The Data Acquisition System for the KOTO Experiment

We developed and built a new system of readout and trigger electronics, based on the waveform digitization and pipeline readout, for the KOTO experiment at J-PARC, Japan. KOTO aims at observing the rare kaon decay $K_{L}\rightarrow\pi^{0}\nu\bar{\nu}$. A total of 4000 readout channels from various detector subsystems are digitized by 14-bit 125-MHz ADC modules equipped with a 10-pole Bessel filter in order to reduce the pile-up effects. The trigger decision is made every 8-ns using the digitized waveform information. To avoid dead time, the ADC and trigger modules have pipelines in their FPGA chips to store data while waiting for the trigger decision. The KOTO experiment performed the first physics run in May 2013. The data acquisition system worked stably during the run.Comment: 5 pages,12 figures, Transactions on Nuclear Science, Proceedings of the 19th Real Time Conference, Preprin

A novel method, digital genome scanning detects KRAS gene amplification in gastric cancers: involvement of overexpressed wild-type KRAS in downstream signaling and cancer cell growth

<p>Abstract</p> <p>Background</p> <p>Gastric cancer is the third most common malignancy affecting the general population worldwide. Aberrant activation of KRAS is a key factor in the development of many types of tumor, however, oncogenic mutations of <it>KRAS </it>are infrequent in gastric cancer. We have developed a novel quantitative method of analysis of DNA copy number, termed digital genome scanning (DGS), which is based on the enumeration of short restriction fragments, and does not involve PCR or hybridization. In the current study, we used DGS to survey copy-number alterations in gastric cancer cells.</p> <p>Methods</p> <p>DGS of gastric cancer cell lines was performed using the sequences of 5000 to 15000 restriction fragments. We screened 20 gastric cancer cell lines and 86 primary gastric tumors for <it>KRAS </it>amplification by quantitative PCR, and investigated <it>KRAS </it>amplification at the DNA, mRNA and protein levels by mutational analysis, real-time PCR, immunoblot analysis, GTP-RAS pull-down assay and immunohistochemical analysis. The effect of <it>KRAS </it>knock-down on the activation of p44/42 MAP kinase and AKT and on cell growth were examined by immunoblot and colorimetric assay, respectively.</p> <p>Results</p> <p>DGS analysis of the HSC45 gastric cancer cell line revealed the amplification of a 500-kb region on chromosome 12p12.1, which contains the <it>KRAS </it>gene locus. Amplification of the <it>KRAS </it>locus was detected in 15% (3/20) of gastric cancer cell lines (8–18-fold amplification) and 4.7% (4/86) of primary gastric tumors (8–50-fold amplification). <it>KRAS </it>mutations were identified in two of the three cell lines in which <it>KRAS </it>was amplified, but were not detected in any of the primary tumors. Overexpression of KRAS protein correlated directly with increased <it>KRAS </it>copy number. The level of GTP-bound KRAS was elevated following serum stimulation in cells with amplified wild-type <it>KRAS</it>, but not in cells with amplified mutant <it>KRAS</it>. Knock-down of <it>KRAS </it>in gastric cancer cells that carried amplified wild-type <it>KRAS </it>resulted in the inhibition of cell growth and suppression of p44/42 MAP kinase and AKT activity.</p> <p>Conclusion</p> <p>Our study highlights the utility of DGS for identification of copy-number alterations. Using DGS, we identified <it>KRAS </it>as a gene that is amplified in human gastric cancer. We demonstrated that gene amplification likely forms the molecular basis of overactivation of KRAS in gastric cancer. Additional studies using a larger cohort of gastric cancer specimens are required to determine the diagnostic and therapeutic implications of <it>KRAS </it>amplification and overexpression.</p

Shallow Magmatic Hydrothermal Eruption in April 2018 on Ebinokogen Ioyama Volcano in Kirishima Volcano Group, Kyushu, Japan

The Kirishima Volcano Group is a volcanic field ideal for studying the mechanism of steam-driven eruptions because many eruptions of this type occurred in the historical era and geophysical observation networks have been installed in this volcano. We made regular geothermal observations to understand the hydrothermal activity in Ebinokogen Ioyama Volcano. Geothermal activity resumed around the Ioyama from December 2015. A steam blowout occurred in April 2017, and a hydrothermal eruption occurred in April 2018. Geothermal activity had gradually increased before these events, suggesting intrusion of the magmatic component fluids in the hydrothermal system under the volcano. The April 2018 eruption was a magmatic hydrothermal eruption caused by the injection of magmatic fluids into a very-shallow hydrothermal system as a bottom&ndash;up fluid pressurization, although juvenile materials were not identifiable. Additionally, the upwelling of mixed magma&ndash;meteoric fluids to the surface as a kick was observed just before the eruption to cause the top&ndash;down flashing of April 2018. A series of events was generated in the shallower hydrothermal regime consisting of multiple systems divided by conductive caprock layers

