Search

Batch process generally has varying dynamic characteristic that causes low fault detection rate and high false alarm rate, and it is necessary and urgent to monitor batch process. This paper proposes a global enhanced multiple neighborhoods preserving embedding based fault detection strategy for dynamic batch process. Firstly, the angle neighbor is defined and selected to compensate for the insufficient expression for the spatial similarity of samples only by using the distance neighbor, and the time neighbor is introduced to describe the time correlations between samples. These three types of neighbors can fully characterize the similarity of the samples in time and space. Secondly, considering the minimum reconstruction error and the order information of three types of neighbors, an enhanced objective function is constructed to prevent the loss of order information when neighborhood preserving embedding (NPE) calculates the reconstruction weights. Furthermore, the enhanced objective function and a global objective function are organically combined to extract both global and local features, to describe process dynamics and visualize process data in a low-dimensional space. Finally, a monitoring index based on support vector data description is constructed to eliminate adverse effects of non-Gaussian data for monitoring performance. The advantages of the proposed method over principal component analysis, neighborhood preserving embedding, dynamic principal component analysis and time NPE are demonstrated by a numerical example and the penicillin fermentation process simulation.

Purpose Gastric cancer stem cells (CSCs) are important for the initiation, growth, recurrence, and metastasis of gastric cancer, due to their chemo-resistance and indefinite proliferation. Herein, to eliminate gastric CSCs, we developed novel CSC-targeting glioma-associated oncogene homolog 1 (Gli1) small interfering RNA (siRNA) nanoparticles that are specifically guided by a di-stearoyl-phosphatidyl-ethanolamine- hyaluronic-acid (DSPE-HA) single-point conjugate, as an intrinsic ligand of the CD44 receptor. We refer to these as targeting Gli1 siRNA nanoparticles. Methods We used the reductive amination reaction method for attaching amine groups of DSPE to aldehydic group of hyaluronic acid (HA) at the reducing end, to synthesize the DSPE-HA single-point conjugate. Next, targeting Gli1 siRNA nanoparticles were prepared using the layer-by-layer assembly method. We characterized the stem cellular features of targeting Gli1 siRNA nanoparticles, including their targeting efficiency, self-renewal capacity, the migration and invasion capacity of gastric CSCs, and the penetration ability of 3D tumor spheroids. Next, we evaluated the therapeutic efficacy of the targeting Gli1 siRNA nanoparticles by using in vivo relapsed tumor models of gastric CSCs. Results Compared with the multipoint conjugates, DSPE-HA single-point conjugates on the surface of nanoparticles showed significantly higher binding affinities with CD44. The targeting Gli1 siRNA nanoparticles significantly decreased Gli1 protein expression, inhibited CSC tumor spheroid and colony formation, and suppressed cell migration and invasion. Furthermore, in vivo imaging demonstrated that targeting Gli1 siRNA nanoparticles accumulated in tumor tissues, showing significant antitumor recurrence efficacy in vivo. Conclusion In summary, our targeting Gli1 siRNA nanoparticles significantly inhibited CSC malignancy features by specifically blocking Hedgehog (Hh) signaling both in vitro and in vivo, suggesting that this novel siRNA delivery system that specifically eliminates gastric CSCs provides a promising targeted therapeutic strategy for gastric cancer treatment.

XiPAF (Xi’an 200MeV Proton Application Facility) is a project to fulfill the need for the experimental simulation of the space radiation environment. It comprises a 7 MeV H⁻ linac, a 60-230 MeV proton synchrotron, and experimental stations. The Installation of the synchrotron, beamline and one experimental station were completed at the end of December 2019, and commissioning has just begun. Circulating beam around the synchrotron was observed on the first day of operation, and now 10-200 MeV proton beam directly extracted from the synchrotron had been transported to the experimental station for user experiments. The results of the commissioning and data analysis are presented in this paper., Proceedings of the 12th International Particle Accelerator Conference, IPAC2021, Campinas, SP, Brazil

The beam commissioning of the capture and acceleration process on the XiPAF (Xi’an 200MeV Proton Application Facility) synchrotron has been carried out. The efficiency of the experiment results has been compared with the simulation results. At present, the efficiency of the capture process with single-harmonic is about 73%, and the acceleration efficiency is about 82%, and the simulation results are 77% and 96% without space charge effect, respectively. In order to improve efficiency, dual-harmonic was used during the capture and acceleration process. During the experiment, the capture efficiency was increased by 5%, and the acceleration efficiency was increased by 4%. The capture efficiency decreases with the increase of the maximum RF voltages. We analyzed the reasons for the decrease in capture efficiency. In the next step, further verification will be carried out through experiments under different conditions., Proceedings of the 12th International Particle Accelerator Conference, IPAC2021, Campinas, SP, Brazil

