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Pharmacological relevance Paclitaxel (PTX) is currently the only botanical drug that can control the growth of cancer cells. Paclitaxel is widely used in the treatment of breast cancer, ovarian cancer, uterine cancer, non-small cell lung cancer and other cancers. Aim Folate receptor and integrin α v β 3 are highly expressed on the surface of human breast cancer cells MCF-7. Folic acid and arginine-glycine-aspartate (Arg-Gly-Asp, RGD) tripeptide sequence have a high affinity for folate receptor and integrin α v β 3, respectively. To enhance the effect on breast cancer, we constructed the folate acid and RGD peptide dual-targeted (MSNs-NH2-FA-RGD) drug-carrier based on mesoporous silica nanoparticles. Methods The structure of mesoporous nanocarriers was characterized by Fourier transform infrared spectroscopy, nitrogen adsorption-desorption analysis, transmission electron microscopy, laser particle size analyzer, and thermogravimetric analysis. Paclitaxel was chosen as the model drug. The targeting-ability was verified by observing the uptake of mesoporous carriers loaded with rhodamine in MCF-7, MCF-10A, and HeLa cells using a fluorescence microscope. The cytotoxicity of the blank carrier MSNs-NH2-FA-RGD and the efficacy of the drug carrier PTX@MSNs-NH2-FA-RGD were assessed by cell experiments. Results The characterization showed successful construction of a dual-targeted mesoporous silica nanocarrier. Obvious differences were detected in the fluorescence intensity of the three cell lines. The results of the pharmacological tests indicated that the blank nanoparticles do not cause any apparent toxicity on these cells. The IC50 of free PTX and PTX@MSNs-NH2-FA-RGD on MCF-7 cells line treated for 48 h were 35.25±2.57 ng·ml-1 and 22.21±3.4 ng·ml-1 respectively, which indicated that the inhibitory efficacy of PTX@MSNs-NH2-FA-RGD on MCF-7 was 1.6 times than that of free PTX. Conclusions The dual-targeted nanocarrier MSNs-NH2-FA-RGD could target breast cancer cells, and sever as a potential candidate in future of drug development.

Background Due to the low rate of regional recurrence (RR) in early-stage breast cancer with pT1-2 and negative sentinel lymph node biopsy (SLNB), no regional therapy is suggested for them. However, whether there is a subset of patients who were with high risk of regional failure and may benefit from regional treatment is still unknown. The current study was designed to identify the patients with high risk of RR, thereby providing clues for enhanced regional therapy. Methods We analyzed a total of 1124 breast cancer patients with pT1-2N0 from May 2004 to Dec 2014. All the patients were treated with breast-conservation surgery (BCS) and adjuvant whole-breast radiotherapy. The regional recurrence-free survival (RRFS), local regional recurrence-free survival (LRRFS), disease-free survival (DFS) and overall survival (OS) were assessed by using the Kaplan–Meier method. Cox proportional hazards regression was performed to detect factors in predicting the RRFS. Results In multivariable analysis, both T stage and molecular type were significant predictors of RRFS. Patients with T2 stage had a lower RRFS than those with T1stage. Triple-negative patients were more likely to suffer regional failure than the patients with other molecular types. The two predictors were then employed to divide all the patients into three groups based on the risk level of RR. Patients with both T2 and triple-negative molecular type had the lower RRFS, LRRFS, DFS and OS than the patients with one or no risk factor. Conclusion For early-stage breast cancer patients with negative SLNB, those who were with both T2 stage and triple-negative molecular type had a high rate of RR and enhance regional therapy may be needed for them.

Background: Whether concurrent chemotherapy could bring about better oncological outcomes in elderly patients receiving definitive radiotherapy is still unknown. So, the purpose of this study was to find out whether it is essential for elderly patients to undergo concurrent chemotherapy. Methods: We performed a retrospective study of 246 elderly cervical cancer patients who were treated with definitive radiotherapy or chemo-radiation between August 2004 and August 2015. All patients were divided into two groups according to whether they were receiving concurrent chemotherapy or not. Overall survival (OS) and disease-free survival (DFS) were compared between the two groups. Recurrence patterns were also analyzed. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, local recurrence-free survival, and distant metastasis-free survival (DMFS). Results: The 5-year OS in the radiotherapy and chemo-radiation groups were 72.89% and 82.25%, respectively. A significant difference was found between the two groups (P=0.016). The 5-year DFS in the radiotherapy and chemo-radiaton groups were 58.19% and 75.52%, respectively, also with a significant difference between the two groups (P=0.028). Further subgroup analysis showed that in patients with negative lymph nodes, there were no differences in both OS and DFS between patients who did and did not receive concurrent chemotherapy. However, in patients with positive lymph nodes, patients who received concurrent chemotherapy acquired better OS and DFS than those who did not. Multivariable analysis showed that concurrent chemotherapy was an independent predictor of DFS and DMFS. Conclusion: Concurrent chemotherapy could improve oncological outcomes in elderly cervical cancer patients with positive lymph nodes, but not in those with negative lymph nodes.

