60Fe and 244Pu deposited on Earth constrain the r-process yields of recent nearby supernovae.

Half of the chemical elements heavier than iron are produced by the rapid neutron capture process (r-process). The sites and yields of this process are disputed, with candidates including some types of supernovae (SNe) and mergers of neutron stars. We search for two isotopic signatures in a sample of Pacific Ocean crust-iron-60 (60Fe) (half-life, 2.6 million years), which is predominantly produced in massive stars and ejected in supernova explosions, and plutonium-244 (244Pu) (half-life, 80.6 million years), which is produced solely in r-process events. We detect two distinct influxes of 60Fe to Earth in the last 10 million years and accompanying lower quantities of 244Pu. The 244Pu/60Fe influx ratios are similar for both events. The 244Pu influx is lower than expected if SNe dominate r-process nucleosynthesis, which implies some contribution from other sources.

Effect of 4-phenylbutyrate and valproate on dominant mutations of WFS1 gene in Wolfram syndrome.

PURPOSE: Wolfram syndrome (WS) is a rare disorder caused by mutations in WFS1 that is characterized by diabetes mellitus, optic atrophy, sensorineural deafness, diabetes insipidus, and neurodegeneration. This disease is usually inherited as an autosomal recessive trait, but an autosomal dominant form has been reported. WFS1 encodes a transmembrane protein, which is a maintenance component of endoplasmic homeostasis. These dominant mutations were thought to increase endoplasmic reticulum (ER) stress. Recent studies suggest that 4-phenylbutyrate (PBA) and valproate (VPA) reduce ER stress. The objective of this study was to analyze the effect of PBA and VPA on dominant WFS1 mutants in vitro. METHODS: We determined whether dominant WFS1 mutants (p.His313Tyr, p.Trp314Arg, p.Asp325_Ile328del, p.Glu809Lys, and p.Glu864Lys) have the dominant negative effect using a luciferase assay of ER stress response element marker as ER stress. Moreover, the rescue of cell apoptosis induced by dominant WFS1 mutants following treatment with PBA or VPA was determined by quantitative real-time PCR of C/EBP homologous protein (CHOP) mRNA expression. RESULTS: These mutants showed the dominant negative effect on the wild-type WFS1. In addition, the levels of ER stress and CHOP mRNA were significantly elevated by all dominant WFS1 mutants. After treatment with PBA or VPA, ER stress and cell apoptosis were reduced in each mutant. CONCLUSIONS: PBA and VPA could reduce the ER stress and cell apoptosis caused by dominant WFS1 mutants.

Estimate of Fukushima-derived radiocaesium in the North Pacific Ocean in summer 2012.

Distributions of radiocaesium (134Cs and 137Cs) derived from the Tokyo Electric Power Company (TEPCO) Fukushima Dai-ichi Nuclear Power Plant (FNPP1) accident in the North Pacific Ocean in the summer of 2012 were investigated. We have estimated the radiocaesium inventory in the surface layer using the optimal interpolation analysis and the subducted amount into the central mode water (CMW) by using vertical profiles of FNPP1-134Cs and mass balance analysis as the first approach. The inventory of the 134Cs in the surface layer in the North Pacific Ocean in August-December 2012 was estimated at 5.1 ± 0.9 PBq on 1 October 2012, which corresponds to 8.6 ± 1.5 PBq when it was decay corrected to the date of the FNPP1 accident, 11 March 2011. It was revealed that 56 ± 10% of the released 134Cs into the North Pacific Ocean, which was estimated at 15.3 ± 2.6 PBq, transported eastward in the surface layer in 2012. The amount of 134Cs subducted in the CMW was estimated to be 2.5 ± 0.9 PBq based on the mass balance among the three domains of the surface layer, subtropical mode water, and CMW.

Novel biallelic SZT2 mutations in 3 cases of early-onset epileptic encephalopathy.

The seizure threshold 2 (SZT2) gene encodes a large, highly conserved protein that is associated with epileptogenesis. In mice, Szt2 is abundantly expressed in the central nervous system. Recently, biallelic SZT2 mutations were found in 7 patients (from 5 families) presenting with epileptic encephalopathy with dysmorphic features and/or non-syndromic intellectual disabilities. In this study, we identified by whole-exome sequencing compound heterozygous SZT2 mutations in 3 patients with early-onset epileptic encephalopathies. Six novel SZT2 mutations were found, including 3 truncating, 1 splice site and 2 missense mutations. The splice-site mutation resulted in skipping of exon 20 and was associated with a premature stop codon. All individuals presented with seizures, severe developmental delay and intellectual disabilities with high variability. Brain MRIs revealed a characteristic thick and short corpus callosum or a persistent cavum septum pellucidum in each of the 2 cases. Interestingly, in the third case, born to consanguineous parents, had unexpected compound heterozygous missense mutations. She showed microcephaly despite the other case and previous ones presenting with macrocephaly, suggesting that SZT2 mutations might affect head size.

