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%.

Impact of an infectious disease specialist on antifungal use: an interrupted time-series analysis in a tertiary hospital in Tokyo.

BACKGROUND: Antimicrobial stewardship programmes are considered essential for optimizing antimicrobial use in order to improve patient outcomes, reduce the number of adverse sequelae, prevent resistance, and ensure cost-effective therapy. AIM: To assess the efficacy and the limitations of antifungal antimicrobial stewardship programmes. METHODS: A bundle to manage infectious diseases was implemented in our hospital in October 2010. Data regarding antimicrobial use density (AUD) from April 2006 to May 2016 were collected. Trends in AUD were assessed using an interrupted time-series model for three separate periods: the pre-bundle, the bundle implementation, and the long-term follow-up periods. The primary and secondary outcomes were AUD (defined daily dose (DDD) per 1000 patient-days) of intravenous antifungals and expenditure on antifungals per fiscal year, respectively. FINDINGS: The AUD for all intravenous antifungals decreased from 26.1 in 2006 to 9.9 in 2015. Whereas the change in the trend during the pre-bundle period was not significant (slope: 0.062; 95% confidence interval (CI): -0.180 to 0.305), a significant decrease was observed in the bundle implementation period (slope: -0.535; 95% CI: -0.907 to -0.164). The trend slowed during the long-term follow-up period (slope: -0.040; 95% CI: -0.218 to 0.138). Total expenditure on antifungals decreased by 73%, from ¥52,354,411 in fiscal year 2006 to ¥14,073,099 in fiscal year 2015. CONCLUSION: The bundle significantly reduced the use of antifungals and decreased costs over time, but this effect was limited in that it had stabilized within three years.

Search for nucleon decay via n→ν[over ¯]π0 and p→ν[over ¯]π+ in Super-Kamiokande.

We present the results of searches for nucleon decay via n→ν[over ¯]π0 and p→ν[over ¯]π+ using data from a combined 172.8 kt·yr exposure of Super-Kamiokande-I,-II, and-III. We set lower limits on the partial lifetime for each of these modes: τn→ν[over ¯]π0>1.1×10(33) years and τp→ν[over ¯]π+>3.9×10(32) years at a 90% confidence level.

Search for trilepton nucleon decay via p→e+νν and p→µ+νν in the Super-Kamiokande experiment.

The trilepton nucleon decay modes p→e+νν and p→µ+νν violate |Δ(B-L)| by two units. Using data from a 273.4 kt yr exposure of Super-Kamiokande a search for these decays yields a fit consistent with no signal. Accordingly, lower limits on the partial lifetimes of τp→e+νν>1.7×10(32) years and τp→µ+νν>2.2×10(32) years at a 90% confidence level are obtained. These limits can constrain Grand Unified Theories which allow for such processes.

Search for dinucleon decay into kaons in Super-Kamiokande.

A search for the dinucleon decay pp → K+ K+ has been performed using 91.6 kton·yr data from Super-Kamiokande-I. This decay provides a sensitive probe of the R-parity-violating parameter λ112''. A boosted decision tree analysis found no signal candidates in the data. The expected background was 0.28±0.19 atmospheric neutrino induced events and the estimated signal detection efficiency was 12.6%±3.2%. A lower limit of 1.7×10(32) years has been placed on the partial lifetime of the decay O16 → C14K+ K+ at 90% C.L. A corresponding upper limit of 7.8×10(-9) has been placed on the parameter λ112''.

First indication of terrestrial matter effects on solar neutrino oscillation.

We report an indication that the elastic scattering rate of solar B8 neutrinos with electrons in the Super-Kamiokande detector is larger when the neutrinos pass through Earth during nighttime. We determine the day-night asymmetry, defined as the difference of the average day rate and average night rate divided by the average of those two rates, to be [-3.2 ± 1.1(stat) ± 0.5(syst)]%, which deviates from zero by 2.7 σ. Since the elastic scattering process is mostly sensitive to electron-flavored solar neutrinos, a nonzero day-night asymmetry implies that the flavor oscillations of solar neutrinos are affected by the presence of matter within the neutrinos' flight path. Super-Kamiokande's day-night asymmetry is consistent with neutrino oscillations for 4 × 10(-5) eV(2) ≤ Δm 2(21) ≤ 7 × 10(-5) eV(2) and large mixing values of θ12, at the 68% C.L.

Evidence for the appearance of atmospheric tau neutrinos in super-Kamiokande.

