抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

The accumulation and extrusion of Ca2+ in the pre- and postsynaptic compartments play a critical role in initiating plastic changes in biological synapses. To emulate this fundamental process in electronic devices, we developed diffusive Ag-in-oxide memristors with a temporal response during and after stimulation similar to that of the synaptic Ca2+ dynamics. In situ high-resolution transmission electron microscopy and nanoparticle dynamics simulations both demonstrate that Ag atoms disperse under electrical bias and regroup spontaneously under zero bias because of interfacial energy minimization, closely resembling synaptic influx and extrusion of Ca2+, respectively. The diffusive memristor and its dynamics enable a direct emulation of both short- and long-term plasticity of biological synapses, representing an advance in hardware implementation of neuromorphic functionalities.

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Memristors with diffusive dynamics as synaptic emulators for neuromorphic computing

A memristor is a resistive device with an inherent memory. The theoretical concept of a memristor was connected to physically measured devices in 2008 and since then there has been rapid progress in the development of such devices, leading to a series of recent demonstrations of memristor-based neuromorphic hardware systems. Here, we evaluate the state of the art in memristor-based electronics and explore where the future of the field lies. We highlight three areas of potential technological impact: on-chip memory and storage, biologically inspired computing and general-purpose in-memory computing. We analyse the challenges, and possible solutions, associated with scaling the systems up for practical applications, and consider the benefits of scaling the devices down in terms of geometry and also in terms of obtaining fundamental control of the atomic-level dynamics. Finally, we discuss the ways we believe biology will continue to provide guiding principles for device innovation and system optimization in the field. This Perspective evaluates the state of the art in memristor-based electronics and explores the future development of such devices in on-chip memory, biologically inspired computing and general-purpose in-memory computing.

The future of electronics based on memristive systems

Modern computers are based on the von Neumann architecture in which computation and storage are physically separated: data are fetched from the memory unit, shuttled to the processing unit (where computation takes place) and then shuttled back to the memory unit to be stored. The rate at which data can be transferred between the processing unit and the memory unit represents a fundamental limitation of modern computers, known as the memory wall. In-memory computing is an approach that attempts to address this issue by designing systems that compute within the memory, thus eliminating the energy-intensive and time-consuming data movement that plagues current designs. Here we review the development of in-memory computing using resistive switching devices, where the two-terminal structure of the devices, their resistive switching properties, and direct data processing in the memory can enable area- and energy-efficient computation. We examine the different digital, analogue, and stochastic computing schemes that have been proposed, and explore the microscopic physical mechanisms involved. Finally, we discuss the challenges in-memory computing faces, including the required scaling characteristics, in delivering next-generation computing. This Review Article examines the development of in-memory computing using resistive switching devices.

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In-memory computing with resistive switching devices

A neuromorphic device based on the stable electrochemical fine-tuning of the conductivity of an organic ionic/electronic conductor is realized. These devices show high linearity, low noise and extremely low switching voltage. The brain is capable of massively parallel information processing while consuming only ∼1–100 fJ per synaptic event1,2. Inspired by the efficiency of the brain, CMOS-based neural architectures3 and memristors4,5 are being developed for pattern recognition and machine learning. However, the volatility, design complexity and high supply voltages for CMOS architectures, and the stochastic and energy-costly switching of memristors complicate the path to achieve the interconnectivity, information density, and energy efficiency of the brain using either approach. Here we describe an electrochemical neuromorphic organic device (ENODe) operating with a fundamentally different mechanism from existing memristors. ENODe switches at low voltage and energy ( 500 distinct, non-volatile conductance states within a ∼1 V range, and achieves high classification accuracy when implemented in neural network simulations. Plastic ENODes are also fabricated on flexible substrates enabling the integration of neuromorphic functionality in stretchable electronic systems6,7. Mechanical flexibility makes ENODes compatible with three-dimensional architectures, opening a path towards extreme interconnectivity comparable to the human brain.

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A non-volatile organic electrochemical device as a low-voltage artificial synapse for neuromorphic computing

Memristors have been extensively studied for data storage and low-power computation applications. In this study, we show that memristors offer more than simple resistance change. Specifically, the dynamic evolutions of internal state variables allow an oxide-based memristor to exhibit Ca2+-like dynamics that natively encode timing information and regulate synaptic weights. Such a device can be modeled as a second-order memristor and allow the implementation of critical synaptic functions realistically using simple spike forms based solely on spike activity.

