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Atomically two-dimensional (2D) materials have generated widespread interest for novel electronics and optoelectronics. Specially, owing to atomically thin 2D structure, the electronic bandgap of 2D semiconductors can be engineered by manipulating the surrounding dielectric environment. In this work, we develop an effective and controllable approach to manipulate dielectric properties of h-BN through gallium ions (Ga+) implantation for the first time. And the maximum surface potential difference between the intrinsic h-BN (h-BN) and the Ga+ implanted h-BN (Ga+-h-BN) is up to 1.3 V, which is characterized by Kelvin probe force microscopy. More importantly, the MoTe2 transistor stacked on Ga+-h-BN exhibits p-type dominated transfer characteristic, while the MoTe2 transistor stacked on the intrinsic h-BN behaves as n-type, which enable to construct MoTe2 heterojunction through dielectric engineering of h-BN. The dielectric engineering also provides good spatial selectivity and allows to build MoTe2 heterojunction based on a single MoTe2 flake. The developed MoTe2 heterojunction shows stable anti-ambipolar behaviour. Furthermore, we preliminarily implemented a ternary inverter based on anti-ambipolar MoTe2 heterojunction. Ga+ implantation assisted dielectric engineering provides an effective and generic approach to modulate electric bandgap for a wide variety of 2D materials. And the implementation of ternary inverter based on anti-ambipolar transistor could lead to new energy-efficient logical circuit and system designs in semiconductors.

Efficient modulation of carrier concentration is fundamentally important for tailoring the electronic and photoelectronic properties of semiconducting materials. Photoinduced doping is potentially a promising way to realize such a goal for atomically thin nanomaterials in a rapid and defect-free manner. However, the wide applications of photoinduced doping in nanomaterials are severely constrained by the low doping concentration and poor stability that can be reached. Here, we propose a novel photoinduced doping mechanism based on the external photoelectric effect of metal coating on nanomaterials to significantly enhance the achievable doping concentration and stability. This approach is preliminarily demonstrated by an MX2 (M is Mo or Re; X is S or Se) nanoflake modified through a simple process of sequentially depositing and annealing an Au layer on the surface of the flake. Under ultraviolet (UV) light illumination, the modified MX2 achieves degenerated n-type doping density of 1014 cm-2 rapidly according to the experimentally observed >104 times increment in the channel current. The doping level persists after the removal of UV illumination with a nonobservable decrease over 1 day in vacuum (less than 23% over 7 days under an ambient environment). This photoinduced doping approach may contribute a major leap to the development of photocontrollable nanoelectronics.

High-performance p–n junctions based on atomically thin two-dimensional (2D) materials are the fundamental building blocks for many nanoscale functional devices that are ideal for future electronic and optoelectronic applications. The lateral p–n homojunctions with conveniently tunable band offset outperform vertically stacked ones, however, the realization of lateral p–n homojunctions usually require efficient carrier-type modulation in a single 2D material flake, which remains a tech challenge. In this work, we have realized effective carrier-type modulation in a single MoSe2 flake, and thus, a lateral MoSe2 p–n homojunction is achieved by sequential treatment of air rapid thermal annealing and triphenylphosphine (PPh3) solution coating. The rapid thermal annealing modulates MoSe2 flakes from naturally n-type doping to degenerated p-type doping and improves the hole mobility of the MoSe2 field effect transistors from 0.2 to 71.5 cm2·V–1·s–1. Meanwhile, the n-doping of MoSe2 is increased by drop-coating ...

Transition metal dichalcogenides (TMDCs) have recently become spotlighted as nanomaterials for future electronic and optoelectronic devices. In this work, we develop an effective approach to enhance the electronic and optoelectronic performances of WSe2-based devices by N2O plasma treatment. The hole mobility and sheet density increase by 2 and 5 orders of magnitude, reaching 110 cm2 V-1 s-1 and 2.2 × 1012 cm-2, respectively, after the treatment. At the same time, the contact resistance (Rc) between WSe2 and its metal electrode drop by 5 orders of magnitude from 1.0 GΩ μm to 28.4 kΩ μm. The WSe2 photoconductor exhibits superior performance with high responsivity (1.5 × 105 A W-1), short response time (2 ms), high detectivity (3.6 × 1013 Jones) and very large photoconductive gain (106). We have also built a lateral p-n junction on a single piece of WSe2 flake by selective plasma exposure. The junction reaches an exceedingly high rectifying ratio of 106, an excellent photoresponsivity of 2.49 A W-1 and a fast response of 8 ms. The enhanced optoelectronic performance is attributed to band-engineering through the N2O plasma treatment, which can potentially serve as an effective and versatile approach for device engineering and optimization in a wide range of electronic and optoelectronic devices based on 2D materials.

De novo CD5 positive diffuse large B cell lymphoma (CD5+ DLBCL) has poor survival in the era of immunochemotherapy. We conducted a multi-center retrospective study to explore the clinicopathologic characteristics, genomic profiling and prognostic elements of 61 CD5+ DLBCL and 60 CD5- DLBCL patients in China. In contrast with CD5- DLBCL, elderly onset, advanced stage, central nervous system (CNS) involvement, as well as MYC/BCL-2 and P53 overexpression were more prevalent in CD5+ DLBCL. In addition, most of CD5+ DLBCL patients were of non-germinal center B-cell-like (non-GCB) and activated B-cell-like (ABC) subtype according to immunohistochemistry and Lymph2Cx assay. Genetic analysis by next generation sequencing (NGS) showed the proportion of MCD subtype in CD5+ DLBCL was higher than that of CD5- DLBCL (50% vs 5%, p = 0.0007). Compared with CD5- cohort, CD5+ DLBCL patients showed poorer 5-year overall survival (OS) (70.9% vs 39.0%, p76 years, advanced stage, CNS involvement and hypoalbuminemia were independent factors associated with poor prognosis in CD5+ DLBCL. In conclusion, CD5+ DLBCL conveyed poor prognosis and showed distinctive clinicopathologic characteristics and predominant genetic features of ABC and MCD subtypes. Disclosures No relevant conflicts of interest to declare.

Hemophagocytic lymphohistiocytosis (HLH) is an immune disorder with rapid progression and poor survival. Individual treatment strategy is restricted, due to the absence of precise stratification criteria. In this multicenter retrospective study, we aimed to develop a feasible prognostic model for adult HLH in China. A total of 270 newly diagnosed patients of adult HLH were retrieved from Huaihai Lymphoma Working Group (HHLWG), of whom 184 from 5 medical centers served as derivation cohort, and 86 cases from 3 other centers served as validation cohort. X-Tile program and Maxstat analysis were used to identify optimal cut-off points of continuous variables; univariate and multivariate Cox analysis were used for variables selection, and Kaplan-Meier curve was used to analyze the value of variables on prognosis. The C-index, brier score and calibration curve were used for model validation. Multivariate analysis showed that age, creatinine, albumin, platelet, lymphocyte ratio and alanine aminotransferase were independent prognostic factors. By rounding up the hazard ratios from 6 significant variables, a maximum of 9 points was assigned. The final scoring model of HHLWG-HPI was identified with four risk groups: low risk (≤3 pts), low-intermediate risk (4 pts), high-intermediate risk (5-6 pts), and high risk (≥7 pts), with 5-year overall survival rates of 68.5%, 35.2%, 21.3%, and 10.8%, respectively. The C-indexes were 0.796 and 0.758 in derivation and validation cohort by using bootstrap resampling program. In conclusion, the HHLWG-HPI model provides a feasible and accurate stratification system for individualized treatment strategy in adult HLH. Disclosures No relevant conflicts of interest to declare.

