Advanced Glycation End-Products Induce Apoptosis of Vascular Smooth Muscle Cells: A Mechanism for Vascular Calcification

Vascular calcification, especially medial artery calcification, is associated with cardiovascular death in patients with diabetes mellitus and chronic kidney disease (CKD). To determine the underlying mechanism of vascular calcification, we have demonstrated in our previous report that advanced glycation end-products (AGEs) stimulated calcium deposition in vascular smooth muscle cells (VSMCs) through excessive oxidative stress and phenotypic transition into osteoblastic cells. Since AGEs can induce apoptosis, in this study we investigated its role on VSMC apoptosis, focusing mainly on the underlying mechanisms. A rat VSMC line (A7r5) was cultured, and treated with glycolaldehyde-derived AGE-bovine serum albumin (AGE3-BSA). Apoptotic cells were identified by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. To quantify apoptosis, an enzyme-linked immunosorbent assay (ELISA) for histone-complexed DNA fragments was employed. Real-time PCR was performed to determine the mRNA levels. Treatment of A7r5 cells with AGE3-BSA from 100 µg/mL concentration markedly increased apoptosis, which was suppressed by Nox inhibitors. AGE3-BSA significantly increased the mRNA expression of NAD(P)H oxidase components including Nox4 and p22^phox, and these findings were confirmed by protein levels using immunofluorescence. Dihydroethidisum assay showed that compared with cBSA, AGE3-BSA increased reactive oxygen species level in A7r5 cells. Furthermore, AGE3-induced apoptosis was significantly inhibited by siRNA-mediated knockdown of Nox4 or p22^phox. Double knockdown of Nox4 and p22^phox showed a similar inhibitory effect on apoptosis as single gene silencing. Thus, our results demonstrated that NAD(P)H oxidase-derived oxidative stress are involved in AGEs-induced apoptosis of VSMCs. These findings might be important to understand the pathogenesis of vascular calcification in diabetes and CKD.     

A Natural Bone Cement—A Laboratory Novelty Led to the Development of Revolutionary New Biomaterials

Research on calcium phosphate chemistry at NIST led to the discovery of the worlds first self-hardening calcium phosphate cements (CPC) in 1987. Laboratory, animal, and clinical studies were conducted to develop CPC into clinically useful biomaterials. The combination of self-hardening capability and high biocompatibility makes CPC a unique material for repairing bone defects. Near perfect adaptation of the cement to the tissue surfaces in a defect, and a gradual resorption followed by new bone formation are some of the other distinctive advantages of this biomaterial. In 1996 a CPC, consisting of tetracalcium phosphate and dicalcium phosphate anhydrous, was approved by the Food and Drug Administration (FDA) for repairing cranial defects in humans, thus becoming the first material of its kind available for clinical use. This paper will review the course of the development, the physical and chemical properties, and clinical applications of CPC.     

Toward integrated product and process life cycle planning—An environmental perspective

Life cycle engineering (LCE) is a key concept for promoting environmentally sustainable practices among manufacturing firms. A major hurdle in the implementation of LCE is the lack of a systematic and strategic method to design or plan an entire product life cycle. To address this issue, this keynote provides a framework for life cycle development and proposes the concept of life cycle planning. This paper aims to provide explicit and systematic methodologies for life cycle planning by reviewing this research area. Practical cases that employ life cycle planning are also illustrated. Finally, some research directions are suggested.     

Effects of material strain rate sensitivity in low speed impact between two identical spheres

This paper investigates the effects of strain rate sensitivity on the impact of two identical spheres. The spheres made of SUJ2 steel were impacted by using pendulum setup. The coefficients of restitution (COR) and contact durations were obtained experimentally. Static tensile test and Split Hopkinson pressure bar tests were conducted to identify the material properties of the sphere. And finite element simulations of the impacts between two identical spheres were carried out using LS-DYNA software. The simulation results fit well to the experimental results and they were compared to the results of elasto-plastic simulations which ignored the material strain rate sensitivity. It was found that the strain rate sensitive sphere showed the higher COR than those from the sphere which ignored the material strain rate sensitivity. Therefore, the material strain rate sensitivity has remarkable effect on the impact of two identical spheres even in the low speed impact. However, the influences of the material strain rate sensitivity on the contact durations were small.     

