Virus-Based Nanoreactors with GALT Activity for Classic Galactosemia Therapy

Enzymatic nanoreactors were obtained by galactose-1-phosphate uridylyl-transferase (GALT) encapsulation into plant virus capsids by a molecular self-assembly strategy. The aim of this work was to produce virus-like nanoparticles containing GALT for an enzyme-replacement therapy for classic galactosemia. The encapsulation efficiency and the catalytic constants of bio-nanoreactors were determined by using different GALT and virus coat protein ratios. The substrate affinity of nanoreactors was slightly lower than that of the free enzyme; the activity rate was 16 % of the GALT free enzyme. The enzymatic nanoreactors without functionalization were internalized into different cell lines including fibroblast and kidney cells, but especially into hepatocytes. The enzymatic nanoreactors are an innovative enzyme preparation with potential use for the treatment of classic galactosemia.     

[2.2]Paracyclophane-Based TCN-201 Analogs as GluN2A-Selective NMDA Receptor Antagonists

Recent studies have shown the involvement of GluN2A subunit-containing NMDA receptors in various neurological and pathological disorders. In the X-ray crystal structure, TCN-201 ( 1 ) and analogous pyrazine derivatives 2 and 3 adopt a U-shape (hairpin) conformation within the binding site formed by the ligand binding domains of the GluN1 and GluN2A subunits. In order to mimic the resulting π/π-interactions of two aromatic rings in the binding site, a [2.2]paracyclophane system was designed to lock these aromatic rings in a parallel orientation. Acylation of [2.2]paracyclophane ( 5 ) with oxalyl chloride and chloroacetyl chloride and subsequent transformations led to the oxalamide 7 , triazole 10 and benzamides 12 . The GluN2A inhibitory activities of the paracyclophane derivatives were tested with two-electrode voltage clamp electrophysiology using Xenopus laevis oocytes expressing selectively functional NMDA receptors with GluN2A subunit. The o-iodobenzamide 12 b with the highest similarity to TCN-201 showed the highest GuN2A inhibitory activity of this series of compounds. At a concentration of 10 μM, 12 b reached 36 % of the inhibitory activity of TCN-201 ( 1 ). This result indicates that the [2.2]paracyclophane system is well accepted by the TCN-201 binding site.     

Managing Water to Minimize Risk in Tailings Storage Facility Design,Construction, and Operation

Mine Water and the Environment - Reducing the amount of water in a milled tailings storage facility (TSF) is the primary way to reduce the risk of a catastrophic failure. In addition, a significant...     

Implementation of periodic boundary conditions for loading of mechanical metamaterials and other complex geometric microstructures using finite element analysis

The implementation of periodic boundary conditions (PBCs) is one of the most important and difficult steps in the computational analysis of structures and materials. This is especially true in cases such as mechanical metamaterials which typically possess intricate geometries and designs which makes finding and implementing the correct PBCs a difficult challenge. In this work, we analyze one of the most common PBCs implementation technique, as well as implement and validate an alternative generic method which is suitable to simulate any possible 2D microstructural geometry with a quadrilateral unit cell regardless of symmetry and mode of deformation. A detailed schematic of how both these methods can be employed to study 3D systems is also presented.

     

Performance Evaluation of Two High‐Shear Impellers in an Unbaffled Stirred Tank

High‐shear impellers (HSIs) are mixers used in industrial stirred tanks to incorporate powders into liquids and break down particle agglomerates. A detailed numerical study of two commercial ring‐style HSIs of laboratory scale was carried out and their performance was compared with the Rushton turbine (RT). It was found that power and pumping numbers or their ratio cannot be simply connected for properly selecting an impeller in applications where highly localized viscous dissipation is desirable. The ratio of the average viscous dissipation in the impeller swept volume to the mean in the entire volume at two constant values of power input turned out to be lower for HSIs compared to that evaluated for RT. However, at higher power input, the dimensionless average viscous dissipation in the blade swept volume was found to be similar for the HSI of two rings and the RT, corroborating the high local viscous dissipation of this HSI when operated at higher speeds.     

