Development of advanced photon calibrator for Kamioka gravitational wave detector (KAGRA).

The Kamioka Gravitational wave detector (KAGRA) cryogenic gravitational-wave observatory has commenced joint observations with the worldwide gravitational wave detector network. Precise calibration of the detector response is essential for accurately estimating parameters of gravitational wave sources. A photon calibrator is a crucial calibration tool used in laser interferometer gravitational-wave observatory, Virgo, and KAGRA, and it was utilized in joint observation 3 with GEO600 in Germany in April 2020. In this paper, KAGRA implemented three key enhancements: a high-power laser, a power stabilization system, and remote beam position control. KAGRA employs a 20 W laser divided into two beams that are injected onto the mirror surface. By utilizing a high-power laser, the response of the detector at kHz frequencies can be calibrated. To independently control the power of each laser beam, an optical follower servo was installed for power stabilization. The optical path of the photon calibrator's beam positions was controlled using pico-motors, allowing for the characterization of the detector's rotation response. Additionally, a telephoto camera and quadrant photodetectors were installed to monitor beam positions, and beam position control was implemented to optimize the mirror response. In this paper, we discuss the statistical errors associated with the measurement of relative power noise. We also address systematic errors related to the power calibration model of the photon calibrator and the simulation of elastic deformation effects using finite element analysis. Ultimately, we have successfully reduced the total systematic error from the photon calibrator to 2.0%.

Manufacture of a 10-km-scale radius-of-curvature surface by use of a thin-film coating technique.

We tried a method of making a 10-km-class large-radius-of-curvature surface that would satisfy both low microroughness (0.1 nm rms) and low waviness (lambda/100) by forming a spherically curved film with a low-loss coating technique on a flat surface produced by mechanical (chemical) polishing. We obtained a SiO2 surface with a 10255 +/- 250-m radius of spherical curvature that had less than lambda/30 waviness and 0.4-nm micro-roughness over a 9-cm-diameter area.

Synaptic connections from large muscle afferents to motoneurones in human lower limbs.

OBJECTIVES: Our study was undertaken to investigate reciprocal inhibition in humans both from ankle flexors to extensors and from ankle extensors to flexors. METHODS: Changes in the firing probability of single motor units in response to electrical stimulation of muscle nerves (the peristimulus time histogram technique) were used to derive the reciprocal projections of muscle spindle Ia afferents to the motoneurones of ankle muscles. Discharges of units in ankle flexors (the tibialis anterior muscle [TA]) and extensors (soleus [SOL] and medial gastrocnemius [MG] muscles) were investigated respectively after stimulation of the posterior tibial (PTN) and common peroneal (CPN) nerves (predominantly on the deep branch). In eight normal subjects aged 24 to 40 years, one motor unit per each muscle was studied. RESULTS: CPN stimulation produced reciprocal Ia inhibition in the SOL of 5 of 7 of them and in the MG of 3 of 5, whereas PTN stimulation produced reciprocal Ia inhibition in the TA of only 2 of 6 subjects. CONCLUSIONS: These findings suggest that at low level contraction reciprocal Ia inhibition from ankle flexors to extensors may be stronger than that from ankle extensors to flexors.

Haemodynamic and splanchnic organ blood flow responses during sevoflurane-induced hypotension in dogs.

BACKGROUND AND OBJECTIVE: The safety of hypotension induced by sevoflurane and splanchnic organ blood flow remains to be clarified. The aim was to investigate the effects of sevoflurane-induced hypotension on systemic haemodynamics and splanchnic organ blood flows in dogs. METHODS: Mean arterial pressure was maintained at 60 mmHg by increasing sevoflurane concentrations. The renal, hepatic and pancreatic blood flows were measured by using the hydrogen clearance method. RESULTS: Hypotension induced by sevoflurane resulted in a 50% decrease of mean arterial pressure due to a 30% reduction in systemic vascular resistance associated with a 30% decrease in cardiac index. The mechanisms causing the lower cardiac index were produced by the decreases in heart rate and left ventricular dP/dt(max). Renal, hepatic and pancreatic blood flow were reduced, but the whole-body oxygen consumption did not change during the hypotensive period. CONCLUSIONS: The haemodynamic changes induced by sevoflurane were caused by the suppression of arterial baroreflexes and myocardial depression, but splanchnic organ blood flows, though reduced, could provide adequate peripheral perfusion to meet the decrease in oxygen supply.

