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Gene fusions can drive tumor development for multiple types of cancer. Currently, many drugs targeting gene fusions are being approved for clinical application. At present, tyrosine receptor kinase (TRK) inhibitors targeting neurotrophic tyrosine receptor kinase (NTRK) gene fusions are among the first "tumor agnostic" drugs approved for pan-cancer use. Representative TRK inhibitors, including larotrectinib and entrectinib, have shown high efficacy for many types of cancer. At the same time, several second-generation drugs designed to overcome first-generation drug resistance are undergoing clinical development. Due to the rarity of NTRK gene fusions in common cancer types and technical issues regarding the complexity of fusion patterns, effectively screening patients for TRK inhibitor treatment in routine clinical practice is challenging. Different detection methods including immunohistochemistry, fluorescence in situ hybridization, reverse transcription-polymerase chain reaction, and (DNA and/or RNA-based) next-generation sequencing have pros and cons. As such, recommending suitable tests for individual patients and ensuring the quality of tests is essential. Moreover, at present, there is a lack of systematic review for the clinical efficacy and development status of first- and second-generation TRK inhibitors. To resolve the above issues, our expert group has reached a consensus regarding the diagnosis and treatment of NTRK gene fusion solid tumors, aiming to standardize clinical practice with the goal of benefiting patients with NTRK gene fusions treated with TRK inhibitors.

High‐throughput gene sequencing has identified various genetic variants as the culprits for some common hereditary cancers. However, the heritability of a substantial proportion of cancers remains unexplained, which may result from rare deleterious mutations hidden in a myriad of nonsense genetic variations. This poses a great challenge to the understanding of the pathology and thus the rational design of effective treatments for affected patients. Here, whole genome sequencing is employed in a representative case in which one monozygotic twin is discordant for lung inflammatory myofibroblastoma to disclose rare tumor‐related mutations. A missense single nucleotide variation rs61955126 T>C in the lysine methyltransferase SETD8 (accession: NM_020382, SETD8C302R) is exposed. It is shown that SETD8 is vital for genomic integrity by promoting faithful DNA replication, and its C302R mutation downregulates the p53/p21 pathway. Importantly, the SETD8C302R mutation significantly increases the sensitivity of cancer cells to WEE1 inhibition. Given that WEE1 inhibitors have shown great promise for clinical approval, these results impart a potential therapeutic approach using WEE1 inhibitor for cancer patients carrying the same mutation, and indicate that genome sequencing and genetic functional studies can be integrated into individualized therapies., Whole genome sequencing on a pair of identical twins discordant for inflammatory myofibroblastoma and following functional studies reveal a missense single nucleotide variation (rs61955126 T>C) in the lysine methyltransferase SETD8 (accession: NM_020382, SETD8C302R). SETD8 promotes faithful DNA replication and genomic integrity, whereas SETD8C302R mutation downregulates the p53/p21 pathway and increases sensitivity of cancer cells to WEE1 inhibition.

The figure of merit (FoM) is defined to evaluate the performance of ULH devices. The trade-offs between operation voltage, transmittance, and response time in uniform lying helix (ULH) cholesteric liquid crystals (CLC) are investigated. Excellent agreement between theory and experiment is achieved. The viewing angle of ULH displays is also studied. Our results give first quantitative demonstration that ULH exhibits a similar viewing angle to IPS. After phase compensation, the isocontrast ratio of ULH can reach >100:1 over 85° viewing cone.

An optimized blue-phase liquid crystal (BPLC) with a moderate dielectric constant, manageable capacitor charging time, high voltage holding ratio, and submillisecond gray-to-gray response time at room temperature is developed. Using protruded triangular IPS electrodes, the operation voltage can be reduced to 15V while keeping ~74% transmittance. Such a BPLC enables single-TFT addressing and 240-Hz operation. Potential application for color-sequential displays is emphasized. Our new approaches have solved the most critical charging time issue and would accelerate the emergence of the long-awaited blue-phase LCDs. The primetime for BPLCD is around the corner.