Forum The role of CIB: some reflections

An explanation for the low innovation activity in construction is put forward. The central argument is that the current theory of construction is one root cause for low innovation activity. Instead, an explicit and more powerful theory of construction is needed for further innovation, which is ‘to manage new ideas into good currency’. There are three main mechanisms in the current theory of construction which are identified as causing this hindrance. Firstly, production theories in general, as well as construction theories specifically, have been implicit. Therefore, it has not been possible to transfer radical managerial innovations, such as lean production, from manufacturing to construction at a theoretical level. Direct application of this production template to construction has been limited due to the different context of construction in comparison with manufacturing. Secondly, the current theoretical model of construction is based on the transformation model of production. It is argued that the principles of this model are counterproductive, because uncertainty and interdependence are abstracted away. This leads to fragmented and myopic management and inflated variability. Practical examples show that these deficiencies and related practical constraints hinder the implementation of top-down innovations. Thirdly, empirical research shows that also bottom-up innovations - systematic learning and problem solving - are being hindered by the current theory. Thus, the advancement of innovations in construction requires that a new, explicit and valid theory of construction is created, and business models and control methods are developed on the basis of that new theory. Cet article propose une explication concernant le taux bas de l'activité d'innovation dans la secteur du bâtiment. L'argument central étant que la théorie actuelle de la construction est une des raisons fondamentales de cette activité basse d'innover. Au lieu de cela, on a besoin d'une théorie de la construction explicite et plus efficace afin d'innover. Dans la théorie actuelle du bâtiment, il y a trois mécanismes fondamentaux qui sont identifiés comme causes gênant cette innovation. Premièrement, les théories de production en général, ainsi que les théories de la construction en particulier, ont été implicites. Ainsi, il était impossible de transférer des innovations gestionnaires radicales, comme la production allégée (lean production), à partir du domaine de la fabrication à celui du bâtiment à un niveau théorique. L'application directe de ce modèle de production au secteur bâtiment a été limitée à cause du contexte différent de celui-ci en comparaison de celui de la fabrication. Deuxièmement, le modèle théorique actuel de la construction bâtiment est basé sur le modèle de la transformation de production. On avance que les principes de ce modèle agissent négativement sur la productivité parce que l'incertitude et l'interdépendance en sont exclues. Ceci mène à une gestion fragmentée et myope ainsi qu'à une inflation de la variabilité. Des exemples pratiques montrent que ces déficiences et les contraintes pratiques qui leur sont liées, gênent les implémentations des innovations de haut en bas. Troisièmement, une étude empirique montre que les innovations de bas en haut - c'est-à-dire l'apprentissage systématique et la résolution de problèmes - sont gênés par la théorie actuelle. Ainsi, le progrès dan les innovations du secteur bâtiment exige qu'une nouvelle théorie explicite et valide soit créée, et que des modèles d'affaires et des méthodes de contrôle soient développés sur la base de cette nouvelle théorie.     

Single-frame super-resolution in remote sensing: a practical overview

Image acquisition technology is improving very fast from a performance point of view. However, there are physical restrictions that can only be solved using software processing strategies. This is particularly true in the case of super resolution (SR) methodologies. SR techniques have found a fertile application field in airborne and space optical acquisition platforms. Single-frame SR methods may be advantageous for some remote-sensing platforms and acquisition time conditions. The contributions of this article are basically two: (1) to present an overview of single-frame SR methods, making a comparative analysis of their performance in different and challenging remote-sensing scenarios, and (2) to propose a new single-frame SR taxonomy, and a common validation strategy. Finally, we should emphasize that, on the one hand, this is the first time, to the best of our knowledge, that such a review and analysis of single SR methods is made in the framework of remote sensing, and, on the other hand, that the new single-frame SR taxonomy is aimed at shedding some light when classifying some types of single-frame SR methods.     

Lactic acid production using waste generated from sweet potato processing

Organic waste generated from industrial sweet potato canning is estimated to be 30% of incoming raw material with significant residual carbohydrate content. The purpose of this study was to evaluate the potential of waste generated from sweet potato processing material to support the growth of lactic acid bacteria and the production of lactic acid. The waste was comprised of 16.5% solids consisting of 18.5% ash, 4.4% protein, 20.5% simple sugars and 19% soluble starch. Following a screening of three lactic acid bacteria strains, Lactobacillus rhamnosus was deemed the best candidate for lactic acid production. The potential of various dilutions of the enzyme‐hydrolysed waste, with and without pH control, as a fermentation substrate was evaluated. Lactic acid production was highest in hydrolysed waste (without dilution) at pH set point 5.0, yielding 10 g L^?1 in 72 h. Thus, lactic acid, a valuable organic compound, can be generated from sweet potato waste.