Elevated Epstein-Barr virus (EBV) DNA load is common in lymphomas. However, it remains unclear whether the disparity in viral load and its prognostic value in lymphomas are correlated with EBER status. In this retrospective multicenter study, we collected the data of pretreatment whole blood EBV DNA (pre-EBV DNA) and EBER status and evaluated their disparity and prognostic values in lymphomas. A total of 454 lymphoma patients from December 2014 to August 2020 were retrospectively retrieved. Mann-Whitney U test, Kruskal-Wallis test, and Bonferroni's adjustment were used to explore the disparity of EBV DNA and EBER status in lymphomas. Time-dependent receiver operating characteristic analysis and MaxStat analysis were used to determine optimal cut-off points of pre-EBV DNA load. Univariable and multivariable Cox proportional hazards models were established for the estimation of prognostic factors. The positive rate of EBV-DNA in NKTL patients was higher than that in DLBCL, FL, and HL patients, and the median positive pre-EBV copy number of NKTL was also higher than that of FL and DLBCL. EBV-DNA could clearly distinguish the prognosis of DLBCL, NKTL, HL and PTCL, and the integration of EBER status and EBV DNA could differentiate the prognosis of HL patients. Multivariable results revealed that pre-EBV DNA load had an effect on the prognosis of NKTL, FL and DLBCL. The status of pre-EBV DNA and EBER were disparate. Whole blood pre-EBV DNA predicted the prognosis of lymphomas, and the integration of EBV and EBER status could differentiate the prognosis of HL Disclosures No relevant conflicts of interest to declare.

The surface resistance to oil is very important for filtration efficiency, film cleaning and life span of ultrafiltration membranes. The atomic force microscope (AFM) has provided unprecedented opportunities to study interface interactions. In this paper, the probe with an oil droplet modified was used as a force sensor for evaluating the oil resistance of membrane surfaces. The adhesion forces between two types of modified tips and a serial of membrane surfaces in fluid was detected via force curves. On the one hand, the AFM probe with an oil droplet immobilized directly was used to study the adhesion forces between a series of PVF/F127 membranes and a hexadecane droplet. On the other hand, a tip attached polystyrene (PS) microsphere covered with a layer of oil was employed. It was found that the oil antifouling performance of membranes was improved effectively through blending F127 with PVF. As the F127 additive varied from 0% to 60%, adhesion force detected by the AFM probe with an hexadecane droplet immobilized showed a decreasing tendency from 2.84 nN to 0.73 nN. Meanwhile, the average interaction force detected by the second modified tip decreased from 3.39 nN to 0.54 nN. The measured force behavior was in agreement with experimental observations of contact angle measurement, which indicated that the blend membranes had better antifouling.

For water treatment applications, fabricating a high permeation flux membrane with super-strong mechanical strength and excellent long-term antifouling properties remains a great challenge. In this study, robust, antifouling carbon nanotube (CNT) nanohybrid membranes have been fabricated for oil/water separation. Polyethyleneimine (PEI) with abundant amino groups and a hyperbranched structure is utilized to construct a nanocoating on a CNT surface to enhance their hydrophilicity through multiple interactions between PEI and CNTs. Secondly, the vacuum-assisted self-assembly method is utilized to fabricate free-standing membranes by filtration of CNT dispersions. Finally, trimesoyl chloride (TMC) is utilized to post-modify membranes to enhance the mechanical strength and hydrophilicity and change the surface charge through reaction between amino groups and acyl chloride groups as well as hydrolysis of acyl chloride groups into carboxyl groups. The controlled stacking of CNTs renders membranes with a hierarchical nanostructure and a high porosity, leading to high water flux. The physical and chemical crosslinking renders membranes with high mechanical strength, as measured by atomic force microscopy (AFM) and tensile strength tests. The high hydrophilicity and negatively charged surface render membranes with good antifouling properties, as evaluated by filtration experiments of various oil-in-water emulsions. This study may reveal the great prospects of CNT-based membranes with superior comprehensive properties in water treatment relevant applications.

Herein, through a facile and energy-friendly approach, thermally stable manganese-derived amorphous stacked nanosheet (MASNS) coatings with controlled wetting property ranging from superhydrophilicity to superhydrophobicity were synthesized. The superhydrophobic MASNS coating exhibited remarkable selectivity and sensitivity in the solid phase microextraction (SPME) of non-polar aromatic analytes, even amid the abundance of polar compounds, due to the superhydrophobic effect and the stacked lamellar structures. The established method was applied to the determination of polycyclic aromatic hydrocarbons (PAHs), featuring low LODs (i.e., 0.14–0.24 ng L−1) and wide linear ranges (e.g., 10–10000 ng L−1). Extraction and desorption conditions were optimized to unleash the potential of the fiber before it was applied to the analysis of target analytes in real water samples, where satisfactory recoveries were obtained (81.7%–114.2%). This work might provide critical insights for the scalable production of superhydrophobic nanosheets as affordable and high-performance adsorbents.

Herein, a novel solid-phase microextraction (SPME)fiber based on hollow carbon nanobubbles was developed for the analysis of persistent organic pollutants. The hollow carbon nanobubbles (HCNBs), derived from the nanoscale zeoliticimidazolate framework (ZIF-8), not only possessed the ZIF-8-like microporous shell but also created an internal space for analytes storage. This architecture was beneficial to accelerating the mass transfer process and enhancing the enrichment capacity towards target analytes. As a result, the sensitivity of this HCNBs based SPME fiber toward analytes (e.g., BTEX, PAHs and PCBs) was 2–180 times higher compared with the commercial fibers (100 μm PDMS, 65 μm PDMS/DVB or 85 μm PA). In addition, owing to the size-selectivity of the microporous shell, the HCNBs-based SPME fiber showed high extraction ability towards target analytes with low molecule weight. Furthermore, the lifespan of the homemade fiber was evaluated to be more than 100 times attributing to the hard and stable carbon framework. Under optimal working conditions, analytical performance of the fiber towards PCBs with varying chlorination degrees showed a wide linear range (0.05–1000 ng L−1) and low LODs (0.0017–0.0042 ng L−1). Finally, the established method was successfully applied to the determinations of PCBs in three environmental water samples with good recoveries (84.5–117.1%).

