Preparation,characterization and properties of polycaprolactone diol-functionalized multi-walled carbon nanotube/thermoplastic polyurethane composite

Multi-walled carbon nanotubes (MWCNTs) were chemically functionalized to prepare thermoplastic polyurethane (PU) composites with enhanced properties. In order to achieve a high compatibility of functionalized MWCNTs with the PU matrix, polycaprolactone diol (PCL), as one of PU’s monomers, was selectively grafted on the surface of MWCNTs (MWCNT–PCL), while carboxylic acid groups functionalized MWCNTs (MWCNT–COOH) and raw MWCNTs served as control. Both MWCNT–COOH and MWCNT–PCL improved the dispersion of MWCNTs in the PU matrix and interfacial bonding between them at 1 wt% loading fraction. The MWCNT–PCL/PU composite showed the greatest extent of improvement, where the tensile strength and modulus were 51.2% and 33.5% higher than those of pure PU respectively, without sacrificing the elongation at break. The considerable improvement in both mechanical properties and thermal stability of MWCNT–PCL/PU composite should result from the homogeneous dispersion of MWCNT–PCL in the PU matrix and strong interfacial bonding between them.     

Polymer derived ceramic materials from Si,B and MoSiB filler-loaded perhydropolysilazane precursor for oxidation protection

Silica-based coating systems were developed using polymer derived ceramics (PDCs) technology. Ceramic composites on the base of a SiO₂ and SiNO matrix and homogeneously distributed Mo₅SiB₂, SiB₆, Si and B fillers were manufactured. The coating systems have low porosity and provide a high oxidation resistance up to 100 h at 800 °C and 1100 °C in air. The influence of temperature and atmosphere of pyrolysis on the polymer precursor, the volume fraction of filler materials on the chemical composition of compacts as well as their high-temperature oxidation protection was investigated.     

Stability and cytotoxicity study of NiFe2O4 nanocomposites synthesized by co-precipitation and subsequent thermal annealing

In this article, NiFe₂O₄ nanoparticles (NPs) were prepared by co-precipitation method with subsequent thermal annealing leading to obtainment NPs with average sizes of 78 nm. Structure and magnetic analysis were performed by X-ray diffraction, transmission electron microscopy, Mössbauer spectroscopy and vibrating sample magnetometry techniques. Stability of NiFe₂O₄ NPs was evaluated in PBS solution during 20 days. The toxicity of prepared NPs was evaluated in vitro using different cancer cell lines: HeLa (cervical cancer cell), PC-3 (prostate cancer cell). Fibroblasts like cells of L929 obtained from subcutaneous adipose tissue of mouse were used as normal cells. Results indicate successful synthesis of NiFe₂O₄ NPs that exhibit low cytotoxicity in concentration range from 1 to 100 μg/ml. Presented physical and biological results indicate the possibility of application investigated magnetic nanoparticles in hyperthermia, targeted drug delivery, magnetic resonance imaging or cell separation.     

Characterizing physical habitat preferences and thermal refuge occupancy of brook trout (Salvelinus fontinalis) and Atlantic salmon (Salmo salar) at high river temperatures

Anthropogenic influences, including climate change, are increasing river temperatures in northern and temperate regions and threatening the thermal habitats of native salmonids. When river temperatures exceed the tolerance levels of brook trout and Atlantic salmon, individuals exhibit behavioural thermoregulation by seeking out cold‐water refugia – often created by tributaries and groundwater discharge. Thermal infrared (TIR) imagery was used to map cold‐water anomalies along a 53 km reach of the Cains River, New Brunswick. Trout and salmon parr did not use all identified thermal anomalies as refugia during higher river temperature periods (>21°C). Most small‐bodied trout (8–30 cm) were observed in 80% of the thermal anomalies sampled. Large‐bodied trout (>35 cm) required a more specific set of physical habitat conditions for suitable refugia, that is, 100% of observed large trout used 30% of the anomalies sampled and required water depths >65 cm within or adjacent to the anomaly. Densities of trout were significantly higher within anomalies compared with areas of ambient river temperature. Salmon parr were less aligned with thermal anomalies at the observed temperatures, that is, 59% were found in 65% of the sampled anomalies; and densities were not significantly different within/ outside anomalies. Salmon parr appeared to aggregate at 27°C, and after several events over 27°C variability in aggregation behaviour was observed – some fish aggregated at 25°C, others did not. We stipulate this is due to variances of thermal fatigue. Habitat suitability curves were developed for velocity, temperature, depth, substrate, and deep water availability to characterize conditions preferred by fish during high‐temperature events. These findings are useful for managers as our climate warms, and can potentially be used as a tool to help conserve and enhance thermal refugia for brook trout and Atlantic salmon in similar systems.     

