Mechanism of action of the nongenotoxic peroxisome proliferators: role of the peroxisome proliferator-activator receptor alpha

Peroxisome proliferators are a diverse group of chemicals that include several therapeutically used drugs (e.g., hypolipidemic agents), plasticizers and organic solvents used in the chemical industry, herbicides, and naturally occurring hormones. As the name implies, peroxisome proliferators cause an increase in the number and size of peroxisomes in the liver, kidney, and heart tissue of susceptible species, such as rats and mice. Long-term administration of peroxisome proliferators can cause liver cancer in these animals, a response that has been the central issue of research on peroxisome proliferators for many years. Peroxisome proliferators are representative of the class of nongenotoxic carcinogens that cause cancer through mechanisms that do not involve direct DNA damage. The fact that humans are frequently exposed to these agents makes them of particular concern to government regulatory agencies responsible for assuring human safety. Whether frequent exposure to peroxisome proliferators represents a hazard to humans is unknown; however, increased cancer risk has not been shown to be associated with long-term therapeutic administration of the hypolipidemic drugs gemfibrozil, fenofibrate, and clofibrate. To make sound judgments regarding the safety of peroxisome proliferators, the validity of extrapolating results from rodent bioassays to humans must be based on the agents' mechanism of action and species differences in biologic activity and carcinogenicity. The peroxisome proliferator-activated receptor alpha (PPARalpha), a member of the nuclear receptor superfamily, has been found to mediate the activity of peroxisome proliferators in mice. Gene-knockout mice lacking PPARalpha are refractory to peroxisome proliferation and peroxisome proliferator-induced changes in gene expression. Furthermore, PPARalpha-null mice are resistant to hepatocarcinogenesis when fed a diet containing a potent nongenotoxic carcinogen WY-14,643. Recent studies have revealed that humans have considerably lower levels of PPARalpha in liver than rodents, and this difference may, in part, explain the species differences in the carcinogenic response to peroxisome proliferators.     

U.K. Prospective Diabetes Study. XV: Relationship of renin-angiotensin system gene polymorphisms with microalbuminuria in NIDDM

We performed a case-control study to determine whether molecular variants of genes of the renin-angiotensin system were associated with the presence of albuminuria in non-insulin dependent diabetes mellitus (NIDDM). A total of 180 diabetic patients with persistent microalbuminuria [median urinary albumin (interquartile range) of 74 (54 to 126 mg/liter)] were matched with two control groups of diabetic patients without microalbuminuria [median urinary albumin 7 (5 to 10) mg/liter] for variables known to be associated with raised urinary albumin concentration including hemoglobin A1c and triglyceride. One control group was also matched for blood pressure and the other group was not, to allow assessment of interactions with hypertension. Association with the I/D polymorphism of the ACE gene and M235T variant of the angiotensinogen gene (AGT) with microalbuminuria and retinopathy was examined. There were no significant differences in genotype frequency between cases and controls for ACE or AGT irrespective of blood pressure matching. However, among subjects with microalbuminuria, those with the ACE DD genotype had a significantly greater urinary albumin excretion than individuals with a non-DD genotype [median 88 (68 to 170) mg/liter vs. 67 (53 to 113) mg/liter, P < 0.001]. More subjects with the DD than non-DD genotype had persistent albuminuria > 100 mg/liter, twice the upper normal range (60% vs. 38%, P = 0.006). When increased albumin excretion occurs, the presence of the ACE DD genotype appears to be associated with higher urinary albumin levels. No association with retinopathy was observed.     

A deep multi-source adaptation transfer network for cross-subject electroencephalogram emotion recognition

Neural Computing and Applications - In real-world application of affective brain–computer interface (aBCI), individual differences across subjects and non-stationary characteristics of...     

