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To ensure high-precision alignment of large quantities of magnets in Chinese high energy photon source, a high magnetic center measurement efficiency is required. To achieve this, a unique single-turn rotating coil magnetic center calibration system was designed, which simplifies the traditional multi-turn compensated coil with two sets of windings that can be connected. This design reduces measurement time significantly while increasing precision by incorporating a three-coordinate measuring machine. The study presents the system’s general design, mathematical theory, and test results. Tests replacing the coil and magnets and realigning them demonstrated that the precision and measurement efficiency meet the design requirements. The displacement between the magnetic and mechanical axes was within 20 μm, indicating good performance of the well-fabricated and tested ultra-high gradient quadrupole magnet. The optimized rotating coil system design reduces the entire procedure, including magnet installation and alignment, magnetic axis measurement, and magnetic center extraction to fixed points on the magnet, to only a few hours. Several magnets participating in pre-alignment were measured, and tests and practical operation resulted in small magnetic center displacements.

Alignment of superconducting cavities is one of the important issues for the China Spallation Neutron Source Phase II (CSNS II) linac. In order to obtain the cavity displacement in the process of cooling down to the liquid helium temperature, a laser-based Poisson Spot Monitor (PSM) system was newly proposed and a verification system in the laboratory was built. The PSM system uses the diffraction spot formed on the CMOS camera after a beam of parallel laser passes through a spherical target to monitor the position of the measured object, where the spherical target is fixed on the monitored object. The displacement during the cooling process of the cryomodule is replaced by the movement of the high-precision two-axis motorized translation stage. A spherical target is fixed on the translation stage as the monitoring object. A beam of parallel laser passes through the spherical monitoring target to form a Poisson spot image on a CMOS camera. The coordinates of the Poisson spot center are obtained through image processing. Through experiments, the PSM system obtained a high accuracy within 5 μm, which meets the displacement monitoring requirement of the CSNS II cryomodule components. The system is fairly simple and able to be constructed without highly specialized parts and can also be used in other high-precision alignment and monitoring fields.

Overexpression of microRNA-185-5p (miR-185-5p) in glucocorticoid (GC)-sensitive acute lymphoblastic leukemia (ALL) was identified using a microarray and reverse transcription polymerase chain reaction and was further confirmed in ALL cell lines. A reporter assay confirmed that the Rictor-one component of mammalian target of rapamycin complex 2 (mTORC2) is a target of miR-185-5p. Decreased mTORC activity was also confirmed in GC-sensitive patients. Overexpression of miR-185-5p significantly enhanced GC sensitivity in CEM-C1 cells (GC resistance) by increasing the rate of cell apoptosis and cycle arrest, and decreasing cell survival, accompanied by a decrease in mTORC activity and an increase in GC-induced glucocorticoid receptor (GR) expression. Rapamycin, an mTORC1 inhibitor, showed similar effects to miR-185-5p. These results demonstrated that miR-185-5p enhances GC sensitivity via suppression of mTORC activity by enhancing GR autoupregulation and that miR-185-5p is a potential target for the diagnosis and reversion of GC resistance.

Background Systemic chronic active Epstein-Barr virus infection is an extremely rare childhood disease. Since chronic active Epstein-Barr virus infection can trigger the onset of Epstein-Barr virus-associated lymphoproliferative disease. The clinical manifestations of the disease vary according to the site of involvement; therefore, management may be challenging. Currently, there are no standardized guidelines for treating Chronic active Epstein-Barr virus infection effectively. Case presentation We report a case of chronic active Epstein-Barr virus infection in a 5-year-old Chinese boy with intestinal, vascular, and neurological involvement. At age of 2 years and 7 months old, he had hepatomegaly and been diagnosed with Epstein-Barr virus infection. After treatment, he showed some clinical improvement. At age of 3 years and 3 months old, he presented with recurrent fever and diarrhea. Then he received methylprednisolone for 1 year and his symptoms ameliorated. At the age of 5 years, his symptoms recurred and had gastrointestinal hemorrhage and developed polyuria, frequent convulsions and hyponatremia. He was transferred to our hospital for further management. He was unconscious on admission and was diagnosised Epstein-Barr virus-lymphoproliferative disorder, based on the results in situ hybridization of EBV-encoded miRNA in sigmoid colon. Three-dimensional CT angiography demonstrated an aneurysm in the right internal carotid artery. Abdominal CT showed dilatation of vessels in part of the intestinal wall. He was also diagnosised Epstein-Barr virus encephalitis based on the elevated Epstein-Barr virus antibody titers and presence of Epstein-Barr virus DNA in the Cerebrospinal Fluid. A repeated duodenal artery embolization and symptomatic therapy could not control the hemorrhage after admission. He subsequently received treatment with ganciclovir, glucocorticoid, thalidomide, and propranolol. Hemorrhage was controlled in 5 days; his symptoms improved. The fever did not recur and the CSF pressure was also normalized. A follow-up CT at 3 months after admission showed regression of the aneurysm in the right internal carotid artery and the vascular lesion in the duodenum. Discussion and conclusions A new treatment protocol including thalidomide and propranolol resulted in a marked improvement in his clinical symptoms, and shows promise as a novel and effective therapeutic approach for Chronic active Epstein-Barr virus infection-associated lymphoproliferative disorder.

