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Myelodysplastic syndromes (MDS) are clonal neoplasms of the hematopoietic stem cell that result in aberrant differentiation of hematopoietic lineages caused by a wide range of underlying genetic, epigenetic, and other causes. Despite the myriad origins, a recognizable MDS phenotype has been associated with miRNA aberrant expression. A model of aberrant myeloid maturation that mimics MDS was generated using a stable knockdown of miR-378-3p. This model exhibited a transcriptional profile indicating aberrant maturation and function, immunophenotypic and morphologic dysplasia, and aberrant growth that characterizes MDS. Moreover, aberrant signal transduction in response to stimulation specific to the stage of myeloid maturation as indicated by CyTOF mass cytometry was similar to that found in samples from patients with MDS. The aberrant signaling, immunophenotypic changes, cellular growth, and colony formation ability seen in this myeloid model could be reversed with azacytidine, albeit without significant improvement of neutrophil function.

Compared with direct steam generation (DSG), direct vapor generation (DVG) system based on organic working fluid has better application potential in low and medium temperature distributed system. However, there is a lack of understanding of the two-phase flow instability that commonly occurs in DVG systems and can cause fatal damage to the system. In this paper, Ledinegg instability is considered as a common flow instability, and its occurrence characteristics and avoidance strategies are presented. First, a theoretical model was established to study Ledinegg instability of organic working fluid. Then, the effects of heat flux q, inlet subcooling Tc, length-to-diameter ratio L/D and fluid properties are analyzed. Particularly, a characteristic parameter RL representing the possibility of Ledinegg instability is proposed for the first time in performance evaluation of Ledinegg instability. The results show that as L/D decreases from 200 to 100, RL reduces from 0.88 to 0.25. As q increases from 10 kW/m2 to 30 kW/m2, RL increases from 0.54 to 1.03. When Tc is less than 3 °C, RL approaches 0 and Ledinegg instability disappears. With the increase of surface tension σ and the latent heat of vaporization r, the decreases of vapor-liquid density ratio ρsv/ρsl and the decreases of vapor-liquid viscosity ratio μsv/μsl, RL increases. The physical equation describing RL of Ledinegg instability is helpful to guide DVG system to reduce or avoid Ledinegg instability in design and operation.

Studying individuals at increased genetic risk for schizophrenia may generate important theories regarding the emergence of the illness. In this investigation, genetic high-risk individuals (GHR, n = 37) were assessed with functional magnetic resonance imaging and compared to individuals in the first episode of schizophrenia (FESZ, n = 42) and healthy comparison subjects (HCS, n = 59). Measures of functional connectivity and the amplitude of low-frequency fluctuation (ALFF) were obtained in a global, data-driven analysis. The functional connectivity measure, termed degree centrality, assessed each voxel's connectivity with all the other voxels in the brain. GHR and FESZ displayed increased degree centrality globally and locally. On ALFF measures, GHR were indistinguishable from HCS in the majority of areas but resembled FESZ in insula, basal ganglia and hippocampus. FESZ evidenced reduced amplitude of the global neural signal as compared to HCS and GHR. Results support the hypothesis that schizophrenia diathesis involves functional connectivity and ALFF abnormalities. In addition, they further an emerging theory suggesting that increased connectivity and metabolism may be involved in schizophrenia vulnerability and early stages of the illness.

A new series of 3,6-diaryl-1H-pyrazolo[3,4-b]pyridine compounds have been discovered as potent anaplastic lymphoma kinase (ALK) inhibitors. The 4-hydroxyphenyl in the 6-position of 1H-pyrazolo[3,4-b]pyridine were crucial and a fluorine atom substitution could give promising inhibitory activity. The IC50 of compound 9v against ALK was up to 1.58 nM and a binding mechanism was proposed.