We propose a novel pixel circuit using source-follower structure to be independent of frequency effect of blue-phase liquid crystal displays (BPLCDs). Simulation results indicated that required gray-level-voltages across the BPLC could be achieved accurately when a proper threshold voltage of the driving TFT was chosen. We also successfully fabricated a 12.7-inch prototype BPLCD using the proposed pixel circuit driven with a field-sequential-color method of 240 Hz.

Coccidioidomycosis is a fungal infection endemic to south-west USA, north Mexico and parts of Central and South America. We report here a case of primary pulmonary coccidioidomycosis in a previously healthy 14-year-old boy in China, which is considered a non-endemic country. The patient had non-specific symptoms of pulmonary infection, including fever, non-productive cough and night sweats. Both spherules and endospores of Coccidioides immitis were seen histologically following transbronchial biopsy of a cavitary lesion. The patient was treated with amphotericin B and fluconazole. Follow up 6 months post discharge found that the patient made a good recovery.

The characteristics of profiles for wind, temperature and humidity in the baroclinic convective boundary layer on Xizang Plateau were analyzed and discussed based on the observational data of Damxung boundary layer station and the radiosounding data at Lhasa, Gerze and Wuhan during the second field experiment of atmospheric sciences on Qinghai-Xizang Plateau. The results of studies illustrate that the convective boundary layer at daytime on the plateau could develop strongly, with a height of 2 200m which is distinctly higher than that over plain and ocean in middle latitude. The temperature profile in the plateau convective boundary layer has the well mixed characteristics and the maximum value of humidity sometimes appears at certain level in the humidity profile. The budget analyses of heat and water vapour in the plateau convective boundary layer show that the horizontal advection has important effect on the structures of boundary layer. There exists the wind shear phenomenon in the vertical distribution of the average wind speed in the convective boundary layer and the baroclinity formed by the horizontal temperature gradient is the main reason for the formation of the wind shear.

The monthly mean items of energy budget and air temperature, specific humidity and wind vector at 10m over China land and sea areas in 1998 were calculated based on Goddard Earth Observing Data Assimilation System, NASA, United States. The results of model calculation show that the largest surface net radiation of short wave appears in summer (July) in central areas of Xinjiang and Xizang, and reaches a value in high value central area of 275W/m2, and it appears in spring (April) in Yellow Sea and East China Sea with a its value about 250W/m2. The largest surface net radiation of long wave appears in summer (July) in northwestern China, with a value in central area of 125W/m2, and it appears in winter (January) in near China sea areas, with a value of 75–100W/m2. The latent heat flux in near China sea areas in winter (January) is higher than that in other months, its value in central area occurs in southwestern, northern, and northeastern China, and reaches 125W/m2. The calculated results of monthly mean energy budget illustrate that the net flux is transferred from ocean to atmosphere in winter (January) in Yellow Sea and East China Sea, and conversely in summer (July). The net flux value is positive in summer in Xinjiang and central area of Xizang Plateau. The comprehensive analysis for distributions of temperature, humidity and wind vector shows that the water vapour is transported distinctly in summer from South China Sea to eastern China area and from Bay of Bengal to India subcontinent. The water vapour in southwestern area of Xizang comes from its southwestern direction.

A new model for the Doppler sodar antenna was designed and implemented in order to make field experiments it move convenient. The newly assembled digital Doppler sodar is introduced in this paper. The results of comparison experiment illustrated that the wind speed and direction detected by the newly designed sodar are well consistent with those detected by tethersonde, and its functions are equivalent to those of Doppler sodar with a separated antenna previously developed in China and other countries. The newly designed Doppler sodar performed continuous detection for more than 40 days in Tibetan plateau experiment. The detecting results of the Doppler sodar showed that the upward plume motions exist in Dangxiong area, Tibet and that their vertical velocities can reach about 1m/s.

