the study. They were selected either because they belonged to the organizing committee of international associations related to obesity, or because of their research career. The required changes in the questionnaire were made according to the opinions of the participants. Some of these were the result of the group statistical response, whereas others were due to the suggestions made by the participants. A final version of the questionnaire consisting of 63 items was eventually obtained. The present study produced two questionnaires to assess stages and processes of change for weight management. The strength of the study lies in the consensus reached by the panel of experts in order to establish the required content of the questionnaires. The two measures provide useful tools for practitioners who wish to tailor weight-management interventions according to transtheoretical model constructs.

Analysis of SKI-1/S1P prodomain provides insight on maturation and activation of SKI-1/S1P zymogen

SKI-l/SlP protease is a member of the proprotein convertase family, with several functions in cellular metabolism and homeostasis. It is responsible for the processing of several cellular substrates, including ATF6, SREBPs, and GlcNAc-1- phosphotranspherase. Furthermore, SKI-1/SlP is also responsible for maturation of arenavirus surface glycoprotein into GP1 and GP2 subunits. This processing is a strict requirement in order to achieve fully mature and fusion-competent virions. Furthermore, SKI-1/SlP itself is synthesized as an inactive zymogen, requiring sequential autocatalytic processing at several sites (B'/B and C) in its prodomain in order to mature and become fully active. Our project focused on the analysis of SKI- 1/S1P prodomain in the biogenesis of the active enzyme. In this context we have additionally developed and characterized a novel cell-based sensor for assessment of cellular activity of the enzyme, with a potential application in screening for novel SKI- 1/S1P inhibitors. In a first aim we have analysed the relevance of cleavage motifs found in the enzyme prodomain. Using molecular and biochemistry tools we have identified and characterized a novel C' maturation site. Furthermore, we found that SKI-1/SlP autoprocessing results in intermediates whose catalytic domain remains associated with prodomain fragments of different lengths. Contrasting with other proprotein convertases, incompletely matured intermediates of SKI-1/SlP exhibit full catalytic activity toward selected substrates. In a second aim, we turned our attention to the structural basis of SKI-1/SlP N- terminus assisted folding. Studying the folding and activity of prodomain-truncated forms of the enzyme we found that a minimal folding unit is contained in the AB region. Deletion of the BC sequence affected auto-maturation but not folding, and partial activity was retained. However, the BC region seemed required for complete and full activity. Phylogenetic analyses showed that the AB sequence is highly conserved, while the BC fragment is variable in sequence and length. Specifically, replacement of the human prodomain with that of Drosophila, resulted in a fully mature and active chimeric enzyme, suggesting an evolution process of SKI-1/SlP prodomain towards a more complex arrangement and steps of activation. Overall, the additional data we have produced might provide fundamental knowledge crucial for the development of novel SKI-1/SlP inhibitors while also providing new SKI- 1/S1P variants with potential use in crystallization purpose. -- SKI-l/SlP est une protéase membre de la famille des proprotéines convertases (PCs), avec plusieurs fonctions dans le métabolisme cellulaire et de l'homéostasie. Il est responsable pour la maturation de plusieurs substrats cellulaires, y compris ATF6, SREBPs et GlcNAc-1-phosphotranspherase. SKI-l/SlP est également responsable pour la maturation de la glycoprotéine des arénavirus, une exigence stricte pour atteindre des virions infectieuse. Synthétisé comme un zymogène inactif, SKI-l/SlP nécessite d'un traitement autocatalytique séquentiel sur plusieurs sites (B'/B et C) de son prodomaine afin de devenir pleinement active. Notre projet était axé sur l'analyse de SKI-l/SlP prodomaine dans la biogenèse de l'enzyme. Dans ce contexte, nous avons développé un nouveau senseur-cellulaire pour l'évaluation de l'activité de l'enzyme. Ce dernier pourrait avoir une potentielle application dans l'identification de nouveaux inhibiteurs de SKI-l/SlP. Premièrement, nous avons analysé la pertinence des motifs de clivage trouvés dans le prodomaine de l'enzyme. En utilisant des outils moléculaires et biochimiques, nous avons identifié et caractérisé un nouveau site de maturation (C'). Aussi, nous avons constaté que la maturation de SKI-l/SlP a des intermédiaires dont le domaine catalytique reste associé à des fragments du prodomaine de différentes longueurs. Contrastant avec d'autres PCs, les intermédiaires partiellement matures de SKI-1 / SIP présentent une activité catalytique complète envers des substrats spécifiques. Dans un deuxième but nous avons tourné notre attention sur la base structurelle du pliage de SKI-l/SlP assisté par son N-terminus: En étudiant l'activité et pliage des formes tronquées dans le prodomaine de l'enzyme, nous avons constaté qu'une unité de pliage minimale est contenue dans la région de l'AB. La suppression de la séquence d'auto-BC affecte la maturation mais pas le pliage, et l'activité partielle est maintenue. Cependant, la région BC semble nécessaire pour une activité complète. Les analyses phylogénétiques ont montré que la séquence AB est fortement conservée, tandis que le fragment de BC est variable en longueur et en séquence. En particulier, le remplacement du prodomaine humain avec celui de la drosophile, a donné lieu à une enzyme chimérique complètement mature et active. Suggérant un processus d'évolution du prodomaine vers un arrangement et des mesures d'activation plus complexe. Globalement, ces donnees supplémentaires augment les connaissances fondamentales cruciales pour le développement de nouveaux inhibiteurs de SKI-1/ SIP, tout en offrant de nouvelles variantes SKI-1 / SIP dans le but d'obtenir la structure cristallographique de l'enzyme.