Figure S1. Interaction domains between CFLARL and PRMT5 and PRMT1. A HEK293FT cells were transfected with the pcDNA3.1-FLAG-CFLARL plasmids and co-transfected with all sections of PRMT5 and the control plasmid. Then, the cells were harvested and prepared for the IP assay after 16 h. The cells were treated with 20 μmol/L MG132 for 4 h. The precipitated proteins were analyzed by western blotting. B HEK293FT cells were transfected with the pcDNA3.1-FLAG-CFLARL plasmids and co-transfected with the section of PRMT1 and the control plasmid. Then, the cells were harvested and prepared for the IP assay after 16 h. The cells were treated with 20 μmol/L MG132 for 4 h. The precipitated proteins were analyzed by western blotting. C HEK293FT cells were transfected with the pcDNA3.1-MYC-PRMT5 plasmids and co-transfected with all sections of CFLARL and the control plasmid. The cells were the harvested and prepared for the IP assay after 20 h, and the precipitated proteins were analyzed by western blotting. D HEK293FT cells were transfected with the pcDNA3.1-MYC-PRMT1 plasmids and co-transfected with all sections of CFLARL and the control plasmid. The cells were harvested, prepared for the IP assay after 16 h, and treated with 20 μmol/L MG132 for 4 h. The expression of the corresponding protein was calculated as described in (C). Figure S2. PRMT5 and PRMT1 modulated apoptosis in NSCLC cells. A and B H460 cells were seeded in 6-well plates. PcDNA3.1-PRMT5 were transfected for 24 h. Cells were treated with pemetrexed [5.0 μM] for 48 h. Cells were collected for Flow Cytometry analysis. C and D H460 cells were seeded in 6-well plates. PRMT5 siRNA were transfected for 48 h. Cells were treated with pemetrexed [5.0 μM] for 48 h. Cells were collected for Flow Cytometry analysis. E and F A549 cells were seeded in 6-well plates. PRMT1 siRNA were transfected for 48 h. Cells were treated with pemetrexed [5.0 μM] for 48 h. Cells were collected for Flow Cytometry analysis. (DOCX 14 kb)

Two-dimensional (2D) transition metal dichalcogenides (TMDCs) such as tungsten diselenide (WSe2) have spead many interesting physical properties, which may become ideal candidates to develop new generation electronic and optoelectronic devices. In order to reveal essential features of 2D TMDCs, it is necessary to fabricate high-quality devices with reliable electrical contact. We systematically analyze the effect of graphene and metal contacts on performance of multi-layered WSe2 field effect transistors (FETs). The temperature-dependent transport characteristics of both devices are tested. Only graphene-contacted WSe2 FETs are observed with the metal-insulator transition phenomenon which mainly attributes to the ultra-clean contact interface and lowered contact barrier. Further characterization on contact barrier demonstrates that graphene contact enables lower contact barrier with WSe2 than metal contact, since the Fermi level of graphene can be modulated by the gate bias to match the Fermi level of the channel material. We also analyze the carrier mobility of both devices under different temperatures, revealing that graphene contact can reduce the charge scattering of the device caused by ionized impurities and phonon vibrations in low and room temperature regions, respectively. This work is expected to provide reference for fabricating 2D material devices with decent performances.

Donor-derived CD4(+) T lymphocytes are the major effector cells directly involved in the development of graft-versus-host disease (GVHD). As a negative regulator of immune cell differentiation and development, microRNA-150 (miR-150) induces immunological tolerance in CD4(+) T cells after transplantation. However, the specific mechanisms have not been fully elucidated. In this study, we demonstrated that miR-150 is capable of not only inhibiting proliferation and activation of CD4(+) T cells but also promoting apoptosis. Mechanistically, miR-150 targets v-akt murine thymoma viral oncogene homolog 3 (AKT3), and subsequently downregulates B-cell lymphoma 2 (Bcl-2) interacting mediator of cell death (BIM). We have also demonstrated that re-expression of AKT3 reversed miR-150-mediated inhibition of CD4(+) T lymphocyte development. Therefore, we conclude that miR-150 negatively regulates CD4(+) T cell function by inhibiting the AKT3/BIM signaling pathway. These findings also suggest that manipulating the levels of miRNA-150 could be a valuable strategy in prevention and/or treatment of acute graft-versus-host disease.

In Micro-CT (Computed Tomography) system, a series of projection data of sample are collected by the detector as the precision stage rotates step by step. However, the accuracy of projection images is limited by rotation errors during the acquisition process. Therefore, evaluating the performance of precision rotary stage and developing corresponding compensation method are necessary in Micro-CT system. In this paper, a metered system is designed which is composed of four precision capacitive sensors, a precision machined steel cylinder and four flexible hinges. Based on the metered system, a method to calibrate and correct the errors when the precision stage turns is proposed. Firstly, the theoretical analysis is proposed and the imperfect situations are considered. And then, the method has been applied to correct experimental data taken from a microscope type of Micro-CT system. Successful results are shown through evaluating MTF (Modulation Transfer Function) of Micro-CT system. Lastly, a sample of tungsten wire is scanned and the reconstructed images are compared before and after using the calibrated method.

Hydrodynamic force loading platforms for controllable cell mechanical deformation play an essential role in modern cell technologies. Current systems require assistance from specific microstructures thus limiting the controllability and flexibility in cell shape modulation, and studies on real‐time 3D cell morphology analysis are still absent. This article presents a novel platform based on acoustic streaming generated from a gigahertz device for cell shape control and real‐time cell deformation analysis. Details in cell deformation and the restoration process are thoroughly studied on the platform, and cell behavior control at the microscale is successfully achieved by tuning the treating time, intensity, and wave form of the streaming. The application of this platform in cell membrane permeability modulation and analysis is also exploited. Based on the membrane reorganization during cell deformation, the effects of deformation extent and deformation patterns on membrane permeability to micro‐ and macromolecules are revealed. This technology has shown its unique superiorities in cell mechanical manipulation such as high flexibility, high accuracy, and pure fluid force operation, indicating its promising prospect as a reliable tool for cell property study and drug therapy development., This article presents a novel hydrodynamic force loading platform based on acoustic streaming generated from a gigahertz ultrasonic device for controllable cell deformation and real‐time 3D cell shape analysis. The platform is applied for cell membrane permeability modulation, and a novel phenomenon that fast and periodic cell deformation will facilitate the intracellular transportation of large cargos is observed.

Headspace solid-phase microextraction (HS-SPME) of low volatile analytes from complex aqueous samples can be substantially facilitated by elevating the temperature of the samples. However, many SPME coatings prepared from novel sorptive materials may suffer from low stabilities in hot water steam. Herein, a superhydrophobic metal-organic framework (MOF) derived from decorating the metal-oxo nodes of the amino-functionalized UiO-66(Zr) with phenylsilane was prepared and successfully developed into a novel SPME fiber coating. The highest extraction efficiencies towards the semi-volatile ultraviolet (UV) filters were achieved when the aqueous samples were heated up to 100 °C. It was notable that the lab-made coating exhibited extraordinary stability towards hot water steam, probably because the hydrophobic groups capped on the MOF prevented water molecules from entering and deconstructing its lattice. Even after being treated with water steam under 100 °C for 21 h, the extraction performance of the coating remained unchanged, and the crystal structure of the MOF maintained. Furthermore, a negligible matrix effect was observed even in the samples containing humic acid. Under the optimal extraction and thermal desorption conditions, a method for determining UV filters in aqueous samples was established, which possessed low detection limits (0.6–2.1 ng L−1), wide linear ranges (10–50000 ng L−1), good inter-fiber reproducibility (2.3–6.0%, n = 6), and satisfying intra-fiber repeatability (1.8–5.8%, n = 3). The method was successfully applied in quantifying UV filters in environmental water samples. In addition, the lab-made NH2-UiO-66(Zr)-shp-coated fiber was also suitable for the analysis of polycyclic aromatic hydrocarbons (PAHs). This study provided an effective strategy for preparing MOF coatings that can maintain their crystalline structures and high extraction performances in high-temperature steam.