Sofosbuvir Selects for Drug-Resistant Amino Acid Variants in the Zika Virus RNA-Dependent RNA-Polymerase Complex In Vitro

The nucleotide analog sofosbuvir, licensed for the treatment of hepatitis C, recently revealed activity against the Zika virus (ZIKV) in vitro and in animal models. However, the ZIKV genetic barrier to sofosbuvir has not yet been characterized. In this study, in vitro selection experiments were performed in infected human hepatoma cell lines. Increasing drug pressure significantly delayed viral breakthrough (p = 0.029). A double mutant in the NS5 gene (V360L/V607I) emerged in 3 independent experiments at 40–80 µM sofosbuvir resulting in a 3.9 ± 0.9-fold half- maximal inhibitory concentration (IC₅₀) shift with respect to the wild type (WT) virus. A triple mutant (C269Y/V360L/V607I), detected in one experiment at 80 µM, conferred a 6.8-fold IC₅₀ shift with respect to the WT. Molecular dynamics simulations confirmed that the double mutant V360L/V607I impacts the binding mode of sofosbuvir, supporting its role in sofosbuvir resistance. Due to the distance from the catalytic site and to the lack of reliable structural data, the contribution of C269Y was not investigated in silico. By a combination of sequence analysis, phenotypic susceptibility testing, and molecular modeling, we characterized a double ZIKV NS5 mutant with decreased sofosbuvir susceptibility. These data add important information to the profile of sofosbuvir as a possible lead for anti-ZIKV drug development.     

The Critical Role of Passive Permeability in Designing Successful Drugs

Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients.     

Invader amphipods Gmelinoides fasciatus (Stebbing, 1899) inhabiting distant waterbodies demonstrate differences in tolerance and energy metabolism under elevated temperatures

Gmelinoides fasciatus is a successful invasive amphipod (Amphipoda, Crustacea) that dispersed from Lake Baikal to various waterbodies. Here we studied whether Baikal conditions are optimal for G. fasciatus in terms of thermotolerance and investigated lethal temperatures, 70 kDa heat shock protein level, energy metabolism, and antioxidant defense of animals from three geographically distant waterbodies under changing temperatures. We used acute heat exposure to 28 °C to assess the median lethal times and gradual temperature increase from 6 °C to determine the lethal temperatures. Mortality under heat shock was explainable by the baseline content of Hsp70 that correlated with thermal history. But it was not the case under gradual temperature increase where Hsp70 levels became similar and the mortality pattern changed. The most thermotolerant amphipods from the Gulf of Finland demonstrated a higher amount of free glucose during the temperature increase that may be related to the higher salinity of this waterbody and less energy required for ion regulation. Even though concentrations of major physiological ions in Lake Baikal are lower than in Lake Ladoga, G. fasciatus from Ladoga was slightly more sensitive to the gradual temperature increase. This difference could be explained by the influence of high levels of humic and other potentially toxic substances in Lake Ladoga indicated by increased activities of catalase and glutathione S-transferase. Importantly, all G. fasciatus populations accumulated relatively low levels of lactate during the temperature increase, which may reflect the ability of this invasive species to effectively maintain aerobic metabolism under various conditions.     

Calorimetric study of ytterbium orthovanadate YbVO4 polycrystalline ceramics

The heat capacity of ytterbium orthovanadate was first measured by adiabatic calorimetry in the temperature range T?=?12.28–344.06?K. No obvious anomalies were observed on the curve obtained. The values of standard thermodynamic functions in the temperature range T?=?0–400 K were calculated. Based on low-temperature calorimetry data obtained, previously published data on the high-temperature heat capacity of ytterbium orthovanadate were corrected. The anomalous contribution to heat capacity for YbVO₄ was compared with the data known for YbPO₄.