8 research outputs found
Loss of TP53 cooperates with c-MET overexpression to drive hepatocarcinogenesis
No full textHepatocellular carcinoma (HCC) is a deadly malignancy with high genetic heterogeneity. TP53 mutation and c-MET activation are frequent events in human HCCs. Here, we discovered that the simultaneous mutations in TP53 and activation of c-MET occur in ~20% of human HCCs, and these patients show a poor prognosis. Importantly, we found that concomitant deletion of Trp53 and overexpression of c-MET (c-MET/sgp53) in the mouse liver led to HCC formation in vivo. Consistent with human HCCs, RNAseq showed that c-MET/sgp53 mouse HCCs were characterized by activated c-MET and Ras/MAPK cascades and increased tumor cell proliferation. Subsequently, a stably passaged cell line derived from a c-MET/sgp53 HCC and corresponding subcutaneous xenografts were generated. Also, in silico analysis suggested that the MEK inhibitor trametinib has a higher inhibition score in TP53 null human HCC cell lines, which was validated experimentally. We consistently found that trametinib effectively inhibited the growth of c-MET/sgp53 HCC cells and xenografts, supporting the possible usefulness of this drug for treating human HCCs with TP53-null mutations. Altogether, our study demonstrates that loss of TP53 cooperates with c-MET to drive hepatocarcinogenesis in vivo. The c-MET/sgp53 mouse model and derived HCC cell lines represent novel and useful preclinical tools to study hepatocarcinogenesis in the TP53 null background
Specifications and Design of a PM Electric Variable Transmission for Toyota Prius II
No full textThis paper focuses on an analysis of technical requirements for the design of a permanent magnet type electric variable transmission (PM-EVT), which is a novel series-parallel hybrid electric vehicle (HEV) powertrain concept. Similar to the planetary gear train used in the Toyota Prius II, the EVT also realizes the power split function. However, it is implemented in an electromagnetic way rather than in a mechanical way, as is the case for the Prius II with a planetary gear. In this paper, a procedure to define the technical requirements of an EVT is presented. Since the Toyota Prius II is a well-known series-parallel HEV, this vehicle is chosen as a reference. The engine, the battery and other necessary components are kept as input data. A dynamic simulation was performed in order to take into account different driving cycles. Then, based on an analysis of the simulation results (torque, speed and power) the technical requirements of the PM-EVT are defined. Finally, the PMEVT machine is designed. The PM-EVT design results are presented and validated using the finite element method. Author Keywords: Electric variable transmission , Permanent magnet machine , Planetary gear , Series-parallel HEV
Proposal and application of a new way to define the weights in the tendering of highway engineering by the Comprehensive Evaluation Method
No full textThe application of Deviation Minimization Model to determine the cost price in the tendering of highway engineering
No full textQuasi-periodic oscillations of the X-ray burst from the magnetar SGR J1935+2154 and associated with the fast radio burst FRB 200428
No full textThe origin(s) and mechanism(s) of fast radio bursts (FRBs), which are short
radio pulses from cosmological distances, have remained a major puzzle since
their discovery. We report a strong Quasi-Periodic Oscillation(QPO) of 40 Hz in
the X-ray burst from the magnetar SGR J1935+2154 and associated with FRB
200428, significantly detected with the Hard X-ray Modulation Telescope
(Insight-HXMT) and also hinted by the Konus-Wind data. QPOs from magnetar
bursts have only been rarely detected; our 3.4 sigma (p-value is 2.9e-4)
detection of the QPO reported here reveals the strongest QPO signal observed
from magnetars (except in some very rare giant flares), making this X-ray burst
unique among magnetar bursts. The two X-ray spikes coinciding with the two FRB
pulses are also among the peaks of the QPO. Our results suggest that at least
some FRBs are related to strong oscillation processes of neutron stars. We also
show that we may overestimate the significance of the QPO signal and
underestimate the errors of QPO parameters if QPO exists only in a fraction of
the time series of a X-ray burst which we use to calculate the Leahy-normalized
periodogram.Comment: 17 pages, 13 figures, accepted for publication by ApJ. arXiv admin
note: text overlap with arXiv:1212.1011 by other authors. text overlap with
arXiv:1212.1011 by other author