Recent near-Earth supernovae probed by global deposition of interstellar radioactive (60)Fe.

The rate of supernovae in our local Galactic neighbourhood within a distance of about 100 parsecs from Earth is estimated to be one every 2-4 million years, based on the total rate in the Milky Way (2.0 ± 0.7 per century). Recent massive-star and supernova activity in Earth's vicinity may be traced by radionuclides with half-lives of up to 100 million years, if trapped in interstellar dust grains that penetrate the Solar System. One such radionuclide is (60)Fe (with a half-life of 2.6 million years), which is ejected in supernova explosions and winds from massive stars. Here we report that the (60)Fe signal observed previously in deep-sea crusts is global, extended in time and of interstellar origin from multiple events. We analysed deep-sea archives from all major oceans for (60)Fe deposition via the accretion of interstellar dust particles. Our results reveal (60)Fe interstellar influxes onto Earth at 1.5-3.2 million years ago and at 6.5-8.7 million years ago. The signal measured implies that a few per cent of fresh (60)Fe was captured in dust and deposited on Earth. Our findings indicate multiple supernova and massive-star events during the last ten million years at distances of up to 100 parsecs.

Intermittent breath holding during moderate bicycle exercise provokes consistent changes in muscle oxygenation and greater blood lactate response.

AIM: This study examined the effect of intermittent breath holding (IBH) on physiological response, including oxygenation in working muscle, to moderate-intensity exercise. METHODS: Thirteen men performed bicycle exercise for 5 min at 65% of peak oxygen uptake with normal breathing (NB) and with IBH. Muscle oxygenation, concentration changes of oxyhemoglobin (ΔOxy-Hb), deoxyhemoglobin (ΔDeoxy-Hb) and total hemoglobin (ΔTotal-Hb), in the right vastus lateralis were continuously monitored using near-infrared spectroscopy (NIRS). Finger capillary blood samples were taken after exercise for analyzing blood lactate concentration (BLa). RESULTS: NIRS parameters showed acute changes to each BH episode in the IBH condition (Total-Hb and ΔOxy-Hb decreased, ΔDeoxy-Hb increased). Accordingly, in the IBH condition, ΔOxy-Hb was lower (P<0.05) and ΔDeoxy-Hb was higher (P<0.05) compared to that in the NB condition, whereas there was no difference in ΔTotal-Hb in the both conditions. BLa levels were greater (P<0.05) in the IBH condition compare to the NB condition. CONCLUSION: These results suggest that IBH during moderate-intensity exercise provokes consistent changes in muscle oxygenation, leading to lower tissue oxygenation. Our data also indicate that exercise with IBH induces higher BLa.

A prospective, randomized, double-blind, controlled trial on the efficacy of carbon dioxide insufflation in gastric endoscopic submucosal dissection.

BACKGROUND AND STUDY AIMS: Carbon dioxide (CO2) insufflation is expected to be safe and effective in endoscopic submucosal dissection (ESD) as well as in other endoscopic procedures. The present study aimed to clarify the usefulness and safety of CO2 insufflation in gastric ESD. PATIENTS AND METHODS: A total of 102 consecutive patients were randomly assigned to CO2 insufflation (CO2 group, n = 54) or air insufflation (Air group, n = 48). Abdominal pain and distension were chronologically recorded on a 100-mm visual analog scale (VAS). The volume of residual gas in the digestive tract was measured by computed tomography performed immediately after ESD. RESULTS: Abdominal pain on a 100-mm VAS in the CO2 vs. Air group was 4 vs. 3 immediately after ESD, 4 vs. 4 one hour after the procedure, 3 vs. 3 three hours after the procedure, and 1 vs. 4 the next morning, showing no difference between the groups. In addition, there was no difference in abdominal distension on the 100-mm VAS over the time course of the study. The volume of residual gas in the digestive tract in the CO2 group was significantly smaller than that in the Air group (643 mL vs. 1037 mL, P < 0.001). The dose of sedative drugs did not differ between the groups. Neither the incidences of complications nor clinical courses differed between the groups. CONCLUSIONS: Compared with air insufflation, CO2 insufflation during gastric ESD significantly reduced the volume of residual gas in the digestive tract but not the VAS score of abdominal pain and distension.

Separation of pygmy dipole and M1 resonances in 90Zr by a high-resolution inelastic proton scattering near 0°.

