Changes of learning and memory ability associated with neuronal nitric oxide synthase in brain tissues of rats with acute alcoholism

BACKGROUD： Ethanol can influence neural development and the ability of leaming and memory, but its mechanism of the neural toxicity is not clear till now. Endogenous nitric oxide （NO） as a gaseous messenger is proved to play an important role in the formation of synaptic plasticity, transference of neuronal information and the neural development, but excessive nitro oxide can result in neurotoxicity. OBJECTIVE ： To observe the effects of acute alcoholism on the learning and memory ability and the content of neuronal nitric oxide synthase （nNOS） in brain tissue of rats. DESIGN ： A randomized controlled animal experiment. SETTING ： Department of Physiology, Xinxiang Medical College MATERIALS： Eighteen male clean-degree SD rats of 18-22 weeks were raised adaptively for 2 days, and then randomly divided into control group （n = 8） and experimental group （n = 10）. The nNOS immunohistochemical reagent was provided by Beijing Zhongshan Golden Bridge Biotechnology Co.,Ltd. Y-maze was produced by Suixi Zhenghua Apparatus Plant. METHODS ： The experiment was carded out in the laboratory of the Department of Physiology, Xinxiang Medical College from June to October in 2005. ① Rats in the experimental group were intraperitoneally injected with ethanol （2.5 g/kg） which was dissolved in normal saline （20%）. The loss of righting reflex and ataxia within 5 minutes indicated the successful model. Whereas rats in the control group were given saline of the same volume. ② Examinations of learning and memory ability： The Y-maze tests for learning and memory ability were performed at 6 hours after the models establishment. The rats were put into the Y-maze separately. The test was performed in a quiet and dark room. There was a lamp at the end of each of three pathways in Y-maze and the base of maze had electric net. All the lamps of the three pathways were turned on for 3 minutes and then turned off. One lamp was turned on randomly, and the other two delayed automatically. In 5 seconds after alternation, pulsating electric current presented in the base of unsafe area to stimulate rat＇s feet to run to the safe area. The lighting lasted for 15 seconds as one test. Running from unsafe area to safe area at one time in 10 seconds was justified as successful. Such test was repeated for 10 times for each rat and the successful frequency was recorded. The qualified standard of maze test was that the rat ardved in the safe area g times during 10 experiments. The number of trainings for the qualified standard was used to represent the result of spatial learning. ③ Determination of the content of nNOS in brain tissue： After the Y-maze test, the rats were anaesthetized, and blood was let from the incision on right auricle, transcardially perfused via the left ventricle with about 200 mL saline, then fixed by perfusion of 40 g/L paraformaldehyde. Hippocampal CA1 region, corpus striatum and cerebellum were taken to prepare serial freezing coronal sections. The nNOS contents in the brain regions were determined with the immunohistochemical methods to reflect the changes of nitdc oxide in brain tissue. MAIN OUTCOME MEASURES ： The changes of learning and memory ability and the changes of the nNOS contents in the brain tissue of rats with acute alcoholism were observed. RESULTS ： One rat in the experimental group was excluded due to its slow reaction to electdc stimulation in the Y-maze test, and the other 17 rats were involved in the analysis of results. ① The training times to reach qualifying standards of Y-maze in the expedmental group was more than that in the control group [（34.33 ±13.04）, （27.50±8.79） times, P〈 0.05]. ② Forms and numbers of nNOS positive neurons in brain tissue： It could be observed under light microscope that in the hippocampal CA1 region, there were fewer nNOS positive neurons, which were lightly stained, and the processes were not clear enough; But the numbers of the positive neurons which were deeply stained as huffy were obviously increased in the experimental group, the cell body and cyloplasm of process were evenly stained, but the nucleus was not stained. The nNOS positive neurons in corpus stdatum had similar forms and size in the experimental group and control group. The form of the nNOS positive neurons in cerebellum were similar between the two groups. The numbers of nNOS positive neurons in hippocampal CA1 region and corpus striatum in the expedmental group [（18.22±7.47）, （11.38±5.00） cells/high power field] were obviously higher than those in the control group [（10.15±4.24）, （6.15±3.69） cells/high power field. The number of nNOS positive neurons in cerebellum had no significant difference between the two groups [（49.56±18.84）, （44.43±15.42） cells/high power field, P〉 0.05]. CONCLUSION ： Acute alcoholism may impair learning and memory ability, and nitric oxide may be involved in mediating the neurotoxic role of ethanol.

