NEP010, a novel compound with minor structural modification from afatinib, exhibited significantly improved antitumor activity.

Non-small cell lung cancer (NSCLC) is classified into many subclasses according to the specific kinase mutations. The most common mutation is epidermal growth factor receptor (EGFR) somatic mutation, which has promoted the development of several novel drugs (Tyrosine kinase inhibitors, TKIs). Although various TKIs are recommended as targeted therapy for NSCLC with EGFR mutations in NCCN guidelines, not all patients respond equally to the recommended TKIs, which lead to series of novel compound under development to satisfy actual clinical needs. Based on the structure of afatinib, a marketed drug recommended as the first-line therapy for patients with EGFR mutation, NEP010 was synthesized with structural modification. The antitumor efficacy of NEP010 on mouse tumor xenograft models with different EGFR mutations was determined. Results showed that with minor structural modifications on afatinib, the inhibitory effect of NEP010 on EGFR mutant tumors was significantly improved. Pharmacokinetics test was adopted, and compared with afatinib, the increased tissue exposure of NEP010 may be the potential factor responsible for the increased efficacy. Furthermore, tissue distribution test showed a high concentration of NEP010 in the lung which happens to be the target organ of NEP010 in clinical practice. In conclusion, data obtained suggested that NEP010 has an increased anti-tumor effect via improving pharmacokinetics, and may provide a potent therapeutic option for the patients with EGFR mutation of NSCLC in the future.

Whole-Process Risk Management of Soil Amendments for Remediation of Heavy Metals in Agricultural Soil-A Review.

Reducing the mobility and bioavailability of heavy metals in soils by adding exogenous materials is a technology for remediating soils contaminated with heavy metals. Unlike industrial sites, the use of such techniques in agricultural soils requires consideration of not only reducing the mobility of heavy metals but also avoiding adverse effects on soil fertility and the growth of plants. Due to the uncertainty of the stability of amendments applied to agricultural soil, the application of amendments in farmland soil is controversial. This article reviewed the field studies in which amendments were used to immobilize heavy metals, and identified the potential environmental impacts of all aspects of soil amendment usage, including production and processing, transportation, storage, application to soil, long-term stability, and plant absorption. Results of the study indicated that after identifying the environmental risks of the whole process of the application of improvers in agricultural fields, it is necessary to classify the risks according to their characteristics, and design differentiated risk control measures for the safe application of this type of technology.

Stachybotranes A-D, phenylspirodrimanes from the wetland fungus Stachybotrys chartarum with cytotoxic activities.

Four new phenylspirodrimanes, stachybotranes A-D (1-4), along with seven known analogues (5-11), were isolated from the extract of a wetland fungal strain Stachybotrys chartarum DTH12-9. The structures of new compounds were determined by spectroscopic analyses, X-ray crystallographic analysis, and the CD analysis of the in situ formed [Rh2(OCOCF3)4] complex. Compounds 1-3, 5-8, and 10 were evaluated for in vitro cytotoxicity against five human cancer cell lines, HL-60, SMMC-7721, A-549, MCF-7, and SW-480. Compounds 1, 2, and 7 exhibited moderate cytotoxic potency against various human cancer cell lines.

Design, Simulation and Experimental Study of the Linear Magnetic Microactuator.

This paper reports the design, simulation and experimental study of a linear magnetic microactuator for portable electronic equipment and microsatellite high resolution remote sensing technology. The linear magnetic microactuator consists of a planar microcoil, a supporter and a microspring. Its bistable mechanism can be kept without current by external permanent magnetic force, and can be switched by the bidirectional electromagnetic force. The linearization and threshold of the bistable mechanism was optimized by topology structure design of the microspring. The linear microactuator was then fabricated based on non-silicon technology and the prototype was tested. The testing results indicated that the bistable mechanism was realized with a fast response of 0.96 ms, which verified the simulation and analysis.

Effects of Pyrazine Derivatives and Substituted Positions on the Photoelectric Properties and Electromemory Performance of D⁻A⁻D Series Compounds.

Pyrazine derivatives quinoxaline and pyridopyrazine were selected as the acceptors, and benzocarbazole was used as the donor to synthesize four different D⁻A⁻D compounds. The results showed that 2,3-bis(decyloxy)pyridine[3,4-b]pyrazine (DPP) exhibited stronger electron-withdrawing ability than that of 2,3-bis(decyloxy)quinoxaline (DPx), because DPP possesses one more nitrogen (N) atom, resulting in a red-shift of the intramolecular charge transfer (ICT) absorption bands and fluorescent emission spectra for compounds with DPP as the acceptor compared with those that use DPx as the acceptor. The band-gap energy (Eg) of the four D⁻A⁻D compounds were 2.82 eV, 2.70 eV, 2.48 eV, and 2.62 eV, respectively, for BPC-2DPx, BPC-3DPx, BPC-2DPP, and BPC-3DPP. The solvatochromic effect was insignificant when the four compounds were in the ground state, which became significant in an excited state. With increasing solvent polarity, a 30⁻43 nm red shift was observed in the emissive spectra of the compounds. The thermal decomposition temperatures of the four compounds between 436 and 453 °C had very high thermal stability. Resistor-type memory devices based on BPC-2DPx and BPC-2DPP were fabricated in a simple sandwich configuration, Al/BPC-2DPx/ITO or Al/BPC-2DPP/ITO. The two devices showed a binary non-volatile flash memory, with lower threshold voltages and better repeatability.

