[Adiponectin ameliorated pancreatic islet mitochondrial injury induced by chronic intermittent hypoxia].

Objective: To explore the effect of adiponectin (APN) on islet injury induced by chronic intermittent hypoxia (CIH). Methods: Thirty-six SD rats were randomly divided into three groups: Normal control (NC), CIH, and CIH + APN groups. The rats in the CIH and CIH+APN groups received an intermittent hypoxia exposure while the rats in NC group received the room air only. The rats in CIH+APN group received the intravenous injection of APN. The intermittent hypoxia events persisted 8 hours a day and last for 35 days. The fasting blood glucose and fasting insulin were detected at the time of 0, 7, 14, 21, 28, and 35 day. After 35 days, the level of serum adiponectin, and adenosine triphosphate (ATP) level, superoxide dismutase (SOD), malondialdehyde (MDA), the mRNA levels of mitochondrial oxidative phosphorylation function and mitochondrial synthesis gene, and the protein level of mitochondrial and cytoplasmic cytochrome C of pancreatic islet were detected. Results: The glucose and insulin level had no statistically differences among three groups at different time points (all P>0.05). However, compared with NC and CIH+APN groups, CIH reduced the serum adiponectin [(7 265±2 209) ng/ml, (6 536±1 678) ng/ml vs (4 923±1 742) ng/ml, both P<0.05], ATP levels [(30.92±1.12) nmol/mg, (26.55±0.72) nmol/mg vs (20.22±1.47) nmol/mg, both P<0.05], mRNA levels of mitochondria oxidative phosphorylation function and mitochondrial synthesis gene, the activity of SOD, and the rate of mitochondrial/cytoplasmic cytochrome C protein level while increased the MDA level in pancreatic islet. Compared with NC group, the MDA level increased (P<0.05) and the APN level had no statistically difference, while the level of other indicators decreased in CIH+APN group (all P<0.05). Conclusion: APN ameliorates the pancreatic islet injury induced by CIH through inhibition of oxidative stress.

[Effects of chronic intermittent hypoxia on hepatic function and protective mechanism of adiponectin in rats].

Objective: To explore the effect of chronic intermittent hypoxia (CIH) on rats hepatic function, and the protective mechanism of adiponectin (Ad). Methods: Sixty healthy male wistar rats were randomly divided into 4 groups: normal control (NC), NC+ Ad, CIH, and CIH+ Ad groups with 15 rats in each. The rats in CIH and CIH+ Ad groups were exposed to an intermittent hypoxic chamber 8 hours per day for 4 months. Meanwhile, the rats in both the NC and NC + Ad groups were housed with normal pressure air. The rats in the NC+ Ad and CIH+ Ad groups were additionally treated with an intravenous injection of Ad (10 µg), twice a week for 4 months. At the end of experiment, comparison among groups was made about plasma levels of aspartate amino transferase (AST), alanine amino transferase (ALT), degrees of endoplasmic reticulum stress (ERS) and mitochondrium associated cellular apoptosis. Results: No significant difference was detected in all items between NC and NC+ Ad groups (all P>0.05). Plasma hepatic enzyme levels of AST and ALT were significantly higher in CIH group [(319±21) and (113±9) U/L] than those in NC group [(178±19) and (51±9) U/L] and NC+ Ad group [(175±16) and (52±8) U/L] (all P<0.05). Compared NC with NC+ Ad group, there was more remarkable ERS and mitochondrial injury associated cellular apoptosis in hepatic tissues of CIH group. Such pathological changes were less obvious in CIH+ Ad group than in CIH group (all P<0.05). Conclusion: CIH can induce hepatic injury in rats, while Ad supplement may play a protective role possibly through inhibition of ERS and associated pathways of cellular apoptosis.

Kinetic stress and intrinsic flow in a toroidal plasma.

A new mechanism for intrinsic plasma flow has been experimentally identified in a toroidal plasma. For reversed field pinch plasmas with a few percent ß (ratio of plasma pressure to magnetic pressure), measurements show that parallel pressure fluctuations correlated with magnetic fluctuations create a kinetic stress that can affect momentum balance and the evolution of intrinsic plasma flow. This implies kinetic effects are important for flow generation and sustainment.