In a multi-layered groundwater model, achieving accurate spatiotemporal identification and solving the ill-posed problem is the vital topic for model calibration. This study proposes a symmetry rank three vectorized loading scores (SR3 VLS) quasi-Newton algorithm by modifying the Levenberg&ndash, Marquardt algorithm and importing a rank three structure from Broyden&ndash, Fletcher&ndash, Goldfarb&ndash, Shanno algorithm for identification of hydrogeological parameters and spatiotemporal recharge simultaneously. To accelerate directional convergence and approach a global optimum, this study uses a vectorized limited switchable step size in the transmissive groundwater inverse problem. The Hessian approximation rank three uses high and low-rank factor loading scores analyzed from simulated storage fluctuation between adjacent iterations for calculation and matrix correction. Two numerical experiments were designed to validate the proposing algorithm, showing the SR3 VLS quasi-Newton reduced the error percentages of the identified parameters by 1.63% and 9.65% compared to the Jacobian quasi-Newton. The proposing method is applied to the Chou-Shui River alluvial fan groundwater system in Taiwan. Results show that the simulated storage error decreased rapidly in six iterations, and has good head convergence as small as 0.11% with a root-mean-square-error (RMSE) of 0.134 m, indicating that the proposing algorithm reduces the computational cost to converge to the true solution.

Recently, urban flooding has become an important issue due to heavy rainfall and rapid urbanization. For urban flooding, the drainage of stormwater is essential in inundation analysis, including the concentration of overland flow and the transportation in sewer system. However, in the past, the concentration of overland flow has not been well examined, especially under the influence of building structures. In the past, the overland flow in urban area is hard to calculate and causing lots of computation time. Currently, two-dimensional hydraulic models become an important tool for flood planning and management. In this study, we compare two hydraulic numerical models based of grid cell. So, we can flow pattern of overland flow in urban area for better understanding. First one is FLO-2D, which uses full dynamic wave momentum equation to predict the progression of a flood hydrograph. The second model is GSSHA, a physically-based, distributed model, which uses diffusive wave equation as governing equation to execute numerical simulation. With these two hydraulic models, this study focuses on how the constructions affect the water flow during the flood and whether they can be an important factor to influence the drainage system in urbanized area.Keywords: urban flooding simulation, two-dimensional hydraulic model, influence of buildings, rainfall-runoff model, FLO-2D, GSSHA

Cost-benefit analysis (CBA) is often applied at different levels of decision supports. CBA is a systematic approach to estimate the strengths and weaknesses of alternatives for decision makings. In many countries, CBA is required by law and regulation in different fields, including policy-making and public investment. The benefits of practicing the management of watershed conservation also need to be quantified so that decision-makers can understand engineering projects better. Applying CBA in watershed conservation can provide a comparison of total economic gains and losses resulting from practices and reveal impacts on different aspects with economic principles. Nevertheless, to quantify the benefits derived from watershed conservation, an array of technical relationships in various aspects which is still unclear requires to be developed. For this concern, this study examined several perspectives of watershed conservation to propose the framework of CBA in watershed conservation for Taiwan. In this study, we focused on four main kinds of sediment control facilities including check dam, embankment, slope protection, and groundsill work, and described the effect of sediment conservation based on theoretical sediment processes in spatial as well as temporal. We further analyzed their utilities from the perspective of the water supply. In addition to sediment control estimations, this study also determined some economic factors which were not determined in the past. We yielded a demand curve of raw water from the water supplying data and calculated a social discount rate from government bond rates. Also, we suggested adopting a general extreme value method to investigate the benefit under an extreme turbidity event and adopting an alternative costing method to estimate the water quality improvement benefits. This framework is successfully applied in Taiwan for the evaluation of watershed conservation projects. With this framework, engineers could perform economic CBA for reservoir watershed conservations more efficiently, practically, and precisely.Keywords: Watershed conservation, Economic cost-benefit analysis, Sediment control, Reservoir management

