Abstract
KAGRA is a newly built gravitational wave observatory, a laser interferometer with a 3 km arm length, located at Kamioka, Gifu, Japan. In this series of articles we present an overview of ...the baseline KAGRA, for which we finished installing the designed configuration in 2019. This article describes the method of calibration (CAL) used for reconstructing gravitational wave signals from the detector outputs, as well as the characterization of the detector (DET). We also review the physical environmental monitoring (PEM) system and the geophysics interferometer (GIF). Both are used for characterizing and evaluating the data quality of the gravitational wave channel. They play important roles in utilizing the detector output for gravitational wave searches. These characterization investigations will be even more important in the near future, once gravitational wave detection has been achieved, and in using KAGRA in the gravitational wave astronomy era.
A Rare-Cell Detector for Cancer Krivacic, Robert T.; Ladanyi, Andras; Curry, Douglas N. ...
Proceedings of the National Academy of Sciences - PNAS,
07/2004, Volume:
101, Issue:
29
Journal Article
Peer reviewed
Open access
Although a reliable method for detection of cancer cells in blood would be an important tool for diagnosis and monitoring of solid tumors in early stages, current technologies cannot reliably detect ...the extremely low concentrations of these rare cells. The preferred method of detection, automated digital microscopy (ADM), is too slow to scan the large substrate areas. Here we report an approach that uses fiber-optic array scanning technology (FAST), which applies laser-printing techniques to the rare-cell detection problem. With FAST cytometry, laser-printing optics are used to excite 300,000 cells per sec, and emission is collected in an extremely wide field of view, enabling a 500-fold speed-up over ADM with comparable sensitivity and superior specificity. The combination of FAST enrichment and ADM imaging has the performance required for reliable detection of early-stage cancer in blood.
The molecular chaperone heat shock protein-90 (Hsp90) is a promising cancer drug target, but current Hsp90-based therapy has so far shown limited activity in the clinic.
We tested the efficacy of a ...novel mitochondrial-targeted, small-molecule Hsp90 inhibitor, Gamitrinib (GA mitochondrial matrix inhibitor), in the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model. The TRAMP mice receiving 3-week or 5-week systemic treatment with Gamitrinib were evaluated for localised or metastatic prostate cancer, prostatic intraepithelial neoplasia (PIN) or localised inflammation using magnetic resonance imaging, histology and immunohistochemistry. Treatment safety was assessed histologically in organs collected at the end of treatment. The effect of Gamitrinib on mitochondrial dysfunction was studied in RM1 cells isolated from TRAMP tumours.
Systemic administration of Gamitrinib to TRAMP mice inhibited the formation of localised prostate tumours of neuroendocrine or adenocarcinoma origin, as well as metastatic prostate cancer to abdominal lymph nodes and liver. The Gamitrinib treatment had no effect on PIN or prostatic inflammation, and caused no significant animal weight loss or organ toxicity. Mechanistically, Gamitrinib triggered acute mitochondrial dysfunction in RM1 cells, with loss of organelle inner membrane potential and release of cytochrome-c in the cytosol.
The Gamitrinib has pre-clinical activity and favourable tolerability in a genetic model of localised and metastatic prostate cancer in immunocompetent mice. Selective targeting of mitochondrial Hsp90 could provide novel molecular therapy for patients with advanced prostate cancer.
The magnetospheric imaging instrument (MIMI) is a neutral and charged particle detection system on the Cassini orbiter spacecraft designed to perform both global imaging and in-situ measurements to ...study the overall configuration and dynamics of Saturn's magnetosphere and its interactions with the solar wind, Saturn's atmosphere, Titan, and the icy satellites. Further, the Jovian magnetosphere and lo torus will be imaged during Jupiter flyby. The Titan exosphere and its cometary interaction with magnetospheric plasmas will be imaged in detail on each flyby. CHEMS (charge-energy-mass-spectrometer) uses electrostatic deflection, TOF, and energy measurement to determine ion energy, charge state, mass, and 3-D anisotropy in the range 3 to 220 keV/e with good (approximately 0.05 sq cm sr) sensitivity. Similarily, measurements in cis-Jovian space include the first detailed charge state determination of logenic ions and several ENA images of that planet's magnetosphere.
To evaluate the efficacy and safety of perampanel 2, 4, and 8 mg/day added to 1-3 concomitant antiepileptic drugs (AEDs) in patients with uncontrolled partial-onset seizures.
During this ...double-blind, placebo-controlled trial, patients with persisting seizures on 1-3 AEDs were randomized to perampanel 2, 4, and 8 mg/day or placebo following a 6-week baseline phase. Perampanel was titrated weekly by 2 mg/day and maintained at the dose achieved for 13 weeks. Primary endpoints were median percent change in seizure frequency and 50% responder rate. Analysis of covariance was performed on all treated patients with any seizure data (recorded in daily diaries) in the double-blind phase.
A total of 706 patients were randomized and received trial medication; 623 completed the trial. Median percent change in seizure frequency-the primary efficacy endpoint-was -10.7%, -13.6%, -23.3%, and -30.8% for placebo, perampanel 2, 4, and 8 mg/day, respectively. The difference from placebo was statistically significant for perampanel 4 mg/day (p = 0.0026) and 8 mg/day (p < 0.0001). The corresponding 50% responder rates were 17.9%, 20.6%, 28.5%, and 34.9%. The difference from placebo was statistically significant for perampanel 4 mg/day (p = 0.0132) and 8 mg/day (p = 0.0003). An apparent dose response was suggested for dizziness, which was the most frequent treatment-emergent adverse event.
