No / The ω-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA), in the free fatty acid (FFA) form, has been demonstrated,to reduce adenoma number and size in patients with familial adenomatous polyposis. However, the mechanistic basis of the antineoplastic activity of EPA in the colorectum remains unclear. We tested the hypothesis that EPAFFA negatively modulates synthesis of and signaling by prostaglandin (PG) E2 in human colorectal cancer (CRC) cells.,EPA-FFA induced apoptosis of cyclooxygenase (COX)-2-positive human HCA-7 CRC cells in vitro. EPA-FFA in cell,culture medium was incorporated rapidly into phospholipid membranes of HCA-7 human CRC cells and acted as,a substrate for COX-2, leading to reduced synthesis of PGE2 and generation of PGE3. Alone, PGE3 bound and activated,the PGE2 EP4 receptor but with reduced affinity and efficacy compared with its "natural" ligand PGE2. However,,in the presence of PGE2, PGE3 acted as an antagonist of EP4 receptor-dependent 3',5' cyclic adenosine,monophosphate induction in naturally EP4 receptor-positive LoVo human CRC cells and of resistance to apoptosis,in HT-29-EP4 human CRC cells overexpressing the EP4 receptor. We conclude that EPA-FFA drives a COX-2dependent "PGE2-to-PGE3 switch" in human CRC cells and that PGE3 acts as a partial agonist at the PGE2 EP4 receptor.

No / In visual search experiments, the subject looks for a target item in a display containing different distractor items. The reaction time (RT) to find the target is measured as a function of the number of distractors (set size). RT is either constant, or increases linearly, with set size. Here we suggest a two-stage model for search in which items are first selected and then recognized. The selection process is modeled by (a) grouping items into a hierarchical cluster tree, in which each cluster node contains a list of all the features of items in the cluster, called the object file, and (b) recursively searching the tree by comparing target features to the cluster object file to quickly determine whether the cluster could contain the target. This model is able to account for both constant and linear RT versus set size functions. In addition, it provides a simple and accurate account of conjunction searches (e.g., looking for a red N among red Os and green Ns), in particular the variation in search rate as the distractor ratio is varied.

No / To obtain accurate results in the RHX dating of ceramics, it is essential that the RHX measurements are continued until the rate of mass gain is constant with (time)1/4. In this paper, we discuss how the initial stages of mass gain are affected by the specific surface area (SSA) of the ceramic material. The paper provides guidance on experimental protocols to avoid dating results being distorted by relatively early-time mass gain data.

Yes / The imidazotetrazine ring is an acid-stable precursor and prodrug of highly reactive alkyl diazonium ions. We have shown that this reactivity can be managed productively in an aqueous system for the generation of aziridinium ions with 96% efficiency. The new compounds are potent DNA alkylators and have antitumor activity independent of the O6-methylguanine-DNA methyltransferase and DNA mismatch repair constraints that limit the use of Temozolomide.

No / Tissue stem cells and germ line or embryonic stem cells were shown to have reduced oxidative metabolism, which was proposed to be an adaptive mechanism to reduce damage accumulation caused by reactive oxygen species. However, an alternate explanation is that stem cells are less dependent on specialized cytoplasmic functions compared with differentiated cells, therefore, having a high nuclear-to-cytoplasmic volume ratio and consequently a low mitochondrial content. To determine whether stem cells rely or not on mitochondrial respiration, we selectively ablated the electron transport chain in the basal layer of the epidermis, which includes the epidermal progenitor/stem cells (EPSCs). This was achieved using a loxP-flanked mitochondrial transcription factor A (Tfam) allele in conjunction with a keratin 14 Cre transgene. The epidermis of these animals (TfamEKO) showed a profound depletion of mitochondrial DNA and complete absence of respiratory chain complexes. However, despite a short lifespan due to malnutrition, epidermal development and skin barrier function were not impaired. Differentiation of epidermal layers was normal and no proliferation defect or major increase of apoptosis could be observed. In contrast, mice with an epidermal ablation of prohibitin-2, a scaffold protein in the inner mitochondrial membrane, displayed a dramatic phenotype observable already in utero, with severely impaired skin architecture and barrier function, ultimately causing death from dehydration shortly after birth. In conclusion, we here provide unequivocal evidence that EPSCs, and probably tissue stem cells in general, are independent of the mitochondrial respiratory chain, but still require a functional dynamic mitochondrial compartment.

