Random access memory immune to single event upset using a T-resistor

DOEpatents

Ochoa, Jr., Agustin

1989-01-01

In a random access memory cell, a resistance "T" decoupling network in each leg of the cell reduces random errors caused by the interaction of energetic ions with the semiconductor material forming the cell. The cell comprises two parallel legs each containing a series pair of complementary MOS transistors having a common gate connected to the node between the transistors of the opposite leg. The decoupling network in each leg is formed by a series pair of resistors between the transistors together with a third resistor interconnecting the junction between the pair of resistors and the gate of the transistor pair forming the opposite leg of the cell.

A 16K-bit static IIL RAM with 25-ns access time

NASA Astrophysics Data System (ADS)

Inabe, Y.; Hayashi, T.; Kawarada, K.; Miwa, H.; Ogiue, K.

1982-04-01

A 16,384 x 1-bit RAM with 25-ns access time, 600-mW power dissipation, and 33 sq mm chip size has been developed. Excellent speed-power performance with high packing density has been achieved by an oxide isolation technology in conjunction with novel ECL circuit techniques and IIL flip-flop memory cells, 980 sq microns (35 x 28 microns) in cell size. Development results have shown that IIL flip-flop memory cell is a trump card for assuring achievement of a high-performance large-capacity bipolar RAM, in the above 16K-bit/chip area.

Power reduction by power gating in differential pair type spin-transfer-torque magnetic random access memories for low-power nonvolatile cache memories

NASA Astrophysics Data System (ADS)

Ohsawa, Takashi; Ikeda, Shoji; Hanyu, Takahiro; Ohno, Hideo; Endoh, Tetsuo

2014-01-01

Array operation currents in spin-transfer-torque magnetic random access memories (STT-MRAMs) that use four differential pair type magnetic tunnel junction (MTJ)-based memory cells (4T2MTJ, two 6T2MTJs and 8T2MTJ) are simulated and compared with that in SRAM. With L3 cache applications in mind, it is assumed that the memories are composed of 32 Mbyte capacity to be accessed in 64 byte in parallel. All the STT-MRAMs except for the 8T2MTJ one are designed with 32 bit fine-grained power gating scheme applied to eliminate static currents in the memory cells that are not accessed. The 8T2MTJ STT-MRAM, the cell’s design concept being not suitable for the fine-grained power gating, loads and saves 32 Mbyte data in 64 Mbyte unit per 1 Mbit sub-array in 2 × 103 cycles. It is shown that the array operation current of the 4T2MTJ STT-MRAM is 70 mA averaged in 15 ns write cycles at Vdd = 0.9 V. This is the smallest among the STT-MRAMs, about the half of the low standby power (LSTP) SRAM whose array operation current is totally dominated by the cells’ subthreshold leakage.

Test Procedures for Semiconductor Random Access Memories

DTIC Science & Technology

1979-11-01

of each cell exactly complement to each other, the read operations on the base cell in (g) of step 2 following operations ko S odd and in (p) of step...contents of Sko (these cells this address. Furthermore, when more than one contained I at test time and even if the con- cell is accessed then the output

Single Event Upset in Static Random Access Memories in Atmospheric Neutron Environments

NASA Astrophysics Data System (ADS)

Arita, Yutaka; Takai, Mikio; Ogawa, Izumi; Kishimoto, Tadafumi

2003-07-01

Single-event upsets (SEUs) in a 0.4 μm 4 Mbit complementary metal oxide semiconductor (CMOS) static random access memory (SRAM) were investigated in various atmospheric neutron environments at sea level, at an altitude of 2612 m mountain, at an altitude of commercial airplane, and at an underground depth of 476 m. Neutron-induced SEUs increase with the increase in altitude. For a device with a borophosphosilicate glass (BPSG) film, SEU rates induced by thermal neutrons increase with the decrease in the cell charge of a memory cell. A thermal neutron-induced SEU is significant in SRAMs with a small cell charge. With the conditions of small cell charge, thermal neutron-induced SEUs account for 60% or more of the total neutron-induced SEUs. The SEU rate induced by atmospheric thermal neutrons can be estimated by an acceleration test using 252Cf.

Kinetic Inductance Memory Cell and Architecture for Superconducting Computers

NASA Astrophysics Data System (ADS)

Chen, George J.

Josephson memory devices typically use a superconducting loop containing one or more Josephson junctions to store information. The magnetic inductance of the loop in conjunction with the Josephson junctions provides multiple states to store data. This thesis shows that replacing the magnetic inductor in a memory cell with a kinetic inductor can lead to a smaller cell size. However, magnetic control of the cells is lost. Thus, a current-injection based architecture for a memory array has been designed to work around this problem. The isolation between memory cells that magnetic control provides is provided through resistors in this new architecture. However, these resistors allow leakage current to flow which ultimately limits the size of the array due to power considerations. A kinetic inductance memory array will be limited to 4K bits with a read access time of 320 ps for a 1 um linewidth technology. If a power decoder could be developed, the memory architecture could serve as the blueprint for a fast (<1 ns), large scale (>1 Mbit) superconducting memory array.

Multi-floor cascading ferroelectric nanostructures: multiple data writing-based multi-level non-volatile memory devices

NASA Astrophysics Data System (ADS)

Hyun, Seung; Kwon, Owoong; Lee, Bom-Yi; Seol, Daehee; Park, Beomjin; Lee, Jae Yong; Lee, Ju Hyun; Kim, Yunseok; Kim, Jin Kon

2016-01-01

Multiple data writing-based multi-level non-volatile memory has gained strong attention for next-generation memory devices to quickly accommodate an extremely large number of data bits because it is capable of storing multiple data bits in a single memory cell at once. However, all previously reported devices have failed to store a large number of data bits due to the macroscale cell size and have not allowed fast access to the stored data due to slow single data writing. Here, we introduce a novel three-dimensional multi-floor cascading polymeric ferroelectric nanostructure, successfully operating as an individual cell. In one cell, each floor has its own piezoresponse and the piezoresponse of one floor can be modulated by the bias voltage applied to the other floor, which means simultaneously written data bits in both floors can be identified. This could achieve multi-level memory through a multiple data writing process.Multiple data writing-based multi-level non-volatile memory has gained strong attention for next-generation memory devices to quickly accommodate an extremely large number of data bits because it is capable of storing multiple data bits in a single memory cell at once. However, all previously reported devices have failed to store a large number of data bits due to the macroscale cell size and have not allowed fast access to the stored data due to slow single data writing. Here, we introduce a novel three-dimensional multi-floor cascading polymeric ferroelectric nanostructure, successfully operating as an individual cell. In one cell, each floor has its own piezoresponse and the piezoresponse of one floor can be modulated by the bias voltage applied to the other floor, which means simultaneously written data bits in both floors can be identified. This could achieve multi-level memory through a multiple data writing process. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07377d

Lowering data retention voltage in static random access memory array by post fabrication self-improvement of cell stability by multiple stress application

NASA Astrophysics Data System (ADS)

Mizutani, Tomoko; Takeuchi, Kiyoshi; Saraya, Takuya; Kobayashi, Masaharu; Hiramoto, Toshiro

2018-04-01

We propose a new version of the post fabrication static random access memory (SRAM) self-improvement technique, which utilizes multiple stress application. It is demonstrated that, using a device matrix array (DMA) test element group (TEG) with intrinsic channel fully depleted (FD) silicon-on-thin-buried-oxide (SOTB) six-transistor (6T) SRAM cells fabricated by the 65 nm technology, the lowering of data retention voltage (DRV) is more effectively achieved than using the previously proposed single stress technique.

Sub-1-V-60 nm vertical body channel MOSFET-based six-transistor static random access memory array with wide noise margin and excellent power delay product and its optimization with the cell ratio on static random access memory cell

NASA Astrophysics Data System (ADS)

Ogasawara, Ryosuke; Endoh, Tetsuo

2018-04-01

In this study, with the aim to achieve a wide noise margin and an excellent power delay product (PDP), a vertical body channel (BC)-MOSFET-based six-transistor (6T) static random access memory (SRAM) array is evaluated by changing the number of pillars in each part of a SRAM cell, that is, by changing the cell ratio in the SRAM cell. This 60 nm vertical BC-MOSFET-based 6T SRAM array realizes 0.84 V operation under the best PDP and up to 31% improvement of PDP compared with the 6T SRAM array based on a 90 nm planar MOSFET whose gate length and channel width are the same as those of the 60 nm vertical BC-MOSFET. Additionally, the vertical BC-MOSFET-based 6T SRAM array achieves an 8.8% wider read static noise margin (RSNM), a 16% wider write margin (WM), and an 89% smaller leakage. Moreover, it is shown that changing the cell ratio brings larger improvements of RSNM, WM, and write time in the vertical BC-MOSFET-based 6T SRAM array.

Biocompatibility of nanoactuators: stem cell growth on laser-generated nickel-titanium shape memory alloy nanoparticles

NASA Astrophysics Data System (ADS)

Barcikowski, Stephan; Hahn, Anne; Guggenheim, Merlin; Reimers, Kerstin; Ostendorf, Andreas

2010-06-01

Nanoactuators made from nanoparticulate NiTi shape memory alloy show potential in the mechanical stimulation of bone tissue formation from stem cells. We demonstrate the fabrication of Ni, Ti, and NiTi shape memory alloy nanoparticles and their biocompatibility to human adipose-derived stem cells. The stoichiometry and phase transformation property of the bulk alloy is preserved during attrition by femtosecond laser ablation in liquid, giving access to colloidal nanoactuators. No adverse effect on cell growth and attachment is observed in proliferation assay and environmental electron scanning microscopy, making this material attractive for mechanical stimulation of stem cells.

Spin-transfer-torque efficiency enhanced by edge-damage of perpendicular magnetic random access memories

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Kyungmi; Lee, Kyung-Jin, E-mail: kj-lee@korea.ac.kr; Department of Materials Science and Engineering, Korea University, Seoul 136-713

2015-08-07

We numerically investigate the effect of magnetic and electrical damages at the edge of a perpendicular magnetic random access memory (MRAM) cell on the spin-transfer-torque (STT) efficiency that is defined by the ratio of thermal stability factor to switching current. We find that the switching mode of an edge-damaged cell is different from that of an undamaged cell, which results in a sizable reduction in the switching current. Together with a marginal reduction of the thermal stability factor of an edge-damaged cell, this feature makes the STT efficiency large. Our results suggest that a precise edge control is viable formore » the optimization of STT-MRAM.« less

Comparison and statistical analysis of four write stability metrics in bulk CMOS static random access memory cells

NASA Astrophysics Data System (ADS)

Qiu, Hao; Mizutani, Tomoko; Saraya, Takuya; Hiramoto, Toshiro

2015-04-01

The commonly used four metrics for write stability were measured and compared based on the same set of 2048 (2k) six-transistor (6T) static random access memory (SRAM) cells by the 65 nm bulk technology. The preferred one should be effective for yield estimation and help predict edge of stability. Results have demonstrated that all metrics share the same worst SRAM cell. On the other hand, compared to butterfly curve with non-normality and write N-curve where no cell state flip happens, bit-line and word-line margins have good normality as well as almost perfect correlation. As a result, both bit line method and word line method prove themselves preferred write stability metrics.

Design and measurement of fully digital ternary content addressable memory using ratioless static random access memory cells and hierarchical-AND matching comparator

NASA Astrophysics Data System (ADS)

Nishikata, Daisuke; Ali, Mohammad Alimudin Bin Mohd; Hosoda, Kento; Matsumoto, Hiroshi; Nakamura, Kazuyuki

2018-04-01

A 36-bit × 32-entry fully digital ternary content addressable memory (TCAM) using the ratioless static random access memory (RL-SRAM) technology and fully complementary hierarchical-AND matching comparators (HAMCs) was developed. Since its fully complementary and digital operation enables the effect of device variabilities to be avoided, it can operate with a quite low supply voltage. A test chip incorporating a conventional TCAM and a proposed 24-transistor ratioless TCAM (RL-TCAM) cells and HAMCs was developed using a 0.18 µm CMOS process. The minimum operating voltage of 0.25 V of the developed RL-TCAM, which is less than half of that of the conventional TCAM, was measured via the conventional CMOS push–pull output buffers with the level-shifting and flipping technique using optimized pull-up voltage and resistors.

Dynamics of the stress-mediated magnetoelectric memory cell N×(TbCo2/FeCo)/PMN-PT

NASA Astrophysics Data System (ADS)

Preobrazhensky, Vladimir; Klimov, Alexey; Tiercelin, Nicolas; Dusch, Yannick; Giordano, Stefano; Churbanov, Anton; Mathurin, Theo; Pernod, Philippe; Sigov, Alexander

2018-08-01

Stress-mediated magnetoelectric heterostructures represent a very promising approach for the realization of ultra-low energy Random Access Memories. The magnetoelectric writing of information has been extensively studied in the past, but it was demonstrated only recently that the magnetoelectric effect can also provide means for reading the stored information. We hereby theoretically study the dynamic behaviour of a magnetoelectric random access memory cell (MELRAM) typically composed of a magnetostrictive multilayer N × (TbCo2 / FeCo) that is elastically coupled with a 〈0 1 1〉 PMN-PT ferroelectric crystal and placed in a Wheatstone bridge-like configuration. The numerical resolution of the LLG and electrodynamics equation system demonstrates high speed write and read operations with an associated extra-low energy consumption. In this model, the reading energy for a 50 nm cell size is estimated to be less than 5 aJ/bit.

Organic Ferroelectric-Based 1T1T Random Access Memory Cell Employing a Common Dielectric Layer Overcoming the Half-Selection Problem.

PubMed

Zhao, Qiang; Wang, Hanlin; Ni, Zhenjie; Liu, Jie; Zhen, Yonggang; Zhang, Xiaotao; Jiang, Lang; Li, Rongjin; Dong, Huanli; Hu, Wenping

2017-09-01

Organic electronics based on poly(vinylidenefluoride/trifluoroethylene) (P(VDF-TrFE)) dielectric is facing great challenges in flexible circuits. As one indispensable part of integrated circuits, there is an urgent demand for low-cost and easy-fabrication nonvolatile memory devices. A breakthrough is made on a novel ferroelectric random access memory cell (1T1T FeRAM cell) consisting of one selection transistor and one ferroelectric memory transistor in order to overcome the half-selection problem. Unlike complicated manufacturing using multiple dielectrics, this system simplifies 1T1T FeRAM cell fabrication using one common dielectric. To achieve this goal, a strategy for semiconductor/insulator (S/I) interface modulation is put forward and applied to nonhysteretic selection transistors with high performances for driving or addressing purposes. As a result, high hole mobility of 3.81 cm 2 V -1 s -1 (average) for 2,6-diphenylanthracene (DPA) and electron mobility of 0.124 cm 2 V -1 s -1 (average) for N,N'-1H,1H-perfluorobutyl dicyanoperylenecarboxydiimide (PDI-FCN 2 ) are obtained in selection transistors. In this work, we demonstrate this technology's potential for organic ferroelectric-based pixelated memory module fabrication. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Analysis of power gating in different hierarchical levels of 2MB cache, considering variation

NASA Astrophysics Data System (ADS)

Jafari, Mohsen; Imani, Mohsen; Fathipour, Morteza

2015-09-01

This article reintroduces power gating technique in different hierarchical levels of static random-access memory (SRAM) design including cell, row, bank and entire cache memory in 16 nm Fin field effect transistor. Different structures of SRAM cells such as 6T, 8T, 9T and 10T are used in design of 2MB cache memory. The power reduction of the entire cache memory employing cell-level optimisation is 99.7% with the expense of area and other stability overheads. The power saving of the cell-level optimisation is 3× (1.2×) higher than power gating in cache (bank) level due to its superior selectivity. The access delay times are allowed to increase by 4% in the same energy delay product to achieve the best power reduction for each supply voltages and optimisation levels. The results show the row-level power gating is the best for optimising the power of the entire cache with lowest drawbacks. Comparisons of cells show that the cells whose bodies have higher power consumption are the best candidates for power gating technique in row-level optimisation. The technique has the lowest percentage of saving in minimum energy point (MEP) of the design. The power gating also improves the variation of power in all structures by at least 70%.

False Operation of Static Random Access Memory Cells under Alternating Current Power Supply Voltage Variation

NASA Astrophysics Data System (ADS)

Sawada, Takuya; Takata, Hidehiro; Nii, Koji; Nagata, Makoto

2013-04-01

Static random access memory (SRAM) cores exhibit susceptibility against power supply voltage variation. False operation is investigated among SRAM cells under sinusoidal voltage variation on power lines introduced by direct RF power injection. A standard SRAM core of 16 kbyte in a 90 nm 1.5 V technology is diagnosed with built-in self test and on-die noise monitor techniques. The sensitivity of bit error rate is shown to be high against the frequency of injected voltage variation, while it is not greatly influenced by the difference in frequency and phase against SRAM clocking. It is also observed that the distribution of false bits is substantially random in a cell array.

Blanket Gate Would Address Blocks Of Memory

NASA Technical Reports Server (NTRS)

Lambe, John; Moopenn, Alexander; Thakoor, Anilkumar P.

1988-01-01

Circuit-chip area used more efficiently. Proposed gate structure selectively allows and restricts access to blocks of memory in electronic neural-type network. By breaking memory into independent blocks, gate greatly simplifies problem of reading from and writing to memory. Since blocks not used simultaneously, share operational amplifiers that prompt and read information stored in memory cells. Fewer operational amplifiers needed, and chip area occupied reduced correspondingly. Cost per bit drops as result.

Persistence of Epstein-Barr virus in self-reactive memory B cells.

PubMed

Tracy, Sean I; Kakalacheva, Kristina; Lünemann, Jan D; Luzuriaga, Katherine; Middeldorp, Jaap; Thorley-Lawson, David A

2012-11-01

Epstein-Barr virus infection has been epidemiologically associated with the development of multiple autoimmune diseases, particularly systemic lupus erythematosus and multiple sclerosis. Currently, there is no known mechanism that can account for these associations. The germinal-center (GC) model of EBV infection and persistence proposes that EBV gains access to the memory B cell compartment via GC reactions by driving infected cells to differentiate using the virus-encoded LMP1 and LMP2a proteins, which act as functional homologues of CD40 and the B cell receptor, respectively. The ability of LMP2a, when expressed in mice, to allow escape of autoreactive B cells suggests that it could perform a similar role in infected GC B cells, permitting the survival of potentially pathogenic autoreactive B cells. To test this hypothesis, we cloned and expressed antibodies from EBV(+) and EBV(-) memory B cells present during acute infection and profiled their self- and polyreactivity. We find that EBV does persist within self- and polyreactive B cells but find no evidence that it favors the survival of pathogenic autoreactive B cells. On the contrary, EBV(+) memory B cells express lower levels of self-reactive and especially polyreactive antibodies than their uninfected counterparts do. Our work suggests that EBV has only a modest effect on the GC process, which allows it to access and persist within a subtly unique niche of the memory compartment characterized by relatively low levels of self- and polyreactivity. We suggest that this might reflect an active process where EBV and its human host have coevolved so as to minimize the virus's potential to contribute to autoimmune disease.

Immune signatures of protective spleen memory CD8 T cells.

PubMed

Brinza, Lilia; Djebali, Sophia; Tomkowiak, Martine; Mafille, Julien; Loiseau, Céline; Jouve, Pierre-Emmanuel; de Bernard, Simon; Buffat, Laurent; Lina, Bruno; Ottmann, Michèle; Rosa-Calatrava, Manuel; Schicklin, Stéphane; Bonnefoy, Nathalie; Lauvau, Grégoire; Grau, Morgan; Wencker, Mélanie; Arpin, Christophe; Walzer, Thierry; Leverrier, Yann; Marvel, Jacqueline

2016-11-24

Memory CD8 T lymphocyte populations are remarkably heterogeneous and differ in their ability to protect the host. In order to identify the whole range of qualities uniquely associated with protective memory cells we compared the gene expression signatures of two qualities of memory CD8 T cells sharing the same antigenic-specificity: protective (Influenza-induced, Flu-TM) and non-protective (peptide-induced, TIM) spleen memory CD8 T cells. Although Flu-TM and TIM express classical phenotypic memory markers and are polyfunctional, only Flu-TM protects against a lethal viral challenge. Protective memory CD8 T cells express a unique set of genes involved in migration and survival that correlate with their unique capacity to rapidly migrate within the infected lung parenchyma in response to influenza infection. We also enlighten a new set of poised genes expressed by protective cells that is strongly enriched in cytokines and chemokines such as Ccl1, Ccl9 and Gm-csf. CCL1 and GM-CSF genes are also poised in human memory CD8 T cells. These immune signatures are also induced by two other pathogens (vaccinia virus and Listeria monocytogenes). The immune signatures associated with immune protection were identified on circulating cells, i.e. those that are easily accessible for immuno-monitoring and could help predict vaccines efficacy.

Vortex-Core Reversal Dynamics: Towards Vortex Random Access Memory

NASA Astrophysics Data System (ADS)

Kim, Sang-Koog

2011-03-01

An energy-efficient, ultrahigh-density, ultrafast, and nonvolatile solid-state universal memory is a long-held dream in the field of information-storage technology. The magnetic random access memory (MRAM) along with a spin-transfer-torque switching mechanism is a strong candidate-means of realizing that dream, given its nonvolatility, infinite endurance, and fast random access. Magnetic vortices in patterned soft magnetic dots promise ground-breaking applications in information-storage devices, owing to the very stable twofold ground states of either their upward or downward core magnetization orientation and plausible core switching by in-plane alternating magnetic fields or spin-polarized currents. However, two technologically most important but very challenging issues --- low-power recording and reliable selection of each memory cell with already existing cross-point architectures --- have not yet been resolved for the basic operations in information storage, that is, writing (recording) and readout. Here, we experimentally demonstrate a magnetic vortex random access memory (VRAM) in the basic cross-point architecture. This unique VRAM offers reliable cell selection and low-power-consumption control of switching of out-of-plane core magnetizations using specially designed rotating magnetic fields generated by two orthogonal and unipolar Gaussian-pulse currents along with optimized pulse width and time delay. Our achievement of a new device based on a new material, that is, a medium composed of patterned vortex-state disks, together with the new physics on ultrafast vortex-core switching dynamics, can stimulate further fruitful research on MRAMs that are based on vortex-state dot arrays.

Optically Addressable, Ferroelectric Memory With NDRO

NASA Technical Reports Server (NTRS)

Thakoor, Sarita

1994-01-01

For readout, memory cells addressed via on-chip semiconductor lasers. Proposed thin-film ferroelectric memory device features nonvolatile storage, optically addressable, nondestructive readout (NDRO) with fast access, and low vulnerability to damage by ionizing radiation. Polarization switched during recording and erasure, but not during readout. As result, readout would not destroy contents of memory, and operating life in specific "read-intensive" applications increased up to estimated 10 to the 16th power cycles.

Multi-floor cascading ferroelectric nanostructures: multiple data writing-based multi-level non-volatile memory devices.

PubMed

Hyun, Seung; Kwon, Owoong; Lee, Bom-Yi; Seol, Daehee; Park, Beomjin; Lee, Jae Yong; Lee, Ju Hyun; Kim, Yunseok; Kim, Jin Kon

2016-01-21

Multiple data writing-based multi-level non-volatile memory has gained strong attention for next-generation memory devices to quickly accommodate an extremely large number of data bits because it is capable of storing multiple data bits in a single memory cell at once. However, all previously reported devices have failed to store a large number of data bits due to the macroscale cell size and have not allowed fast access to the stored data due to slow single data writing. Here, we introduce a novel three-dimensional multi-floor cascading polymeric ferroelectric nanostructure, successfully operating as an individual cell. In one cell, each floor has its own piezoresponse and the piezoresponse of one floor can be modulated by the bias voltage applied to the other floor, which means simultaneously written data bits in both floors can be identified. This could achieve multi-level memory through a multiple data writing process.

Non-volatile magnetic random access memory

NASA Technical Reports Server (NTRS)

Katti, Romney R. (Inventor); Stadler, Henry L. (Inventor); Wu, Jiin-Chuan (Inventor)

1994-01-01

Improvements are made in a non-volatile magnetic random access memory. Such a memory is comprised of an array of unit cells, each having a Hall-effect sensor and a thin-film magnetic element made of material having an in-plane, uniaxial anisotropy and in-plane, bipolar remanent magnetization states. The Hall-effect sensor is made more sensitive by using a 1 m thick molecular beam epitaxy grown InAs layer on a silicon substrate by employing a GaAs/AlGaAs/InAlAs superlattice buffering layer. One improvement avoids current shunting problems of matrix architecture. Another improvement reduces the required magnetizing current for the micromagnets. Another improvement relates to the use of GaAs technology wherein high electron-mobility GaAs MESFETs provide faster switching times. Still another improvement relates to a method for configuring the invention as a three-dimensional random access memory.

A review of emerging non-volatile memory (NVM) technologies and applications

NASA Astrophysics Data System (ADS)

Chen, An

2016-11-01

This paper will review emerging non-volatile memory (NVM) technologies, with the focus on phase change memory (PCM), spin-transfer-torque random-access-memory (STTRAM), resistive random-access-memory (RRAM), and ferroelectric field-effect-transistor (FeFET) memory. These promising NVM devices are evaluated in terms of their advantages, challenges, and applications. Their performance is compared based on reported parameters of major industrial test chips. Memory selector devices and cell structures are discussed. Changing market trends toward low power (e.g., mobile, IoT) and data-centric applications create opportunities for emerging NVMs. High-performance and low-cost emerging NVMs may simplify memory hierarchy, introduce non-volatility in logic gates and circuits, reduce system power, and enable novel architectures. Storage-class memory (SCM) based on high-density NVMs could fill the performance and density gap between memory and storage. Some unique characteristics of emerging NVMs can be utilized for novel applications beyond the memory space, e.g., neuromorphic computing, hardware security, etc. In the beyond-CMOS era, emerging NVMs have the potential to fulfill more important functions and enable more efficient, intelligent, and secure computing systems.

Light sensitivity of a one transistor-one capacitor memory cell when used as a micromirror actuator in projector applications

NASA Astrophysics Data System (ADS)

Huffman, James Douglas

2001-11-01

The most important issue facing the future business success of the Digital Micromirror Device or DMD™ produced by Texas Instruments is the cost of the actual device. As the business and consumer markets call for higher resolution displays, the array size will have to be increased to incorporate more pixels. The manufacturing costs associated with building these higher resolution displays follow an exponential relation with the number of pixels due to yield loss and reduced number of chips per silicon wafer. Each pixel is actuated by electrostatics that are provided by a memory cell that is built in the underlying silicon substrate. One way to decrease cost of the wafer is to change the memory cell architecture from a static random access configuration or SRAM to a dynamic random access configuration or DRAM. This change has the benefits of having fewer components per area and a lower metal density. This reduction in the component count and metal density has a dramatic effect on the yield of the memory array by reducing the particle sensitivity of the underlying cell. The main drawback to using a DRAM configuration in a display application is the light sensitivity of a charge storage device built in the silicon substrate. As the photons pass through the mechanical micromirrors and illuminate the DRAM cell, the effective electrostatic potential of the memory element used for the mirror actuation is reduced. This dissertation outlines the issues associated with the light sensitivity of a DRAM memory cell as the actuation element for a micromirror. The concept of charge depletion on a silicon capacitor due to recombination of photogenerated carriers is explored and experimentally verified. The effects of the reduced potential on the capacitor on the micromirror are also explored. Optical modeling is used to determine the incoming photon flux to determine the benefits of adding a charge recombination region as part of the DRAM memory cell. Several options are explored to reduce the effect of the incoming photons on the potential of the memory cell. The results will show that a 1T1C memory cell with N-type recombination regions and maximum light shielding is sufficient for a projector application.

Elevated-Confined Phase-Change Random Access Memory Cells

NASA Astrophysics Data System (ADS)

Lee; Koon, Hock; Shi; Luping; Zhao; Rong; Yang; Hongxin; Lim; Guan, Kian; Li; Jianming; Chong; Chong, Tow

2010-04-01

A new elevated-confined phase-change random access memory (PCRAM) cell structure to reduce power consumption was proposed. In this proposed structure, the confined phase-change region is sitting on top of a small metal column enclosed by a dielectric at the sides. Hence, more heat can be effectively sustained underneath the phase-change region. As for the conventional structure, the confined phase-change region is sitting directly above a large planar bottom metal electrode, which can easily conduct most of the induced heat away. From simulations, a more uniform temperature profile around the active region and a higher peak temperature at the phase-change layer (PCL) in an elevated-confined structure were observed. Experimental results showed that the elevated-confined PCRAM cell requires a lower programming power and has a better scalability than a conventional confined PCRAM cell.

Genome-wide RNA profiling of long-lasting stem cell-like memory CD8 T cells induced by Yellow Fever vaccination in humans.

PubMed

Fuertes Marraco, Silvia A; Soneson, Charlotte; Delorenzi, Mauro; Speiser, Daniel E

2015-09-01

The live-attenuated Yellow Fever (YF) vaccine YF-17D induces a broad and polyfunctional CD8 T cell response in humans. Recently, we identified a population of stem cell-like memory CD8 T cells induced by YF-17D that persists at stable frequency for at least 25 years after vaccination. The YF-17D is thus a model system of human CD8 T cell biology that furthermore allows to track and study long-lasting and antigen-specific human memory CD8 T cells. Here, we describe in detail the sample characteristics and preparation of a microarray dataset acquired for genome-wide gene expression profiling of long-lasting YF-specific stem cell-like memory CD8 T cells, compared to the reference CD8 T cell differentiation subsets from total CD8 T cells. We also describe the quality controls, annotations and exploratory analyses of the dataset. The microarray data is available from the Gene Expression Omnibus (GEO) public repository with accession number GSE65804.

Simulation study on heat conduction of a nanoscale phase-change random access memory cell.

PubMed

Kim, Junho; Song, Ki-Bong

2006-11-01

We have investigated heat transfer characteristics of a nano-scale phase-change random access memory (PRAM) cell using finite element method (FEM) simulation. Our PRAM cell is based on ternary chalcogenide alloy, Ge2Sb2Te5 (GST), which is used as a recording layer. For contact area of 100 x 100 nm2, simulations of crystallization and amorphization processes were carried out. Physical quantities such as electric conductivity, thermal conductivity, and specific heat were treated as temperature-dependent parameters. Through many simulations, it is concluded that one can reduce set current by decreasing both electric conductivities of amorphous GST and crystalline GST, and in addition to these conditions by decreasing electric conductivity of molten GST one can also reduce reset current significantly.

Non-volatile, high density, high speed, Micromagnet-Hall effect Random Access Memory (MHRAM)

NASA Technical Reports Server (NTRS)

Wu, Jiin C.; Katti, Romney R.; Stadler, Henry L.

1991-01-01

The micromagnetic Hall effect random access memory (MHRAM) has the potential of replacing ROMs, EPROMs, EEPROMs, and SRAMs because of its ability to achieve non-volatility, radiation hardness, high density, and fast access times, simultaneously. Information is stored magnetically in small magnetic elements (micromagnets), allowing unlimited data retention time, unlimited numbers of rewrite cycles, and inherent radiation hardness and SEU immunity, making the MHRAM suitable for ground based as well as spaceflight applications. The MHRAM device design is not affected by areal property fluctuations in the micromagnet, so high operating margins and high yield can be achieved in large scale integrated circuit (IC) fabrication. The MHRAM has short access times (less than 100 nsec). Write access time is short because on-chip transistors are used to gate current quickly, and magnetization reversal in the micromagnet can occur in a matter of a few nanoseconds. Read access time is short because the high electron mobility sensor (InAs or InSb) produces a large signal voltage in response to the fringing magnetic field from the micromagnet. High storage density is achieved since a unit cell consists only of two transistors and one micromagnet Hall effect element. By comparison, a DRAM unit cell has one transistor and one capacitor, and a SRAM unit cell has six transistors.