A new method for accurately characterizing the tip geometry of critical dimension atomic force microscopy (CD-AFM) has been introduced. A sample type IVPS100-PTB whose line features have vertical sidewall, round corner with a radius of approx. 5 ∼ 6 nm and very low surface roughness has been applied as the tip characterizer. The geometry of the line features has been accurately and traceably calibrated to the lattice constant of crystal silicon. In this paper, detailed measurement strategies and data evaluation algorithms have been introduced, particularly concerning several important influence factors such as the line width roughness of the tip characterizer, measurement noise, measurement point density, and the calculation of the averaged tip geometry. Thorough experimental studies have been carried out, indicating high measurement accuracy of the developed method. For instance, tip geometry of a probe type CDR120 with a nominal tip diameter of 120 nm is reconstructed using two different tip characterizers before, during and after it is applied for a calibration of a user sample. The agreement of all 20 obtained tip profiles reaches 0.4 nm, confirming the high measurement stability, low tip wear as well as the high measurement consistency between two tip characterizers. Furthermore, the results of a nanofeature of the user sample after correcting the tip contribution show a repeatability of approximately 0.3 nm when it is repeatedly measured by a same tip, and a reproducibility of 0.9 nm when it is measured using two different tips, confirming the good performance of the tip correction method as well.

Background CFLARL, also known as c-FLIPL, is a critical anti-apoptotic protein that inhibits activation of caspase 8 in mammalian cells. Previous studies have shown that arginine 122 of CFLARL can be mono-methylated. However, the precise role of arginine methyltransferase of CFLARL remains unknown. PRMT5 and PRMT1, which are important members of the PRMT family, catalyze the transfer of methyl groups to the arginine of substrate proteins. PRMT5 can monomethylate or symmetrically dimethylate arginine residues, while PRMT1 can monomethylate or asymmetrically dimethylate arginine residues. Methods Lung cancer cells were cultured following the standard protocol and the cell lysates were prepared to detect the given proteins by Western Blot analysis, and the protein interaction was assayed by co-immunoprecipitation (Co-IP) or GST pull-down assay. CFLARL ubiquitination level was evaluated by proteasomal inhibitor treatment combined with HA-Ub transfection and WB assay. PRMT1 and PRMT5 genes were knocked down by siRNA technique. Results We show that PRMT5 up-regulated the protein levels of CFLARL by decreasing the ubiquitination and increasing its protein level. Additionally, PRMT1 down-regulated the protein level of CFLARL by increasing the ubiquitination and degradation. The overexpression of PRMT5 can inhibit the interaction between CFLARL and ITCH, which has been identified as an E3 ubiquitin ligase of CFLARL, while overexpressed PRMT1 enhances the interaction between CFLARL and ITCH. Furthermore, we verified that dead mutations of PRMT5 or PRMT1 have the same effects on CFLARL as the wild-type ones have, suggesting it is the physical interaction between CFLAR and PRMT1/5 that regulates CFLARL degradation other than its enzymatic activity. Finally, we showed that PRMT5 and PRMT1 could suppress or facilitate apoptosis induced by doxorubicin or pemetrexed by affecting CFLARL in NSCLC cells. Conclusions PRMT5 and PRMT1 mediate the distinct effects on CFLARL degradation by regulating the binding of E3 ligase ITCH in NSCLC cells. This study identifies a cell death mechanism that is fine-tuned by PRMT1/5 that modulate CFLARL degradation in human NSCLC cells. Electronic supplementary material The online version of this article (10.1186/s13046-019-1064-8) contains supplementary material, which is available to authorized users.

Background Acute myeloid leukemia (AML) is a highly heterogeneous disease. MicroRNAs function as important biomarkers in the clinical prognosis of AML. Methods This study identified miR-425 as a prognostic factor in AML by screening the TCGA dataset. A total of 162 patients with AML were enrolled for the study and divided into chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) groups. Results In the chemotherapy group, patients with high miR-425 expression had significantly longer overall survival (OS) and event-free survival (EFS) compared with patients with low miR-425 expression. In multivariate analyses, high miR-425 expression remained independently predictive of a better OS (HR = 0.502, P = 0.005) and EFS (HR = 0.432, P = 0.001) compared with patients with low miR-425 expression. Then, all patients were divided into two groups based on the median expression levels of miR-425. Notably, the patients undergoing allo-HSCT had significantly better OS (HR = 0.302, P

Efficient modulation of carrier concentration is fundamentally important for tailoring the electronic and photoelectronic properties of semiconducting materials. Photoinduced doping is potentially a promising way to realize such a goal for atomically thin nanomaterials in a rapid and defect-free manner. However, the wide applications of photoinduced doping in nanomaterials are severely constrained by the low doping concentration and poor stability that can be reached. Here, we propose a novel photoinduced doping mechanism based on the external photoelectric effect of metal coating on nanomaterials to significantly enhance the achievable doping concentration and stability. This approach is preliminarily demonstrated by an MX

Two-dimensional transition metal dichalcogenides have been widely applied to electronic and optoelectronic device owing to their remarkable material properties. Many studies present the platform for regulating the contact resistance via various doping schemes. Here, we report the alteration of mechanical properties of few top layers of the WSe

The paper proposes a new intelligent control method to precisely control the tip motion of the atomic force microscopy (AFM). The tip moves up and down at a high rate along the z direction during scanning, requiring the utilization of a rapid feedback controller. The standard proportional-integral (PI) feedback controller is commonly used in commercial AFMs to enable topography measurements. The controller's response performance is determined by the set of the proportional (P) parameter and the integral (I) parameter. However, the two parameters cannot be automatically altered simultaneously according to the scanning speed and the surface topography during continuors scanning, leading to an inaccurate measurement. Thus a new intelligent controller combining the fuzzy controller and the PI controller is put forward in the paper. The new controller automatically selects the most appropriate PI parameters to achieve a fast response rate on basis of the tracking errors. In the experimental setup, the new controller is realized with a digital signal process (DSP) system, implemented in a conventional AFM system. Experiments are carried out by comparing the new method with the standard PI controller. The results demonstrate that the new method is more robust and effective for the precise tip motion control, corresponding to the achievement of a highly qualified image by shortening the response time of the controller.