Bit rate transparent interferometric noise mitigation utilizing the nonlinear modulation curve of electro-absorption modulator.

we propose a bit-rate transparent interferometric noise mitigation scheme utilizing the nonlinear modulation curve of electro-absorption modulator (EAM). Both the zero-slope region and the linear modulation region of the nonlinear modulation curve are utilized to suppress interferometric noise and enlarge noise margin of degraded eye diagrams. Using amplitude suppression effect of the zero-slope region, interferometric noise at low frequency range is suppressed successfully. Under different signal to noise ratio (SNR), we measured the power penalties at bit error rate (BER) of 10<(-9) with and without EAM interferometric noise suppression. By using our proposed scheme, power penalty improvement of 8.5 dB is achieved in a signal with signal-to-noise ratio of 12.5 dB. BER results at various bit rates are analyzed, error floors for each BER curves are removed, significantly improvement in receiver sensitivity and widely opened eye diagrams are resulted.

High-speed tunable microwave photonic notch filter based on phase modulator incorporated Lyot filter.

A high-speed tunable microwave photonic notch filter with ultrahigh rejection ratio is presented, which is achieved by semiconductor optical amplifier (SOA)-based single-sideband modulation and optical spectral filtering with a phase modulator-incorporated Lyot (PM-Lyot) filter. By varying the birefringence of the phase modulator through electro-optic effect, electrically tuning of the microwave photonic notch filter is experimentally achieved at tens of gigahertz speed. The use of SOA-polarizer based single-sideband modulation scheme provides good sideband suppression over a wide frequency range, resulting in an ultrahigh rejection ratio of the microwave photonic notch filter. Stable filter spectrum with bandstop rejection ratio over 60 dB is observed over a frequency tuning range from 1.8 to 10 GHz. Compare with standard interferometric notch filter, narrower bandwidth and sharper notch profile are achieved with the unique PM-Lyot filter, resulting in better filter selectivity. Moreover, bandwidth tuning is also achieved through polarization adjustment inside the PM-Lyot filter, that the 10-dB filter bandwidth is tuned from 0.81 to 1.85 GHz.

Self-interference cancellation using dual-drive Mach-Zehnder modulator for in-band full-duplex radio-over-fiber system.

In this paper, we design a self-interference cancellation (SIC) scheme for in-band full-duplex (IBFD) radio-over-fiber (RoF) systems based on wavelength division multiplexing passive optical network (WDM-PON) architectures. By using a single dual-drive Mach-Zehnder modulator (DDMZM), over various bands up to 25 GHz, this proposed SIC system can simultaneously cancel the in-band downlink (DL) self-interference and modulate the recovered uplink (UL) radio frequency (RF) signal. OFDM-RF signals are used to study the cancellation performances of optical SIC system for the first time. Experimental results show more than 32-dB cancellation depth over 250-MHz bandwidth within 1-GHz RF band, as well as 300-MHz within 2.4-GHz and 400-MHz within 5-GHz band. As for 2.4-GHz RF band, 390.63-Mbps 16-QAM OFDM UL signal buried by strong in-band DL OFDM signal is well recovered. For broadband applications, more than 27-dB cancellation depth is achieved over 10 MHz~25 GHz wideband, so that up to 25 GHz RF band can be expanded for this IBFD WDM-RoF system.

Wideband co-site interference cancellation based on hybrid electrical and optical techniques.

A wideband co-site co-channel interference cancellation system (ICS), based on hybrid electrical and optical techniques, is proposed and is experimentally demonstrated. The demonstrated cancellation system subtracts the in-band wideband interfering signal from the received signal, such that the weak signal of interest (SOI) can be recovered. Our system utilizes a broadband radio frequency (RF) Balun transformer to invert the phase of the interfering signal, while electro-absorption modulated lasers are used for converting the RF signals into the optical domain to enable fine adjustment with the hybrid ICS. We experimentally achieve 45 dB of cancellation over a 220 MHz bandwidth, and over 57 dB of cancellation for a 10 MHz bandwidth, at a center frequency of 900 MHz. The proposed system also experimentally shows good cancellation (30 dB) over an enormously wide bandwidth of 5.5 GHz. To the best of our knowledge, this is the first demonstration of such a wide bandwidth cancellation with good cancellation depth. This property is extremely useful when there are multiple interference signals at various frequency bands. The proposed hybrid ICS has a spurious-free dynamic range of 93.2 dBm/Hz(2/3). Moreover, a 10 Gb/s SOI is recovered from a strong interfering signal, sweeping over 3 GHz bandwidth. A widely open eye diagram, as well as error-free bit-error rate measurements, is experimentally achieved, with the use of the hybrid ICS. The approach also works well for various frequency bands that are within the bandwidth of the Balun transformer and electro-absorption modulated lasers.

