Improvements of PKU PMECRIS for continuous hundred hours CW proton beam operation.

In order to improve the source stability, a long term continuous wave (CW) proton beam experiment has been carried out with Peking University compact permanent magnet 2.45 GHz ECR ion source (PKU PMECRIS). Before such an experiment a lot of improvements and modifications were completed on the source body, the Faraday cup and the PKU ion source test bench. At the beginning of 2015, a continuous operation of PKU PMECRIS for 306 h with more than 50 mA CW beam was carried out after success of many short term tests. No plasma generator failure or high voltage breakdown was observed during that running period and the proton source reliability is near 100%. Total beam availability, which is defined as 35-keV beam-on time divided by elapsed time, was higher than 99% [S. X. Peng et al., Chin. Phys. B 24(7), 075203 (2015)]. A re-inspection was performed after another additional 100 h operation (counting time) and no obvious sign of component failure was observed. Counting the previous source testing time together, this PMECRs longevity is now demonstrated to be greater than 460 h. This paper is mainly concentrated on the improvements for this long term experiment.

Duty factor variation possibility from 1% to 100% with PKU microwave driven Cs-free volume H⁻ sources.

Microwave driven cesium-free volume H(-) sources, that have the ability to deliver tens of mA H(-) at 35 keV both in CW and 10% duty factor (100 Hz/1 ms), were developed at Peking University (PKU) [S. X. Peng et al., in Proceeding of IPAC 2015, WEPWA027, Richmond, Virginia, USA, 3-8 May 2015]. Recently, special efforts were paid on the investigation of duty factor variation possibility from 1% to 100% with them. Most of the experiments were carried out with a pulsed length (τ) of 1 ms and different intervals of 99 ms, 49 ms, 39 ms, 29 ms, 19 ms, 9 ms, 4 ms, 2 ms, 1 ms, 0.5 ms, and 0 ms, respectively. Other experiments were focused on CW operation and fixed duty factor of 1%. Experimental results prove that PKU H(-) sources can deliver tens of mA H(-) at duty factor from 1% to 100%. The RF power efficiency increases steadily with the increasing of duty factor from 1% to CW at a fixed pulsed length. Under a given duty factor and pulsed length, RF power efficiency keeps constant and the H(-) current increases with RF power linearly. Details will be presented in the paper.

Study on space charge compensation in negative hydrogen ion beam.

Negative hydrogen ion beam can be compensated by the trapping of ions into the beam potential. When the beam propagates through a neutral gas, these ions arise due to gas ionization by the beam ions. However, the high neutral gas pressure may cause serious negative hydrogen ion beam loss, while low neutral gas pressure may lead to ion-ion instability and decompensation. To better understand the space charge compensation processes within a negative hydrogen beam, experimental study and numerical simulation were carried out at Peking University (PKU). The simulation code for negative hydrogen ion beam is improved from a 2D particle-in-cell-Monte Carlo collision code which has been successfully applied to H(+) beam compensated with Ar gas. Impacts among ions, electrons, and neutral gases in negative hydrogen beam compensation processes are carefully treated. The results of the beam simulations were compared with current and emittance measurements of an H(-) beam from a 2.45 GHz microwave driven H(-) ion source in PKU. Compensation gas was injected directly into the beam transport region to modify the space charge compensation degree. The experimental results were in good agreement with the simulation results.

GAL-021, a new intravenous BKCa-channel blocker, is well tolerated and stimulates ventilation in healthy volunteers.