Molecular regulation of effector and memory T cell differentiation

PubMed Central

Chang, John T; Wherry, E John; Goldrath, Ananda W

2015-01-01

Immunological memory is a cardinal feature of adaptive immunity and an important goal of vaccination strategies. Here we highlight advances in the understanding of the diverse T lymphocyte subsets that provide acute and long-term protection from infection. These include new insights into the transcription factors, and the upstream ‘pioneering’ factors that regulate their accessibility to key sites of gene regulation, as well as metabolic regulators that contribute to the differentiation of effector and memory subsets; ontogeny and defining characteristics of tissue-resident memory lymphocytes; and origins of the remarkable heterogeneity exhibited by activated T cells. Collectively, these findings underscore progress in delineating the underlying pathways that control diversification in T cell responses but also reveal gaps in the knowledge, as well as the challenges that arise in the application of this knowledge to rationally elicit desired T cell responses through vaccination and immunotherapy. PMID:25396352

All-optical clocked flip-flops and random access memory cells using the nonlinear polarization rotation effect of low-polarization-dependent semiconductor optical amplifiers

NASA Astrophysics Data System (ADS)

Wang, Yongjun; Liu, Xinyu; Tian, Qinghua; Wang, Lina; Xin, Xiangjun

2018-03-01

Basic configurations of various all-optical clocked flip-flops (FFs) and optical random access memory (RAM) based on the nonlinear polarization rotation (NPR) effect of low-polarization-dependent semiconductor optical amplifiers (SOA) are proposed. As the constituent elements, all-optical logic gates and all-optical SR latches are constructed by taking advantage of the SOA's NPR switch. Different all-optical FFs (AOFFs), including SR-, D-, T-, and JK-types as well as an optical RAM cell were obtained by the combination of the proposed all-optical SR latches and logic gates. The effectiveness of the proposed schemes were verified by simulation results and demonstrated by a D-FF and 1-bit RAM cell experimental system. The proposed all-optical clocked FFs and RAM cell are significant to all-optical signal processing.

Ferroelectric symmetry-protected multibit memory cell

NASA Astrophysics Data System (ADS)

Baudry, Laurent; Lukyanchuk, Igor; Vinokur, Valerii M.

2017-02-01

The tunability of electrical polarization in ferroelectrics is instrumental to their applications in information-storage devices. The existing ferroelectric memory cells are based on the two-level storage capacity with the standard binary logics. However, the latter have reached its fundamental limitations. Here we propose ferroelectric multibit cells (FMBC) utilizing the ability of multiaxial ferroelectric materials to pin the polarization at a sequence of the multistable states. Employing the catastrophe theory principles we show that these states are symmetry-protected against the information loss and thus realize novel topologically-controlled access memory (TAM). Our findings enable developing a platform for the emergent many-valued non-Boolean information technology and target challenges posed by needs of quantum and neuromorphic computing.

Atomic memory access hardware implementations

DOEpatents

Ahn, Jung Ho; Erez, Mattan; Dally, William J

2015-02-17

Atomic memory access requests are handled using a variety of systems and methods. According to one example method, a data-processing circuit having an address-request generator that issues requests to a common memory implements a method of processing the requests using a memory-access intervention circuit coupled between the generator and the common memory. The method identifies a current atomic-memory access request from a plurality of memory access requests. A data set is stored that corresponds to the current atomic-memory access request in a data storage circuit within the intervention circuit. It is determined whether the current atomic-memory access request corresponds to at least one previously-stored atomic-memory access request. In response to determining correspondence, the current request is implemented by retrieving data from the common memory. The data is modified in response to the current request and at least one other access request in the memory-access intervention circuit.

Memory as Perception of the Past: Compressed Time inMind and Brain.

PubMed

Howard, Marc W

2018-02-01

In the visual system retinal space is compressed such that acuity decreases further from the fovea. Different forms of memory may rely on a compressed representation of time, manifested as decreased accuracy for events that happened further in the past. Neurophysiologically, "time cells" show receptive fields in time. Analogous to the compression of visual space, time cells show less acuity for events further in the past. Behavioral evidence suggests memory can be accessed by scanning a compressed temporal representation, analogous to visual search. This suggests a common computational language for visual attention and memory retrieval. In this view, time functions like a scaffolding that organizes memories in much the same way that retinal space functions like a scaffolding for visual perception. Copyright © 2017 Elsevier Ltd. All rights reserved.

Unified random access memory (URAM) by integration of a nanocrystal floating gate for nonvolatile memory and a partially depleted floating body for capacitorless 1T-DRAM

NASA Astrophysics Data System (ADS)

Ryu, Seong-Wan; Han, Jin-Woo; Kim, Chung-Jin; Kim, Sungho; Choi, Yang-Kyu

2009-03-01

This paper describes a unified memory (URAM) that utilizes a nanocrystal SOI MOSFET for multi-functional applications of both nonvolatile memory (NVM) and capacitorless 1T-DRAM. By using a discrete storage node (Ag nanocrystal) as the floating gate of the NVM, high defect immunity and 2-bit/cell operation were achieved. The embedded nanocrystal NVM also showed 1T-DRAM operation (program/erase time = 100 ns) characteristics, which were realized by storing holes in the floating body of the SOI MOSFET, without requiring an external capacitor. Three-bit/cell operation was accomplished for different applications - 2-bits for nonvolatility and 1-bit for fast operation.

High Density Memory Based on Quantum Device Technology

NASA Technical Reports Server (NTRS)

vanderWagt, Paul; Frazier, Gary; Tang, Hao

1995-01-01

We explore the feasibility of ultra-high density memory based on quantum devices. Starting from overall constraints on chip area, power consumption, access speed, and noise margin, we deduce boundaries on single cell parameters such as required operating voltage and standby current. Next, the possible role of quantum devices is examined. Since the most mature quantum device, the resonant tunneling diode (RTD) can easily be integrated vertically, it naturally leads to the issue of 3D integrated memory. We propose a novel method of addressing vertically integrated bistable two-terminal devices, such as resonant tunneling diodes (RTD) and Esaki diodes, that avoids individual physical contacts. The new concept has been demonstrated experimentally in memory cells of field effect transistors (FET's) and stacked RTD's.

Ferroelectric symmetry-protected multibit memory cell

DOE PAGES

Baudry, Laurent; Lukyanchuk, Igor; Vinokur, Valerii M.

2017-02-08

Here, the tunability of electrical polarization in ferroelectrics is instrumental to their applications in information-storage devices. The existing ferroelectric memory cells are based on the two-level storage capacity with the standard binary logics. However, the latter have reached its fundamental limitations. Here we propose ferroelectric multibit cells (FMBC) utilizing the ability of multiaxial ferroelectric materials to pin the polarization at a sequence of the multistable states. Employing the catastrophe theory principles we show that these states are symmetry-protected against the information loss and thus realize novel topologically-controlled access memory (TAM). Our findings enable developing a platform for the emergent many-valuedmore » non-Boolean information technology and target challenges posed by needs of quantum and neuromorphic computing.« less

TLR4 signaling augments B lymphocyte migration and overcomes the restriction that limits access to germinal center dark zones

PubMed Central

Hwang, Il-Young; Park, Chung; Harrison, Kathleen

2009-01-01

B lymphocyte–intrinsic Toll-like receptor (TLR) signals amplify humoral immunity and can exacerbate autoimmune diseases. We identify a new mechanism by which TLR signals may contribute to autoimmunity and chronic inflammation. We show that TLR4 signaling enhances B lymphocyte trafficking into lymph nodes (LNs), induces B lymphocyte clustering and interactions within LN follicles, leads to sustained in vivo B cell proliferation, overcomes the restriction that limits the access of nonantigen-activated B cells to germinal center dark zones, and enhances the generation of memory and plasma cells. Intravital microscopy and in vivo tracking studies of B cells transferred to recipient mice revealed that TLR4-activated, but not nonstimulated, B cells accumulated within the dark zones of preexisting germinal centers even when transferred with antigen-specific B cells. The TLR4-activated cells persist much better than nonstimulated cells, expanding both within the memory and plasma cell compartments. TLR-mediated activation of B cells may help to feed and stabilize the spontaneous and ectopic germinal centers that are so commonly found in autoimmune individuals and that accompany chronic inflammation. PMID:19917774

Cross-point-type spin-transfer-torque magnetoresistive random access memory cell with multi-pillar vertical body channel MOSFET

NASA Astrophysics Data System (ADS)

Sasaki, Taro; Endoh, Tetsuo

2018-04-01

In this paper, from the viewpoint of cell size and sensing margin, the impact of a novel cross-point-type one transistor and one magnetic tunnel junction (1T–1MTJ) spin-transfer-torque magnetoresistive random access memory (STT-MRAM) cell with a multi-pillar vertical body channel (BC) MOSFET is shown for high density and wide sensing margin STT-MRAM, with a 10 ns writing period and 1.2 V V DD. For that purpose, all combinations of n/p-type MOSFETs and bottom/top-pin MTJs are compared, where the diameter of MTJ (D MTJ) is scaled down from 55 to 15 nm and the tunnel magnetoresistance (TMR) ratio is increased from 100 to 200%. The results show that, benefiting from the proposed STT-MRAM cell with no back bias effect, the MTJ with a high TMR ratio (200%) can be used in the design of smaller STT-MRAM cells (over 72.6% cell size reduction), which is a difficult task for conventional planar MOSFET based design.

Simulation of Voltage SET Operation in Phase-Change Random Access Memories with Heater Addition and Ring-Type Contactor for Low-Power Consumption by Finite Element Modeling

NASA Astrophysics Data System (ADS)

Gong, Yue-Feng; Song, Zhi-Tang; Ling, Yun; Liu, Yan; Li, Yi-Jin

2010-06-01

A three-dimensional finite element model for phase change random access memory is established to simulate electric, thermal and phase state distribution during (SET) operation. The model is applied to simulate the SET behaviors of the heater addition structure (HS) and the ring-type contact in the bottom electrode (RIB) structure. The simulation results indicate that the small bottom electrode contactor (BEC) is beneficial for heat efficiency and reliability in the HS cell, and the bottom electrode contactor with size Fx = 80 nm is a good choice for the RIB cell. Also shown is that the appropriate SET pulse time is 100 ns for the low power consumption and fast operation.

Redirection to the bone marrow improves T cell persistence and antitumor functions.

PubMed

Khan, Anjum B; Carpenter, Ben; Santos E Sousa, Pedro; Pospori, Constandina; Khorshed, Reema; Griffin, James; Velica, Pedro; Zech, Mathias; Ghorashian, Sara; Forrest, Calum; Thomas, Sharyn; Gonzalez Anton, Sara; Ahmadi, Maryam; Holler, Angelika; Flutter, Barry; Ramirez-Ortiz, Zaida; Means, Terry K; Bennett, Clare L; Stauss, Hans; Morris, Emma; Lo Celso, Cristina; Chakraverty, Ronjon

2018-05-01

A key predictor for the success of gene-modified T cell therapies for cancer is the persistence of transferred cells in the patient. The propensity of less differentiated memory T cells to expand and survive efficiently has therefore made them attractive candidates for clinical application. We hypothesized that redirecting T cells to specialized niches in the BM that support memory differentiation would confer increased therapeutic efficacy. We show that overexpression of chemokine receptor CXCR4 in CD8+ T cells (TCXCR4) enhanced their migration toward vascular-associated CXCL12+ cells in the BM and increased their local engraftment. Increased access of TCXCR4 to the BM microenvironment induced IL-15-dependent homeostatic expansion and promoted the differentiation of memory precursor-like cells with low expression of programmed death-1, resistance to apoptosis, and a heightened capacity to generate polyfunctional cytokine-producing effector cells. Following transfer to lymphoma-bearing mice, TCXCR4 showed a greater capacity for effector expansion and better tumor protection, the latter being independent of changes in trafficking to the tumor bed or local out-competition of regulatory T cells. Thus, redirected homing of T cells to the BM confers increased memory differentiation and antitumor immunity, suggesting an innovative solution to increase the persistence and functions of therapeutic T cells.

Method and device for maximizing memory system bandwidth by accessing data in a dynamically determined order

NASA Technical Reports Server (NTRS)

Schwab, Andrew J. (Inventor); Aylor, James (Inventor); Hitchcock, Charles Young (Inventor); Wulf, William A. (Inventor); McKee, Sally A. (Inventor); Moyer, Stephen A. (Inventor); Klenke, Robert (Inventor)

2000-01-01

A data processing system is disclosed which comprises a data processor and memory control device for controlling the access of information from the memory. The memory control device includes temporary storage and decision ability for determining what order to execute the memory accesses. The compiler detects the requirements of the data processor and selects the data to stream to the memory control device which determines a memory access order. The order in which to access said information is selected based on the location of information stored in the memory. The information is repeatedly accessed from memory and stored in the temporary storage until all streamed information is accessed. The information is stored until required by the data processor. The selection of the order in which to access information maximizes bandwidth and decreases the retrieval time.

Long-term reliable physically unclonable function based on oxide tunnel barrier breakdown on two-transistors two-magnetic-tunnel-junctions cell-based embedded spin transfer torque magnetoresistive random access memory

NASA Astrophysics Data System (ADS)

Takaya, Satoshi; Tanamoto, Tetsufumi; Noguchi, Hiroki; Ikegami, Kazutaka; Abe, Keiko; Fujita, Shinobu

2017-04-01

Among the diverse applications of spintronics, security for internet-of-things (IoT) devices is one of the most important. A physically unclonable function (PUF) with a spin device (spin transfer torque magnetoresistive random access memory, STT-MRAM) is presented. Oxide tunnel barrier breakdown is used to realize long-term stability for PUFs. A secure PUF has been confirmed by evaluating the Hamming distance of a 32-bit STT-MRAM-PUF fabricated using 65 nm CMOS technology.

Gas-Sensing Flip-Flop Circuits

NASA Technical Reports Server (NTRS)

Buehler, Martin G.; Blaes, Brent R.; Williams, Roger; Ryan, Margaret A.

1995-01-01

Gas-sensing integrated circuits consisting largely of modified static random-access memories (SRAMs) undergoing development, building on experience gained in use of modified SRAMs as radiation sensors. Each SRAM memory cell includes flip-flop circuit; sensors exploit metastable state that lies between two stable states (corresponding to binary logic states) of flip-flop circuit. Voltages of metastable states vary with exposures of gas-sensitive resistors.

Electrically-controlled nonlinear switching and multi-level storage characteristics in WOx film-based memory cells

NASA Astrophysics Data System (ADS)

Duan, W. J.; Wang, J. B.; Zhong, X. L.

2018-05-01

Resistive switching random access memory (RRAM) is considered as a promising candidate for the next generation memory due to its scalability, high integration density and non-volatile storage characteristics. Here, the multiple electrical characteristics in Pt/WOx/Pt cells are investigated. Both of the nonlinear switching and multi-level storage can be achieved by setting different compliance current in the same cell. The correlations among the current, time and temperature are analyzed by using contours and 3D surfaces. The switching mechanism is explained in terms of the formation and rupture of conductive filament which is related to oxygen vacancies. The experimental results show that the non-stoichiometric WOx film-based device offers a feasible way for the applications of oxide-based RRAMs.

Realisation of all 16 Boolean logic functions in a single magnetoresistance memory cell

NASA Astrophysics Data System (ADS)

Gao, Shuang; Yang, Guang; Cui, Bin; Wang, Shouguo; Zeng, Fei; Song, Cheng; Pan, Feng

2016-06-01

Stateful logic circuits based on next-generation nonvolatile memories, such as magnetoresistance random access memory (MRAM), promise to break the long-standing von Neumann bottleneck in state-of-the-art data processing devices. For the successful commercialisation of stateful logic circuits, a critical step is realizing the best use of a single memory cell to perform logic functions. In this work, we propose a method for implementing all 16 Boolean logic functions in a single MRAM cell, namely a magnetoresistance (MR) unit. Based on our experimental results, we conclude that this method is applicable to any MR unit with a double-hump-like hysteresis loop, especially pseudo-spin-valve magnetic tunnel junctions with a high MR ratio. Moreover, after simply reversing the correspondence between voltage signals and output logic values, this method could also be applicable to any MR unit with a double-pit-like hysteresis loop. These results may provide a helpful solution for the final commercialisation of MRAM-based stateful logic circuits in the near future.Stateful logic circuits based on next-generation nonvolatile memories, such as magnetoresistance random access memory (MRAM), promise to break the long-standing von Neumann bottleneck in state-of-the-art data processing devices. For the successful commercialisation of stateful logic circuits, a critical step is realizing the best use of a single memory cell to perform logic functions. In this work, we propose a method for implementing all 16 Boolean logic functions in a single MRAM cell, namely a magnetoresistance (MR) unit. Based on our experimental results, we conclude that this method is applicable to any MR unit with a double-hump-like hysteresis loop, especially pseudo-spin-valve magnetic tunnel junctions with a high MR ratio. Moreover, after simply reversing the correspondence between voltage signals and output logic values, this method could also be applicable to any MR unit with a double-pit-like hysteresis loop. These results may provide a helpful solution for the final commercialisation of MRAM-based stateful logic circuits in the near future. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr03169b

Soft-error tolerance and energy consumption evaluation of embedded computer with magnetic random access memory in practical systems using computer simulations

NASA Astrophysics Data System (ADS)

Nebashi, Ryusuke; Sakimura, Noboru; Sugibayashi, Tadahiko

2017-08-01

We evaluated the soft-error tolerance and energy consumption of an embedded computer with magnetic random access memory (MRAM) using two computer simulators. One is a central processing unit (CPU) simulator of a typical embedded computer system. We simulated the radiation-induced single-event-upset (SEU) probability in a spin-transfer-torque MRAM cell and also the failure rate of a typical embedded computer due to its main memory SEU error. The other is a delay tolerant network (DTN) system simulator. It simulates the power dissipation of wireless sensor network nodes of the system using a revised CPU simulator and a network simulator. We demonstrated that the SEU effect on the embedded computer with 1 Gbit MRAM-based working memory is less than 1 failure in time (FIT). We also demonstrated that the energy consumption of the DTN sensor node with MRAM-based working memory can be reduced to 1/11. These results indicate that MRAM-based working memory enhances the disaster tolerance of embedded computers.

Design of a magnetic-tunnel-junction-oriented nonvolatile lookup table circuit with write-operation-minimized data shifting

NASA Astrophysics Data System (ADS)

Suzuki, Daisuke; Hanyu, Takahiro

2018-04-01

A magnetic-tunnel-junction (MTJ)-oriented nonvolatile lookup table (LUT) circuit, in which a low-power data-shift function is performed by minimizing the number of write operations in MTJ devices is proposed. The permutation of the configuration memory cell for read/write access is performed as opposed to conventional direct data shifting to minimize the number of write operations, which results in significant write energy savings in the data-shift function. Moreover, the hardware cost of the proposed LUT circuit is small since the selector is shared between read access and write access. In fact, the power consumption in the data-shift function and the transistor count are reduced by 82 and 52%, respectively, compared with those in a conventional static random-access memory-based implementation using a 90 nm CMOS technology.

Memory Applications Using Resonant Tunneling Diodes

NASA Astrophysics Data System (ADS)

Shieh, Ming-Huei

Resonant tunneling diodes (RTDs) producing unique folding current-voltage (I-V) characteristics have attracted considerable research attention due to their promising application in signal processing and multi-valued logic. The negative differential resistance of RTDs renders the operating points self-latching and stable. We have proposed a multiple -dimensional multiple-state RTD-based static random-access memory (SRAM) cell in which the number of stable states can significantly be increased to (N + 1)^ m or more for m number of N-peak RTDs connected in series. The proposed cells take advantage of the hysteresis and folding I-V characteristics of RTD. Several cell designs are presented and evaluated. A two-dimensional nine-state memory cell has been implemented and demonstrated by a breadboard circuit using two 2-peak RTDs. The hysteresis phenomenon in a series of RTDs is also further analyzed. The switch model provided in SPICE 3 can be utilized to simulate the hysteretic I-V characteristics of RTDs. A simple macro-circuit is described to model the hysteretic I-V characteristic of RTD for circuit simulation. A new scheme for storing word-wide multiple-bit information very efficiently in a single memory cell using RTDs is proposed. An efficient and inexpensive periphery circuit to read from and write into the cell is also described. Simulation results on the design of a 3-bit memory cell scheme using one-peak RTDs are also presented. Finally, a binary transistor-less memory cell which is only composed of a pair of RTDs and an ordinary rectifier diode is presented and investigated. A simple means for reading and writing information from or into the memory cell is also discussed.

Set statistics in conductive bridge random access memory device with Cu/HfO{sub 2}/Pt structure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Meiyun; Long, Shibing, E-mail: longshibing@ime.ac.cn; Wang, Guoming

2014-11-10

The switching parameter variation of resistive switching memory is one of the most important challenges in its application. In this letter, we have studied the set statistics of conductive bridge random access memory with a Cu/HfO{sub 2}/Pt structure. The experimental distributions of the set parameters in several off resistance ranges are shown to nicely fit a Weibull model. The Weibull slopes of the set voltage and current increase and decrease logarithmically with off resistance, respectively. This experimental behavior is perfectly captured by a Monte Carlo simulator based on the cell-based set voltage statistics model and the Quantum Point Contact electronmore » transport model. Our work provides indications for the improvement of the switching uniformity.« less

Digital MOS integrated circuits

NASA Astrophysics Data System (ADS)

Elmasry, M. I.

MOS in digital circuit design is considered along with aspects of digital VLSI, taking into account a comparison of MOSFET logic circuits, 1-micrometer MOSFET VLSI technology, a generalized guide for MOSFET miniaturization, processing technologies, novel circuit structures for VLSI, and questions of circuit and system design for VLSI. MOS memory cells and circuits are discussed, giving attention to a survey of high-density dynamic RAM cell concepts, one-device cells for dynamic random-access memories, variable resistance polysilicon for high density CMOS Ram, high performance MOS EPROMs using a stacked-gate cell, and the optimization of the latching pulse for dynamic flip-flop sensors. Programmable logic arrays are considered along with digital signal processors, microprocessors, static RAMs, and dynamic RAMs.

Scandium doped Ge2Sb2Te5 for high-speed and low-power-consumption phase change memory

NASA Astrophysics Data System (ADS)

Wang, Yong; Zheng, Yonghui; Liu, Guangyu; Li, Tao; Guo, Tianqi; Cheng, Yan; Lv, Shilong; Song, Sannian; Ren, Kun; Song, Zhitang

2018-03-01

To bridge the gap of access time between memories and storage systems, the concept of storage class memory has been put forward based on emerging nonvolatile memory technologies. For all the nonvolatile memory candidates, the unpleasant tradeoff between operation speed and retention seems to be inevitable. To promote both the write speed and the retention of phase change memory (PCM), Sc doped Ge2Sb2Te5 (SGST) has been proposed as the storage medium. Octahedral Sc-Te motifs, acting as crystallization precursors to shorten the nucleation incubation period, are the possible reason for the high write speed of 6 ns in PCM cells, five-times faster than that of Ge2Sb2Te5 (GST) cells. Meanwhile, an enhanced 10-year data retention of 119 °C has been achieved. Benefiting from both the increased crystalline resistance and the inhibited formation of the hexagonal phase, the SGST cell has a 77% reduction in power consumption compared to the GST cell. Adhesion of the SGST/SiO2 interface has been strengthened, attributed to the reduced stress by forming smaller grains during crystallization, guaranteeing the reliability of the device. These improvements have made the SGST material a promising candidate for PCM application.

Total Ionizing Dose Influence on the Single-Event Upset Sensitivity of 130-nm PD SOI SRAMs

NASA Astrophysics Data System (ADS)

Zheng, Qiwen; Cui, Jiangwei; Liu, Mengxin; Zhou, Hang; Liu, Mohan; Wei, Ying; Su, Dandan; Ma, Teng; Lu, Wu; Yu, Xuefeng; Guo, Qi; He, Chengfa

2017-07-01

Effect of total ionizing dose (TID) on single-event upset (SEU) hardness of 130 nm partially depleted (PD) silicon-on-insulator (SOI) static random access memories (SRAMs) is investigated in this paper. The measurable synergistic effect of TID on SEU sensitivity of 130-nm PD SOI SRAM was observed in our experiment, even though that is far less than micrometer and submicrometer devices. Moreover, SEU cross section after TID irradiation has no dependence on the data pattern that was applied during TID exposure: SEU cross sections are characterized by TID data pattern and its complement data pattern are decreased consistently rather than a preferred state and a nonpreferred state as micrometer and sub-micrometer SRAMs. The memory cell test structure allowing direct measurement of static noise margin (SNM) under standby operation was designed using identical memory cell layout of SRAM. Direct measurement of the memory cell SNM shows that both data sides' SNM is decreased by TID, indicating that SEU cross section of 130-nm PD SOI SRAM will be increased by TID. And, the decreased SNM is caused by threshold shift in memory cell transistors induced by “radiation-induced narrow channel effect”.

Resistive RAMs as analog trimming elements

NASA Astrophysics Data System (ADS)

Aziza, H.; Perez, A.; Portal, J. M.

2018-04-01

This work investigates the use of Resistive Random Access Memory (RRAM) as an analog trimming device. The analog storage feature of the RRAM cell is evaluated and the ability of the RRAM to hold several resistance states is exploited to propose analog trim elements. To modulate the memory cell resistance, a series of short programming pulses are applied across the RRAM cell allowing a fine calibration of the RRAM resistance. The RRAM non volatility feature makes the analog device powers up already calibrated for the system in which the analog trimmed structure is embedded. To validate the concept, a test structure consisting of a voltage reference is evaluated.

Disturbance characteristics of half-selected cells in a cross-point resistive switching memory array

NASA Astrophysics Data System (ADS)

Chen, Zhe; Li, Haitong; Chen, Hong-Yu; Chen, Bing; Liu, Rui; Huang, Peng; Zhang, Feifei; Jiang, Zizhen; Ye, Hongfei; Gao, Bin; Liu, Lifeng; Liu, Xiaoyan; Kang, Jinfeng; Wong, H.-S. Philip; Yu, Shimeng

2016-05-01

Disturbance characteristics of cross-point resistive random access memory (RRAM) arrays are comprehensively studied in this paper. An analytical model is developed to quantify the number of pulses (#Pulse) the cell can bear before disturbance occurs under various sub-switching voltage stresses based on physical understanding. An evaluation methodology is proposed to assess the disturb behavior of half-selected (HS) cells in cross-point RRAM arrays by combining the analytical model and SPICE simulation. The characteristics of cross-point RRAM arrays such as energy consumption, reliable operating cycles and total error bits are evaluated by the methodology. A possible solution to mitigate disturbance is proposed.

Piezotronic nanowire-based resistive switches as programmable electromechanical memories.

PubMed

Wu, Wenzhuo; Wang, Zhong Lin

2011-07-13

We present the first piezoelectrically modulated resistive switching device based on piezotronic ZnO nanowire (NW), through which the write/read access of the memory cell is programmed via electromechanical modulation. Adjusted by the strain-induced polarization charges created at the semiconductor/metal interface under externally applied deformation by the piezoelectric effect, the resistive switching characteristics of the cell can be modulated in a controlled manner, and the logic levels of the strain stored in the cell can be recorded and read out, which has the potential for integrating with NEMS technology to achieve micro/nanosystems capable for intelligent and self-sufficient multidimensional operations.

Random Telegraph Signal-Like Fluctuation Created by Fowler-Nordheim Stress in Gate Induced Drain Leakage Current of the Saddle Type Dynamic Random Access Memory Cell Transistor

NASA Astrophysics Data System (ADS)

Kim, Heesang; Oh, Byoungchan; Kim, Kyungdo; Cha, Seon-Yong; Jeong, Jae-Goan; Hong, Sung-Joo; Lee, Jong-Ho; Park, Byung-Gook; Shin, Hyungcheol

2010-09-01

We generated traps inside gate oxide in gate-drain overlap region of recess channel type dynamic random access memory (DRAM) cell transistor through Fowler-Nordheim (FN) stress, and observed gate induced drain leakage (GIDL) current both in time domain and in frequency domain. It was found that the trap inside gate oxide could generate random telegraph signal (RTS)-like fluctuation in GIDL current. The characteristics of that fluctuation were similar to those of RTS-like fluctuation in GIDL current observed in the non-stressed device. This result shows the possibility that the trap causing variable retention time (VRT) in DRAM data retention time can be located inside gate oxide like channel RTS of metal-oxide-semiconductor field-effect transistors (MOSFETs).

Preliminary design for a standard 10 sup 7 bit Solid State Memory (SSM)

NASA Technical Reports Server (NTRS)

Hayes, P. J.; Howle, W. M., Jr.; Stermer, R. L., Jr.

1978-01-01

A modular concept with three separate modules roughly separating bubble domain technology, control logic technology, and power supply technology was employed. These modules were respectively the standard memory module (SMM), the data control unit (DCU), and power supply module (PSM). The storage medium was provided by bubble domain chips organized into memory cells. These cells and the circuitry for parallel data access to the cells make up the SMM. The DCU provides a flexible serial data interface to the SMM. The PSM provides adequate power to enable one DCU and one SMM to operate simultaneously at the maximum data rate. The SSM was designed to handle asynchronous data rates from dc to 1.024 Mbs with a bit error rate less than 1 error in 10 to the eight power bits. Two versions of the SSM, a serial data memory and a dual parallel data memory were specified using the standard modules. The SSM specification includes requirements for radiation hardness, temperature and mechanical environments, dc magnetic field emission and susceptibility, electromagnetic compatibility, and reliability.

Genome accessibility is widely preserved and locally modulated during mitosis

PubMed Central

Hsiung, Chris C.-S.; Morrissey, Christapher S.; Udugama, Maheshi; Frank, Christopher L.; Keller, Cheryl A.; Baek, Songjoon; Giardine, Belinda; Crawford, Gregory E.; Sung, Myong-Hee; Hardison, Ross C.

2015-01-01

Mitosis entails global alterations to chromosome structure and nuclear architecture, concomitant with transient silencing of transcription. How cells transmit transcriptional states through mitosis remains incompletely understood. While many nuclear factors dissociate from mitotic chromosomes, the observation that certain nuclear factors and chromatin features remain associated with individual loci during mitosis originated the hypothesis that such mitotically retained molecular signatures could provide transcriptional memory through mitosis. To understand the role of chromatin structure in mitotic memory, we performed the first genome-wide comparison of DNase I sensitivity of chromatin in mitosis and interphase, using a murine erythroblast model. Despite chromosome condensation during mitosis visible by microscopy, the landscape of chromatin accessibility at the macromolecular level is largely unaltered. However, mitotic chromatin accessibility is locally dynamic, with individual loci maintaining none, some, or all of their interphase accessibility. Mitotic reduction in accessibility occurs primarily within narrow, highly DNase hypersensitive sites that frequently coincide with transcription factor binding sites, whereas broader domains of moderate accessibility tend to be more stable. In mitosis, proximal promoters generally maintain their accessibility more strongly, whereas distal regulatory elements tend to lose accessibility. Large domains of DNA hypomethylation mark a subset of promoters that retain accessibility during mitosis and across many cell types in interphase. Erythroid transcription factor GATA1 exerts site-specific changes in interphase accessibility that are most pronounced at distal regulatory elements, but has little influence on mitotic accessibility. We conclude that features of open chromatin are remarkably stable through mitosis, but are modulated at the level of individual genes and regulatory elements. PMID:25373146

Realisation of all 16 Boolean logic functions in a single magnetoresistance memory cell.

PubMed

Gao, Shuang; Yang, Guang; Cui, Bin; Wang, Shouguo; Zeng, Fei; Song, Cheng; Pan, Feng

2016-07-07

Stateful logic circuits based on next-generation nonvolatile memories, such as magnetoresistance random access memory (MRAM), promise to break the long-standing von Neumann bottleneck in state-of-the-art data processing devices. For the successful commercialisation of stateful logic circuits, a critical step is realizing the best use of a single memory cell to perform logic functions. In this work, we propose a method for implementing all 16 Boolean logic functions in a single MRAM cell, namely a magnetoresistance (MR) unit. Based on our experimental results, we conclude that this method is applicable to any MR unit with a double-hump-like hysteresis loop, especially pseudo-spin-valve magnetic tunnel junctions with a high MR ratio. Moreover, after simply reversing the correspondence between voltage signals and output logic values, this method could also be applicable to any MR unit with a double-pit-like hysteresis loop. These results may provide a helpful solution for the final commercialisation of MRAM-based stateful logic circuits in the near future.