Pyroelectric infrared detector for precision earth sensor

Two new types of infrared detectors have been developed for the precision earth sensor in the three axis stabilized satellite, Engineering Test Satellite VI (ETS-VI). Both detectors have a pair of infrared sensing elements, each of which is made of a pyroelectric material and mounted on an immersion lens. A-type element is a flake of lead titanate ceramic, and B-type is a sputtered epitaxial film of calcium-modified lead titanate. The precision earth sensor consists of a scanning mirror and an infrared telescope containing an objective lens, plus either type of infrared detector. Detectivity of each type at 120Hz, which is the nominal frequency of the earth sensor's signal, is 1.5×10⁹Hz^1/2/W(A-type) and 2.7×10⁹Hz^1/2/W(B-type) at 14～16.25μm. Each value is 2.5 and 4.5 times as high as the previous model in ETS-V. A-type detector passed the space environmental test and the random error cf attitude measurement was 0.03 deg with the preliminary model of the earth sensor being ahead of the breadboard model. This measurement accuracy is nearly equal to that of the foremost earth sensor. A-type was chosen as the detector for ETS-VI. The random error of the earth sensor with B-type detector is 0.012deg, smaller than a half of the A-type sensor's error. Investigation of B-type is being continued in order to confirm its reliability for space use.     

Expansion of a static analysis-based out-of-plane maximum inelastic seismic response estimation method for steel arch bridges to in-plane response estimation

We have previously proposed a static analysis-based method for estimating the maximum out-of-plane inelastic seismic response of upper-deck steel arch bridges. The method is developed on the basis of the numerical examinations of 6 upper-deck steel arch bridge models. It employs free vibration analysis, response spectrum method and equal energy assumption for the estimation of maximum out-of-plane response. Correction functions are proposed to modify the estimates by the equal energy assumption. In the current study, applicability of the same procedure to the estimation of maximum in-plane response is discussed. It is found that the method can be used also for the maximum in-plane response estimation by only modifying the pushover analysis procedure. The validity of the method is demonstrated for the same parametric models through further numerical evaluations.     

Examination of sex-hormonal activity of some additives for PVDC film

Stabilizers (epoxidized linseed oil and epoxidized soybean oil) and plasticizers (acetyl tributyl citrate, diacetyl monolauryl glyceride and dibutyl sebacate) commonly used in polyvinylidene chloride (PVDC) films and extracts of such films were investigated for estrogenic and androgenic activity by means of estrogen receptor (ER) and androgen receptor (AR) competitive ligand-binding assays. Further, in in vivo experiments, ovariectomized Sprague-Dawley rats were observed for uterine wet weight change, uterine endometrium hyperplasia and vaginal mucosa cornification, following administration of each test compound or extract orally (0.5 or 500 mg/kg) or subcutaneously (0.5 or 100 mg/kg). No significant response or change was observed with any of the test compounds or extracts, either in vitro or in vivo. The results thus indicate that neither the stabilizers and plasticizers used in PVDC films, nor their extracts, exert sex-hormonal activity.     

Effect ofin Situ cooling on superconductivity of artificially layered BSCCO films with 2223 structure

Thin BSCCO films with the 2223 structure were deposited onto MgO substrate kept at 665°C by applying a sequential sputtering method using metallic Bi and Sr-Ca-Cu-O targets. The resultant films were then cooled under various oxygen partial pressures and cooling rates. It was found that the oxygen partial pressure and substrate temperature during cooling affect significantly the development of superconductivity of the as-deposited films. When the films were cooled stepwise under a critical oxygen partial pressure around 0.3 torr, the as-deposited films showed either superconductivity or nonsuperconductivity behavior. HRTEM images of the films showed no essential difference in the modulated structure, suggesting that the excess oxygen in the Bi-O double layers is the same and not the cause of the different superconducting behavior in the as-deposited films.