Structure-Activity Relationship Explorations and Discovery of a Potent Antagonist for the Free Fatty Acid Receptor 2

Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, there is still a need for improved compounds. One of the most potent and frequently used antagonists is the amide-substituted phenylbutanoic acid known as CATPB ( 1 ). We here report the structure-activity relationship exploration of this compound, leading to the identification of homologues with increased potency. The preferred compound 37 (TUG-1958) was found, besides improved potency, to have high solubility and favorable pharmacokinetic properties.     

Precipitous weakening of quartz at the α–β phase inversion

Crystalline quartz has long been identified as among the weakest of abundant crustal minerals. This weakness is particularly evident around the α–β phase inversion at 573°C, in which Si–O bonds undergo a displacive structural transformation from trigonal to hexagonal symmetry. Here we present data using indentation testing methodologies that highlight the precipitous extent of the transformational weakening. Although the indentations are localized over relatively small specimen contact areas, the data quantify the essential deformation and fracture properties of quartz in a predominantly (but not exclusively) compressive stress field, at temperatures and pressures pertinent to conditions in the earth's crust.     

Cocaine Induces Cytoskeletal Changes in Cardiac Myocytes: Implications for Cardiac Morphology

Cocaine is one of the most widely abused illicit drugs worldwide and has long been recognised as an agent of cardiac dysfunction in numerous cases of drug overdose. Cocaine has previously been shown to up-regulate cytoskeletal rearrangements and morphological changes in numerous tissues; however, previous literature observes such changes primarily in clinical case reports and addiction studies. An investigation into the fundamental cytoskeletal parameters of migration, adhesion and proliferation were studied to determine the cytoskeletal and cytotoxic basis of cocaine in cardiac cells. Treatment of cardiac myocytes with cocaine increased cell migration and adhesion (p < 0.05), with no effect on cell proliferation, except with higher doses eliciting (1–10 μg/mL) its diminution and increase in cell death. Cocaine downregulated phosphorylation of cofilin, decreased expression of adhesion modulators (integrin-β3) and increased expression of ezirin within three hours of 1 μg/mL treatments. These functional responses were associated with changes in cellular morphology, including alterations in membrane stability and a stellate-like phenotype with less compaction between cells. Higher dose treatments of cocaine (5–10 μg/mL) were associated with significant cardiomyocyte cell death (p < 0.05) and loss of cellular architecture. These results highlight the importance of cocaine in mediating cardiomyocyte function and cytotoxicity associated with the possible loss of intercellular contacts required to maintain normal cell viability, with implications for cardiotoxicity relating to hypertrophy and fibrogenesis.     

Status of Mysis diluviana in Lake Ontario in 2013: Lower abundance but higher fecundity than in the 1990s

Mysis diluviana is a major component of prey fish diets in the Great Lakes, so annual production of M. diluviana is important for understanding and modeling energy flow through Great Lakes food webs. However, only three lake-wide measurements of M. diluviana annual production in Lake Ontario are currently available (1971, 1990, 1995). During 2013, lake-wide coverage of Lake Ontario was achieved during four periods from April to November. Annual mean density and biomass of M. diluviana in 2013 were 99?#/m² (SE: 8) and 318?mg?dw/m² (SE: 28) – approximately half of values observed in 1990s. M. diluviana comprised 13–30% of offshore zooplankton biomass in each period. Reproduction peaked in fall, with mean brood size of 32 embryos (range: 11–49), at least 10% larger than in 1990s. Generation time was two years from embryo to initial reproduction. Growth rates were 0.052?mm/d for the age-0 cohort and 0.027?mm/d for the age-1 cohort. Age-0 growth rate was significantly higher than in 1980s–90s (0.035?mm/d). Annual production in 2013 was 0.85?g?dw/m²/yr (SE: 0.03) which was 30–40% of values observed in 1990 and 1995 (2.23 and 2.53?g/m²/yr). Annual production to biomass ratio (P/B) in 2013 was 2.65?/yr which was 80–85% of values observed in 1990 and 1995 (3.24 and 3.11?/yr), but this difference was not statistically significant. Our results suggest that changes in annual production over time can be estimated using changes in biomass over time and a mean P/B ratio.     