Haemodynamic and splanchnic organ blood-flow responses to hypotension induced by the calcitonin gene-related peptide and sodium nitroprusside in dogs.

BACKGROUND AND OBJECTIVE: To elucidate the effects of various degrees of hypotension induced by the calcitonin gene-related peptide (CGRP) on the splanchnic circulation, we investigated the renal and hepatic blood flow during hypotension induced by either the calcitonin gene-related peptide or sodium nitroprusside in the isoflurane-anaesthetized dog. METHODS: Anaesthesia was maintained with 1.3% isoflurane in oxygen. After the baseline period, mean arterial pressure was reduced to 60 mmHg in the CGRP60 and nitroprusside groups, and to 50 mmHg in the CGRP50 group. The splanchnic organ blood flow was measured by hydrogen clearance. RESULTS: The cardiac index in the CGRP60 group increased (P < 0.01), but in the CGRP50 group it decreased (P < 0.01), and in the nitroprusside group it remained unchanged during hypotension. Mean pulmonary artery and pulmonary capillary wedge pressures in the CGRP60 group remained unchanged, but in the CGRP50 and nitroprusside groups they decreased (P < 0.01) during hypotension. Cardiac contractility in the CGRP60 group remained unchanged, whereas in the CGRP50 and nitroprusside groups it was reduced (P < 0.01) during hypotension. Renal blood flow in the CGRP60 group was relatively well maintained but in the CGRP50 and nitroprusside groups it was reduced (P < 0.01) throughout the observation. Hepatic blood flow in all three groups was reduced (P < 0.01) during hypotension. The reductions in hepatic blood flow between the Calcitonin gene-related peptide groups were associated with a dose-dependent decrease in mean arterial pressure. CONCLUSIONS: The results suggest that calcitonin gene-related peptide acts as an arteriolar vasodilator at low doses but as a vasodilator of the arteriolar and venous systems at higher doses, and that profound hypotension induced by the calcitonin gene-related peptide may impair splanchnic circulation.

A model for evaluation of arterial thrombosis following interventional procedures.

A model to assess thrombus formation following vascular injury was evaluated using various interventional systems. The model consisted of a 'stretchable' shunt box that served as an arteriovenous shunt between the carotid artery and jugular vein in dogs. Arterial homografts obtained from both carotid and femoral arteries were mounted between two plastic connectors attached to either side of the shunt box. The opposing walls of the shunt box were then stretched apart to achieve the original length of the arteries. The arterial side of the box was connected to the ipsilateral carotid artery and the venous side was connected to the contralateral jugular vein. Haemostasis valves were placed at the exit ports on the venous side of the shunt box. These were used as an access to the various interventional catheters into the lumens of the homografts. Interventions were performed prior to initiating blood flow. After the interventions, 111indium-labelled platelets were injected on the arterial side of the shunt box and arterial blood flow initiated across the shunt. After one hour of circulation through the shunt box, the blood flow was interrupted, and the homografts were perfusion-fixed with glutaraldehyde and segments removed for radioactive counts and processed for histology. This shunt box was then used to compare platelet adhesion and thrombus formation after balloon angioplasty (BA) to direct laser (LA) and laser-thermal angioplasty (LTA). A total of 28 arteries were used from seven dogs. In each experiment, one homograft was used as control, and three other homografts were treated with either BA, LA or LTA. Following the interventions, 111indium-labelled platelets were injected and circulated for one hour using the dog's native circulation. Labelled platelet counts for BA (19102+/-4869/cm2; mean +/- SE) were significantly greater than LA (7038+/-980/cm2), thermal LTA (5189+/-1961/cm2), and control (1575+/-541/cm2), respectively (p<0.05, ANOVA). Histology examination showed few platelets at LA, LTA and control sites whereas extensive platelet adhesion was noted at BA treated sites. The model provided a means to conduct simultaneous comparison of several interventions under similar conditions. In this case thermal treatment of the arterial homografts had the least amount of platelet adhesion.

Two-element-cavity femtosecond Cr(4+):YAG laser operating at a 2.6-GHz repetition rate.