This study developed a multi-layer hydrodynamic and sediment transport model for simulating tides and the estuarine flows. The flow circulation in an estuary shows complicated mixing and stratification patterns due to the combined effects from currents and tides. This kind of issues becomes more important in Taiwan in line with the more and more frequent sediment flushing operation which led to high sediment concentration flow at the estuary. In some applications, three-dimensional (3D) models solving full Navier-Stokes equations were used. However, the extremely high computational cost, especially for the large-scale environmental problems, is always a serious concern. In the past years, continuous efforts have been devoted to the development of efficient quasi-three-dimensional models under hydrostatic and Boussinesq assumptions. Following the same state-of-the-art modelling strategy, this study develops a multi-layer shallow-water and sediment transport model with finite volume method. In this model, a terrain following coordinate with high local resolution is used to vertically divide the computational domain into multiple layers to better addressing bottom topography and velocity profile. Our model is rigorously validated against several benchmark cases including winddriven circulation, subcritical flow over a hump, tidal wave propagation, and sediment transport. The grid convergence test and accuracy both are in good agreement with analytical solutions. Subsequently, the model is applied to investigate the estuary dynamics and sediment transport under different conditions, e.g., flow discharges, bottom slopes, wind shears and tidal variations. Overall, the results show a relationship between flow conditions and sediment transport. Later, some scenarios for various upstream inflow and sediment concentration will be examined to assess the reservoir operation rules. Keywords: shallow water, sediment transport, multi-layer, hydrostatic, Boussinesq Assumption, a finite volume characteristics (FVC) method

Background: Triggering receptor expressed on myeloid cells (TREM)-1is identified as a major upstream proatherogenic receptor. However, the cellular processes modulated by TREM-1 in the development of atherosclerosis and plaque destabilization has not been fully elucidated. In this study, we investigated the effects of TREM-1 on dendritic cell maturation and dendritic cell–mediated T-cell activation induced by oxidized low-density lipoprotein (ox-LDL) in atherogenesis. Methods: Human peripheral blood monocytes were differentiated to dendritic cells and stimulated by ox-LDL. Naive autologous T cells were co-cultured with pretreated dendritic cells.The expressionof TREM-1 and the production of inflammatory cytokines were assessed by real-time PCR, western blot and ELISA.The expression of immune factors was determined with FACS to evaluate dendritic cell maturation and T-cell activation. Results: Stimulation with ox-LDL promoted dendritic cell maturation, TREM-1 expression and T-cell activation, and exposure of T cells to ox-LDL-treated dendritic cells induced production of interferon-γ and IL-17. Blocking TREM-1 suppressed dendritic cell maturation with low expression of CD1a, CD40, CD86 and HLA-DR, decreased production of TNF-α, IL-1β, IL-6 and MCP-1, and increased secretion of TGF-β and IL-10. In addition, stimulation of ox-LDL induced miR-155, miR-27, Let-7c and miR-185 expression, whereas inhibition of TREM-1 repressed miRNA-155. Silencing TREM-1 or miRNA-155 increased SOCS1 expression induced by ox-LDL. T cells derived from carotid atherosclerotic plaques or healthy individuals showed similar result patterns. Conclusion: These data suggest that TREM-1 modulates maturation of dendritic cells and activation of plaque T cells induced by ox-LDL, a pivotal player in atherogenesis.

We propose a uniform backfire-to-endfire leaky-wave antenna (LWA) based on a topological one-way waveguide under external bias magnetic field. We systematically analyze the dispersion, showing that the proposed structure supports leaky mode arisen from total internal reflection. By means of tuning frequency or magnetic field, we obtain fixed-bias frequency and fixed-frequency bias LWA with continuous beam scanning from backward, broadside to forward direction. More importantly, we, for the first time, demonstrate that this proposed LWA shows mechanical tunability, allowing us to manipulate the radiation direction from backward, broadside to forward direction by mechanically tuning the air layer thickness. The simulated results show that our system exhibits super low 3dB beam width, high radiation efficiency as well as high antenna gain. Being provided such multiple controlled (especially mechanically) beam scanning manners, the present LWA paves an advanced approach for continuous beam scanning, holding a great potential for applications in modern communication and radar system.

Inspired by the ‘advanced’ Western experience, China has implemented the New Curriculum Reform promoting learner-centred education since 2001. The OECD has identified this reform as a key feature contributing to Shanghai’s ‘PISA success’, worthy in turn of re-imitation by the West. Drawing upon official documents and interview data, this article shows that learner-centred education has been well accepted in rhetoric, which has led to more time being given to pupil activities. However, in reality, teaching and learning practices have continued to reflect what Confucian scholars have persistently advocated. Moreover, this article illustrates that the ‘round trip’ of learner-centred education between the East and the West has only taken place on the surface. The Chinese government has relied on the transformed Western concept for policy legitimacy, while international policy agencies have nevertheless deployed the case of China as an ideal exemplar to justify this Western concept as a global ‘best pr...

