A compact stilbene crystal neutron spectrometer for NBI-heated plasma neutron diagnostics at EAST.

Stilbene crystal detectors are widely used as fast neutron measurement tools based on recoil proton detection, such as liquid scintillators. A compact stilbene crystal neutron spectrometer (CSCNS) has been installed at the Experimental Advanced Superconducting Tokamak (EAST) to obtain information on fuel ions produced in the plasma core because of its merits of good n/γ discrimination capability, high detection efficiency, and fast response. For the first time, CSCNS has been used for neutron emission spectroscopy measurements in EAST plasmas with neutral beam injection (NBI) heating. The CSCNS has the same horizontal line of sight as the time-of-flight enhanced diagnostics neutron spectrometer. Under NBI heating scenarios, the time trace of the neutron yield monitored by the CSCNS is similar to the one monitored by a standard 235U fission chamber. The experimental pulse height spectra are also similar to the simulated ones generated by folding the simulated neutron energy spectrum with the detector response functions. These results demonstrate the capability of the CSCNS for neutron diagnostics and the study of fast-ion physics in EAST.

Suppression of ovulation in the rat by an orally active antagonist of luteinizing hormone-releasing hormone.

A synthetic antagonist of luteinizing hormone-releasing hormone blocked ovulation in rats in a dose-dependent manner when given by gavage on the afternoon of proestrus. Ovulation was delayed for at least 1 day in all animals given 2 milligrams of antogonist and in some of the animals treated with 1 or 0.5 milligram. Oral administration of 2 milligrams also blocked the preovulatory surge of luteinizing hormone. This demonstration that antagonists of luteinizing hormone-releasing hormone can have oral antiovulatory activity clearly enhances their therapeutic potential.

Correlations of IL-6 and CRP gene polymorphisms with pulmonary heart disease.

OBJECTIVE: To explore the correlations of interleukin-6 (IL-6) and C-reactive protein (CRP) gene polymorphisms with pulmonary heart disease (PHD). PATIENTS AND METHODS: A total of 98 patients with PHD and 102 healthy persons receiving physical examinations were enrolled. Their general clinical information was collected, and the levels of IL-6 and CRP in the plasma were determined. The pulmonary functions and blood gas were detected, and the TaqMan-minor groove binder (MGB) probe was used to detect the polymorphisms of IL-6 rs1800796 and CRP rs1800796. RESULTS: Observation group had higher levels of IL-6 and CRP than control group (p<0.05). The forced expiratory volume in 1 second (FEV1) (%), FEV1/forced vital capacity (FVC) ratio (%), and arterial partial pressure of oxygen (PaO2) in observation group were lower than those in control group (p<0.05), but the arterial partial pressure of carbon dioxide (PaCO2) was higher than that in control group (p<0.05). There were differences in the distribution frequencies of the genotypes and alleles of IL-6 rs1800796 and CRP rs1800796 between the two groups (p<0.05). CONCLUSIONS: IL-6 and CRP are correlated with the onset of PHD, and there are also correlations between the polymorphisms of IL-6 rs1800796 and CRP rs2794521 and the disease.

Velocity-space sensitivity of the compact neutron emission spectrometers at EAST.

Several compact neutron spectrometers are now installed at EAST (Experimental Advanced Superconducting Tokamak) to obtain information on fuel ions produced in the core of the plasma. In this paper, a stilbene crystal neutron spectrometer and an EJ301 liquid scintillator neutron spectrometer with n-γ discrimination capability will be discussed. Both spectrometers have a horizontal line of sight, while at different positions. In the last few experiment campaigns at EAST, they all proved to be reliable diagnostics for auxiliary heated D-D plasmas. Taking the response function simulated by dedicated Geant4 models into consideration, the velocity-space sensitivities given by the instrument-specific weight function of the beam-thermal part of neutron energy spectra in D-D plasmas are derived for both spectrometers with the Genesis code. This method makes it possible to directly relate the contribution of different deuteron velocity space regions to events in each channel of the neutron spectrum measured by the two instruments: http://rsi-htpd.peerx-press.org/.

Velocity-space sensitivity of time-of-flight neutron spectrometer at EAST in deuterium plasma.

