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Use the JavaFX platform to create rich-client Java applications and discover how you can use this powerful Java-based UI platform, which is capable of handling large-scale data-driven business applications for PC as well as mobile and embedded devices. The expert authors cover the new more modular JavaFX 9 APIs, development tools and best practices, as well as providing code examples that explore the exciting new features provided with JavaFX 9, part of Oracle's Java 9 release.

The current therapies to treat hepatitis B virus (HBV) infection are limited. Recently, clustered regularly interspaced short palindromic repeat (CRISPR) systems, originally identified in bacteria and archaea, have been found to consist of an RNA-based adaptive immune system that degrades complimentary sequences of invading plasmids and viruses. Here, we studied the effects of the CRISPR/CRISPR-associated Cas9 system that was targeted to the surface antigen (HBsAg)-encoding region of HBV, both in a cell culture system and in vivo . The HBsAg levels in the media of the cells and in the sera of mice were analyzed by a quantitative enzyme-linked immunosorbent assay. The HBV DNA levels were assessed by quantitative PCR and HBsAg expression in mouse livers was assessed by an immunohistochemical assay. The amount of HBsAg secreted in the cell culture and mouse serum was reduced by CRISPR/Cas9 treatment. Immunohistochemistry analyses showed almost no HBsAg-positive cells in the liver tissue of CRISPR/Cas9-S1+X3-treated mice. The CRISPR/Cas9 system efficiently produced mutations in HBV DNA. Thus, CRISPR/Cas9 inhibits HBV replication and expression in vitro and in vivo and may constitute a new therapeutic strategy for HBV infection.

PtSe 2 and CuSe monolayers obtained by selenization of a metal substrate are shown to intrinsically form periodic patterns by varying the amount of Se atoms deposited. These patterns are used for the localized absorption of molecules and nanoclusters. Two-dimensional (2D) materials have been studied extensively as monolayers 1 , 2 , 3 , 4 , 5 , vertical or lateral heterostructures 6 , 7 , 8 . To achieve functionalization, monolayers are often patterned using soft lithography and selectively decorated with molecules 9 , 10 . Here we demonstrate the growth of a family of 2D materials that are intrinsically patterned. We demonstrate that a monolayer of PtSe 2 can be grown on a Pt substrate in the form of a triangular pattern of alternating 1T and 1H phases. Moreover, we show that, in a monolayer of CuSe grown on a Cu substrate, strain relaxation leads to periodic patterns of triangular nanopores with uniform size. Adsorption of different species at preferred pattern sites is also achieved, demonstrating that these materials can serve as templates for selective self-assembly of molecules or nanoclusters, as well as for the functionalization of the same substrate with two different species.

Cosmological models in which dark matter consists of cold elementary particles predict that the dark halo population should extend to masses many orders of magnitude below those at which galaxies can form 1 – 3 . Here we report a cosmological simulation of the formation of present-day haloes over the full range of observed halo masses (20 orders of magnitude) when dark matter is assumed to be in the form of weakly interacting massive particles of mass approximately 100 gigaelectronvolts. The simulation has a full dynamic range of 30 orders of magnitude in mass and resolves the internal structure of hundreds of Earth-mass haloes in as much detail as it does for hundreds of rich galaxy clusters. We find that halo density profiles are universal over the entire mass range and are well described by simple two-parameter fitting formulae 4 , 5 . Halo mass and concentration are tightly related in a way that depends on cosmology and on the nature of the dark matter. For a fixed mass, the concentration is independent of the local environment for haloes less massive than those of typical galaxies. Haloes over the mass range of 10 −3 to 10 11 solar masses contribute about equally (per logarithmic interval) to the luminosity produced by dark matter annihilation, which we find to be smaller than all previous estimates by factors ranging up to one thousand 3 . Simulations of formation of dark matter haloes ranging in size from Earth mass to clusters of galaxies find a universal halo density structure spanning 20 orders of magnitude in mass.