An extended smart driver model considering electronic throttle angle changes with memory

Based on the fact that the electronic throttle angle effect performs well in the traditional car following model,this paper attempts to introduce the electronic throttle angle into the smart driver model(SDM)as an acceleration feedback control term,and establish an extended smart driver model considering electronic throttle angle changes with memory(ETSDM).In order to show the practicability of the extended model,the next generation simulation(NGSIM)data was used to calibrate and evaluate the extended model and the smart driver model.The calibration results show that,compared with SDM,the simulation value based on the ETSDM is better fitted with the measured data,that is,the extended model can describe the actual traffic situation more accurately.Then,the linear stability analysis of ETSDM was carried out theoretically,and the stability condition was derived.In addition,numerical simulations were explored to show the influence of the electronic throttle angle changes with memory and the driver sensitivity on the stability of traffic flow.The numerical results show that the feedback control term of electronic throttle angle changes with memory can enhance the stability of traffic flow,which shows the feasibility and superiority of the proposed model to a certain extent.

Changes in hippocampal neurons and memory function during the developmental stage of newborn rats with hypoxic-ischemic encephalopathy

BACKGROUND: Under the normal circumstance, there exist some synapses with inactive functions in central nervous system (CNS), but these functions are activated following nerve injury. At the early stage of brain injury, the abnormal functions of brain are varied, and they have very strong plasticity and are corrected easily. OBJECTIVE: To observe the changes of neuronal morphology in hippocampal CA1 region and memory function in newborn rats with hypoxic-ischemic encephalopathy(HIE) from ischemia 6 hours to adult. DESIGN: Completely randomized grouping, controlled experiment. SETTING: Taian Health Center for Women and Children; Taishan Medical College. MATERIALS: Altogether 120 seven-day-old Wistar rats, of clean grade, were provided by the Experimental Animal Center, Shandong University of Traditional Chinese Medicine. Synaptophysin (SYN) polyclonal antibody was provided by Maixin Biological Company, Fuzhou. METHODS: This experiment was carried out in the Laboratory of Morphology, Taishan Medical College between October 2000 and December 2003. ① The newborn rats were randomly divided into 2 groups: model group and control group, 60 rats in each group. Five rats were chosen from each group at postoperative 6 hours, 24 hours, 72 hours, 7 days, 2 weeks and 3 weeks separately for immunohistochemical staining. Fifteen newborn rats were chosen from each group at postoperative 4 weeks and 2 months separately for testing memory ability (After test, 5 rats from each group were sacrificed and used for immunohistochemical staining)② The right common carotid artery of newborn rats of model group was ligated under the anesthetized status. After two hours of incubation, the rats were placed for 2 hours in a container filled with nitrogen oxygen atmosphere containing 0.08 volume fraction of oxygen, thus, HIE models were created; As for the newborn rats in the control group, only blood vessels were isolated, and they were not ligated and hypoxia-treated. ③ Thalamencephal tissue sections of newborn rats of two groups were performed DAB developing and haematoxylin slight staining. Cells with normal nucleous in 250 μm-long granular layer which started from hippocampal CA1 region were counted with image analysis system under high-fold optical microscope (×600), and the thickness of granular layer was measured. The absorbance (A) of positive reactant of SYN in immunohistochemically-stained CA1 region was measured. Learning and memory ability were measured with step through test 3 times successively. ④ t test and paired t test were used for comparing intergroup and intragroup difference of measurement data respectively, and Chi-square for comparing the difference of enumeration data. MAIN OUTCOME MEASURES: Comparison of cytological changes in hippocampal CA1 region and memory ability at different postoperative time points between two groups. RESULTS: Totally 120 newborn rats were involved in the result analysis. ① Cell morphological changes in hippocampal CA1 region: In the control group, with aging, perikaryon, nucleus and nucleolus in cortex of parietal lobe were significantly increased, Nissl body was compacted, the amount of neurons was declined, but the A of SYN positive reactant was relatively increased. In the model group, at postoperative each time point, neurons were seriously shrunk and dark-stained, nucleus was contracted, chromatin was condensed, nucleolus was unclear, even cells disappeared, especially the cells in 6 hours and 24 hours groups. The amount of neurons with normal morphology in hippocampal CA1 region and granular layer thickness in the model group at postoperative each time point were significantly less or smaller than those in the control group at postoperative 6 hours respectively (t =3.002-1.254, P < 0.01). The A value of SYN positive reactant at postoperative 2, 3 and 4 weeks was significantly higher than that at previous time point (t =2.011-2.716,P < 0.05-0.01). ② Test results of learning and memory ability: In the first test, there was no significant difference in the ratio of rats which kept memory ability between two groups (P > 0.05); In the third test, the ratio of rats which kept memory ability in the model group was significantly lower than that in the control group at postoperative 4 weeks and 2 months[53%(8/15),100%(15/15);60%(9/15),93%(14/15),χ 2=2.863,2.901,P < 0.01]. CONCLUSION: The destroyed hippocampal structure induces the decrease of learning and memory ability of developmental rats. Early interference can increase the quality of neurons and also promote functional development of the nervous system.

