Observation of Coulomb-Assisted Nuclear Bound State of Ξ

In an emulsion-counter hybrid experiment performed at J-PARC, a Ξ^{-} absorption event was observed which decayed into twin single-Λ hypernuclei. Kinematic calculations enabled a unique identification of the reaction process as Ξ^{-}+^{14}N→_{Λ}^{10}Be+_{Λ}^{5}He. For the binding energy of the Ξ^{-} hyperon in the Ξ^{-}-^{14}N system a value of 1.27±0.21 MeV was deduced. The energy level of Ξ^{-} is likely a nuclear 1p state which indicates a weak ΞN-ΛΛ coupling.

Phylogenetic and phylodynamic analyses of hepatitis C virus subtype 1a in Okinawa, Japan.

Okinawa Island, located in Southern Japan, has a higher prevalence rate of hepatitis C virus subtype 1a (HCV-1a) infection than that in mainland Japan. Okinawa has a history of US military occupation after World War II. To elucidate the transmission history of HCV-1a in Okinawa, 26 whole-genome sequences were obtained from 29 patients during 2011-2016. Phylogenetic trees were reconstructed to identify the origin and characteristics of HCV-1a in Okinawa with epidemiological information. A phylogenetic tree based on whole-genome sequencing revealed that all of the samples were located below the US branches. Additionally, we identified one cluster comprised of 17 strains (Okinawa, n = 16; United States, n = 1). The majority of the patients in this cluster were people who inject drugs (PWID), indicating the presence of a people who inject drugs (PWID) cluster. Subsequently, Bayesian analyses were employed to reveal viral population dynamics. Intriguingly, a phylodynamic analysis uncovered a substantial increase in effective population size of HCV-1a from 1965 to 1980 and a slight increase in mid-2000, which were associated with an increase in illicit drug use in Okinawa. The estimated divergence time of the PWID cluster was 1967.6 (1964.2-1971.1). These findings suggest that HCV-1a was introduced into Okinawa from the United States in the late 1960s, coincident with the Vietnam War. Subsequently, HCV-1a might have spread among the Japanese population with the spread of injecting drug use. Our study provides an understanding of HCV transmission dynamics in Okinawa, as well as the key role of PWID in HCV transmission.

Spatiotemporal structures of edge limit-cycle oscillation before L-to-H transition in the JFT-2M tokamak.

In this Letter, we report analyses of spatiotemporal dynamics of turbulence and structure in the limit-cycle oscillation (LCO) that precedes an L-to-H transition. Zonal flows are not observed during LCO, and the oscillation is the periodic generations or decays of barrier with edge-localized mean flow. Oscillatory Reynolds stress is found to be too small to accelerate the LCO flow, by considering the dielectric constant in magnetized toroidal plasmas. Propagation of changes of the density gradient and turbulence amplitude into the core is also observed.

Ab initio study on the hydrogen desorption from MH-NH3 (M = Li, Na, K) hydrogen storage systems.

The hydrogen storage system LiH + NH(3) ↔ LiNH(2) + H(2) is one of the most promising hydrogen storage systems, where the reaction yield can be increased by replacing Li in LiH with other alkali metals (Na or K) in order of Li < Na < K. In this paper, we have studied the alkali metal M (M = Li, Na, K) dependence of the reactivity of MH with NH(3) by calculating the potential barrier of the H(2) desorption process from the reaction of an M(2)H(2) cluster with an NH(3) molecule based on the ab initio structure optimization method. We have shown that the height of the potential barrier becomes lower in order of Li, Na, and K, where the difference of the potential barrier in Li and Na is relatively smaller than that in Na and K, and this tendency is consistent with the recent experimental results. We have also shown that the H-H distance of the H(2) dimer at the transition state takes larger distance and the change of the potential energy around the transition state becomes softer in order of Li, Na, and K. There are almost no M dependence in the charge of the H atom in NH(3) before the reaction, while that of the H atom in M(2)H(2) takes larger negative value in order of Li, Na, and K. We have also performed molecular dynamics simulations on the M(2)H(2)-NH(3) system and succeeded to reproduce the H(2) desorption from the reaction of Na(2)H(2) with NH(3).

