Surface roughness and filler particles characterization of resin‐based composites

The purpose of this study was to evaluate the surface roughness (Ra), and the morphology and composition of filler particles of different composites submitted to toothbrushing and water storage. Disc‐shaped specimens (15 mm × 2 mm) were made from five composites: two conventional (Z100?, and Filtek? Supreme Ultra Universal, 3M), one “quick‐cure” (Estelite ∑ Quick, Tokuyama), one fluoride‐releasing (Beautiful II, Shofu), and one self‐adhering (Vertise Flow, Kerr) composite. Samples were finished/polished using aluminum oxide discs (Sof‐Lex, 3M), and their surfaces were analyzed by profilometry (n = 5) and scanning electron microscopy (SEM; n = 3) at 1 week and after 30,000 toothbrushing cycles and 6‐month water storage. Ra data were analyzed by two‐way analysis of variance and Tukey's test (α = 0.05). Filler particles morphology and composition were analyzed by SEM and X‐ray dispersive energy spectroscopy, respectively. Finishing/polishing resulted in similar Ra for all the composites, while toothbrushing and water storage increased the Ra of all the tested materials, also changing their surface morphology. Beautifil II and Vertise Flow presented the highest Ra after toothbrushing and water storage. Filler particles were mainly composed of silicon, zirconium, aluminum, barium, and ytterbium. Size and morphology of fillers, and composition of the tested composites influenced their Ra when samples were submitted to toothbrushing and water storage.     

Simulation-based design and optimization of refrigeration cassettes

A model-driven design and optimization methodology for sizing the components of refrigeration cassettes for light commercial applications (i.e., cooling capacities ranging from 0.5 to 1.5 kW) is presented. Mathematical models were devised for each of the system components and their numerical results were compared with experimental data taken with different cassettes. It was found that the model predictions for the working pressures, power consumption, cooling capacity and coefficient of performance (COP) showed maximum deviations of ±10%. A genetic optimization algorithm was used to design the condenser and evaporator and also to select the compressor model based on an objective function which considers both the COP and cost. The optimization led to two improved cassette designs, which were assembled and tested. One of the optimized cassettes showed a COP/cost ratio approximately 50% higher than that of the baseline system.     

Development of Potent Inhibitors of the Mycobacterium tuberculosis Virulence Factor Zmp1 and Evaluation of Their Effect on Mycobacterial Survival inside Macrophages

The enzyme Zmp1 is a zinc‐containing peptidase that plays a critical role in the pathogenicity of Mycobacterium tuberculosis. Herein we describe the identification of a small set of Zmp1 inhibitors based on a novel 8‐hydroxyquinoline‐2‐hydroxamate scaffold. Among the synthesized compounds, N‐(benzyloxy)‐8‐hydroxyquinoline‐2‐carboxamide ( 1 c ) was found to be the most potent Zmp1 inhibitor known to date, and its binding mode was analyzed both by kinetics studies and molecular modeling, identifying critical interactions of 1 c with the zinc ion and residues in the active site. The effect of 1 c on intracellular Mycobacterium survival was assayed in J774 murine macrophages infected with M. tuberculosis H37Rv or M. bovis BCG and human monocyte‐derived macrophages infected with M. tuberculosis H37Rv. Cytotoxicity and genotoxicity were also assessed. Overall, inhibitor 1 c displays interesting in vitro antitubercular properties worthy of further investigation.     

