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A liquid crystal (LC)-based double dipole terahertz phase shifter is proposed. The block model is utilized in simulations to analysis the influence of inhomogeneity of the LC substrate. The sensitive parameters of the double dipole are simulated and analyzed. An array consisting of 30 × 30 patch elements is designed and fabricated. Experimental results exhibit that the phase shift is over 360° in the range of 355.8–358.8 GHz at 1 kHz, at an applied AC bias in the 0–50 V range. The phase change at different frequencies of AC bias voltage is also investigated, and the effect of the frequency of AC bias voltage is expressed by the coefficient of the amplitude of the bias voltage.

This article reports on the investigation, manufacture, and testing of a liquid crystal (LC)-based tunable terahertz (THz) metamaterial (MM) metal-dielectric-metal (MDM) structure, which has low insertion loss (IL) and large modulation depth (MD). The demonstrated structure consists of two parallel layers of a quartz dielectric surrounding two copper layers. The copper structures were printed on the inner surfaces of the upper and lower surfaces of the quartz substrate, to form periodic arrays of sub-wavelength circular loops. The transmission characteristics and the LC parameters are calculated and analyzed for THz electromagnetic (EM) waves in the frequency range from 220 to 330 GHz. The experimental results show that at 285.45 GHz, 294.8 GHz, 305.91 GHz, and 314.38 GHz, the IL is below 4.08 dB and an intensity MD greater than 70.56% is available for THz EM waves with normal incidence. By varying the voltage applied to the LC layer (0–4.8 V), which contains the MDM structure, the frequency corresponding to the valley is decreased to 285.45 GHz, with a frequency tunability greater than 13.5%. The theoretical calculations and experimental results are in good agreement. The MDM structure shows good prospects for THz modulators and switches, due to its excellent performance and simple planar geometry.

We present a reflective spatial phase shifter which operates at terahertz regime above 325 GHz. The controllable permittivity of the nematic liquid crystals was utilized to realize a tunable terahertz (THz) reflective phase shifter. The reflective characteristics of the terahertz electromagnetic waves and the liquid crystal parameters were calculated and analyzed. We provide the simulation results for the effect of the incident angle of the plane wave on the reflection. The experiment was carried out considering an array consisting of 30 × 30 patch elements, printed on a 20 × 20 mm quartz substrate with 1-mm thickness. The phase shifter provides a tunable phase range of 300° over the frequency range of 325 to 337.6 GHz. The maximum phase shift of 331° is achieved at 330 GHz. The proposed phase shifter is a potential candidate for THz applications, particularly for reconfigurable reflectarrays.

The respiratory tract is heavily populated with innate immune cells, but the mechanisms that control such cells are poorly defined. Here we found that the E3 ubiquitin ligase TRIM29 was a selective regulator of the activation of alveolar macrophages, the expression of type I interferons and the production of proinflammatory cytokines in the lungs. We found that deletion of TRIM29 enhanced macrophage production of type I interferons and protected mice from infection with influenza virus, while challenge of Trim29−/− mice with Haemophilus influenzae resulted in lethal lung inflammation due to massive production of proinflammatory cytokines by macrophages. Mechanistically, we demonstrated that TRIM29 inhibited interferon-regulatory factors and signaling via the transcription factor NF-κB by degrading the adaptor NEMO and that TRIM29 directly bound NEMO and subsequently induced its ubiquitination and proteolytic degradation. These data identify TRIM29 as a key negative regulator of alveolar macrophages and might have important clinical implications for local immunity and immunopathology.

Under hypersonic flight conditions, the sharp cowl-lip leading edges have to be blunted because of the severe aerodynamic heating. This paper proposes four cowl-lip blunting methods and studies the corresponding flow characteristics and performances of the generic hypersonic inlets by numerical simulation under the design conditions of a flight Mach number of 6 and an altitude of 26 km. The results show that the local shock interference patterns in the vicinity of the blunted cowl-lips have a substantial influence on the flow characteristics of the hypersonic inlets even though the blunting radius is very small, which contribute to a pronounced degradation of the inlet performance. The Equal Length blunting Manner (ELM) is the most optimal in that a nearly even reflection of the ramp shock produces an approximately straight and weak cowl reflection shock. The minimal total pressure loss, the lowest cowl drag, maximum mass-capture and the minimal aeroheating are achieved for the hypersonic inlet. For the other blunting manners, the ramp shock cannot reflect evenly and produces more curved cowl reflection shock. The Type V shock interference pattern occurs for the Cross Section Cutting blunting Manner (CSCM) and the strongest cowl reflection shock gives rise to the largest flow loss and drag. The cowl-lip blunted by the other two blunting manners is subjected to the shock interference pattern that transits with an increase in the blunting radius. Accordingly, the peak heat flux does not fall monotonously with the blunting radius increasing. Moreover, the cowl-lip surface suffers from severe aerothermal load when the shear layer or the supersonic jet impinges on the wall.