Immune cell activation by bacterial CpG-DNA through myeloid differentiation marker 88 and tumor necrosis factor receptor-associated factor (TRAF)6.

Transition of immature antigen presenting cells (APCs) to the state of professional APCs is essential for initiation of cell-mediated immune responses to pathogens. Signal transduction via molecules of the Toll-like receptor (TLR)/interleukin 1 receptor (IL-1R) pathway is critical for activation of APCs either by pathogen-derived pattern ligands like lipopolysaccharides (LPS) or by CD40 ligation through T helper cells. The capacity of bacterial DNA (CpG-DNA) to induce APCs to differentiate into professional APCs represents an interesting discovery. However, the signaling pathways involved are poorly understood. Here we show that CpG-DNA activates the TLR/IL-1R signaling pathway via the molecules myeloid differentiation marker 88 (MyD88) and tumor necrosis factor receptor-associated factor 6 (TRAF6), leading to activation of kinases of the IkappaB kinase complex and the c-jun NH(2)-terminal kinases. Moreover, cells of TLR2- and TLR4-deficient mice are activated by CpG-DNA, whereas cells of MyD88-deficient mice do not respond. The data suggest that CpG-DNA initiates signaling via the TLR/IL-1R pathway in APCs in a manner similar to LPS and to T helper cell-mediated CD40 ligation. Activation of the TLR/IL-1R signaling pathway by foreign bacterial DNA may be one way to initiate innate defense mechanisms against infectious pathogens in vivo.

The absence of interleukin 1 receptor-related T1/ST2 does not affect T helper cell type 2 development and its effector function.

T1/ST2, an orphan receptor with homology with the interleukin (IL)-1 receptor family, is expressed constitutively and stably on the surface of T helper type 2 (Th2) cells, but not on Th1 cells. T1/ST2 is also expressed on mast cells, which are critical for Th2-mediated effector responses. To evaluate whether T1/ST2 is required for Th2 responses and mast cell function, we have generated T1/ST2-deficient (T1/ST2(-/-)) mice and examined the roles of T1/ST2. Naive CD4(+) T cells isolated from T1/ST2(-/-) mice developed to Th2 cells in response to IL-4 in vitro. T1/ST2(-/-) mice showed normal Th2 responses after infection with the helminthic parasite Nippostrongylus brasiliensis as well as in the mouse model of allergen-induced airway inflammation. In addition, differentiation and function of bone marrow-derived cultured mast cells were unaffected. These findings demonstrate that T1/ST2 does not play an essential role in development and function of Th2 cells and mast cells.

Phencyclidine affects firing activity of basolateral amygdala neurons related to social behavior in rats.

Negative symptoms of schizophrenia, such as social withdrawal and blunted affect, usually persist for a long period, making rehabilitation difficult. Many studies have demonstrated a close relationship between function of the amygdala and social behavior. Normal social behavior is disturbed in animals administered phencyclidine (PCP), which is now considered a reliable pharmacological model of schizophrenia. Recent studies have reported that disruption of social behavior in PCP-treated rats involved dysfunction of the amygdala. Disturbance of function of the amygdala has also been reported in schizophrenic patients. However, no study has yet examined the effects of PCP on the firing activity of amygdala neurons. In the present study, we recorded the unit activity of basolateral amygdala neurons while rats engaged in socially interactive behavior. After identifying the response properties of recorded neurons, we then recorded the same neurons with systemic PCP administration. Approximately half of the neurons recorded from exhibited an increase in spontaneous discharge rate during social interaction. Only a few neurons exhibited suppression of discharge rate during social interaction. Systemic administration of PCP induced long-lasting activation in half of the neurons that exhibited an increase in firing rate during social interaction. PCP activated half of basolateral amygdala neurons related to socially interactive behavior, and might in this fashion produce dysfunction of social behavior.