Background The tumor–node–metastasis (TNM) staging system does not perform well for guiding individualized induction or adjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). We attempted to externally validate the Pan’s nomogram, developed based on the 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system, for patients with locoregionally advanced disease. In addition, we investigated the reliability of Pan’s nomogram for selection of participants in future clinical trials. Methods This study included 535 patients with locoregionally advanced NPC who were treated between March 2007 and January 2012. The 5-year overall survival (OS) rates were calculated using the Kaplan–Meier method and compared with predicted outcomes. The calibration was tested using calibration plots and the Hosmer–Lemeshow test. Discrimination ability, which was assessed using the concordance index, as compared with other predictors. Results Pan’s nomogram was observed to underestimate the 5-year OS of the entire cohort by 8.65% [95% confidence interval (CI) − 9.70 to − 7.60%, P

Stent implantation has been proven to be safe and has become the first-line intervention for May-Thurner syndrome (MTS), with satisfactory mid-term patency rates and clinical outcomes. Recent research has demonstrated that catheter-directed thrombolysis is the preferred strategy when MTS is combined with deep vein thrombosis after self-expanding stent placement. However, the stent used for the venous system was developed based on the experience obtained in the treatment of arterial disease. Consequently, relatively common corresponding complications may come along later, which include stent displacement, deformation, and obstruction. Different measures such as adopting a stent with a larger diameter, improving stent flexibility, and increasing stent strength have been employed in order to prevent these complications. The ideal venous stent is presently being evaluated and will be introduced in detail in this review.

This study investigated the preparation of ethylene-vinyl acetate copolymer (EVA) and silicone rubber blends using a melt-blending method. EVA/Silicone-D blends were prepared by using peroxide (Dicumyl peroxide, DCP) as a crosslinking agent. The microstructure, thermal properties, and shape memory behavior were investigated for the EVA/Silicone-D blends. DCP not only could assist the crosslinking of EVA and silicone, but also increase the compatibility of blends. Silicone tended to endow the prepared EVA/silicone shape memory blends with high thermal stability, hydrophobicity, and recovery magnitude. The crystal orientation and crosslinking effects of EVA/Silicone-D blends played key roles in the shape memory behavior. Two-dimensional X-ray diffraction analysis revealed the increased crystal orientation with increasing loads. The one-way shape memory results demonstrated that both Rf (shape fixing ratio) and Rr (shape recovery ratio) values were above 97% after three consecutive shape memory cycles. From two-way shape memory results, it was observed that Ract, actuation magnitudes, contributed from the cooling-induced elongation increased with increasing loads and EVA contents. In addition, owing to this increased molecular orientation with increasing loads, the entropy-driven contribution relative to the overall actuation magnitudes increased accordingly. However, the shape memory response was hindered, when the load exceeded a critical value. With increasing silicone contents, the entropy-driven contribution decreased due to the reduced orientation degree at the tighter networks or increased crystalline EVA contents in the blends.

ObjectivesThe optimal interval between surgery and adjuvant treatment has not yet been found in cervical cancer. And whether patients with different FIGO stage should choose different interval is unknown. The purpose of this study was to evaluate whether interval has a different effect on oncologic outcome for patients with different tumor stages.MethodsWe performed a retrospective study of 226 cervical cancer patients who were treated by surgery and adjuvant therapy from May 2005 to August 2015. All patients were divided into 2 groups according to the interval of 5 weeks. Overall survival (OS) and disease-free survival (DFS) were compared between patients with interval shorter and longer than 5 weeks in the whole group and subgroups. Recurrence patterns were also analyzed. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, local recurrence-free survival and distant metastasis-free survival for patients with stage IB2–IIA.ResultsFor patients with stage IA2–IB1, the 5-year OS and DFS were similar between groups of short and long interval with also the comparable results of local and distant failure. For patients with IB2–IIA, both the OS and DFS in the short-interval group were higher than that in the long-interval group. Besides, the rates of local recurrence were found higher in the group of long interval compared with short interval. Multivariable analysis indicated that time interval was an independent predictor of DFS and local recurrence-free survival for patients with stage IB2–IIA.ConclusionsIn cervical cancer patients, time interval between surgery and adjuvant therapy may have different effects on the prognosis in different FIGO stages.