The Time-Of-Flight Enhanced Diagnostics (TOFED) neutron spectrometer with a double-ring structure has been installed at the Experimental Advanced Superconducting Tokamak (EAST) to perform advanced neutron emission spectroscopy diagnosis for deuterium plasma. In order to reduce the random coincidence from the background neutrons and gamma-rays, TOFED was moved outside the experimental hall and placed in the newly-built nuclear diagnostics laboratory in 2017. In this paper, the instrument-specific weight functions of TOFED are derived by taking the instrument response matrix and the radial line of sight in this new layout into consideration. The results show that the instrument is predominantly sensitive to counter-passing particles in the region where time-of-flights < 69.4 ns, while events at higher time-of-flights (corresponding lower neutron energies) are mostly representative of co-passing ions. The instrument-specific weight functions express the relationship between data in a given channel of the spectrum and the velocity space region that contributes to that. The results can be applied for energetic particle physics studies at EAST, in particular to compare data from different diagnostic techniques.

Junctophilin 3 expresses in pancreatic beta cells and is required for glucose-stimulated insulin secretion.

It is well accepted that junctophilin (JPHs) isoforms act as a physical bridge linking plasma membrane and endoplasmic reticulum (ER) for channel crosstalk in excitable cells. Our purpose is to investigate whether JPHs are involved in the proper communication between Ca(2+) influx and subsequent Ca(2+) amplification in pancreatic beta cells, thereby participating in regulating insulin secretion. The expression of JPH isoforms was examined in human and mouse pancreatic tissues, and JPH3 expression was found in both the beta cells. In mice, knockdown of Jph3 (si-Jph3) in islets decreased glucose-stimulated insulin secretion (GSIS) accompanied by mitochondrial function impairment. Si-Jph3 lowered the insulin secretory response to Ca(2+) signaling in the presence of glucose, and reduced [Ca(2+)]c transient amplitude triggered by caffeine. Si-Jph3 also attenuated mitofusin 2 expression, thereby disturbing the spatial organization of ER-mitochondria contact in islets. These results suggest that the regulation of GSIS by the KATP channel-independent pathways is partly impaired due to decrease of JPH3 expression in mouse islets. JPH3 also binds to type 2 ryanodine receptors (RyR2) in mouse and human pancreatic tissues, which might contribute to Ca(2+) release amplification in GSIS. This study demonstrates some previously unrecognized findings in pancreatic tissues: (1) JPH3 expresses in mouse and human beta cells; (2) si-Jph3 in mouse primary islets impairs GSIS in vitro; (3) impairment in GSIS in si-Jph3 islets is due to changes in RyR2-[Ca(2+)]c transient amplitude and ER-mitochondria contact.

Status of neutron diagnostics on the experimental advanced superconducting tokamak.

Neutron diagnostics have become a significant means to study energetic particles in high power auxiliary heating plasmas on the Experimental Advanced Superconducting Tokamak (EAST). Several kinds of neutron diagnostic systems have been implemented for time-resolved measurements of D-D neutron flux, fluctuation, emission profile, and spectrum. All detectors have been calibrated in laboratory, and in situ calibration using 252Cf neutron source in EAST is in preparation. A new technology of digitized pulse signal processing is adopted in a wide dynamic range neutron flux monitor, compact recoil proton spectrometer, and time of flight spectrometer. Improvements will be made continuously to the system to achieve better adaptation to the EAST's harsh γ-ray and electro-magnetic radiation environment.

Development of the radial neutron camera system for the HL-2A tokamak.

A new radial neutron camera system has been developed and operated recently in the HL-2A tokamak to measure the spatial and time resolved 2.5 MeV D-D fusion neutron, enhancing the understanding of the energetic-ion physics. The camera mainly consists of a multichannel collimator, liquid-scintillation detectors, shielding systems, and a data acquisition system. Measurements of the D-D fusion neutrons using the camera have been successfully performed during the 2015 HL-2A experiment campaign. The measurements show that the distribution of the fusion neutrons in the HL-2A plasma has a peaked profile, suggesting that the neutral beam injection beam ions in the plasma have a peaked distribution. It also suggests that the neutrons are primarily produced from beam-target reactions in the plasma core region. The measurement results from the neutron camera are well consistent with the results of both a standard (235)U fission chamber and NUBEAM neutron calculations. In this paper, the new radial neutron camera system on HL-2A and the first experimental results are described.

Measurement and simulation of the response function of time of flight enhanced diagnostics neutron spectrometer for beam ion studies at EAST tokamak.