A high-resolution measurement of inelastic proton scattering off (90)Zr near 0° was performed at 295 MeV with a focus on a pronounced strength previously reported in the low-energy tail of giant dipole resonance. A forest of fine structure was observed in the excitation energy region 7-12 MeV. A multipole decomposition analysis of the angular distribution for the forest was carried out using the ECIS95 distorted-wave Born approximation code with the Hartree-Fock plus random-phase approximation model of E1 and M1 transition densities and inclusion of E1 Coulomb excitation. The analysis separated pygmy dipole and M1 resonances in the forest at E(PDR)=9.15±0.18 MeV with Γ(PDR)=2.91±0.64 MeV and at E(M1)=9.53±0.06 MeV with Γ(M1)=2.70±0.17 MeV in the Lorentzian function, respectively. The B(E1)↑ value for pygmy dipole resonance over 7-11 MeV is 0.75±0.08 e(2)fm(2), which corresponds to 2.1±0.2% of the Thomas-Reiche-Kuhn sum rule.

A pilot study to assess mediastinal emphysema after esophageal endoscopic submucosal dissection with carbon dioxide insufflation.

BACKGROUND AND AIMS: Mediastinal emphysema sometimes develops following esophageal endoscopic submucosal dissection (ESD) without perforation because the esophagus has no serosa. Carbon dioxide (CO2) insufflation during esophageal ESD may reduce the incidence of mediastinal emphysema. The aim of the present study was to compare the incidence and severity of post-ESD mediastinal emphysema in patients receiving CO2 insufflation vs. standard air insufflation during esophageal ESD. PATIENTS AND METHODS: A total of 27 patients who had undergone esophageal ESD with insufflation of CO2 between July 2009 and March 2010 were enrolled in this study (CO2 group). Another 105 patients who had undergone esophageal ESD with air insufflation between March 2004 and May 2009 were included as historical controls (air group). Multi-detector row computed tomography (MDCT) was carried out immediately after ESD. A conventional chest radiograph was taken the next day. Mediastinal emphysema findings on MDCT and radiography were compared between the groups. RESULTS: Mediastinal emphysema detected by chest radiography was 0 % in the CO2 group vs. 6.6 % in the air group (n.s.). Mediastinal emphysema on MDCT was significantly less frequent in the CO2 group compared with the air group (30 % vs. 63 %; P = 0.002). The severity of mediastinal emphysema also tended to be lower in the CO2 group. CONCLUSIONS: Whereas mediastinal emphysema detected by radiography is not so common, MDCT immediately after ESD revealed a certain prevalence of post-ESD mediastinal emphysema. Insufflation of CO2 rather than air during esophageal ESD significantly reduced postprocedural mediastinal emphysema. CO2 can be considered as insufflating gas for esophageal ESD.

Significant relationship between local angle at fused segments and C2-7 angle: Average duration of longer than 20 years after anterior cervical discectomy and fusion.

BACKGROUND: The authors have focused their attention to the radiological durability of cervical sagittal alignment after anterior cervical discectomy and fusion (ACDF) using autologous bone grafting. MATERIALS AND METHODS: Among the patients who underwent ACDF with trans-unco-discal (TUD) approach between 1976 and 1997, 22 patients (16 males and 6 females) made return visits for a clinical evaluation. Patients with trauma or previously treated by anterior cervical fusion or by posterior decompression were excluded from the present study. Clinical evaluation included adjacent segment degeneration (ASD), osseous fusion, local angle at the fused segments and C2-7 angle of cervical spine. RESULTS: The duration after ACDF ranged from 13 to 34 years with an average of 21.3 ± 7.0 years. A single level fusion was done on 8 patients, 2 levels on 11 patients, 3 levels on 2 patients, and 4 levels on 1 patient. Imaging studies indicated that 12 of the 22 patients (54.5%) were graded as having symptomatic ASD. Osseous bony fusion at ACDF was recognized in all cases. None of the patients demonstrated kyphotic malalignment of the cervical spine. Average degrees of local angle at the fused segments and the C2-7 angle were 7.06 and 17.6, respectively. Statistical analysis indicated a significant relationship between the local at the fused segments and C2-7 angles. CONCLUSIONS: Sagittal alignment of the cervical spine was durable long after ACDF when the local angle at the fused segments was well stabilized.

Normal variation of diffusion tensor parameters of the spinal cord in healthy subjects at 3.0-Tesla.