As a nano-Newton level force sensor, an AFM probe with a protein-modified tip could be used to investigate the antifouling properties of different ultrafiltration membranes. In this paper, the spring constants of the cantilevers of AFM probes were calibrated with a SI-traceable measurement system consisting of a precision balance, an optical lever and nano-positioning stages. The calibration system for the measured AFM cantilevers has less than 3% uncertainty, highly narrowing the large range given by the distributers. Thus, the adhesion forces between the AFM probes with different immobilized proteins and various ultrafiltration membranes could be compared with each other using force curves. The antifouling universality of a specific membrane (polyvinyl formal, PVF) towards multiple proteins (bovine serum albumin, lysozyme, catalase and fibrinogen) could be studied comprehensively. The results reveal that the antifouling property of membranes becomes better through blending F127 with PVF for all four foulants, so the antifouling universality of the membrane was improved effectively. The membrane with 60% F127 addition had the best antifouling properties. Comparison experiments of protein absorption and water contact angle have also been done. As the F127 additive varied from 0% to 60%, the amount of protein adsorption on the surface of the membranes decreased significantly and the water contact angle decreased from 58.6° to 47.1°, which indicated that the blend membranes had better antifouling universality. The experimental results agreed with AFM force curve experiments very well.

Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy diagnosed in children and is a malignant disorder that originates from one single hematopoietic precursor committed to B- or T-cell lineage. C-C chemokine receptor type 5 (CCR5) is a chemokine and chemokine receptor pair playing critical roles in tumorigenesis. A highly potent competitive antagonist of CCR5, maraviroc, recently has been identified with suppression of cancer cells aggressive in a variety of cancers. However, the effects of maraviroc on ALL cells have not yet been defined. Here we report that CCR5 selective inhibitor significantly inhibited ALL cells SUP-B15 growth and induced SUP-B15 cells to undergo cell apoptosis. This cell apoptosis was associated with increased levels of cleavage of caspase-3 and caspase-9, and Poly (ADP-ribose) polymerase (PARP). Moreover, we demonstrated that maraviroc strongly inhibited SUP-B15 cells migration to C-X-C motif chemokine ligand 12 (CXCL12) and CXCL13, and adhesion to fibronectin and vascular cell adhesion molecule 1 (VCAM-1) in vitro. Importantly, CCR5-activated signaling proteins Janus Kinase 1 (JAK1), JAK2 and signal transducer and activator of transcription (STAT3) were inhibited by maraviroc. Finally, maraviroc suppressed the growth of SUP-B15 xenograft tumors in athymic mice. Collectively, this study demonstrated that CCR5 inhibition by maraviroc has the potential for the treatment of human ALL.

A series of novel isoxazolyl chalcones were synthesized and evaluated for their activities in vitro against four types of human non-small cell lung cancer cells, including H1792, H157, A549 and Calu-1 cells. The preliminary biological screening showed that compounds 5d and 5f – i exhibited significant cytotoxicity, particularly, compounds 5f and 5h were identified as the most potent anticancer agents with IC 50 values 1.35–2.07 μM and 7.27–11.07 μM against H175, A549 and Calu-1 cell lines, respectively. Compounds 5f–i could induce apoptosis in A549 cells by death receptor 5 (DR5) mediated extrinsic pathways. The preliminary structure–activity relationship study showed that compounds bearing electron withdrawing groups (EWG) at the 2-position of the phenyl ring in Ar group were more effective than those with EWG at 4-position. These results further demonstrated that the scaffolds designed in this work might lead to the discovery of novel anti-lung cancer agents.

Diffuse large B cell lymphoma (DLBCL) is the most common type lymphoma and the standard therapy R-CHOP regimen has made most patients complete remission, however, 30-40% patients still remains be refractory or relapsed and have a dismal outcome, indicating standard cytotoxic therapy also has limits in these patients. Therefore, it is essential to identify novel therapeutic targets and agents to understand the depth molecular pathogenesis mechanism of DLBCL and overcome the relapsed/refractory. EHMT2 abnormally expression has been discovered in various kinds of malignant cells, and its higher expression may be concerned with poor prognostic of these cancers. BIX-01294 is a small molecule compound which specifically inhibits EHMT2 activity and induces demethylation of H3K9. However, the role of BIX-01294 and the involvement of EHMT2 in DLBCL is not well study now. In the present study, we first examined the expression of EHMT2 and found EHMT2 were downregulated both in protein and mRNA levels. To determine the effect of BIX-01294 on DLBCL cells growth status, CCK-8 assay was preformed to detect the viability. BIX-01294 exhibited notable proliferation suppression in a dose-dependent manner in DLBCL cells, no matter the ABC type or GCB type cells. Then flow cytometry analysis was carried out to investigate the cell cycle distribution when treated with BIX-01294. The cells in G1 phase were increased in a dose-dependent fashion both in U2932 and SUDHL2 cells, and accompanied by the population in S phase was decreased. Furthermore, we preformed flow cytometric assay to elucidate apoptotic effect and found that BIX-01294 treatment induced U2932 and SUDHL2 apoptosis. By western blot and RT-qPCR, we also showed that the expression of anti-apoptotic protein c-FLIP was decreased and the level of DR4 and DR5 was upregulated. Conformably, BIX-01294 down-regulated anti-apoptotic protein Mcl-1 expression and up-regulated pro-apoptotic protein Bax level, indicating BIX-01294 activates exogenous and endogenous apoptotic signaling pathway in human DLBCL cells. We also showed both protein and mRNA levels of LC3B increased when cells treated with BIX-01294 in DLBCL cells, proves BIX-01294 also triggers autophagy. To elucidate the mechanism of BIX-01294-induced apoptosis and autophagy in DLBCL cells, we studied the active stage of ER (endoplasmic reticulum) stress. We examined the expression of GRP78, CHOP, ATF3 and ATF4, which were regarded as important protein markers of ER stress and found that their expression were all enhanced in a dose-dependent fashion, indicate BIX-01294 activates ER stress. We then wondered whether ATF3 and ATF4 influenced apoptosis and autophagy induced by BIX-01294. We conducted shRNA to inhibit ATF3 or ATF4 expression and found inhibition of ATF3 or ATF4 upregulation decreased the expression of LC3B, indicating ATF3 and ATF4 were contributed to BIX-01294 induced autophagy. CCK8 assay showed that the viability was increased in ATF3 or ATF4 abrogated cells after exposure to BIX-01294. Consistently, the percentage of apoptosis was significantly decreased in ATF3 or ATF4 knockdown cells than control cells by Annexin-V staining flow cytometry. In our experiments, we also showed that suppressed ATF4 expression inhibited ATF3 and CHOP expression in DLBCL cells. In conclusion, we showed that with the increased concentration of BIX-01294, the cell survival rate of DLBCL was obviously inhibited and cell cycle was arrested in G1 phase. BIX-01294 induced DLBCL cells apoptosis and autophagy. Furtherly, we explored one of the underlying mechanisms is through activating the ER stress pathway. We speculated that BIX-01294 treatment induces ATF4 upregulation, and then promotes ATF3 and CHOP expression, subsequently contributes to BIX-01294-mediated autophagy and apoptosis. Disclosures No relevant conflicts of interest to declare.