Background Endothelial cells are sensitive to changes in both blood components and mechanical stimuli. Endothelial cells may undergo phenotypic changes, such as changes in adhesion protein expression, under different shear stress conditions. Such changes may impact platelet and monocyte adhesion to endothelial cells. This phenomenon is linked to chronic vascular inflammation and the development of atherosclerosis. In the present study, we investigated the effects of ginkgolide B on platelet and monocyte adhesion to human umbilical vein endothelial cells (HUVECs) under different conditions of laminar shear stress. Methods Platelet and monocyte adhesion to endothelial cells was determined by the Bioflux 1000. HUVECs were incubated with ginkgolide B or aspirin for 12 h, and then TNFα was added for 2 h to induce the inflammatory response under conditions of 1 and 9 dyn/cm2 laminar shear stress. The protein expression was analyzed by Western blot. Results The number of platelets that adhered was greater under conditions of 1 dyn/cm2 than under conditions of 9 dyn/cm2 of laminar shear stress (74.8 ± 19.2 and 59.5 ± 15.1, respectively). Ginkgolide B reduced the tumor necrosis factor α (TNFα)-induced increase in platelet and monocyte adhesion to HUVECs at 1 and 9 dyn/cm2 of laminar shear stress. In TNFα-treated HUVECs, the number of monocytes that adhered was greater under conditions of 1 dyn/cm2 of laminar shear stress compared with 9 dyn/cm2 (29.1 ± 4.9 and 22.7 ± 3.7, respectively). Ginkgolide B inhibited the TNFα-induced expression of vascular cell adhesion molecule-1(VCAM-1), VE-cadherin, and Cx43 in HUVECs at 1 and 9 dyn/cm2. The expression of these proteins was not different between 1 and 9 dyn/cm2. Conclusions Ginkgolide B suppressed platelet and monocyte adhesion under different conditions of laminar shear stress. Moreover, ginkgolide B reduced VCAM-1, VE-cadherin and Cx43 expression in TNFα-treated HUVECs under laminar shear stress. This suggested that ginkgolide B might shed light on the treatment of inflammation in atherosclerosis.

Objective To investigate the effects of necroptosis induced by vibrio vulnificus cytolysin (VVc) on immortalized bone marrow-derived macrophage cell line (iBMDM) and its mechanism. Methods The iBMDM were divided into five groups, control group, VVc(2μg/ml) group, VVc(4μg/ml) group, Necrostatin-1 (Nec-1)+VVc(2μg/ml) group, Nec-1+VVc(4μg/ml) group based on the concentration of VVc and whether the cells received receptor interacting protein 1 (RIP1). In the RIP1 inhibited groups, iBMDM was pretreated with Nec-1 (5μmol/L) before stimulation with VVc. Cells and culture supernatant were harvested at 2h after the challenge by cytolysin. Lactate dehydrogenase (LDH) activity in cell-culture supernatant following VVc stimulation was determined to evaluate cell death. The cell state was detected by flow cytometry with Annexin V/propidium iodide staining, and the expression of phosphorylated mixed lineage kinase domain-like (MLKL) and pyroptosis- and necroptosis-related proteins (caspase-1, caspase-11, gasdermin D) were detected by Western blotting. Results The LDH level in the culture supernatant was increased in the groups stimulated by VVc and could also be inhibited by pretreatment with Nec-1 (P＜0.05). Compared with control and RIP1- inhibited groups, the VVc-treatment induced a high amount of the double positive staining cells in the VVc group (P＜0.05). In the RIP1 inhibited groups, Nec-1 pretreatment could significantly decrease the levels of pMLKL (P＜0.05), compared with VVc group. None of the cleaved pyroptosis-related protein was detected by Western blotting. Conclusion Necroptosis induced by RIP1 may play an important role in VVc injury model of iBMDM, furthermore, Nec-1 could reduce the degree of injury after VVc challenge. DOI: 10.11855/j.issn.0577-7402.2018.05.11

This paper presents three observer/Kalman filter identification (OKID) approaches and develops a robust observer-based optimal linear quadratic digital tracker (LQDT) for the five-degree-of-freedom (five-DOF) sampled-data active magnetic bearing (AMB) system with various disturbances. The more detailed objectives are: (i) to construct both an equivalent linear time-invariant discrete-time model and its state estimator via the proposed OKID approaches for the AMB system, which might be an unknown nonlinear time-varying unstable system with both a specified rotation speed and a sampling rate; (ii) to provide an adaptive disturbance estimation scheme, which establishes an equivalent input disturbance (EID) estimator for the AMB system with unexpected disturbances; and (iii) to develop a robust observer-based optimal LQDT for the sampled-data AMB system with both a pre-specified time-varying speed and unexpected disturbances. The developed LQDT is able to recover the displacement of the rotor to the p...

