Effect of temperature on heavy ion-induced single event transient on 16-nm FinFET inverter chains

The variations of single event transient(SET)pulse width of high-LET heavy ion irradiation in 16-nm-thick bulk silicon fin field-effect transistor(Fin FET)inverter chains with different driven strengths are measured at different temperatures.Three-dimensional(3D)technology computer-aided design simulations are carried out to study the SET pulse width and saturation current varying with temperature.Experimental and simulation results indicate that the increase in temperature will enhance the parasitic bipolar effect of bulk Fin FET technology,resulting in the increase of SET pulse width.On the other hand,the increase of inverter driven strength will change the layout topology,which has a complex influence on the SET temperature effects of Fin FET inverter chains.The experimental and simulation results show that the device with the strongest driven strength has the least dependence on temperature.

Neuro-bone tissue engineering:emerging mechanisms,potential strategies,and current challenges

The skeleton is a highly innervated organ in which nerve fibers interact with various skeletal cells.Peripheral nerve endings release neurogenic factors and sense skeletal signals,which mediate bone metabolism and skeletal pain.In recent years,bone tissue engineering has increasingly focused on the effects of the nervous system on bone regeneration.Simultaneous regeneration of bone and nerves through the use of materials or by the enhancement of endogenous neurogenic repair signals has been proven to promote functional bone regeneration.Additionally,emerging information on the mechanisms of skeletal interoception and the central nervous system regulation of bone homeostasis provide an opportunity for advancing biomaterials.However,comprehensive reviews of this topic are lacking.Therefore,this review provides an overview of the relationship between nerves and bone regeneration,focusing on tissue engineering applications.We discuss novel regulatory mechanisms and explore innovative approaches based on nerve–bone interactions for bone regeneration.Finally,the challenges and future prospects of this field are briefly discussed.

中西医结合预防脊柱术后深静脉血栓形成的研究进展

本文对近年来中西医方法预防脊柱骨科术后深静脉血栓形成(deep venous thrombosis,DVT)的研究进展进行综述,采取中西医结合的方法包括西医预防、中医预防、中西医结合预防,早期针对性地干预DVT形成的高危因素,探讨其特点和优势,为临床治疗提供客观依据。虽然目前已尝试多种预防手段预防DVT并取得良好的效果,但目前仍存在对病人的症状早期认识不到位、预防方法及具体实施方法不一、缺乏系统指南等问题。

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.

Effect of thermal exposure on microstructure and mechanical properties of Al-Si-Cu-Ni-Mg alloy produced by different casting technologies

The effect of thermal exposure at 350 ℃ for 200 h on microstructure and mechanical properties was investigated for Al-Si-Cu-Ni-Mg alloy, which was produced by permanent mold casting(PMC) and high pressure die casting(HPDC). The SEM and IPP software were used to characterize the morphology of Si phase in the studied alloys. The results show that the thermal exposure provokes spheroidization and coarsening of eutectic Si particles. The ultimate tensile strength of the HPDC alloy after thermal exposure is higher than that of the PMC alloy at room temperature. However, the TEPMC and TEHPDC alloys have similar tensile strength around 67 MPa at 350 ℃. Due to the coarsening of eutectic Si, the TEPMC alloy exhibits better creep resistance than the TEHPDC alloy under studied creep conditions. Therefore, the alloys with small size of eutectic Si are not suitably used at 350 ℃.

Friction and wear behavior of Mg–11Y–5Gd–2Zn–0.5Zr(wt%)alloy with oil lubricant

The sliding friction and wear behaviors of Mg-11Y-5Gd-2Zn-0.5Zr （wt%） alloy were investigated under oil lubricant condition by pin-on-disk configuration with a constant sliding distance of 1,000 m in the temperature range of 25-200℃. Results indicate that the volumetric wear rates and average friction coefficients decrease with the increase of sliding speeds, and increase with the increase of test temperature below 150℃. The hard and thermally stable Mg12（Y,Gd）Zn phase with long-period stacking order structure in the alloy presents significant wear resistance, The wear mechanism below 100℃ is abrasive wear as a result of plastic extrusion deformation. The corporate effects of severe abrasive, oxidative, and delaminating wear result in the tribological mechanism above 100℃.

