Background

Alcohol dependence is a complex psychiatric disorder demanding development of novel pharmacotherapies. Because the cyclic adenosine monophosphate (cAMP) signaling cascade has been implicated in mediating behavioral responses to alcohol, key components in this cascade may serve as potential treatment targets. Phosphodiesterase-4 (PDE4), an enzyme that specifically catalyzes the hydrolysis of cAMP, represents a key point in regulating intracellular cAMP levels. Thus, it was of interest to determine whether PDE4 was involved in the regulation of alcohol use and abuse.



Methods

Male Fawn-Hooded (FH/Wjd) rats were tested for 5% (v/v) ethanol (EtOH) and 10% (w/v) sucrose operant oral self-administration following treatment with the selective PDE4 inhibitor rolipram (0.0125, 0.025, or 0.05 mg/kg, subcutaneous [s.c.]); rolipram at higher doses (0.05, 0.1, and 0.2 mg/kg, s.c.) was tested to determine its impact on the intake of EtOH, sucrose, or water using the 2-bottle choice drinking paradigm. Subsequent open-field testing was performed to evaluate the influence of higher doses of rolipram on locomotor activity.



Results

Acute administration of rolipram dose-dependently reduced operant self-administration of 5% EtOH, but had no effect on 10% sucrose responding. Time-course assessment revealed significant decreases in EtOH consumption after rolipram (0.1, 0.2 mg/kg) treatment in continuous- and intermittent access to EtOH at 5% or 10%, respectively. Moreover, chronic rolipram treatment time-dependently decreased 5% EtOH consumption and preference during treatment days and after the termination of rolipram administration. Rolipram at the highest doses (0.1 and 0.2 mg/kg) did decrease locomotor activity, but the effect lasted only 10 and 20 minutes, respectively, which did not likely alter long-term EtOH drinking.



Conclusions

These results suggest that PDE4 plays a role in alcohol seeking and consumption behavior. Drugs interfering with PDE4 may be a potential pharmacotherapy for alcohol dependence.

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The Phosphodiesterase-4 (PDE4) Inhibitor Rolipram Decreases Ethanol Seeking and Consumption in Alcohol-Preferring Fawn-Hooded Rats

Brucine (BRU) extracted from the seeds of Strychnos nux-vomica L is glycine receptor antagonist. We hypothesize that BRU may modify alcohol consumption by acting at glycine receptors, and evaluated the pharmacodynamic profiles and adverse effects of BRU in rat models of alcohol abuse. Alcohol-preferring Fawn-Hooded (FH/Wjd) rats were administered BRU (10, 20 or 30 mg/kg, sc). The effects of BRU on alcohol consumption were examined in ethanol 2-bottle-choice drinking paradigm, ethanol/sucrose operant self-administration paradigm and 5-d ethanol deprivation test. In addition, open field test was used to assess the general locomotor activity of FH/Wjd rats, and conditioned place preference (CPP) was conducted to assess conditioned reinforcing effect. In ethanol 2-bottle-choice drinking paradigm, treatment with BRU for 10 consecutive days dose-dependently decreased the ethanol intake associated with a compensatory increase of water intake, but unchanged the daily total fluid intake and body weight. In ethanol/sucrose operant self-administration paradigms, BRU (30 mg/kg) administered before each testing session significantly decreased the number of lever presses for ethanol and the ethanol intake, without affecting the number of sucrose (10%) responses, total sucrose intake, and the number of lever presses for water. Acute treatment with BRU (30 mg/kg) completely suppressed the deprivation-induced elevation of ethanol consumption. Treatment with BRU (10, 20, and 30 mg/kg) did not alter locomotion of FH/Wjd rats, nor did it produce place preference or aversion. BRU selectively decreases ethanol consumption with minimal adverse effects. Therefore, BRU may represent a new pharmacotherapy for alcoholism.

