Insoluble Vascular Amyloid Deposits Trigger Disruption of the Neurovascular Unit in Alzheimer’s Disease Brains

Alzheimer’s disease (AD) is a neurodegenerative disease, characterized histopathologically by intra-neuronal tau-related lesions and by the accumulation of amyloid β-peptide (Aβ) in the brain parenchyma and around cerebral blood vessels. According to the vascular hypothesis of AD, an alteration in the neurovascular unit (NVU) could lead to Aβ vascular accumulation and promote neuronal dysfunction, accelerating neurodegeneration and dementia. To date, the effects of insoluble vascular Aβ deposits on the NVU and the blood–brain barrier (BBB) are unknown. In this study, we analyze different Aβ species and their association with the cells that make up the NVU. We evaluated post-mortem AD brain tissue. Multiple immunofluorescence assays were performed against different species of Aβ and the main elements that constitute the NVU. Our results showed that there are insoluble vascular deposits of both full-length and truncated Aβ species. Besides, insoluble aggregates are associated with a decrease in the phenotype of the cellular components that constitute the NVU and with BBB disruption. This approach could help identify new therapeutic targets against key molecules and receptors in the NVU that can prevent the accumulation of vascular fibrillar Aβ in AD.     

Advances in Applying Computer-Aided Drug Design for Neurodegenerative Diseases

Neurodegenerative diseases (NDs) including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease are incurable and affect millions of people worldwide. The development of treatments for this unmet clinical need is a major global research challenge. Computer-aided drug design (CADD) methods minimize the huge number of ligands that could be screened in biological assays, reducing the cost, time, and effort required to develop new drugs. In this review, we provide an introduction to CADD and examine the progress in applying CADD and other molecular docking studies to NDs. We provide an updated overview of potential therapeutic targets for various NDs and discuss some of the advantages and disadvantages of these tools.     

Synthesis and self-association in aqueous media of poly(ethylene oxide)/poly(ethyl glycidyl carbamate) amphiphilic block copolymers

New temperature sensitive AB, ABA, and BAB amphiphilic block copolymers consisting of hydrophilic poly(ethylene oxide) and hydrophobic poly(ethyl glycidyl carbamate) blocks were synthesized by anionic polymerization followed by chemical modification reactions. The self-association of the block copolymers in aqueous media was studied by UV-vis spectroscopy and dynamic and static light scattering. The obtained block copolymers spontaneously form micelles in aqueous media. The critical micellization concentration varied from 0.5 to 4 g/L depending on the copolymer architecture and composition. The influence of the temperature upon the self-association of the block copolymers was investigated. The increase of temperature did not affect the value of the critical micellization concentration, but led to the formation of better defined micelles with narrow size distribution.     

X-ray photoelectron spectroscopic study of the oxidation and reduction of a cerium(III) oxide/cerium foil substrate

X-ray photoelectron spectroscopy has been used to examine the nature of the oxide overlayers on a passivated cerium metal foil as a function of a variety of oxidation and reduction treatments. Oxidation of a clean uncontaminated cerium(III) oxide surface is facile at room temperature and produces non-stoichiometric ceria (CeO_2–x) at oxygen doses as low as 10 L. At higher doses the overlayer thickens, and after a dose of 160 L the layer depth exceeds the Ce 3d photoelectron attenuation distance of about 20 Å. High pressure treatment of the foil in oxygen (0.5 bar at RT and 473 K) produces CeO₂ in a high degree of crystallographic order such that O 1s photoelectron intensities are increased above that expected from a randomly oriented powder. An attempt to reduce the CeO₂ layer formed by controlled oxidation with CO (633 K, 14 h, 0.6 bar) results in the formation of a carbonated surface layer. Results following attempts to reoxidise this layer are discussed.     

Fatty acid selectivity of lipases: Erucic acid from rapeseed oil

The fatty acid selectivity of several commercial lipases was evaluated in the hydrolysis of high-erucic acid rapeseed oil (HEARO). The lipase ofPseudomonas cepacia catalyzed virtually complete hydrolysis of the oil (94–97%), while that ofGeotrichum candidum discriminated strongly against erucic acid, especially in esterification. A two-step process is suggested for obtaining a highly enriched erucic acid in which theG. candidum lipase is employed to selectively esterify the fatty acid residues of unsaturated C-18, and shorter chain acids, from a mixture of HEARO fatty acids obtained from total hydrolysis of the oil withP. cepacia lipase.     