Scoring of reflux symptoms associated with scleroderma and the usefulness of rabeprazole.

OBJECTIVE: The high frequency of gastroesophageal reflux disease (GERD) as a complication of scleroderma (systemic sclerosis, SSc) calls for treatment with powerful acid suppressants such as proton pump inhibitors (PPI). The present study used a GERD-specific questionnaire to assess the symptoms of GERD in SSc patients, and examine the effectiveness of rabeprazole (RPZ) for treating the symptoms of GERD. METHODS: The Frequency Scale for the Symptoms of GERD (FSSG), a medical questionnaire developed in Japan for evaluating GERD, and the Visual Analogue Scale (VAS) were used to evaluate GERD symptoms and the degree of pain, respectively, in 151 SSc subjects. These tools were also used to assess the effect of 8 weeks' treatment with the PPI RPZ (10 mg/day). RESULTS: Data on age and gender, and FSSG and VAS scores before treatment and after 4 and 8 weeks' RPZ treatment, were available for 84 subjects. The mean FSSG score was 13.9+/-9.7 before treatment, 8.3+/-8.1 after 4 weeks of treatment, and 7.0+/-7.0 after 8 weeks of treatment; the score reduction was significant (p<0.001) indicating the effectiveness of RPZ in improving subjective GERD symptoms. The VAS scores revealed a significant improvement in pain after both 4 and 8 weeks compared with baseline scores. Six subjects experienced adverse effects and five discontinued the analysis during the period. CONCLUSION: Administration of RPZ 10 mg/day is effective for the control of the symptoms of GERD associated with SSc. In addition to assessing the symptoms of GERD, the FSSG questionnaire can be used to evaluate the therapeutic effect of drugs.

Reconstruction of carbon atoms around a point defect of a graphene: a hybrid quantum/classical molecular-dynamics simulation.

We have investigated the rearrangement of carbon atoms around a point defect of a graphene using a hybrid ab initio/classical molecular-dynamics (MD) simulation method, in which 36 carbon atoms surrounding a point defect are treated by the ab initio MD method and the other 475 carbon atoms relatively far from the point defect are treated by the classical MD method. We have confirmed a formation of a 5-1DB defect (a pentagon and a dangling bond) from the time dependence of atomic configurations and electron density distributions obtained by our simulation. We have found that the pentagon is formed in two different positions around the point defect, and that the two positions appear alternately during the simulation, the frequency of which increases with increasing temperature.

Correlation of motility and neuronal integrity with a focus on the grade of intestinal allograft rejection.

Intestinal graft motility after small bowel transplantation (SBT) is poorly characterized. The aim of this study was to compare motor patterns with myenteric neuronal cell population as a parameter of graft viability at various degrees of acute cellular rejection (ACR). Three grades of ACR were achieved in orthotopic allografts. Syngeneic transplants and allografts with immunosuppression served as controls. Motor activities were recorded using strain gauge force transducers and analyzed visually. Quantifications of myenteric neurons in whole mounts of intestinal grafts were used to evaluate neuronal population. A typical migrating motor complex (MMC) was found in syngeneic and allogenic transplants with immunosuppression. A high prevalence of discrete clustered contractions (DCC) and nonpropagating contractions (NPC) without MMC was seen in moderately and severely rejected allografts. Neuronal cell loss in the allografts, which could be one of the causes of motor dysfunction, was noted in moderate rejection (19.3%) and progressed until severe rejection (60.1%). Monitoring motility patterns in SBT could be an effective tool for assessing intestinal rejection. Allograft dysmotility, such as absence of MMC and high prevalence of DCC or NPC, could be useful markers of progression of acute rejection and help guide treatment decisions.

Aberrant DNA methylation of the Src kinase Hck, but not of Lyn, in Philadelphia chromosome negative acute lymphocytic leukemia.

