A high-resolution transmission-type x-ray spectrometer designed for observation of the Kα transitions of highly charged high-Z ions

High-resolution reflection-type crystal spectrometers have been used for x-ray energies up to 13 keV, e.g., the K-shell radiation of heliumlike Kr. In order to extend crystal spectrometer measurements to higher energy x rays from higher-Z elements, we employ the crystal in transmission. The geometry we use is known as DuMond geometry. Using such a transmission-type crystal x-ray spectrometer, we have measured the K-shell radiation of various highly charged high-Z ions. In particular, we present a measurement of the 1s2p 1P1→1s2 1S0 transition in heliumlike xenon, Xe52+. For this transition, we measure a linewidth of 34 eV, which demonstrates that the resolving power we achieved with the new spectrometer is on the order of 100

Laboratory Measurements of Fe XXIV L-Shell Line Emission

Recent ASCA spectra exhibit discrepancies with the relative line intensities of various Fe XXIII and XXIV L-shell emission lines predicted by standard plasma emission codes. To address this issue, we have carried out a series of high-resolution, broadband measurements of Fe XXIV line emission using an electron beam ion trap facility. X-ray lines produced in the trap are detected and resolved using Bragg crystal spectrometers. We report measurements of 3 → 2 and 4 → 2 transitions, which result primarily from electron impact excitation. Overall, good agreement is found with distorted wave calculations

Laboratory Measurements of Fe XXIV L-Shell Line Emission

Recent ASCA spectra exhibit discrepancies with the relative line intensities of various Fe XXIII and XXIV L-shell emission lines predicted by standard plasma emission codes. To address this issue, we have carried out a series of high-resolution, broadband measurements of Fe XXIV line emission using an electron beam ion trap facility. X-ray lines produced in the trap are detected and resolved using Bragg crystal spectrometers. We report measurements of 33 2 and 43 2 transitions, which result primarily from electron impact excitation. Overall, good agreement is found with distorted wave calculations

Measurement and interpretation of the polarization of the x-ray line emission of heliumlike Fe XXV excited by an electron beam

The linear polarization of the 1s2p 1P1→1s2 1S0 resonance line, the 1s2p 3P1,2→1s2 1S0 intercombination lines, and the 1s2s 3S1→1s2 1S0 forbidden line was measured in heliumlike Fe XXV excited near threshold by a monoenergetic electron beam. The measurement was carried out with a high-resolution x-ray spectrometer employing a set of two analyzing crystals that acted as polarizers by selectively reflecting the individual polarization components. A value of +0.56-0.08+0.17 was determined for the polarization of the 1P1 line, -0.53-0.02+0.05 for the 3P2 line, -0.22-0.02+0.05 for the 3P1 line, and -0.076-0.007+0.007 for the 3S1 line. The measurements were compared with results from a relativistic distorted-wave calculation, which was carried out for a number of mid-Z heliumlike ions (Mg10+–Kr34+), and good agreement was found. By contrast, disagreement was noted with predictions based on Coulomb-Born calculations, allowing us to distinguish between theoretical approaches

Overview of the current spectroscopy effort on the Livermore electron beam ion traps

An overview is given of the current spectroscopic effort on the Livermore electron beam ion trap facilities. The effort focuses on four aspects: spectral line position, line intensity, temporal evolution, and line shape. Examples of line position measurements include studies of the K-shell transitions in heliumlike Kr34+ and the 2s-2p intrashell transitions in lithiumlike Th87+ and U89+, which provide benchmark values for testing the theory of relativistic and quantum electrodynamical contributions in high-Z ions. Examples of line intensity measurements are provided by measurements of the electron-impact excitation and dielectronic recombination cross sections of the heliumlike transition-metal ions Ti20+ through Co25+. A discussion of radiative lifetime measurements of metastable levels in heliumlike ions is given to illustrate our time-resolved spectroscopy techniques in the microsecond range. We also present a measurement of the spectral lineshape that illustrates the very low ion temperatures that can be achieved in an EBIT

Comparison of explicit calculations for n = 3 to 8 dielectronic satellites of the FeXXV K. alpha. resonance line with experimental data from the Tokamak Fusion Test Reactor

