Proof-of-Principle Experiment for Testing Strong-Field Quantum Electrodynamics with Exotic Atoms: High Precision X-Ray Spectroscopy of Muonic Neon.

To test bound-state quantum electrodynamics (BSQED) in the strong-field regime, we have performed high precision x-ray spectroscopy of the 5g-4f and 5f- 4d transitions (BSQED contribution of 2.4 and 5.2 eV, respectively) of muonic neon atoms in the low-pressure gas phase without bound electrons. Muonic atoms have been recently proposed as an alternative to few-electron high-Z ions for BSQED tests by focusing on circular Rydberg states where nuclear contributions are negligibly small. We determined the 5g_{9/2}- 4f_{7/2} transition energy to be 6297.08±0.04(stat)±0.13(syst) eV using superconducting transition-edge sensor microcalorimeters (5.2-5.5 eV FWHM resolution), which agrees well with the most advanced BSQED theoretical prediction of 6297.26 eV.

Deexcitation Dynamics of Muonic Atoms Revealed by High-Precision Spectroscopy of Electronic K X Rays.

We observed electronic K x rays emitted from muonic iron atoms using superconducting transition-edge sensor microcalorimeters. The energy resolution of 5.2 eV in FWHM allowed us to observe the asymmetric broad profile of the electronic characteristic Kα and Kß x rays together with the hypersatellite K^{h}α x rays around 6 keV. This signature reflects the time-dependent screening of the nuclear charge by the negative muon and the L-shell electrons, accompanied by electron side feeding. Assisted by a simulation, these data clearly reveal the electronic K- and L-shell hole production and their temporal evolution on the 10-20 fs scale during the muon cascade process.

A practical superconducting-microcalorimeter X-ray spectrometer for beamline and laboratory science.

We describe a series of microcalorimeter X-ray spectrometers designed for a broad suite of measurement applications. The chief advantage of this type of spectrometer is that it can be orders of magnitude more efficient at collecting X-rays than more traditional high-resolution spectrometers that rely on wavelength-dispersive techniques. This advantage is most useful in applications that are traditionally photon-starved and/or involve radiation-sensitive samples. Each energy-dispersive spectrometer is built around an array of several hundred transition-edge sensors (TESs). TESs are superconducting thin films that are biased into their superconducting-to-normal-metal transitions. The spectrometers share a common readout architecture and many design elements, such as a compact, 65 mK detector package, 8-column time-division-multiplexed superconducting quantum-interference device readout, and a liquid-cryogen-free cryogenic system that is a two-stage adiabatic-demagnetization refrigerator backed by a pulse-tube cryocooler. We have adapted this flexible architecture to mate to a variety of sample chambers and measurement systems that encompass a range of observing geometries. There are two different types of TES pixels employed. The first, designed for X-ray energies below 10 keV, has a best demonstrated energy resolution of 2.1 eV (full-width-at-half-maximum or FWHM) at 5.9 keV. The second, designed for X-ray energies below 2 keV, has a best demonstrated resolution of 1.0 eV (FWHM) at 500 eV. Our team has now deployed seven of these X-ray spectrometers to a variety of light sources, accelerator facilities, and laboratory-scale experiments; these seven spectrometers have already performed measurements related to their applications. Another five of these spectrometers will come online in the near future. We have applied our TES spectrometers to the following measurement applications: synchrotron-based absorption and emission spectroscopy and energy-resolved scattering; accelerator-based spectroscopy of hadronic atoms and particle-induced-emission spectroscopy; laboratory-based time-resolved absorption and emission spectroscopy with a tabletop, broadband source; and laboratory-based metrology of X-ray-emission lines. Here, we discuss the design, construction, and operation of our TES spectrometers and show first-light measurements from the various systems. Finally, because X-ray-TES technology continues to mature, we discuss improvements to array size, energy resolution, and counting speed that we anticipate in our next generation of TES-X-ray spectrometers and beyond.

Developments in Time-Division Multiplexing of X-ray Transition-Edge Sensors.

Time-division multiplexing (TDM) is a mature scheme for the readout of arrays of transition-edge sensors (TESs). TDM is based on superconducting-quantum-interference-device (SQUID) current amplifiers. Multiple spectrometers based on gamma-ray and X-ray microcalorimeters have been operated with TDM readout, each at the scale of 200 sensors per spectrometer, as have several astronomical cameras with thousands of sub-mm or microwave bolometers. Here we present the details of two different versions of our TDM system designed to read out X-ray TESs. The first has been field-deployed in two 160-sensor (8 columns × 20 rows) spectrometers and four 240-sensor (8 columns × 30 rows) spectrometers. It has a three-SQUID-stage architecture, switches rows every 320 ns, and has total readout noise of 0.41 µΦ0/√Hz. The second, which is presently under development, has a two-SQUID-stage architecture, switches rows every 160 ns, and has total readout noise of 0.19 µΦ0/√Hz. Both quoted noise values are non-multiplexed and referred to the first-stage SQUID. In a demonstration of this new architecture, a multiplexed 1-column × 32-row array of NIST TESs achieved average energy resolution of 2.55±0.01 eV at 6 keV.

