Direct Measurement of Thermal Fluctuation of High-Q Pendulum

We achieved for the first time a direct measurement of the thermal fluctuation of a pendulum in an off-resonant region using a laser interferometric gravitational wave detector. These measurements have been well identified for over one decade by an agreement with a theoretical prediction, which was derived by a fluctuation-dissipation theorem. Thermal fluctuation is dominated by the contribution of resistances in coil-magnet actuator circuits. When we tuned these resistances, the noise spectrum also changed according to a theoretical prediction. The measured thermal noise level corresponds to a high quality factor on the order of 10^5 of the pendulum.Comment: 10 pages, 4 figure

Thermal-noise-limited underground interferometer CLIO

We report on the current status of CLIO (Cryogenic Laser Interferometer Observatory), which is a prototype interferometer for LCGT (Large Scale Cryogenic Gravitational-Wave Telescope). LCGT is a Japanese next-generation interferometric gravitational wave detector featuring the use of cryogenic mirrors and a quiet underground site. The main purpose of CLIO is to demonstrate a reduction of the mirror thermal noise by cooling the sapphire mirrors. CLIO is located in an underground site of the Kamioka mine, 1000 m deep from the mountain top, to verify its advantages. After a few years of commissioning work, we have achieved a thermal-noise-limited sensitivity at room temperature. One of the main results of noise hunting was the elimination of thermal noise caused by a conductive coil-holder coupled with a pendulum through magnets.Comment: 10 pages, 6 figures, Proceedings of the 8th Edoardo Amaldi Conference on Gravitational Wave

Reduction of thermal fluctuations in a cryogenic laser interferometric gravitational wave detector

The thermal fluctuation of mirror surfaces is the fundamental limitation for interferometric gravitational wave (GW) detectors. Here, we experimentally demonstrate for the first time a reduction in a mirror's thermal fluctuation in a GW detector with sapphire mirrors from the Cryogenic Laser Interferometer Observatory at 17\,K and 18\,K. The detector sensitivity, which was limited by the mirror's thermal fluctuation at room temperature, was improved in the frequency range of 90\,Hz to 240\,Hz by cooling the mirrors. The improved sensitivity reached a maximum of $2.2 \times 10^{-19}\,\textrm{m}/\sqrt{\textrm{Hz}}$ at 165\,Hz.Comment: Accepted for publication in Physical Review Letters, 5 pages, 2 figure

Experimental model for the irradiation-mediated abscopal effect and factors influencing this effect

Radiotherapy (RT) is the primary treatment for cancer. Ionizing radiation from RT induces tumor damage at the irradiated site, and, although clinically infrequent, may cause regression of tumors distant from the irradiated site-a phenomenon known as the abscopal effect. Recently, the abscopal effect has been related to prolongation of overall survival time in cancer patients, though the factors that influence the abscopal effect are not well understood. The aim of this study is to clarify the factors influencing on abscopal effect. Here, we established a mouse model in which we induced the abscopal effect. We injected MC38 (mouse colon adenocarcinoma) cells subcutaneously into C57BL/6 mice at two sites. Only one tumor was irradiated and the sizes of both tumors were measured over time. The non-irradiated-site tumor showed regression, demonstrating the abscopal effect. This effect was enhanced by an increase in the irradiated-tumor volume and by administration of anti-PD1 antibody. When the abscopal effect was induced by a combination of RT and anti-PD1 antibody, it was also influenced by radiation dose and irradiated-tumor volume. These phenomena were also verified in other cell line, B16F10 cells (mouse melanoma cells). These findings provide further evidence of the mechanism for, and factors that influence, the abscopal effect in RT

Combination treatment with highly bioavailable curcumin and NQO1 inhibitor exhibits potent antitumor effects on esophageal squamous cell carcinoma

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most intractable cancers, so the development of novel therapeutics has been required to improve patient outcomes. Curcumin, a polyphenol from Curcuma longa, exhibits various health benefits including antitumor effects, but its clinical utility is limited because of low bioavailability. Theracurmin® (THC) is a highly bioavailable curcumin dispersed with colloidal submicron particles. Methods: We examined antitumor effects of THC on ESCC cells by cell viability assay, colony and spheroid formation assay, and xenograft models. To reveal its mechanisms, we investigated the levels of reactive oxygen species (ROS) and performed microarray gene expression analysis. According to those analyses, we focused on NQO1, which involved in the removal of ROS, and examined the effects of NQO1-knockdown or overexpression on THC treatment. Moreover, the therapeutic effect of THC and NQO1 inhibitor on ESCC patient-derived xenografts (PDX) was investigated. Results: THC caused cytotoxicity in ESCC cells, and suppressed the growth of xenografted tumors more efficiently than curcumin. THC increased ROS levels and activated the NRF2–NMRAL2P–NQO1 expressions. Inhibition of NQO1 in ESCC cells by shRNA or NQO1 inhibitor resulted in an increased sensitivity of cells to THC, whereas overexpression of NQO1 antagonized it. Notably, NQO1 inhibitor significantly enhanced the antitumor effects of THC in ESCC PDX tumors. Conclusions: These findings suggest the potential usefulness of THC and its combination with NQO1 inhibitor as a therapeutic option for ESCC