AIMS: The purposes of the present study were to clarify the normal variation and to determine the normal reference values of diffusion tensor (DT) parameters (mean diffusivity [MD] and fractional anisotropy [FA]) of the spinal cord in single-shot fast spin-echo-based sequence at 3.0-Tesla (3T). MATERIALS AND METHODS: Thirty healthy subjects (mean age = 44.2 years, range = 20-72 years) were enrolled for this study. Mean values of MD and FA in six spinal levels (C2/3, C3/4, C4/5, C5/6, C6/7, and C7/Th1) were measured. Mean values, variances, and distributions of the MD and FA in each spinal level were analyzed. Age-dependent change of MD and FA as well as correlation between MD and FA was also analyzed. RESULTS: At all spinal levels, the values can be considered to be Gaussian distribution in MD but not in FA. A significant statistical negative correlation was observed between aging and the values of MD (r = 0.429, P = 0.018), but insignificant between the values of FA (P = 0.234). A slight significant statistical negative correlation was observed between the values of MD and FA (r = 0.156, P = 0.037). One way repeated measures analysis of variance indicated the significant difference between the spinal levels in both MD (P = 0.003) and FA (P < 0.0001). CONCLUSIONS: The analyzed data in the present study would be helpful for comparison when investigating the spinal condition of spinal disorders.

Autism spectrum disorder is related to endoplasmic reticulum stress induced by mutations in the synaptic cell adhesion molecule, CADM1.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an unknown molecular pathogenesis. A recent molecular focus has been the mutated neuroligin 3, neuroligin 3(R451C), in gain-of-function studies and for its role in induced impairment of synaptic function, but endoplasmic reticulum (ER) stress induced by mutated molecules also deserves investigation. We previously found two missense mutations, H246N and Y251S, in the gene-encoding synaptic cell adhesion molecule-1 (CADM1) in ASD patients, including cleavage of the mutated CADM1 and its intracellular accumulation. In this study, we found that the mutated CADM1 showed slightly reduced homophilic interactions in vitro but that most of its interactions persist. The mutated CADM1 also showed morphological abnormalities, including shorter dendrites, and impaired synaptogenesis in neurons. Wild-type CADM1 was partly localized to the ER of C2C5 cells, whereas mutated CADM1 mainly accumulated in the ER despite different sensitivities toward 4-phenyl butyric acid with chemical chaperone activity and rapamycin with promotion activity for degradation of the aggregated protein. Modeling analysis suggested a direct relationship between the mutations and the conformation alteration. Both mutated CADM1 and neuroligin 3(R451C) induced upregulation of C/EBP-homologous protein (CHOP), an ER stress marker, suggesting that in addition to the trafficking impairment, this CHOP upregulation may also be involved in ASD pathogenesis.

Impaired hippocampal synaptic function in secretin deficient mice.

Secretin is a gut peptide hormone that is also expressed in the CNS. To explore the potential neuroactive role of secretin in the brain, we have generated secretin deficient mice. Secretin deficient mice demonstrated impairment in synaptic plasticity (significant reduction in long term potentiation (LTP) induction and LTP maintenance) in the CA1 area of the hippocampus. Using a beta-galactosidase (lacZ) reporter in the targeted allele and secretin antibody staining, we have detected secretin gene expression in the hippocampus, cerebellum, and the brain stem in adult mouse brain. In the hippocampus, secretin was expressed in the dentate gyrus, the hilus, and the molecular layer. These findings suggest that secretin is involved in synaptic function in the adult brain.

M1 gamma strength for zirconium nuclei in the photoneutron channel.

Photoneutron cross sections were measured for 91Zr, 92Zr, and 94Zr near the neutron separation energy with quasimonochromatic gamma rays. The data exhibit some extra components around the neutron threshold. A coherent analysis of the photoneutron data for 92Zr together with the neutron capture on 91Zr based on the microscopic Hartree-Fock-Bogoliubov plus quasiparticle random-phase approximation model for the E1 strength has revealed the presence of an M1 resonance at 9 MeV. The microscopic approach systematically shows the same M1 strength in the photoneutron cross section for 91Zr and 94Zr. The total M1 strength is about 75% larger than the strength predicted by the systematics, being qualitatively consistent with the giant M1 resonance observed in the inelastic proton scattering.

Comparison of bronchodilatory properties of transdermal and inhaled long-acting beta 2-agonists.