One-way electromagnetic mode that is guided by the mechanism of total internal reflection (TIR) can be realized in terahertz regime. In the optical system consisting of a dielectric layer sandwiched between magnetized semiconductor and metal, the one-way TIR mode can be immune to backscattering at imperfections. This mode possesses a broad band when high-order TIR modes are suppressed in the relevant semiconductor bandgap. Furthermore, it is shown that compared with one-way surface magnetoplasmons, the one-way TIR mode can more effectively match with the fundamental mode of conventional optical waveguide.

In this study, we developed a method to assess influence of different medical tubing on biofilm formation by A. baumannii. The results of biofilm quantification and scanning electron microscopy showed that the biofilm formation susceptibility of different tubing materials was rubber latex > polyvinyl chloride > silicone.

The formation of tectonic magmatic-related emerald deposits necessarily invokes a mixing model of Be-rich granitic rocks and Cr and/or V-rich surrounding rocks. However, there has been continuing debate on the deposit genesis, with the essential controversy being the relative significance of magma versus metamorphism in mineralizing as well as the key triggers for emerald deposition. The Dayakou emerald deposit genetically related to the Cretaceous granitic magmatism and hosted within the Neoproterozoic metasedimentary rocks is an ideal study case to probe into the above outstanding issue. In this paper, three hydrothermal mineralization and related alteration stages have been recognized in Dayakou, comprised of the greisenization and early emerald mineralization in high-temperature hydrothermal condition (stage-I; peak at 380 °C to 480 °C), the silicification and main emerald mineralization in medium–high temperature fluid (stage-II; peak at 300 °C to 360 °C) and the late carbonate alteration and scheelite mineralization (stage-III). Analysis results of fluid inclusion and C–H–O isotopes of emeralds and associated minerals suggest that ore-forming fluids belong to the H2O–NaCl ± CO2 system with minor H2S, CH4, and N2, exsolved from the Cretaceous granites and gradually interacted with the surrounding metamorphic rocks. We combine the new data with those reported in earlier studies to further propose a genesis scenario for the Dayakou deposit, in which Be-bearing fluids originally exsolved from peraluminous melts and fluoride complexes may be an effective transport proxy for Be in hydrothermal fluids. Fluid boiling during fluid ascent leads to the significant fractionation and enrichment of elements and the escape of volatiles (e.g., HF, H2O, CO2) in ore system. Meanwhile, sustained fluid-rock interaction (e.g., greisenization) increasingly extracts Cr, V and Ca into fluids to facilitate mineral precipitation, wherein the crystallization of fluoride minerals would cause the destabilization of Be-F complexes. Our study indicates that fluid boiling and fluid-rock interactions are the primary triggers for emerald deposition.

BackgroundPancreatic ductal adenocarcinoma (PDA) is a lethal malignancy characterized by a highly suppressive tumor microenvironment. Despite this, engineered T cell therapy has promise for effectively targeting PDA. To identify the underlying mechanisms of antigen-specific engineered T cell immunosuppression in PDA, we create novel TCR knock-in mouse models for a robust and standardized source of naïve mesothelin (Msln)-specific T cells.MethodsSpecifically, we integrate two murine mesothelin-specific TCRs into the physiologic Trac locus in primary murine T cells and zygotes using CRISPR/Cas9 and rAAV expressing the TCR DNA. Simultaneously using CRISPR/Cas9, Msln was disrupted to circumvent T cell tolerance.ResultsThis strategy resulted in the rapid generation of homozygous TCR Trac knock-in mice and with homozygous null mutations in Msln. In these TCR-exchanged (TRex) mice, most T cells expressed the 1045 (high affinity) or 7431 (low affinity) as determined by tetramer staining. TRex T cells exhibit a naïve phenotype and rapidly differentiate into effector T cells upon antigenic stimulation. While the high affinity 1045 TCR elicits function in CD4 T cells, the lower affinity 7431 T cells exhibit a higher functional avidity and less TCR downregulation when antigen is limiting. Historical TCR transgenic T cells, in which the TCR is randomly integrated into the genome, exhibit increased PD1, CD25, and CD69, decreased functionality, and a bias to CD25-Foxp3+ Treg as compared to T cells from TRex mice. Further, TCR Trac integration in primary T cells retain superior function following repetitive antigenic stimulations retrovirally transduced T cells. Adoptive transfer of 1045 TRex T cells significantly prolongs survival of mice bearing autochthonous PDA. When combined with a vaccine, 1045 TRex T cells cause involution of the fibroinflammatory tumor stroma.ConclusionsIn sum, we rapidly generate mice that physiologically express the desired TCR, circumventing the shortcomings of standard T cell engineering strategies and TCR transgenic models.Ethics ApprovalUniversity of Minnesota Institutional Animal Care and Use Committee approved all animal studies to Dr. Ingunn Stromnes (2005-38115A.) Generation of TCR knockin (KI) animals was performed in the Mouse Genetic Laboratory at the University of Minnesota.