Role of nonlinear coupling and density fluctuations in magnetic-fluctuation-induced particle transport.

Three-wave nonlinear coupling among spatial Fourier modes of density and magnetic fluctuations is directly measured in a magnetically confined toroidal plasma. Density fluctuations are observed to gain (lose) energy from (to) either equilibrium or fluctuating fields depending on the mode number. Experiments indicate that nonlinear interactions alter the phase relation between density and magnetic fluctuations, leading to strong particle transport.

Fast-particle-driven Alfvénic modes in a reversed field pinch.

Alfvénic modes are observed due to neutral beam injection for the first time in a reversed field pinch plasma. Modeling of the beam deposition and slowing down shows that the velocity and radial localization are high. This allows instability drive from inverse Landau damping of a bump-on-tail in the parallel distribution function or from free energy in the fast ion density gradient. Mode switching from a lower frequency toroidal mode number n=5 mode that scales with beam injection velocity to a higher frequency n=4 mode with Alfvénic scaling is observed.

Elevated expression of both MDR1 and MMP-2 genes in metastasized lymph node of invasive ductal breast cancer.

BACKGROUND: There is emerging evidence that matrix metalloproteinase (MMP)-2 plays a crucial role in cancer invasion/metastasis. However, little evidence is available about the connections of multidrug resistance protein 1 (MDR1) and cancer invasion/metastasis so far. AIM: To investigate the expression of MDR1 and MMP2 in primary breast tumors and their corresponding metastasized lymph nodes. MATERIALS AND METHODS: Only lymph nodes which were pathologically identified as metastases were included in this study to compare with the corresponding primary tumor. We determined the expression of MDR1 and MMP2 in primary breast tumor and its metastasized lymph node specimens of 21 patients. The quantitative real-time polymerase chain reaction (Q-RT-PCR) technique was used to assess the MDR1 and MMP2 RNA expression levels in primary breast tumor and lymph nodal specimens. Target gene copies were normalized using beta-actin (beta-actin) gene copies. Tumor characteristics and number of metastatic lymph nodes were gathered from the pathology reports. RESULTS: The Q-RT-PCR data showed that MDR1 expression in metastasized lymph node was higher than that of their corresponding primary tumors (p < 0.05), MMP2 expression in metastasized lymph nodes was also even higher compared with their matched primary tumors (p < 0.01). But SPSS bivariate correlation analysis revealed that MDR1 expression in lymph node was not correlated with MMP-2 expression in lymph node, number of metastasized lymph nodes and tumor size (p > 0.05). MDR1 expression in primary tumors was highly correlated with in corresponding lymph node metastases (p < 0.01 r = 0.795). CONCLUSIONS: All those indicated that MMP-2 should play an important role in the lymph node metastasis. However, further clinical studies with larger sample size need to be performed to verify these findings.

Non-inductive plasma vertical position measurement for the 1056 s discharge on EAST.

Vertical position stability plays a crucial role in maintaining safe and reliable plasma operation for long-pulse fusion devices. In general, the vertical position is measured by using inductive magnetic coils installed inside the vacuum vessel; however, the integration drift effects are inherent for steady-state or long-pulse plasma operation. Developing a non-magnetic approach provides a fusion reactor-relevant steady-state solution that avoids the negative impact of integration drift. In this paper, we compare the non-inductively determined vertical position achieved by line-integrated interferometer and polarimeter measurements to that employing an inductive flux loop for a 1056 s discharge recently achieved on EAST (Experimental Advanced Superconducting Tokamak). Experimental results show that the non-inductive measurement is more robust than flux loops after 300 s if the integrator is not reset to suppress integrator drift. Real-time vertical position control using the non-inductive system is proposed for the next EAST experimental campaign.

Bifurcation to 3D helical magnetic equilibrium in an axisymmetric toroidal device.

