The Potential Role of Small-Molecule PERK Inhibitor LDN-0060609 in Primary Open-Angle Glaucoma Treatment

Primary open-angle glaucoma (POAG) constitutes the most common type of glaucoma. Emerging evidence suggests that Endoplasmic Reticulum (ER) stress and the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-mediated Unfolded Protein Response (UPR) signaling pathway play a key role in POAG pathogenesis. Thus, the main aim of the study was to evaluate the effectiveness of the PERK inhibitor LDN-0060609 in cellular model of glaucoma using primary human trabecular meshwork (HTM) cells. To evaluate the level of the ER stress marker proteins, Western blotting and TaqMan gene expression assay were used. The cytotoxicity was measured by XTT, LDH assays and Giemsa staining, whereas genotoxicity via comet assay. Changes in cell morphology were assessed by phase-contrast microscopy. Analysis of apoptosis was performed by caspase-3 assay and flow cytometry (FC), whereas cell cycle progression by FC. The results obtained have demonstrated that LDN-0060609 triggered a significant decrease of ER stress marker proteins within HTM cells with induced ER stress conditions. Moreover, LDN-0060609 effectively increased viability, reduced DNA damage, increased proliferation, restored normal morphology, reduced apoptosis and restored normal cell cycle distribution of HTM cells with induced ER stress conditions. Thereby, PERK inhibitors, such as LDN-0060609, may provide an innovative, ground-breaking treatment strategy against POAG.     

Effects of Radiation and Hydrogen on the Fracture Resistance of Borosilicate Glasses

In this study, short bar fracture toughness samples were used to determine the effects of radiation and hydrogen on the resistance to fracture of vitreous silica and four commercial borosilicate glasses. The results showed that neither exposure to 10¹⁰ rads of γ-radiation nor saturation to a room-temperature-equivalent exposure of 408 atm of hydrogen had an effect on fracture resistance. Nevertheless, when samples were saturated with hydrogen and then exposed to radiation, resistance to fracture increased significantly in some of the glasses. The increase in the resistance to fracture correlated directly with the increase in concentration of hydroxyl and hydride groups created by exposure to radiation and hydrogen. The concentration of these groups differs with glass composition and accounts for the difference in behavior between the types of glass studied.     

Structural and transport effects of doping perfluorosulfonic acid polymers with the heteropoly acids, H3PW12O40 or H4SiW12O40

A perfluorosulfonic acid (PFSA) polymer with pendant side chain -O(CF₂)₄SO₃H was doped with the heteropoly acids (HPAs), H₃PW₁₂O₄₀ and H₄SiW₁₂O₄₀. Infrared spectroscopy revealed a strong interaction between the HPA and the PFSA ionomer. Modes associated with the peripheral bonds of the HPA were shifted to lower wave numbers when doped into PFSA membranes. Small-angle X-ray scattering (SAXS) measurements showed the presence of large crystallites of HPA in the membrane with d spacings of ca. 10 Å, close to the lattice spacing observed in bulk HPA crystals. Under wet conditions the HPA was more dispersed and constrained the size of the sulfonic acid clusters to 20 Å at a 5 wt% HPA doping level, the same as in the vacuum treated ionomer samples. Under conditions of minimum hydration the HPA decreased the E_a for the self-diffusion of water from 27 to 15 kJ mol⁻¹. The reverse trend was seen under 100% RH conditions. Proton conductivity measurements showed improved proton conductivity of the HPA doped PFSAs at a constant dew point of 80 °C for all temperatures up to 120 °C and at all relative hummidities up to 80%. The activation energy for proton conduction generally was lower than for the undoped materials at RH ≤80%. Significantly the E_a was 1/2 that of the undoped material at RHs of 40 and 60%. A practical proton conductivity of 113 mS cm⁻¹ was observed at 100 °C and 80% RH.     

