Leptomeningeal metastases (LM) are more frequent in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the ...purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM.
Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled.
A total of 28 patients were enrolled in this cohort; CSF and plasma were available in 26 patients, respectively. Driver genes were detected in 100% (26/26), 84.6% (22/26), and 73.1% (19/26) of samples comprising CSF cell-free DNA (cfDNA), CSF precipitates, and plasma, respectively; 92.3% (24/26) of patients had much higher allele fractions in CSF cfDNA than the other two media. Unique genetic profiles were captured in CSF cfDNA compared with those in plasma and primary tissue. Multiple copy number variations (CNVs) were mainly identified in CSF cfDNA, and MET copy number gain identified in 47.8% (11/23) of patients was the most frequent one, while other CNVs included ERBB2, KRAS, ALK, and MYC. Moreover, loss of heterozygosity (LOH) of TP53 was identified in 73.1% (19/26) CSF cfDNA, which was much higher than that in plasma (2/26, 7.7%; P<0.001). There was a trend towards a higher frequency of concomitant resistance mutations in patients with TP53 LOH than those without (70.6% versus 33.3%; P=0.162). EGFR T790M was identified in CSF cfDNA of 30.4% (7/23) of patients who experienced TKI progression.
CSF cfDNA could reveal the unique genetic profiles of LM and should be considered as the most representative liquid biopsy medium for LM in EGFR-mutant NSCLC.
To elucidate the cytotoxicity mechanism of Garnoderma triterpenes, a chemoproteomic study using five purified ganoderic acids, ganoderic acid F (GAF), ganoderic acid K (GAK), ganoderic B (GAB), ...ganoderic acid D (GAD) and ganoderic acid AM1 (GAAM1) was conducted. GAF, GAK, GAB, GAD and GAAM1 treatment for 48 h inhibited the proliferation of HeLa human cervical carcinoma cells with IC
50 values of 19.5±0.6
μM, 15.1±0.5
μM, 20.3±0.4
μM, 17.3±0.3
μM, 19.8±0.7
μM, respectively. The protein expression profiles of HeLa cells treated with each ganoderic acid at dose of 15
μM for 48
h were checked using two-dimensional electrophoresis (2-DE). The possible target-related proteins of ganoderic acids, i.e. proteins with same change tendency in all five ganoderic acids-treated groups compared with control, were identified using MALDI-TOF MS/MS. Twelve proteins including human interleukin-17E, eukaryotic translation initiation factor 5A (eIF5A), peroxiredoxin 2, ubiquilin 2, Cu/Zn-superoxide dismutase, 14-3-3 beta/alpha, TPM4-ALK fusion oncoprotein type 2, PP2A subunit A PR65-alpha isoform, nucleobindin-1, heterogeneous nuclear ribonucleoprotein K, reticulocalbin 1 and chain A of DJ-1 protein were identified. Ganoderic acids might exert their cytotoxicity by altering proteins involved in cell proliferation and/or cell death, carcinogenosis, oxidative stress, calcium signaling and ER stress.
A new model for thermal buckling of an anisotropic elastic composite beam consisting of a dielectric core and two thin semiconductor surface layers is developed. The field equations and boundary ...conditions for the beam are obtained by using the piezoelectricity, flexoelectricity, strain gradient elasticity and semiconductor theories and the kinematic relations for a Timoshenko beam. The current model includes piezoelectric, flexoelectric and semiconducting effects simultaneously, unlike existing models. A variational formulation based on the principle of minimum potential energy is employed for the dielectric core, where the contribution of the two thin semiconductor surface layers is incorporated through the work done by the free charge density. Two simplified models for piezoelectric and flexoelectric composite beams incorporating the semiconducting effect are obtained as two special cases of the new model for the dielectric composite beam. Thermal buckling of a simply supported composite beam with a piezoelectric or flexoelectric core and two thin semiconductor surface layers is analytically studied by directly applying the two simplified models, leading to the determination of the critical buckling temperature and concentration perturbation of free carriers in the composite beam. Numerical results show that the presence of the piezoelectric or flexoelectric effect results in an increased critical buckling temperature, while the inclusion of the semiconducting effect leads to a reduced value in both cases. In addition, it is seen that the redistributions of free carriers in the piezoelectric composite beam are uniform, whereas those in the flexoelectric composite beam are non-uniform along the beam thickness direction.