We report the first direct measurement of the internal magnetic field structure associated with a 3D helical equilibrium generated spontaneously in the core of an axisymmetric toroidal plasma containment device. Magnetohydrodynamic equilibrium bifurcation occurs in a reversed-field pinch when the innermost resonant magnetic perturbation grows to a large amplitude, reaching up to 8% of the mean field strength. Magnetic topology evolution is determined by measuring the Faraday effect, revealing that, as the perturbation grows, toroidal symmetry is broken and a helical equilibrium is established.

Development of Faraday rotation measurements on Keda Reconnection eXperiment (KRX) device.

The Faraday-effect based polarimeter and interferometer are developed for non-perturbation magnetic field and density measurements on the Keda Reconnection eXperiment (KRX) device. The magnetic reconnection is externally driven by a pair of parallel current plates. To design this instrument and provide an alternative way to facilitate theory-experiment comparisons via forward modeling of the diagnostics process with full plasma dynamics given by simulation, we develop a synthetic diagnostics based on 2D photonic integrated circuit simulation for magnetic reconnection on the KRX. The view-line geometry is optimized and wavelengths (1 mm) of the polarimeter and interferometer are selected to ensure the sensitivity of measurement on the KRX. We have simulated magnetic reconnection on the x-line (x-z plane) with horizontal viewing and vertical viewing for line of sight measurements. It is found that the current sheet width and indicator of magnetic reconnection can be inferred directly from the dynamics of Faraday rotation even with the line-integrated character of polarimeter-interferometer diagnostics.

Novel peptidic dual GLP-1/glucagon receptor agonist alleviates diabetes and diabetic complications in combination with low-intensity ultrasound.

OBJECTIVE: To design and evaluate a novel oxyntomodulin (OXM) derivative with albumin-binding helix domain and dual GLP-1 receptor (GLP-1R) and glucagon receptor (GcgR) activation activity to achieve metabolize improvement on the diabetes-related complication. MATERIALS AND METHODS: Mutation (D-Ser2) on OXM was performed and then different helix albumin-binding domains were fused to the mutated OXM via a thrombin-cleavable linker to generate seven fusion peptides, named LM01-LM07. Seven LM peptides were synthesized and screened via in vitro receptor activation test, albumin binding measurement and protease cleavage assay to select potent candidate peptide for further in vivo study. Moreover, acute and chronic efficacy studies were conducted to evaluate the efficacy of selected candidate using db/db mice. RESULTS: LM06, as selected OXM derivative, exhibited higher albumin-binding affinity, sustained-release efficiency and balanced activation activities on both GLP-1R and GcgR compared with other ones. Moreover, LM06 was demonstrated with improved hypoglycemic and insulinotropic abilities in receptor-deficient mice via activating GLP-1R. In addition, prolonged anti-diabetic efficacies of LM06 were demonstrated via hypoglycemic duration assay and OGTT in db/db mice. Further pharmacokinetic test of LM06 in both rats and monkeys identified improved half-life and other metabolic characteristics. Nevertheless, 8-week subcutaneously dosed LM06 in db/db mice achieved prominent efficacies on glucostasis, weight-lowering, pancreatic function and adipogenesis via activating GLP-1R and GcgR. Moreover, LM06 also could accelerate diabetic skin wound closure in combination with low-intensity ultrasound. CONCLUSIONS: LM06, as a long-acting dual GLP-1R/GcgR agonist, exerts potential as a once-weekly therapeutic candidate against diabetes-related complication in combination with low-intensity ultrasound.

Error correction associated with stray light for Faraday-effect polarimetry system on EAST.

The polarimeter-interferometer system with 11 double-pass radial-view measurement chords has the ability to provide electron density and plasma current profiles, making it exceptionally useful in daily operation on the Experiment Advanced Superconducting Tokamak. However, due to limited optical access and intrinsic feedback, the stray lights arising from spurious reflections along the optical path (unwanted reflections from various optical components/mounts and transmissive optical elements such as windows, waveplates, and lenses as well as the detectors) distort the Faraday rotation measurements. Furthermore, the feedback light from the retro-reflector which is used to realize the double-pass configuration makes it even worse. A data processing approach to decrease the stray light influence is reported in this paper. Based on the theoretical model developed, the Faraday rotation angle is extracted by subtracting the deviation term which can be calculated with a simplified model. With this approach, the Faraday rotation oscillation during density ramp-up can be reduced from 2°-5° to 0.5°-1.5°, which reduces the Faraday rotation measurement errors significantly.