The 2.5 MeV TOFED (Time-Of-Flight Enhanced Diagnostics) neutron spectrometer with a double-ring structure has been installed at Experimental Advanced Superconducting Tokamak (EAST) to perform advanced neutron emission spectroscopy diagnosis of deuterium plasmas. This work describes the response function of the TOFED spectrometer, which is evaluated for the fully assembled instrument in its final layout. Results from Monte Carlo simulations and dedicated experiments with pulsed light sources are presented and used to determine properties of light transport from the scintillator. A GEANT4 model of the TOFED spectrometer was developed to calculate the instrument response matrix. The simulated TOFED response function was successfully benchmarked against measurements of the time-of-flight spectra for quasi-monoenergetic neutrons in the energy range of 1-4 MeV. The results are discussed in relation to the capability of TOFED to perform beam ion studies on EAST.

Endomorphins: novel endogenous mu-opiate receptor agonists in regions of high mu-opiate receptor density.

Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2, EM-1) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2, EM-2) are peptides recently isolated from brain that show the highest affinity and selectivity for the mu (morphine) opiate receptor of all the known endogenous opioids. The endomorphins have potent analgesic and gastrointestinal effects. At the cellular level, they activate G-proteins (35S-GTP gamma-S binding) and inhibit calcium currents. Support for their role as endogenous ligands for the mu-opiate receptor includes their localization by radioimmunoassay and immunocytochemistry in central nervous system regions of high mu receptor density. Intense EM-2 immunoreactivity is present in the terminal regions of primary afferent neurons in the dorsal horn of the spinal cord and in the medulla near high densities of mu receptors. Chemical (capsaicin) and surgical (rhizotomy) disruption of nociceptive primary afferent neurons depletes the immunoreactivity, implicating the primary afferents as the source of EM-2. Thus, EM-2 is well-positioned to serve as an endogenous modulator of pain in its earliest stages of perception. In contrast to EM-2, which is more prevalent in the spinal cord and lower brainstem, EM-1 is more widely and densely distributed throughout the brain than EM-2. The distribution is consistent with a role for the peptides in the modulation of diverse functions, including autonomic, neuroendocrine, and reward functions as well as modulation of responses to pain and stress.

Chemical characterization of angiotensin I in porcine follicular fluid.

In the search for novel neuropeptides in porcine follicular fluid (pff) using smooth muscle contractile activity as a response parameter, a substance with a marked activity was isolated in a pure form. By amino acid analysis and sequential study, this substance has been chemically revealed to be angiotensin I. A much smaller amount of additional activity was isolated and found to be angiotensin II, as determined by radioimmunoassay. Radioimmunoassays for angiotensin I and II confirmed that the amount of angiotensin I determined was much greater than that of angiotensin II. A comparative study of the extractions, however, indicated a large amount of angiotensin I had been generated from angiotensinogen by endogenous renin in the follicular fluid which could be activated during extraction and ultrafiltration at a low pH. These findings are consistent with the previous reports that described a high concentration of prorenin in the follicular fluid, acid activation of prorenin to renin and the subsequent generation of angiotensin I from endogenous angiotensinogen.

Isolation of relatively large amounts of endomorphin-1 and endomorphin-2 from human brain cortex.

Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) were previously isolated from bovine brain. Both peptides showed the greatest selectivity and affinity for the mu opiate receptor of any endogenous substance found to date and may serve as natural ligands for the mu-opiate receptor. We have purified them from the fronto-parietal cortex of human brain tissue by solid phase extraction and high performance liquid chromatography. Peptide content was followed by a specific and sensitive radioimmunoassay with an antibody that was generated against endomorphin-1. The isolated endomorphins showed full biological activity. The tetrapeptides were found in human brain in much higher amounts than in bovine frontal cortex.

Endomorphin 1 and 2, endogenous ligands for the mu-opioid receptor, decrease cardiac output, and total peripheral resistance in the rat.

