Assessment of the relationship between genotypic status of a DT-diaphorase point mutation and enzymatic activity

DT-diaphorase, a cytosolic reductase, has been implicated as an activator of chemotherapeutic prodrugs and a detoxifier of certain potentially carcinogenic xenobiotics. A common C to T nucleotide 609 substitution in DT-diaphorase cDNA has been associated with protein instability and reduced catalytic activity. The degree to which the allelic status of the substitution correlates with enzymatic activity was assessed in 45 normal human skin fibroblast strains using a PCR-RFLP assay. Included in this study was the 3437T strain, which is unique in that it is heterozygous for the polymorphism yet contains undetectable enzymatic activity. An allele-specific RT-PCR-RFLP technique attributed this phenomenon to exclusive DT-diaphorase mRNA expression from the variant allele. Overlap in activities was observed between individual strains homozygous for the wild-type allele and heterozygotes, but the former group displayed enzymatic activity that was on average 2-fold higher. Western blot analysis of the two strains in this panel that are homozygous for the variant allele revealed that they express relatively low amounts of DT-diaphorase protein, consistent with the role of the substitution in protein instability. This work confirms that genotypic status is a reliable initial estimate of DT-diaphorase activity. © 2000 Cancer Research Campaig

The VELA-X-Pulsar Wind Nebula Revisited with Four Years of Fermi Large Area Telescope Observations

The Vela supernova remnant (SNR) is the closest SNR to Earth containing an active pulsar, the Vela pulsar (PSR B0833-45). This pulsar is an archetype of the middle-aged pulsar class and powers a bright pulsar wind nebula (PWN), Vela-X, spanning a region of 2deg 3deg south of the pulsar and observed in the radio, X-ray, and very high energy -ray domains. The detection of the Vela-X PWN by the Fermi Large Area Telescope (LAT) was reported in the first year of the mission. Subsequently, we have reinvestigated this complex region and performed a detailed morphological and spectral analysis of this source using 4 yr of Fermi-LAT observations. This study lowers the threshold for morphological analysis of the nebula from 0.8 GeV to 0.3 GeV, allowing for the inspection of distinct energy bands by the LAT for the first time. We describe the recent results obtained on this PWN and discuss the origin of the newly detected spatial features

Fermi-Lat and WMAP Observations of the Puppis a Supernova Remnant

We report the detection of GeV gamma-ray emission from the supernova remnant Puppis A with the Fermi Gamma-Ray Space Telescope. Puppis A is among the faintest supernova remnants yet detected at GeV energies, with a luminosity of only 2.710(exp 34) (D/2.2 kpc)(exp 2) erg s(exp 1) between 1 and 100 GeV. The gamma-ray emission from the remnant is spatially extended, with a morphology matching that of the radio and X-ray emission, and is well described by a simple power law with an index of 2.1. We attempt to model the broadband spectral energy distribution, from radio to gamma-rays, using standard nonthermal emission mechanisms. To constrain the relativistic electron population we use 7 years of WMAP data to extend the radio spectrum up to 93 GHz. Both leptonic and hadronic dominated models can reproduce the nonthermal spectral energy distribution, requiring a total content of cosmic ray (CR) electrons and protons accelerated in Puppis A of at least WCR is approx. (1 - 5)10 (exp 49) erg

Adiabatically coupled systems and fractional monodromy

We present a 1-parameter family of systems with fractional monodromy and adiabatic separation of motion. We relate the presence of monodromy to a redistribution of states both in the quantum and semi-quantum spectrum. We show how the fractional monodromy arises from the non diagonal action of the dynamical symmetry of the system and manifests itself as a generic property of an important subclass of adiabatically coupled systems

Spontaneous DC Current Generation in a Resistively Shunted Semiconductor Superlattice Driven by a TeraHertz Field

We study a resistively shunted semiconductor superlattice subject to a high-frequency electric field. Using a balance equation approach that incorporates the influence of the electric circuit, we determine numerically a range of amplitude and frequency of the ac field for which a dc bias and current are generated spontaneously and show that this region is likely accessible to current experiments. Our simulations reveal that the Bloch frequency corresponding to the spontaneous dc bias is approximately an integer multiple of the ac field frequency.Comment: 8 pages, Revtex, 3 Postscript figure