The influence of SLCO1B1 (OATP1B1) gene polymorphisms on response to statin therapy.

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are well established in the treatment of hypercholesterolaemia and the prevention of coronary artery disease. Despite this, there is wide inter-individual variability in response to statin therapy, in terms of both lipid-lowering and adverse drug reactions. The major site of statin action is within hepatocytes and recent interest has focussed on genetic variation in hepatic influx and efflux transporters for their potential to explain these differences. In this review we explore current literature regarding the pharmacokinetic and pharmacodynamic influence of the common c.388A>G and c.521T>C single-nucleotide polymorphisms (SNPs) within the solute carrier organic anion transporter 1B1 (SLCO1B1) gene, encoding the organic anion transporter polypeptide 1B1 (OATP1B1) influx transporter. We discuss their potential to predict the efficacy of statin therapy and the likelihood that patients will experience adverse effects.

Characterization and calibration of a multilayer coated Wolter optic for an imager on the Z-machine at Sandia National Laboratories.

The need for a time-resolved monochromatic x-ray imaging diagnostic at photon energies >15 keV has motivated the development of a Wolter optic to study x-ray sources on the Z-machine at Sandia National Laboratories. The work is performed in both the LLNL's x-ray calibration facility and SNL's micro-focus x-ray lab. Characterizations and calibrations include alignment, measurement of throughput within the field of view (FOV), the point-spread function within the FOV both in and out of focus, and bandpass in the FOV. These results are compared with ray tracing models, showing reasonable agreement.

An x-ray optic calibration facility for high energy density diagnostics.

A facility to calibrate x-ray imaging optics was built at Lawrence Livermore National Laboratory to support high energy density (HED) and inertial confinement fusion (ICF) diagnostics such as those at the National Ignition Facility and the Sandia Z-Machine. Calibration of the spectral reflectivity and resolution of these x-ray diagnostics enable absolute determination of the x-ray flux and wavelengths generated in the HED and ICF experiments. Measurement of the optic point spread function is used to determine spatial resolution of the optic. This facility was constructed to measure (1) the x-ray reflectivity to ±5% over a spectral range from 5 to 60 keV; (2) point spread functions with a resolution of 50 µm (currently) and 13 µm (future) in the image plane; and (3) optic distance relative to the x-ray source and detector to within ±100 µm in each dimension. This article describes the capabilities of the calibration facility, concept of operations, and initial data from selected x-ray optics.

Design and raytrace simulations of a multilayer-coated Wolter x-ray optic for the Z machine at Sandia National Laboratories.

Recent breakthroughs in the fabrication of small-radii Wolter optics for astrophysics allow high energy density facilities to consider such optics as novel x-ray diagnostics at photon energies of 15-50 keV. Recently, the Lawrence Livermore National Laboratory, Sandia National Laboratories (SNL), the Smithsonian Astrophysical Observatory, and the NASA Marshall Space Flight Center jointly developed and fabricated the first custom Wolter microscope for implementation in SNL's Z machine with optimized sensitivity at 17.5 keV. To achieve spatial resolution of order 100-200 microns over a field of view of 5 × 5 × 5 mm3 with high throughput and narrow energy bandpass, the geometry of the optic and its multilayer required careful design and optimization. While the geometry mainly influences resolution and the field of view of the diagnostic, the mirror coating determines the spectral response and throughput. Here we outline the details of the design and fabrication process for the first multilayer-coated Wolter I optic for SNL's Z machine (Z Wolter), including its W/Si multilayer, and present results of raytrace simulations completed to predict and verify the performance of the optic.

A Wolter imager on the Z machine to diagnose warm x-ray sources.

A new Wolter x-ray imager has been developed for the Z machine to study the emission of warm (>15 keV) x-ray sources. A Wolter optic has been adapted from observational astronomy and medical imaging, which uses curved x-ray mirrors to form a 2D image of a source with 5 × 5 × 5 mm3 field-of-view and measured 60-300-µm resolution on-axis. The mirrors consist of a multilayer that create a narrow bandpass around the Mo Kα lines at 17.5 keV. We provide an overview of the instrument design and measured imaging performance. In addition, we present the first data from the instrument of a Mo wire array z-pinch on the Z machine, demonstrating improvements in spatial resolution and a 350-4100× increase in the signal over previous pinhole imaging techniques.

Measurements of the hard-x-ray reflectivity of iridium.

In connection with the design of a hard-x-ray telescope for the Constellation X-Ray Observatory we measured the reflectivity of an iridium-coated zerodur substrate as a function of angle at 55, 60, 70, and 80 keV at the National Synchrotron Light Source of Brookhaven National Laboratory. The optical constants were derived from the reflectivity data. The real component of the index of refraction is in excellent agreement with theoretical values at all four energies. However, the imaginary component, which is related to the mass attenuation coefficient, is 50% to 70% larger at 55, 60, and 70 keV than theoretical values.