New readout and data-acquisition system in an electron-tracking Compton camera for MeV gamma-ray astronomy (SMILE-II)

For MeV gamma-ray astronomy, we have developed an electron-tracking Compton camera (ETCC) as a MeV gamma-ray telescope capable of rejecting the radiation background and attaining the high sensitivity of near 1 mCrab in space. Our ETCC comprises a gaseous time-projection chamber (TPC) with a micro pattern gas detector for tracking recoil electrons and a position-sensitive scintillation camera for detecting scattered gamma rays. After the success of a first balloon experiment in 2006 with a small ETCC (using a 10$\times$10$\times$15 cm$^3$ TPC) for measuring diffuse cosmic and atmospheric sub-MeV gamma rays (Sub-MeV gamma-ray Imaging Loaded-on-balloon Experiment I; SMILE-I), a (30 cm)$^{3}$ medium-sized ETCC was developed to measure MeV gamma-ray spectra from celestial sources, such as the Crab Nebula, with single-day balloon flights (SMILE-II). To achieve this goal, a 100-times-larger detection area compared with that of SMILE-I is required without changing the weight or power consumption of the detector system. In addition, the event rate is also expected to dramatically increase during observation. Here, we describe both the concept and the performance of the new data-acquisition system with this (30 cm)$^{3}$ ETCC to manage 100 times more data while satisfying the severe restrictions regarding the weight and power consumption imposed by a balloon-borne observation. In particular, to improve the detection efficiency of the fine tracks in the TPC from $\sim$10\% to $\sim$100\%, we introduce a new data-handling algorithm in the TPC. Therefore, for efficient management of such large amounts of data, we developed a data-acquisition system with parallel data flow.Comment: 11 pages, 24 figure

ADH Responses to Thoracic and Abdominal Surgery under Epidural Anesthesia

Changes of plasma ADH concentration were studied during thoracic and abdominal operations under epidural anesthesia comnbimed with nitrous oxide inhalation. In abdominal surgeries, ADH level was elevated by operative invasion as usually reported, significantly by peritoneal irritation particularly. In thoracic surgeries, on the other hand, ADH level showed a rise by operative invasion, but little significant change was observed by irritation to the pleura. There was no significant difference in ADH level between the high frequency positive-pressure ventilation group and the intermittent positive-pressure ventilation group

Effects of Histamine Receptor Blockers and the Rate of Administration of Morphine on Cardiovascular System

Blood pressure reduction during the high dose morphine anesthesia was investigated from the point of view of histamine receptor blockers and the rate of morphine administration. It was found as the results that blood pressure reduction was prevented by the administration of the histamine receptor blockers, and the effect was almost equivalent to that caused by morphine with the rate of infusion at 2 mg/min. Safer anesthesia may be performed in term of blood pressure reduction when H1 and H2 receptor blockers and a slow infusion of morphine with small divided doses are given

Resveratrol promotes expression of SIRT1 and StAR in rat ovarian granulosa cells: an implicative role of SIRT1 in the ovary

<p>Abstract</p> <p>Background</p> <p>Resveratrol is a natural polyphenolic compound known for its beneficial effects on energy homeostasis, and it also has multiple properties, including anti-oxidant, anti-inflammatory, and anti-tumor activities. Recently, silent information regulator genes (Sirtuins) have been identified as targets of resveratrol. Sirtuin 1 (SIRT1), originally found as an NAD⁺-dependent histone deacetylase, is a principal modulator of pathways downstream of calorie restriction, and the activation of SIRT1 ameliorates glucose homeostasis and insulin sensitivity. To date, the presence and physiological role of SIRT1 in the ovary are not known. Here we found that SIRT1 was localized in granulosa cells of the human ovary.</p> <p>Methods</p> <p>The physiological roles of resveratrol and SIRT1 in the ovary were analyzed. Immunohistochemistry was performed to localize the SIRT1 expression. SIRT1 protein expression of cultured cells and luteinized human granulosa cells was investigated by Western blot. Rat granulosa cells were obtained from diethylstilbestrol treated rats. The cells were treated with increasing doses of resveratrol, and subsequently harvested to determine mRNA levels and protein levels. Cell viability was tested by MTS assay. Cellular apoptosis was analyzed by caspase 3/7 activity test and Hoechst 33342 staining.</p> <p>Results</p> <p>SIRT1 protein was expressed in the human ovarian tissues and human luteinized granulosa cells. We demonstrated that resveratrol exhibited a potent concentration-dependent inhibition of rat granulosa cells viability. However, resveratrol-induced inhibition of rat granulosa cells viability is independent of apoptosis signal. Resveratrol increased mRNA levels of SIRT1, LH receptor, StAR, and P450 aromatase, while mRNA levels of FSH receptor remained unchanged. Western blot analysis was consistent with the results of quantitative real-time RT-PCR assay. In addition, progesterone secretion was induced by the treatment of resveratrol.</p> <p>Conclusions</p> <p>These results suggest a novel mechanism that resveratrol could enhance progesterone secretion and expression of luteinization-related genes in the ovary, and thus provide important implications to understand the mechanism of luteal phase deficiency.</p