Super-Kamiokande atmospheric neutrino data were fit with an unbinned maximum likelihood method to search for the appearance of tau leptons resulting from the interactions of oscillation-generated tau neutrinos in the detector. Relative to the expectation of unity, the tau normalization is found to be 1.42 ± 0.35(stat)(-0.12)(+0.14)(syst) excluding the no-tau-appearance hypothesis, for which the normalization would be zero, at the 3.8σ level. We estimate that 180.1 ± 44.3(stat)(-15.2)(+17.8) (syst) tau leptons were produced in the 22.5 kton fiducial volume of the detector by tau neutrinos during the 2806 day running period. In future analyses, this large sample of selected tau events will allow the study of charged current tau neutrino interaction physics with oscillation produced tau neutrinos.

Anti-aging effects of oligomeric proanthocyanidins isolated from persimmon fruits.

Senescence-accelerated mouse prone/8 (SAMP8), a murine model of accelerated senescence, shows age-related deficits in learning and memory. The oral administration of oligomers improved spatial and object recognition impairment in SAMP8. The expression of phosphorylated neurofilament-H was significantly elevated in the hippocampal CA1. This indicates that oligomers induce an increase in the density of axons. To investigate the protective mechanisms of oligomers against brain dysfunction with aging, we carried out a receptor tyrosine kinase phosphorylation antibody array, and clarified that the administration of oligomers led to an increase in the phosphorylation of vascular endothelial growth factor receptor (VEGFR)-2, suggesting the neuroprotective role of oligomers. The phosphorylation of VEGFR-2 was more markedly increased in the hypothalamus and choroid plexus than in other brain regions of SAMP8. Memory in oligomer-treated mice was impaired by SU1498, a VEGFR-2-specific antagonist. Elucidating the relationship between memory impairment with aging and VEGFR-2 signaling may provide new suggestions for protection against memory deficit in the aging brain. In addition, we revealed that the administration of oligomers extended the life span of SAMP8. Oligomers elevated SIRT1 expression, which is recognized as an essential factor for life span extension in the brain. However, the administration of oligomers did not induce stereotypical behaviors such as rearing, jumping, or hanging from the lid of a cage, while food restriction increased these frequencies without a significant change in motor function. The present study suggests the promising role of oligomers as an anti-aging agent to extend life span.

Creatinine and HMH (5-hydroxy-1-methylhydantoin, NZ-419) as intrinsic hydroxyl radical scavengers.

Creatinine (Crn) is one of the main intrinsic hydroxyl radical (•OH) scavengers and an ideal one for healthy or normal mammals, although this fact has not yet become widely accepted. Our results from urinary data estimated that ca. 0.4-0.6% of Crn is used daily to scavenge •OH in normal mammals [ca. 50 µmole and ca. 400 pmole of •OH in healthy subjects and normal rats, respectively]. In human subjects, Crn reacts non-enzymatically with •OH to form creatol (CTL: 5-hydroxycreatinine) and demethylcreatinine (DMC) in a one to one ratio, and CTL partially decomposes to methylguanidine (MG). And so, the scavenged mole of •OH by Crn is nearly equal to their molar total sum (CTL + MG + DMC) or 2 × (CTL + MG). The molar ratio of (scavenged •OH)/Crn in healthy subjects and normal rats are 4.4 and 6.0 mmole/mole, respectively, i.e. almost similar, but in patients with chronic kidney disease (CKD) the ratio increases up to ca. 60 mmole/mole in proportion to the severity of CKD. Since the level of Crn might not be enough to scavenge all •OH, and MG starts accumulating as a uremic toxin, Crn is not really the ideal scavenger. 5-Hydroxy-1-methylhydantoin (HMH, NZ-419), a Crn metabolite, is another antioxidant, having •OH scavenging ability, and has been shown to inhibit the progression of CKD in rats in stead of Crn, if sufficient amounts are given orally.

Search for differences in oscillation parameters for atmospheric neutrinos and antineutrinos at Super-Kamiokande.

We present a search for differences in the oscillations of antineutrinos and neutrinos in the Super-Kamiokande-I, -II, and -III atmospheric neutrino sample. Under a two-flavor disappearance model with separate mixing parameters between neutrinos and antineutrinos, we find no evidence for a difference in oscillation parameters. Best-fit antineutrino mixing is found to be at (Δm2,sin2 2θ)=(2.0×10(-3) eV2, 1.0) and is consistent with the overall Super-K measurement.