Five-channel tunable W-band Doppler backscattering system in the experimental advanced superconducting tokamak.

A 5-channel Doppler backscattering system has been designed and installed in the Experimental Advanced Superconducting Tokamak (EAST). Through an I/Q-type double sideband modulator and a frequency multiplier, an array of finely spaced (Δf = 400 MHz) frequencies that span 1.6 GHz has been created. The center of the array bandwidth is tunable within the range of 75-97.8 GHz, which covers most of the W band (75-110 GHz). The incident angle can be adjusted from -4° to 12°, and the wavenumber range is 4-15 cm-1 with a wavenumber resolution of Δk/k ≤ 0.35. Ray tracing is used to calculate the scattering location and the scattering wavenumber. This article details the hardware design, the ray tracing, and the preliminary experimental results from EAST plasmas.

Correlation polarimetry for broadband magnetic fluctuation measurements.

Correlation techniques have been successfully utilized for plasma diagnostics like electron cyclotron emission to reduce measurement noise. We present the first application of such a technique to Faraday-effect polarimetry measurements on the Madison Symmetric Torus (MST). The MST far infrared (FIR) interferometer-polarimeter diagnostic utilizes 11 vertical chords with a chord separation of 7-8 cm and a heterodyne detection system for fluctuation measurements up to several hundred kHz. The planar-diode mixers viewing each chord represent independent noise sources; modifying the optical setup so that two different mixers view the same chord allows cross correlation between the two independent signals to reduce the noise floor in fluctuation measurements. In this manner, the noise floor in both interferometry and polarimetry measurements in reversed-field pinch discharges has been reduced by a factor of 20-30. The correlation polarimeter provides a sensitive measurement of broadband magnetic fluctuations.

A Faraday-effect polarimeter for fast magnetic dynamics measurement on DIII-D.

A Faraday-effect-based radial-interferometer-polarimeter diagnostic has been developed to explore fast magnetic dynamics in high-performance DIII-D plasmas. The instrument measures radial magnetic field perturbations using three chords positioned near the magnetic axis. Newly developed solid-state sources operating at 650 GHz provide phase noise down to 0.01°/ k H z and tunable bandwidth up to 10 MHz. Various systematic errors which can contaminate the polarimetric measurement have been investigated in detail. Distortion of circular polarization due to non-ideal optical components is calibrated using a rotating quarter wave plate technique. The impact of perpendicular magnetic field, i.e., the Cotton-Mouton effect, is evaluated. The error due to non-collinearity of probe beams is minimized to less than 0.5° for electron density up to 7 × 1019 m-3 by alignment optimization. Optical feedback, due to multiple reflections induced by the double-pass configuration, is identified and reduced. Coherent and broadband high-frequency magnetic fluctuations for DIII-D H-mode plasmas are observed.

Effects of stray lights on Faraday rotation measurement for polarimeter-interferometer system on EAST.

A double-pass radially view 11 chords polarimeter-interferometer system has been operated on the experimental advanced superconducting tokamak and provides important current profile information for plasma control. Stray light originating from spurious reflections along the optical path (unwanted reflections from various optical components/mounts and transmissive optical elements such as windows, waveplates, and lens as well as the detectors) and also direct feedback from the retro-reflector used to realize the double-pass configuration can both contribute to contamination of the Faraday rotation measurement accuracy. Modulation of the Faraday rotation signal due to the interference from multiple reflections is observable when the interferometer phase (plasma density) varies with time. Direct reflection from the detector itself can be suppressed by employing an optical isolator consisting of a λ/4-waveplate and polarizer positioned in front of the mixer. A Faraday angle oscillation during the density ramping up (or down) can be reduced from 5°-10° to 1°-2° by eliminating reflections from the detector. Residual modulation arising from misalignment and stray light from other sources must be minimized to achieve accurate measurements of Faraday rotation.

Non-inductive vertical position measurements by Faraday-effect polarimetry on EAST tokamak.