Antarctic micrometeorites collected at the Dome Fuji Station

Antarctic micrometeorites (AMMs) were found among the precipitated fine particles recovered from a water tank in the Dome Fuji Station. These AMMs had been contained in the recent fallen snow around the station. Initial processing of the precipitated particles revealed that they were dominated by natural and artificial terrestrial materials, thus a series of processes were developed to separate AMMs from terrestrial particles. The recovery rate of AMMs by the processes was approximately 45% in weight, which was determined from a weight ratio of recovered/accreted AMMs. The micro-morphology and major-element concentration of the recovered AMMs were characterized. They appear to have been heated upon atmospheric entry to varying temperatures and can be classified into two major types based on the degree of heating : (1) fine-grained, irregular-shaped, partial-melted micrometeorites with chondritic composition, and (2) total-melted spherical micrometeorites with chondritic composition except for volatile elements. A digital catalog for the AMMs identified in this study was established on the web site [URL : http : //dust. cc. gakushuin. ac. jp/], in which optical characteristics, high-resolution images, and chemical compositions of individual AMMs are presented. The AMMs listed in the catalog are the first Japanese collection of extraterrestrial dust. The criterion and techniques developed for the selection and initial analysis of AMMs are applicable for the dust samples that are being collected by the 39th Japanese Antarctic Research Expedition team

HER2 G776S mutation promotes oncogenic potential in colorectal cancer cells when accompanied by loss of APC function

Clinical cancer genome sequencing detects oncogenic variants that are potential targets for cancer treatment, but it also detects variants of unknown significance. These variants may interact with each other to influence tumor pathophysiology, however, such interactions have not been fully elucidated. Additionally, the effect of target therapy for those variants also unclarified. In this study, we investigated the biological functions of a HER2 mutation (G776S mutation) of unknown pathological significance, which was detected together with APC mutation by cancer genome sequencing of samples from a colorectal cancer (CRC) patient. Transfection of the HER2 G776S mutation alone slightly increased the kinase activity and phosphorylation of HER2 protein, but did not activate HER2 downstream signaling or alter the cell phenotype. On the other hand, the HER2 G776S mutation was shown to have strong oncogenic potential when loss of APC function was accompanied. We revealed that loss of APC function increased Wnt pathway activity but also increased RAS-GTP, which increased ERK phosphorylation triggered by HER2 G776S transfection. In addition, afatinib, a pan-HER tyrosine kinase inhibitor, suppressed tumor growth in xenografts derived from HER2 G776S-transfected CRC cells. These findings suggest that this HER2 mutation in CRC may be a potential therapeutic target

Visceral fat obesity is the key risk factor for the development of reflux erosive esophagitis in 40–69-years subjects

[Background] Visceral fat obesity can be defined quantitatively by abdominal computed tomography, however, the usefulness of measuring visceral fat area to assess the etiology of gastrointestinal reflux disease has not been fully elucidated. [Methods] A total of 433 healthy subjects aged 40–69 years (234 men, 199 women) were included in the study. The relationship between obesity-related factors (total fat area, visceral fat area, subcutaneous fat area, waist circumference, and body mass index) and the incidence of reflux erosive esophagitis was investigated. Lifestyle factors and stomach conditions relevant to the onset of erosive esophagitis were also analyzed. [Results] The prevalence of reflux erosive esophagitis was 27.2% (118/433; 106 men, 12 women). Visceral fat area was higher in subjects with erosive esophagitis than in those without (116.6 cm2 vs. 64.9 cm2, respectively). The incidence of erosive esophagitis was higher in subjects with visceral fat obesity (visceral fat area ≥ 100 cm2) than in those without (61.2% vs. 12.8%, respectively). Visceral fat obesity had the highest odds ratio (OR) among obesity-related factors. Multivariate analysis showed that visceral fat area was associated with the incidence of erosive esophagitis (OR = 2.18), indicating that it is an independent risk factor for erosive esophagitis. In addition, daily alcohol intake (OR = 1.54), gastric atrophy open type (OR = 0.29), and never-smoking history (OR = 0.49) were also independently associated with the development of erosive esophagitis. [Conclusions] Visceral fat obesity is the key risk factor for the development of reflux erosive esophagitis in subjects aged 40–69 years