Clinical trial of thalidomide combined with radiotherapy in patients with esophageal cancer

AIM:To investigate the short-term efficacy and tolerability of radiotherapy plus thalidomide in patients with esophageal cancer(EC).METHODS:Serum samples from 86 EC patients were collected before,during,and after radiotherapy,and the vascular endothelial growth factor(VEGF)level was examined by ELISA.According to the change in serum VEGF level during radiotherapy,the patients were divided into two groups:in the drug group,VEGF level was increased or remained unchanged,and thalidomide was administered up to the end of radiotherapy;in the non-drug group,VEGF level was decreased and radiotherapy was given alone.Thirty healthy volunteers served as controls.The efficacy and safety of radiotherapy plus thalidomide therapy were investigated.RESULTS:The 86 EC patients had a significantly higher level of VEGF compared with the 30 healthy controls before radiotherapy(P<0.01),and the VEGF level was significantly correlated with primary tumor size,lymph node metastasis,histopathologic type,and clinical stage(P<0.01).Of 83 evaluable cases,VEGF level was significantly decreased after radiotherapy in32 patients in the drug group(P<0.05),with an effective rate of 71.88%.The incidence of dizziness and/or burnout in the drug group and non-drug group was62.50%and 15.69%,respectively(P=0.000),and the incidence of somnolence was 12.50%and 0%,respectively(P=0.019).No significant differences were observed.CONCLUSION:Thalidomide can down-regulate serum VEGF level in EC patients,and combined with radiotherapy may improve treatment outcome.Thalidomide was well tolerated by EC patients.

Heavy-ion and pulsed-laser single event effects in 130-nm CMOS-based thin/thick gate oxide anti-fuse PROMs

Single event effects of 1-T structure programmable read-only memory(PROM) devices fabricated with a 130-nm complementary metal oxide semiconductorbased thin/thick gate oxide anti-fuse process were investigated using heavy ions and a picosecond pulsed laser. The cross sections of a single event upset(SEU) for radiationhardened PROMs were measured using a linear energy transfer(LET) ranging from 9.2 to 95.6 MeV cm^2mg^(-1).The result indicated that the LET threshold for a dynamic bit upset was ～ 9 MeV cm^2mg^(-1), which was lower than the threshold of ～ 20 MeV cm^2mg^(-1) for an address counter upset owing to the additional triple modular redundancy structure present in the latch. In addition, a slight hard error was observed in the anti-fuse structure when employing209 Bi ions with extremely high LET values(～ 91.6 MeV cm^2mg^(-1)) and large ion fluence(～ 1×10~8 ions cm^(-2)). To identify the detailed sensitive position of a SEU in PROMs, a pulsed laser with a 5-μm beam spot was used to scan the entire surface of the device.This revealed that the upset occurred in the peripheral circuits of the internal power source and I/O pairs rather than in the internal latches and buffers. This was subsequently confirmed by a ^(181)Ta experiment. Based on the experimental data and a rectangular parallelepiped model of the sensitive volume, the space error rates for the used PROMs were calculated using the CRèME-96 prediction tool. The results showed that this type of PROM was suitable for specific space applications, even in the geosynchronous orbit.

Survivin-positive circulating tumor cells as a marker for metastasis of hepatocellular carcinoma

BACKGROUND Circulating tumor cells(CTCs)and survivin are indicators for tumor stage and metastasis,as well as epitheliomesenchymal transition,in various cancers,including hepatocellular cancer(HCC).AIM To explore the potential of survivin-positive CTCs,specifically,as a marker for tumor progression in HCC patients.METHODS We examined the survivin expression pattern in CTCs obtained from 179 HCC patients,and investigated the in vitro effects of survivin silencing and overexpression on the proliferation and invasion of HCC cells.CTC count and survivin expression in patient samples were examined using RNA in situ hybridization.RESULTS All 179 patients were positive for CTC markers,and 94.41%of the CTCs were positive for survivin.The CTC and survivin-positive CTC counts were significantly higher in the HCC patients than in the normal controls,and were significantly associated with tumor stage and degree of differentiation.Further,survivin overexpression was found to induce HepG2 cell proliferation,reduce apoptosis,and improve invasive ability.CONCLUSION Survivin shows upregulated expression(indicative of anti-apoptotic effects)in HCC.Thus,survivin-positive CTCs are promising as a predictor of HCC prognosis and metastasis,and their accurate measurement may be useful for the management of this cancer.

Geant4 simulation of proton-induced single event upset in three-dimensional die-stacked SRAM device

Geant4 Monte Carlo simulation results of the single event upset(SEU)induced by protons with energy ranging from 0.3 MeV to 1 GeV are reported.The SEU cross section for planar and three-dimensional(3D)die-stacked SRAM are calculated.The results show that the SEU cross sections of the planar device and the 3D device are different from each other under low energy proton direct ionization mechanism,but almost the same for the high energy proton.Besides,the multi-bit upset(MBU)ratio and pattern are presented and analyzed.The results indicate that the MBU ratio of the 3D die-stacked device is higher than that of the planar device,and the MBU patterns are more complicated.Finally,the on-orbit upset rate for the 3D die-stacked device and the planar device are calculated by SPACE RADIATION software.The calculation results indicate that no matter what the orbital parameters and shielding conditions are,the on-orbit upset rate of planar device is higher than that of 3D die-stacked device.

