Human AKR1C Isoforms Oxidize the Potent Proximate Carcinogen 7,12-DMBA-3,4-diol in the Human Lung A549 Carcinoma Cell Line

Aldo-keto reductases (AKRs) oxidize structurally diverse PAH trans -dihydrodiols to yield reactive and redox active o -quinones. This study examined the ability of AKR1C2 and AKR1C4 to oxidize PAH trans -dihydrodiols of the benz[ a ]anthracene series. The enzymes oxidized 100% of the racemic trans -dihydrodiols and the highest utilization ratios were observed for the more potent proximate carcinogens 7,12-dimethylbenz[ a ]anthracene-3,4-diol (DMBA-3,4-diol) and 7-methylbenz[ a ]anthracene-3,4-diol (7-MBA-3,4-diol). Human multiple tissue expression array analysis revealed high expression of AKR1C isoforms in the human lung carcinoma cell line A549. Both Western blot analysis using AKR1C9 antisera and enzymatic assays using 1-acenapthanol as substrate confirmed the presence of active AKR1C enzymes in A549 cells. To determine the importance of AKR1C-mediated trans -dihydrodiol oxidation in A549 cells, DMBA-3,4-diol was incubated with cell lysates in the presence of 2-mercaptoethanol. Liquid chromatography/mass spectrometric analysis identified peaks that corresponded to the synthetically prepared mono- and bis -thioether conjugates of DMBA-3,4-dione confirming the ability of these cells to oxidize DMBA-3,4-diol to the corresponding o -quinone. Together, these studies demonstrate the importance of human AKR1Cs in PAH activation and their possible role in lung cancer.     

Software Implementation of Biological Repository for Human Genetic Material

To provide biological specimens for scientific studies, the Medical Automation Research Center (MARC) designed and constructed a large-scale device that emphasizes the use of robotics and automation to integrate many associated laboratory operations. These included analysis, dilution, archival storage, and retrieval of purified human-derived specimens. Designers of automated biological repositories are challenged by complex engineering problems. In this paper, we present an overview of the biological repository (biorepository) and give details of the software architecture.     

Drilling Fluid Considerations in Design of Engineered Horizontal Directional Drilling Installations

A literature review is presented that identifies a number of areas where procedures for the engineering design of bored installations in soil using horizontal directional drilling (HDD) can be improved through a more realistic consideration of drilling fluid drag effects and skin friction coefficients. The current HDD practice of calculating annular frictional pressure loss caused by drilling fluid drag based on the assumption of concentric annular flow of a Bingham plastic fluid is demonstrated to be overly conservative. Consequently, critical design parameters, such as depth of cover, which affects crossing length, and drilling equipment size, which is selected based on anticipated pulling load, cannot be optimized. This can result in overly conservative design and unnecessary construction costs. Parameter values currently employed in HDD pulling load prediction are challenged suggesting that the viscous shear of drilling fluid is significantly less than typically quoted and that the friction coefficients often employed are not representative of all skin friction effects in HDD. A new real-time monitoring cell for large-scale HDD is described that can be used to optimize installations and to assess and update current prediction models.     

The water needs for LDV transportation in the United States

Concern over increased demand for petroleum, reliable fuel supply, and global climate change has resulted in the US government passing new Corporate Average Fuel Economy standards and a Renewable Fuels Standard. Consequently, the fuel mix for light duty vehicle (LDV) travel in the United States will change over the coming years. This paper explores the embodied water consumption and withdrawal associated with two projections for future fuel use in the US LDV sector. This analysis encompasses conventional and unconventional fossil fuels, corn ethanol, cellulosic ethanol, soy biodiesel, electricity, and hydrogen. The existing mandate in the US to blend ethanol into gasoline had effectively committed 3300 billion liters of irrigation water in 2005 (approximately 2.4% of US 2005 fresh water consumption) for producing fuel for LDVs. With current irrigation practices, fuel processing, and electricity generation, it is estimated that by 2030, approximately 14,000 billion liters of water per year will be consumed and 23,000–27,000 billion liters withdrawn to produce fuels used in LDVs. Irrigation for biofuels dominates projected water usage for LDV travel, but other fuels (coal to liquids, oil shale, and electricity via plug-in hybrid vehicles) will also contribute appreciably to future water consumption and withdrawal, especially on a regional basis.     

A novel mechanism of cochlear excitation during simultaneous stimulation and pressure relief through the round window

The round window (RW) membrane provides pressure relief when the cochlea is excited by sound. Here, we report measurements of cochlear function from guinea pigs when the cochlea was stimulated at acoustic frequencies by movements of a miniature magnet which partially occluded the RW. Maximum cochlear sensitivity, corresponding to subnanometre magnet displacements at neural thresholds, was observed for frequencies around 20 kHz, which is similar to that for acoustic stimulation. Neural response latencies to acoustic and RW stimulation were similar and taken to indicate that both means of stimulation resulted in the generation of conventional travelling waves along the cochlear partition. It was concluded that the relatively high impedance of the ossicles, as seen from the cochlea, enabled the region of the RW not occluded by the magnet, to act as a pressure shunt during RW stimulation. We propose that travelling waves, similar to those owing to acoustic far-field pressure changes, are driven by a jet-like, near-field component of a complex pressure field, which is generated by the magnetically vibrated RW. Outcomes of research described here are theoretical and practical design principles for the development of new types of hearing aids, which use near-field, RW excitation of the cochlea.