Different drug incorporation routes in ethylene oxide based copolymers

Coumarin is successfully incorporated in poly(ethylene oxide)‐poly(propylene oxide) block copolymers functionalized with terminal alkynes, PEO‐b‐PPO‐b‐GPE, by click reactions at atmospheric pressure and in CO₂ supercritical conditions (scCO₂). The presence of glycidyl propargyl ether (GPE), an alkynyl‐terminated monomer, in the copolymer chain allows the covalent attachment of the coumarin by click chemistry, obtaining polymer–drug conjugates. First, the most suitable synthesis procedure for the above‐mentioned copolymers was established. Then, the click reactions were carried out confirming the coumarin attachment by Fourier transform IR and ¹H NMR analyses, achieving good yields in both cases with a coumarin content of about 9.3 wt% and avoiding the use of toxic solvents in the case of scCO₂. In addition, thanks to the amphiphilic character of the copolymer due to the presence of hydrophilic (PEO) and hydrophobic (PPO) segments, micelle formation is also possible and was confirmed by dynamic light scattering and high resolution SEM. Finally, coumarin incorporation was achieved by micelle formation using the direct dissolution method in order to compare the polymer–drug system properties. This second route allows a drug entrapment efficiency of 14 wt% to be reached. In both cases, the size of the polymeric micelles obtained is in a suitable range to enable permeability. However, an interesting point is the reduction in the size of the micelles with increase in the GPE percentage and with the covalent attachment of the coumarin to the copolymer, which is supposed to improve their permeability. © 2019 Society of Chemical Industry     

Effects of pluronic F68 micellization on the viability of neuronal cells in culture

Triblock copolymers with surface‐active properties, referred to as Pluronic, have shown potential medical applications such as drug delivery to selective targets in the human body. In particular, the transport of anti‐inflammatory substances to the brain is required for illness treatment, thus the study of delivery agents that cross the blood–brain barrier is relevant. In this article we study the effects of the micelle formation on the morphologic and cytotoxic properties of Pluronic F68. We determinate the critical micellar concentration (CMC) by standard tensiometric and absorbance measurements, and also we analyze the morphology of polymers by atomic force microscopy. Our observations indicate that the morphological properties of F68 are drastically modified in the CMC range, as well as the ability to increase the viability of neuroblastoma cells maintained under culture conditions, as compared with nontreated cells. Our conclusions highlight the close correlation between morphological and physiochemical properties of Pluronic, which must be further understood in order to achieve highly controlled pharmacological uses. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 2159–2164, 2013     

Heat inactivation of Listeria innocua in broth and food products under non-isothermal conditions

The objective of this work was to study the effect of three linear temperature profiles (heating rates of 1.5, 1.8 and 2.6 °C/min, from 20 to 65 °C) on Listeria innocua inactivation in liquid medium. The inactivation was also analyzed in artificially contaminated parsley (heating rate of 1.8 °C/min) and throughout a frying process, using a pre-cooked frozen food as case study. Inactivation showed a sigmoidal behaviour and all data was fitted with a Gompertz-inspired model. Results demonstrated that, in liquid media, Listeria inactivation is influenced by the temperature profile used. As heating rate increases, the shoulder decreases and the tail effect disappears. If Listeria was in parsley, its heat resistance increased (for identical experimental conditions in broth). Besides model adequacy was proven in all studied situations, the heating rate affected parameters’ precision.     

DSD: document sparse-based denoising algorithm

Pattern Analysis and Applications - In this paper, we present a sparse-based denoising algorithm for scanned documents. This method can be applied to any kind of scanned documents with satisfactory...     

Probabilistic failure analysis for real glass components under general loading conditions

In this paper, the generalized local model (GLM) is applied to derive the primary failure cumulative distribution function (PFCDF) of annealed glass in order to achieve the failure prediction of structural glass. The uniqueness of the glass characterization is demonstrated irrespective of the test, specimen size, and geometry used. Consequently, the strength of glass is unequivocally derived in a probabilistic way as a material property, so that the definition of normalized testing specimens in international standards might be put under question. Furthermore, the application of the GLM to the results assessment allows to ensure a correct transferability of the laboratory data from simple specimens to the practical design of real glass components and vice versa. The feasibility of the GLM to characterize the strength of annealed glass from different test types is illustrated by means of an extensive experimental program.     

CRISPR/Cas9-RNA interference system for combinatorial metabolic engineering of Saccharomyces cerevisiae

The yeast Saccharomyces cerevisiae is widely used in industrial biotechnology for the production of fuels, chemicals, food ingredients, food and beverages, and pharmaceuticals. To obtain high-performing strains for such bioprocesses, it is often necessary to test tens or even hundreds of metabolic engineering targets, preferably in combinations, to account for synergistic and antagonistic effects. Here, we present a method that allows simultaneous perturbation of multiple selected genetic targets by combining the advantage of CRISPR/Cas9, in vivo recombination, USER assembly and RNA interference. CRISPR/Cas9 introduces a double-strand break in a specific genomic region, where multiexpression constructs combined with the knockdown constructs are simultaneously integrated by homologous recombination. We show the applicability of the method by improving cis,cis-muconic acid production in S. cerevisiae through simultaneous manipulation of several metabolic engineering targets. The method can accelerate metabolic engineering efforts for the construction of future cell factories.