BACKGROUND: Potassium-channels in the carotid body and the brainstem are important regulators of ventilation. The BKCa-channel contains response elements for CO, O2, and CO2. Its block increases carotid body signalling, phrenic nerve activity, and respiratory drive. GAL-021, a new BKCa-channel blocker, increases minute ventilation in rats and non-human primates. This study assessed the single-dose safety, tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of GAL-021 in healthy volunteers. METHODS: Thirty subjects participated in a nine-period, randomized, double-blinded, placebo-controlled, crossover, ascending dose, first-in-human study with i.v. infusions of 0.1-0.96 mg kg(-1) h(-1) for 1 h and intermediate doses up to 4 h. RESULTS: Adverse event rates were generally similar among dose levels and between placebo- and GAL-021-treated subjects. At higher GAL-021 doses, a mild/moderate burning sensation at the infusion site occurred during the infusion. No clinically significant changes in vital signs or clinical chemistries were noted. Minute ventilation increased (AUE0-1 h ≈ 16%, P<0.05) and end-tidal carbon dioxide ([Formula: see text]) decreased (AUE0-1 h ≈ 6%, P<0.05) during the first hour at 0.96 mg kg(-1) h(-1) with 1/2-maximal [Formula: see text] and [Formula: see text]-change occurring by 7.5 min. Drug concentration rose rapidly during the infusion and decreased rapidly initially (distribution t1/2 of 30 min) and then more slowly (terminal t1/2 of 5.6 h). CONCLUSIONS: GAL-021 was safe and generally well tolerated with adverse events comparable with placebo except for an infusion site burning sensation. GAL-021 stimulated ventilation at the highest doses suggesting that greater infusion rates may be required for maximum PD effects. GAL-021 had PK characteristics consistent with an acute care medication.

Commissioning and operation of the deuteron injector for PKUNIFTY project.

PKUNIFTY (PeKing University Neutron Imaging FaciliTY), a thermal neutron imaging facility based on a 2 MeV RFQ accelerator, has been constructed at Peking University. Its deuteron injector, which consists of a 2.45 GHz permanent magnet electron cyclotron resonance (PMECR) deuteron ion source and a two-solenoid low energy beam transport (LEBT), aims at producing and delivering 50 mA, 50 keV deuteron beam with a duty factor of 10% (1 ms, 100 Hz). In the preliminary tests of RFQ accelerator, the ECR ion source and LEBT are required to operate at various duty factors (from 1% to 10%). The deuteron ion source has been tested with different pulse widths for this reason. In order to optimize the transmission parameters, the beam current at the exit of RFQ as a function of solenoids tuning and steering magnets tuning are carefully studied. The beam emittance at the entrance of RFQ has been measured with space charge compensation by different argon gas (RG) pressure from 1.6 × 10(-4) Pa to 4.7 × 10(-3) Pa. The measuring results show the best compensating pressure is 3.5 × 10(-3) Pa with a minimal normalized rms emittance of 0.12 pi mm mrad. During the commissioning, we found the purity of deuteron gas is an important factor which severely affects ECR discharge and plasma intensity inside the ion source chamber. The detailed experimental results obtained during the commissioning are discussed in this paper.

Plasma studies of the permanent magnet electron cyclotron resonance ion source at Peking University.

At Peking University (PKU) we have developed several 2.45 GHz Permanent Magnet Electron Cyclotron Resonance ion sources for PKUNIFTY, SFRFQ, Coupled RFQ&SFRFQ, and Dielectric-Wall Accelerator (DWA) projects (respectively, 50 mA of D(+), 10 mA of O(+), 10 mA of He(+), and 50 mA of H(+)). In order to improve performance of these ion sources, it is necessary to better understand the principal factors that influence the plasma density and the atomic ion fraction. Theoretical analysis about microwave transmission and cut-off inside the discharge chamber were carried out to study the influence of the discharge chamber diameters. As a consequence, experimental studies on plasma density and ion fraction with different discharge chamber sizes have been carried out. Due to the difficulties in measuring plasma density inside the discharge chamber, the output beam current was measured to reflect the plasma density. Experimental results show that the plasma density increases to the maximum and then decreases significantly as the diameter changed from 64 mm to 30 mm, and the atomic ion fraction has the same tendency. The maximum beam intensity was obtained with the diameter of 35 mm, but the maximum atomic ion fraction with a diameter of 40 mm. The experimental results are basically accordant with the theoretical calculation. Details are presented in this paper.

Handling radiation generated during an ion source commissioning.