Three-Dimensional Simulations of RESET Operation in Phase-Change Random Access Memory with Blade-Type Like Phase Change Layer by Finite Element Modeling

An optimized device structure for reducing the RESET current of phase-change random access memory （PCRAM） with blade-type like （BTL） phase change layer is proposed. The electrical thermal analysis of the BTL cell and the blade heater contactor structure by three-dimensional finite element modeling are compared with each other during RESET operation. The simulation results show that the programming region of the phase change layer in the BTL cell is much smaller, and thermal electrical distributions of the BTL cell are more concentrated on the TiN/GST interface. The results indicate that the BTL cell has the superiorities of increasing the heating efficiency, decreasing the power consumption and reducing the RESET current from 0.67mA to 0.32mA. Therefore, the BTL cell will be appropriate for high performance PCRAM device with lower power consumption and lower RESET current.

Threshold switching uniformity in In_2Se_3 nanowire-based phase change memory

The uniformity of threshold voltage and threshold current in the In2 Se3 nanowire-based phase change memory （PCM） devices is investigated. Based on the trap-limited transport model, amorphous layer thickness, trap density, and trap depth are considered to clarify their influences upon the threshold voltage and threshold current through simulations.

Current Controlled Relaxation Oscillations in Ge_2Sb_2Te_5-Based Phase Change Memory Devices

The relaxation oscillation of the phase change memory （PCM） devices based on the Ge2Sb2Te5 material is investigated by applying square current pulses. The current pulses with different amplitudes could be accurately given by the independently designed current testing system. The relaxation oscillation across the PCM device could be measured using an oscilloscope. The oscillation duration decreases with time, showing an inner link with the shrinking threshold voltage Vth. However, the relaxation oscillation would not terminate until the remaining voltage Von reaches the holding voltage Vh. This demonstrates that the relaxation oscillation might be controlled by Von. The increasing current amplitudes could only quicken the oscillation velocity but not be able to eliminate it, which indicates that the relaxation oscillation might be an inherent behavior for the PCM cell.