Ga-doped indium oxide nanowire phase change random access memory cells

NASA Astrophysics Data System (ADS)

Jin, Bo; Lim, Taekyung; Ju, Sanghyun; Latypov, Marat I.; Kim, Hyoung Seop; Meyyappan, M.; Lee, Jeong-Soo

2014-02-01

Phase change random access memory (PCRAM) devices are usually constructed using tellurium based compounds, but efforts to seek other materials providing desirable memory characteristics have continued. We have fabricated PCRAM devices using Ga-doped In2O3 nanowires with three different Ga compositions (Ga/(In+Ga) atomic ratio: 2.1%, 11.5% and 13.0%), and investigated their phase switching properties. The nanowires (˜40 nm in diameter) can be repeatedly switched between crystalline and amorphous phases, and Ga concentration-dependent memory switching behavior in the nanowires was observed with ultra-fast set/reset rates of 80 ns/20 ns, which are faster than for other competitive phase change materials. The observations of fast set/reset rates and two distinct states with a difference in resistance of two to three orders of magnitude appear promising for nonvolatile information storage. Moreover, we found that increasing the Ga concentration can reduce the power consumption and resistance drift; however, too high a level of Ga doping may cause difficulty in achieving the phase transition.

SiGe epitaxial memory for neuromorphic computing with reproducible high performance based on engineered dislocations

NASA Astrophysics Data System (ADS)

Choi, Shinhyun; Tan, Scott H.; Li, Zefan; Kim, Yunjo; Choi, Chanyeol; Chen, Pai-Yu; Yeon, Hanwool; Yu, Shimeng; Kim, Jeehwan

2018-01-01

Although several types of architecture combining memory cells and transistors have been used to demonstrate artificial synaptic arrays, they usually present limited scalability and high power consumption. Transistor-free analog switching devices may overcome these limitations, yet the typical switching process they rely on—formation of filaments in an amorphous medium—is not easily controlled and hence hampers the spatial and temporal reproducibility of the performance. Here, we demonstrate analog resistive switching devices that possess desired characteristics for neuromorphic computing networks with minimal performance variations using a single-crystalline SiGe layer epitaxially grown on Si as a switching medium. Such epitaxial random access memories utilize threading dislocations in SiGe to confine metal filaments in a defined, one-dimensional channel. This confinement results in drastically enhanced switching uniformity and long retention/high endurance with a high analog on/off ratio. Simulations using the MNIST handwritten recognition data set prove that epitaxial random access memories can operate with an online learning accuracy of 95.1%.

76 FR 73676 - Certain Dynamic Random Access Memory Devices, and Products Containing Same; Receipt of Complaint...

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Generation-based memory synchronization in a multiprocessor system with weakly consistent memory accesses

DOEpatents

Ohmacht, Martin

2017-08-15

In a multiprocessor system, a central memory synchronization module coordinates memory synchronization requests responsive to memory access requests in flight, a generation counter, and a reclaim pointer. The central module communicates via point-to-point communication. The module includes a global OR reduce tree for each memory access requesting device, for detecting memory access requests in flight. An interface unit is implemented associated with each processor requesting synchronization. The interface unit includes multiple generation completion detectors. The generation count and reclaim pointer do not pass one another.

Generation-based memory synchronization in a multiprocessor system with weakly consistent memory accesses

DOEpatents

Ohmacht, Martin

2014-09-09

In a multiprocessor system, a central memory synchronization module coordinates memory synchronization requests responsive to memory access requests in flight, a generation counter, and a reclaim pointer. The central module communicates via point-to-point communication. The module includes a global OR reduce tree for each memory access requesting device, for detecting memory access requests in flight. An interface unit is implemented associated with each processor requesting synchronization. The interface unit includes multiple generation completion detectors. The generation count and reclaim pointer do not pass one another.

76 FR 55417 - In the Matter of Certain Dynamic Random Access Memory and Nand Flash Memory Devices and Products...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-07

... Access Memory and Nand Flash Memory Devices and Products Containing Same; Notice of Institution of... importation, and the sale within the United States after importation of certain dynamic random access memory and NAND flash memory devices and products containing same by reason of infringement of certain claims...

Non-volatile memory based on the ferroelectric photovoltaic effect

PubMed Central

Guo, Rui; You, Lu; Zhou, Yang; Shiuh Lim, Zhi; Zou, Xi; Chen, Lang; Ramesh, R.; Wang, Junling

2013-01-01

The quest for a solid state universal memory with high-storage density, high read/write speed, random access and non-volatility has triggered intense research into new materials and novel device architectures. Though the non-volatile memory market is dominated by flash memory now, it has very low operation speed with ~10 μs programming and ~10 ms erasing time. Furthermore, it can only withstand ~105 rewriting cycles, which prevents it from becoming the universal memory. Here we demonstrate that the significant photovoltaic effect of a ferroelectric material, such as BiFeO3 with a band gap in the visible range, can be used to sense the polarization direction non-destructively in a ferroelectric memory. A prototype 16-cell memory based on the cross-bar architecture has been prepared and tested, demonstrating the feasibility of this technique. PMID:23756366

75 FR 14467 - In the Matter of: Certain Dynamic Random Access Memory Semiconductors and Products Containing...

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... Access Memory Semiconductors and Products Containing Same, Including Memory Modules; Notice of... the sale within the United States after importation of certain dynamic random access memory semiconductors and products containing same, including memory modules, by reason of infringement of certain...

76 FR 80964 - Certain Dynamic Random Access Memory Devices, and Products Containing Same; Institution of...

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Genome accessibility is widely preserved and locally modulated during mitosis.

PubMed

Hsiung, Chris C-S; Morrissey, Christapher S; Udugama, Maheshi; Frank, Christopher L; Keller, Cheryl A; Baek, Songjoon; Giardine, Belinda; Crawford, Gregory E; Sung, Myong-Hee; Hardison, Ross C; Blobel, Gerd A

2015-02-01

Mitosis entails global alterations to chromosome structure and nuclear architecture, concomitant with transient silencing of transcription. How cells transmit transcriptional states through mitosis remains incompletely understood. While many nuclear factors dissociate from mitotic chromosomes, the observation that certain nuclear factors and chromatin features remain associated with individual loci during mitosis originated the hypothesis that such mitotically retained molecular signatures could provide transcriptional memory through mitosis. To understand the role of chromatin structure in mitotic memory, we performed the first genome-wide comparison of DNase I sensitivity of chromatin in mitosis and interphase, using a murine erythroblast model. Despite chromosome condensation during mitosis visible by microscopy, the landscape of chromatin accessibility at the macromolecular level is largely unaltered. However, mitotic chromatin accessibility is locally dynamic, with individual loci maintaining none, some, or all of their interphase accessibility. Mitotic reduction in accessibility occurs primarily within narrow, highly DNase hypersensitive sites that frequently coincide with transcription factor binding sites, whereas broader domains of moderate accessibility tend to be more stable. In mitosis, proximal promoters generally maintain their accessibility more strongly, whereas distal regulatory elements tend to lose accessibility. Large domains of DNA hypomethylation mark a subset of promoters that retain accessibility during mitosis and across many cell types in interphase. Erythroid transcription factor GATA1 exerts site-specific changes in interphase accessibility that are most pronounced at distal regulatory elements, but has little influence on mitotic accessibility. We conclude that features of open chromatin are remarkably stable through mitosis, but are modulated at the level of individual genes and regulatory elements. © 2015 Hsiung et al.; Published by Cold Spring Harbor Laboratory Press.

SRAM As An Array Of Energetic-Ion Detectors

NASA Technical Reports Server (NTRS)

Buehler, Martin G.; Blaes, Brent R.; Lieneweg, Udo; Nixon, Robert H.

1993-01-01

Static random-access memory (SRAM) designed for use as array of energetic-ion detectors. Exploits well-known tendency of incident energetic ions to cause bit flips in cells of electronic memories. Design of ion-detector SRAM involves modifications of standard SRAM design to increase sensitivity to ions. Device fabricated by use of conventional complementary metal oxide/semiconductor (CMOS) processes. Potential uses include gas densimetry, position sensing, and measurement of cosmic-ray spectrum.

Deflate decompressor

DOEpatents

Hamlet, Jason R [Albuquerque, NM; Robertson, Perry J [Albuquerque, NM; Pierson, Lyndon G [Albuquerque, NM; Olsberg, Ronald R [Albuquerque, NM

2012-02-28

A deflate decompressor includes at least one decompressor unit, a memory access controller, a feedback path, and an output buffer unit. The memory access controller is coupled to the decompressor unit via a data path and includes a data buffer to receive the data stream and temporarily buffer a first portion the data stream. The memory access controller transfers fixed length data units of the data stream from the data buffer to the decompressor unit with reference to a memory pointer pointing into the memory buffer. The feedback path couples the decompressor unit to the memory access controller to feed back decrement values to the memory access controller for updating the memory pointer. The decrement values each indicate a number of bits unused by the decompressor unit when decoding the fixed length data units. The output buffer unit buffers a second portion of the data stream after decompression.

Felix Hoppe-Seyler Lecture 1997. Protective antibody responses against viruses.

PubMed

Zinkernagel, R M

1997-08-01

Neutralizing antibody responses against the acute cytopathic vesicular stomatitis virus (VSV) have been studied in mice to evaluate their general characteristics including specificity, self-/non-self discrimination and memory. IgM responses are generated very early, by day 3 to 4, in a T helper cell-independent fashion and without VSV having polyclonal activating capacities. The order of the glycoprotein tips on the virus envelope (multiple, 8-10 nm distance, paracrystalline) exhibiting the neutralizing determinants are key to this prompt response. These paracrystalline identical multimeric antigens are characteristic of infectious agents and are always reacted against by B cells. Self-antigens that are accessible to B cells in the intact host are either monomeric in serum or mobile multimers on cell surfaces; these configurations need contact dependent or contact independent T help, respectively. Because T help is tolerant against self-antigens, no anti-self B cell responses are usually induced against monomeric self-antigens. If collagen or DNA (rigid multimeric self-antigens) become accessible, however, they may become targets of auto-antibody responses. The antibody repertoire against VSV is partially contained in the germline and partially is generated by somatic mutation; they seem not to undergo affinity-maturation. In any case protection against lethal infection is dependent upon strictly T helper cell dependent IgG generated by day 6 to 7 and reaches a protective level of about 1-10 micrograms/ml. Interesting affinity/avidity and onrate above a minimal threshold are of no apparent advantage for protection in vivo. Maintenance of these antibody levels by antigen depots, and not the presence of memory B cells alone, is key to providing protective immunological memory. Collectively these data suggest that studying biologically important protective antibody responses may modify some of the parameters that have been defined by studying hapten specific antibody responses.

75 FR 44283 - In the Matter of Certain Dynamic Random Access Memory Semiconductors and Products Containing Same...

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2010-07-28

... Random Access Memory Semiconductors and Products Containing Same, Including Memory Modules; Notice of a... importation of certain dynamic random access memory semiconductors and products containing same, including memory modules, by reason of infringement of certain claims of U.S. Patent Nos. 5,480,051; 5,422,309; 5...

The Matter with Listening Comprehension Isn't the Ear: Hardware and Software.

ERIC Educational Resources Information Center

Harvey, T. Edward

1978-01-01

Reviews some technological advances and classroom games which may be used to increase listening comprehension skills in the foreign language classroom. These include the Random Access Memory (RAM), the Sens-it-Cell, and the SCUCHO game. (AM)

An automatic analyzer of solid state nuclear track detectors using an optic RAM as image sensor

NASA Astrophysics Data System (ADS)

Staderini, Enrico Maria; Castellano, Alfredo

1986-02-01

An optic RAM is a conventional digital random access read/write dynamic memory device featuring a quartz windowed package and memory cells regularly ordered on the chip. Such a device is used as an image sensor because each cell retains data stored in it for a time depending on the intensity of the light incident on the cell itself. The authors have developed a system which uses an optic RAM to acquire and digitize images from electrochemically etched CR39 solid state nuclear track detectors (SSNTD) in the track count rate up to 5000 cm -2. On the digital image so obtained, a microprocessor, with appropriate software, performs image analysis, filtering, tracks counting and evaluation.

Endurance Enhancement and High Speed Set/Reset of 50 nm Generation HfO2 Based Resistive Random Access Memory Cell by Intelligent Set/Reset Pulse Shape Optimization and Verify Scheme

NASA Astrophysics Data System (ADS)

Higuchi, Kazuhide; Miyaji, Kousuke; Johguchi, Koh; Takeuchi, Ken

2012-02-01

This paper proposes a verify-programming method for the resistive random access memory (ReRAM) cell which achieves a 50-times higher endurance and a fast set and reset compared with the conventional method. The proposed verify-programming method uses the incremental pulse width with turnback (IPWWT) for the reset and the incremental voltage with turnback (IVWT) for the set. With the combination of IPWWT reset and IVWT set, the endurance-cycle increases from 48 ×103 to 2444 ×103 cycles. Furthermore, the measured data retention-time after 20 ×103 set/reset cycles is estimated to be 10 years. Additionally, the filamentary based physical model is proposed to explain the set/reset failure mechanism with various set/reset pulse shapes. The reset pulse width and set voltage correspond to the width and length of the conductive-filament, respectively. Consequently, since the proposed IPWWT and IVWT recover set and reset failures of ReRAM cells, the endurance-cycles are improved.

Integration of SrBi2Ta2O9 thin films for high density ferroelectric random access memory

NASA Astrophysics Data System (ADS)

Wouters, D. J.; Maes, D.; Goux, L.; Lisoni, J. G.; Paraschiv, V.; Johnson, J. A.; Schwitters, M.; Everaert, J.-L.; Boullart, W.; Schaekers, M.; Willegems, M.; Vander Meeren, H.; Haspeslagh, L.; Artoni, C.; Caputa, C.; Casella, P.; Corallo, G.; Russo, G.; Zambrano, R.; Monchoix, H.; Vecchio, G.; Van Autryve, L.

2006-09-01

Ferroelectric random access memory (FeRAM) is an attractive candidate technology for embedded nonvolatile memory, especially in applications where low power and high program speed are important. Market introduction of high-density FeRAM is, however, lagging behind standard complementary metal-oxide semiconductor (CMOS) because of the difficult integration technology. This paper discusses the major integration issues for high-density FeRAM, based on SrBi2Ta2O9 (strontium bismuth tantalate or SBT), in relation to the fabrication of our stacked cell structure. We have worked in the previous years on the development of SBT-FeRAM integration technology, based on a so-called pseudo-three-dimensional (3D) cell, with a capacitor that can be scaled from quasi two-dimensional towards a true three-dimensional capacitor where the sidewalls will importantly contribute to the signal. In the first phase of our integration development, we integrated our FeRAM cell in a 0.35μm CMOS technology. In a second phase, then, possibility of scaling of our cell is demonstrated in 0.18μm technology. The excellent electrical and reliability properties of the small integrated ferroelectric capacitors prove the feasibility of the technology, while the verification of the potential 3D effect confirms the basic scaling potential of our concept beyond that of the single-mask capacitor. The paper outlines the different material and technological challenges, and working solutions are demonstrated. While some issues are specific to our own cell, many are applicable to different stacked FeRAM cell concepts, or will become more general concerns when more developments are moving into 3D structures.

Compact modeling of CRS devices based on ECM cells for memory, logic and neuromorphic applications.

PubMed

Linn, E; Menzel, S; Ferch, S; Waser, R

2013-09-27

Dynamic physics-based models of resistive switching devices are of great interest for the realization of complex circuits required for memory, logic and neuromorphic applications. Here, we apply such a model of an electrochemical metallization (ECM) cell to complementary resistive switches (CRSs), which are favorable devices to realize ultra-dense passive crossbar arrays. Since a CRS consists of two resistive switching devices, it is straightforward to apply the dynamic ECM model for CRS simulation with MATLAB and SPICE, enabling study of the device behavior in terms of sweep rate and series resistance variations. Furthermore, typical memory access operations as well as basic implication logic operations can be analyzed, revealing requirements for proper spike and level read operations. This basic understanding facilitates applications of massively parallel computing paradigms required for neuromorphic applications.

Influence of carbon content on the copper-telluride phase formation and on the resistive switching behavior of carbon alloyed Cu-Te conductive bridge random access memory cells

NASA Astrophysics Data System (ADS)

Devulder, Wouter; Opsomer, Karl; Franquet, Alexis; Meersschaut, Johan; Belmonte, Attilio; Muller, Robert; De Schutter, Bob; Van Elshocht, Sven; Jurczak, Malgorzata; Goux, Ludovic; Detavernier, Christophe

2014-02-01

In this paper, we investigate the influence of the carbon content on the Cu-Te phase formation and on the resistive switching behavior in carbon alloyed Cu0.6Te0.4 based conductive bridge random access memory (CBRAM) cells. Carbon alloying of copper-tellurium inhibits the crystallization, while attractive switching behavior is preserved when using the material as Cu-supply layer in CBRAM cells. The phase formation is first investigated in a combinatorial way. With increasing carbon content, an enlargement of the temperature window in which the material stays amorphous was observed. Moreover, if crystalline phases are formed, subsequent phase transformations are inhibited. The electrical switching behavior of memory cells with different carbon contents is then investigated by implementing them in 580 μm diameter dot TiN/Cu0.6Te0.4-C/Al2O3/Si memory cells. Reliable switching behavior is observed for carbon contents up to 40 at. %, with a resistive window of more than 2 orders of magnitude, whereas for 50 at. % carbon, a higher current in the off state and only a small resistive window are present after repeated cycling. This degradation can be ascribed to the higher thermal and lower drift contribution to the reset operation due to a lower Cu affinity towards the supply layer, leading cycle-after-cycle to an increasing amount of Cu in the switching layer, which contributes to the current. The thermal diffusion of Cu into Al2O3 under annealing also gives an indication of the Cu affinity of the source layer. Time of flight secondary ion mass spectroscopy was used to investigate this migration depth in Al2O3 before and after annealing, showing a higher Cu, Te, and C migration for high carbon contents.

Simplified ZrTiO x -based RRAM cell structure with rectifying characteristics by integrating Ni/n + -Si diode.

PubMed

Lin, Chia-Chun; Wu, Yung-Hsien; Chang, You-Tai; Sun, Cherng-En

2014-01-01

A simplified one-diode one-resistor (1D1R) resistive switching memory cell that uses only four layers of TaN/ZrTiO x /Ni/n(+)-Si was proposed to suppress sneak current where TaN/ZrTiO x /Ni can be regarded as a resistive-switching random access memory (RRAM) device while Ni/n(+)-Si acts as an Schottky diode. This is the first RRAM cell structure that employs metal/semiconductor Schottky diode for current rectifying. The 1D1R cell exhibits bipolar switching behavior with SET/RESET voltage close to 1 V without requiring a forming process. More importantly, the cell shows tight resistance distribution for different states, significantly rectifying characteristics with forward/reverse current ratio higher than 10(3) and a resistance ratio larger than 10(3) between two states. Furthermore, the cell also displays desirable reliability performance in terms of long data retention time of up to 10(4) s and robust endurance of 10(5) cycles. Based on the promising characteristics, the four-layer 1D1R structure holds the great potential for next-generation nonvolatile memory technology.

Perpendicular STT_RAM cell in 8 nm technology node using Co1/Ni3(1 1 1)||Gr2||Co1/Ni3(1 1 1) structure as magnetic tunnel junction

NASA Astrophysics Data System (ADS)

Varghani, Ali; Peiravi, Ali; Moradi, Farshad

2018-04-01

The perpendicular anisotropy Spin-Transfer Torque Random Access Memory (P-STT-RAM) is considered to be a promising candidate for high-density memories. Many distinct advantages of Perpendicular Magnetic Tunnel Junction (P-MTJ) compared to the conventional in-plane MTJ (I-MTJ) such as lower switching current, circular cell shape that facilitates manufacturability in smaller technology nodes, large thermal stability, smaller cell size, and lower dipole field interaction between adjacent cells make it a promising candidate as a universal memory. However, for small MTJ cell sizes, the perpendicular technology requires new materials with high polarization and low damping factor as well as low resistance area product of a P-MTJ in order to avoid a high write voltage as technology is scaled down. A new graphene-based STT-RAM cell for 8 nm technology node that uses high perpendicular magnetic anisotropy cobalt/nickel (Co/Ni) multilayer as magnetic layers is proposed in this paper. The proposed junction benefits from enough Tunneling Magnetoresistance Ratio (TMR), low resistance area product, low write voltage, and low power consumption that make it suitable for 8 nm technology node.

Inverse Resistance Change Cr2Ge2Te6-Based PCRAM Enabling Ultralow-Energy Amorphization.

PubMed

Hatayama, Shogo; Sutou, Yuji; Shindo, Satoshi; Saito, Yuta; Song, Yun-Heub; Ando, Daisuke; Koike, Junichi

2018-01-24

Phase-change random access memory (PCRAM) has attracted much attention for next-generation nonvolatile memory that can replace flash memory and can be used for storage-class memory. Generally, PCRAM relies on the change in the electrical resistance of a phase-change material between high-resistance amorphous (reset) and low-resistance crystalline (set) states. Herein, we present an inverse resistance change PCRAM with Cr 2 Ge 2 Te 6 (CrGT) that shows a high-resistance crystalline reset state and a low-resistance amorphous set state. The inverse resistance change was found to be due to a drastic decrease in the carrier density upon crystallization, which causes a large increase in contact resistivity between CrGT and the electrode. The CrGT memory cell was demonstrated to show fast reversible resistance switching with a much lower operating energy for amorphization than a Ge 2 Sb 2 Te 5 memory cell. This low operating energy in CrGT should be due to a small programmed amorphous volume, which can be realized by a high-resistance crystalline matrix and a dominant contact resistance. Simultaneously, CrGT can break the trade-off relationship between the crystallization temperature and operating speed.

Inflammatory memory sensitizes skin epithelial stem cells to tissue damage.

PubMed

Naik, Shruti; Larsen, Samantha B; Gomez, Nicholas C; Alaverdyan, Kirill; Sendoel, Ataman; Yuan, Shaopeng; Polak, Lisa; Kulukian, Anita; Chai, Sophia; Fuchs, Elaine

2017-10-26

The skin barrier is the body's first line of defence against environmental assaults, and is maintained by epithelial stem cells (EpSCs). Despite the vulnerability of EpSCs to inflammatory pressures, neither the primary response to inflammation nor its enduring consequences are well understood. Here we report a prolonged memory to acute inflammation that enables mouse EpSCs to hasten barrier restoration after subsequent tissue damage. This functional adaptation does not require skin-resident macrophages or T cells. Instead, EpSCs maintain chromosomal accessibility at key stress response genes that are activated by the primary stimulus. Upon a secondary challenge, genes governed by these domains are transcribed rapidly. Fuelling this memory is Aim2, which encodes an activator of the inflammasome. The absence of AIM2 or its downstream effectors, caspase-1 and interleukin-1β, erases the ability of EpSCs to recollect inflammation. Although EpSCs benefit from inflammatory tuning by heightening their responsiveness to subsequent stressors, this enhanced sensitivity probably increases their susceptibility to autoimmune and hyperproliferative disorders, including cancer.

Accessing memory

DOEpatents

Yoon, Doe Hyun; Muralimanohar, Naveen; Chang, Jichuan; Ranganthan, Parthasarathy

2017-09-26

A disclosed example method involves performing simultaneous data accesses on at least first and second independently selectable logical sub-ranks to access first data via a wide internal data bus in a memory device. The memory device includes a translation buffer chip, memory chips in independently selectable logical sub-ranks, a narrow external data bus to connect the translation buffer chip to a memory controller, and the wide internal data bus between the translation buffer chip and the memory chips. A data access is performed on only the first independently selectable logical sub-rank to access second data via the wide internal data bus. The example method also involves locating a first portion of the first data, a second portion of the first data, and the second data on the narrow external data bus during separate data transfers.

GPU acceleration of particle-in-cell methods

NASA Astrophysics Data System (ADS)

Cowan, Benjamin; Cary, John; Meiser, Dominic

2015-11-01

Graphics processing units (GPUs) have become key components in many supercomputing systems, as they can provide more computations relative to their cost and power consumption than conventional processors. However, to take full advantage of this capability, they require a strict programming model which involves single-instruction multiple-data execution as well as significant constraints on memory accesses. To bring the full power of GPUs to bear on plasma physics problems, we must adapt the computational methods to this new programming model. We have developed a GPU implementation of the particle-in-cell (PIC) method, one of the mainstays of plasma physics simulation. This framework is highly general and enables advanced PIC features such as high order particles and absorbing boundary conditions. The main elements of the PIC loop, including field interpolation and particle deposition, are designed to optimize memory access. We describe the performance of these algorithms and discuss some of the methods used. Work supported by DARPA contract W31P4Q-15-C-0061 (SBIR).

Working memory capacity and retrieval limitations from long-term memory: an examination of differences in accessibility.

PubMed

Unsworth, Nash; Spillers, Gregory J; Brewer, Gene A

2012-01-01

In two experiments, the locus of individual differences in working memory capacity and long-term memory recall was examined. Participants performed categorical cued and free recall tasks, and individual differences in the dynamics of recall were interpreted in terms of a hierarchical-search framework. The results from this study are in accordance with recent theorizing suggesting a strong relation between working memory capacity and retrieval from long-term memory. Furthermore, the results also indicate that individual differences in categorical recall are partially due to differences in accessibility. In terms of accessibility of target information, two important factors drive the difference between high- and low-working-memory-capacity participants. Low-working-memory-capacity participants fail to utilize appropriate retrieval strategies to access cues, and they also have difficulty resolving cue overload. Thus, when low-working-memory-capacity participants were given specific cues that activated a smaller set of potential targets, their recall performance was the same as that of high-working-memory-capacity participants.

Memory availability and referential access

PubMed Central

Johns, Clinton L.; Gordon, Peter C.; Long, Debra L.; Swaab, Tamara Y.

2013-01-01

Most theories of coreference specify linguistic factors that modulate antecedent accessibility in memory; however, whether non-linguistic factors also affect coreferential access is unknown. Here we examined the impact of a non-linguistic generation task (letter transposition) on the repeated-name penalty, a processing difficulty observed when coreferential repeated names refer to syntactically prominent (and thus more accessible) antecedents. In Experiment 1, generation improved online (event-related potentials) and offline (recognition memory) accessibility of names in word lists. In Experiment 2, we manipulated generation and syntactic prominence of antecedent names in sentences; both improved online and offline accessibility, but only syntactic prominence elicited a repeated-name penalty. Our results have three important implications: first, the form of a referential expression interacts with an antecedent’s status in the discourse model during coreference; second, availability in memory and referential accessibility are separable; and finally, theories of coreference must better integrate known properties of the human memory system. PMID:24443621

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baudry, Laurent; Lukyanchuk, Igor; Vinokur, Valerii M.

Here, the tunability of electrical polarization in ferroelectrics is instrumental to their applications in information-storage devices. The existing ferroelectric memory cells are based on the two-level storage capacity with the standard binary logics. However, the latter have reached its fundamental limitations. Here we propose ferroelectric multibit cells (FMBC) utilizing the ability of multiaxial ferroelectric materials to pin the polarization at a sequence of the multistable states. Employing the catastrophe theory principles we show that these states are symmetry-protected against the information loss and thus realize novel topologically-controlled access memory (TAM). Our findings enable developing a platform for the emergent many-valuedmore » non-Boolean information technology and target challenges posed by needs of quantum and neuromorphic computing.« less

Circuit-Switched Memory Access in Photonic Interconnection Networks for High-Performance Embedded Computing

DTIC Science & Technology

2010-07-22

dependent , providing a natural bandwidth match between compute cores and the memory subsystem. • High Bandwidth Dcnsity. Waveguides crossing the chip...simulate this memory access architecture on a 2S6-core chip with a concentrated 64-node network lIsing detailed traces of high-performance embedded...memory modulcs, wc placc memory access poi nts (MAPs) around the pcriphery of the chip connected to thc nctwork. These MAPs, shown in Figure 4, contain

A hybrid magnetic/complementary metal oxide semiconductor three-context memory bit cell for non-volatile circuit design

NASA Astrophysics Data System (ADS)

Jovanović, B.; Brum, R. M.; Torres, L.

2014-04-01

After decades of continued scaling to the beat of Moore's law, it now appears that conventional silicon based devices are approaching their physical limits. In today's deep-submicron nodes, a number of short-channel and quantum effects are emerging that affect the manufacturing process, as well as, the functionality of the microelectronic systems-on-chip. Spintronics devices that exploit both the intrinsic spin of the electron and its associated magnetic moment, in addition to its fundamental electronic charge, are promising solutions to circumvent these scaling threats. Being compatible with the CMOS technology, such devices offer a promising synergy of radiation immunity, infinite endurance, non-volatility, increased density, etc. In this paper, we present a hybrid (magnetic/CMOS) cell that is able to store and process data both electrically and magnetically. The cell is based on perpendicular spin-transfer torque magnetic tunnel junctions (STT-MTJs) and is suitable for use in magnetic random access memories and reprogrammable computing (non-volatile registers, processor cache memories, magnetic field-programmable gate arrays, etc). To demonstrate the potential our hybrid cell, we physically implemented a small hybrid memory block using 45 nm × 45 nm round MTJs for the magnetic part and 28 nm fully depleted silicon on insulator (FD-SOI) technology for the CMOS part. We also report the cells measured performances in terms of area, robustness, read/write speed and energy consumption.

The dynamic interplay between acute psychosocial stress, emotion and autobiographical memory.

PubMed

Sheldon, Signy; Chu, Sonja; Nitschke, Jonas P; Pruessner, Jens C; Bartz, Jennifer A

2018-06-06

Although acute psychosocial stress can impact autobiographical memory retrieval, the nature of this effect is not entirely clear. One reason for this ambiguity is because stress can have opposing effects on the different stages of autobiographical memory retrieval. We addressed this issue by testing how acute stress affects three stages of the autobiographical memory retrieval - accessing, recollecting and reconsolidating a memory. We also investigate the influence of emotion valence on this effect. In a between-subjects design, participants were first exposed to an acute psychosocial stressor or a control task. Next, the participants were shown positive, negative or neutral retrieval cues and asked to access and describe autobiographical memories. After a three to four day delay, participants returned for a second session in which they described these autobiographical memories. During initial retrieval, stressed participants were slower to access memories than were control participants; moreover, cortisol levels were positively associated with response times to access positively-cued memories. There were no effects of stress on the amount of details used to describe memories during initial retrieval, but stress did influence memory detail during session two. During session two, stressed participants recovered significantly more details, particularly emotional ones, from the remembered events than control participants. Our results indicate that the presence of stress impairs the ability to access consolidated autobiographical memories; moreover, although stress has no effect on memory recollection, stress alters how recollected experiences are reconsolidated back into memory traces.

Accessing Information in Working Memory: Can the Focus of Attention Grasp Two Elements at the Same Time?

ERIC Educational Resources Information Center

Oberauer, Klaus; Bialkova, Svetlana

2009-01-01

Processing information in working memory requires selective access to a subset of working-memory contents by a focus of attention. Complex cognition often requires joint access to 2 items in working memory. How does the focus select 2 items? Two experiments with an arithmetic task and 1 with a spatial task investigate time demands for successive…

78 FR 35645 - Certain Static Random Access Memories and Products Containing Same; Commission Determination...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-13

... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-792] Certain Static Random Access Memories and Products Containing Same; Commission Determination Affirming a Final Initial Determination..., and the sale within the United States after importation of certain static random access memories and...

Analog Nonvolatile Computer Memory Circuits

NASA Technical Reports Server (NTRS)

MacLeod, Todd

2007-01-01

In nonvolatile random-access memory (RAM) circuits of a proposed type, digital data would be stored in analog form in ferroelectric field-effect transistors (FFETs). This type of memory circuit would offer advantages over prior volatile and nonvolatile types: In a conventional complementary metal oxide/semiconductor static RAM, six transistors must be used to store one bit, and storage is volatile in that data are lost when power is turned off. In a conventional dynamic RAM, three transistors must be used to store one bit, and the stored bit must be refreshed every few milliseconds. In contrast, in a RAM according to the proposal, data would be retained when power was turned off, each memory cell would contain only two FFETs, and the cell could store multiple bits (the exact number of bits depending on the specific design). Conventional flash memory circuits afford nonvolatile storage, but they operate at reading and writing times of the order of thousands of conventional computer memory reading and writing times and, hence, are suitable for use only as off-line storage devices. In addition, flash memories cease to function after limited numbers of writing cycles. The proposed memory circuits would not be subject to either of these limitations. Prior developmental nonvolatile ferroelectric memories are limited to one bit per cell, whereas, as stated above, the proposed memories would not be so limited. The design of a memory circuit according to the proposal must reflect the fact that FFET storage is only partly nonvolatile, in that the signal stored in an FFET decays gradually over time. (Retention times of some advanced FFETs exceed ten years.) Instead of storing a single bit of data as either a positively or negatively saturated state in a ferroelectric device, each memory cell according to the proposal would store two values. The two FFETs in each cell would be denoted the storage FFET and the control FFET. The storage FFET would store an analog signal value, between the positive and negative FFET saturation values. This signal value would represent a numerical value of interest corresponding to multiple bits: for example, if the memory circuit were designed to distinguish among 16 different analog values, then each cell could store 4 bits. Simultaneously with writing the signal value in the storage FFET, a negative saturation signal value would be stored in the control FFET. The decay of this control-FFET signal from the saturation value would serve as a model of the decay, for use in regenerating the numerical value of interest from its decaying analog signal value. The memory circuit would include addressing, reading, and writing circuitry that would have features in common with the corresponding parts of other memory circuits, but would also have several distinctive features. The writing circuitry would include a digital-to-analog converter (DAC); the reading circuitry would include an analog-to-digital converter (ADC). For writing a numerical value of interest in a given cell, that cell would be addressed, the saturation value would be written in the control FFET in that cell, and the non-saturation analog value representing the numerical value of interest would be generated by use of the DAC and stored in the storage FFET in that cell. For reading the numerical value of interest stored in a given cell, the cell would be addressed, the ADC would convert the decaying control and storage analog signal values to digital values, and an associated fast digital processing circuit would regenerate the numerical value from digital values.