Rayleigh backscattering noise suppression based on real-time heterodyne receiver for loop-back WDM-PON.

In this paper, we propose a Rayleigh backscattering (RB) noise mitigation scheme based on the use of real-time heterodyne receiver for loop-back wavelength division multiplexing passive optical network (WDM-PON). Heterodyne detection has been utilized to increase the upstream receiver sensitivity, while an electro-absorption modulator (EAM) is used to simultaneously turn heterodyning bipolar signal into single polar signal and mitigate accumulated carrier RB noise. With the help of the nonlinear negative-slope transfer function of EAM, low frequency interference noise is suppressed successfully. RB noise mitigation performance is studied over 45-km single mode fiber (SMF) transmission, and the optical-signal-to-Rayleigh-noise-ratio (OSRNR) is reduced to 15.6 dB, when bias voltage of EAM is at -4 V. Through utilizing this real-time heterodyne receiver in single fiber loop-back structure, upstream error free transmission is realized with receiver sensitivity of -25 dBm.

High-speed wavelength tunable DPSK demodulation using a phase modulator based loop mirror filter.

A high-speed wavelength tunable differential phase-shift-keying (DPSK) signal demodulator is presented using a phase modulator (PM) based fiber loop mirror filter. By controlling the birefringence of the PM inside the loop through electro-optic effect, wavelength tuning speed of tens of GHz and tuning range of over two free spectral ranges are achieved. Stable filter spectra with extinction ratio over 30 dB are obtained through the tuning process. By combining the birefringence of polarization maintaining fiber and PM, error-free demodulation performance is experimentally achieved throughout the wavelength tuning range for DPSK signals with flexible bit-rate range from 2.5 to 10 Gb/s. This design significantly improves the wavelength tuning speed and is potentially valuable for high-speed switching and tuning applications.

Spiral-structured fiber Bragg grating for contact force sensing through direct power measurement.

A high-sensitivity fiber Bragg grating (FBG) force sensor based on direct optical power measurement is presented. The approach utilizes a novel structure where the FBG is mounted on a thin tube-like fixture spirally. Contact force measurement is achieved through direct measurement of the FBG reflection power at a single wavelength using a power meter. The measuring system in our approach is simple and does not require processing of massive amount of spectral data, enabling real-time contact force monitoring. When force is applied to the FBG sensor, the unique spiral structure leads to FBG chirping and reflection spectrum broadening. A proportional relationship and linear fit are found between the force applied (up to 1.55 N) and the optical power reflected by the proposed FBG sensor. An average sensitivity of 11.16 dB/N is experimentally achieved. This design significantly reduces system complexity and improves data processing speed, which has great practical value in real-time FBG sensing applications.

Suppression of Rayleigh backscattering noise using cascaded-SOA and microwave photonic filter for 10 Gb/s loop-back WDM-PON.

In this paper, we present a novel Rayleigh backscattering (RB) noise mitigation scheme based on central carrier suppression for 10 Gb/s loop-back wavelength division multiplexing passive optical network (WDM-PON). Microwave modulated multi-subcarrier optical signal is used as downstream seeding light, while cascaded semiconductor optical amplifier (SOA) are used in the optical network unit (ONU) for suppressing the central carrier of the multi-subcarrier upstream signal. With central carrier suppression, interference generated by carrier RB noise at low frequency region is eliminated successfully. Transmission performance over 45 km single mode fiber (SMF) is studied experimentally, and the optical-signal-to-Rayleigh-noise-ratio (OSRNR) can be reduced to 15 dB with central carrier suppression ratio (CCSR) of 21 dB. Receiver sensitivity is further improved by 6 dB with the use of microwave photonic filter (MPF) for suppressing residual upstream microwave signal and residual carrier RB at high frequency region.

Study of human dopamine sulfotransferases based on gene expression programming.

A quantitative model is developed to predict the Km of 47 human dopamine sulfotransferases by gene expression programming. Each kind of compound is represented by several calculated structural descriptors of moment of inertia A, average electrophilic reactivity index for a C atom, relative number of triple bonds, RNCG relative negative charge, HA-dependent HDSA-1, and HBCA H-bonding charged surface area. Eight fitness functions of the gene expression programming method are used to find the best nonlinear model. The best quantitative model with squared standard error and square of correlation coefficient are 0.096 and 0.91 for training data set, and 0.102 and 0.88 for test set, respectively. It is shown that the gene expression programming-predicted results with fitness function are in good agreement with experimental ones.