A femtosecond Cr(4+):YAG laser with a simple two-element cavity was built. This laser typically attained a repetition rate of 2.64 GHz with a pulse width of 115 fs at a center wavelength of 1540 nm. Output pulses were characterized by second-harmonic generation frequency-resolved optical gating. Alignment of the two-element cavity for mode-locked operation was easy; moreover, the cavity structure has the potential to produce an even higher repetition rate because one can miniaturize it simply by shortening a gain medium length.

Vascular procedures that thermo-coagulate collagen reduce local platelet deposition and thrombus formation: laser and laser-thermal versus balloon angioplasty.

BACKGROUND AND OBJECTIVE: Exposure of the arterial wall matrix to blood leads to platelet deposition resulting in thrombosis. Because heat alters tissue matrix we proposed that heating reduces platelet deposition. STUDY DESIGN/MATERIALS AND METHODS: Sixty arterial homografts (15 dogs) were mounted in an arterio-venous "shunt." Interventions included balloon angioplasty (BA), direct laser (LA), laser-thermal (LTA), and combined LTABA. 111Indium-labeled platelets were circulated, radio activity measured, and homografts processed for histology. RESULTS: Radioactivity count (mean+/- SE) at BA sites (13,853+/-3,192 cpm/cm(2)) was greater than LA (7,038+/-981), LTA (5,294 +/-1,145), LTABA (6,176+/-1,571), and control (1,826+/-339), P<0.05. Electron microscopy showed fewer platelets at LA, LTA, and control than BA sites. BA spread the collagen on the arterial lumen while heat gelled collagen and confined it to the arterial media. CONCLUSIONS: Heating the artery and gelling collagen during LA, LTA, or LTABA significantly reduced thrombogenicity.

Local antithrombotic therapy using a novel porous balloon catheter.

The efficacy of local treatment of thrombosis with low-dose antithrombotic drugs (heparin: 30 U/kg, or argatroban: 0.02 mg/kg) was investigated using a novel porous balloon catheter. This novel balloon catheter can deliver drug into arterial walls without causing vascular trauma. Thrombus formation was significantly inhibited in balloon-injured and locally-treated iliac arteries compared with control balloon-injured arteries in 12 dogs. In the systemic high-dose delivery group (ten times as high as the low dose), thrombus formation in injured arteries was significantly less than that of controls in 7 dogs. Low-dose systemic delivery was not effective at inhibiting this thrombus formation. Thus, local treatment with an antithrombotic drug using this novel porous balloon catheter can prevent thrombosis without influencing systemic coagulability.

Splanchnic organ blood flow during calcitonin gene-related peptide-induced hypotension with or without propranolol in dogs.

UNLABELLED: Propranolol has been used to attenuate reflex tachycardia during induced hypotension. The purpose of the current study was to determine whether propranolol can modify splanchnic organ blood flow during calcitonin gene-related peptide (CGRP)-induced hypotension in dogs anesthetized with 1.3% isoflurane in oxygen. After surgical preparation and hemodynamic stabilization, saline as a control, 0.5 mg/kg and 2.0 mg/kg propranolol (n = 10, each) were administered in a bolus injection 20 min before hypotension was induced. Mean arterial pressure was reduced to 60 mm Hg during 60 min of CGRP infusion. Renal blood flow (RBF), hepatic blood flow (HBF), and pancreatic blood flow (PBF) were measured using the hydrogen clearance method. Cardiac index did not change in all three groups, and heart rate in the control group remained unchanged. In the propranolol groups, however, heart rate decreased (P < 0.01). Plasma norepinephrine (NE), but not epinephrine (E), increased (P < 0.05) after propranolol administration. The NE and E increased (P < 0.01) during induced hypotension in all three groups. NE was higher in the 0.5 mg/kg propranolol group than in the control group. RBF in the control group remained unchanged throughout observation. RBF, HBF, and PBF decreased (P < 0.01) after propranolol and remained decreased during and after induced hypotension. The degrees of decreased HBF and PBF in the control group were less than those in the 2.0 mg/kg propranolol group. In conclusion, pretreatment with propranolol decreases splanchnic organ blood flow further during CGRP-induced hypotension, due in part to increased plasma catecholamine concentrations. IMPLICATIONS: The reductions in splanchnic organ blood flows during CGRP-induced hypotension with propranolol are due to a reflex augmentation in sympathetic vasoconstrictor tone caused by an increase in plasma catecholamine concentrations. These findings suggest that propranolol may impair splanchnic organ blood flow during CGRP-induced hypotension.