Objective Chimeric antigen receptor T (CAR-T) cells therapy demonstrated remarkable efficiency in refractory and relapsed diffuse large B cell lymphoma (R/R DLBCL). Antigen-loss potentially leads to failure after single-target CAR-T cellss therapy. Aim to evaluate the efficiency and safety of double-target CAR-T cellss therapy, we performed a phase Ⅰ/Ⅱ clinical trial of combination anti-CD19 and anti-CD20 CAR-T cellss therapy for R/R DLBCL. Methods A total of 21 patients were enrolled, and patients were monitored for treatment response, toxicity and persistence. Patients received a conditioning regimen of fludarabine and cyclophosphamide followed by infusion of anti-CD19 and anti-CD20 CAR-T cellss. Results Of the 21 patients, 17 had objective response, and the ORR was 81.0% (95% CI, 58 to 95). 11 had CR, the CR rate was 52.4% (95% CI, 26 to 70). 4 of 9 patients in completed remission at 3 months remain in remission by 6 months, the CR rate was 44.4% (95% CI, 14 to 79). The median OS was 8.1 months (95% CI, 7 to 10) and the median PFS was 5.0 months (95% CI, 2 to 8). The median duration response was 6.8 months (95% CI, 4 to 10). Cytokine release syndrome (CRS) occurred in all patients. Of the 21 patients, 15 (71.4%) had grade 1-2 CRS, 6 (28.5%) had severe (≥grade 3) CRS, and no grade 5 CRS occurred. There were 5 patients with different degrees of neurotoxicity, namely CAR-T associated encephalopathy syndrome (CRES). There were 2 cases with grade 3 or above CRES, 5 of them were self-limited, and none of them died of severe CRS or CRES. There were significant differences in peak levels of IL-6 (P=0.004)、ferritin (P=0.008) and CRP (P=0.000) secretion between CRS 1-2 and CRS 3-4 patients within one month after CAR-T cell infusion. In terms of hematological toxicity, there were 11 cases of neutropenia above grade 3 (52.4%), 6 cases of anemia (28.6%) and 6 cases of thrombocytopenia (28.6%). After 12 patients with response and 1 patient without response received CAR-T cell therapy, CD19 cell subsets all disappeared after 2 weeks. The level of serum immunoglobulin in 14 patients with response decreased progressively after 1 week of treatment with CAR-T cells, and maintained at a relatively low level. Eight patients received intravenous immunoglobulin during CAR-T cell therapy. Conclusion Anti-CD19 combined with anti-CD20 CAR-T cell is effective in the treatment of R/R DLBCL patients.2. Anti-CD19 combined with anti-CD20 CAR-T cell therapy has the occurrence of CRS, CRES and hematological toxicity, and adverse reactions could be controlled. This is the first report to our knowledge of successful treatment of combination of anti-CD19 and anti-CD20 CAR-T cellss in R/R DLBCL. Our results provide strong support for further multiple-target CAR-T cells therapy, which could potentially resolve antigen-loss related failure. Disclosures No relevant conflicts of interest to declare.

Natural chalcones have been proved to inhibit cancer cells with therapeutic potential, but the underlying molecular mechanism is still largely unexplored. Here, we identified a novel chalcone, 2'-hydroxy-4',5'-dimethoxychalcone (HDMC) and demonstrated that HDMC induced apoptosis in various nonsmall cell lung cancer cells. Further study showed that HDMC elevated cellular reactive oxygen species (ROS) levels, thus inducing expressions of ATF4 and C/EBP homologous protein (CHOP). Then, death receptor 5 (DR5) was upregulated through ATF4-CHOP axis and eventually resulted in apoptosis. We also found that downregulation of c-FLIPL contributed to HDMC-induced apoptosis. In conclusion, HDMC induces apoptosis in human nonsmall cell lung cancer cells via activation of DR5 signaling pathway, and ROS-mediated ATF4-CHOP axis is involved in the process. Our results further supported the potential for HDMC to be developed as a new antitumor agent for cancer therapy or chemoprevention.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries, and mainly originates from an accumulation of abnormal B cells caused by the dysregulation of cell proliferation and apoptosis rates. The aberration of apoptosis-related genes in CLL cells results in defective apoptosis of CLL cells in response to traditional therapeutic medicine. Plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone), a natural compound from Plumbago zeylinica, has been shown to exhibit pro-apoptotic activities in tumor cells. In the present study, we report that plumbagin effectively inhibited CLL cell viability with a lower dose compared to fludarabine, and inhibited cell proliferation in a dose-dependent manner. In addition, plumbagin promoted accumulation of MEC-1 cells in the S phase, and blocked cell cycle transition of HG3 cells from G0/G1 to S phase. Molecularly, plumbagin markedly induced CLL cell apoptosis through reduction of Bcl-2, but through an increase in the Bax protein level. These results suggest that plumbagin may be considered as a potential anticancer agent for CLL therapy.

PS-341 (bortezomib), a proteasome inhibitor, has been approved for the treatment of multiple myeloma. Our previous work has shown that PS-341 induces death receptor 5 (DR5)–dependent apoptosis and enhances the TNF-related apoptosis-inducing ligand–induced apoptosis in human non–small cell lung cancer cells. However, the definite mechanism remains undefined. In the present study, we reveal that PKCδ and RSK2 mediate PS-341–induced DR5 upregulation, involving coactivation of endoplasmic reticulum (ER) stress. We discovered that PS-341 activated ER stress through elevating the expression of BiP, p-eIF2α, IRE1α, ATF4, ATF3, and CCAAT/enhancer-binding protein homologous protein (CHOP). Further study showed that DR5 upregulation was dependent on ATF4, ATF3, and CHOP expression. Silencing either one of the ATF4, ATF3, and CHOP expression decreased DR5 upregulation and subsequent apoptosis. We determined that ATF4 regulated ATF3 and CHOP expression. Thereafter, ATF3 and CHOP formed a complex and regulated DR5 expression. In addition, we discovered that the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and RSK2 were elevated after PS-341 treatment and inhibition of their phosphorylation using MAP-ERK kinase 1/2 inhibitor decreased the DR5 level, indicating that ERK/RSK2 signaling is involved in DR5 upregulation. Furthermore, we detected the cleavage of PKCδ, and the blockage of PKCδ expression cut down DR5 upregulation and apoptosis. Importantly, knockdown of PKCδ expression decreased the induction of ER stress and the phosphorylation of ERK1/2 and RSK2, suggesting that PKCδ regulates DR5 expression through ERK/RSK2 signaling and ATF4–CHOP/ATF3 axis. Collectively, we show that PS-341 induces PKCδ-dependent DR5 expression through activation of ERK/RSK2 and ER stress signaling pathway. Mol Cancer Ther; 11(10); 2174–82. ©2012 AACR.