Genotype-Dependent Efficacy of a Dual PI3K/mTOR Inhibitor, NVP-BEZ235, and an mTOR Inhibitor, RAD001, in Endometrial Carcinomas

The PI3K (phosphatidylinositol-3-kinase)/mTOR (mammalian target of rapamycin) pathway is frequently activated in endometrial cancer through various PI3K/AKT-activating genetic alterations. We examined the antitumor effect of NVP-BEZ235—a dual PI3K/mTOR inhibitor—and RAD001—an mTOR inhibitor—in 13 endometrial cancer cell lines, all of which possess one or more alterations in PTEN, PIK3CA, and K-Ras. We also combined these compounds with a MAPK pathway inhibitor (PD98059 or UO126) in cell lines with K-Ras alterations (mutations or amplification). PTEN mutant cell lines without K-Ras alterations (n = 9) were more sensitive to both RAD001 and NVP-BEZ235 than were cell lines with K-Ras alterations (n = 4). Dose-dependent growth suppression was more drastically induced by NVP-BEZ235 than by RAD001 in the sensitive cell lines. G1 arrest was induced by NVP-BEZ235 in a dose-dependent manner. We observed in vivo antitumor activity of both RAD001 and NVP-BEZ235 in nude mice. The presence of a MEK inhibitor, PD98059 or UO126, sensitized the K-Ras mutant cells to NVP-BEZ235. Robust growth suppression by NVP-BEZ235 suggests that a dual PI3K/mTOR inhibitor is a promising therapeutic for endometrial carcinomas. Our data suggest that mutational statuses of PTEN and K-Ras might be useful predictors of sensitivity to NVP-BEZ235 in certain endometrial carcinomas

注意欠如多動性障害の最近の話題といずもサマースクール

注意欠如多動性障害（Attention Deficit Hyperactivity Disorder : ADHD）には、睡眠障害の併発、食事栄養の関連、地域サポートなどとの関連が細菌、報告されており、ADHDの行動療法の有効性とも関連している。われわれは、ADHDの行動療法としていずもサマースクールを2010年より施行し、その有効性を検証しつつある。今後、いずもサマースクールにて睡眠の調整、ω-3脂肪酸の積極的な摂取、地域のサポート体制の整備なども併せて指導することにより、ADHDに対して今まで以上の効果が発揮できる可能性が示唆される

TTS in ALS and Synucleinopathies

Takotsubo syndrome (TTS) is an acute cardiac syndrome characterized by regional left ventricular dysfunction with a peculiar circumferential pattern, which typically results in apical ballooning. Evidence indicates a pivotal role of catecholamines in TTS, and researchers have discussed multiple hypotheses on the etiology, including multivessel coronary spasm, myocardial stunning, excessive transient ventricular afterload, and cardiac sympathetic overactivity with local noradrenaline spillover. Although central nervous system disorders, such as stroke and epilepsy, are known to trigger TTS, the incidence and clinical features of TTS in neurodegenerative disorders are poorly understood. Here, we retrospectively examined TTS cases in a single-center cohort composed of 250 patients with amyotrophic lateral sclerosis (ALS) and 870 patients with synucleinopathies [582 patients with Parkinson’s disease (PD), 125 patients with dementia with Lewy bodies (DLB), and 163 patients with multiple system atrophy (MSA)] and identified 4 (1.6%, including 2 women) cases with ALS and no cases with synucleinopathies. Two ALS patients underwent autopsy and the pathological findings were compatible with the chronological changes identified in catecholamine-induced cardiomyopathy. A literature review identified 16 TTS cases with ALS, 1 case each with PD and DLB, and no cases with MSA. When current and previous TTS cases with ALS were concatenated: 55% (11/20) were female; 35% (7/20) had a bulbar-onset and 45% (9/20) had a limb-onset; the mean age of TTS onset was 63.3 ± 9.0 years and the mean interval time from ALS onset to TTS development was 4.9 ± 3.0 years; no (0/16) patients developed TTS within 12 months after ALS onset; 50% (10/20) underwent artificial ventilations; the mortality was 17% (3/18); and most cases had precipitating factors, and TTS development was associated with gastrostomy, tracheostomy, or infections in 45% (9/20) of the patients. This study demonstrated that ALS is a considerable predisposing factor of TTS and that synucleinopathies rarely cause TTS. The distinct TTS incidence between ALS and synucleinopathies may be due to cardiac sympathetic overactivity in ALS and may also be affected by cardiac sympathetic denervation in synucleinopathies. Moreover, the etiology of TTS in ALS may be reasonably explained by the two-hit theory

