Evidence supporting the formation of 2,3-epoxy-3-methylindoline: a reactive intermediate of the pneumotoxin 3-methylindole

The existence of a cytochrome P450-dependent 2,3-epoxide of the potent pneumotoxin 3-methylindole was indirectly confirmed using stable isotope techniques and mass spectrometry. Determination of hydride shift and incorporation of labeled oxygen in 3-methyloxindole and 3-hydroxy-3-methyloxindole, metabolites that may be in part dependent on the presence of the epoxide, were utilized as indicators of the epoxide's existence. One mechanism for the formation of 3-methyloxindole involves cytochrome P450-mediated epoxidation followed by ring opening requiring a hydride shift from C-2 to C-3. Through incubations of goat lung microsomes with [2-2H]-3-methylindole, the retention of 2H in 3-methyloxindole was found to be 81%, indicating a majority of the oxindole was produced by the mechanism described above. 3-Hydroxy-3-methylindolenine is an imine reactive intermediate that could be produced by ring opening of the 2,3-epoxide. The imine may be oxidized to 3-hydroxy-3-methyloxindole by the cytosolic enzyme aldehyde oxidase. Activities of this putative detoxification enzyme were determined in both hepatic and pulmonary tissues from goats, rats, mice, and rabbits, but the activities could not be correlated to the relative susceptibilities of the four species to 3-methylindole toxicity. The 18O incorporation into either 3-methyloxindole or 3-hydroxy-3-methyloxindole from both 18O2 and H218O was determined. The 18O incorporation into 3-methyloxindole from 18O2 was 91%, strongly implicating a mechanism requiring cytochrome P450-mediated oxygenation. Incorporation of 18O into 3-hydroxy-3-methyloxindole indicated that the alcohol oxygen originated from molecular oxygen, also implicating an epoxide precursor. These studies demonstrate the existence of two new reactive intermediates of 3-methylindole and describe the mechanisms of their formation and fate.     

Oleamide potentiates benzodiazepine-sensitive gamma-aminobutyric acid receptor activity but does not alter minimum alveolar anesthetic concentration

Short-term exposure to ozone at peak ambient levels induces neutrophil influx and impairs lung function in healthy humans. In order to investigate the mechanisms contributing to neutrophil recruitment and to examine the role of T-cells in the acute inflammatory response, we exposed 12 healthy humans to 0.2 parts per million (ppm) of ozone and filtered air on two separate occasions for 2 h with intermittent periods of rest and exercise (minute ventilation = 30 L x min(-1)). Fibreoptic bronchoscopy was performed 6 h after the end of exposures. Total protein, tryptase, histamine, myeloperoxidase, interleukin (IL)-8 and growth-related oncogene-alpha (Gro-alpha) were measured and total and differential cell counts were performed in bronchoalveolar lavage (BAL) fluid. Flow cytometry was performed on BAL cells to study total T-cells, T-cell receptors (alphabeta and gammadelta), T-cell subsets (CD4+ and CD8+ cells) and activated T-cell subsets (CD25+). Using immunohistochemistry, neutrophils, mast cells, total T-cell numbers, T-cell subsets, CD25+ T-cells and leukocyte endothelial adhesion molecules including P-selectin, E-selectin, intercellular adhesion molecule (ICAM)-1 and vascular adhesion molecule (VCAM)-1 were quantified in the bronchial biopsies. Paired samples were available from nine subjects. Following ozone exposure there was a threefold increase in the proportion of polymorphonuclear neutrophils (PMNs) (p=0.07) and epithelial cells (p=0.05) in BAL fluid. This was accompanied by increased concentrations of IL-8 (p=0.01), Gro-alpha (p=0.05) and total protein (p=0.058). A significant positive correlation was demonstrated between the two chemokines and proportion of PMNs in BAL fluid. After ozone exposure there was a significant decrease in the CD4/CD8 ratio (p=0.05) and the proportion of activated CD4+ (p=0.01) and CD8+ T-cells (p=0.04). However, no significant changes were demonstrable in any of the inflammatory markers studied in the biopsies. Short-term exposure of healthy humans to 0.2 ppm ozone induced a neutrophil influx in peripheral airways at 6 h post exposure, but no apparent inflammatory response in proximal airways. This response seems to be mediated at least in part by interleukin-8 and growth-related oncogene-alpha.     

A wafer-scale 3-D circuit integration technology

The rationale and development of a wafer-scale three-dimensional (3-D) integrated circuit technology are described. The essential elements of the 3-D technology are integrated circuit fabrication on silicon-on-insulator wafers, precision wafer-wafer alignment using an in-house-developed alignment system, low-temperature wafer-wafer bonding to transfer and stack active circuit layers, and interconnection of the circuit layers with dense-vertical connections with sub-/spl Omega/ 3-D via resistances. The 3-D integration process is described as well as the properties of the four enabling technologies. The wafer-scale 3-D technology imposes constraints on the placement of the first lithographic level in a wafer-stepper process. Control of wafer distortion and wafer bow is required to achieve submicrometer vertical vias. Three-tier digital and analog 3-D circuits were designed and fabricated. The performance characteristics of a 3-D ring oscillator, a 1024 /spl times/ 1024 visible imager with an 8-/spl mu/m pixel pitch, and a 64 /spl times/ 64 Geiger-mode laser radar chip are described.     