Strong-interaction shifts and widths of kaonic helium isotopes.

The kaonic 3He and 4He [Formula: see text] transitions in gaseous targets were observed by the SIDDHARTA experiment. The X-ray energies of these transitions were measured with large-area silicon-drift detectors using the timing information of the [Formula: see text] pairs produced by the DAΦNE [Formula: see text] collider. The strong-interaction shifts and widths both of the kaonic 3He and 4He 2p states were determined, which are much smaller than the results obtained by the previous experiments. The "kaonic helium puzzle" (a discrepancy between theory and experiment) was now resolved.

Preliminary study of kaonic deuterium X-rays by the SIDDHARTA experiment at DAΦNE.

The study of the [Formula: see text] system at very low energies plays a key role for the understanding of the strong interaction between hadrons in the strangeness sector. At the DAΦNE electron-positron collider of Laboratori Nazionali di Frascati we studied kaonic atoms with [Formula: see text] and [Formula: see text], taking advantage of the low-energy charged kaons from Φ-mesons decaying nearly at rest. The SIDDHARTA experiment used X-ray spectroscopy of the kaonic atoms to determine the transition yields and the strong interaction induced shift and width of the lowest experimentally accessible level (1s for H and D and 2p for He). Shift and width are connected to the real and imaginary part of the scattering length. To disentangle the isospin dependent scattering lengths of the antikaon-nucleon interaction, measurements of [Formula: see text] and of [Formula: see text] are needed. We report here on an exploratory deuterium measurement, from which a limit for the yield of the K-series transitions was derived: [Formula: see text] and [Formula: see text] (CL 90%). Also, the upcoming SIDDHARTA-2 kaonic deuterium experiment is introduced.

Measurements of the strong-interaction widths of the kaonic (3)He and (4)He 2p levels.

The kaonic (3)He and (4)He X-rays emitted in the [Formula: see text] transitions were measured in the SIDDHARTA experiment. The widths of the kaonic (3)He and (4)He 2p states were determined to be [Formula: see text], and [Formula: see text], respectively. Both results are consistent with the theoretical predictions. The width of kaonic (4)He is much smaller than the value of [Formula: see text] determined by the experiments performed in the 70's and 80's, while the width of kaonic (3)He was determined for the first time.

First measurement of kaonic helium-3 X-rays.

The first observation of the kaonic (3)He 3d→2p transition was made, using slow K- mesons stopped in a gaseous (3)He target. The kaonic atom X-rays were detected with large-area silicon drift detectors using the timing information of the K+K- pairs of ϕ-meson decays produced by the DAΦNE e+e- collider. The strong interaction shift of the kaonic (3)He 2p state was determined to be -2±2(stat)±4(syst) eV.

Ischemic preconditioning attenuates cardiac sympathetic nerve injury via ATP-sensitive potassium channels during myocardial ischemia.

BACKGROUND: During myocardial ischemia, massive norepinephrine (NE) is released from the cardiac sympathetic nerve terminals, reflecting the sympathetic nerve injury. A brief preceding ischemia can reduce infarct size; this is known as ischemic preconditioning (PC). The effect of PC on sympathetic nerves, however, including its underlying mechanisms in dog hearts, has remained unclear. Thus, this study was designed to elucidate whether the activation of ATP-sensitive potassium (K(ATP)) channels is involved in the mechanism of cardiac sympathetic nerve protection conferred by PC. METHODS AND RESULTS: Interstitial NE concentration was measured by the in situ cardiac microdialysis method in 45 anesthetized dogs. Five minutes of ischemia followed by 5 minutes of reperfusion was performed as PC. In the controls, the dialysate NE concentration (dNE) increased 15-fold after the 40-minute ischemia. PC decreased dNE at 40-minute ischemia by 59% (P<0.01), which was reversed by glibenclamide. A K(ATP) channel opener, nicorandil (25 microg. kg(-1). min(-1) IV), decreased dNE at 40 minutes of ischemia by 76% (P<0.01), which was also reversed by glibenclamide. During the PC procedure, no significant increase in dNE was detected, even with the uptake-1 inhibitor desipramine. CONCLUSIONS: Cardiac sympathetic nerve injury during myocardial ischemia was attenuated by PC via the activation of K(ATP) channels, but the trigger of the PC effect is unlikely to be NE release in dog hearts.