Quantitation of volatile compounds in heated triolein by static headspace capillary gas chromatography/infrared spectroscopy-mass spectrometry

Static headspace and capillary gas chromatography/infrared spectroscopy-mass spectrometry were used to collect, separate, identify and quantitate the oxidative and thermal decomposition products in heated triolein. Approximately 4 L of triolein was heated in a deep-fat fryer at 190°C for 12 h each day for a total of 60 h, until it contained>-20% polymeric material. The concentration of heptane and octane increased after 12 h heating, then decreased upon further heating, while the concentration of volatile aldehydes decreased gradually during heating. After 12 h of heating, the concentrations of the major volatiles changed as follows: heptane (16.36 to 30.17 ppm), octane (24.48 to 40.77 ppm), heptanal (21.68 ppm to 9.11 ppm), octanal (35.53 to 36.64 ppm), nonanal (68.95 to 43.16 ppm), (E)-2-decenal (135.00 to 89.00 ppm) and (E)-2-undecenal (88.50 to 61.00 ppm). After 60 h of heating, when the oil contained over 20% polymeric material, the concentrations of heptane, octane, heptanal, octanol, nonanal, (E)-2-decenal and (E)-2-undecenal were 5.16, 4.39, 5.45, 7.02, 18.07, 12.50 and 6.00 ppm, respectively.     

Molybdenum Oxycarbide and Tungsten Oxycarbide Coatings on Silicon Carbide Fibers

The strength and toughness of fibrous composites depend on the interface properties which control the bonding between the fibers and matrices. One method of controlling the interface involves coating the fiber with an appropriate material. In a previous study, it was found that there is a definite advantage in using low coating temperatures to prevent fibers from degrading. We therefore were interested in a report that Mo₂C could be deposited from Mo(CO)₆ at temperatures as low as 300° to 475°C. Our studies indicated that the material was not Mo₂C, but an oxycarbide, which, with an analogous tungsten oxycarbide coating, was applied to SiC yarns. Both oxycarbides could be converted to the metals by heat-treating in N₂.     

Reaction kinetics modeling and thermal properties of epoxy–amines as measured by modulated‐temperature DSC. II. Network‐forming DGEBA + MDA

Reaction‐induced vitrification takes place in the network‐forming epoxy–amine system diglycidyl ether of bisphenol A (DGEBA) + methylenedianiline (MDA) when the glass‐transition temperature (T_g) rises above the cure temperature (T_cure). This chemorheological transition results in diffusion‐controlled reaction and can be followed simultaneously with the reaction rate in modulated‐temperature DSC (MTDSC). To predict the effect of T_cure and the NH/epoxy molar mixing ratio (r) on the reaction rate in chemically controlled conditions, a mechanistic approach was used based on the nonreversing heat flow and heat capacity MTDSC signals, in which the reaction steps of primary (E_1OH = 44 kJ mol^?1) and secondary amine (E_2OH = 48 kJ mol^?1) with the epoxy–hydroxyl complex predominating. The diffusion factor DF as defined by the Rabinowitch approach expresses whether the chemical reaction rate or the diffusion rate determines the overall reaction rate. A model based on the free volume theory together with an Arrhenius temperature dependency was used to calculate the diffusion rate constant in DF as a function of conversion (x) and T_cure. The relation between x, r, and T_g, needed in this model, can be predicted with the Couchman equation. An experimental approximation for DF is the mobility factor DF* obtained from the heat capacity signal at a modulation frequency of 1/60 Hz, normalized for the effect of the reaction heat capacity in the liquid state and the change in C_p in the glassy region with x and T_cure. In this way, an optimized set of diffusion parameters was obtained that, together with the optimized kinetic parameters set, can predict the reaction rate for different cure schedules and for stoichiometric and off‐stoichiometric mixtures. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 91: 2814–2833, 2004     

Volatile Emissions Triggered by Multiple Herbivore Damage: Beet Armyworm and Whitefly Feeding on Cotton Plants

Plants are commonly attacked by more than one species of herbivore, potentially causing the induction of multiple, and possibly competing, plant defense systems. In the present paper, we determined the interaction between feeding by the phloem feeder silverleaf whitefly (SWF), Bemisia tabaci Gennadius (B-biotype = B. argentifolii Bellows and Perring), and the leaf-chewing beet armyworm (BAW), Spodoptera exigua Hübner, with regard to the induction of volatile compounds from cotton plants. Compared to undamaged control plants, infestation with SWF did not induce volatile emissions or affect the number and density of pigment glands that store volatile and nonvolatile terpenoid compounds, whereas infestation by BAW strongly induced plant volatile emission. When challenged by the two insect herbivores simultaneously, volatile emission was significantly less than for plants infested with only BAW. Our results suggest that tritrophic level interactions between cotton, BAW, and natural enemies of BAW, that are known to be mediated by plant volatile emissions, may be perturbed by simultaneous infestation by SWF. Possible mechanisms by which the presence of whiteflies may attenuate volatile emissions from caterpillar-damaged cotton plants are discussed.     