The synchrotron of XiPAF (Xi’an 200MeV proton application Facility) is a compact proton synchrotron, which using H⁻ stripping injection and phase space painting scheme. Now XiPAF is under commissioning with some achievements, the current intensity after injection reach 43mA, the corresponding particle number is 2.3·10¹¹, and the injection efficiency is 57%. The simulation results by PyOrbit show that the injection efficiency is 77%. In this paper, we report how the injection intensity and efficiency were optimized. We analyzed the difference between simulation and experiments, and quantitatively investigate the factors affecting injection efficiency through experiments., Proceedings of the 12th International Particle Accelerator Conference, IPAC2021, Campinas, SP, Brazil

We present, in this paper, the beam dynamics design of a linac injector with laser-accelerated carbon-ions for a medical synchrotron. In the design, the initial transverse divergence is reduced by two apertures. The beam is focused transversely through a quadrupole triplet lens downstream the apertures. The output energy spread of the extracted beam at the exit of the injector is compressed from ±6% to ±0.6% by a debuncher and a bend magnet system to meet the injection requirement for the synchrotron. By changing the width of imaging slit of the bend magnet system, the beam with energy of 4±0.024 MeV/u is extracted, and the particle number per shot and transverse emittances of the beam at the exit of the injector can be regulated through adjusting the slit height. The dynamics design can pave the way for the future concept research of the synchrotron injector., Proceedings of the 12th International Particle Accelerator Conference, IPAC2021, Campinas, SP, Brazil

Xi’an 200 MeV Proton Application Facility (XiPAF) is a project to fulfill the need for the experimental simulation of the space radiation environment. It comprises a 7 MeV H⁻ linac, a 60~230 MeV proton synchrotron, and experimental stations. Slow extraction commissioning for 60 MeV proton beam in XiPAF synchrotron has been finished. After commissioning, the maximal experiment extraction efficiency with the RF-knockout (RF-KO) method can up to 85%. The reason for beam loss has been analyzed and presented in this paper. Besides, an experiment of multiple energy extraction has been conducted in XiPAF synchrotron. The proton beams of 3 different energies were successfully extracted in 1.54 s., Proceedings of the 12th International Particle Accelerator Conference, IPAC2021, Campinas, SP, Brazil

The beam generated after slow extraction of the synchrotron is always not uniform and asymmetrical in transverse distribution. In practice, radiation therapy or radiation irradiation requires a high degree of uniformity of beam spot. Therefore, it is necessary to adjust the beam distribution with a nonlinear magnet and other elements on the transport line from synchrotron ring to beam target station. Nonlinear magnet has high requirements on beam quality. Before passing through the nonlinear magnet field, the beam center can be adjusted by taking advantage of the gradient change distribution of the nonlinear magnet’s transverse field map to achieve uniform distribution at the target station. As an example, we use the parameters of heavy ions of XiPAF (Xi’an 200MeV Proton Application Facility) to simulate the beam transport from synchrotron ring to beam target station., Proceedings of the 12th International Particle Accelerator Conference, IPAC2021, Campinas, SP, Brazil

