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

Memristive devices are electrical resistance switches that can retain a state of internal resistance based on the history of applied voltage and current. These devices can store and process information, and offer several key performance characteristics that exceed conventional integrated circuit technology. An important class of memristive devices are two-terminal resistance switches based on ionic motion, which are built from a simple conductor/insulator/conductor thin-film stack. These devices were originally conceived in the late 1960s and recent progress has led to fast, low-energy, high-endurance devices that can be scaled down to less than 10 nm and stacked in three dimensions. However, the underlying device mechanisms remain unclear, which is a significant barrier to their widespread application. Here, we review recent progress in the development and understanding of memristive devices. We also examine the performance requirements for computing with memristive devices and detail how the outstanding challenges could be met.

Memristive devices for computing

中枢神経系疾患の治療は正常細胞（ニューロン）の機能維持を目的とするが，脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い．一方，脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める．いずれの場合にも，細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である．現在のところ最も研究の進んでいる細胞死の型はアポトーシスである．そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する．

Neuroscience 細胞死：最近の知見

Despite much progress in semiconductor integrated circuit technology, the extreme complexity of the human cerebral cortex, with its approximately 10(14) synapses, makes the hardware implementation of neuromorphic networks with a comparable number of devices exceptionally challenging. To provide comparable complexity while operating much faster and with manageable power dissipation, networks based on circuits combining complementary metal-oxide-semiconductors (CMOSs) and adjustable two-terminal resistive devices (memristors) have been developed. In such circuits, the usual CMOS stack is augmented with one or several crossbar layers, with memristors at each crosspoint. There have recently been notable improvements in the fabrication of such memristive crossbars and their integration with CMOS circuits, including first demonstrations of their vertical integration. Separately, discrete memristors have been used as artificial synapses in neuromorphic networks. Very recently, such experiments have been extended to crossbar arrays of phase-change memristive devices. The adjustment of such devices, however, requires an additional transistor at each crosspoint, and hence these devices are much harder to scale than metal-oxide memristors, whose nonlinear current-voltage curves enable transistor-free operation. Here we report the experimental implementation of transistor-free metal-oxide memristor crossbars, with device variability sufficiently low to allow operation of integrated neural networks, in a simple network: a single-layer perceptron (an algorithm for linear classification). The network can be taught in situ using a coarse-grain variety of the delta rule algorithm to perform the perfect classification of 3 × 3-pixel black/white images into three classes (representing letters). This demonstration is an important step towards much larger and more complex memristive neuromorphic networks.

Training and operation of an integrated neuromorphic network based on metal-oxide memristors

A number of recent efforts have attempted to design accelerators for popular machine learning algorithms, such as those involving convolutional and deep neural networks (CNNs and DNNs). These algorithms typically involve a large number of multiply-accumulate (dot-product) operations. A recent project, DaDianNao, adopts a near data processing approach, where a specialized neural functional unit performs all the digital arithmetic operations and receives input weights from adjacent eDRAM banks.This work explores an in-situ processing approach, where memristor crossbar arrays not only store input weights, but are also used to perform dot-product operations in an analog manner. While the use of crossbar memory as an analog dot-product engine is well known, no prior work has designed or characterized a full-fledged accelerator based on crossbars. In particular, our work makes the following contributions: (i) We design a pipelined architecture, with some crossbars dedicated for each neural network layer, and eDRAM buffers that aggregate data between pipeline stages. (ii) We define new data encoding techniques that are amenable to analog computations and that can reduce the high overheads of analog-to-digital conversion (ADC). (iii) We define the many supporting digital components required in an analog CNN accelerator and carry out a design space exploration to identify the best balance of memristor storage/compute, ADCs, and eDRAM storage on a chip. On a suite of CNN and DNN workloads, the proposed ISAAC architecture yields improvements of 14.8×, 5.5×, and 7.5× in throughput, energy, and computational density (respectively), relative to the state-of-the-art DaDianNao architecture.