Experimental demonstration of a second-order memristor and its ability to biorealistically implement synaptic plasticity.

Reservoir computing systems utilize dynamic reservoirs having short-term memory to project features from the temporal inputs into a high-dimensional feature space. A readout function layer can then effectively analyze the projected features for tasks, such as classification and time-series analysis. The system can efficiently compute complex and temporal data with low-training cost, since only the readout function needs to be trained. Here we experimentally implement a reservoir computing system using a dynamic memristor array. We show that the internal ionic dynamic processes of memristors allow the memristor-based reservoir to directly process information in the temporal domain, and demonstrate that even a small hardware system with only 88 memristors can already be used for tasks, such as handwritten digit recognition. The system is also used to experimentally solve a second-order nonlinear task, and can successfully predict the expected output without knowing the form of the original dynamic transfer function. Reservoir computing facilitates the projection of temporal input signals onto a high-dimensional feature space via a dynamic system, known as the reservoir. Du et al. realise this concept using metal-oxide-based memristors with short-term memory to perform digit recognition tasks and solve non-linear problems.

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Reservoir computing using dynamic memristors for temporal information processing

Memristors have attracted broad interest as a promising candidate for future memory and computing applications. Particularly, it is believed that memristors can effectively implement synaptic functions and enable efficient neuromorphic systems. Most previous studies, however, focus on implementing specific synaptic learning rules by carefully engineering external programming parameters instead of focusing on emulating the internal cause that leads to the apparent learning rules. Here, it is shown that by taking advantage of the different time scales of internal oxygen vacancy (VO) dynamics in an oxide-based memristor, diverse synaptic functions at different time scales can be implemented naturally. Mathematically, the device can be effectively modeled as a second-order memristor with a simple set of equations including multiple state variables. Not only is this approach more biorealistic and easier to implement, by focusing on the fundamental driving mechanisms it allows the development of complete theoretical and experimental frameworks for biologically inspired computing systems.

Biorealistic Implementation of Synaptic Functions with Oxide Memristors through Internal Ionic Dynamics

Time-series analysis including forecasting is essential in a range of fields from finance to engineering. However, long-term forecasting is difficult, particularly for cases where the underlying models and parameters are complex and unknown. Neural networks can effectively process features in temporal units and are attractive for such purposes. Reservoir computing, in particular, can offer efficient temporal processing of recurrent neural networks with a low training cost, and is thus well suited to time-series analysis and forecasting tasks. Here, we report a reservoir computing hardware system based on dynamic tungsten oxide (WOx) memristors that can efficiently process temporal data. The internal short-term memory effects of the WOx memristors allow the memristor-based reservoir to nonlinearly map temporal inputs into reservoir states, where the projected features can be readily processed by a linear readout function. We use the system to experimentally demonstrate two standard benchmarking tasks: isolated spoken-digit recognition with partial inputs, and chaotic system forecasting. A high classification accuracy of 99.2% is obtained for spoken-digit recognition, and autonomous chaotic time-series forecasting has been demonstrated over the long term. A reservoir computer system based on dynamic tungsten oxide memristors can be used to perform time-series analysis, demonstrating isolated spoken-digit recognition with partial inputs and chaotic system forecasting.

Temporal data classification and forecasting using a memristor-based reservoir computing system

To solve the "big data" problems that are hindered by the Von Neumann bottleneck and semiconductor device scaling limitation, a new efficient in-memory computing architecture based on crossbar array is developed. The corresponding basic operation principles and design rules are proposed and verified using emerging nonvolatile devices such as very low-power resistive random access memory (RRAM). To prove the computing architecture, we demonstrate a parallel 1-bit full adder (FA) both by experiment and simulation. A 4-bit multiplier (Mult.) is further obtained by a programed 2-bit Mult. and 2-bit FA.

Wen Ma

Papers

Experimental demonstration of a second-order memristor and its ability to biorealistically implement synaptic plasticity.

Reservoir computing using dynamic memristors for temporal information processing

Biorealistic Implementation of Synaptic Functions with Oxide Memristors through Internal Ionic Dynamics

Temporal data classification and forecasting using a memristor-based reservoir computing system

Efficient in-memory computing architecture based on crossbar arrays