A synthesis of cephalostatin 1 from hecogenin is described in detail. The gram-scale synthesis of south part features a Baeyer–Villiger oxidation of hecogenin to 16,20-diol, a selective oxidation of C16 OH with Dess–Martin periodinane, a Rh(I)-catalyzed C15 C16 double bond shift to C14 C15 position, and a Hg(OAc)2-mediated spiroketal formation from cyclic enol ethers with alkenyl side chain at 2-position. Key transformations in the synthesis of north part, also on gram scale, include an abnormal Baeyer–Villiger oxidation of hecogenin to the corresponding dinorcholanic lactone, where a catalytic amount of iodine acts as a traceless and catalytic switch, an umpolung of steroidal 22-aldehyde to forge C22 C23 bond with good stereochemical control, a cascade spiroketal-forming process to establish DEF rings in one operation, and a selective oxidation of C3 OH. There are also other noteworthy transformations that, although not used in our final route, are valuable and could be applied to other syntheses, including: intra- or intermolecular SN2′ processes of C14-heteroatom-substituted C15 C16 alkenes, an unprecedented rearrangement of β-adduct of D-ring dienes and singlet oxygen, a chelation-controlled methylallylation of C23 aldehyde, and so on.

High-risk forms of B-acute lymphoblastic leukemia (B-ALL) remain a therapeutic challenge. Leukemia-initiating cells (LICs) self-renew and spark relapse and therefore have been the subject of intensive investigation; however, the properties of LICs in high-risk B-ALL are not well understood. Here, we use single-cell transcriptomics and quantitative xenotransplantation to understand LICs in MLL-rearranged (MLL-r) B-ALL. Compared with reported LIC frequencies in acute myeloid leukemia (AML), engraftable LICs in MLL-r B-ALL are abundant. Although we find that multipotent, self-renewing LICs are enriched among phenotypically undifferentiated B-ALL cells, LICs with the capacity to replenish the leukemic cellular diversity can emerge from more mature fractions. While inhibiting oxidative phosphorylation blunts blast proliferation, this intervention promotes LIC emergence. Conversely, inhibiting hypoxia and glycolysis impairs MLL-r B-ALL LICs, providing a therapeutic benefit in xenotransplantation systems. These findings provide insight into the aggressive nature of MLL-r B-ALL and provide a rationale for therapeutic targeting of hypoxia and glycolysis.

Hematopoiesis changes over life to meet the demands of maturation and aging. Here, we find that the definitive hematopoietic stem and progenitor cell (HSPC) compartment is remodeled from gestation into adulthood, a process regulated by the heterochronic Lin28b/let-7 axis. Native fetal and neonatal HSPCs distribute with a pro-lymphoid/erythroid bias with a shift toward myeloid output in adulthood. By mining transcriptomic data comparing juvenile and adult HSPCs and reconstructing coordinately activated gene regulatory networks, we uncover the Polycomb repressor complex 1 (PRC1) component Cbx2 as an effector of Lin28b/let-7's control of hematopoietic maturation. We find that juvenile Cbx2

Wind tunnel studies are conducted to investigate the wind load effect of a representative single-column-supported two-plate billboard structure. Firstly, synchronous pressure measurement on the billboard of a rigid model in wind tunnel is carried out. The alongwind, acrosswind and torsional loads at different wind directions are analyzed. Simplified pressure distributions causing alongwind and torsional loads at the most unfavorable wind directions are presented. Secondly, an aeroelastic model test is conducted and the response at the base of supporting column is obtained from force balance measurement. The measured responses are also compared with the analytical predictions to validate the effectiveness of analytical approach. This analysis sheds new insight on the aerodynamic admittance function and aerodynamic damping. A simplified approach for the analysis of torsional response is introduced in terms of effective eccentricity coefficient. This study provides comprehensive wind load testing data and analytical approach for prediction of wind-induced response of two-plate billboard structures.

This paper addresses analysis of dynamic buffeting response of a hinged transmission line (conductor) under nonstationary wind excitations. The nonstationary wind speed is characterized by deterministic time-varying mean and stochastic fluctuating components. The wind load on the conductor is quantified using quasi-steady theory. The wind-induced response of the conductor is decomposed into deterministic time-varying mean and stochastic dynamic components. The time-varying mean response is determined by nonlinear static analysis with an analytical solution. The stochastic dynamic response is determined through quasi-static analysis in terms of influence function around the time-varying mean equilibrium. A closed-form formulation is presented for calculating time-varying standard derivation of response. The cumulative distribution function of the extreme response over a given time duration is then calculate using mean upcrossing rate theory of nonstationary random process. The effectiveness and accuracy of the proposed analytical framework are verified through response time history analysis using a nonlinear finite element model. The response characteristics of conductor under various nonstationary winds are examined through a parametric study.