The mesoscale process is separated from a cold front passage by the spectral analysis of the turbulent data obtained from a tower in Beijing. Then the mesoscale fluxes are estimated according to the Taylor hypothesis. The results show that the turbulent momentum flux is much higher than the mesoscale momentum flux when the background wind is high, while the mesoscale flux can not be ignored when the background wind is low. The mesoscale sensible heat flux is influenced by many factors. Generally, the mesoscale sensible heat flux is higher than the turbulent sensible heat flux after the cold front. The analysis of the turbulent flux parameterization shows that it is necessary to include the modification of the mesoscale disturbance when parameterization method is applied on a long time scale. A reasonable parameterization method for flux calculations should include the turbulent flux, the mesoscale flux and the mesoscale modification on the turbulent flux.

Based on the data of STORM-FEST (STorm-scale Operational and Research Meteorology-Front Experiment System Test) carried out near the boundary between Kansas and Nebraska, U. S. in 1992, the vertical distributions of temperature, humidity and wind velocity in the baroclinic convective boundary layer were analysed. The results showed that the temperature and humidity were well mixed in the convective boundary layer. The wind velocity was also well mixed, but there existed wind shear sometime. Under conditions with and without wind shear the turbulent kinetic energy budget was calculated. Finally. The possible reasons of wind shear formation in the convective boundary layer were discussed.

Background Beta-defensin-2 (BD-2) plays an important role in host defense against pathogenic microbe challenge by its direct antimicrobial activity and immunomodulatory functions. The present study aimed to determine whether genetic up-regulation of rat BD-2 (rBD-2) could ameliorate chronic Pseudomonas aeruginosa lung infection in rats. Methods Plasmid-encoding rBD-2 was delivered to lungs in vivo using linear polyethylenimine at 48 h before challenging with seaweed alginate beads containing P. aeruginosa. Macroscopic and histopathological changes of the lungs, bacterial loads, inflammatory infiltration, and the levels of cytokines/chemokines [interleukin (IL)-1β, tumor necrosis factor (TNF)-α, kertinocyte-derived chemokine (KC), macrophage inflammatory protein-2 (MIP-2)] were measured at 3 and 7 days post-infection (p.i.). Results The overexpression of rBD-2 resulted in a significant increase in animal survival rate (at 3 days p.i.), a significant decrease in bacterial loads in the lungs (at 3 and 7 days p.i.), and significantly milder lung pathology. In addition, the overexpression of rBD-2 led to increased infiltration of polymorphonuclear neutrophils (PMN), and elevated protein expression of cytokines/chemokines (IL-1β, TNF-α, KC and MIP-2) at the early stage of infection (at 3 days p.i.), at the same time as being dramatically decreased at the later stage of infection (at 7 days p.i.). Conclusions Genetic up-regulation of rBD-2 increased animal survival rate, and reduced bacterial loads in lungs after bacterial infection. The overexpression of rBD-2 also modulated the production of several cytokines/chemokines and increased PMN recruitment at the early stage of infection. Our findings indicate that the enhancement of BD-2 may be an efficacious intervention for chronic P. aeruginosa lung infection. Copyright © 2010 John Wiley & Sons, Ltd.

Blue phase liquid crystal displays (BPLCDs) have attracted considerable attention in recent years because of its many advantages. However, BPLCDs exhibit narrow temperature range, high driving voltage, and tough process. In our works, polymer-stabilized technology using newly optimized BPLC material was applied to enlarge BP temperature range. In order to overcome high driving voltage, 2D1G design was used to apply conventional source driver IC for cost. Furthermore, novel groove cell structure which could gain more effective electric field without adding special masks for the groove was successfully implemented. Finally, 10-inch BPLCDs was demonstrated by optimization of ODF process.

We reported a new characterization of polymer stabilized blue phase liquid crystal (PSBPLC) by using CIE examination. The results of CIE curve rendered a remarkable turning point when BPII formed in the test cell. We believe this new finding will be useful in manufacturing PSBPLC displays.