Insulin effects on CYP2E1, 2B, 3A, and 4A expression in primary cultured rat hepatocytes

Although hyperketonemia and/or altered growth hormone secretion caused by diabetes have been implicated in enhanced CYP2E1, 2B, 3A and 4A expression, the effect of insulin on hepatic P450 expression, in the absence of associated metabolic/hormonal alterations, remains unknown. Primary cultured rat hepatocytes have been shown (Zangar et al., Drug Metab. Dispos., 23:681, 1995) to express stable and inducible CYP2E1 mRNA and protein levels, and provide an excellent system for mechanistic examination of the effect of insulin on CYP2E1, 2B, 3A and 4A expression. Maintaining primary rat hepatocytes in culture in the absence of insulin for 48, 72, or 96 h increased CYP2E1 mRNA levels 5-, 11-, and 4-fold, respectively, relative to cells maintained in the presence of the standard concentration of 1 microM insulin. In contrast, CYP2B mRNA levels increased only approximately 2-fold in the absence of insulin, when compared with the presence of 1 microM insulin. CYP2E1 and 2B protein levels were increased 6.7- and 3.8-fold, respectively, in cells cultured for 96 h in the absence of insulin as compared with those cultured in medium containing 1 microM insulin. Concentration-response studies revealed that decreasing the concentration of insulin below 10 nM (i.e. 1 nM, 0.1 nM, no insulin) increased CYP2E1 mRNA levels 4-, 7-, and 11-fold, respectively. In contrast, no such concentration-dependence was observed for CYP2B mRNA expression. As CYP3A and 4A expression is also elevated in diabetic rats, the effects of insulin on these P450s was also examined. CYP3A mRNA levels were unaltered and CYP4A mRNA levels were decreased marginally (approximately 50%) by the absence of insulin relative to levels in cells cultured in the presence of 1 microM insulin over 96 h in culture. The results of this study provide evidence that insulin itself, in the absence of other diabetes-induced metabolic or hormonal alterations, affects CYP2E1 and 2B, but not CYP3A or 4A, expression in primary cultured rat hepatocytes. Furthermore, CYP2E1 expression is differentially regulated by insulin relative to CYP2B, 3A or 4A. This study also demonstrates that decreasing the concentration of insulin in the culture medium provides a method by which CYP2E1 levels can be increased in primary cultured hepatocytes to facilitate mechanistic studies on the regulation of CYP2E1 expression.     

Dewatering of Sewage Sludge

Dewatering of sewage sludges is usually carried out using belt filter presses or centrifuges. The ability to remove water from sludges by mechanical dewatering is a property of both the sludge and the equipment used for dewatering. Newer high-solids centrifuges can remove more water than a belt press but require a higher chemical conditioning dose. The Gt value, the product of the mean velocity gradient and the shear time, has been found to be a useful parameter for characterizing the shear in mechanical dewatering equipment. Dewatering can be considered a two-step process, filtration followed by expression. The expression step is the most important of these and the benefits of various sludge processing techniques and conditioning chemical types remains a fruitful area of research.     

Influence of thickness and processing history on fatigue fracture of nylon 66. Part II: Crack tip morphology

Fatigue crack propagation rates in injection molded nylon 66 were previously shown to be strongly affected by prior processing history. To provide a physical basis for the observed acceleration in crack growth rates, microtomed sections were cut through the tips of stable fatigue cracks and examined by optical microscopy. A reduction in spherulite size occurs with reprocessing along with an accompanying decrease in the amount of deformation at the crack tip. For the initially processed nylon 66 this deformation consists of a vast array of independently initiated craze-like zones. Patchy type regions observed on the fatigue fracture surface are similar in size to the initially formed crazed zones. Crack advance occurs by the breakdown and coalescence of the crazed regions via matrix shearing. The extensive damage zone is believed to result in a reduction in stress intensity at the crack tip thereby reducing the crack propagation rates. For the reprocessed nylon 66, one observes fewer crazes and a sharper fatigue crack tip with a consequent acceleration in crack propagation rates and a smoother fracture surface.     