Objective. HMGCS2 is the rate-limiting enzyme of ketogenesis, which is vital for tumor initiation or metastasis. The aim of this study is to determine the relationship between HMGCS2 and tumor angiogenesis.Materials and Methods. The study consisted of 100 cases with colorectal cancer and healthy control, the expression of HMGCS2 and the microvessel density (MVD) (marker: CD31) were analyzed by immunohistochemistry and tube formation, and the centration ofβ-hydroxybutyrate in serum was assessed by biochemical analysis.Results. The results showed that HMGCS2 expression is significantly reduced in colorectal cancer compared with healthy control, which is inversely correlated with MVD in colorectal cancer by IHC analysis. What is more, knockdown HMGCS2 expression in HT-29 cells significantly contributed endothelial cell tube formation.Conclusion. These findings implying HMGCS2 may have a negative regulation of tumor angiogenesis and provide an approach to inhibit tumor angiogenesis.

Although a series of cationic polymers has been designed and synthesized by various kinds of strategies, the lower transfection efficiency and higher cytotoxicity are still a major problem for successful gene therapy. In this study, a novel cation polyphosphoramide (denoted as PPA) with amino moieties in the main chain was synthesized by polycondensation of ethyl dichlorophosphate with N1-(2-aminoethyl)-N1-(1-methyl)-1, 2-ethanediamine and investigated as non-viral vectors for gene transfection in target cells. Gel retardation analysis showed that PPA could efficiently retard the mobility of DNA at a lower N/P ratio. The size and zeta potential measurements found that these PPA/pDNA polycomplexes exhibited a decreased size and increased zeta potential. The cytotoxicity assay further revealed that PPA was non-toxic to different cells even at higher concentrations. It was also observed that polyionic complexes at a lower ratio of PPA/DNA (3 : 1) exhibited higher transfection efficiency. Interestingly, protein phosphorylation and a luciferase reporter assay showed that overexpression of the target gene (GFP-PKD2) transfected with PPA could enhance phosphorylation of PKD2, downstream IκB degradation and luciferase reporter activity of NF-κB signalling pathway in response to PMA, the agonist for PKD2 and NF-κB activation, indicating that the synthesized PPA could effectively deliver more than one exogenous genes into target cells and their proteins showed a functional role in target cells. More importantly, Western blotting and immunofluoescence staining of NF-κB p65 nuclear translocation showed that siRNA could be also delivered by PPA effectively, and exhibited silencing of the target gene as well as the signaling pathway in A549 cancer cells and HeLa cells. These results suggested that this novel cation polyphosphoramide could be used as an efficient carrier for plasmid and siRNA in future gene therapy applications.

Conjugated polymer nanoparticles (PPE nanoparticles) are fabricated by the self-assembly of novel amphiphilic poly(phenyleneethynylenes). The morphology and cytotoxicity of PPE nanoparticles were investigated. Moreover, confocal fluorescence microscopy and flow cytometry assay revealed the effective internalization of PPE nanoparticles. PPE nanoparticles were also used as a carrier for drug delivery systems. Upon encapsulating an anticancer drug, DOX, PPE nanoparticles exhibited high drug loading efficiency (26.6 wt%) and good release properties. Subsequently, DOX loaded PPE nanoparticles were investigated by employing dynamic light scattering and transmission electron microscopy. Finally, cell uptake, cytotoxicity and Western blotting analysis were carried out, which revealed that PPE nanoparticles successfully deliver the drug into cancer cells and retain the anticancer bioactivity of DOX. All these results indicated that this new type of PPE nanoparticles would be a promising drug delivery system for therapeutic delivery and/or bioimaging applications.

