Two-step seismic limit state design procedure based on non-linear LRFD and dynamic response analyses

Recently, the limit state design (LSD) or performance-based design have got popularity in the field of building design in Japan as well as in other countries. In the two design methods the structural reliability theory plays an essential role in setting design criteria as well as demonstrating the target reliability level to society. However, the conventional load and resistance factor design (LRFD) has been basically formulated supposing that safety checking is done on the basis of linear assumption of member forces and displacement. Therefore, when applying the LRFD for seismic design, for more accurate treatment of the non-linearity, a new procedure has to be explored especially for the ultimate limit state. Although several procedures for the structural reliability evaluation, treating non-linear displacement responses, have been proposed, they require complex procedures that may not be used in the practical design process. Accordingly, for applying it to a seismic LSD format based on the probabilistic concept, it is essential to manage two important requirements at the same time, accuracy and simplicity of procedure. In the present study, a new design format using the following two-step procedure is proposed to maintain both accuracy and simplicity; (1) a non-linear LRFD formulation, and (2) a formulation based on non-linear dynamic response analysis. Also, two design examples are presented.     

Nicotinamide Mononucleotide Protects against Retinal Dysfunction in a Murine Model of Carotid Artery Occlusion

Cardiovascular abnormality-mediated retinal ischemia causes severe visual impairment. Retinal ischemia is involved in enormous pathological processes including oxidative stress, reactive gliosis, and retinal functional deficits. Thus, maintaining retinal function by modulating those pathological processes may prevent or protect against vision loss. Over the decades, nicotinamide mononucleotide (NMN), a crucial nicotinamide adenine dinucleotide (NAD⁺) intermediate, has been nominated as a promising therapeutic target in retinal diseases. Nonetheless, a protective effect of NMN has not been examined in cardiovascular diseases-induced retinal ischemia. In our study, we aimed to investigate its promising effect of NMN in the ischemic retina of a murine model of carotid artery occlusion. After surgical unilateral common carotid artery occlusion (UCCAO) in adult male C57BL/6 mice, NMN (500 mg/kg/day) was intraperitoneally injected to mice every day until the end of experiments. Electroretinography and biomolecular assays were utilized to measure ocular functional and further molecular alterations in the retina. We found that UCCAO-induced retinal dysfunction was suppressed, pathological gliosis was reduced, retinal NAD⁺ levels were preserved, and the expression of an antioxidant molecule (nuclear factor erythroid-2-related factor 2; Nrf2) was upregulated by consecutive administration of NMN. Our present outcomes first suggest a promising NMN therapy for the suppression of cardiovascular diseases-mediated retinal ischemic dysfunction.     

Analgesic Effect of Tranilast in an Animal Model of Neuropathic Pain and Its Role in the Regulation of Tetrahydrobiopterin Synthesis

Trigeminal neuralgia is unilateral, lancinating, episodic pain that can be provoked by routine activities. Anticonvulsants, such as carbamazepine, are the drugs of choice; however, these possess side-effects. Microvascular decompression is the most effective surgical technique with a higher success rate, although occasionally causes adverse effects. The potential treatment for this type of pain remains unmet. Increased tetrahydrobiopterin (BH4) levels have been reported in association with axonal injury. This study aimed to evaluate the effect of tranilast on relieving neuropathic pain in animal models and analyze the changes in BH4 synthesis. Neuropathic pain was induced via infraorbital nerve constriction. Tranilast, carbamazepine, or saline was injected intraperitoneally to assess the rat’s post-intervention pain response. In the von Frey’s test, the tranilast and carbamazepine groups showed significant changes in the head withdrawal threshold in the ipsilateral whisker pad area. The motor coordination test showed no changes in the tranilast group, whereas the carbamazepine group showed decreased performance, indicating impaired motor coordination. Trigeminal ganglion tissues were used for the PCR array analysis of genes that regulate the BH4 pathway. Downregulation of the sepiapterin reductase (Spr) and aldoketo reductase (Akr) genes after tranilast injection was observed compared to the pain model. These findings suggest that tranilast effectively treats neuropathic pain.     