The effects of Cl-induced alloying in Pt–Sn/Al2O3 catalysts on butane/H2 reactions

The effects of oxidation/reduction regeneration treatments, with and without 1,2-dichloropropane present as a chlorinating agent, on the structure of Pt(3%)–Sn(4.5%)/Al₂O₃ catalysts have been correlated with selectivities for butane/H₂ reactions. Particles of Pt⁰ fin Cl-free catalysts were partly covered by Sn⁰, but retained exposed ensembles of Pt atoms which were active for isomerisation, hydrogenolysis and dehydrogenation reactions, the latter becoming dominant at high reaction temperatures. Coking reduced Pt ensemble size and, hence, also favoured high selectivities for dehydrogenation as hydrogenolysis and isomerisation sites became poisoned. In contrast, the addition of 1,2-dichloropropane in an oxychlorination step before reduction promoted 1:1 Pt⁰–Sn⁰ alloy formation after reduction, the proportion of the total Pt in alloy being enhanced by increasing 1,2-dichloropropane concentration and oxychlorination temperature. The alloy surfaces were inactive for isomerisation and hydrogenolysis reactions, giving dehydrogenation as the sole catalytic reaction.     

A New Level-Set Model for the Representation of Non-Smooth Geometries

In Starinshak et al. (J Comput Phys 262(1):1–16, 2014), we proposed a new level-set model for representing multimaterial flows in multiple space dimensions. Rather than associating each level-set function with the boundary of a material, the new model associates each level-set function with a pair of materials and the interface that separates them. In this paper, we extend the model to represent geometries with non-smooth boundaries. The model uses multiple level-set functions to describe the shape boundary, typically with one level-set function per smooth boundary segment. Sign information is collected from all level-set functions and a voting algorithm is used to determine the interior/exterior of the geometric shape. The model is well suited for representing boundaries with singularities; it offers significant improvement over standard level-set approaches, both in shape preservation and area conservation; and it eliminates the need for costly redistancing of the level-set function. Numerical examples illustrate the superior performance of the proposed model.     

Interval type-2 fuzzy weighted support vector machine learning for energy efficient biped walking

An interval type-2 fuzzy weighted support vector machine (IT2FW-SVM) is proposed to address the problem of high energy consumption for biped walking robots. Different from the traditional machine learning method of ‘copy learning’, the proposed IT2FW-SVM obtains lower energy cost and larger zero moment point (ZMP) stability margin using a novel strategy of ‘selective learning’, which is similar to human selections based on experience. To handle the uncertainty of the experience, the learning weights in the IT2FW-SVM are deduced using an interval type-2 fuzzy logic system (IT2FLS), which is an extension of the previous weighted SVM. Simulation studies show that the existing biped walking which generates the original walking samples is improved remarkably in terms of both energy efficiency and biped dynamic balance using the proposed IT2FW-SVM.     

Bulk and suspension polymerization of styrene in the presence of n-pentane. An evaluation of monofunctional and bifunctional initiation

The plasticizing effect of n-pentane on the rate of bulk free radical polymerization of styrene and molecular weight distribution development has been modeled on the basis of the free volume theory for both monofunctional and bifunctional initiation. A strong decrease in the reaction rate in the late stages of the polymerization, due to the displacement of the onset of the gel effect, has been observed for both types of initiation. This decrease in the polymerization rate limited the terminal conversion to values well below 100% for mono-functional initiation. However, in bifunctionally initiated polymerization, terminal conversions close to 100% were obtained in spite of the decrease in reaction rate. Contrary to what was expected, the molecular weight distribution obtained at terminal conversion was almost completely insensitive to these changes in polymerization rate. This phenomenon is explained in terms of limited transfer to monomer reactions when n-pentane is present in the system. In suspension polymerization, the limiting conversion and plasticizing effects of n-pentane in monofunctionally initiated systems, caused enhanced coalescence leading to suspension set-up. In bifunctionally initiated systems this enhanced coalescence was completely overcome by the short duration of the particle growth stage, owing to high polymerization rates, and stable suspensions were achieved. For these systems the particle size distributions obtained were similar to that of suspension polystyrene without n-pentane. © 1993 John Wiley & Sons, Inc.