Hongjuan Yao,1 Lan Sun,2 Jingcao Li,2 Xiaofei Zhou,1 Rui Li,1 Rongguang Shao,1 Yingge Zhang,2 Liang Li1 1Key Laboratory of Antibiotic Bioengineering of National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology (IMB), Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing 100050, People’s Republic of China; 2Key Laboratory of Nanopharmacology and Nanotoxicology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, People’s Republic of ChinaCorrespondence: Liang LiKey Laboratory of Antibiotic Bioengineering of National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology (IMB), Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing 100050, People’s Republic of ChinaTel +86 10-63165824Fax +86 10-63027302Email liliang@imb.pumc.edu.cnYingge ZhangBeijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Haidian, Beijing 100850, People’s Republic of ChinaTel +86 10-66930654Fax +86 10-68211656Email zhangyg58@126.comPurpose: Gastric cancer stem cells (CSCs) are important for the initiation, growth, recurrence, and metastasis of gastric cancer, due to their chemo-resistance and indefinite proliferation. Herein, to eliminate gastric CSCs, we developed novel CSC-targeting glioma-associated oncogene homolog 1 (Gli1) small interfering RNA (siRNA) nanoparticles that are specifically guided by a di-stearoyl-phosphatidyl-ethanolamine- hyaluronic-acid (DSPE-HA) single-point conjugate, as an intrinsic ligand of the CD44 receptor. We refer to these as targeting Gli1 siRNA nanoparticles.Methods: We used the reductive amination reaction method for attaching amine groups of DSPE to aldehydic group of hyaluronic acid (HA) at the reducing end, to synthesize the DSPE-HA single-point conjugate. Next, targeting Gli1 siRNA nanoparticles were prepared using the layer-by-layer assembly method. We characterized the stem cellular features of targeting Gli1 siRNA nanoparticles, including their targeting efficiency, self-renewal capacity, the migration and invasion capacity of gastric CSCs, and the penetration ability of 3D tumor spheroids. Next, we evaluated the therapeutic efficacy of the targeting Gli1 siRNA nanoparticles by using in vivo relapsed tumor models of gastric CSCs.Results: Compared with the multipoint conjugates, DSPE-HA single-point conjugates on the surface of nanoparticles showed significantly higher binding affinities with CD44. The targeting Gli1 siRNA nanoparticles significantly decreased Gli1 protein expression, inhibited CSC tumor spheroid and colony formation, and suppressed cell migration and invasion. Furthermore, in vivo imaging demonstrated that targeting Gli1 siRNA nanoparticles accumulated in tumor tissues, showing significant antitumor recurrence efficacy in vivo.Conclusion: In summary, our targeting Gli1 siRNA nanoparticles significantly inhibited CSC malignancy features by specifically blocking Hedgehog (Hh) signaling both in vitro and in vivo, suggesting that this novel siRNA delivery system that specifically eliminates gastric CSCs provides a promising targeted therapeutic strategy for gastric cancer treatment.Keywords: Hedgehog (Hh) pathway, Gli1 siRNA, gastric cancer stem cells, di-stearoyl-phosphatidyl-ethanolamine-hyaluronic acid (DSPE-HA) single-point conjugate, therapeutic siRNA nanoparticles

Non-small cell lung carcinoma (NSCLC) is a malignant tumour with poor prognosis and high mortality. Platinum-based dual-agent chemotherapy is the main therapeutic regimen for this disease. In recent years, because of the introduction of molecular targeted therapy, various targeted therapeutic agents against epidermal growth factor receptor (EGFR) have been rapidly developed, which has become a research hotspot for NSCLC treatment. Here, we review the latest studies describing the features and types of EGFR pathogenic mutations, currently established EGFR-tyrosine kinase inhibitors from the first to fourth generation, including their action mechanisms, acquired resistance, and clinical applications, and potential challenges and perspectives that current researchers should address.

This paper introduces a high-performance code Li-track for beam dynamics simulation of synchrotrons. It is a parallel multi-particle tracking program written entirely in C++ and therefore has a high computational speed. The overall design of Li-track is based on object-oriented mode, and the implemented element model can be easily reused to build different synchrotron lattice. The symplectic integral algorithm is used to ensure there are no physical errors in a long-term simulation. This code has been used for the slow extraction simulation of XiPAF synchrotron and the results will be given in this paper., Proceedings of the 10th Int. Particle Accelerator Conf., IPAC2019, Melbourne, Australia

The magnets are being constructed for Xi'an Proton Application Facility (XiPAF) synchrotron. A study is started to obtain the specifications and tolerances of the magnets to avoid beam lost by the excessive magnetic field errors. The study includes the effect of field and alignment errors of the magnets on the closed orbit and beam optics. Also a preliminary study of effect due to multipole components in dipole and quadrupole magnets on dynamic aperture has been done. The tolerances of dipole and quadrupole magnets on field errors, including multipole components, and alignment errors are described in this paper., Proceedings of the 9th Int. Particle Accelerator Conf., IPAC2018, Vancouver, BC, Canada

Xi an Proton Application Facility (XiPAF) which consists of one 230 MeV proton accelerator and irradiation stations, will be constructed in Xi an city, Shaanxi, China. The facility is composed of a 230 MeV synchrotron, a 7 MeV H⁻ linac injector and two experimental stations. It can provide a flux of 10⁵~10⁸ p/cm²/s with the uniformity of better than 90% on the 10 cm×10 cm sample. The overall design of XiPAF accelerator is presented in this paper. And the progress of project is reported also., Proceedings of the 13th Symposium on Accelerator Physics, SAP2017, Jishou, China