Left ventricular volumes, ejection fraction, and regional wall motion calculated with gated technetium-99m tetrofosmin SPECT in reperfused acute myocardial infarction at super-acute phase: comparison with left ventriculography.

BACKGROUND: Noninvasive assessment of acute myocardial infarction (AMI) requires information about both myocardial perfusion and left ventricular (LV) function. The automated quantification of electrocardiographic-gated myocardial scintigraphy with technetium-99m tetrofosmin (QGS) can provide this information. METHODS AND RESULTS: Coronary arteriography, QGS, and left ventriculography (LVG) were performed in 229 patients with reperfused AMI within 2 days after onset. All infarcted vascular territories (229 segments) were visualized with scintigraphic perfusion images. The mean wall motion score (WMS) was 15.9+/-2.8 by means of QGS and 16.3+/-2.9 by means of LVG. The correlation between WMS obtained by means of QGS and that obtained by means of LVG was close (y = 0.913x + 1.016, r = 0.94, P<.001), but that obtained by means of QGS was significantly lower than that obtained by means of LVG (P<.0001). Total agreement for the assessment of regional wall motion reached 75 % (kappa, 0.66). Although the LV values obtained by means of QGS and LVG correlated well (end-diastolic volume, r = 0.67, P<.0001; end-systolic volume, r = 0.79, P<.0001; ejection fraction, r = 0.78, P<.0001), end-diastolic volume and ejection fraction tended to be underestimated with QGS. CONCLUSION: QGS data were considered to be useful in detecting infarcted vascular territory and LV function, even in AMI, within 2 days after onset.

Assessment of right artrial mapping and P wave-triggered signal-average in patients with paroxysmal atrial fibrillation.

To assess right atrial mapping and P wave-triggered signal-averaged electrocardiogram (ECG) in patients with paroxysmal atrial fibrillation (PAF), this study examined right atrial electrograms using atrial mapping and parameters by P wave-triggered signal-averaged ECG in 39 patients without sick sinus syndrome. Subjects were divided into those with PAF (n = 13; 60+/-13 years old) and a control group (n = 26; 49+/-19 years old). The total number of abnormal right atrial electrograms per patient was significantly greater in the PAF group (3.2+/-1.9) than in the control group (1.1+/-0.9; P < .001). The longest duration of right atrial electrogram in the PAF group tended to be greater than that in the control group (P = .06). The filtered P wave duration was significantly longer in the PAF group than in the control group (144+/-21 vs 125+/-14 ms [P < .002]). The values of the root mean square of P wave-triggered signal-averaged ECG 15 ms from the onset (RMSi 15) and 20 ms from the offset (RMSe 20) were significantly lower in the PAF group (1.1+/-0.4 microV, 1.4+/-0.5 microV) than in the control group (1.9+/-1.1 microV [P < .02], 2.1+/-0.9 microV [P < .01]). The total number of right atrial electrograms in patients with RMSi 15 of < or =1.5 microV was significantly greater than in patients with RMSi 15 of >1.5 microV (2.2+/-1.8 vs 1.3+/-1.3 [P < .05]). Thus, the total number of abnormal right atrial electrograms per patient, the total filtered P wave duration, RMSi 15, and RMSe 20 may be good indices of PAF in patients without sick sinus syndrome. RMSi 15 may reflect the total number of the abnormal right atrial electrograms per patient.

Calpain inhibitor-1 reduces infarct size and DNA fragmentation of myocardium in ischemic/reperfused rat heart.

Myocardial ischemia/reperfusion activates a calcium-dependent protease, calpain, in the ischemic myocytes. It is not known whether calpain is involved in the mechanism of ischemia/reperfusion injury in hearts. Thus the purpose of this study was to clarify the effect of a selective calpain inhibitor (CAI) on infarct size and the extent of DNA damage in ischemic/reperfused rat hearts. Rats were divided in four groups (n = 7 each). In saline group, 0.3 ml of saline was administered (i.v.) 10 min before 30-min coronary occlusion followed by 6-h reperfusion. In vehicle group, 0.3 ml of 10% dimethyl sulfoxide (DMSO) was administered 10 min before the 30-min ischemia. CAI (0.5 mg/kg) was administered 10 min before the 30-min ischemia (CAI-A group) and 10 min before the 6-h reperfusion period (CAI-B group). Infarct size was detected with triphenyl tetrazolium chloride, and DNA fragmentation was detected by agarose gel electrophoresis and by in situ nick end labeling (ISEL). Infarct size was significantly smaller in the CAI-A group compared with the vehicle group (13+/-9% vs. 48+/-12%; p < 0.01), and the incidence of ISEL-positive myocyte nuclei in the subendocardial region was significantly reduced in the CAI-A group compared with the vehicle group (26+/-3% vs. 59+/-6%; p < 0.01). However, the effects of CAI in CAI-B group were not significant. Activation of calpain is involved in the mechanism of ischemia/reperfusion injury, and the preischemic administration of CAI was effective in reducing myocardial infarct size and the DNA damage of the myocytes in ischemic/reperfused rat heart.

