// Liangshun You 1 , Hui Liu 1 , Jian Huang 2 , Wanzhuo Xie 1 , Jueying Wei 1 , Xiujin Ye 1 , Wenbin Qian 1 1 Institute of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, P.R. China 2 Department of Hematology, The Fourth Affiliated Hospital, College of Medicine, Zhejiang University, Yiwu 322000, P.R. China Correspondence to: Wenbin Qian, email: qianwenb@hotmail.com Keywords: BCR/ABL, T315I mutation, chronic myeloid leukemia, JNJ-26854165 Received: May 14, 2016 Accepted: December 05, 2016 Published: December 15, 2016 ABSTRACT Chronic myeloid leukemia (CML) is a clonal malignant disease caused by the expression of BCR/ABL. MDM2 (human homolog of the murine double minute-2) inhibitors such as Nutlin-3 have been shown to induce apoptosis in a p53-dependent manner in CML cells and sensitize cells to Imatinib. Here, we demonstrate that JNJ-26854165, an inhibitor of MDM2, inhibits proliferation and triggers cell death in a p53-independent manner in various BCR/ABL-expressing cells, which include primary leukemic cells from patients with CML blast crisis and cells expressing the Imatinib-resistant T315I BCR/ABL mutant. The response to JNJ-26854165 is associated with the downregulation of BCR/ABL dependently of proteosome activation. Moreover, in all tested CML cells, with the exception of T315I mutation cells, combining JNJ-26854165 and tyrosine kinase inhibitor (TKI) Imatinib or PD180970 leads to a synergistic effect. In conclusion, our results suggest that JNJ-26854165, used either alone or in combination with TKIs, represents a promising novel targeted approach to overcome TKI resistance and improve patient outcome in CML.
This paper presents a novel transmission line which has a constant phase shifter over a wide band, referenced to a uniform transmission line. The novel transmission line is loaded with lumped element. Compared with the conventional coupled line phase shifter, the configuration shows good performance with simplicity in both design and fabrication. And the use of lumped elements make the size more compact, especially for low band phase shifter design. To verify the configuration, a 90 degree phase shifter using a transmission line loaded with a capacitor and an inductor is designed. Excellent performance is achieved with small insertion loss and phase deviation over a bandwidth of 116%. The operating frequency ranges from 824 MHz to 2690 MHz, covering the bands of mobile communication 2G, 3G and 4G.
A dual-band dual-polarized low-profile antenna loaded with an artificial magnetic conductor (AMC) reflector is proposed for 5G base stations. The proposed antenna consists of a pair of crossed dual-band rectangular dipoles and an AMC reflector, which operates as the perfect magnetic conductor (PMC) in the lower band and the perfect electric conductor (PEC) in the upper band. By using the AMC reflector instead of the conventional PEC reflector, the distance between the dipole radiator and the reflector can be reduced from 0.25λ 0 to 0.14λ 0 (where λ 0 is the free-space wavelength at 3.45 GHz) without performance degradation. Simulated results show that the proposed antenna has an impedance bandwidth of 3.2-3.7 GHz and 4.8-5.0 GHz, covering the sub-6 GHz spectra for 5G mobile communications in China. The simulated antenna peak gains are 8.1 dBi in the lower band and 6.2 dBi in the upper band. The port isolation of the proposed antenna is better than 20 dB within the 5G operating band.
Abstract This paper presents a compact quad-band bandpass filter. The filter is realized by multi-embedded stub-load resonators. By utilizing multi-embedded structure, the whole filter exhibits a compact size. And due to the multi-section stub-loaded lines, four passbands can be realized and the center frequency of the four passbands can be controlled individually to accommodate different communication protocols. Moreover, by using 0° degree feed structure, there are two transmission zeros locates at left and right side of a passband, which greatly enhance the selectivity. To validate the proposed idea, a quad-band bandpass filter, which operates at 2/2.7/3.45/4.55 GHz is implemented. The insertion loss is smaller than 2 dB and return loss is better than 10 dB. Good agreement between the predicted and measured results demonstrates the proposed idea.
