To accommodate the gait and balance disorder of the elderly with age progression and the occurrence of various senile diseases, this paper proposes a novel gait balance training robot (G-Balance) ...based on a six degree-of-freedom parallel platform. Using the platform movement and IMU wearable sensors, two training modes, i.e., active and passive, are developed to achieve vestibular stimulation. Virtual reality technology is applied to achieve visual stimulation. In the active training mode, the elderly actively exercises to control the posture change of the platform and the switching of the virtual scene. In the passive training mode, the platform movement is combined with the virtual scene to simulate bumpy environments, such as earthquakes, to enhance the human anti-interference ability. To achieve a smooth switching of the scene, continuous speed and acceleration of the platform motion are required in some scenarios, in which a trajectory planning algorithm is applied. This paper describes the application of the trajectory planning algorithm in the balance training mode and the optimization of jerk (differential of acceleration) based on cubic spline planning, which can reduce impact on the joint and enhance stability.
As the core component of an intelligent neuromorphic computer system, reliable synaptic devices process vast amounts of data with high computing speed and low energy consumption. In this work, the ...ion‐doped eco‐friendly solution‐processed indium oxide (InOx)/aluminum oxide (AlOx) electrolyte gate transistors (EGTs) with typical and reliable synaptic behavior are proposed. The lithium ions doped into the AlOx solid‐state layer to facilitate the generation of electrical double layers and doped into InOx to improve the stability of long‐term potentiation/depression cyclic update and enhance the synaptic plasticity. Finally, an artificial neural network simulator is well designed to electrocardiogram signal recognition based on the Gmax/Gmin ratio and nonlinearity of weight update curve. According to the results, the device possesses tremendous potential for biosignal prediction and neural intervention. Moreover, for the first time, the recognition accuracy of the abnormality of the cardiovascular can reach over 94.8% obtained from the confusion matrix. Consequently, this research article presents a stable and robust neuromorphic device for biosignal recognition based on solid‐state EGTs via the synaptic long‐term plasticity.
The neuromorphic computing for the prediction of cardiovascular abnormalities and recognition of matrix data based on eco‐friendly synaptic electrolyte gate transistor is proposed to realize the integrated storage and computing function. An artificial neural network simulator is well designed to realize digital image and electrocardiogram signal recognition based on the Gmax/Gmin and nonlinearity of the electrolyte gate transistors.
Background
The first‐line standard treatment of non‐small cell lung cancer (NSCLC) with EGFR mutation is EGFR‐tyrosine kinase inhibitors (TKIs). However, most patients will develop acquired ...resistance after 9–13 months. This study investigated novel molecular mechanisms of acquired resistance to EGFR‐TKIs to identify a potential new treatment for EGFR‐TKI resistant NSCLC patients.
Methods
We established an EGFR‐TKI resistant cell line (HCC827‐TR) by culturing the HCC827‐P cell line through continuous erlotinib culture. We used Sanger sequencing, RT‐PCR, and western blot to rule out known resistance mechanisms in HCC827‐TR cells, including EGFR‐T790M and MET, PTEN, or EGFR expression changes. Next‐generation sequencing was performed and identified differentially expressed genes between two cell lines and examined the genes with GO and KEGG pathway database analyses. We also examined the molecular alterations in COSMIC and GDSC databases and performed hazard predictions using SIFT, PolyPhen‐2, Mutation Taster, and CADD.
Results
Our results identified FGF2 as a differentially expressed gene with a G101T point mutation in HCC827‐TR cells that showed high mutation frequency and hazard score. HCC827‐TR cells showed elevated FGF2 compared to parental cells. It is noteworthy that treatment with the FGFR inhibitor AZD4547 could restore the sensitivity of HCC872‐TR cells to erlotinib.
Conclusions
An erlotinib‐resistant cell line HCC827‐TR was successfully constructed and we identified the EGFR‐TKI resistance mechanism involving the FGF2 gene mutation. Targeted inhibition of the FGF2/FGFR signaling pathway may effectively restore the sensitivity of the resistant cells to erlotinib. These results suggest a novel treatment strategy for EGFR‐TKI resistant NSCLC patients.
Key points
Significant findings of the study: Identifies a novel molecular mechanism for EGFR‐TKI acquired resistance.
What this study adds: A potential novel strategy for the treatment of EGFR‐TKI resistant NSCLC patients.