A new solid‐state mode of hot corrosion at temperatures below 700°C

Preliminary results on a single‐crystal nickel‐based superalloy indicated that hot corrosion can occur at temperatures as low as 550°C, where liquid formation, generally believed to be responsible for Type II hot corrosion, is not predicted. Additional tests were conducted on pure‐nickel samples at 650°C and below to more clearly elucidate the mechanism of this very low‐temperature hot corrosion. Environments in dry air and O₂‐(2.5, 10, 100, and 1000) ppm SO₂ were studied. Based on the results obtained, a solid‐state corrosion mechanism was inferred. The mechanism relies on the formation of a previously unreported compound phase, which was identified using transmission electron microscope analysis that indicated the stoichiometry of Na₂Ni₂SO₅. Furthermore, it was nanocrystalline in structure and metastable. It was deduced that the Na₂Ni₂SO₅ formation was responsible for the rapid nickel transport required for the observed accelerated corrosion process. Moreover, its eventual decomposition resulted in a mixed product of porous NiO with embedded particles of Na₂SO₄. Application of the proposed mechanism to nickel‐based alloys is discussed.     

Trans-differentiation of human adipose-derived mesenchymal stem cells into cardiomyocyte-like cells on decellularized bovine myocardial extracellular matrix-based films

In this study, we aimed at fabricating decellularized bovine myocardial extracellular matrix-based films (dMEbF) for cardiac tissue engineering (CTE). The decellularization process was carried out utilizing four consecutive stages including hypotonic treatment, detergent treatment, enzymatic digestion and decontamination, respectively. In order to fabricate the dMEbF, dBM were digested with pepsin and gelation process was conducted. dMEbF were then crosslinked with N-hydroxysuccinimide/1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide (NHS/EDC) to increase their durability. Nuclear contents of native BM and decellularized BM (dBM) tissues were determined with DNA content analysis and agarose-gel electrophoresis. Cell viability on dMEbF for 3rd, 7th, and 14th days was assessed by MTT assay. Cell attachment on dMEbF was also studied by scanning electron microscopy. Trans-differentiation capacity of human adipose-derived mesenchymal stem cells (hAMSCs) into cardiomyocyte-like cells on dMEbF were also evaluated by histochemical and immunohistochemical analyses. DNA contents for native and dBM were, respectively, found as 886.11?±?164.85 and 47.66?±?0.09?ng/mg dry weight, indicating a successful decellularization process. The results of glycosaminoglycan and hydroxyproline assay, and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), performed in order to characterize the extracellular matrix (ECM) composition of native and dBM tissue, showed that the BM matrix was not damaged during the proposed method. Lastly, regarding the histological study, dMEbF not only mimics native ECM, but also induces the stem cells into cardiomyocyte-like cells phenotype which brings it the potential of use in CTE.     

Thermodynamic performance analysis of three solid oxide fuel cell and gas microturbine hybrid systems for application in auxiliary power units

In this study, three different configurations of a solid oxide fuel cell and gas microturbine hybrid system are evaluated for application in auxiliary power units. The first configuration is a common hybrid system in auxiliary power units, utilizing a fuel cell stack in the structure of the gas turbine cycle. The other configurations use two series and parallel fuel cell stacks in the structure of the gas turbine cycle. The main purpose of this research is thermodynamic analysis, evaluation of the performance of the proposed hybrid systems in similar conditions, and selection of an appropriate system in terms of efficiency, power generation, and entropy generation rate. In this study, the utilized fuel cells were subjected to electrochemical, thermodynamic, and thermal analyses and their working temperatures were calculated under various working conditions. Results indicate that the hybrid system with two series stacks had maximum power generation and efficiency compared with the other two cases. Moreover, the simple hybrid system and the system with two parallel stacks had relatively equal pure power generation and efficiency. According to the investigations, hybrid system with two series fuel cell stacks, which had 3424 and 1712 cells, respectively, can achieve the electrical efficiency of over 48%. A hybrid system with two parallel fuel cell stacks, in which each stack had 2568 cells, had the electrical efficiency of 46.3%. Findings suggested that maximum electrical efficiency occurred between the pressure ratios of 5–6 in the proposed hybrid systems.     

Effect of sand and clay fouling on the shear strength of railway ballast for different ballast gradations

Ballast contamination by fine materials such as sand and clay in railway track at arid regions is an important issue that causes track instability problems and settlement due to reduction of shear strength of ballast. In this paper, the results of direct shear box test conducted on clean ballast, sand-fouled ballast and clay-fouled ballast for different ballast gradations are reported and discussed. For this purpose, three different fouling amounts according to fouling index are added to clean ballast. Test results show that by increasing the fouling percentage, the ballast shear strength always decreases both for sand and clay fouled ballast. However, the amount of shear strength reduction is low at high normal stresses. Clay contamination has more adverse effect on the shear strength of ballast compared with sand contamination. Also, the results of tests for evaluation of gradation effect on shear strength of fouled ballast which are conducted on various gradations according to American Railway Engineering and Maintenance-of-Way Association, show that the maximum particle size as well as uniformity coefficient affect the shear strength of ballast. Also, an empirical equation is presented to observe the effect of ballast gradation on reduction of shear strength with regard to amount of fouling material and normal stress.