A novel ratiometric fluorescent probe based on hydroxylnaphthalene 2-cyanoacrylate was developed to act as a luminescent probe for biological fluoride ion detection. The probe is responsive and highly selective for fluoride ions over other common anions; it also exhibits a very low detection limit of 8.54 μM. The deprotonation of the phenol moieties leads to a fluorescent change in the probe. The biological applications of the probe were also evaluated and it was found to exhibit a low cytotoxicity, a good water solubility and membrane permeability. The probe was, therefore, employed as a sensing probe for the detection of fluoride ions in living cells.

An improved three-dimensional inverse heat conduction procedure is proposed to quantitatively solve the steady-state tool-chip interface temperature in dry turning. The infrared method is utilized to measure the temperature on the rake face of the insert in transient cooling process after the feed motion is halted. With the experimentally measured temperature data, the 3-D heat conduction model of the cutter and an optimization scheme are used to solve the effective heat flux on tool-chip interface and the interface temperature during turning. This inverse procedure facilitates the determination of the temperature at tool-chip interface in dry turning process, which is still a challenge for existing experimental and numerical methods.

Aiming to effectively remove the cutting heat in machining process, the cutting tool with heat pipe cooling has been developed in recent years; however, there were few reports on the quantitative investigation of temperature at the tool-chip interface of this tool. In this work, a heat pipe cooling system was used to decrease the temperature of the cutter. The temperature at defined locations of the cutter in the dry turning of an AISI-1045 steel was obtained by the cutting test. The finite difference solution and an inverse procedure were used to determine the tool-chip interface temperature. It was found that with the increase of cutting speed, the tool-chip interface temperature and effective heat flux of the cutter will increase. The tool-chip interface temperature could be reduced by the heat pipe cooling. The temperature reduction was more obvious in higher cutting speed.

A novel fluorescent probe based on heteroatom containing styrylcyanine is synthesized. The fluorescence of probe is bright green in basic and neutral media but dark orange in strong acidic environments, which could be reversibly switched. Such behavior enables it to work as a fluorescent pH sensor in the solution state and a chemosensor for detecting acidic and basic volatile organic compounds. Analyses by NMR spectroscopy confirm that the protonation or deprotonation of pyridinyl moiety is responsible for the sensing process. In addition, the fluorescent microscopic images of probe in live cells and zebrafish are achieved successfully, suggesting that the probe has good cell membrane permeability and low cytotoxicity.

To investigate AXIN1-related CSRNP1 gene expression and the mechanism of its transcriptional regulation in TGF-β1-induced tumor cells.Human lung carcinoma A549 cells or human prostate cancer PC3 cells were treated with TGF-β1 at different doses (0, 20, 40, and 80 ng/ml) or at 20 ng/ml for 0, 8, 12, or 24 h, and the dose and time effect of TGF-β1 on CSRNP1 mRNA expression in the tumor cells were evaluated with real-time RT-PCR. A549 cells were also treated with TGF-β1 and cycloheximide to clarify whether CSRNP1 expression induced by TGF-β1 required de novo protein synthesis. A549 cells transfected with pcDNA3.1, flag-SMAD3, or flag-SMAD3-mu, after serum starvation, were treated with or without TGF-β1 (20 ng/mL) for 24 h, and the overexpression of wild-type SMAD3 and dominant negative SMAD3-mu mutant were confirmed by Western blotting. The effect of SMAD3 or SMAD3-mu overexpression on CSRNP1 mRNA expression was also measured by real-time RT-PCR.In both A549 and PC3 cells, TGF-β1 dose- and time-dependently stimulated CSRNP1 expression, which required de novo protein synthesis in A549 cells. Overexpression of wild-type SMAD3 significantly increased the expression of CSRNP1 mRNA induced by TGF-β1, while overexpression of dominant negative SMAD3 mutant remarkably reduced CSRNP1 mRNA expression in response to TGF-β1 in A549 cells.TGF-β1 may contribute to CSRNP1 expression through SMAD3 activation and downstream signaling in tumor cells.