[Radiofrequency catheter ablation therapy in elderly patients with supraventricular tachycardia].

138 patients with Wolf-Parkinson-White (WPW) syndrome (n = 96), atrioventricular nodal reentrant tachycardia (AVNRT; n = 27) and the other supraventricular tachycardia (n = 15), were divided into two groups, a control group (less than 65 years old; n = 108) and an elderly group (more than 66 years old; n = 30). We then estimated the success rate and safety of radiofrequency ablation for supraventricular tachycardia in elderly patients. For WPW syndrome, there were 76 (97%) successes and 9 (13%) recurrences in the control group (n = 78). In the elderly group of WPW patients, the number of successes was 18 (100%) and the number of recurrences one (63%). In 27 patients with AVNRT, the number of successes was 26 (96%) and there were no recurrences. In 15 patients with some other supraventricular tachycardia, there were 11 patients (73%) successes and one recurrence (11%). Major complications consisted of cardiac tamponade in 2 patients, dissecting aneurysm in one patient and cerebral embolism in one patients. All major complications occurred in patients with WPW syndrome. The cause of the complications, except the cerebral embolism was manipulation of the electrical or ablation catheter. Three of four patients with major complications belonged to the control group. It is possible that radiofrequency catheter ablation for supraventricular tachycardia in elderly patients is safe and highly effective. However, it is still invasive therapy. Ablation on a left accessory pathway by the transaortic valve approach especially needs meticulous care.

Altered cardiac mechanism and sarcoplasmic reticulum function in pressure overload-induced cardiac hypertrophy in rats.

Cardiac sarcoplasmic reticulum (SR) sequesters Ca2+ and plays a crucial role in the regulation of intracellular Ca2+. Its functional properties are central to the excitation-contraction (E-C) cycle of cardiac muscle. In this study, we examined the hypothesis that alterations in SR function occur during the development of hypertrophy of the left ventricle (LV) induced in rats by pressure overload secondary to abdominal aortic coarctation. Ten days, 4 and 8 weeks after the operation, hemodynamic parameters were measured using a catheter-tip manometer. The SR vesicles of hypertrophic LV (group A) and sham-operated LV (group S) at each stage were used to study Ca2+ release and uptake, and to characterize the ryanodine receptor. Moderate hypertrophy was observed in group A even at the earliest stage. Systolic LV pressure and peak +dP/dt were significantly increased in group A. There were no significant change in diastolic LV pressure in either group at any stage. Hemodynamic data indicated that LV function in group A was enhanced during the development of the hypertrophy. The amount of Ca2+ release and uptake, and the number of ryanodine binding sites on the SR were higher in group A than in group S at both early and middle stages. However, 8 weeks after the operation, SR activity was normal, even though cardiac function was still augmented. Our results indicated that LV hypertrophy induced by pressure overload is associated with altered intracellular Ca2+ regulation, as reflected by the increased Ca2+ release and uptake functions of the SR and the quantitative change in the number of ryanodine receptors during the early stages of the development of hypertrophy. Therefore, alterations in the SR Ca2+ transport capacity could account, at least in part, for the alterations in E-C coupling seen in hypertrophy.

[Effective low-dose amiodarone therapy for ventricular tachycardia complicated with ischemic heart disease and poor left ventricular function in an elderly patient].

A 71-year-old man who had ischemic heart disease with poor left ventricular function and ventricular tachycardia was admitted to hospital for evaluation. Cardiac catheterization was performed on August 19, 1996, and right coronary arteriography revealed total occlusion at segment 3. Left coronary arteriography revealed total occlusion at segment 6, and a lesion at segment 13 was 75% occluded. Partial collateral flow from the right ventricular branch to the left anterior descending artery was demonstrated, and the left ventricular ejection fraction was 24%. Recurrent ventricular tachycardia followed by pre-syncope occurred from August 23, 1996, and the patient underwent emergency coronary artery bypass surgery to the left anterior descending artery and circumflex artery using saphenous vein grafts. Ventricular tachycardia followed by pre-syncope occurred frequently after the bypass surgery, and antiarrhythmic agents (Vaughan Williams classification Ia and Ib groups) were ineffective. He received amiodarone (100 mg/day after a loading dose of 200 mg/day for 2 weeks) from September 6, 1996. His symptoms of arrhythmia decreased, and side effects have not been observed. Low-dose amiodarone was effective in this case of ischemic heart disease with left ventricular dysfunction and sustained ventricular tachycardia.