Abnormal expression of activating/inhibitory receptors leads to natural killer (NK) cells dysfunction in tumor. Here we show that programmed cell death protein 1 (PD-1), a well-known immune checkpoint of T cells, is highly expressed on peripheral and tumor-infiltrating NK cells from patients with digestive cancers including esophageal, liver, colorectal, gastric and biliary cancer. The increased PD-1 expression on NK cells indicates poorer survival in esophageal and liver cancers. Blocking PD-1/PD-L1 signaling markedly enhances cytokines production and degranulation and suppresses apoptosis of NK cells in vitro . PD-1/PD-L1 exerts inhibitory effect through repressing the activation of PI3K/AKT signaling in NK cells. More importantly, a PD-1 blocking antibody was found to significantly suppress the growth of xenografts in nude mice, and this inhibition of tumor growth was completely abrogated by NK depletion. These findings strongly suggested that PD-1 is an inhibitory regulator of NK cells in digestive cancers. PD-1 blockade might be an efficient strategy in NK cell-based tumor immunotherapy.

A new Timoshenko beam model is developed using a modified couple stress theory and a surface elasticity theory. A variational formulation based on Hamilton’s principle is employed, which leads to the simultaneous determination of the equations of motion and complete boundary conditions for a Timoshenko beam. The new model contains a material length scale parameter accounting for the microstructure effect in the bulk of the beam and three surface elasticity constants describing the mechanical behavior of the beam surface layer. The inclusion of these additional material constants enables the new model to capture the microstructure-and surface energy-dependent size effect. In addition, both bending and axial deformations are considered, and the Poisson effect is incorporated in the current model, unlike existing Timoshenko beam models. The new beam model includes the models considering only the microstructure dependence or the surface energy effect as limiting cases and recovers the Bernoulli–Euler beam model incorporating the two effects as a special case. Also, the current model reduces to the classical Timoshenko beam model when the microstructure dependence, surface energy and Poisson’s effect are all suppressed. To demonstrate the new model, the static bending and free vibration problems of a simply supported beam are analytically solved by directly applying the general formulas derived. The numerical results for the static bending problem reveal that both the deflection and rotation of the simply supported beam predicted by the new model are smaller than those predicted by the classical Timoshenko beam model. In addition, the differences in both the deflection and rotation predicted by the two models are very large when the beam thickness is small, but they are diminishing with the increase of the beam thickness. Similar trends are observed for the free vibration problem, where it is shown that the natural frequency predicted by the new model is higher than that given by the classical model, with the difference between them being significantly large for very thin beams. These predicted trends of the size effect in beam bending at the micron scale agree with those observed experimentally.

A new model for anisotropic magneto-electro-elastic Mindlin plates is developed by using an extended modified couple stress theory. The equations of motion and complete boundary conditions are simultaneously obtained by a variational formulation based on Hamilton’s principle. The new anisotropic magneto-electro-elastic plate model includes the models for orthotropic and transversely isotropic magneto-electro-elastic Mindlin plates and the model for isotropic Mindlin plates, all incorporating the microstructure effect, as special cases. To illustrate the new model, the static bending and free vibration problems of a simply supported transversely isotropic magneto-electro-elastic plate are analytically solved by directly applying the general formulas derived. For the static bending problem, the numerical results reveal that the deflection, rotation, electric potential, and magnetic potential of the simply supported plate predicted by the current non-classical model are always smaller than those predicted by the classical elasticity-based model, and the differences are significant when the plate thickness is very small but is diminishing as the thickness increases. For the free vibration problem, it is found that the natural frequency predicted by the new plate model is higher than that predicted by the classical model, and the difference is quite large for very thin plates.

