Photostability Enhancement of Dual-Luminophore Pressure-Sensitive Paint by Adding Antioxidants.

Antioxidants were applied to a dual-luminophore pressure-sensitive paint (PSP), and the effects on photodegradation caused by exposure to excitation light were studied. Three types of antioxidants that are commonly used for the photostability enhancement of polymers were added to a dual-luminophore PSP, and degradation rates and pressure/temperature sensitivities were investigated by coupon-based tests. One-hour-long aging tests were performed in a pressure chamber with a continuous excitation light source under dry air and argon atmospheres at 100 kPa and 20 °C. As a result of the aging tests, a singlet oxygen quencher type antioxidant was found to reduce the degradation rate by 91% when compared with the dual-luminophore PSP without antioxidants. This implies that singlet oxygen has a dominant role in the photodegradation mechanism of the dual-luminophore PSP.

Practical Fast-Response Anodized-Aluminum Pressure-Sensitive Paint Using Chemical Adsorption Luminophore as Optical Unsteady Pressure Sensor.

We developed and evaluated an anodized-aluminum pressure-sensitive paint (AA-PSP) with new formulations of free-base porphyrin, H2TCPP, as an optical unsteady pressure sensor. The luminophore H2TCPP has quite a short fluorescent lifetime (2.4 ns on the condition of the AA-PSP). The fluorescence spectroscopy result shows that the excitation wavelength of H2TCPP corresponds to violet-colored (425 nm) and green-colored (longer than 520 nm) lights. The pressure sensitivity is sufficiently high for the pressure sensor (0.33-0.51%/kPa) and the temperature sensitivity is very low (0.07-1.46%/K). The photodegradation of the AA-PSPs is not severe in both excitation light sources of the green LED and the Nd:YAG laser. The resonance tube experiment result shows the cut-off frequency of the AA-PSPs is over 9.0 kHz, and the results of the shock tube experiment show the 10 µs order time constant of the normal shock wave.

Computational study on aeroacoustic fields of a transitional supersonic jet.

Aeroacoustic fields of a supersonic free jet at the Mach and Reynolds numbers of 2.1 and 70 000, respectively, of the transitional conditions are computationally investigated by large-eddy simulations. The supersonic transitional jets of different shear layer thicknesses without disturbances and those of the fixed shear layer thickness with disturbances are computationally investigated, and the effects of the shear layer thickness and the disturbance are discussed. The position of the transition and the turbulence intensity in the vicinity of the transition are clearly affected by those parameters. The turbulent fluctuation along the shear layer and the resulting intensity of the generated Mach waves are substantially attenuated by decreasing the shear layer thickness or adding the disturbance. A 5 dB increase in the sound pressure level is observed. This relatively lower increment in the sound pressure level compared with the 10-20 dB increase in the subsonic jet case is discussed as being due to the transition process promoted by the spiral mode in the supersonic jet case, unlike the axisymmetric case in the subsonic jet case. This point is confirmed by the linear stability analysis, the proper orthogonal decomposition analysis, and the visualization of vortex structures in the transition region.

First lift-off and flight performance of a tailless flapping-wing aerial robot in high-altitude environments.

Flapping flight of animals has captured the interest of researchers due to their impressive flight capabilities across diverse environments including mountains, oceans, forests, and urban areas. Despite the significant progress made in understanding flapping flight, high-altitude flight as showcased by many migrating animals remains underexplored. At high-altitudes, air density is low, and it is challenging to produce lift. Here we demonstrate a first lift-off of a flapping wing robot in a low-density environment through wing size and motion scaling. Force measurements showed that the lift remained high at 0.14 N despite a 66% reduction of air density from the sea-level condition. The flapping amplitude increased from 148 to 233 degrees, while the pitch amplitude remained nearly constant at 38.2 degrees. The combined effect is that the flapping-wing robot benefited from the angle of attack that is characteristic of flying animals. Our results suggest that it is not a simple increase in the flapping frequency, but a coordinated increase in the wing size and reduction in flapping frequency enables the flight in lower density condition. The key mechanism is to preserve the passive rotations due to wing deformation, confirmed by a bioinspired scaling relationship. Our results highlight the feasibility of flight under a low-density, high-altitude environment due to leveraging unsteady aerodynamic mechanisms unique to flapping wings. We anticipate our experimental demonstration to be a starting point for more sophisticated flapping wing models and robots for autonomous multi-altitude sensing. Furthermore, it is a preliminary step towards flapping wing flight in the ultra-low density Martian atmosphere.