Femtosecond Cr(4+):YAG laser with an L-fold cavity operating at a 1.2-GHz repetition rate.

Pulses of 55-fs width and 1.2-GHz repetition rate at 1.52 mum are generated from an L-fold cavity Cr(4+):YAG laser by optimization of the lasing-beam mode inside the gain medium. The pulse width is comparable with that obtained from a standard Z-fold cavity. The pulses are characterized by a second-harmonic-generation frequency-resolved optical gating method. The pulse shape deviates from a sech(2) function because of its broad shoulders. With further miniaturization it should be possible to extend the Cr(4+):YAG mode-locked operation to multigigahertz rates.

Eicosapentaenoic acid inhibits vasopressin-activated Ca2+ influx and cell proliferation in rat aortic smooth muscle cell lines.

The purpose of this study was to clarify how eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, modulates the vascular action of vasopressin in rat aortic smooth muscle cell lines. The effects of EPA on Ca2+ mobilization and DNA synthesis elicited by vasopressin were investigated and compared to those of Ca2+ channel blocking agents, by means of Ca2+ measurements and the incorporation of [3H]thymidine. Patch-clamp techniques were also employed. Vasopressin (100 nM) elicited an initial peak of intracellular Ca2+ ([Ca2+]i), followed by a sustained phase due to Ca2+ entry. Nifedipine or nicardipine (1 microM), a potent L-type Ca2+ channel blocker, partly inhibited the sustained phase, but La3+ completely abolished it. EPA (10 microM) also inhibited it even in the presence of nicardipine. Under voltage-clamp conditions with CsCl-internal solution, depolarizing pulses positive to -30 mV from a holding potential of -40 mV elicited a slow inward current. The inward current was blocked by La3+, nicardipine, and nifedipine (1 microM), suggesting that the inward current mainly consisted of the voltage-dependent L-type Ca2+ channel (ICa.L). EPA (1-30 microM) also inhibited ICa.L in a concentration-dependent manner. The inhibitory effect of EPA was observed at concentrations higher than 1 microM, and its half-maximal inhibitory concentration (IC50) was 7.6 microM. Vasopressin induced a long-lasting inward current at a holding potential of -40 mV. The vasopressin-induced current was considered as a non-selective cation current (Icat) with a reversal potential of approximately +0 mV. Both nifedipine and nicardipine (10 microM) failed to inhibit it significantly, but La3+ completely abolished Icat. EPA also inhibited vasopressin-induced Icat in a concentration-dependent manner; its IC50 value was 5.9 microM. Vasopressin (100 nM) stimulated [3H]thymidine incorporation. Exclusion of extracellular Ca2+ with EGTA or La3+ markedly inhibited it. EPA (3-30 microM) also inhibited the incorporation induced by vasopressin, while nifedipine and nicardipine (1 microM) only partly inhibited it. These results suggested that EPA, unlike nifedipine and nicardipine, inhibited vasopressin-induced Ca2+-entry and proliferation in rat vascular smooth muscle cells, where the inhibitory effects of EPA on Icat as well as ICa.L might be involved. Thus, EPA would exert hypotensive and antiatherosclerotic effects.

Vector analysis of the hemodynamics of atherogenesis in the human thoracic aorta using MR velocity mapping.