This study focuses on unraveling the microphysical origins of the nonlinear elastic effects, which are pervasive in the Earth's crust. Here, we examine the influence of grain shape on the elastic nonlinearity of granular assemblies. We find that the elastic nonlinearity of angular sand particles is of the same order of magnitude as that previously measured in spherical glass beads. However, while the elastic nonlinearity of glass beads increases by an order of magnitude with RH that of sand particles is rather RH independent. We attribute this difference to the angularity of sand particles: absorbed water on the spherical grains weakens the junctions making them more nonlinear, while no such effect occurs in sand due to grain interlocking. Additionally, for one of the nonlinear parameters that likely arises from shearing/partial slip of the grain junctions, we observe a sharp amplitude threshold in sand which is not observed in glass beads. Plain Language Summary Our main goal is to understand the origin of nonlinear elastic effects in granular materials like rocks. These nonlinear effects are critical in part because they are responsible for the small changes in seismic wave speed, and therefore stiffness, of the Earth's crust. Monitoring these changes is important as they might represent predictors of upcoming earthquakes, and they also play a role in the dynamic triggering of earthquakes. Here we study the effect of grain shape and relative humidity (RH) on the nonlinear elastic properties of granular media. To do this, we use granular media of well‐controlled grain size and composition, namely angular fine sand particles. We find that their elastic nonlinearity is of the same order of magnitude as that previously measured in spherical glass beads, however, and unlike in glass beads, we observe little to no dependence with RH. We attribute this lack of changes with RH in sand to grain interlocking, and the fact that absorbed water on the grains is unable to weaken the grain junctions and the granular assembly. Key Points The elastic nonlinearity of angular, fine sand particles is rather independent of relativity humidity (RH) level This is in contrast with observations made in spherical glass beads, which show an increase in elastic nonlinearity with RH We attribute this RH independence in sand to grain interlocking that prevents adsorbed water from weakening the grain junctions

Aberrant activation of c-kit proto-oncogene contributes to abnormal cell proliferation by altering the tyrosine kinase signaling and constitutes a crucial impetus for leukemogenesis. Epigenetic silencing of tumor-suppressive microRNAs (miRNAs) is a key oncogenic mechanism for the activation of oncogenes in tumors. In this study, several miRNAs potentially binding to the 3′-untranslated region of human c-kit mRNA were screened by luciferase reporter assays. Among these miRNAs, miR-193a was embedded in a CpG island and epigenetically repressed by promoter hypermethylation in acute myeloid leukemia (AML) cell lines and primary AML blasts, but not in normal bone marrow cells. Importantly, miR-193a levels were inversely correlated with c-kit levels measured in 9 leukemia cell lines and 27 primary AML samples. Restoring miR-193a expression in AML cells harboring c-kit mutation and/or overexpression, either by synthetic miR-193a transfection or by DNA hypomethylating agent 5-azacytidine (5-aza) treatment, resulted in a significant reduction in c-kit expression at both RNA and protein levels and inhibition of cell growth. The growth-inhibitory activity of miR-193a was associated with apoptosis and granulocytic differentiation. Moreover, 5-aza-induced c-kit reduction could be partially blocked by miR-193a inhibitor, leading to a reversal of antiproliferative and proapoptotic effects of 5-aza. These data reveal a critical role for methylation-repressed miR-193a in myeloid leukemogenesis and the therapeutic promise of upregulating miR-193a expression for c-kit -positive AML.

A non-classical Mindlin plate model is developed using a modified couple stress theory. The equations of motion and boundary conditions are obtained simultaneously through a variational formulation based on Hamilton’s principle. The new model contains a material length scale parameter and can capture the size effect, unlike the classical Mindlin plate theory. In addition, the current model considers both stretching and bending of the plate, which differs from the classical Mindlin plate model. It is shown that the newly developed Mindlin plate model recovers the non-classical Timoshenko beam model based on the modified couple stress theory as a special case. Also, the current non-classical plate model reduces to the Mindlin plate model based on classical elasticity when the material length scale parameter is set to be zero. To illustrate the new Mindlin plate model, analytical solutions for the static bending and free vibration problems of a simply supported plate are obtained by directly applying the general forms of the governing equations and boundary conditions of the model. The numerical results show that the deflection and rotations predicted by the new model are smaller than those predicted by the classical Mindlin plate model, while the natural frequency of the plate predicted by the former is higher than that by the latter. It is further seen that the differences between the two sets of predicted values are significantly large when the plate thickness is small, but they are diminishing with increasing plate thickness.