Platinum and Palladium Organometallic Compounds: Disrupting the Ergosterol Pathway in Trypanosoma cruzi

Current treatment for Chagas’ disease is based on two drugs, Nifurtimox and Benznidazol, which have limitations that reduce the effectiveness and continuity of treatment. Thus, there is an urgent need to develop new, safe and effective drugs. In previous work, two new metal-based compounds with trypanocidal activity, Pd-dppf-mpo and Pt-dppf-mpo, were fully characterized. To unravel the mechanism of action of these two analogous metal-based drugs, high-throughput omics studies were performed. A multimodal mechanism of action was postulated with several candidates as molecular targets. In this work, we validated the ergosterol biosynthesis pathway as a target for these compounds through the determination of sterol levels by HPLC in treated parasites. To understand the molecular level at which these compounds participate, two enzymes that met eligibility criteria at different levels were selected for further studies: phosphomevalonate kinase (PMK) and lanosterol 14-α demethylase (CYP51). Molecular docking processes were carried out to search for potential sites of interaction for both enzymes. To validate these candidates, a gain-of-function strategy was used through the generation of overexpressing PMK and CYP51 parasites. Results here presented confirm that the mechanism of action of Pd-dppf-mpo and Pt-dppf-mpo compounds involves the inhibition of both enzymes.     

Algebraic surrogate-based process optimization using Bayesian symbolic learning

Here, we propose a strategy for the global optimization of process flowsheets, a fundamental problem in process systems engineering, based on algebraic surrogates that are built from rigorous simulations via Bayesian symbolic regression. The applied method provides a closed-form expression that can be optimized to global optimality using state-of-the-art solvers, where BARON or ANTIGONE were the solvers of choice. When predicting unseen test data, the algebraic models show a similar accuracy level compared to traditional surrogates based on Gaussian processes. However, they can be more easily optimized to global optimality due to their analytical closed-form structure, which allows the user to apply well-established global deterministic solvers. We show the capabilities of our approach in several case studies, ranging from process units to full flowsheets. The performance of our approach is assessed by comparing the CPU time for model building, the prediction accuracy of the identified model, and the CPU time for the subsequent optimization with a proven benchmark.     

The crystallization of polypropylene in multiwall carbon nanotube‐based composites

The crystallization process of isotactic polypropylene (iPP) was studied under both dynamic and isothermal conditions for a series of multiwall carbon nanotube (MWCNT) composites with nanotube concentrations between 0.1 and 1.0% by weight. The nucleation activity of the nanofillers was confirmed for both dynamic and isothermal crystallization, and was shown to be composition dependent. The effect of the nanofiller on the crystallization of iPP was discussed using the temperature coefficients obtained to determine the interfacial free energy and free energy of nucleation. The basal interfacial free energy decreased with respect to that of neat iPP by up to 15% for as little as 0.1% MWCNT, subsequently decreasing linearly with increasing nanotube concentration. This behavior is in line with the crystallization behavior of iPP with conventional nucleating agents. POLYM. COMPOS., 2011. © 2010 Society of Plastics Engineers     

In‐Situ Growth of Ultrathin Films of NiFe‐LDHs: Towards a Hierarchical Synthesis of Bamboo‐Like Carbon Nanotubes

The synthesis of ultrathin films (UTFs) of NiFe‐LDHs has been achieved by means of an in situ hydrothermal approach, leading to a flat disposition of the LDH crystallites on the substrate, in clear contrast to the most common perpendicular orientation reported to date. Experimental factors like time of synthesis or the nature of the substrate, seem to play a crucial role during the growing process. The 2D morphology of the NiFe‐LDH crystallites was kept after a calcination procedure, leading to a topotactic transformation into mixed‐metal oxide platelets. Hereby, in order to study the catalytic behavior of our samples, a chemical vapor deposition process is explored upon the as‐synthesized films. In presence of a carbon source (ethylene), these films catalyze a preferential low‐temperature (550 °C) growth of bamboo‐like carbon nanotubes, in stark contrast to the different mixture of carbon nanoforms obtained from the bulk samples. This work opens the door for the development of UTFs based on LDHs, which may be of utmost importance in a wide range of potential applications ranging from magnetic storage, catalysis or biomedical applications, to electrochemical batteries, anti‐corrosion and superhydrophobic coatings.     