Connective tissue growth factor (CTGF/CCN2) is involved in extracellular matrix production, tumor cell proliferation, adhesion, migration, and metastasis. Recent studies have shown that CTGF expression is elevated in precursor B-acute lymphoblastic leukemia (ALL) and that increased expression of CTGF is associated with inferior outcome in B-ALL. In this study, we characterized the functional role and downstream signaling pathways of CTGF in ALL cells. First, we utilized lentiviral shRNA to knockdown CTGF in RS4;11 and REH ALL cells expressing high levels of CTGF mRNA. Silencing of CTGF resulted in significant suppression of leukemia cell growth compared to control vector, which was associated with AKT/mTOR inactivation and increased levels of cyclin-dependent kinase inhibitor p27. CTGF knockdown sensitized ALL cells to vincristine and methotrexate. Treatment with an anti-CTGF monoclonal antibody, FG-3019, significantly prolonged survival of mice injected with primary xenograft B-ALL cells when co-treated with conventional chemotherapy (vincristine, L-asparaginase and dexamethasone). Data suggest that CTGF represents a targetable molecular aberration in B-ALL, and blocking CTGF signaling in conjunction with administration of chemotherapy may represent a novel therapeutic approach for ALL patients.

DNA methylation and BLC-2 are potential therapeutic targets in acute myeloid leukemia (AML). We investigated pharmacologic interaction between the DNA methyltransferase inhibitor 5-azacytidine (5-AZA) and the BCL-2 inhibitor ABT-737. Increased BCL-2 expression determined by reverse phase protein analysis was associated with poor survival in AML patients with unfavorable cytogenetics (n = 195). We found that 5-AZA, which itself has modest apoptotic activity, acts synergistically with ABT-737 to induce apoptosis. The 5-AZA/ABT-737 combination enhanced mitochondrial outer membrane permeabilization, as evidenced by effective conformational activation of BAX and ∆ψ(m) loss. Although absence of p53 limited apoptotic activities of 5-AZA and ABT-737 as single agents, the combination synergistically induced apoptosis independent of p53 expression. 5-AZA down-regulated MCL-1, known to mediate resistance to ABT-737, in a p53-independent manner. The 5-AZA/ABT-737 combination synergistically induced apoptosis in AML cells in seven of eight patients. 5-AZA significantly reduced MCL-1 levels in two of three samples examined. Our data provide a molecular rationale for this combination strategy in AML therapy.

On the basis of model test and theoretical analysis of velocity and pressure distributions, an hypothesis is presented that the distribution of tangential velocity in radial direction seems to be a combinational distribution of a quasi-free vortex and a quasiforced vortex for the discharge tunnel of rotary-obstruction composite inner energy dissipation. The variations of corresponding parameters about the hypothesis are obtained under test conditions in this paper. The formula of pressure distribution in radial direction is deduced theoretically, and the theoretical values of pressure distribution computed by the formula are well consistent with the measured ones, showing that the formula is correct and can be applied to the computation and analysis of pressure distribution of this discharge tunnel.

Triple-negative breast cancer (TNBC) is a unique subgroup defined by a lack expression of ER (estrogen receptor), PR(progesterone receptor) and HER2 (human epidermal growth factor receptor 2), which has distinctly biological, clinical and pathological characteristics. This subgroup has close relationship with basal-like and BRCA1 (breast cancer susceptibility gene-1) breast cancers. Since endocrine and HER2-targered therapy can not be applied, chemotherapy is the major mean of therapy. Some studies show that TNBC is sensitive to taxol, platinum and anthracycline-based chemotherapy. Furthermore, targeted therapy to EGFR (epidermal growth factor receptor), c-kit (stem cell factor receptor) and PARP (poly ADP-ribose polymerase) inhibitor may show better anticancer activity. We will review this subgroup of breast cancer as the following three aspects, biological characteristics, clinicopathology characteristics and therapy strategy.