78 FR 25767 - Certain Static Random Access Memories and Products Containing Same; Commission Determination To...

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2013-05-02

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Low latency and persistent data storage

DOEpatents

Fitch, Blake G; Franceschini, Michele M; Jagmohan, Ashish; Takken, Todd E

2014-02-18

Persistent data storage is provided by a method that includes receiving a low latency store command that includes write data. The write data is written to a first memory device that is implemented by a nonvolatile solid-state memory technology characterized by a first access speed. It is acknowledged that the write data has been successfully written to the first memory device. The write data is written to a second memory device that is implemented by a volatile memory technology. At least a portion of the data in the first memory device is written to a third memory device when a predetermined amount of data has been accumulated in the first memory device. The third memory device is implemented by a nonvolatile solid-state memory technology characterized by a second access speed that is slower than the first access speed.

System and method for programmable bank selection for banked memory subsystems

DOEpatents

Blumrich, Matthias A.; Chen, Dong; Gara, Alan G.; Giampapa, Mark E.; Hoenicke, Dirk; Ohmacht, Martin; Salapura, Valentina; Sugavanam, Krishnan

2010-09-07

A programmable memory system and method for enabling one or more processor devices access to shared memory in a computing environment, the shared memory including one or more memory storage structures having addressable locations for storing data. The system comprises: one or more first logic devices associated with a respective one or more processor devices, each first logic device for receiving physical memory address signals and programmable for generating a respective memory storage structure select signal upon receipt of pre-determined address bit values at selected physical memory address bit locations; and, a second logic device responsive to each of the respective select signal for generating an address signal used for selecting a memory storage structure for processor access. The system thus enables each processor device of a computing environment memory storage access distributed across the one or more memory storage structures.

Carbon nanomaterials for non-volatile memories

NASA Astrophysics Data System (ADS)

Ahn, Ethan C.; Wong, H.-S. Philip; Pop, Eric

2018-03-01

Carbon can create various low-dimensional nanostructures with remarkable electronic, optical, mechanical and thermal properties. These features make carbon nanomaterials especially interesting for next-generation memory and storage devices, such as resistive random access memory, phase-change memory, spin-transfer-torque magnetic random access memory and ferroelectric random access memory. Non-volatile memories greatly benefit from the use of carbon nanomaterials in terms of bit density and energy efficiency. In this Review, we discuss sp2-hybridized carbon-based low-dimensional nanostructures, such as fullerene, carbon nanotubes and graphene, in the context of non-volatile memory devices and architectures. Applications of carbon nanomaterials as memory electrodes, interfacial engineering layers, resistive-switching media, and scalable, high-performance memory selectors are investigated. Finally, we compare the different memory technologies in terms of writing energy and time, and highlight major challenges in the manufacturing, integration and understanding of the physical mechanisms and material properties.

Design of a memory-access controller with 3.71-times-enhanced energy efficiency for Internet-of-Things-oriented nonvolatile microcontroller unit

NASA Astrophysics Data System (ADS)

Natsui, Masanori; Hanyu, Takahiro

2018-04-01

In realizing a nonvolatile microcontroller unit (MCU) for sensor nodes in Internet-of-Things (IoT) applications, it is important to solve the data-transfer bottleneck between the central processing unit (CPU) and the nonvolatile memory constituting the MCU. As one circuit-oriented approach to solving this problem, we propose a memory access minimization technique for magnetoresistive-random-access-memory (MRAM)-embedded nonvolatile MCUs. In addition to multiplexing and prefetching of memory access, the proposed technique realizes efficient instruction fetch by eliminating redundant memory access while considering the code length of the instruction to be fetched and the transition of the memory address to be accessed. As a result, the performance of the MCU can be improved while relaxing the performance requirement for the embedded MRAM, and compact and low-power implementation can be performed as compared with the conventional cache-based one. Through the evaluation using a system consisting of a general purpose 32-bit CPU and embedded MRAM, it is demonstrated that the proposed technique increases the peak efficiency of the system up to 3.71 times, while a 2.29-fold area reduction is achieved compared with the cache-based one.

Nonvolatile random access memory

NASA Technical Reports Server (NTRS)

Wu, Jiin-Chuan (Inventor); Stadler, Henry L. (Inventor); Katti, Romney R. (Inventor)

1994-01-01

A nonvolatile magnetic random access memory can be achieved by an array of magnet-Hall effect (M-H) elements. The storage function is realized with a rectangular thin-film ferromagnetic material having an in-plane, uniaxial anisotropy and inplane bipolar remanent magnetization states. The thin-film magnetic element is magnetized by a local applied field, whose direction is used to form either a 0 or 1 state. The element remains in the 0 or 1 state until a switching field is applied to change its state. The stored information is detcted by a Hall-effect sensor which senses the fringing field from the magnetic storage element. The circuit design for addressing each cell includes transistor switches for providing a current of selected polarity to store a binary digit through a separate conductor overlying the magnetic element of the cell. To read out a stored binary digit, transistor switches are employed to provide a current through a row of Hall-effect sensors connected in series and enabling a differential voltage amplifier connected to all Hall-effect sensors of a column in series. To avoid read-out voltage errors due to shunt currents through resistive loads of the Hall-effect sensors of other cells in the same column, at least one transistor switch is provided between every pair of adjacent cells in every row which are not turned on except in the row of the selected cell.

76 FR 2336 - Dynamic Random Access Memory Semiconductors From the Republic of Korea: Final Results of...

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... DEPARTMENT OF COMMERCE International Trade Administration [C-580-851] Dynamic Random Access Memory... administrative review of the countervailing duty order on dynamic random access memory semiconductors from the... following events have occurred since the publication of the preliminary results of this review. See Dynamic...

75 FR 20564 - Dynamic Random Access Memory Semiconductors from the Republic of Korea: Extension of Time Limit...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-20

... DEPARTMENT OF COMMERCE International Trade Administration [C-580-851] Dynamic Random Access Memory Semiconductors from the Republic of Korea: Extension of Time Limit for Preliminary Results of Countervailing Duty... access memory semiconductors from the Republic of Korea, covering the period January 1, 2008 through...

Accessibility versus Accuracy in Retrieving Spatial Memory: Evidence for Suboptimal Assumed Headings

ERIC Educational Resources Information Center

Yerramsetti, Ashok; Marchette, Steven A.; Shelton, Amy L.

2013-01-01

Orientation dependence in spatial memory has often been interpreted in terms of accessibility: Object locations are encoded relative to a reference orientation that affords the most accurate access to spatial memory. An open question, however, is whether people naturally use this "preferred" orientation whenever recalling the space. We…

Low latency and persistent data storage

DOEpatents

Fitch, Blake G; Franceschini, Michele M; Jagmohan, Ashish; Takken, Todd

2014-11-04

Persistent data storage is provided by a computer program product that includes computer program code configured for receiving a low latency store command that includes write data. The write data is written to a first memory device that is implemented by a nonvolatile solid-state memory technology characterized by a first access speed. It is acknowledged that the write data has been successfully written to the first memory device. The write data is written to a second memory device that is implemented by a volatile memory technology. At least a portion of the data in the first memory device is written to a third memory device when a predetermined amount of data has been accumulated in the first memory device. The third memory device is implemented by a nonvolatile solid-state memory technology characterized by a second access speed that is slower than the first access speed.

More than a feeling: Emotional cues impact the access and experience of autobiographical memories.

PubMed

Sheldon, Signy; Donahue, Julia

2017-07-01

Remembering is impacted by several factors of retrieval, including the emotional content of a memory cue. Here we tested how musical retrieval cues that differed on two dimensions of emotion-valence (positive and negative) and arousal (high and low)-impacted the following aspects of autobiographical memory recall: the response time to access a past personal event, the experience of remembering (ratings of memory vividness), the emotional content of a cued memory (ratings of event arousal and valence), and the type of event recalled (ratings of event energy, socialness, and uniqueness). We further explored how cue presentation affected autobiographical memory retrieval by administering cues of similar arousal and valence levels in a blocked fashion to one half of the tested participants, and randomly to the other half. We report three main findings. First, memories were accessed most quickly in response to musical cues that were highly arousing and positive in emotion. Second, we observed a relation between a cue and the elicited memory's emotional valence but not arousal; however, both the cue valence and arousal related to the nature of the recalled event. Specifically, high cue arousal led to lower memory vividness and uniqueness ratings, but cues with both high arousal and positive valence were associated with memories rated as more social and energetic. Finally, cue presentation impacted both how quickly and specifically memories were accessed and how cue valence affected the memory vividness ratings. The implications of these findings for views of how emotion directs the access to memories and the experience of remembering are discussed.

The chromatin accessibility signature of human immune aging stems from CD8+ T cells.

PubMed

Ucar, Duygu; Márquez, Eladio J; Chung, Cheng-Han; Marches, Radu; Rossi, Robert J; Uyar, Asli; Wu, Te-Chia; George, Joshy; Stitzel, Michael L; Palucka, A Karolina; Kuchel, George A; Banchereau, Jacques

2017-10-02

Aging is linked to deficiencies in immune responses and increased systemic inflammation. To unravel the regulatory programs behind these changes, we applied systems immunology approaches and profiled chromatin accessibility and the transcriptome in PBMCs and purified monocytes, B cells, and T cells. Analysis of samples from 77 young and elderly donors revealed a novel and robust aging signature in PBMCs, with simultaneous systematic chromatin closing at promoters and enhancers associated with T cell signaling and a potentially stochastic chromatin opening mostly found at quiescent and repressed sites. Combined analyses of chromatin accessibility and the transcriptome uncovered immune molecules activated/inactivated with aging and identified the silencing of the IL7R gene and the IL-7 signaling pathway genes as potential biomarkers. This signature is borne by memory CD8 + T cells, which exhibited an aging-related loss in binding of NF-κB and STAT factors. Thus, our study provides a unique and comprehensive approach to identifying candidate biomarkers and provides mechanistic insights into aging-associated immunodeficiency. © 2017 Ucar et al.

The chromatin accessibility signature of human immune aging stems from CD8+ T cells

PubMed Central

Marches, Radu; Rossi, Robert J.; Uyar, Asli; Wu, Te-Chia; Stitzel, Michael L.; Palucka, A. Karolina

2017-01-01

Aging is linked to deficiencies in immune responses and increased systemic inflammation. To unravel the regulatory programs behind these changes, we applied systems immunology approaches and profiled chromatin accessibility and the transcriptome in PBMCs and purified monocytes, B cells, and T cells. Analysis of samples from 77 young and elderly donors revealed a novel and robust aging signature in PBMCs, with simultaneous systematic chromatin closing at promoters and enhancers associated with T cell signaling and a potentially stochastic chromatin opening mostly found at quiescent and repressed sites. Combined analyses of chromatin accessibility and the transcriptome uncovered immune molecules activated/inactivated with aging and identified the silencing of the IL7R gene and the IL-7 signaling pathway genes as potential biomarkers. This signature is borne by memory CD8+ T cells, which exhibited an aging-related loss in binding of NF-κB and STAT factors. Thus, our study provides a unique and comprehensive approach to identifying candidate biomarkers and provides mechanistic insights into aging-associated immunodeficiency. PMID:28904110

Optical memories in digital computing

NASA Technical Reports Server (NTRS)

Alford, C. O.; Gaylord, T. K.

1979-01-01

High capacity optical memories with relatively-high data-transfer rate and multiport simultaneous access capability may serve as basis for new computer architectures. Several computer structures that might profitably use memories are: a) simultaneous record-access system, b) simultaneously-shared memory computer system, and c) parallel digital processing structure.

Correlative transmission electron microscopy and electrical properties study of switchable phase-change random access memory line cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oosthoek, J. L. M.; Kooi, B. J., E-mail: B.J.Kooi@rug.nl; Voogt, F. C.

2015-02-14

Phase-change memory line cells, where the active material has a thickness of 15 nm, were prepared for transmission electron microscopy (TEM) observation such that they still could be switched and characterized electrically after the preparation. The result of these observations in comparison with detailed electrical characterization showed (i) normal behavior for relatively long amorphous marks, resulting in a hyperbolic dependence between SET resistance and SET current, indicating a switching mechanism based on initially long and thin nanoscale crystalline filaments which thicken gradually, and (ii) anomalous behavior, which holds for relatively short amorphous marks, where initially directly a massive crystalline filament ismore » formed that consumes most of the width of the amorphous mark only leaving minor residual amorphous regions at its edges. The present results demonstrate that even in (purposely) thick TEM samples, the TEM sample preparation hampers the probability to observe normal behavior and it can be debated whether it is possible to produce electrically switchable TEM specimen in which the memory cells behave the same as in their original bulk embedded state.« less

Correlative transmission electron microscopy and electrical properties study of switchable phase-change random access memory line cells

NASA Astrophysics Data System (ADS)

Oosthoek, J. L. M.; Voogt, F. C.; Attenborough, K.; Verheijen, M. A.; Hurkx, G. A. M.; Gravesteijn, D. J.; Kooi, B. J.

2015-02-01

Phase-change memory line cells, where the active material has a thickness of 15 nm, were prepared for transmission electron microscopy (TEM) observation such that they still could be switched and characterized electrically after the preparation. The result of these observations in comparison with detailed electrical characterization showed (i) normal behavior for relatively long amorphous marks, resulting in a hyperbolic dependence between SET resistance and SET current, indicating a switching mechanism based on initially long and thin nanoscale crystalline filaments which thicken gradually, and (ii) anomalous behavior, which holds for relatively short amorphous marks, where initially directly a massive crystalline filament is formed that consumes most of the width of the amorphous mark only leaving minor residual amorphous regions at its edges. The present results demonstrate that even in (purposely) thick TEM samples, the TEM sample preparation hampers the probability to observe normal behavior and it can be debated whether it is possible to produce electrically switchable TEM specimen in which the memory cells behave the same as in their original bulk embedded state.

Resistive Switching of Ta2O5-Based Self-Rectifying Vertical-Type Resistive Switching Memory

NASA Astrophysics Data System (ADS)

Ryu, Sungyeon; Kim, Seong Keun; Choi, Byung Joon

2018-01-01

To efficiently increase the capacity of resistive switching random-access memory (RRAM) while maintaining the same area, a vertical structure similar to a vertical NAND flash structure is needed. In addition, the sneak-path current through the half-selected neighboring memory cell should be mitigated by integrating a selector device with each RRAM cell. In this study, an integrated vertical-type RRAM cell and selector device was fabricated and characterized. Ta2O5 as the switching layer and TaOxNy as the selector layer were used to preliminarily study the feasibility of such an integrated device. To make the side contact of the bottom electrode with active layers, a thick Al2O3 insulating layer was placed between the Pt bottom electrode and the Ta2O5/TaOxNy stacks. Resistive switching phenomena were observed under relatively low currents (below 10 μA) in this vertical-type RRAM device. The TaOxNy layer acted as a nonlinear resistor with moderate nonlinearity. Its low-resistance-state and high-resistance-state were well retained up to 1000 s.

Making working memory work: The effects of extended practice on focus capacity and the processes of updating, forward access, and random access

PubMed Central

Price, John M.; Colflesh, Gregory J. H.; Cerella, John; Verhaeghen, Paul

2014-01-01

We investigated the effects of 10 hours of practice on variations of the N-Back task to investigate the processes underlying possible expansion of the focus of attention within working memory. Using subtractive logic, we showed that random access (i.e., Sternberg-like search) yielded a modest effect (a 50% increase in speed) whereas the processes of forward access (i.e., retrieval in order, as in a standard N-Back task) and updating (i.e., changing the contents of working memory) were executed about 5 times faster after extended practice. We additionally found that extended practice increased working memory capacity as measured by the size of the focus of attention for the forward-access task, but not for variations where probing was in random order. This suggests that working memory capacity may depend on the type of search process engaged, and that certain working-memory-related cognitive processes are more amenable to practice than others. PMID:24486803

How intention and monitoring your thoughts influence characteristics of autobiographical memories.

PubMed

Barzykowski, Krystian; Staugaard, Søren Risløv

2018-05-01

Involuntary autobiographical memories come to mind effortlessly and unintended, but the mechanisms of their retrieval are not fully understood. We hypothesize that involuntary retrieval depends on memories that are highly accessible (e.g., intense, unusual, recent, rehearsed), while the elaborate search that characterizes voluntary retrieval also produces memories that are mundane, repeated or distant - memories with low accessibility. Previous research provides some evidence for this 'threshold hypothesis'. However, in almost every prior study, participants have been instructed to report only memories while ignoring other thoughts. It is possible that such an instruction can modify the phenomenological characteristics of involuntary memories. This study aimed to investigate the effects of retrieval intentionality (i.e., wanting to retrieve a memory) and selective monitoring (i.e., instructions to report only memories) on the phenomenology of autobiographical memories. Participants were instructed to (1) intentionally retrieve autobiographical memories, (2) intentionally retrieve any type of thought (3) wait for an autobiographical memory to spontaneously appear, or (4) wait for any type of thought to spontaneously appear. They rated the mental content on a number of phenomenological characteristics both during retrieval and retrospectively following retrieval. The results support the prediction that highly accessible memories mostly enter awareness unintended and without selective monitoring, while memories with low accessibility rely on intention and selective monitoring. We discuss the implications of these effects. © 2017 The British Psychological Society.

Electrical characteristics of paraelectric lead lanthanum zirconium titanate thin films for dynamic random access memory applications

NASA Astrophysics Data System (ADS)

Jones, R. E., Jr.; Maniar, P. D.; Olowolafe, J. O.; Campbell, A. C.; Mogab, C. J.

1992-02-01

Paraelectric lead lanthanum zirconium titanate (PLZT) films, 150 nm thick, were deposited using a spin-coat, sol-gel process followed by a 650 °C oxygen anneal. X-ray diffraction indicated complete conversion to the perovskite phase. Sputter-deposited platinum electrodes were employed with the PLZT films to form thin-film capacitors with the best combination of high charge storage density (26.1 μC/cm2 at 3 V and 36.4 μC/cm2 at 5 V) and leakage current density (0.2 μA/cm2 at 3 V and 0.5 μA/cm2 at 5 V ) reported to date. The electrical characteristics of these thin-film capacitors meet the requirements for a planar bit cell capacitor for 64-Mbit dynamic random access memories.

UPC++ Programmer’s Guide (v1.0 2017.9)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bachan, J.; Baden, S.; Bonachea, D.

UPC++ is a C++11 library that provides Asynchronous Partitioned Global Address Space (APGAS) programming. It is designed for writing parallel programs that run efficiently and scale well on distributed-memory parallel computers. The APGAS model is single program, multiple-data (SPMD), with each separate thread of execution (referred to as a rank, a term borrowed from MPI) having access to local memory as it would in C++. However, APGAS also provides access to a global address space, which is allocated in shared segments that are distributed over the ranks. UPC++ provides numerous methods for accessing and using global memory. In UPC++, allmore » operations that access remote memory are explicit, which encourages programmers to be aware of the cost of communication and data movement. Moreover, all remote-memory access operations are by default asynchronous, to enable programmers to write code that scales well even on hundreds of thousands of cores.« less

UPC++ Programmer’s Guide, v1.0-2018.3.0

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bachan, J.; Baden, S.; Bonachea, Dan

UPC++ is a C++11 library that provides Partitioned Global Address Space (PGAS) programming. It is designed for writing parallel programs that run efficiently and scale well on distributed-memory parallel computers. The PGAS model is single program, multiple-data (SPMD), with each separate thread of execution (referred to as a rank, a term borrowed from MPI) having access to local memory as it would in C++. However, PGAS also provides access to a global address space, which is allocated in shared segments that are distributed over the ranks. UPC++ provides numerous methods for accessing and using global memory. In UPC++, all operationsmore » that access remote memory are explicit, which encourages programmers to be aware of the cost of communication and data movement. Moreover, all remote-memory access operations are by default asynchronous, to enable programmers to write code that scales well even on hundreds of thousands of cores.« less

Mapping virtual addresses to different physical addresses for value disambiguation for thread memory access requests

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gala, Alan; Ohmacht, Martin

A multiprocessor system includes nodes. Each node includes a data path that includes a core, a TLB, and a first level cache implementing disambiguation. The system also includes at least one second level cache and a main memory. For thread memory access requests, the core uses an address associated with an instruction format of the core. The first level cache uses an address format related to the size of the main memory plus an offset corresponding to hardware thread meta data. The second level cache uses a physical main memory address plus software thread meta data to store the memorymore » access request. The second level cache accesses the main memory using the physical address with neither the offset nor the thread meta data after resolving speculation. In short, this system includes mapping of a virtual address to a different physical addresses for value disambiguation for different threads.« less

Effects of Glycogen Synthase Kinase-3β Inhibitor TWS119 on Proliferation and Cytokine Production of TILs From Human Lung Cancer.

PubMed

Tang, Ying Ying; Sheng, Si Yuan; Lu, Chuan Gang; Zhang, Yu Qing; Zou, Jian Yong; Lei, Yi Yan; Gu, Yong; Hong, Hai

2018-06-05

The canonical Wnt-β-catenin signaling pathway arrests the differentiation of T cells and plays an important role in phenotypic maintenance of naive T cells and stem cell-like memory T cells in human peripheral blood, but its effect on tumor-infiltrating lymphocytes (TILs) from non-small cell lung cancer is little known. In this study, we showed that glycogen synthase kinase-3β inhibitor TWS119 has different effects on CD4 and CD8 T cells in TILs. TWS119 preserved the expansion of naive T cell and CD8 stem cell-like memory T cells, and induced CD8 effector T-cell proliferation in TILs. To further determine whether TWS119 impaired the effector function of TILs, TILs were stimulated with polyclonal stimulation, IL-2 and IFN-γ production were detected. Our data showed that TWS119 does not affect the production of IFN-γ in TILs compared with the control group; whereas TWS119 inhibited IFN-γ secretion of T cells from healthy donor. IL-2 production in CD4 central memory T cells and CD4 effector memory T cells from TILs was significantly increased with the TWS119 treatment; TWS119 also promoted the secretion of IL-2 in all cell subsets of CD8 TILs. These findings reveal that TWS119 has a distinct effect on the proliferation and cytokine production of TILs, and provide new insights into the clinical application of TILs with TWS119 treatment for the adoptive immunotherapy.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Braiman, Yehuda; Neschke, Brendan; Nair, Niketh S.

Here, we study memory states of a circuit consisting of a small inductively coupled Josephson junction array and introduce basic (write, read, and reset) memory operations logics of the circuit. The presented memory operation paradigm is fundamentally different from conventional single quantum flux operation logics. We calculate stability diagrams of the zero-voltage states and outline memory states of the circuit. We also calculate access times and access energies for basic memory operations.

Is random access memory random?

NASA Technical Reports Server (NTRS)

Denning, P. J.

1986-01-01

Most software is contructed on the assumption that the programs and data are stored in random access memory (RAM). Physical limitations on the relative speeds of processor and memory elements lead to a variety of memory organizations that match processor addressing rate with memory service rate. These include interleaved and cached memory. A very high fraction of a processor's address requests can be satified from the cache without reference to the main memory. The cache requests information from main memory in blocks that can be transferred at the full memory speed. Programmers who organize algorithms for locality can realize the highest performance from these computers.

Distributed multiport memory architecture

NASA Technical Reports Server (NTRS)

Kohl, W. H. (Inventor)

1983-01-01

A multiport memory architecture is diclosed for each of a plurality of task centers connected to a command and data bus. Each task center, includes a memory and a plurality of devices which request direct memory access as needed. The memory includes an internal data bus and an internal address bus to which the devices are connected, and direct timing and control logic comprised of a 10-state ring counter for allocating memory devices by enabling AND gates connected to the request signal lines of the devices. The outputs of AND gates connected to the same device are combined by OR gates to form an acknowledgement signal that enables the devices to address the memory during the next clock period. The length of the ring counter may be effectively lengthened to any multiple of ten to allow for more direct memory access intervals in one repetitive sequence. One device is a network bus adapter which serially shifts onto the command and data bus, a data word (8 bits plus control and parity bits) during the next ten direct memory access intervals after it has been granted access. The NBA is therefore allocated only one access in every ten intervals, which is a predetermined interval for all centers. The ring counters of all centers are periodically synchronized by DMA SYNC signal to assure that all NBAs be able to function in synchronism for data transfer from one center to another.

Super non-linear RRAM with ultra-low power for 3D vertical nano-crossbar arrays.

PubMed

Luo, Qing; Xu, Xiaoxin; Liu, Hongtao; Lv, Hangbing; Gong, Tiancheng; Long, Shibing; Liu, Qi; Sun, Haitao; Banerjee, Writam; Li, Ling; Gao, Jianfeng; Lu, Nianduan; Liu, Ming

2016-08-25

Vertical crossbar arrays provide a cost-effective approach for high density three-dimensional (3D) integration of resistive random access memory. However, an individual selector device is not allowed to be integrated with the memory cell separately. The development of V-RRAM has impeded the lack of satisfactory self-selective cells. In this study, we have developed a high performance bilayer self-selective device using HfO2 as the memory switching layer and a mixed ionic and electron conductor as the selective layer. The device exhibits high non-linearity (>10(3)) and ultra-low half-select leakage (<0.1 pA). A four layer vertical crossbar array was successfully demonstrated based on the developed self-selective device. High uniformity, ultra-low leakage, sub-nA operation, self-compliance, and excellent read/write disturbance immunity were achieved. The robust array level performance shows attractive potential for low power and high density 3D data storage applications.

Making working memory work: the effects of extended practice on focus capacity and the processes of updating, forward access, and random access.

PubMed

Price, John M; Colflesh, Gregory J H; Cerella, John; Verhaeghen, Paul

2014-05-01

We investigated the effects of 10h of practice on variations of the N-Back task to investigate the processes underlying possible expansion of the focus of attention within working memory. Using subtractive logic, we showed that random access (i.e., Sternberg-like search) yielded a modest effect (a 50% increase in speed) whereas the processes of forward access (i.e., retrieval in order, as in a standard N-Back task) and updating (i.e., changing the contents of working memory) were executed about 5 times faster after extended practice. We additionally found that extended practice increased working memory capacity as measured by the size of the focus of attention for the forward-access task, but not for variations where probing was in random order. This suggests that working memory capacity may depend on the type of search process engaged, and that certain working-memory-related cognitive processes are more amenable to practice than others. Copyright © 2014 Elsevier B.V. All rights reserved.

Uniform Self-rectifying Resistive Switching Behavior via Preformed Conducting Paths in a Vertical-type Ta2O5/HfO2-x Structure with a Sub-μm(2) Cell Area.

PubMed

Yoon, Jung Ho; Yoo, Sijung; Song, Seul Ji; Yoon, Kyung Jean; Kwon, Dae Eun; Kwon, Young Jae; Park, Tae Hyung; Kim, Hye Jin; Shao, Xing Long; Kim, Yumin; Hwang, Cheol Seong

2016-07-20

To replace or succeed the present NAND flash memory, resistive switching random access memory (ReRAM) should be implemented in the vertical-type crossbar array configuration. The ReRAM cell must have a highly reproducible resistive switching (RS) performance and an electroforming-free, self-rectifying, low-power-consumption, multilevel-switching, and easy fabrication process with a deep sub-μm(2) cell area. In this work, a Pt/Ta2O5/HfO2-x/TiN RS memory cell fabricated in the form of a vertical-type structure was presented as a feasible contender to meet the above requirements. While the fundamental RS characteristics of this material based on the electron trapping/detrapping mechanisms have been reported elsewhere, the influence of the cell scaling size to 0.34 μm(2) on the RS performance by adopting the vertical integration scheme was carefully examined in this work. The smaller cell area provided much better switching uniformity while all the other benefits of this specific material system were preserved. Using the overstressing technique, the nature of RS through the localized conducting path was further examined, which elucidated the fundamental difference between the present material system and the general ionic-motion-related bipolar RS mechanism.

Programmable DMA controller

NASA Technical Reports Server (NTRS)

Hendry, David F. (Inventor)

1993-01-01

In a data system having a memory, plural input/output (I/O) devices and a bus connecting each of the I/O devices to the memory, a direct memory access (DMA) controller regulating access of each of the I/O devices to the bus, including a priority register storing priorities of bus access requests from the I/O devices, an interrupt register storing bus access requests of the I/O devices, a resolver for selecting one of the I/O devices to have access to the bus, a pointer register storing addresses of locations in the memory for communication with the one I/O device via the bus, a sequence register storing an address of a location in the memory containing a channel program instruction which is to be executed next, an ALU for incrementing and decrementing addresses stored in the pointer register, computing the next address to be stored in the sequence register, computing an initial contents of each of the register. The memory contains a sequence of channel program instructions defining a set up operation wherein the contents of each of the registers in the channel register is initialized in accordance with the initial contents computed by the ALU and an access operation wherein data is transferred on the bus between a location in the memory whose address is currently stored in the pointer register and the one I/O device enabled by the resolver.

zorder-lib: Library API for Z-Order Memory Layout

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nowell, Lucy; Edward W. Bethel

2015-04-01

This document describes the motivation for, elements of, and use of the zorder-lib, a library API that implements organization of and access to data in memory using either a-order (also known as "row-major" order) or z-order memory layouts. The primary motivation for this work is to improve the performance of many types of data- intensive codes by increasing both spatial and temporal locality of memory accesses. The basic idea is that the cost associated with accessing a datum is less when it is nearby in either space or time.

Efficient accesses of data structures using processing near memory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jayasena, Nuwan S.; Zhang, Dong Ping; Diez, Paula Aguilera

Systems, apparatuses, and methods for implementing efficient queues and other data structures. A queue may be shared among multiple processors and/or threads without using explicit software atomic instructions to coordinate access to the queue. System software may allocate an atomic queue and corresponding queue metadata in system memory and return, to the requesting thread, a handle referencing the queue metadata. Any number of threads may utilize the handle for accessing the atomic queue. The logic for ensuring the atomicity of accesses to the atomic queue may reside in a management unit in the memory controller coupled to the memory wheremore » the atomic queue is allocated.« less

Face classification using electronic synapses

NASA Astrophysics Data System (ADS)

Yao, Peng; Wu, Huaqiang; Gao, Bin; Eryilmaz, Sukru Burc; Huang, Xueyao; Zhang, Wenqiang; Zhang, Qingtian; Deng, Ning; Shi, Luping; Wong, H.-S. Philip; Qian, He

2017-05-01

Conventional hardware platforms consume huge amount of energy for cognitive learning due to the data movement between the processor and the off-chip memory. Brain-inspired device technologies using analogue weight storage allow to complete cognitive tasks more efficiently. Here we present an analogue non-volatile resistive memory (an electronic synapse) with foundry friendly materials. The device shows bidirectional continuous weight modulation behaviour. Grey-scale face classification is experimentally demonstrated using an integrated 1024-cell array with parallel online training. The energy consumption within the analogue synapses for each iteration is 1,000 × (20 ×) lower compared to an implementation using Intel Xeon Phi processor with off-chip memory (with hypothetical on-chip digital resistive random access memory). The accuracy on test sets is close to the result using a central processing unit. These experimental results consolidate the feasibility of analogue synaptic array and pave the way toward building an energy efficient and large-scale neuromorphic system.

Face classification using electronic synapses.