Distributed manufacturing for electrified chemical processes in a microgrid

To alleviate the greenhouse gas emissions by the chemical industry, electrification has been proposed as a solution where electricity from renewable sources is used to power processes. The adoption of renewable energy is complicated by its spatial and temporal variations. To address this challenge, we investigate the potential of distributed manufacturing for electrified chemical processes installed in a microgrid. We propose a multiscale mixed-integer linear programming model for locating modular electrified plants, renewable-based generating units, and power lines in a microgrid that includes monthly transportation and hourly scheduling decisions. We propose a K-means clustering-based aggregation disaggregation matheuristic to solve the model efficiently. The model and algorithm are tested using a case study with 20 candidate locations in Western Texas. Additionally, we define a new concept, “the Value of the Multi-scale Model,” to demonstrate the additional economic benefits of our model compared with a single-scale model.     

Characterization of pulp calcifications and changes in their composition after treatments with citric acid and ethylenediaminetetraacetic acid solutions

The ectopic calcifications of non-mineralized tissues can occur in several forms throughout life, such as pulpal calcification. The presence of pulp stones is a challenge in endodontic treatment because they partially or fully obliterate the pulp chamber hindering access to root canals and their subsequent shaping. This study aimed to determine their crystallographic properties and evaluate the capacity of citric acid (CA) and ethylenediaminetetraacetic acid (EDTA) to promote the demineralization of pulp calcifications. The samples were obtained from patients with indications of endodontic treatment, and the radiographic examination was suggestive of pulp stone in at least one permanent tooth. The samples were isolated and analyzed by scanning electron microscopy/energy-dispersive x-ray spectroscopy (SEM/EDX). The Fourier Transform by high resolution-transmission electron microscopy, Raman microscopy, and X-ray diffraction (XRD) were used to identify the mineral phase and crystallographic characteristics. To evaluate the effect of CA and EDTA on the crystallinity of calcifications, they were submerged into these two individual solutions and the changes were assessed in situ by Raman spectroscopy. The SEM images obtained from calcifications demonstrated irregular morphologies. EDX of sample surfaces shows a high presence of oxygen, carbon, calcium, and phosphorous, however, other elements such as sodium, magnesium, nitrogen, chlorine, potassium, sulfur, and zinc were identified in less quantity. According to Raman, XRD, and high-resolution transmission electron microscopy, the predominant mineral phase identified in the pulpal calcification was a poor crystallinity apatite. According to in situ analyses, the effect of CA and EDTA was observed on the signals of PO₄³⁻ and CH₂ groups corresponding to inorganic and organic components. The changes with CA were evident at 7 min while the effect of EDTA was observed until 15 min of treatment. All results indicate that pulp stones have a heterogeneous composition principally composed of apatite with low crystallinity. The solubility of these pathological minerals is adequate using solutions such as EDTA or CA; however, the effectivity depends on the mineralization grade of calcifications, time, and concentration of exposition to this chemical.     

A feasible strategy for tailoring stable spray-coated electrolyte layer in micro-tubular solid oxide fuel cells

By this work, the viability of the spray coating as a cost-effective and reliable technique for the coating of Ce_0.9Gd_0.1O_1.95 (GDC) electrolyte layer on the mini-tubular NiO–GDC anodes based a solid oxide fuel cell (SOFC) fabrication was assessed. The compatibility of the anode and electrolyte was analyzed by using XRD. The variation in thickness and morphology of the electrolyte film as a function of the coating cycles was discussed with optical and scanning electron microscopes. By similar formulation, the coating of La_0.6Sr_0.4Fe_0.8Co_0.2O₃ –Ce_0.9Gd_0.1O_2–δ (LSCF–GDC) was performed to achieve porous cathode. An individual micro-tubular anode supported cell with configuration NiO–GDC/GDC/LSCF–GDC as anode/electrolyte/cathode was tested in the SOFC mode with humidified hydrogen as fuel and stationary air as oxidant. The fabricated mini-SOFC prototype that generated a maximum power density of 0.510 W/cm² at 600°C signifies the potential of this industrially scalable low-cost coating technique.