This study addresses the estimation of buffeting response of overhead conductor based on random vibration theory with closed-form formulations. Special attention is placed on the determination of static deformation with consideration of geometric nonlinearity, and its influence on the dynamic modal properties, aerodynamic modal damping and buffeting response. The dynamic response around the static equilibrium is separated into background and resonant components, which are calculated by using influence function and modal analysis, respectively. The aerodynamic modal damping ratios are estimated in closed-form formulations in which the influence of static swing of the conductor plane is explicitly accounted. Example studies presented in this study illustrate the accuracy and effectiveness of this linear buffeting analysis framework through comparison with nonlinear finite element model (FEM) analysis in the time domain. The importance of consideration of static deformation is revealed for the prediction of alongwind displacement and tension, especially, the resonant response component. The contributions of modal responses to various resonant responses are also examined.

We have investigated the dry etching of Al0.12GaAs/Al0.9GaAs Distributed Bragg Reflectors (DBRs) using photoresist mask in Inductively Coupled Plasma system with Cl2/BCl3/Ar chemistry. Resultant etch rate/etch profiles are studied as a function of ICP process parameters and photoresist mask sidewall profile. The vertical and inclined sidewalls were obtained via controlling mixing gas proportion. Enhancing physical effect in etching, photoresist mask patterns could transfer to etched substrate. In the end, controllable sidewall profile, smooth etch surface and repeatable process of Al0.12GaAs/Al0.9GaAs DBRs etching were achieved.

Surface passivation in InP-based High Electron Mobility Transistors (HEMTs) plays an important role in reducing or eliminating their surface effects which limit both direct-current (DC) and radio-frequency (RF) performances. In the present work, effect of surface passivation was studied using an ultra-thin 20 nm PECVD Si 3 N 4 layer. In DC performance, after passivation, its maximum transconductance ( g m , MAX ) is increased up to 1200 mS/mm. It is found that, by scaling the thickness of Si 3 N 4 layer, the increase in C gd after passivation can be effectively limited verified by small-signal modeling. As a result, S -parameter measurements demonstrate an increase in extracted f max up to 450 GHz after passivation. The results show that, by using an ultra-thin Si 3 N 4 surface passivation, its RF performance can be improved in InP-based HEMTs.

In this work, experiments were carried out to compare the phase separation performance of double branching T-junction with that of single branching T-junction. The inlet and outlet branches of double T-junction were arranged horizontally with the inner diameter of 8 mm. R134a was used as the working fluid. The inlet mass flow rate (mass flux) was set at 10, 15, 20, 25 g s−1 (199, 298, 398, 497 kg m−2 s−1) and the inlet quality was set at 0.3, 0.5, 0.7 respectively in the experiment of single T-junction. It is concluded that the inlet mass flux has little influence on phase separation while the phase separation efficiency drops sharply with the increase of inlet quality, which is consistent with the conclusions in literature. The experimental data is also compared with the predicted values generated by theoretical models based on air-water and it is found that there is no model suitable for refrigerants. Furthermore, a comparative study between single T-junction and double T-junction was carried out from two perspectives: separation performance comparison of different branches and comparison between single and double T-junctions. The results show that the double T-junction performance is greatly affected by inlet quality and mass split ratio of the first branch, and not always higher than that of single T-junction for horizontal arrangement. Finally, predicting equations of outlet quality of double T-junction are correlated based on experimental data, which have a high predicting accuracy under the high mass split ratio conditions.

A Rh(III)-catalyzed aldehyde C–H bond functionalization of salicylaldehydes with arylboronic acids has been developed, with features of mild reaction condition and high efficiency. Furthermore, the functionalized 2-hydroxybenzophenone could be subject to divergent synthesis of heterocycles.