Electrophysiologic effects of a class I antiarrhythmic agent, cibenzoline, on the refractoriness and conduction of the human atrium in vivo.

We investigated the effects of a class I antiarrhythmic drug, cibenzoline, on human atrial muscle in vivo. Electrophysiologic measurements were performed in 44 patients (mean age 49 +/- 15 years), before and after an intravenous infusion of cibenzoline 1.4 mg/kg in 5 min. Extrastimuli at a basic cycle length (BCL) of 500 ms were delivered from the right atrial appendage. The effective refractory period of the right atrium (ERP-A), the conduction time from the high right atrium to the coronary sinus, maximum conduction delay (Max. CD), repetitive atrial firing zone (RAFZ), fragmented atrial activity zone (FAAZ), and conduction delay zone (CDZ) were measured. Patients were divided into two groups according to whether repetitive atrial firing (RAF) was induced (group A, n = 18) or not (group B, n = 26). Cibenzoline increased ERP-A from 198 +/- 25 to 214 +/- 26 ms (p < 0.05) and decreased Max. CD from 55 +/- 23 to 43 +/- 19 ms (p < 0.05). There were significant decreases in the RAFZ (10 +/- 17 to 4 +/- 10 ms, p < 0.05), the FAAZ (20 +/- 25 to 12 +/- 18, ms p < 0.05), and the CDZ (41 +/- 21 to 32 +/- 19 ms, p < 0.05). Cibenzoline significantly increased ERP.A (186 +/- 25 to 212 +/- 26 ms, p < 0.05) in group A, but not in group B. There were significant decreases in the RAFZ [25 +/- 19 to 9 +/- 15 ms (p < 0.05) and FAAZ 22 +/- 29 to 11 +/- 21 ms, (p < 0.05)] in group A, but not in group B. The results suggest that cibenzoline can suppress paroxysmal atrial fibrillation by prolongation of ERP-A and may also have preferential effects on the substrate of atrial fibrillation and RAF.

Synthesis and adrenergic beta-blocking activity of some 1,3-benzodioxole derivatives.

A series of 1,3-benzodioxole derivatives was synthesized. We found four compounds (2,3,10 and 11 in Table IV) to have about the same order of beta-blocking activity as that of sotalol. In addition, it is of interest that some of the compounds (2-4) were found to have hypotensive activites, although they were about one-tenth of that of hydralazine. Sotalol did not produce any change in blood pressure, and propranolol raised the blood pressure.

Antiarrhythmic action of a new beta-adrenergic blocking agent, 6-(2-hydroxy-3-isopropylaminopropyloxy)-benzothiazole succinate (KF-577), compared with that of propranolol.

The antiarrhythmic activity of a new beta-adrenergic blocking agent, 6-(2-hydroxy-3-isopropylaminopropyloxy)-benzothiazole succinate (KF-577), was compared with that of propranolol. KF-577 antagonized ouabain-induced arrhythmias in normal and bilaterally vagotomized guinea pigs; its antagonistic activity was equal to that of propranolol. Reserpinization greatly reduced ouabain intoxication and neither of the two beta-blockers produced further reduction. Aconitine-induced arrhythmias in rats were not antagonized by the two agents. In intact guinea pigs, the reduction of ouabain intoxication by both beta-blockers could not exceed that produced by simulataneous infusion of KCl, and vice versa. In isolated guinea pig atria, propranolol was about 10 times more effective than KF-577 in reducing the ouabain intoxication. The antiaarhythmic activity of KF-577 paralleled its beta-blocking activity in the isolated preparations but not in the intact animals.

Electrophysiologically determined quinidine-like actions of a beta-adrenergic blocking agent, 1-(7-indenyloxy)-3-isopropylaminopropane-2-ol hydrochloride (YB-2).

Since 1-(7-indenyloxy)-3-isopropylaminopropane-2-ol hydrochloride (YB-2) has been reported to be a potent beta-adrenergic blocking agent with antiarrhythmic effects, the electrophysiological effects of this compound on guinea-pig and canine heart muscle were examined. YB-2 was found to have typical quinidine-like actions such as decrease in rate of rise of the action potential, prolongation of refractory period and decrease in conduction velocity.