Radiation is an important issue, which should be carefully treated during the design and commissioning of an ion source. Measurements show that X-rays are generated around the ceramics column of an extraction system when the source is powered up to 30 kV. The X-ray dose increases greatly when a beam is extracted. Inserting the ceramic column into a metal vacuum box is a good way to block X-ray emission for those cases. Moreover, this makes the online test of an intense H(+) ion beam with energy up to 100 keV possible. However, for deuteron ion source commissioning, neutron and gamma-ray radiation become a serious topic. In this paper, we will describe the design of the extraction system and the radiation doses of neutrons and gamma-rays measured at different D(+) beam energy during our 2.45 GHz deuteron electron cyclotron resonance ion source commissioning for PKUNIFTY (PeKing University Neutron Imaging FaciliTY) project at Peking University.

A 2.45 GHz electron cyclotron resonance proton ion source and a dual-lens low energy beam transport.

The structure and preliminary commissioning results of a new 2.45 GHz ECR proton ion source and a dual-lens low energy beam transport (LEBT) system are presented in this paper. The main magnetic field of the ion source is provided by a set of permanent magnets with two small electro-solenoid magnets at the injection and the extraction to fine tune the magnetic field for better microwave coupling. A 50 keV pulsed proton beam extracted by a three-electrode mechanism passes through the LEBT system of length of 1183 mm. This LEBT consists of a diagnosis chamber, two Glaser lenses, two steering magnets, and a final beam defining cone. A set of inner permanent magnetic rings is embedded in each of the two Glaser lenses to produce a flatter axial-field to reduce the lens aberrations.

Deuteron injector for Peking University Neutron Imaging Facility project.

The deuteron injector developed for the PKUNIFTY (Peking University Neutron Imaging Facility) has been installed and commissioned at Peking University (PKU). The injector system must transfer 50 keV 50 mA of D(+) ion beam to the entrance of the 2 MeV radio frequency quadrupole (RFQ) with 10% duty factor (1 ms, 100 Hz). A compact 2.45 GHz permanent magnet electron cyclotron resonance (PMECR) ion source and a 1.36 m long low energy beam transport (LEBT) line using two solenoids was developed as the deuteron injector. A φ5 mm four-quadrant diaphragm was used to simulate the entrance of RFQ electrodes. The beam parameters are measured after this core with an emittance measurement unit (EMU) and a bending magnet for ion fraction analysis at the end of injector. During the commissioning, 77 mA of total deuteron beam was extracted from PMECR and 56 mA of pure D(+) beam that passed through the φ5 mm four-quadrant diaphragm was obtained at the position of RFQ entrance with the measured normalized rms emittance 0.12-0.16π mm mrad. Ion species analysis results show that the deuteron fraction is as high as 99.5%. All of the parameters satisfy PKUNIFTY's requirements. In this paper, we will describe the deuteron injector design and report the commissioning results as well as the initial operation.

Intense beams from gases generated by a permanent magnet ECR ion source at PKU.

An electron cyclotron resonance (ECR) ion source is designed for the production of high-current ion beams of various gaseous elements. At the Peking University (PKU), the primary study is focused on developing suitable permanent magnet ECR ion sources (PMECRs) for separated function radio frequency quadrupole (SFRFQ) accelerator and for Peking University Neutron Imaging Facility. Recently, other kinds of high-intensity ion beams are required for new acceleration structure demonstration, simulation of fusion reactor material irradiation, aviation bearing modification, and other applications. So we expanded the ion beam category from O(+), H(+), and D(+) to N(+), Ar(+), and He(+). Up to now, about 120 mA of H(+), 83 mA of D(+), 50 mA of O(+), 63 mA of N(+), 70 mA of Ar(+), and 65 mA of He(+) extracted at 50 kV through a φ 6 mm aperture were produced by the PMECRs at PKU. Their rms emittances are less than 0.2 π mm mrad. Tungsten samples were irradiated by H(+) or He(+) beam extracted from this ion source and H∕He holes and bubbles have been observed on the samples. A method to produce a high intensity H∕He mixed beam to study synergistic effect is developed for nuclear material irradiation. To design a He(+) beam injector for coupled radio frequency quadruple and SFRFQ cavity, He(+) beam transmission experiments were carried out on PKU low energy beam transport test bench and the transmission was less than 50%. It indicated that some electrode modifications must be done to decrease the divergence of He(+) beam.

Preliminary studies on space charge compensation by analyzing residual argon gas ion signals.