Effect of long-term streptozotocin-induced diabetes on coronary vasoconstriction in isolated perfused rat heart.

The primary goal of this study was to investigate the effect of long-term (9 months) streptozotocin (STZ)-induced diabetes on the coronary vasoconstrictor responses to vasoactive agents such as high K(+), acetylcholine (ACh), endothelin-1 (ET-1), and the calcium-channel activator Bay K 8644. For this, we used isolated rat hearts perfused at constant flow rate. Each of the four agents caused dose-dependent increases in perfusion pressure in isolated hearts from age-matched control and STZ-induced diabetic rats. The dose-response curves for high K(+), ACh, and ET-1 were shifted to the left, so that at some lower doses of these agents the increased perfusion pressure was greater in coronary arteries obtained from diabetic rats than in those from control rats. On the other hand, the maximum contractile response induced by each of these agents was lower in the diabetic perfused heart. The Bay K 8644-induced contractile response was significantly greater in the coronary arteries of diabetic rats than in those of control rats. A threshold-constrictor concentration of Bay K 8644 (1 nM) potentiated the ACh-induced vasoconstriction in coronary arteries from both groups, and the potentiated responses were greater in diabetic rats than in controls at lower concentrations of ACh (100 nM and 1 microM). These findings suggest that the coronary artery contractile responses to lower concentrations of ACh or ET-1 are exaggerated in long-term STZ-induced diabetic hearts. These changes may be due to alterations in the activity of voltage-gated Ca(2+) channels.

The proteasome inhibitor bortezomib inhibits the growth of canine malignant melanoma cells in vitro and in vivo.

Canine malignant melanomas are highly aggressive and fatal neoplasms. In the present report, 21 drugs that target specific signalling pathways were screened for their growth inhibitory activity on three canine malignant melanoma cell lines. The proteasome inhibitor bortezomib inhibited the growth of these cell lines. The growth inhibitory properties of bortezomib were then examined using nine canine malignant melanoma cell lines. Bortezomib demonstrated potent growth inhibitory activity in all cell lines with calculated IC50 values of 3.5-5.6 nM. Because suppression of the NF-κB pathway by preventing proteasomic degradation of I κB is an important mechanism of the anti-tumour activity of bortezomib, the activation status of and the effect of bortezomib on the NF-κB pathway were examined using a canine malignant melanoma cell line, CMM-1. The NF-κB pathway was constitutively activated in CMM-1 cells and bortezomib efficiently suppressed this activated pathway. Using a CMM-1 xenograft mouse model, bortezomib also significantly inhibited tumour growth via suppression of tumour cell proliferation. Collectively, these findings suggest that bortezomib has growth inhibitory activity against canine malignant melanomas potentially through suppression of the constitutively activated NF-κB pathway. Targeted therapy using bortezomib could therefore be beneficial in the management of canine malignant melanomas.

FilGAP, a Rho/Rho-associated protein kinase-regulated GTPase-activating protein for Rac, controls tumor cell migration.

Tumor cells exhibit two interconvertible modes of cell motility referred to as mesenchymal and amoeboid migration. Mesenchymal mode is characterized by elongated morphology that requires high GTPase Rac activation, whereas amoeboid mode is dependent on actomyosin contractility induced by Rho/Rho-associated protein kinase (ROCK) signaling. While elongated morphology is driven by Rac-induced protrusion at the leading edge, how Rho/ROCK signaling controls amoeboid movement is not well understood. We identified FilGAP, a Rac GTPase-activating protein (GAP), as a mediator of Rho/ROCK-dependent amoeboid movement of carcinoma cells. We show that depletion of endogenous FilGAP in carcinoma cells induced highly elongated mesenchymal morphology. Conversely, forced expression of FilGAP induced a round/amoeboid morphology that requires Rho/ROCK-dependent phosphorylation of FilGAP. Moreover, depletion of FilGAP impaired breast cancer cell invasion through extracellular matrices and reduced tumor cell extravasation in vivo. Thus phosphorylation of FilGAP by ROCK appears to promote amoeboid morphology of carcinoma cells, and FilGAP contributes to tumor invasion.

Diabetes-associated changes and role of N epsilon-(carboxymethyl)lysine in big ET-1-induced coronary vasoconstriction.