Two-dimensional transition metal dichalcogenides have been widely applied to electronic and optoelectronic device owing to their remarkable material properties. Many studies present the platform for regulating the contact resistance via various doping schemes. Here, we report the alteration of mechanical properties of few top layers of the WSe2 flake which are processed by air stable n-doping of N2O with a constant gas flow through mild plasma and present better manufacturability and friability. The single-line nanoscratching experiments on the WSe2 flakes with different doping time reveal that the manufacturable depths are positively correlated with the exposure time at a certain range and tend to be stable afterwards. Meanwhile, material characterization by x-ray photoelectron spectroscopy confirms that the alteration of mechanical properties is owing to the creation of Se vacancies and substitution of O atoms, which breaks the primary molecular structure of the WSe2 flakes. The synchronous Kelvin probe force microscopy and topography results of ROI nanoscratching of a stepped WSe2 sample confirmed that the depth of the degenerate doping is five layers, which was consistent with the single-line scratching experiments. Our results reveal the interrelationship of the mechanical property, chemical bonds and work function changes of the doped WSe2 flakes.

The aim of this study was to evaluate the role of NLRP3 inflammasome on BU/CY-induced liver inflammation in mice after HSCT. HSCT mice model was established through infusion of 5 × 106 bone marrow mononuclear cells after conditioned with BU/CY. On day 7, 14, 21 and 28 after HSCT, mice were sacrificed for analysis of liver inflammation, cytokine secretion, NLRP3 expression and caspase-1 activation as well as release of ATP and high-mobility group protein B1 (HMGB1). Furthermore, NLRP3 selective inhibitor (BAY 11-7082) was administrated into mice after HSCT to evaluate its effects on liver inflammation. Severe liver inflammation and damage with elevated secretion of IL-1β and IL-18 were found in mice after HSCT. Meanwhile, elevated expressions of NLRP3 and caspase-1 activation in liver were found. In addition, increased release of ATP and HMGB1 were observed. Selective inhibition of NLRP3 decreased caspase-1 activation and secretion of IL-1β and IL-18. Furthermore, NLRP3 inhibition also reduced infiltration of macrophages and neutrophils and improved liver function. In conclusion, NLRP3 was involved in BU/CY-induced liver inflammation after HSCT and selectively inhibited it ameliorated liver inflammation and improved liver function, suggesting targeting NLRP3 might be a new approach in the prophylaxis of liver inflammation after HSCT.

Atomic force microscope (AFM) is very useful in nano-scale force measurement. Lateral force is typically used in nanoscratch and surface friction measurement based on AFM. As one of the most important parameters to obtain lateral force, the lateral spring constant of AFM cantilever probe is of great significance and needs to be quantitative calibrated. Lateral torsion and lateral force of the cantilever are two parameters need to be measured in lateral spring constant calibration. In this article, we develop a calibration system and introduce a calibration method using an AFM head and an electromagnetic balance. An aluminium column with a known angel on top is placed on the weighing pan of the balance. The cantilever is precisely positioned in the AFM head, then approaches and bends on the aluminium column. During this procedure, the bending force and the lateral torsion of the cantilever are synchronously measured by the balance and an optical lever system, respectively. Then the lateral spring constant is calculated with a formula. By using this method, three kinds of rectangular cantilever are calibrated. The relative standard deviations of the calibration results are smaller than 2%.

With nano-level spatial and force resolution, atomic force microscope (AFM) becomes an indispensable nanoindentation measurement instrument for thin films and soft films. To do the research of size effect of the hardness property of thin films, indentation experiments have been done on a gold film with 200 nm thickness and a silicon nitride film with 110 nm thickness. It is possible to change the maximum load forces to get discrete residual depths on the film samples. The contact depths of the gold film are 15.91 nm and 26.67 nm respectively, while the contact depths of the silicon nitride film are 7.82 nm and 10.25 nm respectively. A group of nanoindentation force curves are recorded for the transformation into force-depth curves. Subsequently, a 3D image of the residual indentation can be obtained by in-situ scanning immediately after nanoindentation. The topography data is imported into a Matlab program to estimate the contact area of the indentation. For the gold film, the hardness parameters of 3.31 GPa and 2.57 GPa are calculated under the above two contact depths. And for silicon nitride film, the corresponding results are 6.51GPa and 3.58 GPa. The experimental results illustrate a strong size effect for thin film hardness. The correction of the residual indentation image of the gold film is also done as an initial study. Blind tip reconstruction (BTR) algorithm is introduced to calibrate the tip shape, and more reliable hardness values of 1.15 GPa and 0.94 GPa are estimated.

Atomic force microscope (AFM) is the most prevalent instrument in nanometer measurement. But the tip shape has a great influence on the measurements of surface topography. Blind tip reconstruction (BTR), established by Villarrubia, provides a good solution to this problem, nevertheless, with low precision if the tip characterizer is not appropriate. In order to explore the optimal tip characterizers for precision BTR, a serial of simulation experiments were carried out. First, a tip characterizer was simulated as the combination of a nanosized sphere with a square grating for the BTR of a conical tip. The results show that rotation structures are more suitable for conical tip reconstruction than prismatic structures. Second, a cylinder structure is chosen to verify the validity as an optimal feature for conical tip reconstruction. The simulation results show that if only the equivalent cone angle of the cylinder structure is no more than the tip, such structure is suitable as a tip characterizer. Tip characterizers need to have structure with smaller equivalent cone angle so as to make enough segments of the tip touched by the local maximum point of the sample. The local maximum point of the cylinder is just the top edge. From another point of view, the edge of the pillar has a zero equivalent radius, which is the sharpest feature but not obviously in scale.

Micro-structures 3-D profile measurement is an important measurement content for research on micromachining and characterization of micro-dimension. In this paper, a new method involved 2-D structure template, which guides phase unwrapping, is proposed based on phase-shifting microscopic interferometry. It is fit not only for static measurement but also for dynamic measurement, especially for motion of MEMS devices. 3-D profile of active comb of micro-resonator is obtained by using the method. The theoretic precision in out-of-plane direction is better than 0.5 nm. The in-plane, theoretic precision in micro-structures is better than 0.5 μm. But at the edge of micro-structures, it is on the level of micrometer mainly caused by imprecise edge analysis. Finally, its disadvantages and the following development are discussed.

This paper introduces the TERT-IV prototype developed by Tianjin University. The application of the TERT-IV system to measurement parameters of two-phase flow has been studied. The methods of analyzing measured data of ERT system are presented and applied to identify flow regimes and estimate void fraction. For the several typical flow regimes, the methods of principal component analysis and artificial neural network to identify the two-phase flow regimes is presented, and that is proved to have higher recognition rate by experimental test. For the different phase distribution on a pipe cross-section, the methods of relative changes summation and polynomial regression are used to estimate void fraction, and are proved to be possible by comparing the results of simulation calculation to the analytic results of experimental measured data. The research results show that the method is feasible using feature extraction and analysis data to measure the parameters of two-phase flow under the different flow conditions, and prove that it is possible to monitor on-line the transportation process of air/water two-phase flow using ERT system.

