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.     

Molecular Mechanisms of Fetal Tendon Regeneration Versus Adult Fibrous Repair

Tendinopathies are painful, disabling conditions that afflict 25% of the adult human population. Filling an unmet need for realistic large-animal models, we here present an ovine model of tendon injury for the comparative study of adult scarring repair and fetal regeneration. Complete regeneration of the fetal tendon within 28 days is demonstrated, while adult tendon defects remained macroscopically and histologically evident five months post-injury. In addition to a comprehensive histological assessment, proteome analyses of secretomes were performed. Confirming histological data, a specific and pronounced inflammation accompanied by activation of neutrophils in adult tendon defects was observed, corroborated by the significant up-regulation of pro-inflammatory factors, neutrophil attracting chemokines, the release of potentially tissue-damaging antimicrobial and extracellular matrix-degrading enzymes, and a response to oxidative stress. In contrast, secreted proteins of injured fetal tendons included proteins initiating the resolution of inflammation or promoting functional extracellular matrix production. These results demonstrate the power and relevance of our novel ovine fetal tendon regeneration model, which thus promises to accelerate research in the field. First insights from the model already support our molecular understanding of successful fetal tendon healing processes and may guide improved therapeutic strategies.     

Direct-Ink-Writing of Electroactive Polymers for Sensing and Energy Storage Applications

Considering the high levels of materials used in the fields of electronics and energy storage systems, it is increasingly necessary to take into consideration environmental impact. Thus, it is important to develop devices based on environmentally friendlier materials and/or processes, such as additive manufacturing techniques. In this work, poly(vinylidene fluoride) (PVDF) and poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) are prepared by direct-ink-writing (DIW) by varying solvent evaporation temperature and fill density percentage. Different morphologies for both polymers are obtained, including dense films and porous membranes, as well as different electroactive β-phase content, thermal and mechanical properties. The dielectric constant and piezoelectric d₃₃ coefficient for dense films reaches up to 16 at 1 kHz and 4 pC N⁻¹, respectively for PVDF-HFP with a fill density of 80 and a solvent evaporation temperature of 50 °C. Porous structures are developed for battery separator membranes in lithium-ion batteries, with a highest ionic conductivity value of 3.8 mS cm⁻¹ for the PVDF-HFP sample prepared with a fill density of 100 and a solvent evaporation temperature of 25 °C, the sample showing an excellent cycling performance. It is demonstrated that electroactive films and membranes can be prepared by direct-ink writing suitable for sensors/actuators and energy storage systems.     

Global insight into microwave stoneware firing: Macro and microstructural changes

Industrial competition and environmental concerns lead to the exploration of alternative and energy-efficient technologies for ceramic materials processing. The main objective of this work was to present microwave heating as a viable option for stoneware processing. Stoneware functional properties are presented and discussed, with emphasis on impact strength, water absorption, porosity, and color. Microstructure analyses show that microwave- and gas-fired samples have higher densifications than electrically fired samples. A relevant finding for processing conditions is that microwave firing requires temperatures approximately 100°C lower than those required by conventional firing. Microwave-fired samples’ rupture energies are approximately twice (0.57 ± 0.06 (J)) those of the reference samples (0.26 ± 0.03 (J)), and their water absorptions are approximately one-half (1.5% at 1170°C and 0.8% at 1190°C) of those of the reference samples (2.0%), whereas the water absorption of electrically fired samples at 1180°C has been estimated to be 7.5%. Color analysis also evidences a shift to lower microwave firing temperatures, what is attributed to the enhanced transformations promoted by microwave heating when comparing with the transformations promoted by conventional (gas or electric) heating.     

Surface Pretreatments of Silicon Nitride for CVD Diamond Deposition

The efficiency of different surface pretreatments (four standard chemical etchings and four diamond powder abrasive procedures) on silicon nitride (Si₃N₄) substrates for chemical vapor deposition (CVD) of diamond has been systematically investigated. Blank Si₃N₄ samples were polished with colloidal silica (∼0.25 μm). Diamond nucleation and growth runs were conducted in a microwave plasma chemical vapor deposition apparatus for 10 min and 6 h, respectively. Superior results concerning nucleation density ( N _d∼ 10¹⁰ cm⁻² after 10 min), film uniformity, and grain size (below 2 μm after 6 h) were obtained for the mechanically microflawed samples, revealing that chemical etchings (hot and cold strong acids, molten base or CF₄ plasma) are not crucial for good CVD diamond quality on Si₃N₄.     