The defibrinogenating effect of batroxobin (Defibrase®) in male Wistar rats and the inhibitory effects of the plasma of batroxobin-treated rats on the migration of human vascular smooth muscle cells ...(SMCs) were investigated in vitro. At 1 h after a single intravenous injection of 3.0, 10.0 or 30.0 BU/kg batroxobin (ten rats in each group), the fibrinogen levels in the plasma of the rats decreased to 88.3, 66.2 and 16.5%, respectively, of that in the plasma of control saline-treated rats (261.0±26.7 mg/dl). When the plasma from the batroxobin-treated rats was added to Dulbecco's modified Eagle's medium at a concentration of 0.2% for a vascular SMC migration assay and incubated in a modified Boyden's chamber system at 37°C for 24 h, significant inhibitory effects on vascular SMC migration were observed in the 10.0 (
P<0.05) and 30.0 BU/kg (
P<0.01) batroxobin-treated rats. The plasma of batroxobin-treated rats as well as standard rat fibrinogen induced vascular SMC migration in a fibrinogen content-dependent manner except the plasma of the 30.0 BU/kg batroxobin-treated rats. Moreover, the rat serum (0.1∼5.0%) did not show any activity on vascular SMC migration in the present experimental system. These results indicate that the plasma fibrinogen significantly influences vascular SMC migration, and that the inhibitory effect of the plasma of batroxobin-treated rats on vascular SMC migration is related to the defibrinogenating action of batroxobin in vivo.
Cavity optomechanical (COM) sensors, as powerful tools for measuring ultraweak forces or searching for dark matter, have been implemented to date mainly using linear COM couplings. Here, quantum ...force sensing is explored by using a quadratic COM system which is free of bistability and allows accurate measurement of mechanical energy. We find that this system can be optimized to achieve a force sensitivity \(7\) orders of magnitude higher than any conventional linear COM sensor, with experimentally accessible parameters. Further integrating a quadratic COM system with a squeezing medium can lead to another \(3\) orders enhancement, well below the standard quantum limit and reaching the zeptonewton level. This opens new prospects of making and using quantum nonlinear COM sensors in fundamental physics experiments and in a wide range of applications requiring extreme sensitivity.
The title compound, Li(C18H32N3Si2)n, is a convenient ligand‐transfer reagent for the synthesis of metal complexes of this β‐diketiminate ligand. Lithium is coordinated by three N atoms: two are in ...the delocalized NCCCN fragment and one is from the pyridyl in an adjacent molecule. Owing to the coordination of lithium by the pyridyl N atom, the crystal structure displays a one‐dimensional polymeric structure.
Aim： Previous study has shown that endometrial cancers with LKB1 inactivation are highly responsive to mTOR inhibitors. In this study we examined the effect of LKB1 gene status on mTOR inhibitor ...responses in non-small cell lung cancer （NSCLC） cells. Methods： Lung cancer cell lines Calu-1, H460, H1299, H1792, and A549 were treated with the mTOR inhibitors rapamycin or everolimus （RADO01）. The mTOR activity was evaluated by measuring the phosphorylation of 4EBP1 and S6K, the two primary mTOR substrates. Cells proliferation was measured by MTS or sulforhodamine B assays. Results： The basal level of mTOR activity in LKB1 mutant A549 and H460 cells was significantly higher than that in LKB1 wild-type Calu-1 and H1792 cells. However, the LKB1 mutant A549 and H460 cells were not more sensitive to the mTOR inhibitors than the LKB1 wild-type Calu-1 and H1792 cells. Moreover, knockdown of LKB1 gene in H1299 cells did not increase the sensitivity to the mTOR inhibitors. Treatment with rapamycin or RADO01 significantly increased the phosphorylation of AKT in both LKB1 wild-type and LKB1 mutant NSCLC cells, which was attenuated by the PI3K inhibitor LY294002. Furthermore, RADO01 combined with LY294002 markedly enhanced the growth inhibition on LKB1 wild-type H1792 cells and LKI31 mutant A549 cells. Conclusion： LKB1 gene inactivation in NSCLC cells does not increase the sensitivity to the mTOR inhibitors. The negative feedback activation of AKT by mTOR inhibition may contribute to the resistance of NSCLC cells to mTOR inhibitors.
The treatment of LiCH(SiMe
3)
2 with Bu
tCN followed by the addition of
m- and
p-cyanopyridines gave two
tert-butyl- and pyridyl-substituted β-diketiminato lithium complexes
Li
(
L
¯
L
′
)
n
LL’ = ...N(SiMe
3)C(Bu
t)C(H)C(
m-Py)NSiMe
3 (1) and LL’ = = N(SiMe
3)C(Bu
t)C(H)C(
p-Py)NSiMe
3 (2), and a one-dimensional polymeric chain could be observed in their crystal structures.
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