Distinct Incidence of Takotsubo Syndrome Between Amyotrophic Lateral Sclerosis and Synucleinopathies: A Cohort Study

Takotsubo syndrome (TTS) is an acute cardiac syndrome characterized by regional left ventricular dysfunction with a peculiar circumferential pattern, which typically results in apical ballooning. Evidence indicates a pivotal role of catecholamines in TTS, and researchers have discussed multiple hypotheses on the etiology, including multivessel coronary spasm, myocardial stunning, excessive transient ventricular afterload, and cardiac sympathetic overactivity with local noradrenaline spillover. Although central nervous system disorders, such as stroke and epilepsy, are known to trigger TTS, the incidence and clinical features of TTS in neurodegenerative disorders are poorly understood. Here, we retrospectively examined TTS cases in a single-center cohort composed of 250 patients with amyotrophic lateral sclerosis (ALS) and 870 patients with synucleinopathies [582 patients with Parkinson's disease (PD), 125 patients with dementia with Lewy bodies (DLB), and 163 patients with multiple system atrophy (MSA)] and identified 4 (1.6%, including 2 women) cases with ALS and no cases with synucleinopathies. Two ALS patients underwent autopsy and the pathological findings were compatible with the chronological changes identified in catecholamine-induced cardiomyopathy. A literature review identified 16 TTS cases with ALS, 1 case each with PD and DLB, and no cases with MSA. When current and previous TTS cases with ALS were concatenated: 55% (11/20) were female; 35% (7/20) had a bulbar-onset and 45% (9/20) had a limb-onset; the mean age of TTS onset was 63.3 ± 9.0 years and the mean interval time from ALS onset to TTS development was 4.9 ± 3.0 years; no (0/16) patients developed TTS within 12 months after ALS onset; 50% (10/20) underwent artificial ventilations; the mortality was 17% (3/18); and most cases had precipitating factors, and TTS development was associated with gastrostomy, tracheostomy, or infections in 45% (9/20) of the patients. This study demonstrated that ALS is a considerable predisposing factor of TTS and that synucleinopathies rarely cause TTS. The distinct TTS incidence between ALS and synucleinopathies may be due to cardiac sympathetic overactivity in ALS and may also be affected by cardiac sympathetic denervation in synucleinopathies. Moreover, the etiology of TTS in ALS may be reasonably explained by the two-hit theory

Whole-genome resequencing shows numerous genes with nonsynonymous SNPs in the Japanese native cattle Kuchinoshima-Ushi

<p>Abstract</p> <p>Background</p> <p>Because the Japanese native cattle <it>Kuchinoshima-Ushi </it>have been isolated in a small island and their lineage has been intensely protected, it has been assumed to date that numerous and valuable genomic variations are conserved in this cattle breed.</p> <p>Results</p> <p>In this study, we evaluated genetic features of this breed, including single nucleotide polymorphism (SNP) information, by whole-genome sequencing using a Genome Analyzer II. A total of 64.2 Gb of sequence was generated, of which 86% of the obtained reads were successfully mapped to the reference sequence (Btau 4.0) with BWA. On an average, 93% of the genome was covered by the reads and the number of mapped reads corresponded to 15.8-fold coverage across the covered region. From these data, we identified 6.3 million SNPs, of which more than 5.5 million (87%) were found to be new. Out of the SNPs annotated in the bovine sequence assembly, 20,432 were found in protein-coding regions containing 11,713 nonsynonymous SNPs in 4,643 genes. Furthermore, phylogenetic analysis using sequence data from 10 genes (more than 10 kbp) showed that <it>Kuchinoshima-Ushi </it>is clearly distinct from European domestic breeds of cattle.</p> <p>Conclusions</p> <p>These results provide a framework for further genetic studies in the <it>Kuchinoshima-Ushi </it>population and research on functions of SNP-containing genes, which would aid in understanding the molecular basis underlying phenotypic variation of economically important traits in cattle and in improving intrinsic defects in domestic cattle breeds.</p