BMS Derivatives C7-Linked to β-Cyclodextrin and Hyperbranched Polyglycerol Retain Activity against R5-HIV-1NLAD8 Isolates and Can Be Deemed Potential Microbicides

Amides from indole-3-glyoxylic acid and 4-benzoyl-2-methylpiperazine, which are related to entry inhibitors developed by Bristol-Myers Squibb (BMS), have been synthesized with aliphatic chains located at the C7 position of the indole ring. These spacers contain an azido group suitable for the well-known Cu(I)-catalyzed (3+2)-cycloaddition or an activated triple bond for the nucleophilic addition of thiols under physiological conditions. Reaction with polyols (β-cyclodextrin and hyperbranched polyglycerol) decorated with complementary click partners has afforded polyol-BMS-like conjugates that are not cytotoxic (TZM.bl cells) and retain the activity against R5-HIV-1_NLAD8 isolates. Thus, potential vaginal microbicides based on entry inhibitors, which can be called of 4^th generation, are reported here for the first time.     

Evaluation of direct light processing for the fabrication of bioactive ceramic scaffolds: Effect of pore/strut size on manufacturability and mechanical performance

Bioactive ceramic scaffolds for bone regeneration consisting of a three-dimensional mesh of interpenetrating struts with square section were fabricated via Digital Light Processing (DLP). The ability of the technique to manufacture 3D porous structures from β-tricalcium phosphate (β-TCP) powders with different dimensions of struts and pores was evaluated, identifying the possibilities and limitations of the manufacturing process. Small pore sizes were found to seriously complicate the elimination of excess slurry from the scaffold’s innermost pores. The effect of the strut/pore size on the mechanical performance of the scaffolds under compressive stresses was also evaluated, but no significant influence was found. Under compressive stresses, the structures resulted weaker when tested perpendicularly to the printing plane due to interlayer shear failure. Interlayer superficial grooves are proposed as potential failure-controlling defects, which could also explain the lack of a Weibull size effect on the mechanical strength of the fabricated DLP scaffolds.     

Mechanical properties and thermal shock in thin ZrO2–Y2O3–Al2O3 films obtained by the sol-gel method

Thin multilayer coatings of ZrO₂–Y₂O₃–Al₂O₃ were prepared using the sol-gel method and dip-coating technique in order to advance in the study of what influence the incorporation of Al₂O₃ has on films of Y₂O₃-doped ZrO₂, investigating its role in the synthesis of the solutions and in the characteristics and properties of the coatings. After the characterization of the solutions used in the process, the microstructure of the films was studied and their mechanical behaviour and resistance to thermal shock were determined so as to optimize the characteristics and functionality of these coatings. With increased alumina content, 3YSZ-Al₂O₃ (20 mol%), the cubic phase of the zirconia disappeared completely at the sintering temperature used (700 °C), resulting in the tetragonal phase with Al in solution. There was also a decrease in the coatings' hardness and Young's modulus, and an increase in toughness and resistance to thermal shock. These results allow guidelines to be established for the design of multilayer structures that are, tougher, more resistant, and have improved surface properties.     

Characterization of precipitates formed in X7R 0603 BME-MLCC during sintering

In the current study two different batches of X7R-0603 BME-MLCCs displayed dissimilar electrical performance, despite having the same chemical composition, tape casting, and sintering conditions; with the only difference between them being the ore deposits where the raw materials were extracted from to synthesize the BaTiO₃. Specifically, they presented different electrical response to highly accelerated life tests (HALT). Although the chemical analysis of each slip showed the same composition, the trace elements of the BaTiO₃ sources could have acted as dopants or produced different secondary phases. A search for precipitates in the two samples was conducted by means of Scanning (SEM) and Transmission Electron Microscopy (TEM) techniques. SEM observations confirmed the presence of precipitates formed within the structure of the MLCCs exhibiting the greatest decrement in their electrical resistance results during the HALT. In order to further characterize the observed precipitates, samples were prepared by Focused Ion Beam (FIB) lift-out method, to make TEM characterization of specific precipitates feasible. TEM studies were performed on the precipitates to obtain electron diffraction patterns and complementary Energy Dispersive X-Ray Spectroscopy (EDXS) chemical analysis. Based on the crystal and chemical data obtained, it can be concluded that the precipitates are a hexagonal anhydrous silicate oxyapatite phase with a stoichiometry of Ca₃Y₁₆Si₁₀O₁₃, and lattice parameters of a = 0.9353 nm and c = 0.6970 nm; this phase was not found in the JCPDS data base. Differences in raw materials coming from different ore deposits can produce undesired precipitates that affect the electrical performance of MLCCs.     