Two-dimensional (2D) layered molybdenum ditelluride (MoTe2) crystals, featuring a low energy barrier in the crystalline phase transition and a sizable band gap close to that of silicon, are rapidly ...emerging with substantial potential and promise for future nanoelectronics. It has been challenging, however, to realize n-type MoTe2 field-effect transistors (FETs), thus complementary logic, because MoTe2 FETs mainly exhibit p-type behavior. Here, we report a dopant-free method for controlling polarity of MoTe2 FETs by modifying Schottky barriers at their MoTe2–metal contacts via thermal annealing. Upon annealing, MoTe2 FETs encapsulated by hexagonal boron nitride (h-BN) are consistently changed from hole to electron conduction, displaying an on/off current ratio of 105 or higher. When the MoTe2 channel is sandwiched between top and bottom h-BN thin layers (h-BN/MoTe2/h-BN FETs), higher field-effect mobility is attained, up to 48.1 cm2 V–1 s–1 (hole) and 52.4 cm2 V–1 s–1 (electron) before and after thermal annealing, respectively. The thermally controlled FET polarity change further enables high-performance MoTe2 monolithic complementary inverters with gain as high as 36, suggesting this simple and effectual approach may lead to compelling possibilities of rationally controlling transport polarity, on demand, in atomically thin transistors with metal contacts and their 2D integrated circuits.
Micro groove, as a typical surface texture, has played an important role in the development of many advanced fields. This paper introduced an electrochemical machining of micro groove using masked ...porous cathode. A porous metallic plate covered with a mask was prepared as the masked porous cathode. During machining, the masked porous cathode was covered on the workpiece, and the electrolyte could flow into the machining region through the porous structure in the cathode for machining. As the machining unit was closed, the distribution of electrical field was uniform on the machining surface, which could improve the machining accuracy. In addition, the masked porous mask had no damage during machining and could be reused, which improved the machining efficiency. With this method, multiphysics coupling model, including flow field model, electric current model, heat transfer model, reactant transport model, and moving mesh model, was built to investigate their influence on the machining process with different flow modes. The simulation and experiment results indicated that compared with other two flow modes, jet flow mode could provide a high electrolyte velocity in the machining region around the nozzle, and the mass transfer process was enhanced, which was helpful to improve the machining quality. The effect of pulse duty cycle was investigated, and the pulse duty cycle of 20% with the frequency of 2 kHz could further improve the mass transfer process and was preferred to generate micro groove with low standard deviation and roughness. In addition, with the applied voltage rising, the depth of micro groove increased, and increasing the nozzle reciprocating motion number could enhance the mass transfer process during machining, which further improved machining quality. Finally, with the optimized flow mode and machining parameters, a group of ten micro grooves were well generated by using a masked porous cathode with ten micro slits, and the width was about 330 μm with the depth of 45 μm.
The Large High Altitude Air Shower Observatory (LHAASO) is a new generation hybrid cosmic ray observatory which is expected to reveal the mystery of the origin of cosmic rays. The one square ...kilometer array (KM2A) consisting of 5195 Electromagnetic particle Detectors (ED) and 1188 Muon Detectors (MD) is a sub-array of LHAASO. The EDs are designed to measure the density and arriving time of the secondary particles of extensive air showers. The performance of the EDs is tested for the quality control after construction in the laboratory at sea level. In this paper, the performance of more than four thousands EDs is summarized. The performance of all tested EDs meets the design requirements with the time resolution of 1.6 ns, the detection efficiency of 97.8%, charge resolution for single particle of 18.5% and count rate around 480 Hz. Furthermore, one ED is singled out for monitoring of the long-term stability over a period of nearly two years from December 2018 to November 2020.
Background and Aims
Mast cell activation interferes with the effects of allergen‐specific immunotherapy (SIT). Galectin‐1 (Gal‐1) is capable of regulating immune cells’ functions. This study tests ...the hypothesis that administration of Gal‐1 promotes and prolongs the efficacy of SIT via suppressing mast cell activation.