Bioactive constituents of Corni Fructus: The therapeutic use of morroniside, loganin, and 7-O-galloyl-D-sedoheptulose as renoprotective agents in type 2 diabetes.

Corni Fructus, the fruit of Cornus officinalis Sieb. et Zucc. (Cornaceae), is an important crude herb used in Chinese medicine to exhibit several biological activities, including hypoglycemic, antineoplastic, and antimicrobial effects, and to improve liver and kidney functions. We have been investigating the mechanism and bioactive constituents of Corni Fructus using diabetic animal models. Morroniside, loganin, and 7-O-galloyl-D-sedoheptulose, the main active compounds of Corni Fructus, exhibit the same lowering effects of elevated triglyceride, oxidative stress and advanced glycation endproduct (AGE) formation in the kidney of db/db mice. The effects of morroniside and 7-O-galloyl-D-sedoheptulose were mediated through modulation by renal sterol regulatory element binding proteins and nuclear factor-kappa B expression, but the effect of loganin was presumably mediated by hypoglycemic and antioxidant effects in the kidney, and also indirectly by the amelioration of metabolic disorders in other organs such as the liver. These findings led us to conclude that morroniside, loganin, and 7-O-galloyl-D-sedoheptulose would synergistically contribute to the inhibition of metabolic disorders (hyperglycemia and dyslipidemia), oxidative stress, inflammation, as well as AGE formation in the diabetic kidney.

Evaluation of the peroxynitrite scavenging activity of heat-processed ginseng.

To ascertain the principal active peroxynitrite (ONOO(-)) scavenging components of heat-processed Panax ginseng C.A. Meyer (sun ginseng [SG]), the ONOO(-) scavenging activities of fractions and components of SG were compared. The results demonstrated that the ONOO(-) scavenging ability of SG was due to its ether fraction containing phenolic compounds. High-performance liquid chromatography analysis and ONOO(-) scavenging activity tests of the phenolic acids contained in SG identified vanillic acid, ferulic acid, p-coumaric acid, syringic acid, and maltol as the main active ONOO(-) scavenging components of SG. The ONOO(-) scavenging activities of phenolic acids and maltol were dependent on the degrees of their proton donating ability.

High incidence of secondary failure of platelet recovery after autologous and syngeneic peripheral blood stem cell transplantation in acute promyelocytic leukemia.

Secondary failure of platelet recovery (SFPR), which is a delayed decline in platelet count after primary recovery following myeloablative hematopoietic SCT, is a significant problem in allogeneic SCT. However, its clinical characteristics have not been well described in autologous SCT for acute myeloid leukemia. We reviewed 11 consecutive patients who had received autologous or syngeneic SCT for acute promyelocytic leukemia. Seven of 11 patients (64%) had SFPR, which is defined as a decline in the platelet count to less than 30,000/microl for more than 7 days. The median onset of SFPR was day 36 (range, 25-51 days) and the median duration of thrombocytopenia was 13 days (range, 4-25 days). Of nine patients who received busulfan-containing preparative regimens, seven (78%) had SFPR and one had delayed primary platelet count recovery. Neither patient who received cyclophosphamide and total body irradiation as preparative regimens had SFPR. The clinical courses of SFPR were transient and self-limited. SFPR was not associated with relapse of underlying diseases, graft failure or other fatal morbidities. The unexpectedly high prevalence and the characteristics of SFPR may provide additional information on management following autologous SCT for acute myeloid leukemia.

Effect of sun ginseng methanol extract on lipopolysaccharide-induced liver injury in rats.

Sun ginseng (SG) is heat-processed Panax ginseng C.A. Meyer steamed at 120 degrees C, which has ginsenoside-Rg(3), -Rk(1), and -Rg(5) as its main ginsenoside components. The effect of SG on lipopolysaccharide (LPS)-induced liver injury in rats was investigated in this study. Intravenous injection of LPS induced excessive nitric oxide (*NO) generation in serum and increased the hepatic mitochondrial thiobarbituric acid-reactive substance (TBA-RS) level. However, the elevated TBA-RS level was significantly lowered by 15 consecutive days of SG administrations. In addition, up-regulated hepatic inducible nitric oxide synthase and heme oxygenase 1 levels in LPS-treated control rats were significantly lowered and increased, respectively, by 100 mg/kg body weight/day of SG administration. These antioxidant effects were thought to be partially related to the deactivation of nuclear factor-kappaB by SG administration.

Therapeutic potential of heat-processed Panax ginseng with respect to oxidative tissue damage.