A review of compact modeling for phase change memory

Phase change memory(PCM)attracts wide attention for the memory-centric computing and neuromorphic comput-ing.For circuit and system designs,PCM compact models are mandatory and their status are reviewed in this work.Macro mod-els and physics-based models have been proposed in different stages of the PCM technology developments.Compact model-ing of PCM is indeed more complex than the transistor modeling due to their multi-physics nature including electrical,thermal and phase transition dynamics as well as their interactions.Realizations of the PCM operations including threshold switching,set and reset programming in these models are diverse,which also differs from the perspective of circuit simulations.For the purpose of efficient and reliable designs of the PCM technology,open issues and challenges of the compact modeling are also discussed.

Thermal effect of Ge_2Sb_2Te_5 in phase change memory device

In the fabrication of phase change random access memory （PRAM） devices, high temperature thermal processes are inevitable. We investigate the thermal stability of GezSb2Te5 （GST） which is a prototypical phase change material. After high temperature process, voids of phase change material exist at the interface between Ge2Sb2Te5 and substrate in the initial open memory cell. This lower region of GezSb2Te5 is found to be a Te-rich phase change layer. Phase change memory devices are fabricated in different process conditions and examined by scanning electron microscopy and energy dispersive X-ray. It is found that hot-chuck process, nitrogen-doping process, and lower temperature inter-metal dielectric （IMD） deposition process can ease the thermal impact of line-GST PRAM cell.

Crystallization Process of Superlattice-Like Sb/SiO_2 Thin Films for Phase Change Memory Application

After compositing with SiO_2 layers, it is shown that superlattice-like Sb/SiO_2 thin films have higher crystallization temperature（~240°C）, larger crystallization activation energy（6.22 e V）, and better data retention ability（189°C for 10 y）. The crystallization of Sb in superlattice-like Sb/SiO_2 thin films is restrained by the multilayer interfaces. The reversible resistance transition can be achieved by an electric pulse as short as 8 ns for the Sb（3 nm）/SiO_2（7 nm）-based phase change memory cell. A lower operation power consumption of 0.09 m W and a good endurance of 3.0 × 10~6 cycles are achieved. In addition, the superlattice-like Sb（3 nm）/SiO_2（7 nm） thin film shows a low thermal conductivity of 0.13 W/（m·K）.

Characteristics of Sb6Te4/VO2 Multilayer Thin Films for Good Stability and Ultrafast Speed Applied in Phase Change Memory

The Sb6 Te4/VO2 multilayer thin films are prepared by magnetron sputtering and the potential application in phase change memory is investigated in detail. Compared with Sb6 Te4, Sb6 Te4/VO2 multilayer composite thin films have higher phase change temperature and crystallization resistance, indicating better thermal stability and less power consumption. Also, Sb6 Te4/VO2 has a broader energy band of 1.58 eV and better data retention （125℃ for 103/）. The crystallization is suppressed by the multilayer interfaces in Sbf Te4/VO2 thin film with a smaller rms surface roughness for Sbf Te4/VO2 than monolayer Sb4Te6. The picosecond laser technology is applied to study the phase change speed. A short crystallization time of 5.21 ns is realized for the Sb6Te4 （2nm）/VO2 （8nm） thin film. The Sb6 Te4/VO2 multilayer thin film is a potential and competitive phase change material for its good thermal stability and fast phase change speed.

Set Programming Method and Performance Improvement of Phase Change Random Access Memory Arrays

A novel slow-down set waveform is proposed to improve the set performance and a 1 kb phase change random access memory chip fabricated with a 13nm CMOS technology is implemented to investigate the set performance by different set programming strategies based on this new set pulse. The amplitude difference （I1 - I2） of the set pulse is proved to be a crucial parameter for set programming. We observe and analyze the cell characteristics with different I1 - I2 by means of thermal simulations and high-resolution transmission electron microscopy, which reveal that an incomplete set programming will occur when the proposed slow-down pulse is set with an improperly high I1 - I2. This will lead to an amorphous residue in the active region. We also discuss the programming method to avoid the set performance degradations.