An experimental method is related to research the space charge compensation (SCC) effect in low energy intense proton beams by analyzing residual gas (RG) ion signals. The signal curves were measured with an energy spectrometer under the RG pressure from 1.2x10(-3) to 1.6x10(-2) Pa. Most of the data showed a similar trend with our theoretical predicts. From the RG ion energy spectra the potential distribution in the beam was calculated both with and without the SCC effect. Moreover, as a preliminary result, a best compensating point is achieved for the low energy beam transport transmission of 40 KeV, 60 mA H(+) beam in Peking University.

The deuteron injector progress of the Peking University Neutron Imaging Facility project.

A deuteron radio frequency quadrupoles injector h has been developed at Peking University. A permanent magnetic electron cyclotron resonance (ECR) ion source is used in the injector system. A 50 keV 100 mA proton beam has been extracted from the ECR ion source and the measured normalized rms emittance is 0.11-0.14pi mm mrad. A deuteron beam has also been extracted at 50 kV with 83 mA total current and its emittance is less than 0.18pi mm mrad. The proton beam transmission has been investigated on a low energy beam transport test bench, and up to 93% transmission can be reached. The new injector with two solenoids has been designed and is being constructed. All the development results will be presented in this paper.

Upgrade of the extraction system of permanent magnet electron cyclotron resonance ion source.

A set of new ion extraction electrodes have been designed for the permanent magnetic electron cyclotron resonance ion source at Peking University to improve beam quality and transmission. PBGUNS has been used to optimize the extraction electrodes and simulate the beam behavior at the extraction region. The experiments showed that with the new system, the beam half divergence angle can be less than 40 mrad and the normalized rms emittance is about 0.13pi mm mrad when the extracted current is 100 mA at 50 keV in pulse mode. The voltage of the suppression electrode has great effect on beam divergence. The effect of the microwave power and gas flow is also studied.

The influence of magnetic field configuration on an electron cyclotron resonance ion source.

In an electron cyclotron resonance (ECR) ion source, the magnetic field along the axis of the plasma chamber and extraction system is a key parameter. At Peking University, a new 2.45 GHz ECR ion source (PMECR III), dedicated to proton production, has been developed to investigate the influence of the magnetic field on the gas discharge and beam characteristics. The magnetic configuration is provided by two permanent magnet rings independently tunable along the source axis. Moreover, the beam extraction position changes by moving the whole magnetic system along the source axis and by using different lengths of plasma electrode. A brief description of the source is reported and the magnetic field influence results are presented.

Experimental results of an electron cyclotron resonance oxygen source and a low energy beam transport system for 1 MeV integral split ring radio frequency quadruple accelerator upgrade project.

To meet the requirements of developing separated function radio frequency quadruple (rfq) and upgrading the 1 MeV integral split ring rfq accelerator, an electron cyclotron resonance O(+) ion source and low energy beam transport (LEBT) system have been developed. Using two Einzel lenses to focus the beam, more than 6 mA O(+) peak beam current with energy of 22 keV can be easily obtained at the end of LEBT when the duty faction is at 1/6. The normalized root-mean-square emittance of 90% of the beam is about 0.12pi mm mrad. By changing the focusing power of lenses, the beam waist can be shifted from 80 mm before the beam diaphragm 2 to 80 mm after it. The experimental results will be presented in this article.

Study on proton fraction of beams extracted from electron cyclotron resonance ion source.

A permanent magnet electron cyclotron resonance ion source PMECR II is used to generate proton ions for radio frequency quadrupole (RFQ) injection at Peking University (PKU). The proton fractions of the extracted beam were measured at the positions both after extraction system of ion source and the end of low energy beam transport line (LEBT). Experiments show that the proton fraction has a rise time within a beam pulse, and its value varies with pulse width and microwave power. The proton fractions measured at different positions are comparable.

Comparison of the pharmacology of hydroxamate- and carboxylate-based matrix metalloproteinase inhibitors (MMPIs) for the treatment of osteoarthritis.