A full aeroelastic model with one tower two lines to simulate electrical transmission tower-line system was established. Displacements and accelerations of the aeroelastic model of the tower with and without lines under various wind speeds were investigated through boundary layer wind tunnel tests, and the maximum wind loads on, and wind-induced destroyed mode of, the tower-line model were also observed. Meanwhile, the static and dynamic loads on electrical transmission tower transferred from lines were acquired by measuring the strains of the insulators at the ends of lines. The effects of coupling between electrical transmission tower and line on wind-induced vibrations of electrical transmission towers were investigated, and the pattern of wind induced responses along with wind speeds, as well as the characteristics of spectra of wind induced dynamic responses, of the aeroelastic model of the tower with and without line were analyzed. The experimental results indicate that the effects of coupling between transmission tower and line on wind-induced responses of the tower, as well as the across-wind vibration of the tower, must take into consideration in the wind-resistant design of electrical transmission tower; and the reinforcement at the weak parts of electrical transmission tower could effectively increase the survival ability of the tower under strong wind.

Post-combustion CO2 capture (PCC) is considered to be an important technology for reducing carbon dioxide emissions owing to its easy retrofit to power plants. Chemical absorption, adsorption and membrane separation are typical mainstreams in PCC. In technological cluster of CO2 adsorption, temperature swing adsorption (TSA) is one of efficient methods. In recent years, the topic on energy consumption and energy efficiency of TSA is emerging as an urgent response to the possible large-scale deployment of CCS. However, most studies apply mathematical model and simulation method for performance assessment for TSA, without enough specific supports from experiment researches. To conduct an experiment-guided analysis on the energy-efficiency of TSA, a 4-step TSA apparatus was designed and developed. The separation and energy-efficiency performance are the main performance indicators in the analysis. Zeolite 13X-APG was employed in experiment and its selectivity of CO2 over N2 was obtained according to isotherms of two components measured experimentally. Four groups of experiment results were obtained for affect analysis from CO2 concentration, desorption duration, adsorption temperature and desorption temperature to the purity, recovery rate, specific energy consumption and second-law efficiency. The results show that the range of second-law efficiency is between 3.24% and 9.23% with the maximum recovery rate of 83.97% and purity of 94.70%. Increase of desorption temperature and CO2 concentration, decrease of adsorption temperature lead to an improvement of the separation and energy-efficiency performance. There exists a reasonable desorption time demonstrates the sufficient desorption. After the time, the improvement of the separation performance is little and the energy efficiency decreases with an excess heat input. The findings may be useful to optimize the operation strategy for TSA system.

The direct vapor generation with parabolic trough solar collector utilizing organic working fluids has a significant potential of large-scale application. In such a system, the non-uniform heat flux commonly exists outside the collector tube which would result in the unique characteristics of two-phase flow and moreover boiling heat transfer. However, few studies pay attention to the effects of the non-uniform heat flux on flow pattern transitions and flow boiling, which have important influence on the long-term stable operation of the system. Therefore, in this study, an experimental system was established to study the two-phase flow boiling of R-245fa in a horizontal tube under the condition of the non-uniform heat flux. The experiment was performed with the mass flow rate from 192.9 to 385.8 kg/(m2 s), heat fluxes from 9.95 to 35.9 kW/m2 and saturation temperatures from 40 to 60 °C. Using a high-speed camera and the image processing, the differences between the flow pattern with non-uniform and uniform heating were analyzed. A comparison study on four available flow pattern I/A transition lines in the literature has been demonstrated as well. The effects of vapor quality, mass velocity, saturation temperature and heat flux on the two-phase heat transfer coefficient were analyzed. Furthermore, based on the experimental data, the correlation of boiling heat transfer of R245fa under non-uniform heat flux was developed. The results indicate that under the same heat addition, the vapor quality where the non-uniform I/A phase transition is lower than the uniform one. Furthermore, the non-uniform heat flux makes R245fa in the tube easier to form nucleation sites, therefore the nucleation boiling can be significantly enhanced. Taking account of the strengthening factor “S” of nucleate boiling, the new correlation of boiling heat transfer can reproduce 94% of data sets under non-uniform heat flux within the uncertainty of ±20%.