OBJECTIVE: Our study was designed to assess the applicability of MR velocity mapping for vector analysis of the hemodynamics of atherogenesis. SUBJECTS AND METHODS: MR velocity mapping was used to measure axial and nonaxial elements and the length of the wall shear rate (a spatial gradient of near-wall flow velocity parallel to the vessel wall) vector at 16 time points per cardiac cycle at eight anatomic locations of the thoracic aorta in six healthy subjects. An oscillatory shear index (a ratio of blood flow volume in the recessive direction divided by the sum of blood flow volume in both dominant and recessive directions) was introduced for analysis of the degree of oscillation. RESULTS: The time-averaged length, axial element, and nonaxial element of the wall shear rate vector were 118+/-53 sec(-1), 106+/-55 sec(-1), and 33+/-23 sec(-1), respectively. The oscillatory shear index in the axial direction was 0.06+/-0.10 and that in the nonaxial direction was 0.07+/-0.13. At the inner wall of the distal portion of the aortic arch, the length of the wall shear rate was smallest (74+/-32 sec(-1)) and oscillation in the axial direction was largest (0.16+/-0.19). CONCLUSION: Vector analysis of the wall shear rate in the thoracic aorta was successfully done with MR velocity mapping in humans. MR velocity mapping can noninvasively evaluate the hemodynamics of atherogenesis induced by the complicated blood flow.

Influence of cellular incorporation of n-3 eicosapentaenoic acid on intracellular Ca2+ concentration and membrane potential in vascular smooth muscle cells.

Long-term treatment with n-3 eicosapentaenoic acid (EPA) has been shown to exert hypotensive effects and have beneficial effects on atherosclerosis. To elucidate one of the underlying mechanisms of these effects, intracellular calcium concentration [Ca2+]i, and resting membrane potential were measured in rat vascular smooth muscle cells (A7r5 cell) treated with EPA, using Ca2+-sensitive dye fura-2 AM and the patch clamp technique. The alterations in fatty acid compositions of phospholipids and cell migration after treatment with EPA (30 microM) for 6 h-7 days were also examined. After treating cells with EPA, the EPA and DPA (docosapentaenoic acid) content of the phospholipid fraction (mol.%) increased in a time-dependent manner. Alternatively, arachidonic acid (AA) decreased, and then the ratio of EPA and AA (EPA/AA) increased significantly. The resting [Ca2+]i decreased from 170 +/- 46 nM (n = 16) in control cells to 123 +/- 29 nM (n = 16) in cells treated with EPA (30 microM) for 7 days. Vasopressin (100 nM), endothelin-1 (100 nM) and platelet-derived growth factor (PDGF 5 ng/ml) evoked an initial peak of [Ca2+]i, followed by a smaller sustained rise of [Ca2+]i in the presence of extracellular Ca2+. In EPA-treated cells, both the peak and the sustained rise of [Ca2+]i induced by these agonists decreased in comparison to the control cells. EPA treatment also decreased the transient [Ca2+]i rise evoked by these agonists in the absence of extracellular Ca2+. Under the current clamp condition, resting membrane potential was significantly higher in EPA-treated cells (-49.8 +/- 10.4 mV, n = 41) than in control cells (-44.6 +/- 7.4 mV, n = 41, P < 0.05), and the input resistance of the cell was lower in EPA-treated cells, while cell size and capacitance were not statistically different. In addition, long-term treatment with EPA for 7 days significantly inhibited PDGF-induced cell migration. These results suggest that cellular incorporation of n-3 eicosapentaenoic acid attenuates intracellular mechanisms related to changes of [Ca2+]i and affects membrane potential, thereby inhibiting migration of vascular smooth muscle cells. These actions of EPA may contribute to its vasorelaxant and antiatherosclerotic effects.

Testicular histology in experimental uremic rats.

Testicular histology in chronic renal failure was studied using stepwise-nephrectomized and adenine-treated rats. Serum levels of urea nitrogen and creatinine were significantly higher than those in sham-operated and control rats (P < .001). However, the mean tubular diameter was not different among the 4 groups. Numbers of A-spermatogonia, preleptotene and pachytene spermatocytes, and spermatids per 100 Sertoli cells were not different among the 4 groups. It would appear that testicular histology is not influenced by chronic renal failure in rats.

Measuring the diameter of coronary arteries on MR angiograms using spatial profile curves.