Endomorphin 1 and 2 are recently discovered endogenous ligands for the mu-opioid receptor. In the present study, responses to intravenous administration of endomorphin 1 and 2 were investigated in the systemic vascular bed of the rat. Endomorphin 1 and 2 induced dose-related decreases in systemic arterial pressure when injected in doses of 10-100 nmol/kg i.v.. The decreases in systemic arterial pressure in response to endomorphin 1 and 2 were associated with significant decreases in heart rate, cardiac output, and total peripheral resistance. The endogenous ligand for the ORL1 receptor, nociceptin/OFQ had similar effects on systemic arterial pressure, heart rate, cardiac output, and total peripheral resistance in the rat. Injections of isoproterenol (1 microgram/kg i.v.) and calcitonin gene-related peptide (CGRP; 0.3 nmol/kg i.v.), decreased systemic arterial pressure and total peripheral resistance. However these decreases in arterial pressure were associated with increases in heart rate and cardiac output. The results of the present study demonstrate that the endomorphin peptides have significant vasodilator activity in the systemic vascular bed of the rat and show that this response is associated with a decrease in heart rate and cardiac output.

Tyr-MIF-1 binding in brain is not altered by ligands selective for the GABAA/benzodiazepine receptor.

Binding of benzodiazepines to the benzodiazepine gamma-aminobutyric acid (GABA) receptor-chloride channel complex has been shown to be altered by Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2). This raised the possibility of allosteric binding interactions between Tyr-MIF-1 sites and the GABAA receptor complex. We tested this possibility in rat brain by examining the binding of Tyr-MIF-1 to brain membranes in the presence of clonazepam, GABA, a combination of clonazepam and GABA, RO15788, or picrotoxinin. None of the tested substances affected Tyr-MIF-1 binding. We also tested mouse cortex for changes in Tyr-MIF-1 binding in the presence of ligands that bind to the GABA/benzodiazepine/chloride channel complex. Clonazepam, flunitrazepam, RO15788, and picrotoxinin at concentrations ranging from 10(-13) to 10(-5) M, each in the absence or presence of GABA at concentrations ranging from 10(-9) to 10(-5) M, each in the absence or presence of GABA at concentrations ranging from 10(-9) to 10(-6) M, did not significantly alter the binding of Tyr-MIF-1. The results indicate that simple bidirectional allosteric interactions between Tyr-MIF-1 binding sites and benzodiazepine, GABA or chloride channel binding sites are not likely to be the mechanism by which Tyr-MIF-1 affects binding at this complex.

Binding of Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-NH2) and related peptides to mu 1 and mu 2 opiate receptors.

Two endogenous brain peptides (Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-NH2) and Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2)), a cyclized analog and two fragments of Tyr-W-MIF-1, and hemorphin (Tyr-Pro-Trp-Thr) were tested for binding to mu 1 and mu 2 opiate receptor. All these peptides bound to both mu 1 and mu 2 sites in assays optimized to discriminate these subtypes of the mu opiate receptor in membranes from bovine thalamus. The cyclized analog of Tyr-W-MIF-1, previously shown to have potency near that of Tyr-D-Ala-Gly-N-MePhe-Gly-ol (DAMGO) and morphine in producing analgesia after intracerebroventricular (i.c.v.) injection, bound to mu 1 and mu 2 sites with affinities similar to those of DAMGO. Tyr-W-MIF-1, previously shown to induce analgesia after i.c.v. injection but with much higher potency after intrathecal (i.t.) injection, also bound to both mu 1 and mu 2 sites with an affinity between that of morphiceptin and hemorphin. Although the highest ratios of Ki's for mu 2/mu 1 were shown by hemorphin, Tyr-W-MIF-1, and Tyr-W-MIF-1, none of the compounds were significantly different in selectivity. The results indicate that the relatively lower potency of Tyr-W-MIF-1 after i.c.v., compared with i.t. injection, is not due to a lack of binding to mu 1 sites. They suggest that it has relatively high efficacy at mu 2, but low efficacy at mu 1 sites, a possibility that might explain some of the novel properties of these peptides.

Mu, delta, and kappa opiate receptor binding of Tyr-MIF-1 and of Tyr-W-MIF-1, its active fragments, and two potent analogs.