Dielectronic satellite spectra of the FeXXV K{alpha} resonance line observed from the Tokamak Fusion Test Reactor (TFTR) plasmas have been compared with recent explicit calculations for the n = 3 to 8 dielectronic satellites as well as the earlier theoretical predictions, which were based on the 1/n{sup 3} scaling law for n > 4 satellites. The analysis has been performed by least-squares fits of synthetic spectra to the experimental data. The synthetic spectra constructed from both theories are in good agreement with the observed data. However, the electron temperature values obtained from the fit of the present explicit calculations are in better agreement with independent measurements. 20 refs., 4 figs

Inactivation of serum response factor contributes to decrease vascular muscular tone and arterial stiffness in mice

RATIONALE: Vascular smooth muscle (SM) cell phenotypic modulation plays an important role in arterial stiffening associated with aging. Serum response factor (SRF) is a major transcription factor regulating SM genes involved in maintenance of the contractile state of vascular SM cells. OBJECTIVE: We investigated whether SRF and its target genes regulate intrinsic SM tone and thereby arterial stiffness. METHODS AND RESULTS: The SRF gene was inactivated SM-specific knockout of SRF (SRF(SMKO)) specifically in vascular SM cells by injection of tamoxifen into adult transgenic mice. Fifteen days later, arterial pressure and carotid thickness were lower in SRF(SMKO) than in control mice. The carotid distensibility/pressure and elastic modulus/wall stress curves showed a greater arterial elasticity in SRF(SMKO) without modification in collagen/elastin ratio. In SRF(SMKO), vasodilation was decreased in aorta and carotid arteries, whereas a decrease in contractile response was found in mesenteric arteries. By contrast, in mice with inducible SRF overexpression, the in vitro contractile response was significantly increased in all arteries. Without endothelium, the contraction was reduced in SRF(SMKO) compared with control aortic rings owing to impairment of the NO pathway. Contractile components (SM-actin and myosin light chain), regulators of the contractile response (myosin light chain kinase, myosin phosphatase target subunit 1, and protein kinase C-potentiated myosin phosphatase inhibitor) and integrins were reduced in SRF(SMKO). CONCLUSIONS: SRF controls vasoconstriction in mesenteric arteries via vascular SM cell phenotypic modulation linked to changes in contractile protein gene expression. SRF-related decreases in vasomotor tone and cell-matrix attachment increase arterial elasticity in large arteries

Microenvironmental Influence on Pre-Clinical Activity of Polo-Like Kinase Inhibition in Multiple Myeloma: Implications for Clinical Translation

Polo-like kinases (PLKs) play an important role in cell cycle progression, checkpoint control and mitosis. The high mitotic index and chromosomal instability of advanced cancers suggest that PLK inhibitors may be an attractive therapeutic option for presently incurable advanced neoplasias with systemic involvement, such as multiple myeloma (MM). We studied the PLK 1, 2, 3 inhibitor BI 2536 and observed potent (IC50<40 nM) and rapid (commitment to cell death <24 hrs) in vitro activity against MM cells in isolation, as well as in vivo activity against a traditional subcutaneous xenograft mouse model. Tumor cells in MM patients, however, don't exist in isolation, but reside in and interact with the bone microenvironment. Therefore conventional in vitro and in vivo preclinical assays don't take into account how interactions between MM cells and the bone microenvironment can potentially confer drug resistance. To probe this question, we performed tumor cell compartment-specific bioluminescence imaging assays to compare the preclinical anti-MM activity of BI 2536 in vitro in the presence vs. absence of stromal cells or osteoclasts. We observed that the presence of these bone marrow non-malignant cells led to decreased anti-MM activity of BI 2536. We further validated these results in an orthotopic in vivo mouse model of diffuse MM bone lesions where tumor cells interact with non-malignant cells of the bone microenvironment. We again observed that BI 2536 had decreased activity in this in vivo model of tumor-bone microenvironment interactions highlighting that, despite BI 2536's promising activity in conventional assays, its lack of activity in microenvironmental models raises concerns for its clinical development for MM. More broadly, preclinical drug testing in the absence of relevant tumor microenvironment interactions may overestimate potential clinical activity, thus explaining at least in part the gap between preclinical vs. clinical efficacy in MM and other cancers