PubMed

Yao, Peng; Wu, Huaqiang; Gao, Bin; Eryilmaz, Sukru Burc; Huang, Xueyao; Zhang, Wenqiang; Zhang, Qingtian; Deng, Ning; Shi, Luping; Wong, H-S Philip; Qian, He

2017-05-12

Conventional hardware platforms consume huge amount of energy for cognitive learning due to the data movement between the processor and the off-chip memory. Brain-inspired device technologies using analogue weight storage allow to complete cognitive tasks more efficiently. Here we present an analogue non-volatile resistive memory (an electronic synapse) with foundry friendly materials. The device shows bidirectional continuous weight modulation behaviour. Grey-scale face classification is experimentally demonstrated using an integrated 1024-cell array with parallel online training. The energy consumption within the analogue synapses for each iteration is 1,000 × (20 ×) lower compared to an implementation using Intel Xeon Phi processor with off-chip memory (with hypothetical on-chip digital resistive random access memory). The accuracy on test sets is close to the result using a central processing unit. These experimental results consolidate the feasibility of analogue synaptic array and pave the way toward building an energy efficient and large-scale neuromorphic system.

CROSS-DISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Simulation of SET Operation in Phase-Change Random Access Memories with Heater Addition and Ring-Type Contactor for Low-Power Consumption by Finite Element Modeling

NASA Astrophysics Data System (ADS)

Gong, Yue-Feng; Song, Zhi-Tang; Ling, Yun; Liu, Yan; Feng, Song-Lin

2009-11-01

A three-dimensional finite element model for phase change random access memory (PCRAM) is established for comprehensive electrical and thermal analysis during SET operation. The SET behaviours of the heater addition structure (HS) and the ring-type contact in bottom electrode (RIB) structure are compared with each other. There are two ways to reduce the RESET current, applying a high resistivity interfacial layer and building a new device structure. The simulation results indicate that the variation of SET current with different power reduction ways is little. This study takes the RESET and SET operation current into consideration, showing that the RIB structure PCRAM cell is suitable for future devices with high heat efficiency and high-density, due to its high heat efficiency in RESET operation.

A multilevel nonvolatile magnetoelectric memory

NASA Astrophysics Data System (ADS)

Shen, Jianxin; Cong, Junzhuang; Shang, Dashan; Chai, Yisheng; Shen, Shipeng; Zhai, Kun; Sun, Young

2016-09-01

The coexistence and coupling between magnetization and electric polarization in multiferroic materials provide extra degrees of freedom for creating next-generation memory devices. A variety of concepts of multiferroic or magnetoelectric memories have been proposed and explored in the past decade. Here we propose a new principle to realize a multilevel nonvolatile memory based on the multiple states of the magnetoelectric coefficient (α) of multiferroics. Because the states of α depends on the relative orientation between magnetization and polarization, one can reach different levels of α by controlling the ratio of up and down ferroelectric domains with external electric fields. Our experiments in a device made of the PMN-PT/Terfenol-D multiferroic heterostructure confirm that the states of α can be well controlled between positive and negative by applying selective electric fields. Consequently, two-level, four-level, and eight-level nonvolatile memory devices are demonstrated at room temperature. This kind of multilevel magnetoelectric memory retains all the advantages of ferroelectric random access memory but overcomes the drawback of destructive reading of polarization. In contrast, the reading of α is nondestructive and highly efficient in a parallel way, with an independent reading coil shared by all the memory cells.

Single-cell epigenomics: techniques and emerging applications.

PubMed

Schwartzman, Omer; Tanay, Amos

2015-12-01

Epigenomics is the study of the physical modifications, associations and conformations of genomic DNA sequences, with the aim of linking these with epigenetic memory, cellular identity and tissue-specific functions. While current techniques in the field are characterizing the average epigenomic features across large cell ensembles, the increasing interest in the epigenetics within complex and heterogeneous tissues is driving the development of single-cell epigenomics. We review emerging single-cell methods for capturing DNA methylation, chromatin accessibility, histone modifications, chromosome conformation and replication dynamics. Together, these techniques are rapidly becoming a powerful tool in studies of cellular plasticity and diversity, as seen in stem cells and cancer.

Working memory capacity and controlled serial memory search.

PubMed

Mızrak, Eda; Öztekin, Ilke

2016-08-01

The speed-accuracy trade-off (SAT) procedure was used to investigate the relationship between working memory capacity (WMC) and the dynamics of temporal order memory retrieval. High- and low-span participants (HSs, LSs) studied sequentially presented five-item lists, followed by two probes from the study list. Participants indicated the more recent probe. Overall, accuracy was higher for HSs compared to LSs. Crucially, in contrast to previous investigations that observed no impact of WMC on speed of access to item information in memory (e.g., Öztekin & McElree, 2010), recovery of temporal order memory was slower for LSs. While accessing an item's representation in memory can be direct, recovery of relational information such as temporal order information requires a more controlled serial memory search. Collectively, these data indicate that WMC effects are particularly prominent during high demands of cognitive control, such as serial search operations necessary to access temporal order information from memory. Copyright © 2016 Elsevier B.V. All rights reserved.

The potential of multi-port optical memories in digital computing

NASA Technical Reports Server (NTRS)

Alford, C. O.; Gaylord, T. K.

1975-01-01

A high-capacity memory with a relatively high data transfer rate and multi-port simultaneous access capability may serve as the basis for new computer architectures. The implementation of a multi-port optical memory is discussed. Several computer structures are presented that might profitably use such a memory. These structures include (1) a simultaneous record access system, (2) a simultaneously shared memory computer system, and (3) a parallel digital processing structure.

Saying what’s on your mind: Working memory effects on sentence production

PubMed Central

Slevc, L. Robert

2011-01-01

The role of working memory (WM) in sentence comprehension has received considerable interest, but little work has investigated how sentence production relies on memory mechanisms. These three experiments investigated speakers’ tendency to produce syntactic structures that allow for early production of material that is accessible in memory. In Experiment 1, speakers produced accessible information early less often when under a verbal WM load than when under no load. Experiment 2 found the same pattern for given-new ordering, i.e., when accessibility was manipulated by making information given. Experiment 3 addressed the possibility that these effects do not reflect WM mechanisms but rather increased task difficulty by relying on the distinction between verbal and spatial WM: Speakers’ tendency to produce sentences respecting given-new ordering was reduced more by a verbal than by a spatial WM load. These patterns show that accessibility effects do in fact reflect accessibility in verbal WM, and that representations in sentence production are vulnerable to interference from other information in memory. PMID:21767058

Working memory at work: how the updating process alters the nature of working memory transfer.

PubMed

Zhang, Yanmin; Verhaeghen, Paul; Cerella, John

2012-01-01

In three N-Back experiments, we investigated components of the process of working memory (WM) updating, more specifically access to items stored outside the focus of attention and transfer from the focus to the region of WM outside the focus. We used stimulus complexity as a marker. We found that when WM transfer occurred under full attention, it was slow and highly sensitive to stimulus complexity, much more so than WM access. When transfer occurred in conjunction with access, however, it was fast and no longer sensitive to stimulus complexity. Thus the updating context altered the nature of WM processing: The dual-task situation (transfer in conjunction with access) drove memory transfer into a more efficient mode, indifferent to stimulus complexity. In contrast, access times consistently increased with complexity, unaffected by the processing context. This study reinforces recent reports that retrieval is a (perhaps the) key component of working memory functioning. Copyright © 2011 Elsevier B.V. All rights reserved.

Working Memory at Work: How the Updating Process Alters the Nature of Working Memory Transfer

PubMed Central

Zhang, Yanmin; Verhaeghen, Paul; Cerella, John

2011-01-01

In three N-Back experiments, we investigated components of the process of working memory (WM) updating, more specifically access to items stored outside the focus of attention and transfer from the focus to the region of WM outside the focus. We used stimulus complexity as a marker. We found that when WM transfer occurred under full attention, it was slow and highly sensitive to stimulus complexity, much more so than WM access. When transfer occurred in conjunction with access, however, it was fast and no longer sensitive to stimulus complexity. Thus the updating context altered the nature of WM processing: The dual-task situation (transfer in conjunction with access) drove memory transfer into a more efficient mode, indifferent to stimulus complexity. In contrast, access times consistently increased with complexity, unaffected by the processing context. This study reinforces recent reports that retrieval is a (perhaps the) key component of working memory functioning. PMID:22105718

Children's Access to Public Library Services: Prince George's County Memorial Public Library, Maryland, 1980.

ERIC Educational Resources Information Center

Gerhardt, Lillian N.

1981-01-01

Evaluates the Prince George's County Memorial Public Library's approach to providing access to its services for children, and examines policies, regulations, practices, and conditions that affect such access. Six references are cited. (FM)

What versus where: Investigating how autobiographical memory retrieval differs when accessed with thematic versus spatial information.

PubMed

Sheldon, Signy; Chu, Sonja

2017-09-01

Autobiographical memory research has investigated how cueing distinct aspects of a past event can trigger different recollective experiences. This research has stimulated theories about how autobiographical knowledge is accessed and organized. Here, we test the idea that thematic information organizes multiple autobiographical events whereas spatial information organizes individual past episodes by investigating how retrieval guided by these two forms of information differs. We used a novel autobiographical fluency task in which participants accessed multiple memory exemplars to event theme and spatial (location) cues followed by a narrative description task in which they described the memories generated to these cues. Participants recalled significantly more memory exemplars to event theme than to spatial cues; however, spatial cues prompted faster access to past memories. Results from the narrative description task revealed that memories retrieved via event theme cues compared to spatial cues had a higher number of overall details, but those recalled to the spatial cues were recollected with a greater concentration on episodic details than those retrieved via event theme cues. These results provide evidence that thematic information organizes and integrates multiple memories whereas spatial information prompts the retrieval of specific episodic content from a past event.

beachmat: A Bioconductor C++ API for accessing high-throughput biological data from a variety of R matrix types

PubMed Central

Pagès, Hervé

2018-01-01

Biological experiments involving genomics or other high-throughput assays typically yield a data matrix that can be explored and analyzed using the R programming language with packages from the Bioconductor project. Improvements in the throughput of these assays have resulted in an explosion of data even from routine experiments, which poses a challenge to the existing computational infrastructure for statistical data analysis. For example, single-cell RNA sequencing (scRNA-seq) experiments frequently generate large matrices containing expression values for each gene in each cell, requiring sparse or file-backed representations for memory-efficient manipulation in R. These alternative representations are not easily compatible with high-performance C++ code used for computationally intensive tasks in existing R/Bioconductor packages. Here, we describe a C++ interface named beachmat, which enables agnostic data access from various matrix representations. This allows package developers to write efficient C++ code that is interoperable with dense, sparse and file-backed matrices, amongst others. We evaluated the performance of beachmat for accessing data from each matrix representation using both simulated and real scRNA-seq data, and defined a clear memory/speed trade-off to motivate the choice of an appropriate representation. We also demonstrate how beachmat can be incorporated into the code of other packages to drive analyses of a very large scRNA-seq data set. PMID:29723188

beachmat: A Bioconductor C++ API for accessing high-throughput biological data from a variety of R matrix types.

PubMed

Lun, Aaron T L; Pagès, Hervé; Smith, Mike L

2018-05-01

Biological experiments involving genomics or other high-throughput assays typically yield a data matrix that can be explored and analyzed using the R programming language with packages from the Bioconductor project. Improvements in the throughput of these assays have resulted in an explosion of data even from routine experiments, which poses a challenge to the existing computational infrastructure for statistical data analysis. For example, single-cell RNA sequencing (scRNA-seq) experiments frequently generate large matrices containing expression values for each gene in each cell, requiring sparse or file-backed representations for memory-efficient manipulation in R. These alternative representations are not easily compatible with high-performance C++ code used for computationally intensive tasks in existing R/Bioconductor packages. Here, we describe a C++ interface named beachmat, which enables agnostic data access from various matrix representations. This allows package developers to write efficient C++ code that is interoperable with dense, sparse and file-backed matrices, amongst others. We evaluated the performance of beachmat for accessing data from each matrix representation using both simulated and real scRNA-seq data, and defined a clear memory/speed trade-off to motivate the choice of an appropriate representation. We also demonstrate how beachmat can be incorporated into the code of other packages to drive analyses of a very large scRNA-seq data set.

Memory-efficient table look-up optimized algorithm for context-based adaptive variable length decoding in H.264/advanced video coding

NASA Astrophysics Data System (ADS)

Wang, Jianhua; Cheng, Lianglun; Wang, Tao; Peng, Xiaodong

2016-03-01

Table look-up operation plays a very important role during the decoding processing of context-based adaptive variable length decoding (CAVLD) in H.264/advanced video coding (AVC). However, frequent table look-up operation can result in big table memory access, and then lead to high table power consumption. Aiming to solve the problem of big table memory access of current methods, and then reduce high power consumption, a memory-efficient table look-up optimized algorithm is presented for CAVLD. The contribution of this paper lies that index search technology is introduced to reduce big memory access for table look-up, and then reduce high table power consumption. Specifically, in our schemes, we use index search technology to reduce memory access by reducing the searching and matching operations for code_word on the basis of taking advantage of the internal relationship among length of zero in code_prefix, value of code_suffix and code_lengh, thus saving the power consumption of table look-up. The experimental results show that our proposed table look-up algorithm based on index search can lower about 60% memory access consumption compared with table look-up by sequential search scheme, and then save much power consumption for CAVLD in H.264/AVC.

Garnet Random-Access Memory

NASA Technical Reports Server (NTRS)

Katti, Romney R.

1995-01-01

Random-access memory (RAM) devices of proposed type exploit magneto-optical properties of magnetic garnets exhibiting perpendicular anisotropy. Magnetic writing and optical readout used. Provides nonvolatile storage and resists damage by ionizing radiation. Because of basic architecture and pinout requirements, most likely useful as small-capacity memory devices.

Development of Curie point switching for thin film, random access, memory device

NASA Technical Reports Server (NTRS)

Lewicki, G. W.; Tchernev, D. I.

1967-01-01

Managanese bismuthide films are used in the development of a random access memory device of high packing density and nondestructive readout capability. Memory entry is by Curie point switching using a laser beam. Readout is accomplished by microoptical or micromagnetic scanning.

Individual differences in memory span: the contribution of rehearsal, access to lexical memory, and output speed.

PubMed

Tehan, G; Lalor, D M

2000-11-01

Rehearsal speed has traditionally been seen to be the prime determinant of individual differences in memory span. Recent studies, in the main using young children as the subject population, have suggested other contributors to span performance, notably contributions from long-term memory and forgetting and retrieval processes occurring during recall. In the current research we explore individual differences in span with respect to measures of rehearsal, output time, and access to lexical memory. We replicate standard short-term phenomena; we show that the variables that influence children's span performance influence adult performance in the same way; and we show that lexical memory access appears to be a more potent source of individual differences in span than either rehearsal speed or output factors.

Adult Age Differences in Accessing and Retrieving Information from Long-Term Memory.

ERIC Educational Resources Information Center

Petros, Thomas V.; And Others

1983-01-01

Investigated adult age differences in accessing and retrieving information from long-term memory. Results showed that older adults (N=26) were slower than younger adults (N=35) at feature extraction, lexical access, and accessing category information. The age deficit was proportionally greater when retrieval of category information was required.…

Bubble memory module for spacecraft application

NASA Technical Reports Server (NTRS)

Hayes, P. J.; Looney, K. T.; Nichols, C. D.

1985-01-01

Bubble domain technology offers an all-solid-state alternative for data storage in onboard data systems. A versatile modular bubble memory concept was developed. The key module is the bubble memory module which contains all of the storage devices and circuitry for accessing these devices. This report documents the bubble memory module design and preliminary hardware designs aimed at memory module functional demonstration with available commercial bubble devices. The system architecture provides simultaneous operation of bubble devices to attain high data rates. Banks of bubble devices are accessed by a given bubble controller to minimize controller parts. A power strobing technique is discussed which could minimize the average system power dissipation. A fast initialization method using EEPROM (electrically erasable, programmable read-only memory) devices promotes fast access. Noise and crosstalk problems and implementations to minimize these are discussed. Flight memory systems which incorporate the concepts and techniques of this work could now be developed for applications.

Wide-Range Motion Estimation Architecture with Dual Search Windows for High Resolution Video Coding

NASA Astrophysics Data System (ADS)

Dung, Lan-Rong; Lin, Meng-Chun

This paper presents a memory-efficient motion estimation (ME) technique for high-resolution video compression. The main objective is to reduce the external memory access, especially for limited local memory resource. The reduction of memory access can successfully save the notorious power consumption. The key to reduce the memory accesses is based on center-biased algorithm in that the center-biased algorithm performs the motion vector (MV) searching with the minimum search data. While considering the data reusability, the proposed dual-search-windowing (DSW) approaches use the secondary windowing as an option per searching necessity. By doing so, the loading of search windows can be alleviated and hence reduce the required external memory bandwidth. The proposed techniques can save up to 81% of external memory bandwidth and require only 135 MBytes/sec, while the quality degradation is less than 0.2dB for 720p HDTV clips coded at 8Mbits/sec.

Radiation Effects of Commercial Resistive Random Access Memories

NASA Technical Reports Server (NTRS)

Chen, Dakai; LaBel, Kenneth A.; Berg, Melanie; Wilcox, Edward; Kim, Hak; Phan, Anthony; Figueiredo, Marco; Buchner, Stephen; Khachatrian, Ani; Roche, Nicolas

2014-01-01

We present results for the single-event effect response of commercial production-level resistive random access memories. We found that the resistive memory arrays are immune to heavy ion-induced upsets. However, the devices were susceptible to single-event functional interrupts, due to upsets from the control circuits. The intrinsic radiation tolerant nature of resistive memory makes the technology an attractive consideration for future space applications.

Cost-effective, transfer-free, flexible resistive random access memory using laser-scribed reduced graphene oxide patterning technology.

PubMed

Tian, He; Chen, Hong-Yu; Ren, Tian-Ling; Li, Cheng; Xue, Qing-Tang; Mohammad, Mohammad Ali; Wu, Can; Yang, Yi; Wong, H-S Philip

2014-06-11

Laser scribing is an attractive reduced graphene oxide (rGO) growth and patterning technology because the process is low-cost, time-efficient, transfer-free, and flexible. Various laser-scribed rGO (LSG) components such as capacitors, gas sensors, and strain sensors have been demonstrated. However, obstacles remain toward practical application of the technology where all the components of a system are fabricated using laser scribing. Memory components, if developed, will substantially broaden the application space of low-cost, flexible electronic systems. For the first time, a low-cost approach to fabricate resistive random access memory (ReRAM) using laser-scribed rGO as the bottom electrode is experimentally demonstrated. The one-step laser scribing technology allows transfer-free rGO synthesis directly on flexible substrates or non-flat substrates. Using this time-efficient laser-scribing technology, the patterning of a memory-array area up to 100 cm(2) can be completed in 25 min. Without requiring the photoresist coating for lithography, the surface of patterned rGO remains as clean as its pristine state. Ag/HfOx/LSG ReRAM using laser-scribing technology is fabricated in this work. Comprehensive electrical characteristics are presented including forming-free behavior, stable switching, reasonable reliability performance and potential for 2-bit storage per memory cell. The results suggest that laser-scribing technology can potentially produce more cost-effective and time-effective rGO-based circuits and systems for practical applications.

Plasma-Assisted Dry Etching of Ferroelectric Capacitor Modules and Application to a 32M Ferroelectric Random Access Memory Devices with Submicron Feature Sizes

NASA Astrophysics Data System (ADS)

Lee, Sang-Woo; Joo, Suk-Ho; Cho, Sung Lae; Son, Yoon-Ho; Lee, Kyu-Mann; Nam, Sang-Don; Park, Kun-Sang; Lee, Yong-Tak; Seo, Jung-Suk; Kim, Young-Dae; An, Hyeong-Geun; Kim, Hyoung-Joon; Jung, Yong-Ju; Heo, Jang-Eun; Lee, Moon-Sook; Park, Soon-Oh; Chung, U-In; Moon, Joo-Tae

2002-11-01

In the manufacturing of a 32M ferroelectric random access memory (FRAM) device on the basis of 0.25 design rule (D/R), one of the most difficult processes is to pattern a submicron capacitor module while retaining good ferroelectric properties. In this paper, we report the ferroelectric property of patterned submicron capacitor modules with a stack height of 380 nm, where the 100 nm-thick Pb(Zr, Ti)O3 (PZT) films were prepared by the sol-gel method. After patterning, overall sidewall slope was approximately 70° and cell-to-cell node separation was made to be 80 nm to prevent possible twin-bit failure in the device. Finally, several heat treatment conditions were investigated to retain the ferroelectric property of the patterned capacitor. It was found that rapid thermal processing (RTP) treatment yields better properties than conventional furnace annealing. This result is directly related to the near-surface chemistry of the PZT films, as confirmed by X-ray photoelectron spectroscopy (XPS) analysis. The resultant switching polarization value of the submicron capacitor was approximately 30 μC/cm2 measured at 3 V.

Accessibility Limits Recall from Visual Working Memory

ERIC Educational Resources Information Center

Rajsic, Jason; Swan, Garrett; Wilson, Daryl E.; Pratt, Jay

2017-01-01

In this article, we demonstrate limitations of accessibility of information in visual working memory (VWM). Recently, cued-recall has been used to estimate the fidelity of information in VWM, where the feature of a cued object is reproduced from memory (Bays, Catalao, & Husain, 2009; Wilken & Ma, 2004; Zhang & Luck, 2008). Response…

Non-tables look-up search algorithm for efficient H.264/AVC context-based adaptive variable length coding decoding

NASA Astrophysics Data System (ADS)

Han, Yishi; Luo, Zhixiao; Wang, Jianhua; Min, Zhixuan; Qin, Xinyu; Sun, Yunlong

2014-09-01

In general, context-based adaptive variable length coding (CAVLC) decoding in H.264/AVC standard requires frequent access to the unstructured variable length coding tables (VLCTs) and significant memory accesses are consumed. Heavy memory accesses will cause high power consumption and time delays, which are serious problems for applications in portable multimedia devices. We propose a method for high-efficiency CAVLC decoding by using a program instead of all the VLCTs. The decoded codeword from VLCTs can be obtained without any table look-up and memory access. The experimental results show that the proposed algorithm achieves 100% memory access saving and 40% decoding time saving without degrading video quality. Additionally, the proposed algorithm shows a better performance compared with conventional CAVLC decoding, such as table look-up by sequential search, table look-up by binary search, Moon's method, and Kim's method.

Accelerating molecular dynamic simulation on the cell processor and Playstation 3.

PubMed

Luttmann, Edgar; Ensign, Daniel L; Vaidyanathan, Vishal; Houston, Mike; Rimon, Noam; Øland, Jeppe; Jayachandran, Guha; Friedrichs, Mark; Pande, Vijay S

2009-01-30

Implementation of molecular dynamics (MD) calculations on novel architectures will vastly increase its power to calculate the physical properties of complex systems. Herein, we detail algorithmic advances developed to accelerate MD simulations on the Cell processor, a commodity processor found in PlayStation 3 (PS3). In particular, we discuss issues regarding memory access versus computation and the types of calculations which are best suited for streaming processors such as the Cell, focusing on implicit solvation models. We conclude with a comparison of improved performance on the PS3's Cell processor over more traditional processors. (c) 2008 Wiley Periodicals, Inc.

The two faces of selective memory retrieval: recall specificity of the detrimental but not the beneficial effect.

PubMed

Bäuml, Karl-Heinz T; Dobler, Ina M

2015-01-01

Depending on the degree to which the original study context is accessible, selective memory retrieval can be detrimental or beneficial for the recall of other memories (Bäuml & Samenieh, 2012). Prior work has shown that the detrimental effect of memory retrieval is typically recall specific and does not arise after restudy trials, whereas recall specificity of the beneficial effect has not been examined to date. Addressing the issue, we compared in 2 experiments the effects of retrieval and restudy on recall of other items, when access to the study context was (largely) maintained and when access to the study context was impaired (in Experiment 1 by using the listwise directed-forgetting task, in Experiment 2 by using a prolonged retention interval). In both experiments, selective retrieval but not restudy induced forgetting of other items when context access was maintained, which replicates prior work. In contrast, when context access was impaired, both selective retrieval and restudy induced beneficial effects on other memories. These findings suggest that the detrimental but not the beneficial effect of selective memory retrieval is recall specific. The results are consistent with a recent 2-factor account of selective memory retrieval that attributes the detrimental effect to inhibition or blocking but the beneficial effect to context reactivation processes. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Low latency memory access and synchronization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blumrich, Matthias A.; Chen, Dong; Coteus, Paul W.

A low latency memory system access is provided in association with a weakly-ordered multiprocessor system. Each processor in the multiprocessor shares resources, and each shared resource has an associated lock within a locking device that provides support for synchronization between the multiple processors in the multiprocessor and the orderly sharing of the resources. A processor only has permission to access a resource when it owns the lock associated with that resource, and an attempt by a processor to own a lock requires only a single load operation, rather than a traditional atomic load followed by store, such that the processormore » only performs a read operation and the hardware locking device performs a subsequent write operation rather than the processor. A simple prefetching for non-contiguous data structures is also disclosed. A memory line is redefined so that in addition to the normal physical memory data, every line includes a pointer that is large enough to point to any other line in the memory, wherein the pointers to determine which memory line to prefetch rather than some other predictive algorithm. This enables hardware to effectively prefetch memory access patterns that are non-contiguous, but repetitive.« less

Low latency memory access and synchronization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blumrich, Matthias A.; Chen, Dong; Coteus, Paul W.

A low latency memory system access is provided in association with a weakly-ordered multiprocessor system. Bach processor in the multiprocessor shares resources, and each shared resource has an associated lock within a locking device that provides support for synchronization between the multiple processors in the multiprocessor and the orderly sharing of the resources. A processor only has permission to access a resource when it owns the lock associated with that resource, and an attempt by a processor to own a lock requires only a single load operation, rather than a traditional atomic load followed by store, such that the processormore » only performs a read operation and the hardware locking device performs a subsequent write operation rather than the processor. A simple prefetching for non-contiguous data structures is also disclosed. A memory line is redefined so that in addition to the normal physical memory data, every line includes a pointer that is large enough to point to any other line in the memory, wherein the pointers to determine which memory line to prefetch rather than some other predictive algorithm. This enables hardware to effectively prefetch memory access patterns that are non-contiguous, but repetitive.« less

Levels of Neural Progenitors in the Hippocampus Predict Memory Impairment and Relapse to Drug Seeking as a Function of Excessive Methamphetamine Self-Administration

PubMed Central

Recinto, Patrick; Samant, Anjali Rose H; Chavez, Gustavo; Kim, Airee; Yuan, Clara J; Soleiman, Matthew; Grant, Yanabel; Edwards, Scott; Wee, Sunmee; Koob, George F; George, Olivier; Mandyam, Chitra D

2012-01-01

Methamphetamine affects the hippocampus, a brain region crucial for learning and memory, as well as relapse to drug seeking. Rats self-administered methamphetamine for 1 h twice weekly (intermittent-short-I-ShA), 1 h daily (limited-short-ShA), or 6 h daily (extended-long-LgA) for 22 sessions. After 22 sessions, rats from each access group were withdrawn from self-administration and underwent spatial memory (Y-maze) and working memory (T-maze) tests followed by extinction and reinstatement to methamphetamine seeking or received one intraperitoneal injection of 5-bromo-2′-deoxyuridine (BrdU) to label progenitors in the hippocampal subgranular zone (SGZ) during the synthesis phase. Two-hour-old and 28-day-old surviving BrdU-immunoreactive cells were quantified. I-ShA rats performed better on the Y-maze and had a greater number of 2-h-old SGZ BrdU cells than nondrug controls. LgA rats, but not ShA rats, performed worse on the Y- and T-maze and had a fewer number of 2-h-old SGZ BrdU cells than nondrug and I-ShA rats, suggesting that new hippocampal progenitors, decreased by methamphetamine, were correlated with impairment in the acquisition of new spatial cues. Analyses of addiction-related behaviors after withdrawal and extinction training revealed methamphetamine-primed reinstatement of methamphetamine-seeking behavior in all three groups (I-ShA, ShA, and LgA), and this effect was enhanced in LgA rats compared with I-ShA and ShA rats. Protracted withdrawal from self-administration enhanced the survival of SGZ BrdU cells, and methamphetamine seeking during protracted withdrawal enhanced Fos expression in the dentate gyrus and medial prefrontal cortex in LgA rats to a greater extent than in ShA and I-ShA rats. These results indicate that changes in the levels of the proliferation and survival of hippocampal neural progenitors and neuronal activation of hippocampal granule cells predict the effects of methamphetamine self-administration (limited vs extended access) on cognitive performance and relapse to drug seeking and may contribute to the impairments that perpetuate the addiction cycle. PMID:22205547

Dynamically programmable cache

NASA Astrophysics Data System (ADS)

Nakkar, Mouna; Harding, John A.; Schwartz, David A.; Franzon, Paul D.; Conte, Thomas

1998-10-01

Reconfigurable machines have recently been used as co- processors to accelerate the execution of certain algorithms or program subroutines. The problems with the above approach include high reconfiguration time and limited partial reconfiguration. By far the most critical problems are: (1) the small on-chip memory which results in slower execution time, and (2) small FPGA areas that cannot implement large subroutines. Dynamically Programmable Cache (DPC) is a novel architecture for embedded processors which offers solutions to the above problems. To solve memory access problems, DPC processors merge reconfigurable arrays with the data cache at various cache levels to create a multi-level reconfigurable machines. As a result DPC machines have both higher data accessibility and FPGA memory bandwidth. To solve the limited FPGA resource problem, DPC processors implemented multi-context switching (Virtualization) concept. Virtualization allows implementation of large subroutines with fewer FPGA cells. Additionally, DPC processors can parallelize the execution of several operations resulting in faster execution time. In this paper, the speedup improvement for DPC machines are shown to be 5X faster than an Altera FLEX10K FPGA chip and 2X faster than a Sun Ultral SPARC station for two different algorithms (convolution and motion estimation).

Plated wire random access memories

NASA Technical Reports Server (NTRS)

Gouldin, L. D.

1975-01-01

A program was conducted to construct 4096-work by 18-bit random access, NDRO-plated wire memory units. The memory units were subjected to comprehensive functional and environmental tests at the end-item level to verify comformance with the specified requirements. A technical description of the unit is given, along with acceptance test data sheets.

The Dynamics of Access to Groups in Working Memory

ERIC Educational Resources Information Center

Farrell, Simon; Lelievre, Anna

2012-01-01

The finding that participants leave a pause between groups when attempting serial recall of temporally grouped lists has been taken to indicate access to a hierarchical representation of the list in working memory. An alternative explanation is that the dynamics of serial recall solely reflect output (rather than memorial) processes, with the…

Nonpolar resistive memory switching with all four possible resistive switching modes in amorphous LaHoO{sub 3} thin films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sharma, Yogesh; Pavunny, Shojan P.; Katiyar, Ram S., E-mail: rkatiyar@hpcf.upr.edu

2015-09-07

We studied the resistive memory switching in pulsed laser deposited amorphous LaHoO{sub 3} (a-LHO) thin films for non-volatile resistive random access memory applications. Nonpolar resistive switching (RS) was achieved in Pt/a-LHO/Pt memory cells with all four possible RS modes (i.e., positive unipolar, positive bipolar, negative unipolar, and negative bipolar) having high R{sub ON}/R{sub OFF} ratios (in the range of ∼10{sup 4}–10{sup 5}) and non-overlapping switching voltages (set voltage, V{sub ON} ∼ ±3.6–4.2 V and reset voltage, V{sub OFF} ∼ ±1.3–1.6 V) with a small variation of about ±5–8%. Temperature dependent current-voltage (I–V) characteristics indicated the metallic conduction in low resistance states (LRS). We believe that themore » formation (set) and rupture (reset) of mixed conducting filaments formed out of oxygen vacancies and metallic Ho atoms could be responsible for the change in the resistance states of the memory cell. Detailed analysis of I–V characteristics further corroborated the formation of conductive nanofilaments based on metal-like (Ohmic) conduction in LRS. Simmons-Schottky emission was found to be the dominant charge transport mechanism in the high resistance state.« less

Performance of FORTRAN floating-point operations on the Flex/32 multicomputer

NASA Technical Reports Server (NTRS)

Crockett, Thomas W.

1987-01-01

A series of experiments has been run to examine the floating-point performance of FORTRAN programs on the Flex/32 (Trademark) computer. The experiments are described, and the timing results are presented. The time required to execute a floating-point operation is found to vary considerbaly depending on a number of factors. One factor of particular interest from an algorithm design standpoint is the difference in speed between common memory accesses and local memory accesses. Common memory accesses were found to be slower, and guidelines are given for determinig when it may be cost effective to copy data from common to local memory.