The 3rd resonant slow extraction and RF-Knockout technology has been adopted for XiPAF, which was designed for proton therapy and single event effects. The separatrix of stable region will fluctuate in the process of slow extraction due to power ripple, hence influence the uniform of extracted beam and the extraction efficiency. The influence of dipole and quadrupole power ripple is studied in theory and simulated by a MPI parallel multi-particle program, a method of making beam less sensitive to power ripple is discussed and verified by simulation., Proceedings of the 8th Int. Particle Accelerator Conf., IPAC2017, Copenhagen, Denmark

The physics design of the H⁻ charge exchange injection system for Xi’an Proton Application Facility (XiPAF) synchrotron with the missing dipole lattice is discussed. The injection scheme is composed of one septum magnet, three chicane dipoles, two bump magnets and one carbon stripping foil. A 7 μg/cm² carbon foil is chosen for 7 MeV H⁻ beam for high stripping efficiency and low coulomb scattering effect. The simulation results of the horizontal and vertical phase space painting finished by two bumper magnets and mismatching respectively are presented., Proceedings of the 57th ICFA Advanced Beam Dynamics Workshop on High-Intensity and High-Brightness Hadron Beams, HB2016, Malmö, Sweden

We report a design of the 230 MeV proton accelera-tor, the Xi’an Proton Application Facility (XiPAF), which will be located in Xi’an city, China. The facility will provide proton beam with the maximum energy of 230 MeV for the research of the single event effect. The facility, composed of a 230 MeV synchrotron, a 7 MeV H⁻ linac injector and two experimental stations, will provide a flux of 10⁵~10⁸ p/cm²/s with the uni-formity of better than 90% on the 10 cm×10 cm sample., Proceedings of the 57th ICFA Advanced Beam Dynamics Workshop on High-Intensity and High-Brightness Hadron Beams, HB2016, Malmö, Sweden

The physics design of slow extraction for Xi’an Proton Application Facility (XiPAF) synchrotron is discussed. The extraction scheme is composed of two resonant sextupoles, one electrostatic septum (ES) and two septum magnets. The phase space diagram under the Hardt condition at the entrance of ES and the last three turn’s trajectory before extraction are presented. A program is written with C++ to simulate slow extraction process by RF-knockout (RF-KO), the calculation results of dual frequency modulation (FM) and amplitude modulation (AM) are given, and the standard deviation of the fluctuation parameter R1 can be limited 0.2 with optimum parameters under a sampling frequency of about 10 kHz., Proceedings of the 57th ICFA Advanced Beam Dynamics Workshop on High-Intensity and High-Brightness Hadron Beams, HB2016, Malmö, Sweden

We have designed a compact proton synchrotron(7~230 MeV) for applications like proton therapy and space environment study. These applications may require slow extraction from 10~230 MeV. Traditionally, the low energy beam(10~70 MeV) is achieved by energy degradation from high energy beam which may cause beam lose and energy spread increase, because the beam quality may suffer from magnetic remanence, power ripple and strong space charge effects in low energy stage. To achieve high quality beam directly from resonance extraction, we study these effects by performing multi-particle simulation. Methods of improving beam quality are discussed., Proceedings of the 7th Int. Particle Accelerator Conf., IPAC2016, Busan, Korea

For the Xi'an 200 MeV Proton Application Facility (XiPAF), one important thing is to produce more homog-enous beam profile at the target to fulfill the requirements of the beam application. Here the beam line is designed to meet the requirement of beam expansion and homogenization, and the step-like field magnets are employed for the beam spot homogenization. The simulations results including space charge effects and errors show that the beam line can meet the requirements well at the different energies (from 10 MeV to 230 MeV) and different beam spot size (from 20mm to 200mm)., Proceedings of the 7th Int. Particle Accelerator Conf., IPAC2016, Busan, Korea

A compact magnetic alloy (MA) loaded cavity is under development for XiPAF's synchrotron. The cavity contains 6 large size MA cores, each is independently coupled with solid state power amplifier. Two types of MA core are proposed for the project. We have developed a single core model cavity to verify the impedance model and to test the properties of MA cores under high power state. The high power test results are presented and discussed., Proceedings of the 57th ICFA Advanced Beam Dynamics Workshop on High-Intensity and High-Brightness Hadron Beams, HB2016, Malmö, Sweden