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Lower-grade glioma (LGG) is a crucial pathological type of glioma. Prokineticins have not been reported in LGG. Prokineticins as a member of the multifunctional chemokine-like peptide family are divided into two ligands: PROK1 and PROK2. We evaluated the role of PROK1 and PROK2 in LGG using TCGA database. We downloaded the datasets of LGG from TCGA and evaluated the influence of prokineticins on LGG survival by survival module. Correlations between clinical information and prokineticins expression were analyzed using logistic regression. Univariable survival and multivariate Cox analysis was used to compare several clinical characteristics with survival. Correlation between prokineticins and cancer immune infiltrates was explored using CIBERSORT and correlation module of GEPIA. We analyzed genes of PROK1 and PROK2 affecting LGG, screened differentially expressed genes (DEGs), interacted protein-protein with DEGs through the STRING website, then imported the results into the Cytospace software, and calculated the hub genes. To analyze whether hub genes and prokineticins are related, the relationship between PROK1 and PROK2 and hub genes was assessed and shown by heat map. In addition, gene set enrichment analysis (GSEA) was performed using the TCGA dataset. The univariate analysis using logistic regression and PROK1 and PROK2 showed opposite expression differences between tumor and normal tissues ( p < 0.05 ). PRO1 and PROK2 expressions showed significant differences in tumor grade, age, Iiscitrate DeHydrogenase (IDH) status, histological type, and 1P/19q codeletion. Multivariate analysis revealed that the up-regulated PROK1 and PROK2 expression is an independent prognostic factor for bad prognosis. Specifically, prokineticin expression level has significant correlations with infiltrating levels of Th1 cells, NK CD 56bright cells, and Mast cells in LGG. We screened 21 DEGs and obtained 5 hub genes (HOXC10, HOXD13, SOX4, GATA4, HOXA9). GSEA-identified FCMR activation, creation of C4 and C2 activators, and CD22-mediated BCR regulation in gene ontology (GO) were differentially enriched in high PROK1 and PROK2 expression phenotype pathway, cytoplasmic ribosomal proteins, and ribosome and were differentially enriched in the low PROK1 and PROK2 expression phenotype pathway. Prokineticins are a prognostic biomarker and the correlation between hub genes and LGG requires further attention.

The high-power proton beam has wide applications in neutron and neutrino physics, radioactive ion-beam production, ADS systems, proton radiography, and nuclear data measurement, etc. Cyclotrons are intrinsic in continuous-wave beam mode, which has the characteristics of high efficient power conversion rate, compact structure, and relatively low construction cost. A high-power 800-MeV proton cyclotron was proposed by CIAE, and the prestudy on the cyclotron was carried out since the year of 2009. The main magnet is among the most crucial and challenging subsystems. In contrast to low beam current cyclotron, the main magnet system of high beam current cyclotron needs to provide very strong vertical focusing force to avoid the beam blowup caused by dangerous resonances and space charge effects. In this paper, the 3-D modeling and optimizing work on this large-scale magnet system are presented in detail.

Several small cyclotrons have been constructed at CIAE to extract 14-MeV proton beam from 100 to 400 μA for various medical applications, e.g., isotope production. The magnet mapping and shimming for the isochronous field is commonly an iterative process, which is critical for a commercial cyclotron to save the manufacturing time and reduce the cost. A numerical method is established to get the isochronous field by cutting the shimming bars at both sides of the sector pole. The method has been employed to shim the magnet for two small cyclotrons in CIAE. During the shimming process for the second cyclotron, this method has been developed to reduce the number of iterations and overall time for field mapping with the experience from the first cyclotron and accurate results of three-dimensional finite-element simulation. The shimming result shows that it satisfies the requirement of isochronism and focusing characteristics. In this paper, the development of the method is presented in detail, and the improvement for the shimming procedure is illustrated with the shimming data for the two small cyclotrons.

We report a case of a Chinese man who developed retroperitoneal haemorrhage almost 1 year after surgery for pelvic fracture (1). To the best of our knowledge, this type of delayed haemorrhaging is rarely observed in clinical practice. We also review the literature to identify the common causes of retroperitoneal haemorrhage in patients undergoing surgery for pelvic fracture and to examine the aetiology of this case.