Prediction of proton-induced SEE error rates for the VATA160 ASIC

We predict proton single event effect(SEE)error rates for the VATA160 ASIC chip on the Dark Matter Particle Explorer(DAMPE) to evaluate its radiation tolerance.Lacking proton test facilities,we built a Monte Carlo simulation tool named PRESTAGE to calculate the proton SEE cross-sections.PRESTAGE is based on the particle transport toolkit Geant4.It adopts a location-dependent strategy to derive the SEE sensitivity of the device from heavy-ion test data,which have been measured at the HI-13 tandem accelerator of the China Institute of Atomic Energy and the heavy-ion research facility in Lanzhou.The AP-8,SOLPRO,and August 1972 worst-case models are used to predict the average and peak proton fluxes on the DAMPE orbit.Calculation results show that the averaged proton SEE error rate for the VATA160 chip is approximately 2.17×10^(-5)/device/day.Worst-case error rates for the Van Allen belts and solar energetic particle events are 1-3 orders of magnitude higher than the averaged error rate.

Heavy ion‑induced MCUs in 28nm SRAM‑based FPGAs:upset proportions,classifications,and pattern shapes

For modern scaling devices,multiple cell upsets(MCUs)have become a major threat to high-reliability field-programmable gate array(FPGA)-based systems.Thus,both performing the worst-case irradiation tests to provide the actual MCU response of devices and proposing an effective MCU distinction method are urgently needed.In this study,high-and medium-energy heavy-ion irradiations for the configuration random-access memory of 28 nm FPGAs are performed.An MCU extraction method supported by theoretical predictions is proposed to study the MCU sizes,shapes,and frequencies in detail.Based on the extraction method,the different percentages,and orientations of the large MCUs in both the azimuth and zenith directions determine the worse irradiation response of the FPGAs.The extracted largest 9-bit MCUs indicate that high-energy heavy ions can induce more severe failures than medium-energy ones.The results show that both the use of high-energy heavy ions during MCU evaluations and effective protection for the application of high-density 28 nm FPGAs in space are extremely necessary.

Differences in MBUs induced by high-energy and medium-energy heavy ions in 28 nm FPGAs

Multiple-bit upsets(MBUs)have become a threat to modern advanced field-programmable gate arrays(FPGAs)applications in radiation environments.Hence,many investigations have been conducted using mediumenergy heavy ions to study the effects of MBU radiation.However,high-energy heavy ions(HEHIs)greatly affect the size and percentage of MBUs because their ionizationtrack structures differ from those of medium-energy heavy ions.In this study,the different impacts of high-energy and medium-energy heavy ions on MBUs in 28 nm FPGAs as well as their mechanisms are thoroughly investigated.With the Geant4 calculation,more serious energy effects of HEHIs on MBU scales were successfully demonstrated.In addition,we identified worse MBU responses resulting from lowered voltages.The MBU orientation effect was observed in the radiation of different dimensions.The broadened ionization tracks for tilted tests in different dimensions could result in different MBU sizes.The results also revealed that the ionization tracks of tilted HEHIs have more severe impacts on the MBU scales than mediumenergy heavy ions with much higher linear energy transfer.Therefore,comprehensive radiation with HEHIs is indispensable for effective hardened designs to apply highdensity 28 nm FPGAs in deep space exploration.

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.

Thoughts on Development of Green Agriculture and Green Economy——Based on the Survey of Farms in Qinhuangdao

Based on the concept and development process of green agriculture and green economy,the field survey and questionnaire investigation were carried out in Jincheng Specialized Planting Cooperative in Xinji Town,Changli County of Qinhuangdao City. The results show that there are still many problems in the development of green economy and the improvement of green farms in Hebei Province. On this basis,it came up with pertinent measures and recommendations,in the hope of providing theoretical basis and reference for establishment and development of green farms in Hebei Province and most of domestic areas.

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.

Influences of total ionizing dose on single event effect sensitivity in floating gate cells

The influences of total ionizing dose （TID） on the single event effect （SEE） sensitivity of 34-nm and 25-nm NAND flash memories are investigated in this paper. The increase in the cross section of heavy-ion single event upset （SEU） in memories that have ever been exposed to TID is observed, which is attributed to the combination of the threshold voltage shifts induced by 7-rays and heavy ions. Retention errors in floating gate （FG） cells after heavy ion irradiation are observed. Moreover, the cross section of retention error increases if the memory has ever been exposed to TID. This effect is more evident at a low linear energy transfer （LET） value. The underlying mechanism is identified as the combination of the defects induced by 7-rays and heavy ions, which increases the possibility to constitute a multi-trap assisted tunneling （m- TAT） path across the tunnel oxide.