Comprehensive study of the ultrafast photoexcited carrier dynamics in Sb_(2)Te_(3)–GeTe superlattices

Chalcogenide superlattices Sb_(2)Te_(3)-GeTe is a candidate for interfacial phase-change memory(iPCM) data storage devices.By employing terahertz emission spectroscopy and the transient reflectance spectroscopy together,we investigate the ultrafast photoexcited carrier dynamics and current transients in Sb_(2)Te_(3)-GeTe superlattices.Sample orientation and excitation polarization dependences of the THz emission confirm that ultrafast thermo-electric,shift and injection currents contribute to the THz generation in Sb_(2)Te_(3)-GeTe superlattices.By decreasing the thickness and increasing the number of GeTe and Sb_(2)Te_(3) layer,the interlayer coupling can be enhanced,which significantly reduces the contribution from circular photo-galvanic effect(CPGE).A photo-induced bleaching in the transient reflectance spectroscopy probed in the range of~1100 nm to~1400 nm further demonstrates a gapped state resulting from the interlayer coupling.These demonstrates play an important role in the development of iPCM-based high-speed optoelectronic devices.

Phase transformation in Mg Sb_3Te thin films

Mg-doped Sb3Te films are proposed to improve the performance of phase-change memory （PCM）. We prepare Mg- doped Sb3Te films and investigate their crystallization behaviors, structural, optical and electrical properties. We find that Mg-doping can increase the crystallization temperature, enhance the activation energy, and improve the 10-year data retention of Sb3Te. Especially Mg25.19（Sb3Te）74.81 shows higher Tc （~ 190℃） and larger Ea （~ 3.49 eV）, which results in a better data retention maintaining for 10 yr at ~ 112 ℃. Moreover Ra/Rc value is also improved. These excellent properties make Mg-Sb-Te material a promising candidate for the phase-change memory （PCM）.

Polarization readout analysis for multilevel phase change recording by crystallization degree modulation

Four different states of Si15Sb85 and Ge2Sb2Te5 phase change memory thin films are obtained by crystallization degree modulation through laser initialization at different powers or annealing at different temperatures. The polarization characteristics of these two four-level phase change recording media are analyzed systematically. A simple and effective readout scheme is then proposed, and the readout signal is numerically simulated. The results show that a high-contrast polarization readout can be obtained in an extensive wavelength range for the four-level phase change recording media using common phase change materials. This study will help in-depth understanding of the physical mechanisms and provide technical approaches to multilevel phase change recording.

650 ps SET speed in Ge_(2)Sb_(2)Te_(5)phase change memory induced by TiO_(2) dielectric crystal plane

Crystallization speed of phase change material is one of the main obstaclesfor the application of phase change memory(PCM)as storage classmemory in computing systems,which requires the combination ofnonvolatility with ultra-fast operation speed in nanoseconds.Here,wepropose a novel approach to speed up crystallization process of the onlycommercial phase change chalcogenide Ge_(2)Sb_(2)Te_(5)(GST).By employingTiO_(2)as the dielectric layer in phase change device,operation speed of650 ps has been achieved,which is the fastest among existing representativePCM,and is comparable to the programing speed of commercialdynamic random access memory(DRAM).Because of its octahedralatomic configuration,TiO_(2)can provide nucleation interfaces for GST,thus facilitating the crystal growth at the determinate interface area.Ti–O–Ti–O four-fold rings on the(110)plane of tetragonal TiO_(2)is critical forthe fast-atomic rearrangement in the amorphous matrix of GST thatenables ultra-fast operation speed.The significant improvement of operationspeed in PCM through incorporating standard dielectric materialTiO_(2)in DRAM paves the way for the application of phase change memoryin high performance cache-type data storage.

