In vitro interactions between DMSA-coated maghemite nanoparticles and human fibroblasts: A physicochemical and cyto-genotoxical study

Although the current production of oxide nanoparticles may be modest, the wide range of proposed applications and forecasted growth in production has raised questions about the potential impact of these nanoparticles on the environment and human health. Iron oxide nanoparticles have been proposed for an increasing number of biomedical applications although in vitro toxicity depending on the particles coating has been evidenced. The aim of this study was to examine the potential in vitro cyto- and genotoxicity on human dermal fibroblasts of DMSA-coated maghemite nanoparticles (NmDMSA) as a function of well-defined physicochemical states. Well-stabilized NmDMSA produced weak cytotoxic and no genotoxic effects. This is attributed in part to the DMSA coating, which serves as a barrier for a direct contact between nano-oxide and fibroblasts, inhibiting a potential toxic effect.     

Evolution of aroma compounds of murtilla fruits (Ugni molinae Turcz) during storage

BACKGROUND: ‘Murtilla’, ‘mutilla’ or ‘murta’ (Ugni molinae Turcz) is a native Chilean species that produces a small berry fruit with a special aroma, whose volatile compounds have not yet been identified. The fruit may be consumed raw and also as jams, juice, canned products, confections and liquor. RESULTS: At the beginning and end of the storage, 24 volatile compounds were identified in murtilla fruit aroma and the concentration of these compounds in murtilla fruit ranged from 1.2 to 250.5 µg kg^?1 fresh weight. Methyl 2‐methyl butanoate, ethyl butanoate, ethyl 2‐methyl butanoate, methyl hexanoate, ethyl hexanoate, methyl benzoate and ethyl benzoate were the major components, all of which have been reported as potent odors in other aromatic fruits. Based on estimated odor activity value, the most potent compound in the murtilla fruit aroma were ethyl hexanoate and 4‐methoxy‐2,5‐dimethyl‐furan‐3‐one. The statistical analysis showed that the storage produced a distinct effect on the same volatile compounds released from the murtilla ecotypes. CONCLUSION: The volatile compounds identified in murtilla fruit aroma, which may be described as fruity, sweet and floral, have been found in other aromatic fruits. Concerning the aroma, the murtilla fruit from ecotype 19‐1 was shown to be the best in cooled storage. Copyright © 2007 Society of Chemical Industry     

Thermoplastic encapsulations of a sensor platform by high‐temperature injection molding up to 360°C

For bioprotective encapsulated Internet of Things (IoT) electronics for the medical market, especially for cost‐effective, single or multiple use, injection molding will be of major importance. The stresses from the production process pose special challenges for electronics. The aim of the study was the simulative and experimental characterization of the load spectrum from the injection molding process and its effects on electronics. General recommendations for the encapsulation of IoT electronics in polymer matrices were derived. A microcontroller‐controlled temperature sensor board and a suitable injection mold were developed. Eight circumferential NTC‐sensors measured the prevailing thermal load directly on the component during overmolding. A simulation model allowed statements on the loads to be made about individual components, validated in experimental tests. In addition to PP and PMMA, PSU with a melt temperature of 360°C was tested. The temperature influence of the melt could be described as a function of the component position. The loss of adhesion, shrinkage, distortion, cavities, and delamination were analyzed using micrograph analysis. Complete functionality of the electronics was ensured after encapsulation. Optimization strategies were developed for the design of both IoT electronics and the injection mold. Novel concepts such as interlayer or backfill vias could be derived for future research approaches. POLYM. ENG. SCI., 59:1315–1331 2019. © 2019 Society of Plastics Engineers     

Blueberries and Their Anthocyanins: Factors Affecting Biosynthesis and Properties

Abstract: Blueberry is one of the most popular fruits in North America and rich in anthocyanins. Its content in anthocyanins contributes to the health‐beneficial effects of blueberry against several chronic diseases including cardiovascular disorders, neurodegenerative diseases, diabetes, and cancer. This paper summarizes various facts presenting blueberry as a fruit with huge potential for increased future consumption as a health‐enhancing food. Factors affecting the biosynthesis of the various anthocyanins in blueberries, including agronomic and genetic factors, and the possible pathways of biosynthesis of the major anthocyanins present in this plant are discussed. The important health‐beneficial effects associated with blueberry anthocyanins, properties of these anthocyanins leading to the beneficial effects, and food processing parameters leading to the depletion of the amounts of anthocyanins present in the final processed products are also briefly discussed. Furthermore, the general methods of extraction and analyses that have been reported for being successfully applied to blueberry anthocyanins are also reviewed. Practical Application: Blueberries are well known for their nutritional and beneficial health effects, however, information concerning the physiology behind the blueberry beneficial effects is still lacking. There is little or no information on the characterization of growing conditions on anthocyanins in blueberries and research is lagging behind on advanced methods of extracting blueberry anthocyanins.     

Allele-Specific Inhibition of Histone Demethylases

Histone demethylases play a critical role in mammalian gene expression by removing methyl groups from lysine residues in degree- and site-specific manner. To specifically interrogate members and isoforms of this class of enzymes, we have developed demethylase variants with an expanded active site. The mutant enzymes are capable of performing lysine demethylation with wild-type proficiency, but are sensitive to inhibition by cofactor-competitive molecules embellished with a complementary steric “bump”. The selected inhibitors show more than 20-fold selectivity over the wild-type demethylase, thus overcoming issues typical to pharmacological and genetic approaches. The mutant–inhibitor pairs are shown to act on a physiologically relevant full-length substrate. By engineering a conserved amino acid to achieve member-specific perturbation, this study provides a general approach for studying histone demethylases in diverse cellular processes.     