BACKGROUND: Regular use of long-acting bronchodilators is recommended for symptomatic COPD patients. A transdermal type of beta 2-agonist, tulobuterol, was recently developed. This agent shows the pharmacokinetic property of a sustained serum concentration for 24h. However, little has been reported about the bronchodilatory properties of this agent. OBJECTIVES: The aim of the present study was to compare the bronchodilatory action of transdermal beta 2-agonist tulobuterol with that of inhaled long-acting beta 2-agonist salmeterol. METHODS: An open-label, randomized crossover study was performed. Eleven patients with stable COPD were enrolled in the study. Tulobuterol (2mg/day) or salmeterol (50 microg, twice daily) was administered in a randomized, crossover manner. Forced expiratory volume in 1s (FEV1), forced vital capacity (FVC) and inspiratory capacity (IC) were measured before administration, every 2h from 12 to 24h, and at 36 h after the initial administration. RESULTS: Transdermal beta 2-agonist tulobuterol showed an improvement in FEV1, FVC and IC after dosing compared with those at baseline. Salmeterol also improved all parameters of FEV1, FVC and IC, and showed a greater improvement compared with the transdermal beta 2-agonist tulobuterol (p<0.05). The values of the area under the curve (AUC) of FEV1, FVC and IC during the administration of tulobuterol were 2.98+/-1.05, 1.81+/-0.98, 0.75+/-0.85 L h, respectively, and during the administration of salmeterol they were 6.39+/-1.12, 6.61+/-1.34, 4.28+/-0.91 L h, respectively. CONCLUSION: The transdermal beta 2-agonist tulobuterol showed bronchodilatory action for at least 24h by once daily administration. However, its bronchodilatory potency was about three times less than that of the inhaled beta 2-agonist salmeterol.

Survival study by organ disorders in 306 Japanese patients with systemic lupus erythematosus: results from a single center.

Survival rate and causes of death according to the period of diagnosis and four accompanying organ disorders were analyzed in 306 Japanese patients with systemic lupus erythematosus. The survival rate was gradually improved, and the survival rate during 5- and 10-year periods of the patients diagnosed in 1990-2004 was 94 and 92%, 20-year period of those in 1980-1989 was 77%, 30-year period of those in 1975-1979 was 71%, respectively. Survival rate of those with serositis, pulmonary hypertension, and positive family history tended to be reduced, while that of the cases with neuropsychiatric disorder and renal disorder was significantly reduced. Overlapping of these organ disorders was an important factor for a poor prognosis. Bronchopneumonia and cerebrovascular accidents were frequent causes of death, and treatment for anti-phospholipid antibody syndrome and life-style diseases such as hypertension and arteriosclerosis was thought to be important for a good outcome.

Improvement of pulmonary function and dyspnea by tiotropium in COPD patients using a transdermal beta(2)-agonist.

BACKGROUND: A combination of bronchodilators may be effective in the treatment of chronic obstructive pulmonary disease (COPD). We examined the effect of adding a long-acting anti-cholinergic agent (tiotropium) to a transdermal-type beta(2)-agonist (tulobuterol) on dyspnea as well as pulmonary function. METHODS: In a multicentre, randomized, parallel design study, 60 COPD patients treated with the transdermal beta(2)-agonist tulobuterol were divided into a tiotropium added group (Tulo+Tio group, n=40) or transdermal beta(2)-agonist tulobuterol alone group (Tulo group, n=20), and then treated for 4 weeks after a 2 week run-in period. Pulmonary function and a dyspnea (Medical Research Council (MRC)) scale were assessed before and after the treatment. Daily peak expiratory flow (PEF) monitoring was also performed. RESULTS: After 4 weeks, the Tulo+Tio group showed a significant increase in pulmonary function compared with the Tulo group; DeltaFVC (0.31+/-0.06 L vs. 0.06+/-0.05 L, p< 0.01), DeltaFEV(1) (0.15+/-0.03 L vs. -0.02+/-0.02 L, p<0.0001), and DeltaPEF (41.0+/-5.1 L/min vs. 0.5+/-3.5 L/min, p<0.0001). The MRC dyspnea scale was also significantly improved in Tulo+Tio, but not in Tulo group. CONCLUSION: These results suggest that tiotropium caused a significant improvement in both pulmonary function and dyspnea in COPD patients already treated with the transdermal beta(2)-agonist tulobuterol.

Extraction of weak transition strengths via the (3He, t) reaction at 420 MeV.

Differential cross sections for transitions of known weak strength were measured with the (3He, t) reaction at 420 MeV on targets of 12C, 13C, 18O, 26Mg, 58Ni, 60Ni, 90Zr, 118Sn, 120Sn, and 208Pb. Using these data, it is shown that the proportionalities between strengths and cross sections for this probe follow simple trends as a function of mass number. These trends can be used to confidently determine Gamow-Teller strength distributions in nuclei for which the proportionality cannot be calibrated via beta-decay strengths. Although theoretical calculations in the distorted-wave Born approximation overestimate the data, they allow one to understand the main experimental features and to predict deviations from the simple trends observed in some of the transitions.