On Nonuniform Windowing M-ary FSK Data in a DFT-Based Detector

Nonuniform amplitude windowingM-ary frequency shiftkeying (FSK) data prior to demodulation reduces the crosstalk normally caused by Doppler and oscillator drift. A major disadvantage of such nonuniform windowing is the loss in signal detectability as a result of the mismatch between the nonuniform windowed signal and the uniform windowed detectors. This paper is concerned with the tradeoff of nonuniform windowing to combat frequency offset degradation and signal detectability losses caused by the use of such windows in a DFT (discrete Fourier transform)-based detector of noncoherentM-ary FSK. What is shown here is that if a frequency control system can maintain frequency to within a certain deviation (which depends on error rate and nonuniform window), nonuniform windowing is not warranted; on the other hand, if the frequency deviation becomes too large, nonuniform windowing is advised. A technique is developed that will determine this crossover deviation.     

Structural behavior of alkali activated fly ash concrete. Part 1: mixture design, material properties and sample fabrication

Alkali Activated Fly Ash Concrete (AAFAC) is an alternative form of concrete that uses fly ash as a 100 % replacement for ordinary portland cement. In producing AAFAC, fly ash is combined with alkali activators that chemically react to form a binder. When combined further with fine and coarse aggregates and often cured at elevated temperature, a concrete material is produced with strength and stiffness properties similar to ordinary portland cement concrete (OPCC). In this paper fabrication of full scale steel reinforced AAFAC beams is presented. The research scope includes: development of an AAFAC mixture design, fabrication of nine AAFAC beam samples, development of an elevated temperature curing system, temperature measurement during curing, and investigation of hardened AAFAC material properties. Results show AAFAC can be manufactured in the same way as OPCC, and that it has a self consolidating consistency in the fresh state. Curing at 60 °C for 24 h produced very rapid strength gain. Compression strengths at 1 day ranged between 47 and 53 MPa, with 28 days compression strengths ranging from 48 to 55 MPa. Material test results show AAFAC is a brittle material with an approximately linear stress–strain response, and an elastic modulus slightly less than that predicted by ACI 318.     

Power dissipation in clocking wires for clocked molecular quantum-dot cellular automata

In the molecular quantum-dot cellular automata (QCA) paradigm clocking wires are used to produce an electric field which is perpendicular to the device plane of surface-bound molecules and is sinusoidally modulated in space and time. This clocking field guides the data flow through the molecular QCA array. Power is dissipated in clocking wires due to the non-zero resistance of the conductors. We analyze quantitatively the amount of power dissipated in the clocking wires and find that in the relevant parameter range it is fairly small. Dissipation in the molecular devices themselves will likely dominate the energy budget.     

Parent and neutral loss monitoring on a quadrupole ion trap mass spectrometer: screening of acylcarnitines in complex mixtures

A novel and practical technique for performing both parent and neutral loss (P&NL) monitoring experiments on a quadrupole ion trap mass spectrometer is presented. This technique is capable of performing scans analogous to the parent and neutral loss scans routinely applied on tandem-in-space instruments and allows for the screening of a sample to detect analytes of a specific compound class on a chromatographic time-scale. Acylcarnitines were chosen as the model compound class to demonstrate the analytical utility of P&NL monitoring because of their amenability to electrospray ionization (ESI), their unique and informative MS/MS fragmentation pattern, and their importance in biological functions. The [M + H]+ ions of all acylcarnitines dissociate to produce neutral losses of 59 and 161 amu and common product ions at m/z 60, 85, and 144. Both the neutral loss monitoring of 59 amu and the parent ion monitoring of m/z 85 are shown to be capable of identifying acylcarnitine [M + H]+ ions in a synthetic mixture and spiked pig plasma. The neutral loss monitoring of 59 amu is successful in detecting acylcarnitines in an unspiked pig plasma sample.     

Analysis of intact tissue by intermediate-pressure MALDI on a linear ion trap mass spectrometer

The use of an intermediate-pressure matrix-assisted laser desorption/ionization (IP-MALDI) source working at 0.17 Torr on a linear ion trap (LIT) was investigated for the analysis of tissue specimens, in particular, spinal cord sections. MALDI, with 2,5-dihydroxybenzoic acid (DHB) as the matrix, was employed for the detection of phospholipids. The matrix was applied to the tissue using electrospray to avoid analyte migration. The results indicate that analyzing tissue specimens at nontraditional MALDI vacuum pressures is possible. Coupling MALDI to an LIT permits the use of MSn, which is critical for the ability to identify compounds desorbed directly from tissue specimens. Using MSn, ions detected from m/z 600-1000 were characterized as phosphatidlycholines, PC. Specifically, using tandem MS, PC ions could be classified as either [M + H]+ or [M + Na]+ because the fragmentation patterns of protonated and sodiated phosphatidlycholines follow different pathways.     

x86架构丰富联网汽车中的交互体验

引言 随着Web服务、内容和应用的日益普及,包括汽车制造商以及服务和内容提供商在内的众多厂商都迎来了巨大的商机.汽车制造商可以借此提供开放的信息娱乐平台,使之以多种方式连接到互联网,并在平台硬件的支持下高效、灵活而安全地运行最新、最完善的Web应用.本文主要讲述了x86平台架构如何为用户带来丰富的交互式驾驶体验,而这是非PC兼容型平台难以实现的.