OBJECTIVE AND DESIGN: Hydroxamic-and carboxylic-acid based matrix metalloproteinase inhibitors (MMPIs) were compared for their potency against various MMPs, pharmacodynamic properties and in vivo efficacy in a model of cartilage degeneration. MATERIALS AND METHODS: The MMPIs were evaluated for their ability to inhibit human MMPs using the quenched fluorescence assay. The ability of the MMPIs to inhibit the degeneration of the knee joint was evaluated in rats injected intraarticularly with iodoacetate. The amount of MMPI in the plasma and cartilage was determined using liquid chromatography/mass spectrometry/mass spectrometry (LC/ MS/MS). Plasma protein binding was measured by ultrafiltration and unbound MMPI was quantitated using HPLC. RESULTS: The hydroxamic acid based inhibitor PGE-3321996 and the carboxylic acids PGE-2909492 and PGE-6292544 were potent MMP-13 inhibitors, but only the hydroxamic acid PGE 3321996 demonstrated significant inhibition of knee degeneration in the rat iodoacetate model. Both of the carboxylic acids demonstrated superior pharmacokinetic properties and established much higher plasma concentrations than the hydroxamic acid. However, neither of the carboxylic acids was detectable in the cartilage, whereas, the hydroxamic acid was present in both the cartilage and the plasma. The carboxylic acid based MMPIs also demonstrated higher plasma protein binding (>99%) than the hydroxamic acid (79%). CONCLUSIONS: Carboxylic acid-based MMPIs were identified that had superior in vivo plasma exposure compared to a hydroxamic acid inhibitor but lacked in vivo efficacy in the rat iodoacetate model of cartilage degeneration. The lack of in vivo efficacy of the carboxylic acid based MMPIs were probably due to their lack of cartilage penetration which was related to their physicochemical properties.

Formation of MTBE-DNA adducts in mice measured with accelerator mass spectrometry.

Methyl tert-butyl ether (MTBE) is a gasoline oxygenate and antiknock additive substituting for lead alkyls currently in use worldwide. Previous studies have shown that MTBE at very high doses induces tumors in rodents. The aim of the present study was to examine directly the binding ability of MTBE onto DNA, demonstrating its potential genotoxicity. MTBE-DNA adducts and their decay kinetics in mice have been measured by using doubly 14C-labeled MTBE with an advanced, ultrasensitive technique: accelerator mass spectrometry (AMS). It was found that MTBE definitely formed adducts with DNA in mouse lung, liver, and kidney in a log/log linear dose-response relationship. The distribution sequence of DNA adducts in these tissues is: lung > liver > kidney. The level of MTBE-DNA adducts peaked at 12 h postadministration in the lung and peaked at 6 h postadministration in the liver. Then the adducts declined rapidly until 5 days postadministration and thereafter declined much more slowly. To our knowledge, this is the first report on DNA adduction with MTBE in vivo. The mechanism of the formation of MTBE-DNA adducts also is discussed.

Inhibition of nicotine-DNA adduct formation in mice by six dietary constituents.

Nicotine [3-(1-methyl-2-pyrrolidinyl)-pyridine] is a major alkaloid in tobacco products and has proven to be a potential genotoxic compound. Many natural dietary products can suppress the DNA adduction, and hence act as inhibitors of cancer. In this study, we investigated the inhibitory effects of curcumin, garlic squeeze, grapeseed extract, tea polyphenols, vitamin C, and vitamin E on nicotine-DNA adduction in vivo using an ultrasensitive method of accelerator mass spectrometry (AMS). The results demonstrated that all the dietary constituents induced marked dose-dependent decrease in nicotine-DNA adducts as compared with the control. The reduction rate reached about 50% for all agents, except garlic squeeze (40%), even at its highest dose level. Amongst the six agents, grapeseed extract exhibited the strongest inhibition to the DNA adduct formation. Therefore, we may arrive at a point that these dietary constituents are beneficial to prevent the harmful adduct formation, and thus to block the potential carcinogenesis induced by nicotine.

The development of new carboxylic acid-based MMP inhibitors derived from a cyclohexylglycine scaffold.

A series of carboxylic acids was prepared based on cyclohexylglycine scaffolds and tested for potency as matrix metalloproteinase (MMP) inhibitors. Detailed SAR for the series is reported for five enzymes within the MMP family, and a number of inhibitors such as compound 18 display low nanomolar potency for MMP-2 and MMP-13, while selectively sparing MMP-1 and MMP-7.