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Vitamin D receptor (VDR) activation therapy is associated with cardiovascular/survival benefit in chronic kidney disease (CKD), but the mechanism of action is not well understood. The ...aim of this study is to investigate how uremia affects gene expression in aorta and whether VDR activation modulates the uremic effect. DNA microarray technology was used to assess the gene expression profile in aorta prepared from SHAM and 5/6 nephrectomized (NX) rat, a model of Stage 4/5 CKD, treated with or without 0.17 μg/kg paricalcitol, a VDR activator. As expected, paricalcitol at 0.17 μg/kg after two weeks of treatment effectively suppressed serum parathyroid hormone (PTH); no significant difference was observed in ionized calcium or serum phosphorus. Uremia exhibited a significant effect on the gene expression pattern in the aorta, affecting 468 sequences ( ≥1.5-fold changes with p<0.01 vs. SHAM). When the criteria were tightened to ≥ 2-fold changes with p<0.01, uremia still affected 135 target sequences in the rat aorta with 63 up-regulated and 72 down-regulated. Target genes fell into various categories including metabolism and cellular metabolism. Paricalcitol treatment normalized 95 out of the 135 sequences affected by uremia; many of the genes were related to mitochondrial function and oxidative stress. As a follow-up to the microarray analysis, endothelial function was examined. Uremia significantly affected aortic relaxation (−50.0 ± 7.4% in NX rats vs. −96.2 ± 5.3% in SHAM at 30 μM acetylcholine). The endothelial-dependent relaxation response to acetylcholine (Ach) at 30 μM was improved to −58.2 ± 6.0%, −77.5 ± 7.3% and −90.5 ± 4.0% in NX rats treated with paricalcitol at 0.021, 0.042 and 0.083 μg/kg for two weeks, respectively, while blood pressure and heart rate were not changed. PTH suppression alone didn’t improve endothelial function since cinacalcet, a calcimimetic targeting calcium sensing receptor, suppressed PTH without affecting endothelial-dependent vasorelaxation. In conclusion, VDR activation by paricalcitol modulates the effect of uremia on aortic gene expression and endothelial function independent of PTH and blood pressure control, which may be one of the mechanisms responsible for paricalcitol’s cardiovascular benefit in CKD.
Timing methods for depth determination in germanium strip detectors Wulf, E.A.; Ampe, J.; Johnson, W.N. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
06/2003, Volume:
505, Issue:
1-2
Journal Article
Peer reviewed
The ability to measure the interaction depth of a gamma ray in a planar germanium strip detector has been demonstrated using various Constant Fraction Discriminators (CFD) and leading edge ...discriminators. Thick detectors can then be used in Compton telescopes or other detectors that require three-dimensional position resolution. Large systems based on these detectors require many thousands of channels of electronics which necessitates a move to CMOS ASIC readout. Traditional CFDs do not lend themselves to CMOS due to their need for delay lines. Different timing methods better suited for CMOS include leading edge discriminators and falling edge discriminators. The simplest methods seem to work well in the laboratory and indicate that CMOS electronics can be built to read out a thick strip detector with depth resolution. This technique is suitable for a variety of semiconductor detectors.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The continuous deposition of multi-layer oxide films on moving long-length metallic substrates using pulsed laser deposition (PLD) is reported. Epitaxial YBCO/CeO/sub 2//yttria-stabilized zirconia ...(YSZ)/CeO/sub 2/ layers were grown on 1 cm/spl times/10 cm rolled-Ni tape substrates. The Ni tape was heated radiatively and translated while oxide layers were continuously deposited. The thickness and composition along the moving direction were uniform to within /spl plusmn/7% and /spl plusmn/5%, respectively. The biaxial texture of the 10 cm Ni tape was transferred through the buffer layers to the topmost YBCO during the continuous deposition. The in-plane and out-of-plane texturing of YBCO and buffer layers were uniform along the scanning direction with variations less than /spl plusmn/10% and /spl plusmn/5%, respectively. The average transport zero field J/sub c/ (77 K) for numerous 10 cm samples was about 200,000 A/cm/sup 2/, with the highest J/sub c/ and I/sub c/ values at 77 K, 0 T of 270,000 A/cm/sup 2/ and 16.7 A respectively. This study demonstrates the feasibility of continuous multilayer, multi-component oxide film deposition on rolled-textured metal with uniform thickness, composition, and crystallographic orientation using PLD.
Gamma ray polarimetry using a position sensitive germanium detector Kroeger, R.A; Johnson, W.N; Kurfess, J.D ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
10/1999, Volume:
436, Issue:
1
Journal Article
Peer reviewed
Imaging gamma-ray detectors make sensitive polarimeters in the Compton energy regime by measuring the scatter direction of gamma rays. The principle is to capitalize on the angular dependence of the ...Compton scattering cross section to polarized gamma rays and measure the distribution of scatter directions within the detector. This technique is effective in a double-sided germanium detector between roughly 50
keV and 1
MeV. This paper reviews device characteristics important to the optimization of a Compton polarimeter, and summarizes measurements we have made using a device with a 5×5 cm active area, 1
cm thickness, and strip-electrodes on a 2
mm pitch.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Fabrication of epitaxial, high-
J
c, biaxially aligned YBCO thick films on rolling-assisted biaxially-textured substrates (RABiTS) is summarized. The RABiTS technique utilizes standard ...thermomechanical processing to obtain long lengths of flexible, biaxially oriented substrates with smooth surfaces (rms ∽50
nm). The strong biaxial texture of the metal (in-plane 6–7° FWHM) is conferred to the superconductor by deposition of intermediate metal and/or oxide layers which serve both as a chemical as well as a structural buffer. Epitaxial YBCO films grown using laser ablation on RABiTS™ have critical current densities exceeding 10
6 A
cm
−2 at 77
K in zero-field and have field dependences similar to epitaxial films on single crystal ceramic substrates. The texture of the base metal has been achieved in lengths over 1
m and scaleable techniques are being pursued to deposit epitaxial multilayers. Deposited conductors made using this technique offer a potential route for the fabrication of long lengths of high-
J
c wire capable of carrying high currents in high magnetic fields and at elevated temperatures.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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