A graphite based STT-RAM cell with reduction in switching current

NASA Astrophysics Data System (ADS)

Varghani, Ali; Peiravi, Ali

2015-10-01

Spin Transfer Torque Random Access Memory (STT-RAM) is a serious candidate for "universal memory" because of its non-volatility, fast access time, high density, good scalability, high endurance and relatively low power dissipation. However, problems with low write speed and large write current are important existing challenges in STT-RAM design and there is a tradeoff between them and data retention time. In this study, a novel STT-RAM cell structure which uses perfect graphite based Magnetic Tunnel Junction (MTJ) is proposed. First, the cross-section of the structure is selected to be an ellipse of 45 nm and 180 nm dimensions and a six-layer graphite is used as tunnel barrier. By passing a lateral current with a short pulse width (before applying STT current and independent of it) through four middle graphene layers of the tunnel barrier, a 27% reduction in the amplitude of the switching current (for fast switching time of 2 ns) or a 58% reduction in its pulse width is achieved without any reduction in data retention time. Finally, the effect of downscaling of technology on the proposed structure is evaluated. A reduction of 31.6% and 9% in switching current is achieved for 90 and 22 nm cell width respectively by passing sufficient current (100 μA with 0.1 ns pulse width) through the tunnel barrier. Simulations are done using Object Oriented Micro Magnetic Framework (OOMMF).

The evolving roles of memory immune cells in transplantation

PubMed Central

Chen, Wenhao; Ghobrial, Rafik M.; Li, Xian C.

2015-01-01

Memory cells are the products of immune responses but also exert significant impact on subsequent immunity and immune tolerance, thus placing them in a unique position in transplant research. Memory cells are heterogeneous, including not only memory T cells but also memory B cells and innate memory cells. Memory cells are a critical component of protective immunity against invading pathogens, especially in immunosuppressed patients, but they also mediate graft loss and tolerance resistance. Recent studies suggest that some memory cells unexpectedly act as regulatory cells, promoting rather than hindering transplant survival. This functional diversity makes therapeutic targeting of memory cells a challenging task in transplantation. In this article we highlight recent advances in our understanding of memory cells, focusing on diversity of memory cells and mechanisms involved in their induction and functions. We also provide a broad overview on the challenges and opportunities in targeting memory cells in the induction of transplant tolerance. PMID:26102615

Improving the effectiveness of an interruption lag by inducing a memory-based strategy.

PubMed

Morgan, Phillip L; Patrick, John; Tiley, Leyanne

2013-01-01

The memory for goals model (Altmann & Trafton, 2002) posits the importance of a short delay (the 'interruption lag') before an interrupting task to encode suspended goals for retrieval post-interruption. Two experiments used the theory of soft constraints (Gray, Simms, Fu & Schoelles, 2006) to investigate whether the efficacy of an interruption lag could be improved by increasing goal-state access cost to induce a more memory-based encoding strategy. Both experiments used a copying task with three access cost conditions (Low, Medium, and High) and a 5-s interruption lag with a no lag control condition. Experiment 1 found that the participants in the High access cost condition resumed more interrupted trials and executed more actions correctly from memory when coupled with an interruption lag. Experiment 2 used a prospective memory test post-interruption and an eyetracker recorded gaze activity during the interruption lag. The participants in the High access cost condition with an interruption lag were best at encoding target information during the interruption lag, evidenced by higher scores on the prospective memory measure and more gaze activity on the goal-state during the interruption lag. Theoretical and practical issues regarding the use of goal-state access cost and an interruption lag are discussed. Copyright © 2012. Published by Elsevier B.V.

Programmable Direct-Memory-Access Controller

NASA Technical Reports Server (NTRS)

Hendry, David F.

1990-01-01

Proposed programmable direct-memory-access controller (DMAC) operates with computer systems of 32000 series, which have 32-bit data buses and use addresses of 24 (or potentially 32) bits. Controller functions with or without help of central processing unit (CPU) and starts itself. Includes such advanced features as ability to compare two blocks of memory for equality and to search block of memory for specific value. Made as single very-large-scale integrated-circuit chip.

A Review on Resistive Switching in High-k Dielectrics: A Nanoscale Point of View Using Conductive Atomic Force Microscope

PubMed Central

Lanza, Mario

2014-01-01

Metal-Insulator-Metal (MIM) structures have raised as the most promising configuration for next generation information storage, leading to great performance and fabrication-friendly Resistive Random Access Memories (RRAM). In these cells, the memory concept is no more based on the charge storage, but on tuning the electrical resistance of the insulating layer by applying electrical stresses to reach a high resistive state (HRS or “0”) and a low resistive state (LRS or “1”), which makes the memory point. Some high-k dielectrics show this unusual property and in the last years high-k based RRAM have been extensively analyzed, especially at the device level. However, as resistance switching (in the most promising cells) is a local phenomenon that takes place in areas of ~100 nm2, the use of characterization tools with high lateral spatial resolution is necessary. In this paper the status of resistive switching in high-k materials is reviewed from a nanoscale point of view by means of conductive atomic force microscope analyses. PMID:28788561

A compact superconducting nanowire memory element operated by nanowire cryotrons

NASA Astrophysics Data System (ADS)

Zhao, Qing-Yuan; Toomey, Emily A.; Butters, Brenden A.; McCaughan, Adam N.; Dane, Andrew E.; Nam, Sae-Woo; Berggren, Karl K.

2018-07-01

A superconducting loop stores persistent current without any ohmic loss, making it an ideal platform for energy efficient memories. Conventional superconducting memories use an architecture based on Josephson junctions (JJs) and have demonstrated access times less than 10 ps and power dissipation as low as 10-19 J. However, their scalability has been slow to develop due to the challenges in reducing the dimensions of JJs and minimizing the area of the superconducting loops. In addition to the memory itself, complex readout circuits require additional JJs and inductors for coupling signals, increasing the overall area. Here, we have demonstrated a superconducting memory based solely on lithographic nanowires. The small dimensions of the nanowire ensure that the device can be fabricated in a dense area in multiple layers, while the high kinetic inductance makes the loop essentially independent of geometric inductance, allowing it to be scaled down without sacrificing performance. The memory is operated by a group of nanowire cryotrons patterned alongside the storage loop, enabling us to reduce the entire memory cell to 3 μm × 7 μm in our proof-of-concept device. In this work we present the operation principles of a superconducting nanowire memory (nMem) and characterize its bit error rate, speed, and power dissipation.

Fabrication of cross-shaped Cu-nanowire resistive memory devices using a rapid, scalable, and designable inorganic-nanowire-digital-alignment technique (Conference Presentation)

NASA Astrophysics Data System (ADS)

Xu, Wentao; Lee, Yeongjun; Min, Sung-Yong; Park, Cheolmin; Lee, Tae-Woo

2016-09-01

Resistive random-access memory (RRAM) is a candidate next generation nonvolatile memory due to its high access speed, high density and ease of fabrication. Especially, cross-point-access allows cross-bar arrays that lead to high-density cells in a two-dimensional planar structure. Use of such designs could be compatible with the aggressive scaling down of memory devices, but existing methods such as optical or e-beam lithographic approaches are too complicated. One-dimensional inorganic nanowires (i-NWs) are regarded as ideal components of nanoelectronics to circumvent the limitations of conventional lithographic approaches. However, post-growth alignment of these i-NWs precisely on a large area with individual control is still a difficult challenge. Here, we report a simple, inexpensive, and rapid method to fabricate two-dimensional arrays of perpendicularly-aligned, individually-conductive Cu-NWs with a nanometer-scale CuxO layer sandwiched at each cross point, by using an inorganic-nanowire-digital-alignment technique (INDAT) and a one-step reduction process. In this approach, the oxide layer is self-formed and patterned, so conventional deposition and lithography are not necessary. INDAT eliminates the difficulties of alignment and scalable fabrication that are encountered when using currently-available techniques that use inorganic nanowires. This simple process facilitates fabrication of cross-point nonvolatile memristor arrays. Fabricated arrays had reproducible resistive switching behavior, high on/off current ratio (Ion/Ioff) 10 6 and extensive cycling endurance. This is the first report of memristors with the resistive switching oxide layer self-formed, self-patterned and self-positioned; we envision that the new features of the technique will provide great opportunities for future nano-electronic circuits.

Internal filament modulation in low-dielectric gap design for built-in selector-less resistive switching memory application

NASA Astrophysics Data System (ADS)

Chen, Ying-Chen; Lin, Chih-Yang; Huang, Hui-Chun; Kim, Sungjun; Fowler, Burt; Chang, Yao-Feng; Wu, Xiaohan; Xu, Gaobo; Chang, Ting-Chang; Lee, Jack C.

2018-02-01

Sneak path current is a severe hindrance for the application of high-density resistive random-access memory (RRAM) array designs. In this work, we demonstrate nonlinear (NL) resistive switching characteristics of a HfO x /SiO x -based stacking structure as a realization for selector-less RRAM devices. The NL characteristic was obtained and designed by optimizing the internal filament location with a low effective dielectric constant in the HfO x /SiO x structure. The stacking HfO x /SiO x -based RRAM device as the one-resistor-only memory cell is applicable without needing an additional selector device to solve the sneak path issue with a switching voltage of ~1 V, which is desirable for low-power operating in built-in nonlinearity crossbar array configurations.

CD4 memory T cells develop and acquire functional competence by sequential cognate interactions and stepwise gene regulation

PubMed Central

Kaji, Tomohiro; Hijikata, Atsushi; Ishige, Akiko; Kitami, Toshimori; Watanabe, Takashi; Ohara, Osamu; Yanaka, Noriyuki; Okada, Mariko; Shimoda, Michiko; Taniguchi, Masaru

2016-01-01

Memory CD4+ T cells promote protective humoral immunity; however, how memory T cells acquire this activity remains unclear. This study demonstrates that CD4+ T cells develop into antigen-specific memory T cells that can promote the terminal differentiation of memory B cells far more effectively than their naive T-cell counterparts. Memory T cell development requires the transcription factor B-cell lymphoma 6 (Bcl6), which is known to direct T-follicular helper (Tfh) cell differentiation. However, unlike Tfh cells, memory T cell development did not require germinal center B cells. Curiously, memory T cells that develop in the absence of cognate B cells cannot promote memory B-cell recall responses and this defect was accompanied by down-regulation of genes associated with homeostasis and activation and up-regulation of genes inhibitory for T-cell responses. Although memory T cells display phenotypic and genetic signatures distinct from Tfh cells, both had in common the expression of a group of genes associated with metabolic pathways. This gene expression profile was not shared to any great extent with naive T cells and was not influenced by the absence of cognate B cells during memory T cell development. These results suggest that memory T cell development is programmed by stepwise expression of gatekeeper genes through serial interactions with different types of antigen-presenting cells, first licensing the memory lineage pathway and subsequently facilitating the functional development of memory T cells. Finally, we identified Gdpd3 as a candidate genetic marker for memory T cells. PMID:26714588

Memory-Intensive Benchmarks: IRAM vs. Cache-Based Machines

NASA Technical Reports Server (NTRS)

Biswas, Rupak; Gaeke, Brian R.; Husbands, Parry; Li, Xiaoye S.; Oliker, Leonid; Yelick, Katherine A.; Biegel, Bryan (Technical Monitor)

2002-01-01

The increasing gap between processor and memory performance has lead to new architectural models for memory-intensive applications. In this paper, we explore the performance of a set of memory-intensive benchmarks and use them to compare the performance of conventional cache-based microprocessors to a mixed logic and DRAM processor called VIRAM. The benchmarks are based on problem statements, rather than specific implementations, and in each case we explore the fundamental hardware requirements of the problem, as well as alternative algorithms and data structures that can help expose fine-grained parallelism or simplify memory access patterns. The benchmarks are characterized by their memory access patterns, their basic control structures, and the ratio of computation to memory operation.

Some pitfalls in measuring memory in animals.

PubMed

Thorpe, Christina M; Jacova, Claudia; Wilkie, Donald M

2004-11-01

Because the presence or absence of memories in the brain cannot be directly observed, scientists must rely on indirect measures and use inferential reasoning to make statements about the status of memories. In humans, memories are often accessed through spoken or written language. In animals, memory is accessed through overt behaviours such as running down an arm in a maze, pressing a lever, or visiting a food cache site. Because memory is measured by these indirect methods, errors in the veracity of statements about memory can occur. In this brief paper, we identify three areas that may serve as pitfalls in reasoning about memory in animals: (1) the presence of 'silent associations', (2) intrusions of species-typical behaviours on memory tasks, and (3) improper mapping between human and animals memory tasks. There are undoubtedly other areas in which scientists should act cautiously when reasoning about the status of memory.

A Decision Model for Selection of Microcomputers and Operating Systems.

DTIC Science & Technology

1984-06-01

is resilting in application software (for microccmputers) being developed almost exclu- sively tor the IBM PC and compatiole systems. NAVDAC ielt that...location can be indepen- dently accessed. RAN memory is also often called read/ write memory, hecause new information can be written into and read from...when power is lost; this is also read/ write memory. Bubble memory, however, has significantly slower access times than RAM or RON and also is not preva

Interconnected subsets of memory follicular helper T cells have different effector functions.

PubMed

Asrir, Assia; Aloulou, Meryem; Gador, Mylène; Pérals, Corine; Fazilleau, Nicolas

2017-10-10

Follicular helper T cells regulate high-affinity antibody production. Memory follicular helper T cells can be local in draining lymphoid organs and circulate in the blood, but the underlying mechanisms of this subdivision are unresolved. Here we show that both memory follicular helper T subsets sustain B-cell responses after reactivation. Local cells promote more plasma cell differentiation, whereas circulating cells promote more secondary germinal centers. In parallel, local memory B cells are homogeneous and programmed to become plasma cells, whereas circulating memory B cells are able to rediversify. Local memory follicular helper T cells have higher affinity T-cell receptors, which correlates with expression of peptide MHC-II at the surface of local memory B cells only. Blocking T-cell receptor-peptide MHC-II interactions induces the release of local memory follicular helper T cells in the circulating compartment. Our studies show that memory follicular helper T localization is highly intertwined with memory B cells, a finding that has important implications for vaccine design.Tfh cells can differentiate into memory cells. Here the authors describe distinct functional and phenotypic profiles of these memory Tfh cells dependent on their anatomical localization to the lymphoid organs or to the circulation.

Don’t make cache too complex: A simple probability-based cache management scheme for SSDs

PubMed Central

Cho, Sangyeun; Choi, Jongmoo

2017-01-01

Solid-state drives (SSDs) have recently become a common storage component in computer systems, and they are fueled by continued bit cost reductions achieved with smaller feature sizes and multiple-level cell technologies. However, as the flash memory stores more bits per cell, the performance and reliability of the flash memory degrade substantially. To solve this problem, a fast non-volatile memory (NVM-)based cache has been employed within SSDs to reduce the long latency required to write data. Absorbing small writes in a fast NVM cache can also reduce the number of flash memory erase operations. To maximize the benefits of an NVM cache, it is important to increase the NVM cache utilization. In this paper, we propose and study ProCache, a simple NVM cache management scheme, that makes cache-entrance decisions based on random probability testing. Our scheme is motivated by the observation that frequently written hot data will eventually enter the cache with a high probability, and that infrequently accessed cold data will not enter the cache easily. Owing to its simplicity, ProCache is easy to implement at a substantially smaller cost than similar previously studied techniques. We evaluate ProCache and conclude that it achieves comparable performance compared to a more complex reference counter-based cache-management scheme. PMID:28358897

Don't make cache too complex: A simple probability-based cache management scheme for SSDs.

PubMed

Baek, Seungjae; Cho, Sangyeun; Choi, Jongmoo

2017-01-01

Solid-state drives (SSDs) have recently become a common storage component in computer systems, and they are fueled by continued bit cost reductions achieved with smaller feature sizes and multiple-level cell technologies. However, as the flash memory stores more bits per cell, the performance and reliability of the flash memory degrade substantially. To solve this problem, a fast non-volatile memory (NVM-)based cache has been employed within SSDs to reduce the long latency required to write data. Absorbing small writes in a fast NVM cache can also reduce the number of flash memory erase operations. To maximize the benefits of an NVM cache, it is important to increase the NVM cache utilization. In this paper, we propose and study ProCache, a simple NVM cache management scheme, that makes cache-entrance decisions based on random probability testing. Our scheme is motivated by the observation that frequently written hot data will eventually enter the cache with a high probability, and that infrequently accessed cold data will not enter the cache easily. Owing to its simplicity, ProCache is easy to implement at a substantially smaller cost than similar previously studied techniques. We evaluate ProCache and conclude that it achieves comparable performance compared to a more complex reference counter-based cache-management scheme.

MemAxes: Visualization and Analytics for Characterizing Complex Memory Performance Behaviors.

PubMed

Gimenez, Alfredo; Gamblin, Todd; Jusufi, Ilir; Bhatele, Abhinav; Schulz, Martin; Bremer, Peer-Timo; Hamann, Bernd

2018-07-01

Memory performance is often a major bottleneck for high-performance computing (HPC) applications. Deepening memory hierarchies, complex memory management, and non-uniform access times have made memory performance behavior difficult to characterize, and users require novel, sophisticated tools to analyze and optimize this aspect of their codes. Existing tools target only specific factors of memory performance, such as hardware layout, allocations, or access instructions. However, today's tools do not suffice to characterize the complex relationships between these factors. Further, they require advanced expertise to be used effectively. We present MemAxes, a tool based on a novel approach for analytic-driven visualization of memory performance data. MemAxes uniquely allows users to analyze the different aspects related to memory performance by providing multiple visual contexts for a centralized dataset. We define mappings of sampled memory access data to new and existing visual metaphors, each of which enabling a user to perform different analysis tasks. We present methods to guide user interaction by scoring subsets of the data based on known performance problems. This scoring is used to provide visual cues and automatically extract clusters of interest. We designed MemAxes in collaboration with experts in HPC and demonstrate its effectiveness in case studies.

Integrated semiconductor-magnetic random access memory system

NASA Technical Reports Server (NTRS)

Katti, Romney R. (Inventor); Blaes, Brent R. (Inventor)

2001-01-01

The present disclosure describes a non-volatile magnetic random access memory (RAM) system having a semiconductor control circuit and a magnetic array element. The integrated magnetic RAM system uses CMOS control circuit to read and write data magnetoresistively. The system provides a fast access, non-volatile, radiation hard, high density RAM for high speed computing.

Analysis on applicable error-correcting code strength of storage class memory and NAND flash in hybrid storage

NASA Astrophysics Data System (ADS)

Matsui, Chihiro; Kinoshita, Reika; Takeuchi, Ken

2018-04-01

A hybrid of storage class memory (SCM) and NAND flash is a promising technology for high performance storage. Error correction is inevitable on SCM and NAND flash because their bit error rate (BER) increases with write/erase (W/E) cycles, data retention, and program/read disturb. In addition, scaling and multi-level cell technologies increase BER. However, error-correcting code (ECC) degrades storage performance because of extra memory reading and encoding/decoding time. Therefore, applicable ECC strength of SCM and NAND flash is evaluated independently by fixing ECC strength of one memory in the hybrid storage. As a result, weak BCH ECC with small correctable bit is recommended for the hybrid storage with large SCM capacity because SCM is accessed frequently. In contrast, strong and long-latency LDPC ECC can be applied to NAND flash in the hybrid storage with large SCM capacity because large-capacity SCM improves the storage performance.

Adoptive Transfer of Interleukin-21-stimulated Human CD8+ T Memory Stem Cells Efficiently Inhibits Tumor Growth.

PubMed

Chen, Yingshi; Yu, Fei; Jiang, Yawen; Chen, Jingliang; Wu, Kang; Chen, Xinxin; Lin, Yingtong; Zhang, Hui; Li, Linghua; Zhang, Yiwen

2018-05-01

Memory stem T (TSCM) cells, a new subset of memory T cells with self-renewal and multipotent capacities, are considered as a promising candidates for adoptive cellular therapy. However, the low proportion of human TSCM cells in total CD8 T cells limits their utility. Here, we aimed to induce human CD8 TSCM cells by stimulating naive precursors with interleukin-21 (IL-21). We found that IL-21 promoted the generation of TSCM cells, described as CD45RACD45ROCD62LCCR7CD122CD95 cells, with a higher efficiency than that observed with other common γ-chain cytokines. Upon adoptive transfer into an A375 melanoma mouse model, these lymphocytes mediated much stronger antitumor responses. Further mechanistic analysis revealed that IL-21 activated the Janus kinase signal transducer and activator of transcription 3 pathway by upregulating signal transducer and activator of transcription 3 phosphorylation and consequently promoting the expression of T-bet and suppressor of cytokine signaling 1, but decreasing the expression of eomesodermin and GATA binding protein 3. Our findings provide novel insights into the generation of human CD8 TSCM cells and reveal a novel potential clinical application of IL-21.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

Photonic Potential of Haloarchaeal Pigment Bacteriorhodopsin for Future Electronics: A Review.

PubMed

Ashwini, Ravi; Vijayanand, S; Hemapriya, J

2017-08-01

Haloarchaea are known for its adaptation in extreme saline environment. Halophilic archaea produces carotenoid pigments and proton pumps to protect them from extremes of salinity. Bacteriorhodopsin (bR) is a light-driven proton pump that resides in the membrane of haloarchaea Halobacterium salinarum. The photocycle of Bacteriorhodopsin passes through several states from K to O, finally liberating ATP for host's survival. Extensive studies on Bacteriorhodopsin photocycle has provided in depth knowledge on their sequential mechanism of converting solar energy into chemical energy inside the cell. This ability of Bacteriorhodopsin to harvest sunlight has now been experimented to exploit the unexplored and extensively available solar energy in various biotechnological applications. Currently, bacteriorhodopsin finds its importance in dye-sensitized solar cell (DSSC), logic gates (integrated circuits, IC's), optical switching, optical memories, storage devices (random access memory, RAM), biosensors, electronic sensors and optical microcavities. This review deals with the optical and electrical applications of the purple pigment Bacteriorhodopsin.

A High-Performance Cellular Automaton Model of Tumor Growth with Dynamically Growing Domains

PubMed Central

Poleszczuk, Jan; Enderling, Heiko

2014-01-01

Tumor growth from a single transformed cancer cell up to a clinically apparent mass spans many spatial and temporal orders of magnitude. Implementation of cellular automata simulations of such tumor growth can be straightforward but computing performance often counterbalances simplicity. Computationally convenient simulation times can be achieved by choosing appropriate data structures, memory and cell handling as well as domain setup. We propose a cellular automaton model of tumor growth with a domain that expands dynamically as the tumor population increases. We discuss memory access, data structures and implementation techniques that yield high-performance multi-scale Monte Carlo simulations of tumor growth. We discuss tumor properties that favor the proposed high-performance design and present simulation results of the tumor growth model. We estimate to which parameters the model is the most sensitive, and show that tumor volume depends on a number of parameters in a non-monotonic manner. PMID:25346862

Evaluation of Data Retention Characteristics for Ferroelectric Random Access Memories (FRAMs)

NASA Technical Reports Server (NTRS)

Sharma, Ashok K.; Teverovsky, Alexander

2001-01-01

Data retention and fatigue characteristics of 64 Kb lead zirconate titanate (PZT)-based Ferroelectric Random Access Memories (FRAMs) microcircuits manufactured by Ramtron were examined over temperature range from -85 C to +310 C for ceramic packaged parts and from -85 C to +175 C for plastic parts, during retention periods up to several thousand hours. Intrinsic failures, which were caused by a thermal degradation of the ferroelectric cells, occurred in ceramic parts after tens or hundreds hours of aging at temperatures above 200 C. The activation energy of the retention test failures was 1.05 eV and the extrapolated mean-time-to-failure (MTTF) at room temperature was estimated to be more than 280 years. Multiple write-read cycling (up to 3x10(exp 7)) during the fatigue testing of plastic and ceramic parts did not result in any parametric or functional failures. However, operational currents linearly decreased with the logarithm of number of cycles thus indicating fatigue process in PZT films. Plastic parts, that had more recent date code as compared to ceramic parts, appeared to be using die with improved process technology and showed significantly smaller changes in operational currents and data access times.

An Investigation of Unified Memory Access Performance in CUDA

PubMed Central

Landaverde, Raphael; Zhang, Tiansheng; Coskun, Ayse K.; Herbordt, Martin

2015-01-01

Managing memory between the CPU and GPU is a major challenge in GPU computing. A programming model, Unified Memory Access (UMA), has been recently introduced by Nvidia to simplify the complexities of memory management while claiming good overall performance. In this paper, we investigate this programming model and evaluate its performance and programming model simplifications based on our experimental results. We find that beyond on-demand data transfers to the CPU, the GPU is also able to request subsets of data it requires on demand. This feature allows UMA to outperform full data transfer methods for certain parallel applications and small data sizes. We also find, however, that for the majority of applications and memory access patterns, the performance overheads associated with UMA are significant, while the simplifications to the programming model restrict flexibility for adding future optimizations. PMID:26594668

Daily Access to Sucrose Impairs Aspects of Spatial Memory Tasks Reliant on Pattern Separation and Neural Proliferation in Rats

ERIC Educational Resources Information Center

Reichelt, Amy C.; Morris, Margaret J.; Westbrook, Reginald Frederick

2016-01-01

High sugar diets reduce hippocampal neurogenesis, which is required for minimizing interference between memories, a process that involves "pattern separation." We provided rats with 2 h daily access to a sucrose solution for 28 d and assessed their performance on a spatial memory task. Sucrose consuming rats discriminated between objects…

Encoding and Retrieval Processes Involved in the Access of Source Information in the Absence of Item Memory

ERIC Educational Resources Information Center

Ball, B. Hunter; DeWitt, Michael R.; Knight, Justin B.; Hicks, Jason L.

2014-01-01

The current study sought to examine the relative contributions of encoding and retrieval processes in accessing contextual information in the absence of item memory using an extralist cuing procedure in which the retrieval cues used to query memory for contextual information were "related" to the target item but never actually studied.…

Boosting the FM-Index on the GPU: Effective Techniques to Mitigate Random Memory Access.

PubMed

Chacón, Alejandro; Marco-Sola, Santiago; Espinosa, Antonio; Ribeca, Paolo; Moure, Juan Carlos

2015-01-01

The recent advent of high-throughput sequencing machines producing big amounts of short reads has boosted the interest in efficient string searching techniques. As of today, many mainstream sequence alignment software tools rely on a special data structure, called the FM-index, which allows for fast exact searches in large genomic references. However, such searches translate into a pseudo-random memory access pattern, thus making memory access the limiting factor of all computation-efficient implementations, both on CPUs and GPUs. Here, we show that several strategies can be put in place to remove the memory bottleneck on the GPU: more compact indexes can be implemented by having more threads work cooperatively on larger memory blocks, and a k-step FM-index can be used to further reduce the number of memory accesses. The combination of those and other optimisations yields an implementation that is able to process about two Gbases of queries per second on our test platform, being about 8 × faster than a comparable multi-core CPU version, and about 3 × to 5 × faster than the FM-index implementation on the GPU provided by the recently announced Nvidia NVBIO bioinformatics library.

T inflammatory memory CD8 T cells participate to antiviral response and generate secondary memory cells with an advantage in XCL1 production.

PubMed

Jubin, Virginie; Ventre, Erwan; Leverrier, Yann; Djebali, Sophia; Mayol, Katia; Tomkowiak, Martine; Mafille, Julien; Teixeira, Marie; Teoh, Denise Y-L; Lina, Bruno; Walzer, Thierry; Arpin, Christophe; Marvel, Jacqueline

2012-06-01

Besides the classically described subsets of memory CD8 T cells generated under infectious conditions, are T inflammatory memory cells generated under sterile priming conditions, such as sensitization to allergens. Although not fully differentiated as pathogen-induced memory cells, they display memory properties that distinguish them from naive CD8 T cells. Given these memory cells are generated in an antigen-specific context that is devoid of pathogen-derived danger signals and CD4 T cell help, we herein questioned whether they maintained their activation and differentiation potential, could be recruited in an immune response directed against a pathogen expressing their cognate antigen and further differentiate in fully competent secondary memory cells. We show that T inflammatory memory cells can indeed take part to the immune response triggered by a viral infection, differentiate into secondary effectors and further generate typical central memory CD8 T cells and effector memory CD8 T cells. Furthermore, the secondary memory cells they generate display a functional advantage over primary memory cells in their capacity to produce TNF-α and the XCL1 chemokine. These results suggest that cross-reactive stimulations and differentiation of cells directed against allergens or self into fully competent pathogen-induced memory cells might have incidences in inflammatory immuno-pathologies.

Paging memory from random access memory to backing storage in a parallel computer

DOEpatents

Archer, Charles J; Blocksome, Michael A; Inglett, Todd A; Ratterman, Joseph D; Smith, Brian E

2013-05-21

Paging memory from random access memory (`RAM`) to backing storage in a parallel computer that includes a plurality of compute nodes, including: executing a data processing application on a virtual machine operating system in a virtual machine on a first compute node; providing, by a second compute node, backing storage for the contents of RAM on the first compute node; and swapping, by the virtual machine operating system in the virtual machine on the first compute node, a page of memory from RAM on the first compute node to the backing storage on the second compute node.

Optical mass memories

NASA Technical Reports Server (NTRS)

Bailey, G. A.

1976-01-01

Optical and magnetic variants in the design of trillion-bit read/write memories are compared and tabulated. Components and materials suitable for a random access read/write nonmoving memory system are examined, with preference given to holography and photoplastic materials. Advantages and deficiencies of photoplastics are reviewed. Holographic page composer design, essential features of an optical memory with no moving parts, fiche-oriented random access memory design, and materials suitable for an efficient photoplastic fiche are considered. The optical variants offer advantages in lower volume and weight at data transfer rates near 1 Mbit/sec, but power drain is of the same order as for the magnetic variants (tape memory, disk memory). The mechanical properties of photoplastic film materials still leave much to be desired.

BCH codes for large IC random-access memory systems

NASA Technical Reports Server (NTRS)

Lin, S.; Costello, D. J., Jr.

1983-01-01

In this report some shortened BCH codes for possible applications to large IC random-access memory systems are presented. These codes are given by their parity-check matrices. Encoding and decoding of these codes are discussed.

76 FR 35238 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-16

... Static Random Access Memories and Products Containing Same, DN 2816; the Commission is soliciting... importation of certain static random access memories and products containing same. The complaint names as...

Providing the Public with Online Access to Large Bibliographic Data Bases.

ERIC Educational Resources Information Center

Firschein, Oscar; Summit, Roger K.

DIALOG, an interactive, computer-based information retrieval language, consists of a series of computer programs designed to make use of direct access memory devices in order to provide the user with a rapid means of identifying records within a specific memory bank. Using the system, a library user can be provided access to sixteen distinct and…

Memory. Engram cells retain memory under retrograde amnesia.

PubMed

Ryan, Tomás J; Roy, Dheeraj S; Pignatelli, Michele; Arons, Autumn; Tonegawa, Susumu

2015-05-29

Memory consolidation is the process by which a newly formed and unstable memory transforms into a stable long-term memory. It is unknown whether the process of memory consolidation occurs exclusively through the stabilization of memory engrams. By using learning-dependent cell labeling, we identified an increase of synaptic strength and dendritic spine density specifically in consolidated memory engram cells. Although these properties are lacking in engram cells under protein synthesis inhibitor-induced amnesia, direct optogenetic activation of these cells results in memory retrieval, and this correlates with retained engram cell-specific connectivity. We propose that a specific pattern of connectivity of engram cells may be crucial for memory information storage and that strengthened synapses in these cells critically contribute to the memory retrieval process. Copyright © 2015, American Association for the Advancement of Science.

Mechanical memory

DOEpatents

Gilkey, Jeffrey C [Albuquerque, NM; Duesterhaus, Michelle A [Albuquerque, NM; Peter, Frank J [Albuquerque, NM; Renn, Rosemarie A [Alburquerque, NM; Baker, Michael S [Albuquerque, NM

2006-08-15

A first-in-first-out (FIFO) microelectromechanical memory apparatus (also termed a mechanical memory) is disclosed. The mechanical memory utilizes a plurality of memory cells, with each memory cell having a beam which can be bowed in either of two directions of curvature to indicate two different logic states for that memory cell. The memory cells can be arranged around a wheel which operates as a clocking actuator to serially shift data from one memory cell to the next. The mechanical memory can be formed using conventional surface micromachining, and can be formed as either a nonvolatile memory or as a volatile memory.

