Prion diseases: from molecular biology to intervention strategies

Prion diseases are fatal neurodegenerative infectious disorders for which no therapeutic or prophylactic regimens exist. Understanding the molecular process of conformational conversion of the cellular prion protein (PrP(c)) into its pathological isoform (PrP(Sc)) will be necessary to devise effective antiprion strategies. In recent years, new findings in the cell biology of PrP(c), in the molecular pathogenesis of PrP(Sc), and in the cellular quality control mechanisms involved in these scenarios have accumulated. A function of the prion protein in signalling, the possible impact of the proteasome, and aggresomes as intracellular waste deposits have been described. Here, important pathogenetic similarities with the more frequent neurodegenerative disorders are evident. The need for therapeutic, postexposure, and prophylactic possibilities was drastically illustrated by the emergence of variant Creutzfeldt-Jakob disease (vCJD), a new human prion disease caused by bovine spongiform encephalopathy (BSE) derived prions. Although prion infectivity in humans is usually restricted to the central nervous system, in vCJD patients prions are present in the lympho-reticular system, posing a theoretical risk of accidental human-to-human transmission. A variety of chemical antiprion substances have been reported in in vitro and cell culture based assays or in animal studies. Occasionally, they have also made their way into the first human trials. In addition, various promising interference strategies have been devised in transgenic models, although they are usually hard to transfer into nontransgenic in vivo situations. New findings in the fields of peripheral prion pathogenesis and immune system involvement fuelled the search for antiprion strategies formerly considered to be entirely impossible. This opened the door towards classical immunological interference techniques. Remarkably, passive and even active vaccination approaches now seem to be realistic goals.     

Parameter identification and computational simulation of polyurethane foaming process by finite pointset method

Numerical simulation of the polyurethane foaming process is a valuable method to analyze the molding process at an early stage of product development to shorten time-to-market cycles and cut costs by using fewer prototypes. However, this process involves highly coupled thermo-chemo-rheological modeling and needs adequate model parameters’ identification. A theoretical model including chemical reactions and thermo-rheological coupling of conservation equations was developed. Based on the theoretical model, three-dimensional numerical simulation for mold filling of the polyurethane foam was carried out by using Finite Pointset Method (FPM) to predict flow field, flow front advancement, temperature and density distributions during mold filling. A FOAMAT system was used to monitor foam height rise and reaction temperature on a cylindrical test tube and foam viscosity was measured by using a dynamic rotational rheometer with parallel-plate system. The parameters of the model were identified by an inverse analysis method which consists in determining the parameters by comparing the computed quantities to those measured experimentally. The overall modeling was validated by using short shot foams obtained with a panel mold cavity. Mold filling of an automotive underlay carpet cavity was investigated numerically. Flow front results were successfully compared to short shot foams obtained with the industrial mold cavity.     

Intercellular Transport of Nanomaterials is Mediated by Membrane Nanotubes In Vivo

So‐called membrane nanotubes are cellular protrusions between cells whose functions include cell communication, environmental sampling, and protein transfer. It has been previously reported that systemically administered carboxyl‐modified quantum dots (cQDs) are rapidly taken up by perivascular macrophages in skeletal muscle of healthy mice. Expanding these studies, it is found, by means of in vivo fluorescence microscopy on the mouse cremaster muscle, rapid uptake of cQDs not only by perivascular macrophages but also by tissue‐resident cells, which are localized more than 100 μm distant from the closest vessel. Confocal microscopy on muscle tissue, immunostained for the membrane dye DiI, reveals the presence of continuous membranous structures between MHC‐II‐positive, F4/80‐positive cells. These structures contain microtubules, components of the cytoskeleton, which clearly colocalize with cQDs. The cQDs are exclusively found inside endosomal vesicles. Most importantly, by using in vivo fluorescence microscopy, this study detected fast (0.8 μm s^?1, mean velocity), bidirectional movement of cQDs in such structures, indicating transport of cQD‐containing vesicles along microtubule tracks by the action of molecular motors. The findings are the first to demonstrate membrane nanotube function in vivo and they suggest a previously unknown route for the distribution of nanomaterials in tissue.     

How hypertext fosters children’s knowledge acquisition: The roles of text structure and graphical overview

Children in primary and secondary school are asked to go on the Internet for school purposes while research on hypertext has scarcely investigated how children process and learn from hypertext. We therefore examined how hypertext influences children’s knowledge acquisition from expository text. A group of 71 Dutch children (13 years old) from one secondary school for pre-university education participated in the study. In a within-subjects design with four conditions, we compared: regular linear text, regular text with overview, hypertext, and hypertext with overview. Children’s (a) navigation (i.e., reading time and navigation pattern) and (b) learning (i.e., multiple choice knowledge questions and mind maps) was measured. Although reading times did not differ, the children navigated less linearly in both hypertext conditions than in the regular text with overview condition. The four types of text led to the same deep understanding as measured on the text base level. Analyses of the mind maps, however, showed the children to construct richer situation models after reading hypertext or hypertext with an overview relative to regular linear text and regular text with overview. We therefore conclude that hypertext fosters a deeper level of information processing when appropriately designed relative to regular linear text.     

Modeling,classifying and annotating weakly annotated images using Bayesian network

In this paper, we propose a probabilistic graphical model to represent weakly annotated images. We consider an image as weakly annotated if the number of keywords defined for it is less than the maximum number defined in the ground truth. This model is used to classify images and automatically extend existing annotations to new images by taking into account semantic relations between keywords. The proposed method has been evaluated in visual-textual classification and automatic annotation of images. The visual-textual classification is performed by using both visual and textual information. The experimental results, obtained from a database of more than 30,000 images, show an improvement by 50.5% in terms of recognition rate against only visual information classification. Taking into account semantic relations between keywords improves the recognition rate by 10.5%. Moreover, the proposed model can be used to extend existing annotations to weakly annotated images, by computing distributions of missing keywords. Semantic relations improve the mean rate of good annotations by 6.9%. Finally, the proposed method is competitive with a state-of-art model.     

Selective oxidation of H2S in Claus tail-gas over SiC supported NiS2 catalyst

Very high activity and selectivity could be achieved for the direct oxidation of H₂S into elemental sulfur at low reaction temperature (40–60°C), on nickel sulfide supported SiC catalyst. The heterogeneous nature of the support surface (hydrophilic and hydrophobic areas) could explain the important role played by water to maintain a high and stable H₂S conversion level. The formation of a very active superficial nickel oxysulfide phase was proposed in order to explain the activation period necessary at reaction temperatures <60°C. Total selectivity for sulfur was attributed to the very low reaction temperature and the absence of any microporosity in the support.