The relative binding to mu, delta, and kappa opiate receptors was characterized for the brain peptides Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-NH2), and two fragments of Tyr-W-MIF-1 (Tyr-Pro-Trp and Tyr-Pro-Trp-Gly) previously shown to have antagonist as well as agonist activity in the guinea pig ileum. Tyr-MIF-1 had relatively low affinity (Ki = 1 microM at the mu site) but high selectivity (400- and 700-fold greater affinity for mu over delta and mu over kappa binding). Tyr-W-MIF-1 (Ki = 71 nM at the mu site) showed higher affinity binding to all three sites than Tyr-MIF-1 while retaining 200-fold selectivity for mu over delta and kappa receptors. The affinity of the fragments of Tyr-W-MIF-1 was lower for mu but higher for delta receptors. We also tested two cyclized analogs of Tyr-W-MIF-1 that were about 200-fold more active than the parent compound in producing analgesia. These analogs showed higher affinity binding to all three opiate receptors. One of the analogs showed binding affinity to mu sites (Ki = 1.3 nM) that was within 3-fold of that of the potent analog of enkephalin, DAMGO. Thus, brain peptides with an N-terminal Tyr-Pro, rather than the Tyr-Gly-Gly-Phe sequence typical of other endogenous opiates, can provide high selectivity for mu opiate receptors. Analogs based on one of them, Tyr-Pro-Trp-Gly-NH2, show high affinity as well as potent analgesic activity.

Hemorphins, cytochrophins, and human beta-casomorphins bind to antiopiate (TYR-MIE-1) as well as opiate binding sites in rat brain.

Novel peptides with opiate activity, derived from endogenous sources (human and bovine casomorphins from milk, hemorphins from hemoglobin, and cytochrophins from mitochondrial cytochrome b), were tested for their ability to inhibit binding of the brain peptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) to its high affinity sites in rat brain. The order of potency in inhibiting binding of 125I-Tyr-MIF-1 was: hemorphin and bovine casomorphins greater than Tyr-MIF-1 greater than cytochrophins greater than human casomorphins. Naloxone and DAMGO were ineffective at inhibiting Tyr-MIF-1 binding. The results provide evidence that, in addition to their ability to bind to mu opiate receptors, these novel endogenous peptides with opiate activity and a peptide (Tyr-MIF-1) with antiopiate properties also bind to a non-opiate site labeled by Tyr-MIF-1. These sites could be involved in a balance between opiate and antiopiate peptides.

Chronic, but not acute, administration of morphine alters antiopiate (Tyr-MIF-1) binding sites in rat brain.

Opiate addiction could involve a change in the binding of endogenous antiopiates. A candidate for such a role is Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), a brain peptide that can antagonize exogenous and endogenous opiates and bind to opiate receptors. Its primary action, however, may be through its own binding site in brain, which we now report is altered by chronic administration of morphine. Rats given morphine pellets had reduced binding of both iodinated and tritiated Tyr-MIF-1 on day 5, when substantial tolerance is evident. In contrast, mu and delta opiate receptors were increased. Acute injection of an analgesic dose of morphine did not reduce Tyr-MIF-1 binding, indicating that chronic administration is required for the change. These findings open new approaches to the study of addiction by focusing on antiopiate activity.

Endomorphin 1 and 2, endogenous mu-opioid agonists, decrease systemic arterial pressure in the rat.

The endogenous opioid peptides, endomorphin 1 and 2, are newly isolated, potent, and selective mu-opioid receptor agonists. In the present study, responses to endomorphin 1 and 2 were investigated in the systemic vascular bed of the rat. Endomorphin 1 and 2 induced dose-related decreases in systemic arterial pressure when injected in doses of 1-30 nmol/kg i.v. In terms of relative vasodepressor activity, endomorphin 1 and 2 were approximately equipotent with each other and with the ORL1 ligand, nociceptin (orphanin FQ), and were about 10-fold more potent than met-enkephalin in decreasing systemic arterial pressure. Vasodepressor responses to endomorphin 1 and 2 and met-enkephalin, but not to nociceptin, were inhibited by the opioid receptor antagonist, naloxone. These results demonstrate that endomorphin 1 and 2 produce significant naloxone-sensitive decreases in systemic arterial pressure.

Design of a magnetic shielding system for the time of flight enhanced diagnostics neutron spectrometer at Experimental Advanced Superconducting Tokamak.

The novel neutron spectrometer TOFED (Time of Flight Enhanced Diagnostics), comprising 90 individual photomultiplier tubes coupled with 85 plastic scintillation detectors through light guides, has been constructed and installed at Experimental Advanced Superconducting Tokamak. A dedicated magnetic shielding system has been constructed for TOFED, and is designed to guarantee the normal operation of photomultiplier tubes in the stray magnetic field leaking from the tokamak device. Experimental measurements and numerical simulations carried out employing the finite element method are combined to optimize the design of the magnetic shielding system. The system allows detectors to work properly in an external magnetic field of 200 G.