This trial demonstrated that adjunctive perampanel effectively reduced seizure frequency and possessed a favorable tolerability profile in patients ≥12 years with partial-onset seizures (with or without secondary generalization), with a minimum effective dose of 4 mg/day.
This study provides Class I evidence that 4 and 8 mg/day doses of adjunctive perampanel are effective and tolerated in reducing partial-onset seizures.
Background The significance of troponin elevation and clinical utility of troponin testing in ambulatory patients with coronary artery disease (CAD) have not been examined. We sought to investigate ...the prevalence and prognostic value of cardiac troponin T (cTnT) elevation in a population with stable CAD. Methods We studied 987 patients with stable CAD enrolled in the Heart & Soul study who had plasma cTnT measurements before performing exercise treadmill testing. Results Of the studied population, 58 patients or 6.2% had detectable cTnT levels, ≥0.01 ng/mL (0.01-0.72 ng/mL). During a mean follow-up period of 4.3 (0.1-6.5) years, 58.6% of participants with detectable cTnT had cardiovascular events compared with 22.5% of those without detectable cTnT (hazard ratio HR 3.8, 95% CI 2.6-5.4, P < .001). This association remained strong after adjustment for traditional risk factors and C-reactive protein (HR 2.0, 95% CI 1.3-3.1, P = .002). However, after further adjustment for N-terminal pro–B-type natriuretic peptide and echocardiographic parameters of left ventricular function, cTnT elevation was not an independent predictor of cardiovascular events (HR 1.3, 95% CI, 0.8-2.3, P = .28). Conclusions In ambulatory patients with stable CAD, the prevalence of cTnT elevation was 6.2%. Cardiac troponin T elevation detected using the conventional troponin assay was associated with increased risk of adverse cardiovascular outcomes, but its prognostic value was not incremental over N-terminal pro–B-type natriuretic peptide and echocardiographic evidence of cardiac abnormalities.
Overview of KAGRA: KAGRA science Akutsu, T; Arai, K; Aritomi, N ...
Progress of theoretical and experimental physics,
05/2021, Volume:
2021, Issue:
5
Journal Article
Peer reviewed
Open access
Abstract
KAGRA is a newly build gravitational wave observatory, a laser interferometer with 3 km arm length, located in Kamioka, Gifu, Japan. In this paper, one of a series of articles featuring ...KAGRA, we discuss the science targets of KAGRA projects, considering not only the baseline KAGRA (current design) but also its future upgrade candidates (KAGRA+) for the near to middle term ($\sim$5 years).
The conversion and degradation of isoflavones during dry or moist heating at 100, 150 and 200 °C, for varied lengths of time, were kinetically studied. Results showed that, at the early stage, all ...the reaction rates of malonylgenistin (MG), acetylgenistin (AG), genistin (G), and genistein (Ge) increased with increasing temperature and fitted a first-order model, when the concentration changes during heating were analyzed using HPLC. For dry heating, the conversion of MG to G exhibited the highest rate constant (h
−1), followed by MG to AG, AG to G, AG to Ge, G to Ge and MG to Ge. Moist heating showed the same phenomenon; however, the last three conversions were not observed. In addition, MG had the highest degradation rate, followed by G, Ge and AG during dry heating, while the reversed trend occurred for moist heating. Moist heating was more susceptible to conversion and degradation of isoflavones than dry heating. The correlation coefficients (
r
2) ranged from 0.664 to 0.987 for moist heating and 0.688–0.960 for dry heating. The kinetic model developed in this study can be used to predict the concentration changes of isoflavones during dry heating and moist heating.
Most solid tumors undergo hypoxia, leading to rapid cell division, metastasis and expansion of a cell population with hallmarks of cancer stem cells (CSCs). Tumor-selective replication of oncolytic ...adenoviruses may be hindered by oxygen deprivation in tumors. It is desirable to develop a potent oncolytic adenovirus, retaining its antitumor activity even in a hypoxic environment. We have previously generated an Oct4-dependent oncolytic adenovirus, namely Ad9OC, driven by nine copies of the Oct4 response element (ORE) for specifically killing Oct4-overexpressing bladder tumors. Here, we developed a novel Oct4 and hypoxia dual-regulated oncolytic adenovirus, designated AdLCY, driven by both hypoxia response element (HRE) and ORE. We showed that hypoxia-inducible factor (HIF)-2α and Oct4 were frequently overexpressed in hypoxic bladder cancer cells, and HIF-2α was involved in HRE-dependent and Oct4 transactivation. AdLCY exhibited higher cytolytic activities than Ad9OC against hypoxic bladder cancer cells, while sparing normal cells. AdLCY exerted potent antitumor effects in mice bearing human bladder tumor xenografts and syngeneic bladder tumors. It could target hypoxic CD44- and CD133-positive bladder tumor cells. Therefore, AdLCY may have therapeutic potential for targeting hypoxic bladder tumors and CSCs. As Oct4 is expressed in various cancers, AdLCY may be further explored as a broad-spectrum anticancer agent.
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