Bile Acid–Drug Interaction via Organic Anion-Transporting Polypeptide 4C1 Is a Potential Mechanism of Altered Pharmacokinetics of Renally Excreted Drugs

Patients with liver diseases not only experience the adverse effects of liver-metabolized drugs, but also the unexpected adverse effects of renally excreted drugs. Bile acids alter the expression of renal drug transporters, however, the direct effects of bile acids on drug transport remain unknown. Renal drug transporter organic anion-transporting polypeptide 4C1 (OATP4C1) was reported to be inhibited by chenodeoxycholic acid. Therefore, we predicted that the inhibition of OATP4C1-mediated transport by bile acids might be a potential mechanism for the altered pharmacokinetics of renally excreted drugs. We screened 45 types of bile acids and calculated the IC₅₀, K_i values, and bile acid–drug interaction (BDI) indices of bile acids whose inhibitory effect on OATP4C1 was >50%. From the screening results, lithocholic acid (LCA), glycine-conjugated lithocholic acid (GLCA), and taurine-conjugated lithocholic acid (TLCA) were newly identified as inhibitors of OATP4C1. Since the BDI index of LCA was 0.278, LCA is likely to inhibit OATP4C1-mediated transport in clinical settings. Our findings suggest that dose adjustment of renally excreted drugs may be required in patients with renal failure as well as in patients with hepatic failure. We believe that our findings provide essential information for drug development and safe drug treatment in clinics.     

Ru(0) complex catalyzed polyadditionNew synthesis of poly(alkylenebenzoxazole) and poly(alkylenebenzimidazole)

Summary The reactions of α,ω-diyne, HC≡C(CH₂)_mC≡CH (m = 6 and 8), with 3,3'-diaminobenzidine and with 3,3'-diamino-4,4'-dihydroxybiphenyl in the presence of RU₃(CO)₁₂-PPh₃ catalyst give the corresponding poly(alkylenebenzoxazole)s and poly(alkylenebenzimidazole)s, respectively. The former polymers obtained from the equimolar reaction of the monomers are partly soluble in polar organic solvents such as DMF, DMSO, and NMP, while the poly(benzimidazole)s are soluble in these solvents. GPC measurement shows the molecular weights of the polymers, M _n of 4.8−14.1×10³ and M _w of 6.4−19.7×10³. Received: 24 November 1998/Revised version: 21 December 1998/Accepted: 24 December 1998     

Photochemical and thermoelectric utilization of solar energy in a hybrid water-splitting system

A hybrid thermochemical water-splitting cycle using solar energy is proposed and experimental results are presented. The cycle consists of a photochemical reaction conducted in a flat cell with a Fresnel lens and concentrating the remaining solar energy on a thermoelectric generator which produces electric power for the electrolysis steps. The photochemical reaction is:

$\text{2}\text{Fe}{}^{\mathrm{2+}}\text{+}\text{I}{}^{\mathrm{?}}\text{+}\text{light}\text{→2}\text{Fe}{}^{\mathrm{3+}}\text{+3}\text{I}{}^{\mathrm{?}}$

The overall efficiency is estimated to be as high as 15–25%.     

Surface shape measurement by phase-shifting digital holography with a wavelength shift

Surface contouring by phase-shifting digital holography is proposed and verified by experiments and numerical simulations. Digital holograms are recorded before and after mode hopping of a laser diode subject to current tuning, and the difference of the reconstructed phases at each wavelength is computed to deliver surface contours of a diffusely reflecting surface. Since normal incidence on the object is employed, the method does not need the removal of the tilt component and is free from the shadowing effect as advantages over the dual-incidence method proposed before by the first author.     

Synthesis and photophysical properties of structural isomers of novel 2,10-disubstituted benzofuro[2,3-e]naphthoxazole-type fluorescent dyes

Structural isomers of novel 2,10-disubstituted benzofuro[2,3-e]naphthoxazole fluorescent dyes have been synthesized. The phtophysical properties have been investigated in solution and in the solid state. The absorption and fluorescence intensities of the naphth[1,2-d]oxazoles are much stronger than those of the naphth[2,1-d]oxazoles in solution. Moreover, in the solid state, the emission intensities of the former are typically much stronger than those of latter isomers. To understand the differences in photophysical properties, semi-empirical molecular orbital calculations and the X-ray crystallographic analyses have been performed.