Medicinal chemistry strategies towards the development of non-covalent SARS-CoV-2 Mpro inhibitors

The main protease(M^(pro))of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life cycle.The covalent M^(pro)inhibitor nirmatrelvir(in combination with ritonavir,a pharmacokinetic enhancer)and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic use.Effective antiviral drugs are needed to fight the pandemic,while non-covalent M^(pro)inhibitors could be promising alternatives due to their high selectivity and favorable druggability.Numerous non-covalent M^(pro)inhibitors with desirable properties have been developed based on available crystal structures of M^(pro).In this article,we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent M^(pro)inhibitors,followed by a general overview and critical analysis of the available information.Prospective viewpoints and insights into current strategies for the development of non-covalent M^(pro)inhibitors are also discussed.

Discovery of novel sulfonamide substituted indolylarylsulfones as potent HIV-1 inhibitors with better safety profiles

Indolylarylsulfones(IASs) are classical HIV-1 non-nucleoside reverse transcriptase inhibitors(NNRTIs) with a unique scaffold and possess potent antiviral activity.To address the high cytotoxicity and improve safety profiles of IASs,we introduced various sulfonamide groups linked by alkyl diamine chain to explore the entrance channel of non-nucleoside inhibitors binding pocket.48 compounds were designed and synthesized to evaluate their anti-HIV-1 activities and reverse transcriptase inhibition activities.Especially,compound R_(10)L_(4) was endowed with significant inhibitory activity towards wild-type HIV-1(EC_(50(WT))=0.007μmol/L,SI=30,930) as well as a panel of single-mutant strains exemplified by L100I(EC_(50)=0.017μmol/L,SI=13,055),E138K(EC_(50)=0.017μmol/L,SI=13,123) and Y181C(EC_(50)=0.045μmol/L,SI=4753) which were superior to Nevirapine and Etravirine.Notably,R_(10)L_(4) was characterized with significantly reduced cytotoxicity(CC_(50)=216.51μmol/L) and showed no remarkable in vivo toxic effects(acute and subacute toxicity).Moreover,the computer-based docking study was also employed to characterize the binding mode between R_(10)L_(4) and HIV-1 RT.Additionally,R_(10)L_(4) presented an acceptable pharmacokinetic profile.Collectively,these results deliver precious insights for next optimization and indicate that the sulfonamide IAS derivatives are promising NNRTIs for further development.

Endoplasmic Reticulum Stress Induces the Early Appearance of Pro-apoptotic and Anti-apoptotic Proteins in Neurons of Five Familial Alzheimer＇s Disease Mice

Background： Amyloid β （Aβ） deposits and the endoplasmic reticulum stress （ERS） are both well established in the development and progression of Alzheimer＇s disease （AD）. However, the mechanism and role of Aβ-induced ERS in AD-associated pathological progression remain to be elucidated. Methods： The five familial AD （5×FAD） mice and wild-type （WT） mice aged 2, 7, and 12 months were used in the present study. Monis water maze test was used to evaluate their cognitive performance, lmmunofluorescence and Western blot analyses were used to examine the dynamic changes of pro-apoptotic （CCAAT/enhancer-binding protein homologous protein [CHOP] and cleaved caspase-12） and anti-apoptotic factors （chaperone glucose-regulated protein [GRP] 78 and endoplasmic reticulum-associated protein degradation-associated ubiquitin ligase synovial apoptosis inhibitor 1 [SYVN 1]） in the ERS-associated unfolded protein response （UPR） pathway. Results： Compared with age-matched WT mice, 5 xFAD mice showed higher cleaved caspase-3, lower neuron-positive staining at the age of 12 months, but earlier cognitive deficit at the age of 7 months （all P 〈 0.05）. Interestingly, for 2-month-old 5×FAD mice, the related proteins involved in the ERS-associated UPR pathway, including CHOP, cleaved caspase-12, GRP 78, and SYVN 1, were significantly increased when compared with those in age-matched WT mice （all P 〈 0.05）. Moreover, ERS occurred mainly in neurons, not in astrocytes. Conclusions： These findings suggest that compared with those of age-matched WT mice, ERS-associated pro-apoptotic and anti-apoptotic proteins are upregulated in 2-month-old 5×FAD mice, consistent with intracellular Aβ aggregation in neurons.