Photonic crystal (PhC) consisting of a square lattice of ferrite rods with remanence in the air is theoretically investigated. It is shown that such a PhC can possess a large band gap with a nontrivial topological property. By interfacing the PhC with different cladding materials, which have (bulk-mode) band gaps with different topological properties, different types of one-way modes that are immune to backscattering are achieved in the absence of an external magnetic field. It is numerically demonstrated that by using such one-way modes, waves can be flexibly and effectively manipulated in PhC systems without almost any power loss.

Objective To evaluate the effect of intracarotid cold saline infusion (ICSI) on neurological outcomes in canines with cardiac arrest (CA) introduced by severe hypothermia. Methods Restoration of spontaneous circulation (ROSC) after hypothermic CA was induced in 10 Beagle dogs. These 10 dogs were randomly divided into 2 groups (5 each). Dogs in control group were rewarmed using warn water bath, and dogs in experimental group received the bath rewarming plus ICSI for 6 hours to maintain the brain temperature

Objectives We aimed to validate and compare the 7th and 8th edition of AJCC staging systems for non-metastatic nasopharyngeal carcinoma, and proposed staging systems from Hong Kong, Guangzhou, and Guangxi. Materials and methods We retrospectively included 899 patients treated between November 5, 2002 and May 27, 2010. Separation and discrimination of each staging system in overall survival were primarily compared. Results Compared with the 7th AJCC, the 8th AJCC and all proposed staging systems well separated across T-classification. T-classification from Guangzhou seemed to perform best in discrimination (C-index 0.6454), followed by the 8th AJCC (0.6451), the 7th AJCC (0.6386), Hong Kong (0.6376) and Guangxi (0.5889). For N-classification, no staging systems improved the weakness of the 7th AJCC in separating N2 and N1, except that suggestion from Guangzhou showed higher potential ( P = 0.096). Besides, N-classification from Guangzhou had a C-index of 0.6444, larger than that of the 8th AJCC (0.6235), the 7th AJCC (0.6179), Hong Kong (0.6175) and Guangxi (0.6175). Accordingly, stage group of staging system from Guangzhou showed higher discrimination (C-index 0.6839), compared with the 8th AJCC (0.6791), the 7th AJCC (0.6766), Hong Kong (0.6765) and Guangxi (0.6688), despite that stage I and II remained inseparable ( P = 0.322). Conclusions The 8th AJCC staging system appeared to be better than the 7th AJCC. But the proposed staging system from Guangzhou was more likely to improve the separation and discrimination abilities.

Education reforms in England are increasingly justified by borrowing ‘best practices’ of high-performing East Asian societies, including Hong Kong, Singapore and Shanghai. However, taking the reforms of school accountability as an illustrative example, this article argues that there are serious variations between England and its East Asian sources of ‘borrowing’ with regard to the ways in which schools are held to be accountable. How school accountability is organised and operationalised in practice deeply depends on socio-political priorities of each society. Therefore, education policy borrowing from East Asia to England is potentially extremely difficult. Furthermore, this article remains alert to the possibility that the claim (about improving the education system in England through imitating East Asian models) is symbolic rather than practical – symbolic in the sense of producing legitimacy for pre-existing policy agendas.