Using perfused hearts from streptozotocin-induced long-term diabetic rats, we studied the coronary vasoconstrictor effect of the endothelin-1 (ET-1) precursor big ET-1 and also whether this response was modulated by N(epsilon)-(carboxymethyl)lysine (CML; a representative advanced glycation end product that is implicated in the pathogenesis of diabetic vasculopathy). The big ET-1-induced vasoconstriction (a) developed more rapidly (i.e., was greater in the first 30 min) in the diabetic group than in the age-matched controls, and (b) in each group was largely suppressed by phosphoramidon [nonselective endothelin-converting enzyme (ECE)/neutral endopeptidase (NEP) inhibitor] or CGS35066 (selective ECE inhibitor), but not by thiorphan (selective NEP inhibitor). The ET-1 release occurring after treatment with big ET-1, which was greater in diabetic coronary arteries than in the controls, was reduced by CGS35066. The dose-response curve for ET-1 was shifted to the left in the diabetics, so that at some lower doses of ET-1 the vasoconstriction was greater than in the controls. CML enhanced big ET-1- or ET-1-induced vasoconstriction in the controls, but not in the diabetics. Finally, the plasma level of CML was higher in diabetic than in control rats. These findings suggest (a) that the increased responsiveness to big ET-1 shown by diabetic coronary arteries may be attributable both to a more rapid conversion of big ET-1 to ET-1 (by ECE), allowing it to exert its contractile activity, and to an increased vascular sensitivity to ET-1, and (b) that CML may be at least partly responsible for the diabetes-associated enhancement of big ET-1-mediated coronary vasoconstriction.

Effect of N-epsilon-(carboxymethyl)lysine on coronary vasoconstriction in isolated perfused hearts from control and streptozotocin-induced diabetic rats.

Advanced glycation end products (AGEs) derived from glucose are implicated in the pathogenesis of diabetic vascular disease. However, their direct modulatory effects on coronary vascular tone remain unclear. We previously reported that coronary vasoconstriction was induced by acetylcholine (ACh) infusion of the isolated perfused rat heart and that sensitivity was greater in perfused hearts from streptozotocin (STZ)-induced diabetic rats than in those from age-matched controls (Kamata et al., 2008). Here, we investigated the effect of N(epsilon)-(carboxymethyl)lysine (CML), which has one of the main AGE structures, on ACh-induced vasoconstriction in perfused hearts isolated from control and diabetic rats. ACh-induced vasoconstriction was significantly greater in the STZ-induced diabetic group than in the age-matched controls. CML enhanced the ACh-induced vasoconstriction in coronary arteries from control rats, but not in those from STZ-induced diabetic rats. In the controls, the vasoconstriction induced by the calcium-channel activator Bay K 8644 was also enhanced by CML. These CML-mediated enhancements of the vasoconstrictions induced by ACh and Bay K 8644 were significantly suppressed by tempol, a superoxide dismutase mimetic. The plasma CML and glucose levels were each significantly elevated in STZ-induced diabetic rats. These findings suggest (a) that CML augments ACh-induced coronary vasoconstriction, an effect that may be attributable to increased superoxide and to activation of voltage-gated Ca(2+) channels and (b) that this modulating effect may be desensitized in the STZ-induced diabetic heart.

Chronic treatment with losartan (angiotensin II type 1 receptor antagonist) normalizes enhanced acetylcholine-induced coronary vasoconstriction in isolated perfused hearts of type 2 diabetic OLETF rats.

We previously reported that isolated perfused hearts from streptozotocin (STZ)-induced diabetic rats exhibited increases in the sensitivity of the coronary vasoconstriction induced by acetylcholine (ACh) infusion (versus age-matched controls) (Kamata et al., 2008). Here, we examined the ACh-induced coronary vasoconstriction in perfused hearts taken from Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 diabetes model, at the chronic stage of diabetes (38-40 weeks old). The ACh-induced vasoconstriction was greatly enhanced in such rats [versus age-matched control Long-Evans Tokushima Otsuka (LETO) rats]. This enhancement was improved by the chronic administration of the angiotensin II type I receptor (AT(1)-receptor) antagonist losartan (25 mg kg(-1), p.o., for 4 weeks). Further, the enhancement of the ACh-induced vasoconstriction seen in the OLETF group was suppressed by tempol, a superoxide dismutase mimetic. These results suggest that the coronary artery contractile response to ACh is enhanced in type 2 diabetic OLETF rats, and that this enhancement may be attributable to increased AT(1) receptor-mediating signaling and/or to increased oxidative stress.