Neutron-induced single event upset simulation in Geant4 for three-dimensional die-stacked SRAM

Three-dimensional integrated circuits(3D ICs)have entered into the mainstream due to their high performance,high integration,and low power consumption.When used in atmospheric environments,3D ICs are irradiated inevitably by neutrons.In this paper,a 3D die-stacked SRAM device is constructed based on a real planar SRAM device.Then,the single event upsets(SEUs)caused by neutrons with different energies are studied by the Monte Carlo method.The SEU cross-sections for each die and for the whole three-layer die-stacked SRAM device is obtained for neutrons with energy ranging from 1 MeV to 1000 MeV.The results indicate that the variation trend of the SEU cross-section for every single die and for the entire die-stacked device is consistent,but the specific values are different.The SEU cross-section is shown to be dependent on the threshold of linear energy transfer(LETth)and thickness of the sensitive volume(Tsv).The secondary particle distribution and energy deposition are analyzed,and the internal mechanism that is responsible for this difference is illustrated.Besides,the ratio and patterns of multiple bit upset(MBU)caused by neutrons with different energies are also presented.This work is helpful for the aerospace IC designers to understand the SEU mechanism of 3D ICs caused by neutrons irradiation.

Investigation of flux dependent sensitivity on single event effect in memory devices

Heavy-ion flux is an important experimental parameter in the ground based single event tests. The flux impact on a single event effect in different memory devices is analyzed by using GEANT4 and TCAD simulation methods. The transient radial track profile depends not only on the linear energy transfer （LET） of the incident ion, but also on the mass and energy of the ion. For the ions with the energies at the Bragg peaks, the radial charge distribution is wider when the ion LET is larger. The results extracted from the GEANT4 and TCAD simulations, together with detailed analysis of the device structure, are presented to demonstrate phenomena observed in the flux related experiment. The analysis shows that the flux effect conclusions drawn from the experiment are intrinsically connected and all indicate the mechanism that the flux effect stems from multiple ion-induced pulses functioning together and relies exquisitely on the specific response of the device.

Strategy to mitigate single event upset in 14-nm CMOS bulk FinFET technology

Three-dimensional(3 D)TCAD simulations demonstrate that reducing the distance between the well boundary and N-channel metal-oxide semiconductor(NMOS)transistor or P-channel metal-oxide semiconductor(PMOS)transistor can mitigate the cross section of single event upset(SEU)in 14-nm complementary metal-oxide semiconductor(CMOS)bulk Fin FET technology.The competition of charge collection between well boundary and sensitive nodes,the enhanced restoring currents and the change of bipolar effect are responsible for the decrease of SEU cross section.Unlike dualinterlock cell(DICE)design,this approach is more effective under heavy ion irradiation of higher LET,in the presence of enough taps to ensure the rapid recovery of well potential.Besides,the feasibility of this method and its effectiveness with feature size scaling down are discussed.

Isothermal oxidation behavior of scandium and yttrium co-doped B2-type iron-aluminum intermetallics at elevated temperature

B2 FeA1 intermetallic compounds modified with reactive elements （REs） including Sc and Y were fabricated by vacuum arc-melting, and the isothermal oxidation behavior of the RE-doped alloys at 1373 K was investigated. Both Sc and Y single-doping significantly decrease the alumina film growth rate of the alloys. The alumina film growth rate of Sc＋ Y co-doped alloy even further reduces compared to that of the Sc and Y single-doped alloys. The synergistic effect produced by Sc＋ Y codoping on the growth behavior of alumina was discussed. It could be anticipated that the combined additions of Sc and Y which have matched chemical properties might decrease the alumina film growth rate more effectively and provide FeA1 alloys with enhanced oxidation resistance.

Enhanced alumina film adhesion of Hf/Y-doped iron-aluminum alloys during high-temperature oxidation:a new observation

The cyclic oxidation behavior of Hf/Y-doped B2 FeAl intermetallics at 1373 K was investigated.For an undoped FeAl alloy,premature spallation of the alumina film occurs due to the formation of numerous voids at the film/alloy interface and apparent shrinkage in the film.In contrast to this,doping with either Hf or Y significantly improves the interfacial adhesion between the alumina film and the alloy substrate,particularly with Hf-doping.Microstructural observation in combination with Anger electron spectroscopic analysis suggests that in addition to prohibiting interfacial void formation and alleviating film shrinkage,the addition of Hf in the FeAl alloy could consolidate the film/alloy interface by directly participating in chemical bonding across the interface as a Hf ion.This causes the spallation of alumina film from the equiaxed grains/columnar grains interface rather than the bottom of the film.