A new RIB project, Beijing Radioactive Ion-beam Facility (BRIF), has been started at CIAE since 2004. For this project, a 100 MeV high intensity compact cyclotron, CYCIAE-100, is selected as the driving accelerator for radioactive ion beam production. The cyclotron will provide the proton beam of 75–100 MeV with an intensity of 200–500 μA. The features of the cyclotron have already been described in several papers published elsewhere. In this paper the beam dynamics study is reviewed systematically. The basic parameters and numerical calculations results on the static orbit and accelerated orbit are given. The space charge effects, including the mutual interaction of neighboring multiple bunches in the radial direction, are studied with OPAL-CYCL code, and the current limit determined by space charge effects for this machine is predicted by fully 3D simulation.

CYCIAE-100, a 100 MeV H− cyclotron under construction at China Institute of Atomic Energy (CIAE), is an AVF compact cyclotron. With energy above 70 MeV, the straight-edge sector magnet, instead of the spiral one normally used for AVF cyclotrons in this case, is still used to simplify the engineering procedures. The vertical focusing is likely not strong enough at the outer region and the Walkinshaw resonance may occur, if either the permeability decreasing tolerance in large scale pure iron castings and forgings, or the fabrication tolerance during the magnet construction, are seriously excessive. Theoretical investigation and numerical simulation results presented in this paper show that this kind of risk could be avoided by using a set of specially designed asymmetrical shimming bars between the pole edge and dummy Dee of the RF cavity at the outer region. In this way, the vertical focusing at outer radius region will increase substantially. This investigation provides a protective measure for the main magnet construction of CYCIAE-100.

A 14 MeV high intensity cyclotron CYCIAE-14 dedicated to Positron Emission Tomography (PET) is under construction at China Institute of Atomic Energy (CIAE). Based on a set of basic technical requirements for the accelerator and its extracted beam, the cyclotron beam dynamics were studied and the results are presented. Static beam dynamics, beam motion inside the machine under imperfection conditions and beam behavior in the extraction process were also investigated. This work gives an in-depth view of the beam dynamics study, numerical simulation as well as the corresponding results and necessary analyses.

This paper outlines the conceptual design work of a high power proton cyclotron proposed by the China Institute of Atomic Energy (CIAE) for a spallation neutron source, accelerator driven systems, production of radioactive ion beams, and other applications. For this cyclotron the 100 MeV injection proton beam is currently considered to be provided by the CYCIAE-100 cyclotron, which is under construction at CIAE and will be later replaced by a dedicated injector for beam upgrading. In order to minimize beam losses for high intensity operation, large turn separation at the extraction has first priority. After analyzing of different scenarios, including super conducting designs, a warm magnet solution was chosen. The conceptual design, field calculations, RF cavity simulations, etc. will be presented in the paper.

This paper introduces the physics design of a 70 MeV high intensity cyclotron at China Institute of Atomic Energy (CIAE), which is aimed for multiple uses including radioactive ion-beam (RIB) production. The machine adopts a compact structure of four straight sectors, capable of accelerating two kinds of beams, i.e. H− and D− . The proton and deuteron beam will be extracted in dual opposite directions by charge exchange stripping devices. The energy of the extracted proton beam is in the range 35–70 MeV with an intensity up to 700 μA. The corresponding values for the deuteron beam are 18–33 MeV and 40 μA. This paper will present the main characteristics and parameters in the design of the 70 MeV cyclotron, the results of the basic beam dynamics study, as well as the physics in the design of the different systems, including the main magnet, RF, injection and extraction systems, etc.

In order to adequately eliminate 1st harmonic in the magnetic field of the compact cyclotron, CIAE has developed a 1st harmonic shimming method that can be applied to the four-sector compact cyclotron. The amplitude of the 1st harmonic can be reduced by adjusting the azimuthal width of the shimming bars at both sides of the sector in this method. Based on the beam dynamics requirement on the amplitude of 1st harmonic, the principle of 1st harmonic shimming method is illustrated through numerical analysis, and meanwhile, the shimming has been implemented on the magnet of CYCIAE-CRM by processing the azimuthal width using NC milling machining. The shimming result shows that it satisfies the requirement of beam dynamics. The shimming effect using this method is also analyzed and expounded in detail. The extension of this method is conducted so that it can be used to shim β θ at the median plane induced by the installation error of the upper and lower sector poles.