Isolate-Specific Effect of Entomopathogenic Endophytic Fungi on Population Growth of Two-Spotted Spider Mite (Tetranychus urticae Koch) and Levels of Steroidal Glycoalkaloids in Tomato

Journal of Chemical Ecology - Entomopathogenic fungi (EPF) can be experimentally established in several plant species as endophytes. Ecological effects of EPF inoculations on plant growth and...     

Exploration of GH94 Sequence Space for Enzyme Discovery Reveals a Novel Glucosylgalactose Phosphorylase Specificity

The substantial increase in DNA sequencing efforts has led to a rapid expansion of available sequences in glycoside hydrolase families. The ever-increasing sequence space presents considerable opportunities for the search for enzymes with novel functionalities. In this work, the sequence-function space of glycoside hydrolase family 94 (GH94) was explored in detail, using a combined approach of phylogenetic analysis and sequence similarity networks. The identification and experimental screening of unknown clusters led to the discovery of an enzyme from the soil bacterium Paenibacillus polymyxa that acts as a 4-O-β-d -glucosyl-d -galactose phosphorylase (GGalP), a specificity that has not been reported to date. Detailed characterization of GGalP revealed that its kinetic parameters were consistent with those of other known phosphorylases. Furthermore, the enzyme could be used for production of the rare disaccharides 4-O-β-d -glucosyl-d -galactose and 4-O-β-d -glucosyl-l -arabinose. Our current work highlights the power of rational sequence space exploration in the search for novel enzyme specificities, as well as the potential of phosphorylases for rare disaccharide synthesis.     

Development and characterisation of a Y2Ti2O7-based glass-ceramic as a potential oxidation protective coating for titanium suboxide (TiOx)

A silica-based glass-ceramic, with Y₂Ti₂O₇ as the major crystalline phase, is designed, characterised and tested as an oxidation-protective coating for a titanium suboxide (TiO_x) thermoelectric material at temperatures of up to 600 °C. The optimised sinter-crystallisation treatment temperatures are found to be 1300 °C and 855 °C for a duration of 30 min, and this treatment leads to a glass-ceramic with cubic Y₂Ti₂O₇ and CaAl₂Si₂O₈ as crystalline phases. An increase of ~270 °C in the dilatometric softening temperature is observed after devitrification of the parent glass, thus further extending its working temperature range.Excellent adhesion of the glass-ceramic coating to the thermoelectric material is maintained after exposure to a temperature of 600 °C for 120 h under oxidising conditions, thus confirming the effectiveness of the T1 glass-ceramic in protecting the TiO_x material.     

Efficient Design of Pruned Convolutional Neural Networks on FPGA

Journal of Signal Processing Systems - Convolutional Neural Networks (CNNs) have improved several computer vision applications, like object detection and classification, when compared to other...     

Development of a Topical Insulin Polymeric Nanoformulation for Skin Burn Regeneration: An Experimental Approach

Insulin is a peptide hormone with many physiological functions, besides its use in diabetes treatment. An important role of insulin is related to the wound healing process—however, insulin itself is too sensitive to the external environment requiring the protective of a nanocarrier. Polymer-based nanoparticles can protect, deliver, and retain the protein in the target area. This study aims to produce and characterize a topical treatment for wound healing consisting of insulin-loaded poly-DL-lactide/glycolide (PLGA) nanoparticles. Insulin-loaded nanoparticles present a mean size of approximately 500 nm and neutral surface charge. Spherical shaped nanoparticles are observed by scanning electron microscopy and confirmed by atomic force microscopy. SDS-PAGE and circular dichroism analysis demonstrated that insulin preserved its integrity and secondary structure after the encapsulation process. In vitro release studies suggested a controlled release profile. Safety of the formulation was confirmed using cell lines, and cell viability was concentration and time-dependent. Preliminary safety in vivo assays also revealed promising results.     

Botulinum Toxin: From Poison to Possible Treatment for Spasticity in Spinal Cord Injury

Botulism has been known for about three centuries, and since its discovery, botulinum toxin has been considered one of the most powerful toxins. However, throughout the 20th century, several medical applications have been discovered, among which the treatment of spasticity stands out. Botulinum toxin is the only pharmacological treatment recommended for spasticity of strokes and cerebral palsy. Although its use as an adjuvant treatment against spasticity in spinal cord injuries is not even approved, botulinum toxin is being used against such injuries. This article describes the advances that have been made throughout history leading to the therapeutic use of botulinum toxin and, in particular, its application to the treatment of spasticity in spinal cord injury.