Quantitative Assessment of Affinity Selection Performance by Using DNA-Encoded Chemical Libraries

DNA-encoded chemical libraries are often used for the discovery of ligands against protein targets of interest. These large collections of DNA-barcoded chemical compounds are typically screened by using affinity capture methodologies followed by PCR amplification and DNA sequencing procedures. However, the performance of individual steps in the selection procedures has been scarcely investigated, so far. Herein, the quantitative analysis of selection experiments, by using three ligands with different affinity to carbonic anhydrase IX as model compounds, is described. In the first set of experiments, quantitative PCR (qPCR) procedures are used to evaluate the recovery and selectivity for affinity capture procedures performed on different solid-phase supports, which are commonly used for library screening. In the second step, both qPCR and analysis of DNA sequencing results are used to assess the recovery and selectivity of individual carbonic anhydrase IX ligands in a library, containing 360 000 compounds. Collectively, this study reveals that selection procedures can be efficient for ligands with sub-micromolar dissociation constants to the target protein of interest, but also that selection performance dramatically drops if 10⁴ copies per library member are used as the input.     

Development of Phosphodiesterase–Protein-Kinase Complexes as Novel Targets for Discovery of Inhibitors with Enhanced Specificity

Phosphodiesterases (PDEs) hydrolyze cyclic nucleotides to modulate multiple signaling events in cells. PDEs are recognized to actively associate with cyclic nucleotide receptors (protein kinases, PKs) in larger macromolecular assemblies referred to as signalosomes. Complexation of PDEs with PKs generates an expanded active site that enhances PDE activity. This facilitates signalosome-associated PDEs to preferentially catalyze active hydrolysis of cyclic nucleotides bound to PKs and aid in signal termination. PDEs are important drug targets, and current strategies for inhibitor discovery are based entirely on targeting conserved PDE catalytic domains. This often results in inhibitors with cross-reactivity amongst closely related PDEs and attendant unwanted side effects. Here, our approach targeted PDE–PK complexes as they would occur in signalosomes, thereby offering greater specificity. Our developed fluorescence polarization assay was adapted to identify inhibitors that block cyclic nucleotide pockets in PDE–PK complexes in one mode and disrupt protein-protein interactions between PDEs and PKs in a second mode. We tested this approach with three different systems—cAMP-specific PDE8–PKAR, cGMP-specific PDE5–PKG, and dual-specificity RegA–R_D complexes—and ranked inhibitors according to their inhibition potency. Targeting PDE–PK complexes offers biochemical tools for describing the exquisite specificity of cyclic nucleotide signaling networks in cells.     

The effects of porosity,asphalt content and fiberglass incorporation on the tensile strength and resilient modulus of asphalt concrete blends

Asphalt concrete is the prevailing material used for road surface construction. Its adequate characteristics in providing stability, durability and driving safety are controlled by complex interactions between its components. Thus, it is important to estimate the sensitivity of asphalt concrete mechanical properties as a function of its volumetrics. For this study, different combinations between asphalt content (3.5, 5 and 7.5%) and porosity values (above 4%) were used in order to disassociate these properties. The influence of mixing in fiberglass (0.5%) was also analyzed. It was found that porosity is significantly more relevant than the asphalt content in the prediction of tensile strength and resilient modulus of fiber-free asphalt concretes. In fiber-reinforced mixtures, the mechanical properties are improved by increasing the asphalt content, which suggests a better bonding between fibers and aggregates. For both cases, decreasing porosity is beneficial. By grouping both sets of results, it was possible to create a unique theoretical curve for both the tensile strength (q_t) and the resilient modulus (RM). The RM/q_t ratio was 5800 for the fiber-free group, and 3900 for the fiber-reinforced group - suggesting a better fatigue life indicator for asphalt concretes when fibers are added.     

An adaptive clinical decision support system for serving the elderly with chronic diseases in healthcare industry

With the increasing ageing population worldwide, providing effective nursing care planning in nursing homes is important in meeting the expectations of elderly patients and in streamlining the healthcare information process, hence maintaining high‐quality services. Instead of the traditional manual nursing care planning formulation based on expert experience and subjective judgement, this paper describes an adaptive decision support system, namely, the cloud‐based nursing care planning system, to enable decision making in formulating nursing care strategies. By integrating cloud computing technology and the case‐based reasoning (CBR) technique, medical records and documents pertaining to the elderly can be captured in real time, whereas appropriate treatment plans based on past similar treatment records can be formulated. However, the current case adaptation processes in CBR rely on domain experts to modify retrieved cases, which may not satisfy the needs of the elderly. Therefore, text mining is integrated in the case adaptation process of CBR for extracting up‐to‐date medical information from the Internet so that its efficiency can be improved. By conducting a pilot study in a nursing home, it was shown that the time for formulating applicable treatment plans for elderly patients can be reduced, and the service satisfaction level can be enhanced.     

The assessment of compositional changes in Nimonic PE16 by convergent beam electron diffraction

Lattice parameter changes can be detected by the use of a previously established technique which is based upon computer simulation of HOLZ patterns. This simulation technique is then applied to two precipitation phenomena in Nimonic PE16. Firstly, the growth of gamma prime, γ, precipitates from a solid solution is monitored via the decrease in lattice parameter of the parent phase, and secondly the lattice parameter of coarsened, overaged γ is measured for precipitates sited both at grain boundaries and within grains. The variations thus detected between intergranular and intragranular precipitates are attributed to changes in the Ti/Al ratio due to preferential γ coarsening at the grain boundary. The very subtle compositional changes inferred (～1 at. % Ti) would have been very difficult to establish by chemical analysis, but can be easily measured by convergent beam electron diffraction.