NF-κB inducing kinase (NIK), which is considered as the central component of the non-canonical NF-κB pathway, has been proved to be an important target for the regulation of the immune system. In the past few years, NIK inhibitors with various scaffolds have been successively reported, among which type I1/2 inhibitors that can not only bind in the ATP-binding pocket at the DFG-in state but also extend into an additional back pocket, make up the largest proportion of the NIK inhibitors, and are worthy of more attention. In this study, an integration protocol that combines molecule docking, MD simulations, ensemble docking, MM/GB(PB)SA binding free energy calculations, and decomposition was employed to understand the binding mechanism of 21 tricyclic type I1/2 NIK inhibitors. It is found that the docking accuracy is largely dependent on the selection of docking protocols as well as the crystal structures. The predictions given by the ensemble docking based on multiple receptor conformations (MRCs) and the MM/GB(PB)SA calculations based on MD simulations showed higher linear correlations with the experimental data than those given by conventional rigid receptor docking (RRD) methods (Glide, GOLD, and Autodock Vina), highlighting the importance of incorporating protein flexibility in predicting protein-ligand interactions. Further analysis based on MM/GBSA demonstrates that the hydrophobic interactions play the most essential role in the ligand binding to NIK, and the polar interactions also make an important contribution to the NIK-ligand recognition. A deeper comparison of several pairs of representative derivatives reveals that the hydrophobic interactions are vitally important in the structural optimization of analogs as well. Besides, the H-bond interactions with some key residues and the large desolvation effect in the back pocket devote to the affinity distinction. It is expected that our study could provide valuable insights into the design of novel and potent type I1/2 NIK inhibitors.
With the rapid development of wireless communication systems, there is an urgent demand to increase the data rate of wireless communication systems. In this case a wireless system should be a broadband and multiband system and there will be more multiband antennas instead of single band antenna for wireless communication. Then, the design of a broadband and multiband antenna is one of the important things for a wireless communication system. Here we proposed a dual band small antenna for WLAN system. The antenna was designed to be integrated in the print circuit board of a WLAN system. In order to reduce the antenna size, a short pin was added to the antenna element and the ground plan. A bended radiation armis used to get another resonant frequency. The simulated results showed that the antenna have two resonant frequencies in 2.4 GHz and 5.8 GHz which could meet the WLAN system's requirement. In addition to this, the designed antenna had an advantage of easy to produce and no additional cost.
We propose a bent corrugated substrate integrated waveguide (BCSIW) structure that can be used to design a high gain leaky wave antenna (LWA). The design removes the need for a metallic via fabrication process needed for standard substrate integrated waveguides (SIW) and displays superior performance to previously reported structures. We use simulations to compare the performance of the proposed BCSIW LWA to equivalent standard SIW and corrugated SIW (CSIW) structures, as well as experimentally characterize a fabricated BCSIW LWA. Simulation results show that the BCSIW structure can help improve the impedance bandwidth of a slotted LWA by about 14.7% while still maintaining high gain (about 13.2-17.4 dBi) as compared to an LWA based on a CSIW structure. Measurement results indicate that the proposed BCSIW LWA has a wide impedance bandwidth (32.6%) and a high peak gain (12-16.2 dBi) throughout a large frequency range from 22 to 29.2 GHz with a large beam angle range from -69° to -10°.
Abstract Background Most of previous researches on anatomic resection (AR) in early hepatocellular carcinoma (HCC) were conducted in high‐volume centres with controversial results. This study aims to provide evidence of the utilization of AR in early HCC at population level. Methods The Surveillance, Epidemiology, and End Results 18 registries database (2004–2015) of the USA was utilized to identify early HCC cases ≤5 cm. Overall survival and cancer‐specific survival were both analysed. Results A total of 976 AR and 409 wedge resection (WR) cases were identified. For the post‐operative (death within 1 month) and middle‐term (death within 3 years) survival, effect of AR was found to be similar to that of WR after adjusting other covariates. However, for the long‐term (death within 5 years) survival, the therapeutic effect of AR proved to be superior to that of WR (relative risk (RR) 0.655 for overall survival; RR 0.658 for cancer‐specific survival, both P < 0.05). Furthermore, subgroup analyses suggested that patients characterizing as male, tumour size 1–30 mm, vascular invasion and normal alpha‐fetoprotein were more likely to benefit from AR in long‐term prognosis (all P < 0.05). Conclusions This study suggests that AR, when adopted at population level, is a better choice in comparison with WR in early HCC based on the evidences that it could provide equivalent post‐operative, middle‐term prognosis and superior long‐term survival.
Abstract This paper presents a novel balanced filter with enhanced stopband by using discriminating coupling. The proposed design utilizes third-order quarter-wavelength coupled resonators to obtain the filtering responses. Discriminating coupling is applied between feedline and resonator. The circuit is theoretically analyzed and implemented for demonstration. The operating frequency is located at 2.4 GHz and the common-mode rejection is larger than 20 dB up to 9 GHz (3.75 f 0 ). Due to discriminating coupling, the differential mode out-of-band rejection is larger than 20 dB up to 18 GHz (7.5 f 0 ), which shows wide stopband.
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