To explore the functional role of protein kinase D1 (PKD1) in the activation of nuclear factor-κB (NF-κB) signal pathway and NF-κB transcription mediated by Aspergillus fumigatus.A549 cells and HEK293 cells were transfected with green fluorescence protein (GFP) or GFP-PKD1 followed by treatment with 1×10(5) CFU/ml Aspergillus fumigatus conidia for different time lengths. The phosphorylation levels of PKD1, IκB and p65 (pS276) in the transfected cells were measured by Western blotting. A549 cells were transfected with GFP-PKD1 or siRNA-PKD1, and the phosphorylation of IκB and p65 (pS276) was examined. Finally, NF-κB-luc and renilla luciferase reporter pRL-SV40 were cotransfected into GFP- or GFP-PKD1-transfected A549 cells before exposure of the cells to Aspergillus fumigatus conidia for 24 h, and NF-κB transcriptional activity in the cells was determined using dual-luciferase reporter assay.Overexpression of PKD1 significantly increased Aspergillus fumigatus conidia-stimulated phosphorylation of PKD1, IκB and p65 (pS276), whereas PKD1 knockdown by siRNA-PKD1 suppressed IκB and p65 (pS276) phosphorylation. Dual luciferase assay demonstrated that PKD1 overexpression markedly enhanced Aspergillus fumigatus-induced NF-κB transcription in A549 cells.PKD1 may contribute to the activation of NF-κB signal pathway and NF-κB transcription induced by Aspergillus fumigatus.

How to describe 3D moving objects motion model of good adaptability, how to present and store moving objects data in database and realize the self-adaptive dynamic visualization of 3D moving objects with positioning and communication information, are the key problems on data organization and management of 3D moving objects. The information about 3D moving objects are references with the location and time, including the real time geographic information. This paper proposes a new method of multi-scale data organization and management of 3D moving objects based on GIS. The 3D-terrain is rendered with triangle subdivision bi-tree data structure and LOD, which are easy to realize the rapid visualization for 3D moving objects. The experiments show that the propose method is suitable to 3D moving objects in large-scale complex virtual environments.

Although protein kinase D3 (PKD3) has been shown to contribute to prostate cancer cell growth and survival, the role of PKD in prostate cancer cell motility remains unclear. Here, we show that PKD2 and PKD3 promote nuclear factor kappa B (NF-κB) signaling and urokinase-type plasminogen activator (uPA) expression/activation, which are crucial for prostate cancer cell invasion. Silencing of endogenous PKD2 and/or PKD3 markedly decreased prostate cancer cell migration and invasion, reduced uPA and uPA receptor (uPAR) expression and increased plasminogen activator inhibitor-2 (PAI-2) expression. These results were further substantiated by the finding that PKD2 and PKD3 promoted the activity of uPA and matrix metalloproteinase 9 (MMP9). Furthermore, depletion of PKD2 and/or PKD3 decreased the level of binding of the p65 subunit of NF-κB to the promoter of the gene encoding uPA (PLAU), suppressing transcriptional activation of uPA. Endogenous PKD2 and PKD3 interacted with inhibitor of NF-κB (IκB) kinase β (IKKβ); PKD2 mainly regulated the phosphorylated IKK (pIKK)-phosphorylated IκB (pIκB)-IκB degradation cascade, p65 nuclear translocation, and phosphorylation of Ser276 on p65, whereas PKD3 was responsible for the phosphorylation of Ser536 on p65. Conversely, inhibition of uPA transactivation by PKD3 silencing was rescued by constitutive Ser536 p65 phosphorylation, and reduced tumor cell invasion resulting from PKD2 or PKD3 silencing was rescued by ectopic expression of p65. Interestingly, PKD3 interacted with histone deacetylase 1 (HDAC1), suppressing HDAC1 expression and decreasing its binding to the uPA promoter. Moreover, depletion of HDAC1 resulted in recovery of uPA transactivation in PKD3-knockdown cells. Taken together, these data suggest that PKD2 and PKD3 coordinate to promote prostate cancer cell invasion through p65 NF-κB- and HDAC1-mediated expression and activation of uPA.