Yes / Polysialic acid (polySia), an α-2,8-glycosidically linked polymer of sialic acid, is a developmentally regulated posttranslational modification predominantly found on NCAM (neuronal cell adhesion molecule). Whilst high levels are expressed during development, peripheral adult organs do not express polySia-NCAM. However, tumours of neural crest-origin re-express polySia-NCAM: its occurrence correlates with aggressive and invasive disease and poor clinical prognosis in different cancer types, notably including small cell lung cancer (SCLC), pancreatic cancer and neuroblastoma. In neuronal development, polySia-NCAM biosynthesis is catalysed by two polysialyltransferases, ST8SiaII and ST8SiaIV, but it is ST8SiaII that is the prominent enzyme in tumours. The aim of this study was to determine the effect of ST8SiaII inhibition by a small molecule on tumour cell migration, utilising cytidine monophosphate (CMP) as a tool compound. Using immunoblotting we showed that CMP reduced ST8iaII-mediated polysialylation of NCAM. Utilizing a novel HPLC-based assay to quantify polysialylation of a fluorescent acceptor (DMB-DP3), we demonstrated that CMP is a competitive inhibitor of ST8SiaII (Ki = 10 μM). Importantly, we have shown that CMP causes a concentration-dependent reduction in tumour cell-surface polySia expression, with an absence of toxicity. When ST8SiaII-expressing tumour cells (SH-SY5Y and C6-STX) were evaluated in 2D cell migration assays, ST8SiaII inhibition led to significant reductions in migration, while CMP had no effect on cells not expressing ST8SiaII (DLD-1 and C6-WT). The study demonstrates for the first time that a polysialyltransferase inhibitor can modulate migration in ST8SiaII-expressing tumour cells. We conclude that ST8SiaII can be considered a druggable target with the potential for interfering with a critical mechanism in tumour cell dissemination in metastatic cancers. / Yorkshire Cancer Research; EPSRC; Association for International Cancer Research; Jordanian Government PhD scholarship

No / We present a series of iterative methods to examine the problems associated with summed probability functions (SPFs) based on archaeological radiocarbon data. As a case study we use an SPF generated from a substantial radiocarbon data-set from the Irish Later Bronze and Iron Ages. We use simple numerical methods to show that real patterns can be deciphered from SPFs that can be used to trace and evaluate patterns of change. However, our results suggest that SPFs should not be used as a simple index of past human activity. / This research forms part of the project ‘Mobility, Climate and Culture: Re-modelling the Irish Iron Age’, funded by the British Academy through their BARDA scheme. Preliminary data collection was conducted as part of a pilot project funded by the Heritage Council of Ireland.

La perméabilité intrinsèque et la conductivité thermique de la neige sont deux paramètres essentiels pour effectuer l'analyse numérique du comportement thermique de milieux poreux. Plusieurs mesures de ces paramètres ont été effectuées successivement sur des échantillons de neiges compactées recueillis à l'Université Laval. La mesure de la conductivité thermique a été effectuée selon la méthode du fil chaud. Pour la perméabilité intrinsèque, un perméamètre à air à double mur fût conçu pour des expériences en laboratoire. La perméabilité intrinsèque et la conductivité thermique variaient respectivement de 1.1 x 10-8 à 8.0 x 10-11 m2 et de 0.09 à 0.48 W/mK pour des échantillons de neige ayant des porosités s'étalant entre 0.32 et 0.75. Les résultats se comparent bien avec ceux trouvés dans la littérature. Des modèles de prédiction des propriétés ont été examinés pour chacune des propriétés avec la porosité et le diamètre des grains.

La popularité croissante des réseaux sociaux a suscité l’intérêt du monde de l’éducation. En effet, ces réseaux constituent des espaces virtuels qui enrichissent l’expérience pédagogique des membres de la communauté académique. Ces différents membres, étudiants et enseignants, bénéficient des outils qui y sont offerts pour soutenir l’expérience d’apprentissage/enseignement au-delà des cours magistraux officiels. Cet intérêt a donné naissance à un éventail d’outils de développement de réseaux sociaux. Par contre, la littérature n’indique pas de démarche à suivre pour développer des réseaux sociaux à visée pédagogique. À cet effet, nous avons comparé des différents outils disponibles pour le développement de réseaux sociaux, puis proposé un guide pour le développement de réseaux sociaux à visée pédagogique. Ce guide est générique et présente la démarche à entreprendre, en étapes concises et bien détaillées. Nous illustrons l’utilisation du guide que nous avons développé pour un cas réel, à savoir celui de l’université de Koudougou. / Social networks know growing popularity that is attracting more and more education world. They are virtual spaces that enrich the educational experience. A variety of software was proposed to create social networks. But, the literature does not indicate how to proceed to develop educational social networks. To this end, a comparison of available tools to create social network was made and a guide for the development of such networks was proposed. This guide is generic and presents, in concise and well-detailed steps, the approach to be undertaken for developing educational social networks. It can be used independently of the objectives of setting up a given educational social network, and independently of the specific needs of its users. In order to illustrate the use of the guide, we have developed the educational social network of the University of Koudougou.

Cette étude vise à examiner la validité de l’Inventaire des Styles Sociaux TRIMA 2.0 (ISST 2.0) en le comparant à une mesure des Big Five : Le Big Five Inventory français. Cette comparaison permet de mieux situer l’ISST 2.0 par rapport au champ de la personnalité, où les Big Five sont une théorie ascendante. L’étude permet de se familiariser à la fois avec la démarche de validation par comparaison à une autre variable et avec le modèle TRIMA. Un échantillon de 425 participants ont rempli les deux tests, sa composition ne pose pas de problèmes connus. Les données utilisées sont comparables avec celles des précédentes études sur ces tests. Les corrélations propres à l’ISST 2.0 sont similaires à celles de sa validation. Toutes les échelles ont au moins une hypothèse informée ou une relation non attendue. Cette étude fournit donc une démonstration mitigée de la validité de l’ISST 2.0.