A Survey of Phase Change Memory Systems

As the scaling of applications increases, the demand of main memory capacity increases in order to serve large working set. It is difficult for DRAM （dynamic random access memory） based memory system to satisfy the memory capacity requirement due to its limited scalability and high energy consumption. Compared to DRAM, PCM （phase change memory） has better scalability, lower energy leakage, and non-volatility. PCM memory systems have become a hot topic of academic and industrial research. However, PCM technology has the following three drawbacks： long write latency, limited write endurance, and high write energy, which raises challenges to its adoption in practice. This paper surveys architectural research work to optimize PCM memory systems. First, this paper introduces the background of PCM. Then, it surveys research efforts on PCM memory systems in performance optimization, lifetime improving, and energy saving in detail, respectively. This paper also compares and summarizes these techniques from multiple dimensions. Finally, it concludes these optimization techniques and discusses possible research directions of PCM memory systems in future.

Endurance characteristics of phase change memory cells

The endurance characteristics of phase change memory are studied. With operational cycles, the resis- tances of reset and set states gradually change to the opposite direction. What is more, the operational conditions that are needed are also discussed. The thilure and the changes are concerned with the compositional change of the phase change material. An abnormal phenomenon that the threshold voltage decreases slightly at first and then increases is observed, which is due to the coaction of interthce contact and growing active volume size changing.

Crystallization kinetics of Sn_(40)Se_(60) thin films for phase change memory applications

The crystallization kinetics of Sn4oSe6o thin films has been successfully investigated using sheet resis- tance versus temperature measurements. Thermal evaporation was used to deposit the films on ordinary glass sub- strates. The crystallization temperature for Sn4oSe60 thin film was found to be 156.6 -t- 0.3 ~C. In the as-deposited state, the sheet resistance was found to be 195 Mf2/[2, this value declined to 1560 f2/[2] upon annealing. The value of activation energy obtained from the Kissinger plot was 0.62 ＋ 0.07 eV. From the results obtained, SnaoSe60 is a promising alloy for PCM application because of its high electrical contrast, high crystallization temperature, and relatively high activation energy.

Improving the Performance and Energy Efficiency of Phase Change Memory Systems

Phase change memory （PCM） is a promising technology for future memory thanks to its better scalability and lower leakage power than DRAM （dynamic random-access memory）. However, adopting PCM as main memory needs to overcome its write issues, such as long write latency and high write power. In this paper, we propose two techniques to improve the performance and energy-efficiency of PCM memory systems. First, we propose a victim cache technique utilizing the existing buffer in the memory controller to reduce PCM memory accesses. The key idea is reorganizing the buffer into a victim cache structure （RBC） to provide additional hits for the LLC （last level cache）. Second, we propose a chip parallelism-aware replacement policy （CPAR） for the victim cache to further improve performance. Instead of evicting one cache line once, CPAR evicts multiple cache lines that access different PCM chips. CPAR can reduce the frequent victim cache eviction and improve the write parallelism of PCM chips. The evaluation results show that, compared with the baseline, RBC can improve PCM memory system performance by up to 9.4% and 5.4% on average. Combing CPAR with RBC （RBC＋CPAR） can improve performance by up to 19.0% and 12.1% on average. Moreover, RBC and RBC＋CPAR can reduce memory energy consumption by 8.3% and 6.6% on average, respectively.

Investigation and solution of low yield problem for phase change memory with lateral fully-confined structure

This paper mainly focuses on solving the low yield problem for lateral phase change random access memory with a fully confined phase change material node. Improper over-etching and bad step-coverage of physical vapor deposition were the main reasons for the poor contact quality, which leads to the low yield problem. Process improvement was carried out to better control over-etching within 10 nm. Atomic layer deposition process was used to replace physical vapor deposition to guarantee good step coverage. Contrasting cross-sectional photos taken by scanning electron microscopy showed great improvement in contact quality. The atom layer deposition process was demonstrated to have good prospects in nano-contact for phase change memory application.