Mechanical memory

DOEpatents

Gilkey, Jeffrey C [Albuquerque, NM; Duesterhaus, Michelle A [Albuquerque, NM; Peter, Frank J [Albuquerque, NM; Renn, Rosemarie A [Albuquerque, NM; Baker, Michael S [Albuquerque, NM

2006-05-16

A first-in-first-out (FIFO) microelectromechanical memory apparatus (also termed a mechanical memory) is disclosed. The mechanical memory utilizes a plurality of memory cells, with each memory cell having a beam which can be bowed in either of two directions of curvature to indicate two different logic states for that memory cell. The memory cells can be arranged around a wheel which operates as a clocking actuator to serially shift data from one memory cell to the next. The mechanical memory can be formed using conventional surface micromachining, and can be formed as either a nonvolatile memory or as a volatile memory.

FocusStack and StimServer: a new open source MATLAB toolchain for visual stimulation and analysis of two-photon calcium neuronal imaging data.

PubMed

Muir, Dylan R; Kampa, Björn M

2014-01-01

Two-photon calcium imaging of neuronal responses is an increasingly accessible technology for probing population responses in cortex at single cell resolution, and with reasonable and improving temporal resolution. However, analysis of two-photon data is usually performed using ad-hoc solutions. To date, no publicly available software exists for straightforward analysis of stimulus-triggered two-photon imaging experiments. In addition, the increasing data rates of two-photon acquisition systems imply increasing cost of computing hardware required for in-memory analysis. Here we present a Matlab toolbox, FocusStack, for simple and efficient analysis of two-photon calcium imaging stacks on consumer-level hardware, with minimal memory footprint. We also present a Matlab toolbox, StimServer, for generation and sequencing of visual stimuli, designed to be triggered over a network link from a two-photon acquisition system. FocusStack is compatible out of the box with several existing two-photon acquisition systems, and is simple to adapt to arbitrary binary file formats. Analysis tools such as stack alignment for movement correction, automated cell detection and peri-stimulus time histograms are already provided, and further tools can be easily incorporated. Both packages are available as publicly-accessible source-code repositories.

FocusStack and StimServer: a new open source MATLAB toolchain for visual stimulation and analysis of two-photon calcium neuronal imaging data

PubMed Central

Muir, Dylan R.; Kampa, Björn M.

2015-01-01

Two-photon calcium imaging of neuronal responses is an increasingly accessible technology for probing population responses in cortex at single cell resolution, and with reasonable and improving temporal resolution. However, analysis of two-photon data is usually performed using ad-hoc solutions. To date, no publicly available software exists for straightforward analysis of stimulus-triggered two-photon imaging experiments. In addition, the increasing data rates of two-photon acquisition systems imply increasing cost of computing hardware required for in-memory analysis. Here we present a Matlab toolbox, FocusStack, for simple and efficient analysis of two-photon calcium imaging stacks on consumer-level hardware, with minimal memory footprint. We also present a Matlab toolbox, StimServer, for generation and sequencing of visual stimuli, designed to be triggered over a network link from a two-photon acquisition system. FocusStack is compatible out of the box with several existing two-photon acquisition systems, and is simple to adapt to arbitrary binary file formats. Analysis tools such as stack alignment for movement correction, automated cell detection and peri-stimulus time histograms are already provided, and further tools can be easily incorporated. Both packages are available as publicly-accessible source-code repositories1. PMID:25653614

Social Desirability Bias in Smoking Cessation: Effects in the Laboratory and Field

DTIC Science & Technology

2012-03-16

and Child Health Journal, 2(2), 77-83. Bradburn, N., Rips, L., & Shevell, S. (1987). Answering autobiographical questions: the impact of memory ...how accessible smoking outcomes are in an individual’s memory . Research has shown that smokers tend to exhibit greater accessibility for positive...body of research that suggests that acute tobacco abstinence hinders cognitive functioning, such as attention, memory , information processing

Kokkos: Enabling manycore performance portability through polymorphic memory access patterns

DOE PAGES

Carter Edwards, H.; Trott, Christian R.; Sunderland, Daniel

2014-07-22

The manycore revolution can be characterized by increasing thread counts, decreasing memory per thread, and diversity of continually evolving manycore architectures. High performance computing (HPC) applications and libraries must exploit increasingly finer levels of parallelism within their codes to sustain scalability on these devices. We found that a major obstacle to performance portability is the diverse and conflicting set of constraints on memory access patterns across devices. Contemporary portable programming models address manycore parallelism (e.g., OpenMP, OpenACC, OpenCL) but fail to address memory access patterns. The Kokkos C++ library enables applications and domain libraries to achieve performance portability on diversemore » manycore architectures by unifying abstractions for both fine-grain data parallelism and memory access patterns. In this paper we describe Kokkos’ abstractions, summarize its application programmer interface (API), present performance results for unit-test kernels and mini-applications, and outline an incremental strategy for migrating legacy C++ codes to Kokkos. Furthermore, the Kokkos library is under active research and development to incorporate capabilities from new generations of manycore architectures, and to address a growing list of applications and domain libraries.« less

Accessing global data from accelerator devices

DOEpatents

Bertolli, Carlo; O'Brien, John K.; Sallenave, Olivier H.; Sura, Zehra N.

2016-12-06

An aspect includes a table of contents (TOC) that was generated by a compiler being received at an accelerator device. The TOC includes an address of global data in a host memory space. The global data is copied from the address in the host memory space to an address in the device memory space. The address in the host memory space is obtained from the received TOC. The received TOC is updated to indicate that global data is stored at the address in the device memory space. A kernel that accesses the global data from the address in the device memory space is executed. The address in the device memory space is obtained based on contents of the updated TOC. When the executing is completed, the global data from the address in the device memory space is copied to the address in the host memory space.

Application of phase-change materials in memory taxonomy.

PubMed

Wang, Lei; Tu, Liang; Wen, Jing

2017-01-01

Phase-change materials are suitable for data storage because they exhibit reversible transitions between crystalline and amorphous states that have distinguishable electrical and optical properties. Consequently, these materials find applications in diverse memory devices ranging from conventional optical discs to emerging nanophotonic devices. Current research efforts are mostly devoted to phase-change random access memory, whereas the applications of phase-change materials in other types of memory devices are rarely reported. Here we review the physical principles of phase-change materials and devices aiming to help researchers understand the concept of phase-change memory. We classify phase-change memory devices into phase-change optical disc, phase-change scanning probe memory, phase-change random access memory, and phase-change nanophotonic device, according to their locations in memory hierarchy. For each device type we discuss the physical principles in conjunction with merits and weakness for data storage applications. We also outline state-of-the-art technologies and future prospects.

A Cerebellar-model Associative Memory as a Generalized Random-access Memory

NASA Technical Reports Server (NTRS)

Kanerva, Pentti

1989-01-01

A versatile neural-net model is explained in terms familiar to computer scientists and engineers. It is called the sparse distributed memory, and it is a random-access memory for very long words (for patterns with thousands of bits). Its potential utility is the result of several factors: (1) a large pattern representing an object or a scene or a moment can encode a large amount of information about what it represents; (2) this information can serve as an address to the memory, and it can also serve as data; (3) the memory is noise tolerant--the information need not be exact; (4) the memory can be made arbitrarily large and hence an arbitrary amount of information can be stored in it; and (5) the architecture is inherently parallel, allowing large memories to be fast. Such memories can become important components of future computers.

Accessing global data from accelerator devices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bertolli, Carlo; O'Brien, John K.; Sallenave, Olivier H.

2016-12-06

An aspect includes a table of contents (TOC) that was generated by a compiler being received at an accelerator device. The TOC includes an address of global data in a host memory space. The global data is copied from the address in the host memory space to an address in the device memory space. The address in the host memory space is obtained from the received TOC. The received TOC is updated to indicate that global data is stored at the address in the device memory space. A kernel that accesses the global data from the address in the devicemore » memory space is executed. The address in the device memory space is obtained based on contents of the updated TOC. When the executing is completed, the global data from the address in the device memory space is copied to the address in the host memory space.« less

The contribution to immediate serial recall of rehearsal, search speed, access to lexical memory, and phonological coding: an investigation at the construct level.

PubMed

Tehan, Gerald; Fogarty, Gerard; Ryan, Katherine

2004-07-01

Rehearsal speed has traditionally been seen to be the prime determinant of individual differences in memory span. Recent studies, in the main using young children as the participant population, have suggested other contributors to span performance. In the present research, we used structural equation modeling to explore, at the construct level, individual differences in immediate serial recall with respect to rehearsal, search, phonological coding, and speed of access to lexical memory. We replicated standard short-term phenomena; we showed that the variables that influence children's span performance influence adult performance in the same way; and we showed that speed of access to lexical memory and facility with phonological codes appear to be more potent sources of individual differences in immediate memory than is either rehearsal speed or search factors.

Engram Cells Retain Memory Under Retrograde Amnesia

PubMed Central

Ryan, Tomás J.; Roy, Dheeraj S.; Pignatelli, Michele; Arons, Autumn; Tonegawa, Susumu

2017-01-01

Memory consolidation is the process by which a newly formed and unstable memory transforms into a stable long-term memory. It is unknown whether the process of memory consolidation occurs exclusively by the stabilization of memory engrams. By employing learning-dependent cell labeling, we identified an increase of synaptic strength and dendritic spine density specifically in consolidated memory engram cells. While these properties are lacking in the engram cells under protein synthesis inhibitor-induced amnesia, direct optogenetic activation of these cells results in memory retrieval, and this correlates with the retained engram cell-specific connectivity. We propose that a specific pattern of connectivity of engram cells may be crucial for memory information storage and that strengthened synapses in these cells critically contribute to the memory retrieval process. PMID:26023136

Chip architecture - A revolution brewing

NASA Astrophysics Data System (ADS)

Guterl, F.

1983-07-01

Techniques being explored by microchip designers and manufacturers to both speed up memory access and instruction execution while protecting memory are discussed. Attention is given to hardwiring control logic, pipelining for parallel processing, devising orthogonal instruction sets for interchangeable instruction fields, and the development of hardware for implementation of virtual memory and multiuser systems to provide memory management and protection. The inclusion of microcode in mainframes eliminated logic circuits that control timing and gating of the CPU. However, improvements in memory architecture have reduced access time to below that needed for instruction execution. Hardwiring the functions as a virtual memory enhances memory protection. Parallelism involves a redundant architecture, which allows identical operations to be performed simultaneously, and can be directed with microcode to avoid abortion of intermediate instructions once on set of instructions has been completed.

AFSC Standardization Conference, 1553, 1589, 1750, 1760, Ada, November 18-20, 1980, Dayton Convention Center, Dayton, Ohio, Volume II. Proceedings Standards,

DTIC Science & Technology

1980-11-01

4006 DMAE Direct Memory Access Enable: ’Ibis command enables direct memory access (DMA). 4007 I)MAi) Direct Memory Access Disable: This command...72 DLI 72 DLR 72 DM 111 DMAD 30 DMAE 30 DMR 111 ONEG 103 DR 117 DS 104 OSAR 53 141 373 ’., M1L-STD-1750A (USAF) 2 July 1980 OSBI 29 OSCR 54 OSIC 48...in 4.7.7, the connectors shall show no defects detrimental to the operation of the connectors and shall A-7 461 -meet the subsequent test requirements

A short cut to the past: Cueing via concrete objects improves autobiographical memory retrieval in Alzheimer's disease patients.

PubMed

Kirk, Marie; Berntsen, Dorthe

2018-02-01

Older adults diagnosed with Alzheimer's disease (AD) have difficulties accessing autobiographical memories. However, this deficit tends to spare memories dated to earlier parts of their lives, and may partially reflect retrieval deficits rather than complete memory loss. Introducing a novel paradigm, the present study examines whether autobiographical memory recall can be improved in AD by manipulating the sensory richness, concreteness and cultural dating of the memory cues. Specifically, we examine whether concrete everyday objects historically dated to the participants' youth (e.g., a skipping rope), relative to verbal cues (i.e., the verbal signifiers for the objects) facilitate access to autobiographical memories. The study includes 49 AD patients, and 50 healthy, older matched control participants, all tested on word versus object-cued recall. Both groups recalled significantly more memories, when cued by objects relative to words, but the advantage was significantly larger in the AD group. In both groups, memory descriptions were longer and significantly more episodic in nature in response to object-cued recall. Together these findings suggest that the multimodal nature of the object cues (i.e. vision, olfaction, audition, somatic sensation) along with specific cue characteristics, such as time reference, texture, shape, may constrain the retrieval search, potentially minimizing executive function demands, and hence strategic processing requirements, thus easing access to autobiographical memories in AD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Aspects of GPU perfomance in algorithms with random memory access

NASA Astrophysics Data System (ADS)

Kashkovsky, Alexander V.; Shershnev, Anton A.; Vashchenkov, Pavel V.

2017-10-01

The numerical code for solving the Boltzmann equation on the hybrid computational cluster using the Direct Simulation Monte Carlo (DSMC) method showed that on Tesla K40 accelerators computational performance drops dramatically with increase of percentage of occupied GPU memory. Testing revealed that memory access time increases tens of times after certain critical percentage of memory is occupied. Moreover, it seems to be the common problem of all NVidia's GPUs arising from its architecture. Few modifications of the numerical algorithm were suggested to overcome this problem. One of them, based on the splitting the memory into "virtual" blocks, resulted in 2.5 times speed up.

Effect of Atomic Layer Depositions (ALD)-Deposited Titanium Oxide (TiO2) Thickness on the Performance of Zr40Cu35Al15Ni10 (ZCAN)/TiO2/Indium (In)-Based Resistive Random Access Memory (RRAM) Structures

DTIC Science & Technology

2015-08-01

metal structures, memristors, resistive random access memory, RRAM, titanium dioxide, Zr40Cu35Al15Ni10, ZCAN, resistive memory, tunnel junction 16...TiO2 thickness ........................6 1 1. Introduction Resistive-switching memory elements based on metal-insulator-metal (MIM) diodes ...have attracted great interest due to their potential as components for simple, inexpensive, and high-density non-volatile storage devices. MIM diodes

Digital Equipment Corporation VAX/VMS Version 4.3

DTIC Science & Technology

1986-07-30

operating system performs process-oriented paging that allows execution of programs that may be larger than the physical memory allocated to them... to higher privileged modes. (For an explanation of how the four access modes provide memory access protection see page 9, "Memory Management".) A... to optimize program performance for real-time applications or interactive environments. July 30, 1986 - 4 - Final Evaluation Report Digital VAX/VMS

Magnetic Random Access Memory for Embedded Computing

DTIC Science & Technology

2007-10-29

layer, w he free layer hose resistan .  ce  2. Develop and model  data  storage circuits  based  on the MTJ cells. 3. Integrated the MTJ cells into a CMOS...suggested the two methods shown in Fig. 4.5 [95]. The circuit shown at the top of the figure uses NMOS pass transistors to load data , which is the simplest... method but requires careful design to avoid charge sharing and accommodate the data -dependent loading seen at the DATA input. With additional

Analysis of antigen-specific B-cell memory directly ex vivo.

PubMed

McHeyzer-Williams, Louise J; McHeyzer-Williams, Michael G

2004-01-01

Helper T-cell-regulated B-cell memory develops in response to initial antigen priming as a cellular product of the germinal center (GC) reaction. On antigen recall, memory response precursors expand rapidly with exaggerated differentiation into plasma cells to produce the high-titer, high-affinity antibody(Ab) that typifies the memory B-cell response in vivo. We have devised a high-resolution flow cytometric strategy to quantify the emergence and maintenance of antigen-specific memory B cells directly ex vivo. Extended cell surface phenotype establishes a level of cellular diversity not previously appreciated for the memory B-cell compartment. Using an "exclusion transfer" strategy, we ascertain the capacity of two distinct memory B-cell populations to transfer antigen-specific memory into naive adoptive hosts. Finally, we sequence expressed messenger ribonucleic acid (mRNA) from single cells within the population to estimate the level of somatic hypermutation as the best molecular indicator of B-cell memory. In this chapter, we describe the methods used in each of these four sections that serve to provide high-resolution quantification of antigen-specific B-cell memory responses directly ex vivo.

Strong homeostatic TCR signals induce formation of self-tolerant virtual memory CD8 T cells.

PubMed

Drobek, Ales; Moudra, Alena; Mueller, Daniel; Huranova, Martina; Horkova, Veronika; Pribikova, Michaela; Ivanek, Robert; Oberle, Susanne; Zehn, Dietmar; McCoy, Kathy D; Draber, Peter; Stepanek, Ondrej

2018-05-11

Virtual memory T cells are foreign antigen-inexperienced T cells that have acquired memory-like phenotype and constitute 10-20% of all peripheral CD8 + T cells in mice. Their origin, biological roles, and relationship to naïve and foreign antigen-experienced memory T cells are incompletely understood. By analyzing T-cell receptor repertoires and using retrogenic monoclonal T-cell populations, we demonstrate that the virtual memory T-cell formation is a so far unappreciated cell fate decision checkpoint. We describe two molecular mechanisms driving the formation of virtual memory T cells. First, virtual memory T cells originate exclusively from strongly self-reactive T cells. Second, the stoichiometry of the CD8 interaction with Lck regulates the size of the virtual memory T-cell compartment via modulating the self-reactivity of individual T cells. Although virtual memory T cells descend from the highly self-reactive clones and acquire a partial memory program, they are not more potent in inducing experimental autoimmune diabetes than naïve T cells. These data underline the importance of the variable level of self-reactivity in polyclonal T cells for the generation of functional T-cell diversity. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

A semi-floating gate memory based on van der Waals heterostructures for quasi-non-volatile applications

NASA Astrophysics Data System (ADS)

Liu, Chunsen; Yan, Xiao; Song, Xiongfei; Ding, Shijin; Zhang, David Wei; Zhou, Peng

2018-05-01

As conventional circuits based on field-effect transistors are approaching their physical limits due to quantum phenomena, semi-floating gate transistors have emerged as an alternative ultrafast and silicon-compatible technology. Here, we show a quasi-non-volatile memory featuring a semi-floating gate architecture with band-engineered van der Waals heterostructures. This two-dimensional semi-floating gate memory demonstrates 156 times longer refresh time with respect to that of dynamic random access memory and ultrahigh-speed writing operations on nanosecond timescales. The semi-floating gate architecture greatly enhances the writing operation performance and is approximately 106 times faster than other memories based on two-dimensional materials. The demonstrated characteristics suggest that the quasi-non-volatile memory has the potential to bridge the gap between volatile and non-volatile memory technologies and decrease the power consumption required for frequent refresh operations, enabling a high-speed and low-power random access memory.

Cancer immunotherapy and immunological memory.

PubMed

Murata, Kenji; Tsukahara, Tomohide; Torigoe, Toshihiko

2016-01-01

Human immunological memory is the key distinguishing hallmark of the adaptive immune system and plays an important role in the prevention of morbidity and the severity of infection. The differentiation system of T cell memory has been clarified using mouse models. However, the human T cell memory system has great diversity induced by natural antigens derived from many pathogens and tumor cells throughout life, and profoundly differs from the mouse memory system constructed using artificial antigens and transgenic T cells. We believe that only human studies can elucidate the human immune system. The importance of immunological memory in cancer immunotherapy has been pointed out, and the trafficking properties and long-lasting anti-tumor capacity of memory T cells play a crucial role in the control of malignant tumors. Adoptive cell transfer of less differentiated T cells has consistently demonstrated superior anti-tumor capacity relative to more differentiated T cells. Therefore, a human T cell population with the characteristics of stem cell memory is thought to be attractive for peptide vaccination and adoptive cell transfer. A novel human memory T cell population that we have identified is closer to the naive state than previous memory T cells in the T cell differentiation lineage, and has the characteristics of stem-like chemoresistance. Here we introduce this novel population and describe the fundamentals of immunological memory in cancer immunotherapy.

I-V Characteristics of a Static Random Access Memory Cell Utilizing Ferroelectric Transistors

NASA Technical Reports Server (NTRS)

Laws, Crystal; Mitchell, Cody; Hunt, Mitchell; Ho, Fat D.; MacLeod, Todd C.

2012-01-01

I-V characteristics for FeFET different than that of MOSFET Ferroelectric layer features hysteresis trend whereas MOSFET behaves same for both increasing and decreasing VGS FeFET I-V characteristics doesn't show dependence on VDS A Transistor with different channel length and width as well as various resistance and input voltages give different results As resistance values increased, the magnitude of the drain current decreased.

Memory Benchmarks for SMP-Based High Performance Parallel Computers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoo, A B; de Supinski, B; Mueller, F

2001-11-20

As the speed gap between CPU and main memory continues to grow, memory accesses increasingly dominates the performance of many applications. The problem is particularly acute for symmetric multiprocessor (SMP) systems, where the shared memory may be accessed concurrently by a group of threads running on separate CPUs. Unfortunately, several key issues governing memory system performance in current systems are not well understood. Complex interactions between the levels of the memory hierarchy, buses or switches, DRAM back-ends, system software, and application access patterns can make it difficult to pinpoint bottlenecks and determine appropriate optimizations, and the situation is even moremore » complex for SMP systems. To partially address this problem, we formulated a set of multi-threaded microbenchmarks for characterizing and measuring the performance of the underlying memory system in SMP-based high-performance computers. We report our use of these microbenchmarks on two important SMP-based machines. This paper has four primary contributions. First, we introduce a microbenchmark suite to systematically assess and compare the performance of different levels in SMP memory hierarchies. Second, we present a new tool based on hardware performance monitors to determine a wide array of memory system characteristics, such as cache sizes, quickly and easily; by using this tool, memory performance studies can be targeted to the full spectrum of performance regimes with many fewer data points than is otherwise required. Third, we present experimental results indicating that the performance of applications with large memory footprints remains largely constrained by memory. Fourth, we demonstrate that thread-level parallelism further degrades memory performance, even for the latest SMPs with hardware prefetching and switch-based memory interconnects.« less

Effector CD8 T cells dedifferentiate into long-lived memory cells.

PubMed

Youngblood, Ben; Hale, J Scott; Kissick, Haydn T; Ahn, Eunseon; Xu, Xiaojin; Wieland, Andreas; Araki, Koichi; West, Erin E; Ghoneim, Hazem E; Fan, Yiping; Dogra, Pranay; Davis, Carl W; Konieczny, Bogumila T; Antia, Rustom; Cheng, Xiaodong; Ahmed, Rafi

2017-12-21

Memory CD8 T cells that circulate in the blood and are present in lymphoid organs are an essential component of long-lived T cell immunity. These memory CD8 T cells remain poised to rapidly elaborate effector functions upon re-exposure to pathogens, but also have many properties in common with naive cells, including pluripotency and the ability to migrate to the lymph nodes and spleen. Thus, memory cells embody features of both naive and effector cells, fuelling a long-standing debate centred on whether memory T cells develop from effector cells or directly from naive cells. Here we show that long-lived memory CD8 T cells are derived from a subset of effector T cells through a process of dedifferentiation. To assess the developmental origin of memory CD8 T cells, we investigated changes in DNA methylation programming at naive and effector cell-associated genes in virus-specific CD8 T cells during acute lymphocytic choriomeningitis virus infection in mice. Methylation profiling of terminal effector versus memory-precursor CD8 T cell subsets showed that, rather than retaining a naive epigenetic state, the subset of cells that gives rise to memory cells acquired de novo DNA methylation programs at naive-associated genes and became demethylated at the loci of classically defined effector molecules. Conditional deletion of the de novo methyltransferase Dnmt3a at an early stage of effector differentiation resulted in reduced methylation and faster re-expression of naive-associated genes, thereby accelerating the development of memory cells. Longitudinal phenotypic and epigenetic characterization of the memory-precursor effector subset of virus-specific CD8 T cells transferred into antigen-free mice revealed that differentiation to memory cells was coupled to erasure of de novo methylation programs and re-expression of naive-associated genes. Thus, epigenetic repression of naive-associated genes in effector CD8 T cells can be reversed in cells that develop into long-lived memory CD8 T cells while key effector genes remain demethylated, demonstrating that memory T cells arise from a subset of fate-permissive effector T cells.

GPU color space conversion

NASA Astrophysics Data System (ADS)

Chase, Patrick; Vondran, Gary

2011-01-01

Tetrahedral interpolation is commonly used to implement continuous color space conversions from sparse 3D and 4D lookup tables. We investigate the implementation and optimization of tetrahedral interpolation algorithms for GPUs, and compare to the best known CPU implementations as well as to a well known GPU-based trilinear implementation. We show that a 500 NVIDIA GTX-580 GPU is 3x faster than a 1000 Intel Core i7 980X CPU for 3D interpolation, and 9x faster for 4D interpolation. Performance-relevant GPU attributes are explored including thread scheduling, local memory characteristics, global memory hierarchy, and cache behaviors. We consider existing tetrahedral interpolation algorithms and tune based on the structure and branching capabilities of current GPUs. Global memory performance is improved by reordering and expanding the lookup table to ensure optimal access behaviors. Per multiprocessor local memory is exploited to implement optimally coalesced global memory accesses, and local memory addressing is optimized to minimize bank conflicts. We explore the impacts of lookup table density upon computation and memory access costs. Also presented are CPU-based 3D and 4D interpolators, using SSE vector operations that are faster than any previously published solution.

Measuring autobiographical fluency in the self-memory system.

PubMed

Rathbone, Clare J; Moulin, Chris J A

2014-01-01

Autobiographical memory is widely considered to be fundamentally related to concepts of self and identity. However, few studies have sought to test models of self and memory directly using experimental designs. Using a novel autobiographical fluency paradigm, the present study investigated memory accessibility for different levels of self-related knowledge. Forty participants generated 20 "I am" statements about themselves, from which the 1st, 5th, 10th, 15th, and 20th were used as cues in a two-minute autobiographical fluency task. The most salient aspects of the self, measured by both serial position and ratings of personal significance, were associated with more accessible sets of autobiographical memories. This finding supports theories that view the self as a powerful organizational structure in memory. Results are discussed with reference to models of self and memory.

Distinct T helper cell dependence of memory B-cell proliferation versus plasma cell differentiation.

PubMed

Zabel, Franziska; Fettelschoss, Antonia; Vogel, Monique; Johansen, Pål; Kündig, Thomas M; Bachmann, Martin F

2017-03-01

Several memory B-cell subclasses with distinct functions have been described, of which the most effective is the class-switched (CS) memory B-cell population. We have previously shown, using virus-like particles (VLPs), that the proliferative potential of these CS memory B cells is limited and they fail to re-enter germinal centres (GCs). However, VLP-specific memory B cells quickly differentiated into secondary plasma cells (PCs) with the virtue of elevated antibody production compared with primary PCs. Whereas the induction of VLP + memory B cells was strongly dependent on T helper cells, we were wondering whether re-stimulation of VLP + memory B cells and their differentiation into secondary PCs would also require T helper cells. Global absence of T helper cells led to strongly impaired memory B cell proliferation and PC differentiation. In contrast, lack of interleukin-21 receptor-dependent follicular T helper cells or CD40 ligand signalling strongly affected proliferation of memory B cells, but differentiation into mature secondary PCs exhibiting increased antibody production was essentially normal. This contrasts with primary B-cell responses, where a strong dependence on CD40 ligand but limited importance of interleukin-21 receptor was seen. Hence, T helper cell dependence differs between primary and secondary B-cell responses as well as between memory B-cell proliferation and PC differentiation. © 2016 John Wiley & Sons Ltd.

Improving Unipolar Resistive Switching Uniformity with Cone-Shaped Conducting Filaments and Its Logic-In-Memory Application.

PubMed

Gao, Shuang; Liu, Gang; Chen, Qilai; Xue, Wuhong; Yang, Huali; Shang, Jie; Chen, Bin; Zeng, Fei; Song, Cheng; Pan, Feng; Li, Run-Wei

2018-02-21

Resistive random access memory (RRAM) with inherent logic-in-memory capability exhibits great potential to construct beyond von-Neumann computers. Particularly, unipolar RRAM is more promising because its single polarity operation enables large-scale crossbar logic-in-memory circuits with the highest integration density and simpler peripheral control circuits. However, unipolar RRAM usually exhibits poor switching uniformity because of random activation of conducting filaments and consequently cannot meet the strict uniformity requirement for logic-in-memory application. In this contribution, a new methodology that constructs cone-shaped conducting filaments by using chemically a active metal cathode is proposed to improve unipolar switching uniformity. Such a peculiar metal cathode will react spontaneously with the oxide switching layer to form an interfacial layer, which together with the metal cathode itself can act as a load resistor to prevent the overgrowth of conducting filaments and thus make them more cone-like. In this way, the rupture of conducting filaments can be strictly limited to the tip region, making their residual parts favorable locations for subsequent filament growth and thus suppressing their random regeneration. As such, a novel "one switch + one unipolar RRAM cell" hybrid structure is capable to realize all 16 Boolean logic functions for large-scale logic-in-memory circuits.

Vaccine-elicited SIV and HIV envelope-specific IgA and IgG memory B cells in rhesus macaque peripheral blood correlate with functional antibody responses and reduced viremia

PubMed Central

Brocca-Cofano, Egidio; McKinnon, Katherine; Demberg, Thorsten; Venzon, David; Hidajat, Rachmat; Xiao, Peng; Daltabuit-Test, Mara; Patterson, L. Jean; Robert-Guroff, Marjorie

2011-01-01

An effective HIV vaccine requires strong systemic and mucosal, cellular and humoral immunity. Numerous non-human primate studies have investigated memory T cells, but not memory B cells. Humoral immunologic memory is mediated by long-lived antibody-secreting plasma cells and differentiation of memory B cells into short-lived plasma blasts following re-exposure to immunizing antigen. Here we studied memory B cells in vaccinated rhesus macaques. PBMC were stimulated polyclonally using CD40 Ligand, IL-21 and CpG to induce B cell proliferation and differentiation into antibody secreting cells (ASC). Flow cytometry was used for phenotyping and evaluating proliferation by CFSE dilution. B cell responses were quantified by ELISPOT. Methodology was established using PBMC of vaccinated elite-controller macaques that exhibited strong, multi-functional antibody activities. Subsequently, memory B cells elicited by two replicating Ad-recombinant prime/envelope boost regimens were retrospectively evaluated pre- and post- SIV and SHIV challenges. The vaccine regimens induced SIV and HIV Env-specific IgG and IgA memory B cells. Prior to challenge, IgA memory B cells were more numerous than IgG memory B cells, reflecting the mucosal priming immunizations. Pre- and post-challenge memory B cells were correlated with functional antibody responses including antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cell-mediated viral inhibition (ADCVI) and transcytosis inhibition. Post-challenge, Env-specific IgG and IgA memory B cells were correlated with reduced chronic viremia. We conclude that functional antibody responses elicited by our prime/boost regimen were effectively incorporated into the memory B cell pool where they contributed to control of viremia following re-exposure to the immunizing antigen. PMID:21382487

An energy and cost efficient majority-based RAM cell in quantum-dot cellular automata

NASA Astrophysics Data System (ADS)

Khosroshahy, Milad Bagherian; Moaiyeri, Mohammad Hossein; Navi, Keivan; Bagherzadeh, Nader

Nanotechnologies, notably quantum-dot cellular automata, have achieved major attentions for their prominent features as compared to the conventional CMOS circuitry. Quantum-dot cellular automata, particularly owning to its considerable reduction in size, high switching speed and ultra-low energy consumption, is considered as a potential alternative for the CMOS technology. As the memory unit is one of the most essential components in a digital system, designing a well-optimized QCA random access memory (RAM) cell is an important area of research. In this paper, a new five-input majority gate is presented which is suitable for implementing efficient single-layer QCA circuits. In addition, a new RAM cell with set and reset capabilities is designed based on the proposed majority gate, which has an efficient and low-energy structure. The functionality, performance and energy consumption of the proposed designs are evaluated based on the QCADesigner and QCAPro tools. According to the simulation results, the proposed RAM design leads to on average 38% lower total energy dissipation, 25% smaller area, 20% lower cell count, 28% lower delay and 60% lower QCA cost as compared to its previous counterparts.