OBJECTIVE: The spatial profile curve of the nuclear MR intensity across the short axis of a coronary artery in an MR angiogram results in a gradual up-and-down slope lacking sharp definition, which indicates that display parameters may influence edge recognition. Therefore, our study was designed to determine the appropriate window setting and to devise a method of accurately measuring the diameter or width of the artery independent of window parameters. CONCLUSION: The diameter of a coronary artery measured on MR coronary arteriography significantly varied with experimentally selected display parameters. When compared with the diameter on contrast-enhanced coronary arteriograms, the window center on MR angiograms at the midpoint between the peak intensity of the intravascular lumen and the background intensity and the window width of a quarter or a half of the intensity difference between the two were proven to be appropriate. The angiographic diameter corresponded to the diameter obtained at 65% +/- 9% of the peak intensity on the spatial profile curve across the short-axis MR coronary angiogram. Accordingly, 65% of the peak intensity indicates the diameter of the coronary artery. Thus, the intensity profile curve independent of the window setting provided a new method for measurement of the diameter of the coronary artery.

Haemodynamic and catecholamine responses to calcitonin gene-related peptide during volatile anaesthesia.

PURPOSE: Calcitonin gene-related peptide (CGRP) produces vasodilatation, hypotension, and tachycardia. Tachycardia induced by CGRP may be due to sympathetic activation. Volatile anaesthetics attenuate activation of arterial baroreflexes. We examined the haemodynamic and endocrine effects of CGRP infusion (4 micrograms.kg-1) during anaesthesia with either enflurane or isoflurane in dogs. METHODS: Measurements of haemodynamic variables and hormone assays for plasma catecholamines were made before, during, and after CGRP infusion. Anaesthesia consisted of induction with 25 mg.kg-1 pentobarbital, followed by either enflurane (n = 7) or isoflurane (n = 7) to achieve a 1.0 end-tidal minimum alveolar concentration in oxygen 100%. RESULTS: Mean arterial pressure and systemic vascular resistance decreased (P < 0.01) and the reductions in both variables were similar during CGRP infusion in both groups. Cardiac index (CI) was increased (P < 0.01) in the enflurane group throughout the study while CI increased (P < 0.01) only during infusion in the isoflurane group. Heart rate (HR) remained unchanged (from 135 +/- 6 bpm to 134 +/- 7 bpm) in the enflurane group but tended to increase (from 162 +/- 9 bpm to 171 +/- 9 bpm) in the isoflurane group during infusion. Intergroup differences in HR were found (P < 0.05). Plasma epinephrine concentrations increased (from 42.4 +/- 12.7 pg.ml-1 to 115.3 +/- 41.8 pg.ml-1, P < 0.01) during infusion in the isoflurane group. However, these increases were suppressed (from 46.6 +/- 23.2 pg.ml-1 to 64.7 +/- 32.4 pg.ml-1) to a greater extent in the enflurane group. CONCLUSION: The haemodynamic responses, except for HR, of CGRP infusion are similar during enflurane and isoflurane anaesthesia. Suppression of tachycardia induced by CGRP is greater with enflurane than with isoflurane. The differences in HR may be due to the roles of catecholamine responses resulting from the anaesthetic-induced sympathetic suppression.

Haemodynamic effects of hypotension induced by KRN2391 and nicardipine in isoflurane anaesthetized dogs.

PURPOSE: The investigational agent, KRN2391, is a potassium channel opener with a nitrate moiety which possesses potent vasodilatory action. We compared the haemodynamic effect of KRN2391. Induced hypotension with those of nicardipine. METHODS: Sixteen dogs were anaesthetized with isoflurane 1.3% in oxygen (1 MAC). After the baseline period. mean arterial pressure (MAP) was decreased to 60 mmHg for 60 min with an infusion nicardipine (n = 8). RESULTS: The KRN2391- and nicardipine-induced hypotension resulted in maximal decreased systemic vascular resistance of 35% and 25%, increases in cardiac index of 145% and 197%, and stroke volume index of 150% and 212%, respectively, (P < 0.01). There was no change in heart rate. Nicardipine was associated with increases (P < 0.01) in both right atrial and mean pulmonary artery pressures, whereas these variables remained unchanged with KRN2391. Pulmonary capillary wedge pressure decreased with KRN2391 (P < 0.01), but not with nicardipine. CONCLUSION: While both drugs were equally able of inducing hypotension, our results show that the haemodynamic profile of KRN2391- and nicardipine-induced hypotension was a hyperdynamic state expressed by the marked increase in cardiac index with varying changes in right and left ventricular filling pressures, and suggest that KRN2391 may be a useful vasodilator for induced hypotension.