The influences of concentration and modulus of sodium silicate solution and curing mode on the phase composition, microstructure and strength development in the geopolymers prepared using Class F fly ash were investigated. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and MAS NMR were utilized. Results show that the compressive strength increases as sodium silicate solution modulus increases, but when modulus exceeds 1.4, the compressive strength decreases, and it decreases markedly while the modulus is greater than 2.0. The compressive strength was improved by the increase of sodium silicate solution concentration. When the concentration is 32%, the compressive strength reaches the maximum, then it reduces as concentration increasing. Elevated temperature can increase the strength of samples that synthesized from sodium silicate solution with 32% concentration and modulus 1.2. Compared to the strength of the sample cured at 50 °C, the strength of the samples cured at 65 °C and 80 °C are higher at 1 d and 3 d, but the same at 7 d. At high temperature, prolonged curing time will decrease the strength. Long precuring at room temperature before application of heat is beneficial for strength development, and there is about 50% increase in strength of the samples cured at 1 d precuring and 2 d elevated temperature as compared to the strengths of the samples cured for 3 d at elevated temperatures or cured for 28 d at room temperature. The main product of reaction in the geopolymeric material is amorphous alkali aluminosilicate gel.

A field investigation on Quaternary glacial landforms in Laoshan Mountain has discovered many glacial potholes, scouring grooves on top of granite ridges, and large boulders. These erosional landforms were formed by the meltwater from the overlying ice cap, suggesting that there was at least an ice cap covering Laoshan Mountain and the surrounding areas or even a continental ice sheet over the vast area of Shandong Province in the Late Pleistocene. The ice sheet was obstructed by the Laoshan Mountain, Dazhu Mountain and Xiaozhu Mountain in the coastal areas as it moved toward the Yellow Sea. The ice flows eroded the bedrock and carved the weak intersection of the fault systems in the NE and NW directions into a deep channel, which gradually formed a fjord in the area of the Jiaozhou Bay basin by 20.00 ka BP. The seawater gradually invaded the fjord from the beginning of the Holocene (11.00 ka BP) and Jiaozhou Bay was eventually formed. Similar fjords are easily found along the east of China and they share a similar origin because of the Quaternary glaciation in the region.

Two types of flow configurations with bleed in two-dimensional hypersonic flows are numerically examined to investigate their aerodynamic thermal loads and related flow structures at choked conditions. One is a turbulent boundary layer flow without shock impingement where the effects of the slot angle are discussed, and the other is shock wave boundary layer interactions where the effects of slot angle and slot location relative to shock impingement point are surveyed. A key separation is induced by bleed barrier shock on the upstream slot wall, resulting in a localized maximum heat flux at the reattachment point. For slanted slots, the dominating flow patterns are not much affected by the change in slot angle, but vary dramatically with slot location relative to the shock impingement point. Different flow structures are found in the case of normal slot, such as a flow pattern similar to typical Laval nozzle flow, the largest separation bubble which is almost independent of the shock position. Its larger detached distance results in 20% lower stagnation heat flux on the downstream slot corner, but with much wider area suffering from severe thermal loads. In spite of the complexity of the flow patterns, it is clearly revealed that the heat flux generally rises with the slot location moving downstream, and an increase in slot angle from 20 to 40 reduces 50% the heat flux peak at the reattachment point in the slot passage. The results further indicate that the bleed does not raise the heat flux around the slot for all cases except for the area around the downstream slot corner. Among all bleed configurations, the slot angle of 40 located slightly upstream of the incident shock is regarded as the best.

Two easily-prepared pyridine-based derivatives of (Z)-2-(4-amino-phenyl)-3-(pyridine-4-yl)acrylonitrile (I)and (Z)-2-phenyl-3-(pyridin-4-yl)acrylonitrile (II) were designed, synthesised and characterised. Due to the formation of a complex with Hg2+, hence leading to an enhanced ICT effect, I exhibits a visible colour change from light yellow to orange, rendering it suitable for use as a naked-eye sensor for rapid detection of Hg2+ in an aqueous ethanol solution. When mixed with Hg2+, I interacts with Hg2+ in a2:1 (Y1-Hg2+) stoichiometry via a coordination bond with an association constant of 7.7 × 108 M−2 (R2 = 0.96). The present probe I exhibits excellent reproducibility, reversibility, sensitivity and selectivity with the presence of low concentration of Hg2+ (1.74 × 10−10 M).

Nat. Immunol.; doi:10.1038/ni.3580; corrected online 10 October 2016 In the version of this article initially published online, the immunoblots in Figures 1a, 5a, 5b, 5c, 5d, 5f, 6a, 6b, 7a, 7b, 8a and 8b were in color. These have been replaced with black and white immunoblots. The error has been corrected for the print, PDF and HTML versions of this article.