The 14 MeV, 400 μA compact cyclotron is under construction at China Institute of Atomic Energy (CIAE). The design of main magnet and the result of beam dynamics in the cyclotron will be described in this paper, including the choice of main parameters of magnet, the method of shimming isochronous field in the compact cyclotron and optimization of the magnetic field in central region. The beam will be accelerated to 14.6 MeV by optimizing the magnet structure.

For compact cyclotrons, it is a common practice to avoid using adjusting coils to assist the formation of field distribution. However, it is necessary to employ the adjusting coil system in some special cases, as for CYCIAE-100, a high intensity compact cyclotron under construction at CIAE. To limit the cost for the main magnet, the casting steel is used for the top/bottom and return yokes. The imperfection should not be ignored and the harmonic coils on the return yokes will enable the field to reach the requirements easier during the shimming. During the beam commissioning, centering coils are always needed for this compact machine with ~400 turns' acceleration. When the machine is in operation, the field distribution will be changed by several factors, e.g. the thermal deformation, and the trim coils will probably be used to adjust the isochronism. In this paper, the effects of various adjusting coils, including 2 sets of centering coils on the hills in the central region, 8 sets of trim coils in the valleys and 1 set of trim coils on the hills right outside the centering coils, and 1 set of harmonic coils on the 4 return yokes, have been investigated. Then the detail configuration of the adjusting coils, the mechanical design and installation simulation from the coils to the outlet inside the compact machine, will be introduced in the paper. Some experiments, including those for the conductor inside the high vacuum tank, the insulator for high radiation field, and special feed through for high current and high vacuum, etc., are tested and the results will be given as well.

A new radioactive ion beam project, Beijing Radioactive Ion-beam Facility (BRIF), has been started at CIAE since 2004 . In this project, a 100 MeV H- cyclotron, CYCIAE-100, is selected as the driving accelerator providing 75-100 MeV, 200-500 proton beam. CYCIAE-100 is consisting of the main magnet, RF system, ion source and injection system, dual beam extraction system, etc. The progress of this machine had been reported elsewhere . The main magnet is the most critical part and had been numerically simulated and delicately designed . The techniques for main magnet construction are investigated in detail . The construction of this compact style, 450 ton cyclotron magnet has been started since 2007. The imperfection control of the large scale casting steel, the deformation and fabrication tolerance, etc., have all posed a challenge to the capacity limitation of cyclotron lab at CIAE for magnet design, mapping and shimming, and of industry for steel production/machining in the world. The design highlight of the magnet will be briefly introduced and the emphasis in this paper will be given to the construction progress.

The CYCIAE-100 Cyclotron is the main part of the BRIF project at China Institute of Atomic Energy. It is an isochronous compact cyclotron for the acceleration of H-, and it will provide proton beam of 75 MeV ~ 100 MeV with an intensity of 200 ?A ~ 500 ?A. The magnetic pole has the radius of 2000 mm and the magnetic gap is changing gradually from inner radius to outer radius. The maximum filed is 1.3 T and required average isochronous field accuracy is less than 10-4. The difficulties for the design of the magnetic filed measurements device is increased not only due to the field accuracy but also due to the very small space for the compact cyclotron compared with normal machine. This paper describes the field measuring system based on the Hall-probe that has been used for the mapping of field and provides the data for shimming of the cyclotron magnet. The azimuthal and radial position of hall probes will be obtained by optical encoder and linear grating, respective. The overall measurement was estimated to be in the range of ±0.01%.

CYCIAE-100, a 100 MeV H-cyclotron under construction at China Institute of Atomic Energy, is a compact H-cyclotron. Since its upper/bottom and return yokes are each made of a casting steel of large dimension (with final dimension of 6160 mm in diameter and weight of 140 tons each piece), special attention has to be paid to the annealing procedure to insure the magnetic properties of this kind of large scale casting steel pieces with high purity. First, this paper presents an overview of annealing strategies to improve the magnetic properties of large scale casting steel. Then an estimation of heating time during annealing procedure has been made by FEM simulation based on the current status of annealing facility in China and has been indirectly verified by a rule of thumb from the results in TRIUMF design note. Based on that as well as on a close collaboration with CITIC HMC, the manufacturer of large casting steel mill, an agreement on detailed annealing procedure has been reached and issued for production of large casting steel for CYCIAE-100. The results from the practice have been obtained and the detail procedure will be presented in this paper as well.

