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Cytochrome P450s metabolize the naturally occurring nephrotoxin aristolochic acid. Using liver-specific cytochrome P450 reductase-null mice we found that a low but lethal dose of aristolochic acid I was ineffective in wild-type mice. Induction of hepatic CYP1A by 3-methylcholanthrene pretreatment markedly increased the survival rate of wild type mice given higher doses and these mice were protected from aristolochic acid I-induced renal injury. Clearance of aristolochic acid I in null mice was slower compared to control and the 3-methylcholanthrene-pretreated wild type mice. The levels of aristolochic acid I in the kidney and liver were much higher in null mice but much lower in 3-methylcholanthrene-treated compared to control wild type mice. Hepatic microsomes from 3-methylcholanthrene-treated wild type mice had greater activity compared to untreated mice. Finally, aristolochic acid I was more cytotoxic than its major metabolite aristolactam I and this cytotoxicity was decreased in human renal tubular epithelial HK2 cells in the presence of a reconstituted hepatic microsome-cytosol (S9) system. These results indicate that hepatic P450s play an important role in metabolizing aristolochic acid I into less toxic metabolites and thus have a detoxification role in aristolochic acid I-induced kidney injury.

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We demonstrate the existence of an interfacial barrier in blocked impurity band (BIB) detectors using temperature-dependent dark current and corresponding theoretical calculations. Considering the effects of the interfacial barrier, the calculated photoresponse is in good agreement with the experimental results. A dual-excitation model, including the direct excitation over the full barrier and excitation to the band minimum with subsequent tunneling into the blocking layer, is proposed to quantitatively explain the observed photoresponse extension. A concept of extended-mode detection is developed to suggest the option for some selective photoresponse in the terahertz region and open the possibility of extending BIB photoresponse to lower frequency.

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The high-frequency operation of a mid-infrared interband cascade system that consists of a type-I interband cascade laser and an uncooled interband cascade infrared photodetector (ICIP) is demonstrated at room temperature. The 3-dB bandwidth of this system under direct frequency modulation was ∼850 MHz. A circuit model was developed to analyze the high-frequency characteristics. The extracted 3-dB bandwidth for an uncooled ICIP was ∼1.3 GHz, signifying the great potential of interband cascade structures for high-speed applications. The normalized Johnson-noise-limited detectivity of these ICIPs exceeded 109 cm Hz1/2/W at 300 K. These results validate the advantage of ICIPs to achieve both high speed and high sensitivity at high temperatures.