Hck and Lyn are required in Philadelphia chromosome (Ph) positive acute lymphocytic leukemia (ALL). Here, we present evidence that the promoter CpG island of Hck, but not of Lyn, is aberrantly methylated in leukemia. Hck promoter DNA methylation was detected in 13 out of 23 (56.5%) hematopoietic and eight out of 10 (80%) non-hematopoietic cell lines, but not in normal controls. Treatment with 5-aza-2'-deoxycytidine induced demethylation and restoration of Hck mRNA and protein expression. Hck methylation (> or =15%) was detected in nine out of 44 (20%) patients with Ph negative ALL, and in one out 16 (6%) patients with Ph positive ALL, but not in patients with AML or chronic myelogenous leukemia. In this subset of patients, low levels of Hck methylation (10-15%) were observed in 26-30% of patients. Lyn methylation was observed in three out of 28 (10.7%) cell lines, but only in one out of 71 (1.4%) patients. Patients with Ph negative ALL and Hck methylation had a poorer prognosis. These data indicate that Hck may have tumor suppressor properties in BCR-ABL negative leukemia.

[Effectiveness of high frequency jet ventilation introduced immediately after cardiac surgery].

It is important to establish the lung protective strategy strictly for serious respiratory failure after cardiac surgery, because the hemodynamic state is unstable. High frequency jet ventilation (HFJV) was introduced in 5 patients with respiratory failure after cardiac surgery. Two had been diagnosed with acute aortic dissection and 3 with angina pectorlis. Off pump coronary artery bypass grafting was performed in 2 patients. Hemodynamic variables during HFJV were stable, and the duration of HFJV was 9 to 45 hours. Oxygenations improved immediately by the introduction of HFJV in all patients, and no adverse effect was recognized. Therefore, use of HFJV immediately after cardiac surgery might be an effective respiratory therapy of choice for patients with acute lung injury.

Impact of Donor Age on Outcome of Intestinal Transplantation in Japan.

BACKGROUND: Donor age for intestinal transplantation (ITx) is somewhat younger than that for other solid organs. Clear criteria for adequate donors have not been established. There is a donor scarcity for ITx in Japan due to the shortage of young donors. METHODS: We reviewed outcomes associated with ITx in Japan based on donor age for cadaveric and living donation. RESULTS: Standardized report forms were sent to all known ITx programs, asking for information on ITxs performed between 1996 and 2016. All programs responded. Patient and graft survival estimates were obtained using the Kaplan-Meier method. Five institutions provided data on 27 grafts in 24 patients. There were 14 cadaveric and 13 living donor transplants. Median donor age for ITxs was 40 (range, 17-60) years. Graft survival at 5 years was 66% for patients >40 years old (n = 18) and 47% for those <40 years old (n = 9), not a statistically significant difference (P = .49). Graft survival at 5 years was 60% in those >50 years old (n = 5) and 57% for those <50 years old (n = 22), again not a significant difference (P = .27). CONCLUSION: There is no difference in survival between for those with donor age <40 vs >40 years. Donor age for ITx can be extended from >40 to up to 50 years, which may help to mitigate the donor shortage. It will be necessary to clarify the donor criteria for ITx through accumulation of further data on ITx.

Three-Year Prospective Follow-up of Potential Pediatric Candidate for Intestinal Transplantation.

Intestinal transplantation (ITx) is a treatment for refractory intestinal failure (IF). However, the indications for and timing of ITx are still controversial because the course of IF is unknown. We performed a prospective multi-institutional cohort study to identify the prognostic factors for referral to an ITx facility. Patients under 18 years of age in Japan who suffered from IF and had received parenteral nutrition for longer than 6 months were enrolled in this study. They were followed up for 3 years. Seventy-two patients were followed. The mean age at the beginning of the study was 7.0 years. Diagnoses were short gut syndrome (n = 25), motility disorder (n = 45), and other (n = 2). The overall 3-year survival rate was 95%. The 3-year survival rate was 86% in patients with intestinal-failure-associated liver disease (IFALD) (n = 6) compared to 97% in those without IFALD (n = 66) (P = .0003). Furthermore, the 3-year survival rates of patients who did and did not meet the criteria for ITx were 82% (n = 11) and 97% (n = 62), respectively (P = .034). Six (44%) of 14 patients whose performance status (PS) was ≥3 at enrollment were dead or still had a PS ≥ 3 at 3 years. This study indicates that IFALD is a poor prognostic factor in pediatric patients with IF. Our indication for ITx, namely the presence of IFALD or loss of more than 2 parenteral nutrition access sites, seems to be applicable.

