Improvement of the short‐ and long‐term mechanical properties of injection‐molded poly(etheretherketone) and hydroxyapatite nanocomposites

Nanocomposites of polyetheretherketone (PEEK) and hydroxyapatite (HA) nanoparticles treated with a silane coupling agent were successfully prepared by twin screw extrusion and injection molding. Some of the samples were annealed after the injection molding. The silane treatment promoted an improvement of the short‐ and long‐term mechanical properties of the nanocomposites. A higher stress and a six times higher deformation at break and a higher impact strength were observed in the silane‐treated nanocomposites when compared to the nontreated ones. The number of cycles to fail of the treated nanocomposites was almost 200% higher than the number of cycles to fail of the nontreated samples. The treatment also decreased the glass transition temperature and amount of crystallinity of the samples. This improvement in mechanical properties obtained from the silane treatment was attributed to the strengthening of the PEEK/HA interfacial bond, to the plasticization of the PEEK matrix by silane oligomers produced during the processing and to a better dispersion of the HA nanoparticles within the PEEK matrix. Samples annealing, however, diminished all these properties due to the increase in crystallinity. Studies of the short‐ and long‐term mechanical properties of these nanocomposites under physiological conditions and of the proliferation of stem cells are under way. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44476.     

Endothelins inhibit cyclic-AMP induced renin gene expression in cultured mouse juxtaglomerular cells

We have recently described that endothelins-1 to -3 equipotently inhibit cAMP stimulated renin secretion from cultured mouse juxtaglomerular cells by a process involving phospholipase C activation. This study examined the influence of endothelin-2 on renin gene expression in renal juxtaglomerular cells. To this end we semiquantitated renin mRNA levels by competitive RT-PCR in primary cultures of mouse renal juxtaglomerular cells after 20 hours of incubation. We found that endothelin-2 (0.1 to 100 nmol/liter) did not change basal renin gene expression. The adenylate cyclase activator forskolin (3 mumol/ liter) increased renin mRNA levels to 400% of the controls and this stimulation was dose-dependently attenuated by ET-2 to 250% of the control value. The effect of ET-2 was mimicked by the ETB-receptor agonist sarafotoxin S6c. The kinase inhibitor staurosporine (100 nmol/ liter) increased renin secretion and renin mRNA levels. Combination of staurosporine with forskolin produced the same effects on renin secretion and renin mRNA levels as did staurosporine alone. In the presence of both forskolin and staurosporine ET-2 had no significant effect on renin secretion and renin gene expression. The phorbol ester PMA (30 nmol/ liter), which was used to stimulate protein kinase C activity, attenuated cAMP stimulated renin secretion and renin mRNA levels. Lowering the extracellular concentration of calcium by the addition of 1 mmol/liter EGTA did not inhibit the effect of ET-2 on cAMP induced renin secretion and renin gene expression. These findings suggest that endothelins inhibit cAMP stimulated renin gene expression by an event that is mediated via ETB receptors. This inhibitory effect may in part involve protein kinase C activation.     

Improvement of response times in electrochromic switchable nematic emulsions

Electrochromic nematic emulsion can be obtained by fast cooling of isotropic mixtures of electrochromic mixture, nematic liquid crystal and monomers. Films obtained with this procedure show very low saturation fields but rather long relaxation times. In this paper we have doped nematic electrochromic emulsions with surfactant agents, in order to obtain a good compromise between low saturation fields and fast relaxation times. The decay time decreases in a significant way and the saturation field is slightly affected by the addition of small amounts of surfactant.     

Distribution of KIR Genes and Their HLA Ligands in Different Viral Infectious Diseases: Frequency Study in Sicilian Population

Natural killer (NK) cells play a role in defence against viral infections by killing infected cells or by producing cytokines and interacting with adaptive immune cells. Killer immunoglobulin-like receptors (KIRs) regulate the activation of NK cells through their interaction with human leucocyte antigens (HLA). Ninety-six Sicilian patients positive to Human Immunodeficiency Virus-1 (HIV) and ninety-two Sicilian patients positive to SARS-CoV-2 were genotyped for KIRs and their HLA ligands. We also included fifty-six Sicilian patients with chronic hepatitis B (CHB) already recruited in our previous study. The aim of this study was to compare the distribution of KIR–HLA genes/groups of these three different infected populations with healthy Sicilian donors from the literature. We showed that the inhibitory KIR3DL1 gene and the KIR3DL1/HLA-B Bw4 pairing were more prevalent in individual CHB. At the same time, the frequency of HLA-C2 was increased in CHB compared to other groups. In contrast, the HLA-C1 ligand seems to have no contribution to CHB progression whereas it was significantly higher in COVID-19 and HIV-positive than healthy controls. These results suggest that specific KIR–HLA combinations can predict the outcome/susceptibility of these viral infections and allows to plan successful customized therapeutic strategies.     

