First Stability Characterization for a CZT Detection System in an ee Collider Environment.

The SIDDHARTA-2 collaboration has developed a novel X-ray detection system based on cadmium-zinc-telluride (CZT, CdZnTe), marking the first application of this technology at the DAΦNE electron-positron collider at INFN-LNF. This work aims to demonstrate the stability of the detectors' performance in terms of linearity and resolution over short and long periods, thereby establishing their suitability for precise spectroscopic measurements within a collider environment. A reference calibration spectrum is presented in association with findings from assessments of linearity and resolution stability.

High-efficiency generation of pulsed Lyman-α radiation by resonant laser wave mixing in low pressure Kr-Ar mixture.

We report an experimental generation of ns pulsed 121.568 nm Lyman-α radiation by the resonant nonlinear four-wave mixing of 212.556 nm and 845.

Important amino acid residues that confer CYP2C19 selective activity to CYP2C9.

Although CYP2C9 and CYP2C19 display 91% sequence identity at the amino acid level, the two enzymes have distinct substrate specificities for compounds such as diclofenac, progesterone and (S)-mephenytoin. Amino acid substitutions in CYP2C9 were made based on an alignment of CYP2C9, CYP2C19 and monkey CYP2C43 sequences. Mutants of CYP2C9 were expressed in Escherichia coli.

Cynomolgus monkey cytochrome P450 2C43: cDNA cloning, heterologous expression, purification and characterization.

The cDNA of cytochrome P450 (CYP) 2C43 was cloned from cynomolgus monkey liver by RT-PCR. The deduced amino acid sequence showed 93% and 91% identity to human CYP2C9 and CYP2C19, respectively. The cDNA was expressed in Escherichia coli and purified by a series of chromatography steps, yielding a specific content of 11.

Improvement in the expression of CYP2B6 by co-expression with molecular chaperones GroES/EL in Escherichia coli.

Improvement of CYP2B6 expression was examined by co-expression with molecular chaperones GroES/EL. Although a CO-reduced difference spectrum was not detected in Escherichia coli transformed only by the CYP2B6-expressing vector, co-expression of GroES/EL resulted in high-level expression which reached over 2000 nmol P450/L. CYP2B6 was purified from the E.

Functional characterization of single nucleotide polymorphisms with amino acid substitution in CYP1A2, CYP2A6, and CYP2B6 found in the Japanese population.

As a part of the studies conducted by the Pharma SNPs Consortium (PSC), the enzyme activities of CYP1A2, CYP2A6 and CYP2B6 variants with altered amino acids as a result of single nucleotide polymorphisms (SNPs) found among the Japanese population were analyzed under a unified protocol using the same lots of reagents by the laboratories participating in the PSC. Mutations in CYP1A2, CYP2A6 and CYP2B6 were introduced by site-directed mutagenesis and the wild type and mutated CYP molecules were expressed in Escherichia coli. The expressed cytochrome P450s were purified and the enzyme activities were measured in reconstitution systems.

C17,20-lyase inhibitors I. Structure-based de novo design and SAR study of C17,20-lyase inhibitors.

Novel nonsteroidal C(17,20)-lyase inhibitors were synthesized using de novo design based on its substrate, 17 alpha-hydroxypregnenolone, and several compounds exhibited potent C(17,20)-lyase inhibition. However, in vivo activities were found to be short-lasting, and in order to improve the duration of action, a series of benzothiophene derivatives were evaluated. As a result, compounds 9h, (S)-9i, and 9k with nanomolar enzyme inhibition (IC(50)=4-9 nM) and 9e (IC(50)=27 nM) were identified to have powerful in vivo efficacy with extended duration of action.