Delay‐dependent stability for Markovian genetic regulatory networks with time‐varying delays

This paper is concerned with the problem of stochastic stability analysis for a class of genetic regulatory networks with Markovian jump parameters and time‐varying delays. A delay‐dependent stability criterion is derived by using a novel mode‐dependent Lyapunov functional. The derived stability criterion is expressed in terms of linear matrix inequalities and is less conservative than the existing ones in the literature. A numerical example is provided to demonstrate the effectiveness of the proposed stability criterion. Copyright © 2011 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society     

Growth characteristics of β-SiC by chemical vapour deposition

A twin-plane re-entrant corner effect (TPRE) in growth of chemical vapour deposited (CVD) -SiC is described by the film and particles of gas-phase homogeneous nucleation. The structural morphology has been characterized by scanning electron microscopy and transmission electron microscopy. Morphological characteristics of the deposited crystals, such as triangularity, hexagons or facets have been explained in terms of the re-entrant corner effect at twin junctions, which were proposed as preferential growth sites for perfect crystals. For real deposits, screw dislocations and/or the re-entrant corner effect are not expected to be compatible. The majority of chemical vapour deposited SiC crystals have a high defect density comprised of {111} twins and dislocations associated with the process variables. Infrared transmission spectra and electron spectroscopy of chemical analysis indicated that the major chemical bonds of CVD -SiC were Si-C and C-H bonds. The positions of the 1s or 2p corelevel peaks for deposits are described.     

Piezoelectric and acoustic properties of potassium titanyl phosphate (KTP) and its isomorphs

The bulk elastic and piezoelectric properties of potassium titanyl phosphate (KTP) and some of its family members such as RbTiOPO(4 ) (RTP) and RbTiOAsO(4) (RTA) have been determined. The piezoelectric, elastic, and dielectric matrix (P-E-D) of KTP has been completely characterized. Values for the temperature dependence of the expansion coefficients and elastic constants have been obtained, and the effects of variations in dielectric constant on coupling coefficient determined. The major diagonal elements of the piezoelectric and elastic matrices of RTP and RTA were measured as were the thermal expansion coefficient of all the KTP isomorphs, KTP in the temperature range 25-80 degrees C, is shown to have a combination of large coupling coefficients (up to k(t)=38% for hydrothermally grown KTP) and medium temperature dependence coefficients of elastic constant (as low as 40 p.p.m./ degrees C for tau(c33) for hydrothermally grown KTP) that makes it attractive for many piezoelectric applications.     

软件单元测试应用研究及案例分析

单元测试是软件测试过程的第一站,高质量的单元测试是软件质量保证的必要条件,本文就单元测试的概念、测试类型及规程作了简单的阐述,同时就单元测试进行了案例分析。     

Preparation of Protein-Stabilized β-Carotene Nanodispersions by Emulsification–Evaporation Method

This work was initiated to prepare protein-stabilized β-carotene nanodispersions using emulsification–evaporation. A pre-mix of the aqueous phase composed of a protein and hexane containing β-carotene was subjected to high-pressure homogenization using a microfluidizer. Hexane in the resulting emulsion was evaporated under reduced pressures, causing crystallization and precipitation of β-carotene inside the droplets and formation of β-carotene nanoparticles. Sodium caseinate (SC) was the most effective emulsifier among selected proteins in preparing the nanodispersion, with a monomodal β-carotene particle-size distribution and a 17-nm mean particle size. The results were confirmed by transmission-electron microscopy analysis. SC-stabilized nanodispersion also had considerably high ζ-potential (−27 mV at pH 7), suggesting that the nanodispersion was stable against particle aggregation. Increasing the SC concentration decreased the mean particle size and improved the polydispersity of the nanodispersions. Nanodispersions prepared with higher β-carotene concentrations and higher organic-phase ratios resulted in larger β-carotene particles. Although increased microfluidization pressure did not decrease particle size, it did improve the polydispersity of the nanodispersions. Repeating the microfluidization process at 140 MPa caused the nanodispersions to become polydisperse, indicating the loss of emulsifying capacity of SC due to protein denaturation.