Effects of the 2016 Kumamoto earthquakes on the Aso volcanic edifice

Abstract Large earthquakes occurred in the central part of Kumamoto Prefecture on April 14–16, 2016, causing severe damage to the northern segment of the Hinagu faults and the eastern segment of the Futagawa faults. Earthquake surface ruptures appeared along these faults and on the Aso volcanic edifice, which in turn generated landslides. We conducted landform change analysis of the central cones of Aso volcano by using satellite and aerial photographs. First, we categorized the topographical changes as surface scarps, arc-shaped cracks, and linear cracks. Field survey indicated that landslides caused the scarps and arc-shaped cracks, whereas faulting caused the linear cracks. We discovered a surface rupture concentration zone (RCZ) formed three ruptures bands with many surface ruptures and landslides extending from the west foot to the center of the Aso volcanic edifice. The magmatic volcanic vents that formed during the past 10,000 years are located along the north margin of the RCZ. Moreover, the distribution and dip of the core of rupture concentration zone correspond with the Nakadake craters. We conclude that a strong relationship exists between the volcanic vents and fault structures in the central cones of Aso volcano. Graphical abstract

Sex Specification and Heterogeneity of Primordial Germ Cells in Mice.

In mice, primordial germ cells migrate into the genital ridges by embryonic day 13.5 (E13.5), where they are then subjected to a sex-specific fate with female and male primordial germ cells undergoing mitotic arrest and meiosis, respectively. However, the sex-specific basis of primordial germ cell differentiation is poorly understood. The aim of this study was to investigate the sex-specific features of mouse primordial germ cells. We performed RNA-sequencing (seq) of E13.5 female and male mouse primordial germ cells using next-generation sequencing. We identified 651 and 428 differentially expressed transcripts (>2-fold, P < 0.05) in female and male primordial germ cells, respectively. Of these, many transcription factors were identified. Gene ontology and network analysis revealed differing functions of the identified female- and male-specific genes that were associated with primordial germ cell acquisition of sex-specific properties required for differentiation into germ cells. Furthermore, DNA methylation and ChIP-seq analysis of histone modifications showed that hypomethylated gene promoter regions were bound with H3K4me3 and H3K27me3. Our global transcriptome data showed that in mice, primordial germ cells are decisively assigned to a sex-specific differentiation program by E13.5, which is necessary for the development of vital germ cells

The Effects of Early Rehabilitation in the Intensive Care Unit for Patients with Severe COVID-19 Pneumonia: A Retrospective Cohort Study

This retrospective cohort study aimed to examine the rehabilitation effect of patients with coronavirus disease 2019 (COVID-19) in the intensive care unit (ICU) under mechanical ventilation and included ICU patients from a university hospital who received rehabilitation under ventilator control until 31 May 2021. Seven patients were included, and three of them died; thus, the results of the four survivors were examined. The rehabilitation program comprised the extremity range-of-motion training and sitting on the bed&rsquo;s edge. The Sequential Organ Failure Assessment score (median (25&ndash;75th percentiles)) at admission was 7.5 (5.75&ndash;8.5), and the activities of daily living (ADLs) were bedridden, the lowest in the Functional Independence Measure (FIM) and Barthel Index (BI) surveys. Data on the mean time to extubation, ICU length of stay, and ADLs improvement (FIM and BI) during ICU admission were obtained. Inferential analyses were not performed considering the small sample size. The mean time to extubation was 4.9 &plusmn; 1.1 days, and the ICU length of stay was 11.8 &plusmn; 5.0 days. &Delta;FIM was 36.5 (28.0&ndash;40.5), and the &Delta;BI was 22.5 (3.75&ndash;40.0). Moreover, no serious adverse events occurred in the patients during rehabilitation. Early mobilization of patients with COVID-19 may be useful in ADLs improvement during ICU stay

Biological significance of female and male-specific PGC-expressed genes.

<p><b>(A)</b> GO enrichment analysis of FSGs and MSGs. The most highly enriched biological processes based on their respective gene counts are shown (Fisher’s exact test: cut-off < 0.1). <b>(B)</b> Pathway analysis of all transcript lists in female and male PGCs. The lists indicate enriched pathways observed among female and male transcripts, as determined using DAVID (Fisher’s exact test: cut-off <0.1). Sex-specific pathways are highlighted in pink and blue, which denote female- and male-specific, respectively.</p