Supported Molybdenum Carbides Lie Between Metallic and Sulfided Catalysts for Deep HDS

Hydrodesulfurization (HDS) of 4,6-dimethyldibenzothiophene on alumina-supported Mo₂C has been studied. These catalysts are stable and active under deep HDS conditions (0-250 wt ppm S). However, although they are well known to have hydrogenation properties, they lead preferentially to a non-hydrogenated product of the HDS reaction: dimethylbiphenyl. For the same reaction, supported platinum and sulfided molybdenum oxide lead to the hydrogenated products dimethyldicyclohexyl and methylcyclohexyltoluene, respectively. The ranking of HDS activity is as follows: MoS₂/Al₂O₃ < Mo₂C/Al₂O₃ < Pt/SiO₂.     

A two-step reaction mechanism of oxygen release from Pd/CeO2: mathematical modelling based on step gas concentration experiments

Topics in Catalysis - A mathematical model has been developed to study the transient release of oxygen from a 1 wt% Pd/CeO2 catalyst in the 450–550&nbsp;°C range based on alternate...     

Design and analysis of single-factor experiments: Analysis of variance of the effect of rice husk ash and commercial fillers in NR compounds

Summary White rice husk ash (WRHA) and black rice husk ash (BRHA) were incorporated into natural rubber (NR) using a laboratory-sized two-roll mill. A conventional vulcanization system was used for curing and physical tests of the NR vulcanized involved determining of tensile and tear resistances. For comparison purposes, precipitated silica (Zeosil-175) and carbon black (N774) were used too. Using the analysis of variance of single-factor experiments, it can be concluded that: BRHA is non-reinforcing filler and its use is limited to 20 phr; WRHA is semi-reinforcing filler and the variation of filler loading (0 up to 50 phr) causes the maximum variation upon tensile strength of NR compounds; and, that although carbon black and silica are reinforcing fillers, a real reinforcement is reached up to 20 phr for tensile strength.     

Rice husk ash filled natural rubber. I. Overall rate constant determination for the vulcanization process from rheometric data

Black rice husk ash (BRHA) and white rice husk ash (WRHA) were incorporated into natural rubber (NR) using a laboratory‐size two‐roll mill. A conventional vulcanization system (CV) was chosen and cure studies were carried out on a TI‐100 Curometer. The torque curves were obtained at 150, 160, 170, and 180°C. The overall rate and the apparent activation energy for the vulcanization process were calculated for each compound assuming that vulcanization follows first‐order kinetics. For comparison purposes, two commercial fillers, precipitated silica (Zeosil‐175) and carbon black (N762), were also used. It was observed that addition of WRHA to NR compounds increased the cross‐linking rate and lowered the apparent activation energy more markedly than the other fillers. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1194–1203, 2003     

Selective Complexation and Membrane Transport of Guanidinium Salts by Calix[6]arene Amides

The p-tert-butylcalix[6]arene hexamide 2 and syn-1,3,5–trimethoxy-2,4,6-triamide 4 were synthesized by reaction of α-chloro-N,N-diethylacetamide and the corresponding calix[6]arenes 1 and 3 , respectively. ¹H NMR spectroscopy shows that 2 is a mixture of different conformations whereas 4 is fixed in a cone conformation. Extraction experiments, (S-L) and (H₂O–CDCl₃) with picrate salts, indicate that 2 complexes both alkali metal (1:2 complex) and guanidinium salts (1:1 complex) but 4 complexes only guanidinium (1:1 complex). Incorporated in supported liquid membranes (Accurel^® / o-nitrophenyl n-octyl ether) the calixarenes 2 and 4 transport guanidinium salts. The hexamide 2 is a more efficient carrier of guanidinium but the syn-1,3,5-trimethoxy-2,4,6-triamide 4 is much more selective. Both 2 and 4 are sufficiently lipophilic to give membranes that are stable over longer periods (weeks).