Microstructure, tensile properties and creep behavior of Al-12Si-3.5Cu-2Ni-0.8Mg alloy produced by different casting technologies

The relationship between the as-cast microstructure and mechanical properties of the Al-12Si-3.SCu- 2Ni-0.8Mg alloys produced by permanent mold casting （PMC） and high pressure die casting （HPDC） is investigated. The alloys in both PMC and HPDC consist of Al, Si, A15 Cu2 MgsSi6, Al3 CuNi, and Al Cu4Ni phase. However, the microstructure of the HPDC alloy is significantly refined. Compared to the PMC alloy, the ultimate tensile strength of the HPDC alloy is significantly increased from 244 MPa to 310 MPa, while the elongation shows a reverse trend at room temperature. At low stress and temperature range, slight variations of stress exponent and activation energy indicate that the minimum creep rate is controlled by the grain boundary creep. Then the minimum creep rate is higher for the specimen with the smaller grain size, where grain boundary creep is the dominant creep mechanism. At high stress region, the stress exponent for the PMC alloy and HPDC alloy is 5.18 and 3.07, respectively. The different stress exponents and activation energies measured at high stress and high temperature range indicates that the creep mechanism varies with the casting technologies.2017 Published by Elsevier Ltd on behalf of The editorial office of Journal of Materials Science ＆ Technology.

Effects of Zr,Ti and Sc additions on the microstructure and mechanical properties of Al-0.4Cu-0.14Si-0.05Mg-0.2Fe alloys

The evolution of microstructure and mechanical properties of Al-0.4 Cu-0.14 Si-0.05 Mg-0.2 Fe（wt.%）alloys, micro-alloyed with Zr, Ti and Sc, were investigated. The addition of 0.2%Zr to base alloy accelerates the precipitation of Si-rich nano-phase in α-Al matrix, which plays an important role in improving the mechanical properties of an alloy. The tensile strength increases from 102 MPa for the base alloy to 113 MPa for the Zr-modified alloy. Adding 0.2%Zr + 0.2%Ti to base alloy effectively refines a-Al grain size and accelerates the precipitation of Si and Cu elements, leading to heavy segregation at grain boundary.By further adding 0.2%Sc to Zr + Ti modified alloy, the segregation of Si and Cu elements is suppressed and more Si and Cu precipitates appeared in α-Al matrix. Accompanied with the formation of coherent Al;Sc phase, the tensile strength increases from 108 MPa for the Zr + Ti modified alloy to 152 MPa for the Sc-modified alloy. Due to excellent thermal stability of Al;Sc phase, the Sc-modified alloy exhibits obvious precipitation hardening behavior at 350℃, and the tensile strength increases to 203 MPa after holding at 350 ℃ for 200 h.

Transcriptional regulators that differentially control dendrite and axon development

Neurons are the basic units of connectivity in the nervous system. As a signature feature, neurons form polarized structures： dendrites and axons, which integrate either sensory stimuli or inputs from upstream neurons and send outputs to target cells, respectively. The separation of dendritic and axonal compartments is achieved in two steps during development： 1） dendrite and axon specification： how neurites are initially specified as dendrites and axons; and 2） dendrite and axon commitment： how dendrites and axons are committed to distinct compartmental fates and architectures. To understand neural circuit assembly and to correct erroneous dendrite or axon growth in a compartment-specific manner, it is essential to understand the regulatory mechanisms underlying dendrite and axon commitment. Compared to extensive studies on dendrite and axon specification, little is known about the molecular mechanisms exclusively dedicated to dendrite or axon commitment. Recent studies have uncovered the requirement of transcriptional regulation in this process. Here, we review the studies on transcriptional regulators： Darl, p300-SnoN, NeuroD, which have been shown to separate dendrite- and axon-specific growth of the same neuron type after compartmental fates are specified.