Robust Kalman filtering for nonlinear multivariable stochastic systems in the presence of non‐Gaussian noise

The presence of outliers can considerably degrade the performance of linear recursive algorithms based on the assumptions that measurements have a Gaussian distribution. Namely, in measurements there are rare, inconsistent observations with the largest part of population of observations (outliers). Therefore, synthesis of robust algorithms is of primary interest. The Masreliez–Martin filter is used as a natural frame for realization of the state estimation algorithm of linear systems. Improvement of performances and practical values of the Masreliez‐Martin filter as well as the tendency to expand its application to nonlinear systems represent motives to design the modified extended Masreliez–Martin filter. The behaviour of the new approach to nonlinear filtering, in the case when measurements have non‐Gaussian distributions, is illustrated by intensive simulations. Copyright © 2015 John Wiley & Sons, Ltd.     

Technique for accurate stellar polarimetry using CCD cameras

Using a technique for CCD polarimetry, we have obtained stellar polarization data with the 0.9-m telescope on Kitt Peak and with the Tek 2048 CCD camera. Measurements of stars viewed through holes in polarizing filters serve to correct for variations in atmospheric transparency. For the brightest stars the uncertainties in the measured polarization during a single, hour-long, polarimetric sequence are 0.3-0.5%, because of the residual effects of the variations in transparency. For fainter stars we are Poisson noise limited. Our technique provides some advantages over other techniques for CCD polarimetry, primarily because it can be easily integrated into existing photometric systems.     

Social recovery of monkeys isolated for the first year of life: I. Rehabilitation and therapy.

Previous research demonstrated that 12 mo of total social isolation initiated at birth produced severe and seemingly permanent social deficits in rhesus monkeys. Such monkeys exhibited self-clasping, self-mouthing, and other stereotypic, self-directed responses. Recent research has indicated that 6-mo-isolated monkeys could develop social behaviors if exposed to younger, socially unsophisticated "therapist" monkeys. In the present experiment, 4 12-mo isolate-reared monkeys developed appropriate species-typical behavior through the use of adaptation, self-pacing of visual input, and exposure to 4 younger "therapist" monkeys. Adaptation enabled the isolate Ss to become familiar with their postisolation environment, while self-pacing facilitated their watching the therapist Ss' social interactions. The isolates showed a marked decrease in self-directed behaviors following extensive intimate contact with the therapists. Species-typical behaviors significantly increased during this period, so that the isolate behavioral repertoire did not differ substantially from the therapist behavioral repertoire by the end of the therapy period. Results clearly fail to support a critical period for socialization in the rhesus monkey, and an alternative environment-specific learning hypothesis is proposed. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alzheimer paired helical filaments (PHFs) studied by high-resolution TEM: what can vertical Pt-C replication tell us about the organization of the pronase-digested PHF core?

Untreated paired helical filaments (PHFs) and pronase-digested PHF-core filaments were stereoscopically imaged with a freeze-drying vertical platinum-carbon replication preparation method for TEM. The untreated PHF have an average wide region (W) = 22.8 +/- 2.4 nm, a narrow region (T) = 10.6 +/- 1.7 nm, and a helical turn period (L) = 78.6 +/- 13.4. The surfaces of the untreated PHF's fuzzy coat appears disorganized. The widths of the pronase-treated PHF-core filaments were significantly reduced (W(d) = 14.8 +/- 1.2 nm, T(d) = 5.7 +/- 1.0 nm, and L(d) = 75.4 +/- 17 nm). The surfaces of the untreated PHF contained approximately 1.1 nm strands, the same size as tau monomer ( approximately 1.0 nm). The pronase-digested PHF cores mostly contained approximately 1.6 +/- 0.3 nm strands although strand diameters ranged from 0.6-2.5 nm. The strands sometimes appear to be wrapped around the filament axis; less often, they appear to be roughly parallel to the PHF axis, and otherwise appear to be randomly oriented. Images of pronase-digested PHF core images are discussed in relation to the core's biochemical composition, its proposed beta structure, and structural subunit models. Images of the untreated and the pronase-digested PHF support a helical ribbon morphology.     

Investigation of the Electrochemical Stop Etching of Silicon Upon the Fabrication of Cantilevers

Semiconductors - Anisotropic etching in potassium hydroxide (KOH) solution with electrochemical stop is commonly used in the formation of thin silicon membranes of sensitive elements in various...