Free fatty acid inhibition of the insulin induction of glucose-6-phosphate dehydrogenase in rat hepatocyte monolayers

Rat hepatocytes in monolayer culture were utilized to determine if the decrease in glucose-6-phosphate dehydrogenase (G6PD) activity resulting from the ingestion of fat can be mimicked by the addition of fatty acids to a chemically, hormonally defined medium. G6PD activity in cultured hepatocytes was induced several-fold by insulin. Dexamethasone or T3 did not amplify the insulin induction of G6PD. Glucose alone increased G6PD activity in cultured hepatocytes from fasted donors by nearly 500%. Insulin in combination with glucose induced G6PD an additional two-fold. The increase in G6PD activity caused by glucose was greater in hepatocytes isolated from 72 hr-fasted rats as compared to fed donor rats. Such a response was reminiscent of the “overshoot” phenomenon in which G6PD activity is induced well above the normal level by fasting-refeeding rats a high glucose diet. Addition of linoleate to the medium resulted in a significant suppression of insulin’s ability to induce G6PD, but linoleate had no effect on the induction of G6PD activity by glucose alone. A shift to the right in the insulin-response curve for the induction of G6PD also was detected for the induction of malic enzyme and acetyl-CoA carboxylase. Arachidonate (0.25 mM) was a significantly more effective inhibitor of the insulin action than linoleate was. Apparently rat hepatocytes in monolayer culture can be utilized as a model to investigate the molecular mechanism by which fatty acids inhibit the production of lipogenic enzymes. In part, this mechanism of fatty acid inhibition involves desensitization of hepatocytes to the lipogenic action of insulin.     

Sulfonated poly(ether ketone ketone) ionomers as proton exchange membranes

Sulfonated poly(ether ketone ketone) ionomers (SPEKK) with ion‐exchange capacities (IEC) between 0.2 and 3.4 meq/g were prepared by sulfonating PEKK with a mixture of concentrated and fuming sulfuric acids. Sulfonation occurs only on the phenyl rings attached to ether and ketone groups. The glass transition temperature of the dry SPEKK ionomers increased linearly with increasing IEC, and the ionomers were thermally stable to ～250°C, above which desulfonation occurred. Water‐swollen ionomers exhibited microphase separated morphologies, and the average correlation length determined by small angle X‐ray scattering increased with increasing IEC. The proton conductivity of hydrated SPEKK membranes measured by impedance spectroscopy ranged from ～10^–3 to 10^–1 S/cm as the IEC increased from ～1.0 to 2.4 meq/g. Single cell performance curves on membrane‐electrode assemblies (MEA) indicated that the SPEKK membranes approached the performance of Nafion? for an IEC of 2 meq/g. POLYM. ENG. SCI., 45:1081–1091, 2005. © 2005 Society of Plastics Engineers     

Preparation and Characterization of 17O-Enriched Alumina for Nuclear Fusion Damage Experiments

Alumina enriched in ¹⁷O was successfully fabricated from aluminum isopropoxide and water containing the ¹⁷O isotope. This material was necessary for an experiment to study the radiation damage expected in alumina exposed to a nuclear fusion reactor environment. The enrichment levels of specimens subjected to different preparation schedules were measured using a nuclear reaction analysis technique. Replacement of the ¹⁷O isotope in the ceramic by atmospheric oxygen occurred readily. Therefore, successful fabrication of suitably enriched alumina specimens required that all processing steps be performed under vacuum or inertgas environments. The optimum fabrication procedure produced enriched alumina specimens of >99.5% of theoretical density, ∽10-μm grain size, and a flexural strength of 280 MPa.