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Brucine suppresses ethanol intake and preference in alcohol-preferring Fawn-Hooded rats

Abstract In this paper, a piecewise sine waveguide (PWSWG) is proposed as the slow-wave structure (SWS) to develop high-power terahertz (THz) traveling wave tubes (TWTs). The PWSWG is an improvement over the rectangular waveguide wherein its two E-planes simultaneously oscillate up and down along the longitudinal direction. The oscillation curve in the H-plane is a piecewise sine curve formed by inserting line segments into the peaks and troughs of the sine curve. The simulation analysis and experimental verification show that the PWSWG offers the advantages of large interaction impedance and excellent electromagnetic transmission performance. Furthermore, the calculation results of beam–wave interaction show that the TWT based on PWSWG SWS can generate a radiated power of 253.1 W at the typical frequency of 220 GHz, corresponding to a gain of 37.04 dB and an interaction efficiency of 6.92%. Compared with the conventional SWG TWTs, the PWSWG TWT has higher interaction efficiency and shorter saturation tube length. In conclusion, the PWSWG proposed in this paper can be considered a suitable SWS for high-power THz radiation sources. 

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A piecewise sine waveguide for terahertz traveling wave tube

The electron optical systems (EOS) play a vital role in vacuum electron devices (VED). This letter reported the design and experiments of the sheet EOS for the 1.03 THz traveling wave tube (TWT). A high-current-density sheet electron beam (SEB) electron gun generating up to 20.3-mA at 22.4-kV is designed, based on the requirements of this TWT. Due to the very high operating frequency, more than 1 THz, the miniature tunnel and beam waist with a dimension of 0.05 mm * 0.148 mm and 0.025 mm * 0.114 mm, respectively, will lead to a very high beam current density (906.9 A/cm 2 ). Therefore, a 1-Telsa uniform magnetic system is designed, to ensure such a high-current-density SEB passes through the 27-mm tunnel. Finally, the primary experiments indicate that 7.56-mA current reaches the collector.

Sheet Electron Optical System for a 1.03-THz Traveling-Wave Tube

The results of design, simulation and development of W-band traveling-wave tube (TWT) and backward-wave oscillator (BWO) with sheet electron beam and grating slow-wave structure (SWS) are presented. Design of the SWS was optimized to obtain synchronism voltage of 10–12 kV. The results of 3D particle-in-cell (PIC) simulation of beam-wave interaction are presented. The TWT with staggered double-grating SWS provides nearly 30 dB small-signal gain, 15-GHz bandwidth, and up to 50 W power at saturation. The BWO with single grating SWS provides up to 20 W output power. Electron gun providing 0.1-A sheet electron beam is designed and fabricated. Grating SWS is fabricated by a novel technology based on diffusion bonding of alternating copper and molybdenum plates and subsequent chemical etching of copper. Other key components of the device, such as depressed collector, permanent-magnet magnetic focusing system, and vacuum window are designed and currently are under fabrication.

Development and Modeling of W-band Sheet-Beam Tubes with Grating Slow-Wave Structures

This article reports a slow-wave structure (SWS) working at 1 THz which can be fabricated through nano-computer numerical control (nano-CNC) technology for the first time. First, a 1 THz deformed quasi sine waveguide (D-QSWG) SWS has been designed and simulated in this article. To reduce the metal loss of input and output waveguide, a coupler which transit the waveguide to over mode rectangular waveguide has been designed. The simulation result shows that input and output waveguides with this coupler have lower metal loss than that of WR1 rectangular waveguide. To fabricate the designed D-QSWG SWS, tungsten steel endmills have been used. The fabricated SWS has the surface roughness around 58–74 nm, the corresponding effective conductivity is around <inline-formula> <tex-math notation="LaTeX">$2\times 10^{{7}}$ </tex-math></inline-formula>–1.85 <inline-formula> <tex-math notation="LaTeX">$\times 10^{{7}}$ </tex-math></inline-formula> S/m. And the cold test results show that the insertion loss of the fabricated model is less than 30 dB while the reflection loss is less than −15 dB in the frequency range of 0.998–1.016 THz, which has a good consistency with the simulated results. The beam-wave interaction simulation results based on the cold test results show that the designed D-QSWG traveling wave tube (TWT) has the output power of 300 mW, and the 3 dB bandwidth is around 3 GHz.