The very small vibration of a solidly-mounted resonator (SMR) in fluid may trigger a relatively large motion of the covering fluid, which was implied by our protein-related experimental results. Therefore, a series of experimental methods for characterizing the mechanical longitudinal vibration of the SMR and the corresponding out-of-plane dynamic response of the fluid above the SMR surface is described in this paper. A SMR device with theoretical resonance frequency of 2.5 GHz was driven by an amplitude-modulated (AM) signal, in which the amplitude is modulated by a signal of the second resonance frequency of the atomic force microscope (AFM) cantilever. A lock-in amplifier is used to demodulate the vibration response of the AFM cantilever, which is proportional to the amplitude of the sample vibration in contact mode and tapping mode. The amplitude-frequency curve of the SMR surface is obtained in contact mode with a relatively stronger interaction force between the AFM tip and the SMR surface. The amplitude-frequency curve of the motion of the liquid above the SMR device and the peak amplitude of the fluid at different distances above the SMR surface are measured in tapping mode with a relatively weak interaction force between the AFM tip and the fluid sample.

A simple rate adaptive control method is proposed to improve the imaging speed of the atomic force microscope (AFM) in the paper. Conventionally, the probe implemented on the AFM scans the sample surface at a constant rate, resulting in low time efficiency. Numerous attempts have been made to realize high-speed AFMs, while little efforts are put into changing the constant-rate scanning. Here we report a rate adaptive control method based on variable-rate scanning. The method automatically sets the imaging speed for the x scanner through the analysis of the tracking errors in the z direction at each scanning point, thus improving the dynamic tracking performance of the z scanner. The development and functioning of the rate adaptive method are demonstrated, as well as how the approach significantly achieves faster scans and a higher resolution AFM imaging.

Combining electrical resistance tomography (ERT) with the cross-correlation flow measurement technique can provide more information on the flow than usual. A dual-plane ERT system for use on laboratory- and plant-scale process equipment has been developed on the basis of this idea. This paper focuses on the design of it. The principle of measurement of the local gas velocity distribution in a bubbly gas/liquid pipe flow based on pixel-pixel cross correlation of two plane images is described. Methods to improve the real-time performance of the system are also discussed in detail. Initial experimental results illustrate the feasibility of the method presented here.

A multi-electrode inductance flowmeter is a combination of the traditional inductance flowmeter with the electromagnetic tomographic technique. In order to eliminate the random error of data acquisition of the multi-electrode inductance flowmeter, a chord measurement method and a data fusion algorithm are presented. Using the chord measurement method, not only could the number of measurement data be decreased to half that demanded by Engl's equation but also the signal to noise ratio (SNR) of measurement was improved. The algorithm presented was used to fuse abundant data measured at multiple angles and to yield an optimum estimate of the mean flow rate in terms of a minimum mean square error. Simulation results showed that this algorithm was robust and effective.

Vibration isolation system is a prerequisite to achieve high resolution picture using scanning tunnel microscope (STM). The principle of spring damping isolation, staked flat-elastomer isolation, pneumatic isolation, and sandbox damping isolation is introduced. The relationship between resonant frequency of the isolation and the effect is presented. The four resonant frequencies are calculated through Finite Element Analysis (FEA). The four vibration isolations is designed and optimized according to the analysis. The experimental results show that spring damping isolation has the best effect and a transfer ratio of 10 -6 (120dB) can be obtained.

We report on a new chemical sensor based on black phosphorus/molybdenum diselenide van der Waals hetero-junctions. Due to the atomically thin nature of two-dimensional (2D) materials, surface adsorption of gas molecules can effectively modulate the band alignment at the junction interface, making the device a highly sensitive detector for chemical adsorptions. Compared to sensors made of homogeneous nanomaterials, the hetero-junction demonstrates considerably lower detection limit and higher sensitivity toward nitrogen dioxide. Kelvin probe force microscopy and finite element simulations have provided experimental and theoretical explanations for the enhanced performance, proving that chemical adsorption can induce significant changes in band alignment and carrier transport behaviors. The study demonstrates the potential of van der Waals hetero-junction as a new platform for sensing applications, and provides more insights into the interaction between gaseous molecules and 2D hetero-structures.

Pulse laser micromachining technology, as a branch of laser processing technology, has been widely used in MEMS device processing, aviation, instruments fabrication, circuit board design etc.. In this paper, a novel nanosecond pulse laser micromachining system is presented, which consists of nanosecond pulse LASER, optical path mechanical structure, transmission system, motion control system. Nanosecond pulse UV laser, with 355 nm wavelength and 40ns pulse width, is chosen as the light source. Optical path mechanical structure is designed to get ideal result of laser focusing. Motion control system, combining PMAC card with the PC software, can control the 3-D motion platform and complete microstructure processing. By CCD monitoring system, researchers can get real-time detection on the effect of laser beam focusing and processing process.

The atomic force microscope (AFM) is a powerful instrument which can measure the surface of samples at the nanoscale. The resonance of the scanner in xy directions, and the feedback control in the z direction are two major sources of image distortion at high scan speed. In order to improve the scanning speed of the AFM, a low-cost and easy method, which includes sinusoidal scans in the fast scan direction, and an intelligent fuzzy controller in the z direction, is proposed in this paper. The use of a single-frequency driving signal in the fast scan direction allows the scanner to move at a higher speed without exciting its mechanical resonance. The intelligent fuzzy controller automatically selects appropriate PI parameters through the analysis of the tracking errors, thus improving the dynamic tracking performance of the z scanner. The development and functioning of the sinusoidal fast scans and the intelligent fuzzy controller are demonstrated, as well as how this approach significantly achieves faster scans and a higher resolution AFM imaging.

A clamp-on pulsed ultrasound cross-correlation flowmeter has been developed by the authors which can measure the mixture velocity of liquid/solid two-phase flows. Small, well-dispersed solids exist in the calibration and test liquids, which for a given mixture have consistent slip. Allowance for this slip in determining mixture velocity is made by the meter factor obtained during specific calibrations. The flowmeter has been calibrated in a horizontal pipe by comparison with an electromagnetic flowmeter using a well-mixed, low concentration paper pulp (concentration 0.4% by weight, average solids density approximately 1100 kg m −3 ) as the measured medium. The maximum deviation between these two meters is ±4.8% with a confidence level of 99.73%. One prototype of this flowmeter was installed on a pulp pipeline at a paper mill for long-term reliability trails. The results are encouraging. A second prototype was installed in series with an oval gear volumetric flowmeter on a pipeline, in which very high viscosity crude oil flowed. Results show that the cross-correlation flowmeter worked reliably even at velocities less than 0.3 m s −1 ; the maximum difference between the two types of meter was less than ±3%.

A piezoelectronic inchworm-style stepper was designed for probe approaching in scanning probe microscope(SPM). The whole system consists of mechanical structures, hardware control units and PC software control units. Flexible hinges and three PZT stacks were used to constitute the stepper. ANSYS was utilized to analyze and optimize the structure of the mechanism. Three synchronous timing sequences were formed to drive the piezoelectric stacks. The performance of the stepper was tested by the laser interferometer. The deviation of each step is less than 31.2nm. With the advantages of no lubrication, less calorific value and high precision, its potential application is ultra-high vacuum environment.