The compact main magnet structure of CYCIAE-100, the 100 MeV high intensity cyclotron, causes the magnetic filed on the median plane to be highly sensitive to the deformation of the main magnet. The major factors that determine the structural deformation of the magnet are attributed to the mechanical properties of the pure iron, the magnet structure and the external force load. The work presented in this paper adopts the virtual work method and the Maxwell stress tensor method to precisely calculate the electromagnetic force exerted on the main magnet by the code developed by CIAE in combination with other existing codes, e.g., TOSCA and ANSYS. An in-depth analysis and comparison on the force are carried out. On that basis, five different solutions of the main magnet structure are put forward. Then numerical simulation of the magnetic field and the mechanical stress are conducted and the adoption of uneven-height top/bottom yokes is nailed down in the optimal design.

A number of compact cyclotrons accelerating H- ions to energies between 10 MeV and 100 MeV have recently been constructed for research and medical diagnostics/therapy in several countries. However limitations in extracted beam intensity are brought up by inadequate injection efficiency from the ion source into the machine. To improve the optics matching from the external source to machine acceptance, a specially designed small doublet has been developed to replace the traditionally used solenoid in the vertical injection line before the spiral inflector. Due to the narrow space inside the compact cyclotron, the doublet is designed based on the following special consideration: 1) To use the central plug of the main magnet as a part of the return yoke of the doublet; 2) To use the capillary water-cooling conductor for the coil to keep the doublet sufficiently small; 3) To adopt an integral design of the two quadrupoles into one assembly so that they could be installed in the channel of the central plug in high vacuum environment. In this paper, the design of the doublet is introduced. The outer diameter of 118 mm is precisely fit to the central plug of the Verification Facility of High Intensity Cyclotron at CIAE. Its inner diameter is 50 mm for beam injection. It can provide a maximal magnetic field gradient of 2.6 T/m from the measurement. Various kinds of detailed techniques for the doublet fabrication, e.g. the enwinding of capillary water-cooling conductor with outer diameter of 3 mm and inner diameter of 2 mm, the poles and yoke assembling, will be presented. The beam test results will be given as well.

The beam dynamics behaviour in the compact cyclotron central region is investigated. The design study for central region, including the spiral inflector, Dee tip, shield and posts, for three cyclotrons at CIAE will be described in this paper. The code development by CIAE and the UNIX based codes developed by TRIUMF were implemented on WINDOWS/PC by CIAE for the spiral inflector and central region design will be given too.

A 100 MeV H-compact cyclotron is being designed in China Institute of Atomic Energy (CIAE). It will provide a 75–100 MeV, 200–500 μA proton beam for various applications, including serving as a driving accelerator for RIB generation. In this paper, the basic magnet structure, 3D numerical simulation, magnetic material, mechanical design, deformation, imperfection field. will be described in detail respectively. In addition the preparation for construction will be discussed.

As a part of the Upgrade Project of Beijing Tandem Accelerator Laboratory, a 100 MeV compact cyclotron was designed for the generation of high intensity proton beams. Due to the limit of acceptance by the cyclotron central region, a new H− cusp source was developed at China Institute of Atomic Energy. The design of this new source is based on TRIUMF’s experience. More than 10 mA of H− beam with a measured emittance of 0.65 π mm mrad are obtained at a voltage of 28 kV from an extraction hole of 11 mm in diameter. In this article, the structure of the source, the magnetic field configuration of the multicusp and virtual filter, the extraction optics, the test results, and future improvements will be described.