Design and Experiment of 1 THz Slow Wave Structure Fabricated by Nano-CNC Technology

AIM To investigate the characteristics of alcohol-preferring behavior in FH/Wjd rats. METHODS Two-bottle free choice test (5% or 10% ethanol and tap water) was employed to determine the ethanol intake, water intake and ethanol preference, through which the day-night difference of ethanol drinking in FH/Wjd rats was explored. In ethanol deprivation experiment, the effects of 24 h deprivation on ethanol intake and preference in FH/Wjd rats were measured. The operant ethanol self-administration of FH/Wjd rats was observed under fixed ratio ( FR1 ) procedure. RESULTS In two-bottle test, the daily ethanol intake, water intake, and ethanol preference of FH/Wjd rats were ( 4. 3 ± 0. 2 )·g-1kg-·-d-1, (20.1 ±2.3) g·kg-1·d-1, and (82. 9 ±2. 0)%, respectively in 5% ethanol group and (6.4 ± 0.2)g·kg-1 ·d-1, (37.2 ± 2. 7) g · kg-1· d-1 and (69. 2 ± 2. 0)%, respectively in 10% ethanol group. It demonstrated the ethanol and water intake of FH/Wjd rats in 10% ethanol group was more, but the ethanol preference of them was lower than those in 5% ethanol group. The ethanol intake and preference of FH/Wjd rats in night were higher than that in day. There was no day-night differ-ence in water intake. Ethanol deprivation for 24 h produced a significant increase in ethanol intake and ethanol preference in the first hour and 24 h of re-access in FH/Wjd rats. They also substantially increased their ethanol preference in the first hour but not 24 h of re-exposed to ethanol. After 13 training days, the preference of operant ethanol self-administration of FH/ Wjd rats was 49% -64% during 3 test days, which demonstrated that ethanol seeking behavior was successfully established in FH/Wjd rats. CONCLUSION FH/Wjd rats which showed high ethanol intake and preference, robust ethanol deprivation effect, and could develop operant ethanol self-administration behavior in short time, can be used as a genetic animal model of alcoholism.

Characteristics of alcohol-preferring behavior in FH/Wjd rats

Objective: To investigate the clinicopathological features and pathological types and outcome of combined hepatocellular-cholangiocarcinoma (cHCC-CC). Methods: 30 cases of cHCC-CC were collected from Jan 2007 to Jun 2021 at General Hospital of Southern Theatre Command, People's Liberation Army of China, and analyzed the clinicopathological features, immunohistochemistry and outcome. The histological morphology was classified according to the Goodman standard and the fifth edition of World Health Organization (WHO) classification of digestive system tumors. Results: According to the Goodman classification, 9 cases belonged to type Ⅰ (i.e., collision tumor), with a coincidental occurrence of hepatocellular carcinoma and cholangiocarcinoma in the same specimen, and 21 cases were Type Ⅱ or "transitional tumors", in which there were areas of intermediate differentiation and an identifiable transition between hepatocellular carcinoma and cholangiocarcinoma. According to the WHO classification of digestive system tumors (5th Edition), 25 cases were classified in cHCC-CC, and 5 cases were cHCC-CC-Intermediate cell carcinoma. There were 28 males and 2 females, with an average age of 50.4 (31-72) years old. 21 cases accompanied liver cirrhosis, with liver flukes in 1 case and HBsAg positive in 23 cases. Immunohistochemical staining showed nestin was positive in 9 cases, 66.7% died (6/9) and 33.3% (3/9) survived only 6 months. The 1-year recurrence rate was 3.9% for liver resection and 50% for orthotopic liver transplantation, and liver resection has longer median survival time than liver transplantation after recurrence. Conclusions: cHCC-CC is a rare type of primary liver malignant tumor. Preoperative diagnosis is difficult. The definite diagnosis depends on histopathological morphology and immunohistochemical markers. Nestin may be as a prognosis factor, and surgical treatment is preferably liver resection.

[Clinicopathological festures and outcome of combined hepatocellular-cholangiocarcinoma].

In this paper, based on the correlation matrix, the fault detection method of controller is studied based on the fault diagnosis characteristics of environment control and life support system(ECLSS). Combined with the characteristics of actual system fault diagnosis, the reasons for the existence of the feedback loop are analyzed, the different diagnostic effects caused by voltage and current detection methods are compared, and the detection method of breaking the feedback loop by manual testing is proposed. Through modeling and analysis, complete design ideas and methods are provided for improving testability design of controller products, which can help guide Built-In-Test(BIT) design of controllers. 

J Luo

Papers

Design and Experiment of 1 THz Slow Wave Structure Fabricated by Nano-CNC Technology

Characteristics of alcohol-preferring behavior in FH/Wjd rats

[Clinicopathological festures and outcome of combined hepatocellular-cholangiocarcinoma].

Research on a system controller fault detection method based on correlation matrix