In vitro single-unit recordings reveal increased peripheral nerve conduction velocity by focused pulsed ultrasound.

Ultrasound that is widely used in medical diagnosis has drawn growing interests as a noninvasive means of neuromodulation. Focused pulsed ultrasound (FPUS) effectively modulates neural encoding and transmission in the peripheral nervous system (PNS) with unclear mechanism of action, which is further confounded by contradictory experimental outcomes from recordings of compound action potentials (CAP). To address that, we developed a novel in vitro set up to achieve simultaneous single-unit recordings from individual mouse sciatic nerve axon and systematically studied the neuromodulation effects of FPUS on individual axon. Unlike previous CAP recordings, our single-unit recordings afford superior spatial and temporal resolution to reveal the subtle but consistent effects of ultrasonic neuromodulation. Our results indicate that, 1) FPUS did not evoke action potentials directly in mouse sciatic nerve at all the tested intensities (spatial peak temporal average intensity, ISPTA of 0.91 to 28.2 W/cm2); 2) FPUS increases the nerve conduction velocity (CV) in both fast-conducting A- and slow-conducting C- type axons with effects more pronounced at increased stimulus duration and intensity; and 3) effects of increased CV is reversible and cannot be attributed to the change of local temperature. Our results support existing theories of non-thermal mechanisms underlying ultrasonic neuromodulation with low-intensity FPUS, including NICE, flexoelectricity, and solition models. This work also provides a solid experimental basis to further advance our mechanistic understandings of ultrasonic neuromodulation in the PNS.

Decreased Incidence of Acute Cellular Rejection in Low-Muscle-Mass Recipients After Living-donor Liver Transplantation.

BACKGROUND: Sarcopenia has recently been studied as a potential risk factor for mortality and complications after liver transplantation. We investigated the impact of low muscle mass on postoperative outcomes after living-donor liver transplantation. METHODS: Our study population consisted of 100 adult recipients who underwent living-donor liver transplantation in our department between 2005 and 2017. Recipients were divided into a low-muscle-mass group (L group) and a normal-muscle-mass group (N group) based on skeletal muscle index (SMI) values, and postoperative outcomes were compared between the groups. Regarding factors that were significantly different between the groups, multivariate analyses were performed to identify predictive factors. RESULTS: Based on the SMI definition, 47 and 53 of the recipients were categorized as having low muscle mass (L group) and normal muscle mass (N group), respectively. Comparison between the groups revealed a significantly reduced incidence of rejection (10.6% in L group vs 30.2% in N group, P = .017) and increased incidences of bacterial infection (61.7% in L group vs 37.7% in N group, P = .017) in the L group compared with the N group. The survival rate did not differ significantly between the groups. Multivariate analyses indicated that muscle mass was a significant predictive factor for both rejection and bacterial infection. CONCLUSION: It is important to recognize that muscle mass has an impact not only on bacterial infection but also on rejection in recipients with low muscle mass in the postoperative course of living-donor liver transplantation.

Targeted delivery of NK4 to multiple lung tumors by bone marrow-derived mesenchymal stem cells.