Methods
An intestinal allergy mouse model was developed. The coadministration of SIT and Gal‐1 on suppression of the allergic responses, prevention of mast cell activation, and generation of antigen‐specific regulatory T cells (Treg) in the intestine was observed in sensitized mice.
Results
The coadministration of Gal‐1 and SIT markedly suppressed the allergic responses in the mouse intestine vs the use of either SIT alone or Gal‐1 alone. The Gal‐1 binds to the IgE/FcɛRI complexes on the surface of mast cells to prevent mast cell activation during SIT. Gal‐1 promoted the SIT‐generated allergen‐specific Tregs in the intestine of sensitized mice. Coadministration of Gal‐1 and SIT significantly enhanced the efficacy of immunotherapy in suppressing allergic responses in the intestine, which lasted for at least for 12 months.
Conclusions
Long‐term effects of specific immunotherapy on intestinal allergy can be achieved with Gal‐1/SIT therapy by inhibiting mast cell activation and facilitating Treg development.
Absolute calibration of LHAASO WFCTA camera based on LED An, Q.; Bai, Y.X.; Bastieri, D. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
01/2022, Volume:
1021
Journal Article
Peer reviewed
The main scientific goal of the LHAASO WFCTA experiment is to measure the cosmic ray energy spectra and composition from 10 TeV to 1 EeV. Cherenkov photons in the extensive air shower measured by the ...SiPM camera of Cherenkov telescopes can be used to reconstruct the cosmic ray energy. The absolute calibration of the camera is a crucial step to achieve the accurate measurement of the cosmic ray energy spectrum. A multi-wavelength cylindrical illuminator based on LEDs is developed and mounted inside the telescope to calibrate and monitor the camera, and the illuminator’s stability is better than 0.5% under the temperature variation from -26 to 26 °C. A portable probe with a single photoelectron resolution of 21.6% is developed. After calibration by National Institute of Metrology, China (NIM), the probe is taken to the LHAASO site to measure the absolute photon density of the cylindrical illuminator inside the telescope. Based on the illuminator with known photon density, the photon conversion factor of the camera can be calibrated, and the overall calibration uncertainty is less than 2.6%.
Three-dimensional (3D) topologicalWeyl semimetals (TWSs) represent a state of quantum matter with unusual electronic structures that resemble both a '3D graphene' and a topological insulator. Their ...electronic structure displays pairs of Weyl points (through which the electronic bands disperse linearly along all three momentum directions) connected by topological surface states, forming a unique arc-like Fermi surface (FS). Each Weyl point is chiral and contains half the degrees of freedom of a Dirac point, and can be viewed as a magnetic monopole in momentum space. By performing angle-resolved photoemission spectroscopy on the non-centrosymmetric compound TaAs, here we report its complete band structure, including the unique Fermi-arc FS and linear bulk band dispersion across the Weyl points, in agreement with the theoretical calculations1, 2. This discovery not only confirms TaAs as a 3DTWS, but also provides an ideal platform for realizing exotic physical phenomena (for example, negative magnetoresistance, chiral magnetic effects and the quantum anomalous Hall effect) which may also lead to novel future applications.
•Moisture uptake of FRPs (except BFRP) followed: NC > SWSSNC > DW > HPC > SWSSHPC.•The presence of NaCl in simulated concrete led to a less FRPs moisture uptake.•Simulated high performance concrete ...solution leads to less degradation of FRP.•Greater basalt fiber degradation in SWSSC might due to the reaction of Al, Fe, and Mg with alkali and Cl− ions.•CFRP exhibited the best durability in SWSSC, followed by GFRP and then BFRP.
This paper presents an experimental investigation on the degradation of carbon/glass/basalt fiber reinforced polymer (i.e., CFRP/BFRP/GFRP) exposed to simulated seawater sea sand concrete environments (SWSSC) at 25, 40 and 60 °C for 6 months. The presence of NaCl in simulated concrete environment was found beneficial for the moisture uptake of CFRP and GFRP. The greater fiber degradation of BFRP was attributed to its high aluminium, iron and magnesium contents on fibers. Further, FRPs showed greater degradation resistance in high performance concrete solutions that have a lower alkaline content. Thus, CFRP exhibited the best durability to simulated SWSSC environments, followed by GFRP and BFRP.
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