Dentin bond strength and nanoleakage of the adhesive interface after intracoronal bleaching

This study evaluated dentin bond strength (BS) and nanoleakage of non‐ and pre‐etched dentin immediately (T₀,), 7 days (T₇), and 14 days (T₁₄) after bleaching. Bovine incisors (150) were selected and half of them submitted to intrapulpal dentin etching (e). Non‐ and pre‐etched dentin were subjected to the following (n = 15): no bleaching/control (C); 35% carbamide peroxide (CP); 35% hydrogen peroxide (35% HP); 25% hydrogen peroxide (25% HP); and sodium perborate (SP). Bleaching agents were applied to the pulp chamber four times within a 72‐h interval. Afterwards, pulp chamber dentin was prepared for the BS test at different evaluation times (n = 5): T₀, T₇, and T₁₄. Composite blocks were built on pulp chamber and sectioned in slices. Slices were reduced to an hour‐glass shape with a cross‐sectional area of 0.8 mm² and submitted to microtensile BS test. Two additional specimens for each group were prepared for nanoleakage evaluation by transmission electron microscopy (TEM). Results were analyzed by ANOVA (two‐way) and Dunnett's test (p < .05). BS decreased immediately after intracoronal bleaching for both sound and pre‐etched dentin (p < .05). At T₁₄, the BS of non‐etched bleached dentin increased for all groups, whereas the pre‐etched SPe group presented BS similar to the Ce. Nanoleakage within the hybrid layer was perceptible immediately after bleaching, although a decrease in nanoleakage was observed for all groups at T₁₄. Adhesive restorations should be performed 7–14 days after bleaching, according to the bleaching agent used. Intracoronal bleaching should be performed preferably with sodium perborate if previous dentin etching is applied.     

A TR‐FRET‐Based Functional Assay for Screening Activators of CARM1

Epigenetics is an emerging field that demands selective cell‐permeable chemical probes to perturb, especially in vivo, the activity of specific enzymes involved in modulating the epigenetic codes. Coactivator‐associated arginine methyltransferase 1 (CARM1) is a coactivator of estrogen receptor α (ERα), the main target in human breast cancer. We previously showed that twofold overexpression of CARM1 in MCF7 breast cancer cells increased the expression of ERα‐target genes involved in differentiation and reduced cell proliferation, thus leading to the hypothesis that activating CARM1 by chemical activators might be therapeutically effective in breast cancer. Selective, potent, cell‐permeable CARM1 activators will be essential to test this hypothesis. Here we report the development of a cell‐based, time‐resolved (TR) FRET assay that uses poly(A) binding protein 1 (PABP1) methylation to monitor cellular activity of CARM1. The LanthaScreen TR‐FRET assay uses MCF7 cells expressing GFP‐PABP1 fusion protein through BacMam gene delivery system, methyl‐PABP1 specific antibody, and terbium‐labeled secondary antibody. This assay has been validated as reflecting the expression and/or activity of CARM1 and optimized for high throughput screening to identify CARM1 allosteric activators. This TR‐FRET platform serves as a generic tool for functional screening of cell‐permeable, chemical modulators of CARM1 for elucidation of its in vivo functions.     

Arrhythmogenic Cardiomyopathy: Exercise Pitfalls,Role of Connexin-43, and Moving beyond Antiarrhythmics

Arrhythmogenic Cardiomyopathy (ACM), a Mendelian disorder that can affect both left and right ventricles, is most often associated with pathogenic desmosomal variants that can lead to fibrofatty replacement of the myocardium, a pathological hallmark of this disease. Current therapies are aimed to prevent the worsening of disease phenotypes and sudden cardiac death (SCD). Despite the use of implantable cardioverter defibrillators (ICDs) there is no present therapy that would mitigate the loss in electrical signal and propagation by these fibrofatty barriers. Recent studies have shown the influence of forced vs. voluntary exercise in a variety of healthy and diseased mice; more specifically, that exercised mice show increased Connexin-43 (Cx43) expression levels. Fascinatingly, increased Cx43 expression ameliorated the abnormal electrical signal conduction in the myocardium of diseased mice. These findings point to a major translational pitfall in current therapeutics for ACM patients, who are advised to completely cease exercising and already demonstrate reduced Cx43 levels at the myocyte intercalated disc. Considering cardiac dysfunction in ACM arises from the loss of cardiomyocytes and electrical signal conduction abnormalities, an increase in Cx43 expression—promoted by low to moderate intensity exercise and/or gene therapy—could very well improve cardiac function in ACM patients.