On Option Price Information Content and Extraction of Implied Probability Distributions

In this study we used market settlement prices of European call options on stock index futures to extract implied probability distribution function (PDF). The method used produces a PDF of returns of an underlying asset at expiration date from implied volatility smile. With this method, the assumption of lognormal distribution (Black-Scholes model) is tested. The market view of the asset price dynamics can then be used for various purposes (hedging, speculation). We used the so called smoothing approach for implied PDF extraction presented by Shimko (1993). In our analysis we obtained implied volatility smiles from index futures markets (S&P 500 and DAX indices) and standardized them. The method introduced by Breeden and Litzenberger (1978) was then used on PDF extraction. The results show significant deviations from the assumption of lognormal returns for S&P500 options while DAX options mostly fit the lognormal distribution. A deviant subjective view of PDF can be used to form a strategy as discussed in the last section.

Repetitive Deliberate Fires: Critical Review of the Situation and Proposal of a Follow-Up Process and Systematic Analysis

Deliberate fires appear to be borderless and timeless events creating a serious security problem. There have been many attempts to develop approaches to tackle this problem, but unfortunately acting effectively against deliberate fires has proven a complex challenge. This article reviews the current situation relating to deliberate fires: what do we know, how serious is the situation, how is it being dealt with, and what challenges are faced when developing a systematic and global methodology to tackle the issues? The repetitive nature of some types of deliberate fires will also be discussed. Finally, drawing on the reality of repetition within deliberate fires and encouraged by successes obtained in previous repetitive crimes (such as property crimes or drug trafficking), we will argue that the use of the intelligence process cycle as a framework to allow a follow-up and systematic analysis of fire events is a relevant approach. This is the first article of a series of three articles. This first part is introducing the context and discussing the background issues in order to provide a better underpinning knowledge to managers and policy makers planning on tackling this issue. The second part will present a methodology developed to detect and identify repetitive fire events from a set of data, and the third part will discuss the analyses of these data to produce intelligence.