Various contents of Ag nanoparticles were successfully introduced into the N-doped TiO 2 photocatalysts via a hydrothermal procedure in the silver-ammonia solutions with different Ag concentrations. Effects of Ag loading on the structure and properties of N-doped TiO 2 photocatalysts were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Raman spectroscopy, fluorescence spectroscopy (FL), UV–vis spectroscopy, X-ray photoelectron spectroscopy (XPS), and N 2 physical adsorption analysis. The relationship between the stability of N dopants in TiO 2 lattice and the Ag loading content was investigated for the first time. The results confirm that Ag nanoparticles loading on TiO 2 surfaces significantly restrain the escape of the N dopants from the oxide during the hydrothermal process, and the escape rate of N dopants decreased gradually with the increase of Ag loading amount. The dependence of photocatalytic activity on Ag content was also investigated through degradation of rhodamine B (RhB) under visible light irradiation. It was found that the photocatalytic activity increases gradually with increasing Ag content first, and then decreases after exceeding the optimal Ag content. Therefore, the photocatalytic activity of Ag/N co-modified TiO 2 photocatalysts can be adjusted by the Ag content.

Pulmonary artery hypertension (PAH) patients exhibit elevated levels of inflammatory cytokines and infiltration of inflammatory cells in the lung. Concurrently, mutations of bmpr2, the gene encoding the type II receptor of bone morphogenetic proteins (BMP), are found in ∼75% of patients with familial PAH, but a possible nexus between increased inflammation and diminished BMP signaling has hitherto remained elusive. We previously showed that BMP4 triggers nuclear localization of the Myocardin-related transcription factor A (MRTF-A) in human pulmonary artery smooth muscle cells (PASMC), resulting in the induction of contractile proteins. Here we report the BMPR2-dependent repression of a set of inflammatory mediators in response to BMP4 stimulation of PASMC. Forced expression of MRTF-A precisely emulates the anti-inflammatory effect of BMP4, while MRTF-A depletion precludes BMP4-mediated cytokine inhibition. BMP4 and MRTF-A block signaling through NF-κB, the keystone of most pathways leading to inflammatory responses, at the level of chromatin recruitment and promoter activation. Moreover, MRTF-A physically interacts with RelA/p65, the NF-κB subunit endowed with a transcription activation domain. Interestingly, the MRTF-A-NF-κB interaction is mutually antagonistic: stimulation of NF-κB signaling by TNFα, as well as p65 overexpression, hinders MRTF-A activity and the expression of contractile genes. Thus, a molecular inhibitory pathway linking BMP4 signaling, activation of MRTF-A, and inhibition of NF-κB provides insights into the etiology of PAH and a potential focus of therapeutic intervention.

High purity BaTiO3 nanopowders were pressed into pellets and annealed between 100 and 1200 °C. The crystal quality and grain size of the BaTiO3 nanocrystals were characterized by X-ray diffraction measurements. Annealing induces an increase in the grain size from 44 to 82 nm with temperature increasing up to 1200 °C. XRD and Raman spectroscopy studies confirm that all the samples were single phase with a tetragonal structure after annealing at different temperatures. Positron annihilation measurements reveal large number of vacancy defects in the grain boundary region. These interfacial defects remain stable after annealing at temperatures below 400 ° C and begin to disappear rapidly above 700 °C. After annealing at 1200 °C, most of the interfacial defects have been removed. Hysteresis loops are observed for the 100 ° C annealed samples, which indicate ferromagnetism in BaTiO3 nanocrystals. The ferromagnetism becomes a little weaker after annealing at 700 °C, and it disappears after 1200 ° C annealing. This change of ferromagnetism coincides with the defect recovery process after annealing, suggesting that ferromagnetism might originate from the interfacial defects.