The construction of a 100-MeV high-intensity cyclotron, from which proton beam will be extracted through stripping to several proton beam lines for different users, has been completed at China Institute of Atomic Energy. Given that it is the H-ions that are to be accelerated in the machine, the peak field is only 1.35 T. To simplify the fabrication, the pole adopts straight sector instead of the spiral one. Meanwhile, vertical focusing should be sufficiently high to obtain high-current proton beam. All these demands make it particularly difficult for the design and fabrication of the main magnet, which is heavy in weight and challenging to meet precision requirement in fabrication. In the process, we have developed a high-performance parallel computation PIC code for beam dynamics of high-current cyclotrons and for FFAGs, which can be used for beam dynamic simulation at a very precise level. The result is then applied to guide the design, fabrication, installation, magnetic mapping, and shimming of the 416-ton main magnet with a precision requirement up to 0.05 mm. Another challenge is due to the deformations of the magnet without/with the vacuum. The whole map measured in the vacuum has to be completed in such a big machine for the first time in the world. The result shows that all requirements, including the isochronous field, vertical focusing, and imperfection fields, have been satisfied properly. The first beam and the stable beam for an 8-h commissioning test had been achieved on July 4 and July 25, 2014, respectively.

A 2.45 GHz microwave ion source was developed at China Institute of Atomic Energy (CIAE) for proton beam production of over 60 mA [B.-Q. Cui, Y.-W. Bao, L.-Q. Li, W.-S. Jiang, and R.-W. Wang, Proceedings of the High Current Electron Cyclotron Resonance (ECR) Ion Source for Proton Accelerator, APAC-2001, 2001 (unpublished)]. For various proton beam applications, another 2.45 GHz microwave ion source with a compact structure is designed and will be built at CIAE as well for high current proton beam production. It is also considered to be used for the test of H(2)(+) beam, which could be injected into the central region model cyclotron at CIAE, and accelerated to 5 MeV before extraction by stripping. The required ECR magnetic field is supplied by all the permanent magnets rather than electrical solenoids and six poles. The magnetic field distribution provided by this permanent magnets configuration is a large and uniformly volume of ECR zone, with central magnetic field of a magnitude of approximately 875 Gs [T. Taylor and J. S. C. Wills, Nucl. Instrum. Methods Phys. Res. A 309, 37 (1991)]. The field adjustment at the extraction end can be implemented by moving the position of the magnet blocks. The results of plasma, coupling with 2.45 GHz microwave in the ECR zone inside the ion source are simulated by particle-in-cell code to optimize the density by adjusting the magnetic field distribution. The design configuration of the ion source will be summarized in the paper.

In line with the increasing demand for PET cyclotrons in China, the construction of a 14 MeV high intensity compact cyclotron, CYCIAE-14, has been proposed at China Institute of Atomic Energy (CIAE) in 2010 and is scheduled to be finished within two years. The fabrication is in smooth progress, with a majority of the devices ready in place for installation. As a critical part of the cyclotron, the main magnet development is of paramount importance to the successful development of the machine. At present, the main magnet design and fabrication has been accomplished. The physics design of the main magnet, which enables the realization of strong focusing by adopting a 4-sector structure with variable hill gap, will be emphatically introduced in the paper. Meanwhile, the engineering techniques applied to the fabrication will also be presented, in particular the technical challenges encountered in the process. Based on the accomplishment of two sets of main magnets, six more sets of main magnets will be fabricated.

A 70 MeV cyclotron for radioactive ion beam production and other applications has been designed at China Institute of Atomic Energy (CIAE). The main challenge of the magnet design for this particle machine lies in the needs of two isochronous magnetic fields to accelerate H- and D- with charge-mass ratios of 1 and 0.5 respectively. The required isochronisms are achieved by installing removable shims and adjusting the RF frequency. The magnetic fields and beam dynamics design results for both H- and D- beams are described in this paper. The analysis on field imperfections caused by the magnet deformation and the effects of annealing on magnetic properties of materials, are also outlined.

A comprehensive test stand for high-intensity cyclotron development, a 10 MeV 430 μA cyclotron, has been successfully constructed at China Institute of Atomic Energy (CIAE) for the experimental verification of the viability of a 100 MeV high-intensity cyclotron (CYCIAE-100) being constructed at CIAE. The verification includes the overall design technology, detail design and engineering technology for the crucial parts of the machine, e.g. main magnet and beam diagnostics. It will also pave the way for future enhancement of the beam intensity. The test stand consists of a H− ion source, axial injection system, central region, main magnet and coil, RF resonator, stripping extraction, and auxiliary systems, which include the RF power amplifier, high voltage and DC power supplies, electric apparatus, beam diagnostics, control, vacuum, water cooling, pneumatic system, and safety interlock. This paper presents the work regarding the design and sub-system development of the test sand, and the results of the beam commissioning of the machine.