Efflux pumps play an important role in antimicrobial resistance for Acinetobacter baumannii. However, the function of the Emr pump system and the relationship between Emr and drug resistance has not been characterized in A. baumannii. In this study, four possible groups of emr-like genes were found by searching a genome database. Among them, A1S_1772 (emrB) and A1S_1773 (emrA) were demonstrated to be co-transcribed as a single operon. Moreover, during osmotic stress, A1S_1772 showed the largest change in gene expression compared to the other emrB-like genes, and deletion of A1S_1772 (AB ΔemrB) significantly slowed cell growth in 20% sucrose. Using a phenotypic microarray analysis, the AB ΔemrB mutant was more susceptible to colistin and nafcillin, paromomycin, spiramycin, and D,L-serine hydroxmate than the wild type. The spot assay, time kill assay and minimal inhibition concentration determination also indicated that the wild type could tolerate colistin better than the AB ΔemrB mutant. Finally, the increased expression levels of all emrB-like genes, including A1S_0775, A1S_0909, A1S_1772, and A1S_1799, in colistin resistance-induced A. baumannii further supported the possible involvement of the emrB genes in A. baumannii colistin resistance. Together, the Emr pump systems in A. baumannii contribute to adaptation to osmotic stress and resistance to colistin.

TFT-LCD面板在屏幕上有斑点或波浪状Mura，影响液晶显示器的品质，经过图形匹配，缺陷与曝光机机台形貌匹配。通过对异常区域特性分析，发现异常区域的BMCD、BM像素间距存在异常。对原因进行模型分析：玻璃在曝光机基台上局部区域发生弯曲，曝光距离变短，致使BMPR受光区域变小，BMCD会偏小，进而导致区域性透过光不均一产生Mura；玻璃弯曲后BM像素间距相对于设计位置也会发生变化，从而导致漏光产生Mura。经过实验验证，BMCD和像素间距的偏差主要由机台凸起导致glass弯曲引起，可以通过降低吸附压力和研磨机台，来改善CD差异和像素间距偏移，同时像素间距偏移漏光，也可以通过增加CD来改善。最终通过BMCD增加、研磨机台和降低吸附压力措施，Stage Mura不良率由10.05%下降至0.11%。

New technology tends to invite speculation on the future of societies, inspiring visions of both hope and horror. This chapter continues that tradition, exploring the application of emerging technology, such as artificial intelligence (AI), cloud computing, and the Internet of Things (IoT) to processes of governance and learning in education. Drawing on both utopian visions and twin nightmares of machinic-dystopias, the analysis reflects on the application of new technology designed to fulfill the UN’s post-2015 agenda in education. In highlighting divergent traditions, the analysis then shifts to the application of the same technology in China as part of the Chinese Dream, under which the Chinese government aims to become the world leader in AI while revitalizing the nation’s cultural traditions. These ambitions are explored through the introduction of Smart Cities, a system of Social Credit, and Smart Schools. Finally, the chapter reflects on these visions of twenty-first century pedagogy and possible resources for thinking about a future that cannot be fully apprehended.

Acinetobacter baumannii, an important emerging pathogen of nosocomial infections, is known for its ability to form biofilms. Biofilm formation increases the survival rate of A. baumannii on dry surfaces and may contribute to its persistence in the hospital environment, which increases the probability of nosocomial infections and outbreaks. This study was undertaken to characterize the biofilm production of different strains of A. baumannii and the effects of chemical compounds, especially antibiotics, on biofilm formation. In this study, no statistically significant relationship was observed between the ability to form a biofilm and the antimicrobial susceptibility of the A. baumannii clinical isolates. Biofilm formation caused by A. baumannii ATCC 17978 after gene knockout of two-component regulatory system gene baeR, efflux pump genes emrA/emrB and outer membrane coding gene ompA revealed that all mutant strains had less biofilm formation than the wild-type strain, which was further supported by the images from scanning electron microscopy and confocal laser scanning microscopy. The addition of amikacin, colistin, LL-37 or tannic acid decreased the biofilm formation ability of A. baumannii. In contrast, the addition of lower subinhibitory concentration tigecycline increased the biofilm formation ability of A. baumannii. Minimum biofilm eradication concentrations of amikacin, imipenem, colistin, and tigecycline were increased obviously for both wild type and multidrug resistant clinical strain A. baumannii VGH2. In conclusion, the biofilm formation ability of A. baumannii varied in different strains, involved many genes and could be influenced by many chemical compounds.

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We propose a Leaky-Wave Antenna (LWA) based on one-way yttrium-iron-garnet (YIG)-air-metal waveguide. We first analyze the dispersion of the LWA, showing the one-way feature and the radiation loss. Owing to the unique one-way dispersive property, the beam radiated from the LWA can have very narrow beam width, at the same time having large scanning angle. The main beam angle obtained by full-wave simulation is consistent with our theoretical prediction with the aid of the dispersion. For a given frequency, we can realize continuous beam scanning by varying the magnetic field, where the 3 dB beam width is much narrower than previously demonstrated. Our results pave a new way to realize continuous angle scanning at a fix frequency for modern communications.