Objective Cellular and mechanical treatment to prevent heart failure each holds therapeutic promise but together have not been reported yet. The goal of the present study was to determine whether combining a cardiac support device with cell-based therapy could prevent adverse left ventricular remodeling, more than either therapy alone. Methods The present study was completed in 2 parts. In the first part, mesenchymal stem cells were isolated from rodent femurs and seeded on a collagen-based scaffold. In the second part, myocardial infarction was induced in 60 rats. The 24 survivors were randomly assigned to 1 of 4 groups: control, stem cell therapy, cardiac support device, and a combination of stem cell therapy and cardiac support device. Left ventricular function was measured with biweekly echocardiography, followed by end-of-life histopathologic analysis at 6 weeks. Results After myocardial infarction and treatment intervention, the ejection fraction remained preserved (74.9-80.2%) in the combination group at an early point (2 weeks) compared with the control group (66.2-82.8%). By 6 weeks, the combination therapy group had a significantly greater fractional area of change compared with the control group (69.2% ± 6.7% and 49.5% ± 6.1% respectively, P = .03). Also, at 6 weeks, the left ventricular wall thickness was greater in the combination group than in the stem cell therapy alone group (1.79 ± 0.11 and 1.33 ± 0.13, respectively, P = .02). Conclusions Combining a cardiac support device with stem cell therapy preserves left ventricular function after myocardial infarction, more than either therapy alone. Furthermore, stem cell delivery using a cardiac support device is a novel delivery approach for cell-based therapies.

Summaryω-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have beneficial effects on cardiovascular diseases. Cytochrome P-450 (CYP) 2J2 that is expressed in endothelial cells metabolizes arachidonic acids to biologically active epoxyeicosatrienoic acids (EETs) that possess anti-inflammatory and anti-thrombotic effects.We studied the effects of EPA and DHA on the expression of CYP 2J2 mRNA by reverse transcription-polymerase chain reaction in cultured human umbilical vein endothelial cells and found that EPA, but not DHA, increased the expression of CYP 2J2 mRNA in a dose-dependent and a time-dependent manner. EPA-induced CYP 2J2 expression was significantly inhibited by pretreatment with a peroxisome proliferator-activated receptor (PPAR) γ antagonist, GW9662. EPA, but not DHA, caused a significant increase in cellular levels of 11,12-dihydroxyeicosatrienoic acid that is a stable metabolite of 11,12-EET, which was blocked by pretreatment with GW9662.These data demonstrate that EPA increases CYP 2J2 mRNA expression and 11,12-EET production via PPARγ in endothelial cells and indicate a novel protective role of EPA and PPARγ against vascular inflammation.

Fe ions were implanted into ZnO single crystals with multiple energies between 50 and 380 keV up to a total fluence of 12.5 × 1 0 17 cm−2. The crystal quality of Fe+ implanted ZnO was investigated by X-ray diffraction 2 θ scans and ω -rocking curve measurements. The appearance of Fe related diffraction peaks after 700 ° C annealing of the implanted sample indicates possibly formation of Fe nanoparticles. Superconducting quantum interference device measurements revealed ferromagnetic behavior below 250 K for both the as-implanted and post-annealed ZnO. Photoluminescence and Raman scattering as well as X-ray rocking curve measurements all indicate introduction of structural defects after Fe implantation. Some of the defects act as nonradiative recombination centers, and suppress the visible and ultraviolet (UV) emission in ZnO. These defects also break the Raman selection rule, and lead to the activation of some silent phonon modes. Annealing of the implanted sample at 700 ° C causes partial recovery of the defects, however, the X-ray diffraction results of the anneal ZnO show even an improvement of the crystal quality compared with the un-implanted one. This could be attributed to the recovery of the grown-in defects in ZnO.

The γ-ray irradiation effect on poly(vinylidene–trifluoroethylene) 80/20 mol% copolymers was studied. It is found that the irradiation results in the cross-linking in the amorphous area and the carbon–carbon double bond in the copolymer due to dehydrofluorination. The thermal analysis (DTA) data indicate that the irradiation down shifts both the melting temperature and the phase transition temperature, and the irradiation also reduces the crystallinity. It is found that the size of the crystal regions in the copolymer decreases during the irradiation and that the lattice space expanses with the irradiation. The crystal regions with a reduced size might response for the excellent electromechanical properties observed in the irradiated copolymer.