Vertical instability control in an elongated plasma is highly desirable for a tokamak reactor. A multi-channel 694 GHz far-infrared laser-based polarimeter-interferometer system has been used to provide a non-inductive vertical position measurement in the long-pulse EAST tokamak. A detailed comparison of vertical position measurements by polarimetry and external inductive flux loops has been used to validate Faraday-effect polarimetry as an accurate high-time response vertical position sensor.

A novel, tunable, multimodal microwave system for microwave reflectometry system.

Based on a new technique, a tunable, multi-channel system that covers the Q-band (33-55 GHz) is presented in this article. It has a potential use of the Doppler backscattering system diagnostic that can measure the turbulence radial correlation and the perpendicular velocity of turbulence by changing the incident angle. The system consists primarily of a double-sideband (DSB) modulation and a multiplier, which creates four probing frequencies. The probing frequency enables the simultaneous analysis of the density fluctuations and flows at four distinct radial regions in tokamak plasma. The amplitude of the probing frequency can be adjusted by the initial phase of the intermediate frequency (IF) input from the double-sideband, and the typical flatness is less than 10 dB. The system was tested in the lab with a rotating grating, and the results show that the system can operate in the frequency range of 33-55 GHz with a Q-band multitude and that the power of each channel can be adjusted by the phase of the IF input of DSB.

A heterodyne dispersion interferometer for wide bandwidth density measurements on DIII-D.

In order to improve both the density and particularly the temporal resolution beyond previous dispersion interferometers (DIs), a heterodyne technique based on an acousto-optic (AO) cell has been added to the DI. A 40 MHz drive frequency for the AO cell allows density fluctuation measurements into the MHz range. A CO2 laser-based heterodyne DI (HDI) installed on DIII-D has demonstrated that the HDI is capable of tracking the density evolution throughout DIII-D discharges, including disruption events and other rapid transient phenomena. The data also show good agreement with independent density measurements obtained with the existing DIII-D two-color interferometer. The HDI line-integrated density resolution sampled over a 1 s interval is ∼9 × 1017 m-2. Density fluctuations induced by MHD instabilities are also successfully measured by the HDI.

Tests of a full-scale ITER toroidal interferometer and polarimeter (TIP) prototype on the DIII-D tokamak (invited).

A full-scale ITER toroidal interferometer and polarimeter (TIP) prototype, including an active feedback alignment system, has been installed and tested on the DIII-D tokamak. In the TIP prototype, a two-color interferometry measurement of line-integrated density is carried out at 10.59 µm and 5.22 µm using a CO2 and quantum cascade laser, respectively, while a separate polarimetry measurement of the plasma-induced Faraday effect is made at 10.59 µm. The TIP prototype is equipped with a piezo tip/tilt stage active feedback alignment system that minimizes noise in the measurement and keeps the diagnostic aligned throughout DIII-D discharges. The measured phase resolution for the polarimeter and interferometer is 0.05° (100 Hz bandwidth) and 1.9° (1 kHz bandwidth), respectively. The corresponding line-integrated density resolution for the vibration-compensated interferometer is δnL = 1.5 × 1018 m-2, and the magnetic field-weighted line-integrated density from the polarimeter is δnBL = 1.5 × 1019 Tm-2. Both interferometer and polarimeter measurements during DIII-D discharges compare well with the expectations based on calculations using Thomson scattering measured density profiles and magnetic equilibrium reconstructions. Additionally, larger bandwidth interferometer measurements show that the diagnostic is a sensitive monitor of core density fluctuations with demonstrated measurements of Alfvén eigenmodes and tearing modes.

Nonambipolar magnetic-fluctuation-induced particle transport and plasma flow in the MST reversed-field pinch.

First direct measurements of nonambipolar magnetic fluctuation-induced charge transport in the interior of a high-temperature plasma are reported. Global resistive tearing modes drive the charge transport which is measured in the vicinity of the resonant surface for the dominant core resonant mode. Finite charge transport has two important consequences. First, it generates a potential well along with locally strong electric field and electric field shear at the resonant surface. Second, this electric field induces a spontaneous E x B driven zonal flow.