Rapid analysis of multiclass antibiotic residues and some of their metabolites in hospital, urban wastewater and river water by ultra-highperformance liquid chromatography coupled to quadrupole-linear ion trap tandem mass spectrometry

The present work describes the development of a fast and robust analytical method for the determination of 53 antibiotic residues, covering various chemical groups and some of their metabolites, in environmental matrices that are considered important sources of antibiotic pollution, namely hospital and urban wastewaters, as well as in river waters. The method is based on automated off-line solid phase extraction (SPE) followed by ultra-high-performance liquid chromatography coupled to quadrupole linear ion trap tandem mass spectrometry (UHPLC–QqLIT). For unequivocal identification and confirmation, and in order to fulfill EU guidelines, two selected reaction monitoring (SRM) transitions per compound are monitored (the most intense one is used for quantification and the second one for confirmation). Quantification of target antibiotics is performed by the internal standard approach, using one isotopically labeled compound for each chemical group, in order to correct matrix effects. The main advantages of the method are automation and speed-up of sample preparation, by the reduction of extraction volumes for all matrices, the fast separation of a wide spectrum of antibiotics by using ultra-high-performance liquid chromatography, its sensitivity (limits of detection in the low ng/L range) and selectivity (due to the use of tandem mass spectrometry) The inclusion of β-lactam antibiotics (penicillins and cephalosporins), which are compounds difficult to analyze in multi-residue methods due to their instability in water matrices, and some antibiotics metabolites are other important benefits of the method developed. As part of the validation procedure, the method developed was applied to the analysis of antibiotics residues in hospital, urban influent and effluent wastewaters as well as in river water samples

The High Prevalence and Diversity of Chlamydiales DNA within Ixodes ricinus Ticks Suggest a Role for Ticks as Reservoirs and Vectors of Chlamydia-Related Bacteria.

The Chlamydiales order is composed of nine families of strictly intracellular bacteria. Among them, Chlamydia trachomatis, C. pneumoniae, and C. psittaci are established human pathogens, whereas Waddlia chondrophila and Parachlamydia acanthamoebae have emerged as new pathogens in humans. However, despite their medical importance, their biodiversity and ecology remain to be studied. Even if arthropods and, particularly, ticks are well known to be vectors of numerous infectious agents such as viruses and bacteria, virtually nothing is known about ticks and chlamydia. This study investigated the prevalence of Chlamydiae in ticks. Specifically, 62,889 Ixodes ricinus ticks, consolidated into 8,534 pools, were sampled in 172 collection sites throughout Switzerland and were investigated using pan-Chlamydiales quantitative PCR (qPCR) for the presence of Chlamydiales DNA. Among the pools, 543 (6.4%) gave positive results and the estimated prevalence in individual ticks was 0.89%. Among those pools with positive results, we obtained 16S rRNA sequences for 359 samples, allowing classification of Chlamydiales DNA at the family level. A high level of biodiversity was observed, since six of the nine families belonging to the Chlamydiales order were detected. Those most common were Parachlamydiaceae (33.1%) and Rhabdochlamydiaceae (29.2%). "Unclassified Chlamydiales" (31.8%) were also often detected. Thanks to the huge amount of Chlamydiales DNA recovered from ticks, this report opens up new perspectives on further work focusing on whole-genome sequencing to increase our knowledge about Chlamydiales biodiversity. This report of an epidemiological study also demonstrates the presence of Chlamydia-related bacteria within Ixodes ricinus ticks and suggests a role for ticks in the transmission of and as a reservoir for these emerging pathogenic Chlamydia-related bacteria.

Adaptation and validation of the Spanish Version of the 'Survey Work-Home Interaction-NijmeGen' (SWING) to Spanish speaking countries

The purpose of this study is the adaptation and validation of the"Survey Work-Home Interaction NijmeGen" (SWING) developed by Geurts and colleagues to Spanish speaking countries (SWING-SSC). In order to analyze the questionnaire"s psychometric properties, confirmatory factor analysis (CFA) was carried out with a sample of 203 employees from various Spanish-speaking countries. Criterion related validity was tested by examining correlations between the SWING-SSC, and the theoretically relevant variables: health, role conflict, role clarity and supervisor support. Finally, reliability was tested analyzing the internal consistency of the scales. The analyses carried out indicate that SWING-SSC has good psychometric properties. In addition, the present results support the relation of the construct with health, role conflict, role clarity, and supervisor support. This study offers evidence for a sound work-life balance measure that contributes to the encouragement adequate conditions in the workplace, to reduce the conflict between the two spheres of professional and personal life, and to enhance positive relationships.