Most advanced solid tumors metastasize to different organs. However, no gene therapy effective for multiple tumors has yet been developed. Since a unique characteristic of bone marrow-derived mesenchymal stem cells (MSCs) is that they migrate to tumor tissues, we wanted to determine whether MSCs could serve as a vehicle of gene therapy for targeting multiple tumors. First, we confirmed that mouse MSCs preferentially migrate to multiple tumors of the lung in the Colon-26 (C-26) lung metastasis model. Next, MSCs were efficiently transduced with NK4, an antagonist of hepatocyte growth factor (HGF), by an adenoviral vector with an RGD motif. MSCs expressing NK4 (NK4-MSCs) strongly inhibited development of lung metastases in the C-26 lung metastasis model after systemic administration via a tail vein. Treatment with NK4-MSCs significantly prolonged survival of the C-26-tumor-bearing mice by inhibiting tumor-associated angiogenesis and lymphangiogenesis and inducing apoptosis of the tumor cells. MSC-based gene therapy did not induce the severe adverse effects induced by conventional adenoviral vectors. These results indicate that MSCs can serve as a vehicle of gene therapy for targeting multiple lung metastatic tumors.

Activation of medial prefrontal cortex neurons by phencyclidine is mediated via AMPA/kainate glutamate receptors in anesthetized rats.

Phencyclidine (PCP) is a psychotomimetic drug that elicits schizophrenia-like symptoms in healthy individuals, and animals administered PCP are now considered a reliable pharmacological model of schizophrenia. Recent studies have shown that systemically administered PCP produces long-lasting activation of medial prefrontal cortex (mPFC) neurons, and that hyperactivation of mPFC neurons plays a critically important role in the development of PCP-induced behavioral abnormalities. However, the receptors mediating this mPFC activation have not been clearly determined. Here, we examined the effects of local application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an AMPA/kainate glutamate receptor antagonist, scopolamine, a muscarinic acetylcholine receptor antagonist, and mecamylamine, a nicotinic acetylcholine receptor antagonist, on the increase in firing rate of mPFC neurons induced by systemic PCP in anesthetized rats. After tonic activation of mPFC neurons by PCP had been established, CNQX, scopolamine, or mecamylamine was iontophoretically applied or pressure-ejected on the recorded neuron. CNQX suppressed PCP-induced elevation of firing rate to baseline level, though scopolamine and mecamylamine each induced little change in firing rate. These findings suggest that PCP-induced activation of mPFC neurons is mediated primarily via AMPA/kainate glutamate receptors.

Hydrogen desorption from nanostructured graphite: ab initio molecular-dynamics studies.

We have carried out hybrid ab initio/classical molecular-dynamics simulations for the model system of hydrogen-adsorbed nanostructured graphite. We have investigated the effect of the recrystallization of the nanostructured graphite to the bonding states of hydrogen atoms at 1000 K and the desorption mechanism of the hydrogen dimer from the graphite at 2000 K. We have shown that the recrystallization weakens the bond between the hydrogen and the carbon atoms and the desorption of hydrogen atoms, as the hydrogen dimer occurs at 2000 K.

Incidence of elevated procalcitonin and presepsin levels after severe trauma: a pilot cohort study.

Procalcitonin (PCT) and presepsin (PSEP) are useful biomarkers for diagnosing sepsis; however, elevated PCT and PSEP levels may be observed in conditions other than sepsis. We hypothesised that PCT and PSEP levels could increase after severe traumatic injuries. Trauma patients with an Injury Severity Score of ≥16 from October 2013 to September 2015 were enrolled in our study. We examined PCT and PSEP levels and their positive rates on days 0 and 1. PCT and PSEP levels on days 0 and 1 were compared. Risk factors for increasing sepsis biomarker levels were identified by multivariate logistic regression analyses. In this study, 75 patients were included. PCT levels on days 0 and 1 were 0.1±0.4 and 1.8±6.3 ng/ml, respectively (P=0.02). PSEP levels on days 0 and 1 were 221±261 and 222±207 pg/ml, respectively (P=0.98). As per multivariate logistic regression analyses, packed red blood cell (PRBC) transfusion was the only independent risk factor for higher PCT levels on day 1 (P=0.04). Using PCT to diagnose sepsis in trauma patients on day 1 requires caution. PRBC transfusion was found to be a risk factor for increasing PCT levels. On the other hand, PSEP levels were not affected by trauma during the early phases.