Panax ginseng has been reported to exhibit a wide range of pharmacological and physiological actions. A method of heat-processing to enhance the efficacy of ginseng is well established in South Korea based on a long history of ethnopharmacological evidence. We investigated the increase in free radical-scavenging activity of Panax ginseng as a result of heat-processing and its active compounds related to fortified antioxidant activity. In addition, the therapeutic potential of heat-processed ginseng (HPG) with respect to oxidative tissue damage was examined using rat models. Based upon chemical and biological activity tests, the free radical-scavenging active components such as less-polar ginsenosides and maltol in Panax ginseng significantly increased depending on the temperature of heat-processing. According to animal experiments related to oxidative tissue damage, HPG displayed hepatoprotective action by reducing the elevated thiobarbituric acid reactive substance (TBA-RS) level, as well as nuclear factor-kappa B (NF-kappaB) and inducible nitric oxide synthase (iNOS) protein expressions, while increasing heme oxygenase-1 in the lipopolysaccharide-treated rat liver, and HPG also displayed renal protective action by ameliorating physiological abnormalities and reducing elevated TBA-RS, advanced glycation endproduct (AGE) levels, NF-kappaB, cyclooxygenase-2, iNOS, 3-nitrotyrosine, N?-(carboxymethyl)lysine, and receptors for AGE protein expression in the diabetic rat kidney. Therefore, HPG clearly has a therapeutic potential with respect to oxidative tissue damage by inhibiting protein expression related to oxidative stress and AGEs, and further investigations of active compounds are underway. This investigation of specified bioactive constituents is important for the development of scientific ginseng-derived drugs as part of ethnomedicine.

Amla (Emblica officinalis Gaertn.) extracts reduce oxidative stress in streptozotocin-induced diabetic rats.

The antioxidant properties of amla extracts and their effects on the oxidative stress in streptozotocin-induced diabetes were examined in rats. Amla in the form of either the commercial enzymatic extract SunAmla (Taiyo Kagaku Co. Ltd., Yokkaichi, Japan) (20 or 40 mg/kg of body weight/day) or a polyphenol-rich fraction of ethyl acetate extract (10 or 20 mg/kg of body weight/day) was given orally for 20 days to the streptozotocin-induced diabetic rats. Amla extracts showed strong free radical scavenging activity. Amla also showed strong inhibition of the production of advanced glycosylated end products. The oral administration of amla extracts to the diabetic rats slightly improved body weight gain and also significantly alleviated various oxidative stress indices of the serum of the diabetic rats. The elevated serum levels of 5-hydroxymethylfurfural, which is a glycosylated protein that is an indicator of oxidative stress, were significantly reduced dose-dependently in the diabetic rats fed amla. Similarly, the serum level of creatinine, yet another oxidative stress parameter, was also reduced. Furthermore, thiobarbituric acid-reactive substances levels were significantly reduced with amla, indicating a reduction in lipid peroxidation. In addition, the decreased albumin levels in the diabetic rats were significantly improved with amla. Amla also significantly improved the serum adiponectin levels. These results form the scientific basis supporting the efficacy of amla for relieving the oxidative stress and improving glucose metabolism in diabetes.

Solid tumors after hematopoietic stem cell transplantation in Japan: incidence, risk factors and prognosis.

To evaluate the incidence, risk factors and prognosis for solid tumors after hematopoietic stem cell transplantation (HSCT) in Japan, 809 patients who had received HSCT between 1981 and 2000 were retrospectively analyzed. In all, 19 newly diagnosed secondary cancers were observed. The risk for cancer development was 2.8 times as high as that for expected cases. The cumulative incidence ratios at 5 and 10 years were 1.9 and 4.2%, respectively. The risk was significantly elevated for buccal cavity cancer (standard incidental ratio (SIR), 44.42: 95% confidence interval (CI) 17.86-91.51), esophageal cancer (SIR, 22.36: 95% CI 6.09-57.25), and cervical cancer (SIR, 8.58: 95% CI 1.04-31.01). Of 15 patients who developed solid cancers following allografting, 12 had chronic graft-versus-host disease (GVHD), and all 10 patients with squamous cell carcinoma of the buccal cavity or esophagus had chronic GVHD. On multivariate analysis, extensive chronic GVHD and age over 45 years at the time of transplantation were associated with a higher risk for solid cancers. In all, 17 patients received therapy for secondary cancers, nine of whom are still alive and the 5-year probability of survival from the diagnosis is 42.8%. Our data suggest that early detection of secondary cancers is very important in prolonging overall survival.