Ataxia-Telangiectasia Mutated Loss of Heterozygosity in Melanoma

ATM germline pathogenic variants were recently found enriched in high-risk melanoma patients. However, ATM loss of heterozygosity (LOH) has never been investigated in melanoma and, therefore, a causal association with melanoma development has not been established yet. The purpose of this study was to functionally characterize 13 germline ATM variants found in high-risk melanoma patients—and classified by in silico tools as pathogenic, uncertain significance, or benign—using multiple assays evaluating ATM/pATM expression and/or LOH in melanoma tissues and cell lines. We assessed ATM status by Immunohistochemistry (IHC), Western Blot, Whole-Exome Sequencing/Copy Number Variation analysis, and RNA sequencing, supported by Sanger sequencing and microsatellite analyses. For most variants, IHC results matched those obtained with in silico classification and LOH analysis. Two pathogenic variants (p.Ser1135_Lys1192del and p.Ser1993ArgfsTer23) showed LOH and complete loss of ATM activation in melanoma. Two variants of unknown significance (p.Asn358Ile and p.Asn796His) showed reduced expression and LOH, suggestive of a deleterious effect. This study, showing a classic two-hit scenario in a well-known tumor suppressor gene, supports the inclusion of melanoma in the ATM-related cancer spectrum.     

An arc flow formulation to the multitrip production,inventory, distribution,and routing problem with time windows

The multitrip production, inventory, distribution, and routing problem with time windows (MPIDRPTW) is an integrated problem that combines a production and distribution problem, a multitrip vehicle routing problem, and an inventory routing problem. In the MPIDRPTW, a set of customers, which have a time-varying demand during a finite planning horizon, is served by a single production facility. The distribution is accomplished by a fleet of homogeneous vehicles that deliver the customer orders within their specific time windows. Production management has to be done according to the inventories at the facility and at the customers. An exact arc flow model based on a graph is proposed to solve the MPIDRPTW, where the nodes represent instants of time. The main goal of the problem is to minimize the costs associated with the entire system. The proposed approach was implemented and a set of experimental tests were conducted based on a set of adapted instances from the literature.     

Biomarkers Related to Synaptic Dysfunction to Discriminate Alzheimer’s Disease from Other Neurological Disorders

Recently, the synaptic proteins neurogranin (Ng) and α-synuclein (α-Syn) have attracted scientific interest as potential biomarkers for synaptic dysfunction in neurodegenerative diseases. In this study, we measured the CSF Ng and α-Syn concentrations in patients affected by AD (n = 69), non-AD neurodegenerative disorders (n-AD = 50) and non-degenerative disorders (n-ND, n = 98). The concentrations of CSF Ng and α-Syn were significantly higher in AD than in n-AD and n-ND. Moreover, the Aβ42/Ng and Aβ42/α-Syn ratios showed statistically significant differences between groups and discriminated AD patients from n-AD patients, better than Ng or α-Syn alone. Regression analyses showed an association of higher Ng concentrations with MMSE < 24, pathological Aβ 42/40 ratios, pTau, tTau and the ApoEε4 genotype. Aβ 42/Ng was associated with MMSE < 24, an AD-related FDG-PET pattern, the ApoEε4 genotype, pathological Aβ 42 levels and Aβ 42/40 ratios, pTau, and tTau. Moreover, APO-Eε4 carriers showed higher Ng concentrations than non-carriers. Our results support the idea that the Aβ 42/Ng ratio is a reliable index of synaptic dysfunction/degeneration able to discriminate AD from other neurological conditions.     

A traditional aboriginal condiment as an antioxidant agent in the development of biodegradable active packaging

In this study, antioxidant food‐packaging materials were developed by the incorporation of merkén, an aboriginal Chilean spice, into a biodegradable polymer matrix, poly(lactic acid). Antioxidant activity assays and the phenolic content of merkén showed interesting results compared to other condiments, such as oregano and parsley. Active materials with merkén at 3 and 5 wt % were successfully obtained by extrusion. Chromatographic analysis revealed the chemical composition of merkén, and its active material was based on interesting flavonoids and organic acids, such as catechin, myricetin, and gallic and ellagic acids. Scanning electron micrographs showed that the merkén particles accumulated in aggregates; this resulted in an increase in the permeability values and a reduction in the crystallinity and mechanical properties of the polymer matrix. Nevertheless, these materials presented interesting antioxidant activities as radical scavengers on aqueous food simulants. The kinetics of release was dependent on the type of food and the nominal content of merkén in the films. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44692.     

Production of double‐walled nanoparticles containing meloxicam

Double‐walled nanospheres, containing meloxicam, were fabricated with poly‐(D,L ‐lactide‐co‐glycolide) (PLGA) and poly(L ‐lactide) (PLLA) using the solvent evaporation technique. This article discusses the effect of formulation variables [sonication power, sonication time, concentration of poly(vinyl alcohol), organic/aqueous volume ratio in the first emulsion] on the production of double‐walled nanospheres. The involved phase separation of these two polymers was investigated using differential scanning calorimetry. Double‐walled microspheres containing meloxicam were also produced to determine the composition of the shell and core polymer, based on different solubilities of polymers in ethyl acetate, and to examine the inner morphology and drug distribution using optical and fluorescence microscopy. The produced microparticles have shown a double‐walled structure with meloxicam solubilized in the PLGA‐rich phase. Therefore, adjusting the selected formulation variables and using a mass ratio of 1:1 PLLA/PLGA, double‐walled nanospheres where meloxicam is dispersed within the core can be produced. POLYM. ENG. SCI., 2013. © 2012 Society of Plastics Engineers