ISAAC: a convolutional neural network accelerator with in-situ analog arithmetic in crossbars

Crossbar arrays based on two-terminal resistive switches have been proposed as a leading candidate for future memory and logic applications. Here we demonstrate a high-density, fully operational hybrid crossbar/CMOS system composed of a transistor- and diode-less memristor crossbar array vertically integrated on top of a CMOS chip by taking advantage of the intrinsic nonlinear characteristics of the memristor element. The hybrid crossbar/CMOS system can reliably store complex binary and multilevel 1600 pixel bitmap images using a new programming scheme.

A Functional Hybrid Memristor Crossbar-Array/CMOS System for Data Storage and Neuromorphic Applications

Ultra-low energy biologically-inspired neuron and synapse integrated circuits are presented. The synapse includes a spike timing dependent plasticity (STDP) learning rule circuit. These circuits have been designed, fabricated and tested using a 90 nm CMOS process. Experimental measurements demonstrate proper operation. The neuron and the synapse with STDP circuits have an energy consumption of around 0.4 pJ per spike and synaptic operation respectively.

Energy-Efficient Neuron, Synapse and STDP Integrated Circuits

The design and simulation of a scalable neural chip with synaptic electronics using nanoscale memristors fully integrated with complementary metal?oxide?semiconductor (CMOS) is presented. The circuit consists of integrate-and-fire neurons and synapses with spike-timing dependent plasticity (STDP). The synaptic conductance values can be stored in memristors with eight levels, and the topology of connections between neurons is reconfigurable. The circuit has been designed using a 90 nm CMOS process with via connections to on-chip post-processed memristor arrays. The design has about 16 million CMOS transistors and 73?728 integrated memristors. We provide circuit level simulations of the entire chip performing neuronal and synaptic computations that result in biologically realistic functional behavior.

https://iopscience.iop.org/article/10.1088/0957-4484/24/38/384011/pdf

A scalable neural chip with synaptic electronics using CMOS integrated memristors

The disclosed invention provides apparatus and methods that can convert frequencies of time-encoded signals. In one aspect, a down-converter circuit includes low-pass filters, a switch, a time encoder, and an output low-pass filter. In another aspect, an up-converter circuit includes an analog or digital input time encoder, low-pass filters, a switch, an output time encoder, and a time-encoded band-pass filter. In yet another aspect, a complete receiver system is provided. The receiver system can operate effectively with signals in the radio frequency range.

Down-converter and up-converter for time-encoded signals

Scalability and connectivity are two key challenges in designing neuromorphic hardware that can match biological levels. In this paper, we describe a neuromorphic system architecture design that addresses an approach to meet these challenges using traditional complementary metal-oxide-semiconductor (CMOS) hardware. A key requirement in realizing such neural architectures in hardware is the ability to automatically configure the hardware to emulate any neural architecture or model. The focus for this paper is to describe the details of such a programmable front-end. This programmable front-end is composed of a neuromorphic compiler and a digital memory, and is designed based on the concept of synaptic time-multiplexing (STM). The neuromorphic compiler automatically translates any given neural architecture to hardware switch states and these states are stored in digital memory to enable desired neural architectures. STM enables our proposed architecture to address scalability and connectivity using traditional CMOS hardware. We describe the details of the proposed design and the programmable front-end, and provide examples to illustrate its capabilities. We also provide perspectives for future extensions and potential applications.

Jose Cruz-Albrecht

Papers

A Functional Hybrid Memristor Crossbar-Array/CMOS System for Data Storage and Neuromorphic Applications

Energy-Efficient Neuron, Synapse and STDP Integrated Circuits

A scalable neural chip with synaptic electronics using CMOS integrated memristors

Down-converter and up-converter for time-encoded signals

Programming Time-Multiplexed Reconfigurable Hardware Using a Scalable Neuromorphic Compiler