Efficient Machine Learning Approach for Optimizing Scientific Computing Applications on Emerging HPC Architectures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arumugam, Kamesh

Efficient parallel implementations of scientific applications on multi-core CPUs with accelerators such as GPUs and Xeon Phis is challenging. This requires - exploiting the data parallel architecture of the accelerator along with the vector pipelines of modern x86 CPU architectures, load balancing, and efficient memory transfer between different devices. It is relatively easy to meet these requirements for highly structured scientific applications. In contrast, a number of scientific and engineering applications are unstructured. Getting performance on accelerators for these applications is extremely challenging because many of these applications employ irregular algorithms which exhibit data-dependent control-ow and irregular memory accesses. Furthermore,more » these applications are often iterative with dependency between steps, and thus making it hard to parallelize across steps. As a result, parallelism in these applications is often limited to a single step. Numerical simulation of charged particles beam dynamics is one such application where the distribution of work and memory access pattern at each time step is irregular. Applications with these properties tend to present significant branch and memory divergence, load imbalance between different processor cores, and poor compute and memory utilization. Prior research on parallelizing such irregular applications have been focused around optimizing the irregular, data-dependent memory accesses and control-ow during a single step of the application independent of the other steps, with the assumption that these patterns are completely unpredictable. We observed that the structure of computation leading to control-ow divergence and irregular memory accesses in one step is similar to that in the next step. It is possible to predict this structure in the current step by observing the computation structure of previous steps. In this dissertation, we present novel machine learning based optimization techniques to address the parallel implementation challenges of such irregular applications on different HPC architectures. In particular, we use supervised learning to predict the computation structure and use it to address the control-ow and memory access irregularities in the parallel implementation of such applications on GPUs, Xeon Phis, and heterogeneous architectures composed of multi-core CPUs with GPUs or Xeon Phis. We use numerical simulation of charged particles beam dynamics simulation as a motivating example throughout the dissertation to present our new approach, though they should be equally applicable to a wide range of irregular applications. The machine learning approach presented here use predictive analytics and forecasting techniques to adaptively model and track the irregular memory access pattern at each time step of the simulation to anticipate the future memory access pattern. Access pattern forecasts can then be used to formulate optimization decisions during application execution which improves the performance of the application at a future time step based on the observations from earlier time steps. In heterogeneous architectures, forecasts can also be used to improve the memory performance and resource utilization of all the processing units to deliver a good aggregate performance. We used these optimization techniques and anticipation strategy to design a cache-aware, memory efficient parallel algorithm to address the irregularities in the parallel implementation of charged particles beam dynamics simulation on different HPC architectures. Experimental result using a diverse mix of HPC architectures shows that our approach in using anticipation strategy is effective in maximizing data reuse, ensuring workload balance, minimizing branch and memory divergence, and in improving resource utilization.« less

Bim controls IL-15 availability and limits engagement of multiple BH3-only proteins

PubMed Central

Kurtulus, S; Sholl, A; Toe, J; Tripathi, P; Raynor, J; Li, K-P; Pellegrini, M; Hildeman, D A

2015-01-01

During the effector CD8+ T-cell response, transcriptional differentiation programs are engaged that promote effector T cells with varying memory potential. Although these differentiation programs have been used to explain which cells die as effectors and which cells survive and become memory cells, it is unclear if the lack of cell death enhances memory. Here, we investigated effector CD8+ T-cell fate in mice whose death program has been largely disabled because of the loss of Bim. Interestingly, the absence of Bim resulted in a significant enhancement of effector CD8+ T cells with more memory potential. Bim-driven control of memory T-cell development required T-cell-specific, but not dendritic cell-specific, expression of Bim. Both total and T-cell-specific loss of Bim promoted skewing toward memory precursors, by enhancing the survival of memory precursors, and limiting the availability of IL-15. Decreased IL-15 availability in Bim-deficient mice facilitated the elimination of cells with less memory potential via the additional pro-apoptotic molecules Noxa and Puma. Combined, these data show that Bim controls memory development by limiting the survival of pre-memory effector cells. Further, by preventing the consumption of IL-15, Bim limits the role of Noxa and Puma in causing the death of effector cells with less memory potential. PMID:25124553

Bim controls IL-15 availability and limits engagement of multiple BH3-only proteins.

PubMed

Kurtulus, S; Sholl, A; Toe, J; Tripathi, P; Raynor, J; Li, K-P; Pellegrini, M; Hildeman, D A

2015-01-01

During the effector CD8+ T-cell response, transcriptional differentiation programs are engaged that promote effector T cells with varying memory potential. Although these differentiation programs have been used to explain which cells die as effectors and which cells survive and become memory cells, it is unclear if the lack of cell death enhances memory. Here, we investigated effector CD8+ T-cell fate in mice whose death program has been largely disabled because of the loss of Bim. Interestingly, the absence of Bim resulted in a significant enhancement of effector CD8+ T cells with more memory potential. Bim-driven control of memory T-cell development required T-cell-specific, but not dendritic cell-specific, expression of Bim. Both total and T-cell-specific loss of Bim promoted skewing toward memory precursors, by enhancing the survival of memory precursors, and limiting the availability of IL-15. Decreased IL-15 availability in Bim-deficient mice facilitated the elimination of cells with less memory potential via the additional pro-apoptotic molecules Noxa and Puma. Combined, these data show that Bim controls memory development by limiting the survival of pre-memory effector cells. Further, by preventing the consumption of IL-15, Bim limits the role of Noxa and Puma in causing the death of effector cells with less memory potential.

Heap/stack guard pages using a wakeup unit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gooding, Thomas M; Satterfield, David L; Steinmacher-Burow, Burkhard

A method and system for providing a memory access check on a processor including the steps of detecting accesses to a memory device including level-1 cache using a wakeup unit. The method includes invalidating level-1 cache ranges corresponding to a guard page, and configuring a plurality of wakeup address compare (WAC) registers to allow access to selected WAC registers. The method selects one of the plurality of WAC registers, and sets up a WAC register related to the guard page. The method configures the wakeup unit to interrupt on access of the selected WAC register. The method detects access ofmore » the memory device using the wakeup unit when a guard page is violated. The method generates an interrupt to the core using the wakeup unit, and determines the source of the interrupt. The method detects the activated WAC registers assigned to the violated guard page, and initiates a response.« less

CD8 T cell memory: it takes all kinds

PubMed Central

Hamilton, Sara E.; Jameson, Stephen C.

2012-01-01

Understanding the mechanisms that regulate the differentiation and maintenance of CD8+ memory T cells is fundamental to the development of effective T cell-based vaccines. Memory cell differentiation is influenced by the cytokines that accompany T cell priming, the history of previous antigen encounters, and the tissue sites into which memory cells migrate. These cues combine to influence the developing CD8+ memory pool, and recent work has revealed the importance of multiple transcription factors, metabolic molecules, and surface receptors in revealing the type of memory cell that is generated. Paired with increasingly meticulous subsetting and sorting of memory populations, we now know the CD8+ memory pool to be phenotypically and functionally heterogeneous in nature. This includes both recirculating and tissue-resident memory populations, and cells with varying degrees of inherent longevity and protective function. These data point to the importance of tailored vaccine design. Here we discuss how the diversity of the memory CD8+ T cell pool challenges the notion that “one size fits all” for pathogen control, and how distinct memory subsets may be suited for distinct aspects of protective immunity. PMID:23230436

The differential effects of ecstasy/polydrug use on executive components: shifting, inhibition, updating and access to semantic memory.

PubMed

Montgomery, Catharine; Fisk, John E; Newcombe, Russell; Murphy, Phillip N

2005-10-01

Recent theoretical models suggest that the central executive may not be a unified structure. The present study explored the nature of central executive deficits in ecstasy users. In study 1, 27 ecstasy users and 34 non-users were assessed using tasks to tap memory updating (computation span; letter updating) and access to long-term memory (a semantic fluency test and the Chicago Word Fluency Test). In study 2, 51 ecstasy users and 42 non-users completed tasks that assess mental set switching (number/letter and plus/minus) and inhibition (random letter generation). MANOVA revealed that ecstasy users performed worse on both tasks used to assess memory updating and on tasks to assess access to long-term memory (C- and S-letter fluency). However, notwithstanding the significant ecstasy group-related effects, indices of cocaine and cannabis use were also significantly correlated with most of the executive measures. Unexpectedly, in study 2, ecstasy users performed significantly better on the inhibition task, producing more letters than non-users. No group differences were observed on the switching tasks. Correlations between indices of ecstasy use and number of letters produced were significant. The present study provides further support for ecstasy/polydrug-related deficits in memory updating and in access to long-term memory. The surplus evident on the inhibition task should be treated with some caution, as this was limited to a single measure and has not been supported by our previous work.

Performance Evaluation of Remote Memory Access (RMA) Programming on Shared Memory Parallel Computers

NASA Technical Reports Server (NTRS)

Jin, Hao-Qiang; Jost, Gabriele; Biegel, Bryan A. (Technical Monitor)

2002-01-01

The purpose of this study is to evaluate the feasibility of remote memory access (RMA) programming on shared memory parallel computers. We discuss different RMA based implementations of selected CFD application benchmark kernels and compare them to corresponding message passing based codes. For the message-passing implementation we use MPI point-to-point and global communication routines. For the RMA based approach we consider two different libraries supporting this programming model. One is a shared memory parallelization library (SMPlib) developed at NASA Ames, the other is the MPI-2 extensions to the MPI Standard. We give timing comparisons for the different implementation strategies and discuss the performance.

Investigation of resistance switching in SiO x RRAM cells using a 3D multi-scale kinetic Monte Carlo simulator

NASA Astrophysics Data System (ADS)

Sadi, Toufik; Mehonic, Adnan; Montesi, Luca; Buckwell, Mark; Kenyon, Anthony; Asenov, Asen

2018-02-01

We employ an advanced three-dimensional (3D) electro-thermal simulator to explore the physics and potential of oxide-based resistive random-access memory (RRAM) cells. The physical simulation model has been developed recently, and couples a kinetic Monte Carlo study of electron and ionic transport to the self-heating phenomenon while accounting carefully for the physics of vacancy generation and recombination, and trapping mechanisms. The simulation framework successfully captures resistance switching, including the electroforming, set and reset processes, by modeling the dynamics of conductive filaments in the 3D space. This work focuses on the promising yet less studied RRAM structures based on silicon-rich silica (SiO x ) RRAMs. We explain the intrinsic nature of resistance switching of the SiO x layer, analyze the effect of self-heating on device performance, highlight the role of the initial vacancy distributions acting as precursors for switching, and also stress the importance of using 3D physics-based models to capture accurately the switching processes. The simulation work is backed by experimental studies. The simulator is useful for improving our understanding of the little-known physics of SiO x resistive memory devices, as well as other oxide-based RRAM systems (e.g. transition metal oxide RRAMs), offering design and optimization capabilities with regard to the reliability and variability of memory cells.

Enhancing Memory Access for Less Skilled Readers

ERIC Educational Resources Information Center

Smith, Emily R.; O'Brien, Edward J.

2016-01-01

Less skilled readers' comprehension often suffers because they have an impoverished representation of text in long-term memory; this, in turn, increases the difficulty of gaining access to backgrounded information necessary for maintaining coherence. The results of four experiments demonstrated that providing less skilled readers with additional…

Application of phase-change materials in memory taxonomy

PubMed Central

Wang, Lei; Tu, Liang; Wen, Jing

2017-01-01

Abstract Phase-change materials are suitable for data storage because they exhibit reversible transitions between crystalline and amorphous states that have distinguishable electrical and optical properties. Consequently, these materials find applications in diverse memory devices ranging from conventional optical discs to emerging nanophotonic devices. Current research efforts are mostly devoted to phase-change random access memory, whereas the applications of phase-change materials in other types of memory devices are rarely reported. Here we review the physical principles of phase-change materials and devices aiming to help researchers understand the concept of phase-change memory. We classify phase-change memory devices into phase-change optical disc, phase-change scanning probe memory, phase-change random access memory, and phase-change nanophotonic device, according to their locations in memory hierarchy. For each device type we discuss the physical principles in conjunction with merits and weakness for data storage applications. We also outline state-of-the-art technologies and future prospects. PMID:28740557

Attention, working memory, and phenomenal experience of WM content: memory levels determined by different types of top-down modulation.

PubMed

Jacob, Jane; Jacobs, Christianne; Silvanto, Juha

2015-01-01

What is the role of top-down attentional modulation in consciously accessing working memory (WM) content? In influential WM models, information can exist in different states, determined by allocation of attention; placing the original memory representation in the center of focused attention gives rise to conscious access. Here we discuss various lines of evidence indicating that such attentional modulation is not sufficient for memory content to be phenomenally experienced. We propose that, in addition to attentional modulation of the memory representation, another type of top-down modulation is required: suppression of all incoming visual information, via inhibition of early visual cortex. In this view, there are three distinct memory levels, as a function of the top-down control associated with them: (1) Nonattended, nonconscious associated with no attentional modulation; (2) attended, phenomenally nonconscious memory, associated with attentional enhancement of the actual memory trace; (3) attended, phenomenally conscious memory content, associated with enhancement of the memory trace and top-down suppression of all incoming visual input.

Selective memory retrieval can impair and improve retrieval of other memories.

PubMed

Bäuml, Karl-Heinz T; Samenieh, Anuscheh

2012-03-01

Research from the past decades has shown that retrieval of a specific memory (e.g., retrieving part of a previous vacation) typically attenuates retrieval of other memories (e.g., memories for other details of the event), causing retrieval-induced forgetting. More recently, however, it has been shown that retrieval can both attenuate and aid recall of other memories (K.-H. T. Bäuml & A. Samenieh, 2010). To identify the circumstances under which retrieval aids recall, the authors examined retrieval dynamics in listwise directed forgetting, context-dependent forgetting, proactive interference, and in the absence of any induced memory impairment. They found beneficial effects of selective retrieval in listwise directed forgetting and context-dependent forgetting but detrimental effects in all the other conditions. Because context-dependent forgetting and listwise directed forgetting arguably reflect impaired context access, the results suggest that memory retrieval aids recall of memories that are subject to impaired context access but attenuates recall in the absence of such circumstances. The findings are consistent with a 2-factor account of memory retrieval and suggest the existence of 2 faces of memory retrieval. 2012 APA, all rights reserved

On VLSI Design of Rank-Order Filtering using DCRAM Architecture

PubMed Central

Lin, Meng-Chun; Dung, Lan-Rong

2009-01-01

This paper addresses on VLSI design of rank-order filtering (ROF) with a maskable memory for real-time speech and image processing applications. Based on a generic bit-sliced ROF algorithm, the proposed design uses a special-defined memory, called the dual-cell random-access memory (DCRAM), to realize major operations of ROF: threshold decomposition and polarization. Using the memory-oriented architecture, the proposed ROF processor can benefit from high flexibility, low cost and high speed. The DCRAM can perform the bit-sliced read, partial write, and pipelined processing. The bit-sliced read and partial write are driven by maskable registers. With recursive execution of the bit-slicing read and partial write, the DCRAM can effectively realize ROF in terms of cost and speed. The proposed design has been implemented using TSMC 0.18 μm 1P6M technology. As shown in the result of physical implementation, the core size is 356.1 × 427.7μm2 and the VLSI implementation of ROF can operate at 256 MHz for 1.8V supply. PMID:19865599

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gebis, Joseph; Oliker, Leonid; Shalf, John

The disparity between microprocessor clock frequencies and memory latency is a primary reason why many demanding applications run well below peak achievable performance. Software controlled scratchpad memories, such as the Cell local store, attempt to ameliorate this discrepancy by enabling precise control over memory movement; however, scratchpad technology confronts the programmer and compiler with an unfamiliar and difficult programming model. In this work, we present the Virtual Vector Architecture (ViVA), which combines the memory semantics of vector computers with a software-controlled scratchpad memory in order to provide a more effective and practical approach to latency hiding. ViVA requires minimal changesmore » to the core design and could thus be easily integrated with conventional processor cores. To validate our approach, we implemented ViVA on the Mambo cycle-accurate full system simulator, which was carefully calibrated to match the performance on our underlying PowerPC Apple G5 architecture. Results show that ViVA is able to deliver significant performance benefits over scalar techniques for a variety of memory access patterns as well as two important memory-bound compact kernels, corner turn and sparse matrix-vector multiplication -- achieving 2x-13x improvement compared the scalar version. Overall, our preliminary ViVA exploration points to a promising approach for improving application performance on leading microprocessors with minimal design and complexity costs, in a power efficient manner.« less

Multiple memory stores and operant conditioning: a rationale for memory's complexity.

PubMed

Meeter, Martijn; Veldkamp, Rob; Jin, Yaochu

2009-02-01

Why does the brain contain more than one memory system? Genetic algorithms can play a role in elucidating this question. Here, model animals were constructed containing a dorsal striatal layer that controlled actions, and a ventral striatal layer that controlled a dopaminergic learning signal. Both layers could gain access to three modeled memory stores, but such access was penalized as energy expenditure. Model animals were then selected on their fitness in simulated operant conditioning tasks. Results suggest that having access to multiple memory stores and their representations is important in learning to regulate dopamine release, as well as in contextual discrimination. For simple operant conditioning, as well as stimulus discrimination, hippocampal compound representations turned out to suffice, a counterintuitive result given findings that hippocampal lesions tend not to affect performance in such tasks. We argue that there is in fact evidence to support a role for compound representations and the hippocampus in even the simplest conditioning tasks.

Object selection costs in visual working memory: A diffusion model analysis of the focus of attention.

PubMed

Sewell, David K; Lilburn, Simon D; Smith, Philip L

2016-11-01

A central question in working memory research concerns the degree to which information in working memory is accessible to other cognitive processes (e.g., decision-making). Theories assuming that the focus of attention can only store a single object at a time require the focus to orient to a target representation before further processing can occur. The need to orient the focus of attention implies that single-object accounts typically predict response time costs associated with object selection even when working memory is not full (i.e., memory load is less than 4 items). For other theories that assume storage of multiple items in the focus of attention, predictions depend on specific assumptions about the way resources are allocated among items held in the focus, and how this affects the time course of retrieval of items from the focus. These broad theoretical accounts have been difficult to distinguish because conventional analyses fail to separate components of empirical response times related to decision-making from components related to selection and retrieval processes associated with accessing information in working memory. To better distinguish these response time components from one another, we analyze data from a probed visual working memory task using extensions of the diffusion decision model. Analysis of model parameters revealed that increases in memory load resulted in (a) reductions in the quality of the underlying stimulus representations in a manner consistent with a sample size model of visual working memory capacity and (b) systematic increases in the time needed to selectively access a probed representation in memory. The results are consistent with single-object theories of the focus of attention. The results are also consistent with a subset of theories that assume a multiobject focus of attention in which resource allocation diminishes both the quality and accessibility of the underlying representations. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Germinal-center development of memory B cells driven by IL-9 from follicular helper T cells.

PubMed

Wang, Yifeng; Shi, Jingwen; Yan, Jiacong; Xiao, Zhengtao; Hou, Xiaoxiao; Lu, Peiwen; Hou, Shiyue; Mao, Tianyang; Liu, Wanli; Ma, Yuanwu; Zhang, Lianfeng; Yang, Xuerui; Qi, Hai

2017-08-01

Germinal centers (GCs) support high-affinity, long-lived humoral immunity. How memory B cells develop in GCs is not clear. Through the use of a cell-cycle-reporting system, we identified GC-derived memory precursor cells (GC-MP cells) that had quit cycling and reached G0 phase while in the GC, exhibited memory-associated phenotypes with signs of affinity maturation and localized toward the GC border. After being transferred into adoptive hosts, GC-MP cells reconstituted a secondary response like genuine memory B cells. GC-MP cells expressed the interleukin 9 (IL-9) receptor and responded to IL-9. Acute treatment with IL-9 or antibody to IL-9 accelerated or retarded the positioning of GC-MP cells toward the GC edge and exit from the GC, and enhanced or inhibited the development of memory B cells, which required B cell-intrinsic responsiveness to IL-9. Follicular helper T cells (T FH cells) produced IL-9, and deletion of IL-9 from T cells or, more specifically, from GC T FH cells led to impaired memory formation of B cells. Therefore, the GC development of memory B cells is promoted by T FH cell-derived IL-9.

Designing a VMEbus FDDI adapter card

NASA Astrophysics Data System (ADS)

Venkataraman, Raman

1992-03-01

This paper presents a system architecture for a VMEbus FDDI adapter card containing a node core, FDDI block, frame buffer memory and system interface unit. Most of the functions of the PHY and MAC layers of FDDI are implemented with National's FDDI chip set and the SMT implementation is simplified with a low cost microcontroller. The factors that influence the system bus bandwidth utilization and FDDI bandwidth utilization are the data path and frame buffer memory architecture. The VRAM based frame buffer memory has two sections - - LLC frame memory and SMT frame memory. Each section with an independent serial access memory (SAM) port provides an independent access after the initial data transfer cycle on the main port and hence, the throughput is maximized on each port of the memory. The SAM port simplifies the system bus master DMA design and the VMEbus interface can be designed with low-cost off-the-shelf interface chips.

Error free physically unclonable function with programmed resistive random access memory using reliable resistance states by specific identification-generation method

NASA Astrophysics Data System (ADS)

Tseng, Po-Hao; Hsu, Kai-Chieh; Lin, Yu-Yu; Lee, Feng-Min; Lee, Ming-Hsiu; Lung, Hsiang-Lan; Hsieh, Kuang-Yeu; Chung Wang, Keh; Lu, Chih-Yuan

2018-04-01

A high performance physically unclonable function (PUF) implemented with WO3 resistive random access memory (ReRAM) is presented in this paper. This robust ReRAM-PUF can eliminated bit flipping problem at very high temperature (up to 250 °C) due to plentiful read margin by using initial resistance state and set resistance state. It is also promised 10 years retention at the temperature range of 210 °C. These two stable resistance states enable stable operation at automotive environments from -40 to 125 °C without need of temperature compensation circuit. The high uniqueness of PUF can be achieved by implementing a proposed identification (ID)-generation method. Optimized forming condition can move 50% of the cells to low resistance state and the remaining 50% remain at initial high resistance state. The inter- and intra-PUF evaluations with unlimited separation of hamming distance (HD) are successfully demonstrated even under the corner condition. The number of reproduction was measured to exceed 107 times with 0% bit error rate (BER) at read voltage from 0.4 to 0.7 V.

A low-voltage sense amplifier with two-stage operational amplifier clamping for flash memory

NASA Astrophysics Data System (ADS)

Guo, Jiarong

2017-04-01

A low-voltage sense amplifier with reference current generator utilizing two-stage operational amplifier clamp structure for flash memory is presented in this paper, capable of operating with minimum supply voltage at 1 V. A new reference current generation circuit composed of a reference cell and a two-stage operational amplifier clamping the drain pole of the reference cell is used to generate the reference current, which avoids the threshold limitation caused by current mirror transistor in the traditional sense amplifier. A novel reference voltage generation circuit using dummy bit-line structure without pull-down current is also adopted, which not only improves the sense window enhancing read precision but also saves power consumption. The sense amplifier was implemented in a flash realized in 90 nm flash technology. Experimental results show the access time is 14.7 ns with power supply of 1.2 V and slow corner at 125 °C. Project supported by the National Natural Science Fundation of China (No. 61376028).

Phenotypic and Functional Alterations in Circulating Memory CD8 T Cells with Time after Primary Infection.

PubMed

Martin, Matthew D; Kim, Marie T; Shan, Qiang; Sompallae, Ramakrishna; Xue, Hai-Hui; Harty, John T; Badovinac, Vladimir P

2015-10-01

Memory CD8 T cells confer increased protection to immune hosts upon secondary viral, bacterial, and parasitic infections. The level of protection provided depends on the numbers, quality (functional ability), and location of memory CD8 T cells present at the time of infection. While primary memory CD8 T cells can be maintained for the life of the host, the full extent of phenotypic and functional changes that occur over time after initial antigen encounter remains poorly characterized. Here we show that critical properties of circulating primary memory CD8 T cells, including location, phenotype, cytokine production, maintenance, secondary proliferation, secondary memory generation potential, and mitochondrial function change with time after infection. Interestingly, phenotypic and functional alterations in the memory population are not due solely to shifts in the ratio of effector (CD62Llo) and central memory (CD62Lhi) cells, but also occur within defined CD62Lhi memory CD8 T cell subsets. CD62Lhi memory cells retain the ability to efficiently produce cytokines with time after infection. However, while it is was not formally tested whether changes in CD62Lhi memory CD8 T cells over time occur in a cell intrinsic manner or are due to selective death and/or survival, the gene expression profiles of CD62Lhi memory CD8 T cells change, phenotypic heterogeneity decreases, and mitochondrial function and proliferative capacity in either a lymphopenic environment or in response to antigen re-encounter increase with time. Importantly, and in accordance with their enhanced proliferative and metabolic capabilities, protection provided against chronic LCMV clone-13 infection increases over time for both circulating memory CD8 T cell populations and for CD62Lhi memory cells. Taken together, the data in this study reveal that memory CD8 T cells continue to change with time after infection and suggest that the outcome of vaccination strategies designed to elicit protective memory CD8 T cells using single or prime-boost immunizations depends upon the timing between antigen encounters.

Scaling Irregular Applications through Data Aggregation and Software Multithreading

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morari, Alessandro; Tumeo, Antonino; Chavarría-Miranda, Daniel

Bioinformatics, data analytics, semantic databases, knowledge discovery are emerging high performance application areas that exploit dynamic, linked data structures such as graphs, unbalanced trees or unstructured grids. These data structures usually are very large, requiring significantly more memory than available on single shared memory systems. Additionally, these data structures are difficult to partition on distributed memory systems. They also present poor spatial and temporal locality, thus generating unpredictable memory and network accesses. The Partitioned Global Address Space (PGAS) programming model seems suitable for these applications, because it allows using a shared memory abstraction across distributed-memory clusters. However, current PGAS languagesmore » and libraries are built to target regular remote data accesses and block transfers. Furthermore, they usually rely on the Single Program Multiple Data (SPMD) parallel control model, which is not well suited to the fine grained, dynamic and unbalanced parallelism of irregular applications. In this paper we present {\\bf GMT} (Global Memory and Threading library), a custom runtime library that enables efficient execution of irregular applications on commodity clusters. GMT integrates a PGAS data substrate with simple fork/join parallelism and provides automatic load balancing on a per node basis. It implements multi-level aggregation and lightweight multithreading to maximize memory and network bandwidth with fine-grained data accesses and tolerate long data access latencies. A key innovation in the GMT runtime is its thread specialization (workers, helpers and communication threads) that realize the overall functionality. We compare our approach with other PGAS models, such as UPC running using GASNet, and hand-optimized MPI code on a set of typical large-scale irregular applications, demonstrating speedups of an order of magnitude.« less

The influence of training and experience on memory strategy.

PubMed

Patrick, John; Morgan, Phillip L; Smy, Victoria; Tiley, Leyanne; Seeby, Helen; Patrick, Tanya; Evans, Jonathan

2015-07-01

This paper investigates whether, and if so how much, prior training and experience overwrite the influence of the constraints of the task environment on strategy deployment. This evidence is relevant to the theory of soft constraints that focuses on the role of constraints in the task environment (Gray, Simms, Fu, & Schoelles, Psychological Review, 113: 461-482, 2006). The theory explains how an increase in the cost of accessing information induces a more memory-based strategy involving more encoding and planning. Experiments 1 and 3 adopt a traditional training and transfer design using the Blocks World Task in which participants were exposed to training trials involving a 2.5-s delay in accessing goal-state information before encountering transfer trials in which there was no access delay. The effect of prior training was assessed by the degree of memory-based strategy adopted in the transfer trials. Training with an access delay had a substantial carry-over effect and increased the subsequent degree of memory-based strategy adopted in the transfer environment. However, such effects do not necessarily occur if goal-state access cost in training is less costly than in transfer trials (Experiment 2). Experiment 4 used a fine-grained intra-trial design to examine the effect of experiencing access cost on one, two, or three occasions within the same trial and found that such experience on two consecutive occasions was sufficient to induce a more memory-based strategy. This paper establishes some effects of training that are relevant to the soft constraints theory and also discusses practical implications.

Optoelectronic-cache memory system architecture.

PubMed

Chiarulli, D M; Levitan, S P

1996-05-10

We present an investigation of the architecture of an optoelectronic cache that can integrate terabit optical memories with the electronic caches associated with high-performance uniprocessors and multiprocessors. The use of optoelectronic-cache memories enables these terabit technologies to provide transparently low-latency secondary memory with frame sizes comparable with disk pages but with latencies that approach those of electronic secondary-cache memories. This enables the implementation of terabit memories with effective access times comparable with the cycle times of current microprocessors. The cache design is based on the use of a smart-pixel array and combines parallel free-space optical input-output to-and-from optical memory with conventional electronic communication to the processor caches. This cache and the optical memory system to which it will interface provide a large random-access memory space that has a lower overall latency than that of magnetic disks and disk arrays. In addition, as a consequence of the high-bandwidth parallel input-output capabilities of optical memories, fault service times for the optoelectronic cache are substantially less than those currently achievable with any rotational media.

Memory T and memory B cells share a transcriptional program of self-renewal with long-term hematopoietic stem cells

PubMed Central

Luckey, Chance John; Bhattacharya, Deepta; Goldrath, Ananda W.; Weissman, Irving L.; Benoist, Christophe; Mathis, Diane

2006-01-01

The only cells of the hematopoietic system that undergo self-renewal for the lifetime of the organism are long-term hematopoietic stem cells and memory T and B cells. To determine whether there is a shared transcriptional program among these self-renewing populations, we first compared the gene-expression profiles of naïve, effector and memory CD8+ T cells with those of long-term hematopoietic stem cells, short-term hematopoietic stem cells, and lineage-committed progenitors. Transcripts augmented in memory CD8+ T cells relative to naïve and effector T cells were selectively enriched in long-term hematopoietic stem cells and were progressively lost in their short-term and lineage-committed counterparts. Furthermore, transcripts selectively decreased in memory CD8+ T cells were selectively down-regulated in long-term hematopoietic stem cells and progressively increased with differentiation. To confirm that this pattern was a general property of immunologic memory, we turned to independently generated gene expression profiles of memory, naïve, germinal center, and plasma B cells. Once again, memory-enriched and -depleted transcripts were also appropriately augmented and diminished in long-term hematopoietic stem cells, and their expression correlated with progressive loss of self-renewal function. Thus, there appears to be a common signature of both up- and down-regulated transcripts shared between memory T cells, memory B cells, and long-term hematopoietic stem cells. This signature was not consistently enriched in neural or embryonic stem cell populations and, therefore, appears to be restricted to the hematopoeitic system. These observations provide evidence that the shared phenotype of self-renewal in the hematopoietic system is linked at the molecular level. PMID:16492737

Increased numbers of preexisting memory CD8 T cells and decreased T-bet expression can restrain terminal differentiation of secondary effector and memory CD8 T cells.

PubMed

Joshi, Nikhil S; Cui, Weiguo; Dominguez, Claudia X; Chen, Jonathan H; Hand, Timothy W; Kaech, Susan M

2011-10-15

Memory CD8 T cells acquire effector memory cell properties after reinfection and may reach terminally differentiated, senescent states ("Hayflick limit") after multiple infections. The signals controlling this process are not well understood, but we found that the degree of secondary effector and memory CD8 T cell differentiation was intimately linked to the amount of T-bet expressed upon reactivation and preexisting memory CD8 T cell number (i.e., primary memory CD8 T cell precursor frequency) present during secondary infection. Compared with naive cells, memory CD8 T cells were predisposed toward terminal effector (TE) cell differentiation because they could immediately respond to IL-12 and induce T-bet, even in the absence of Ag. TE cell formation after secondary (2°) or tertiary infections was dependent on increased T-bet expression because T-bet(+/-) cells were resistant to these phenotypic changes. Larger numbers of preexisting memory CD8 T cells limited the duration of 2° infection and the amount of IL-12 produced, and consequently, this reduced T-bet expression and the proportion of 2° TE CD8 T cells that formed. Together, these data show that over repeated infections, memory CD8 T cell quality and proliferative fitness is not strictly determined by the number of serial encounters with Ag or cell divisions, but is a function of the CD8 T cell differentiation state, which is genetically controlled in a T-bet-dependent manner. This differentiation state can be modulated by preexisting memory CD8 T cell number and the intensity of inflammation during reinfection. These results have important implications for vaccinations involving prime-boost strategies.

Cerebellar models of associative memory: Three papers from IEEE COMPCON spring 1989

NASA Technical Reports Server (NTRS)

Raugh, Michael R. (Editor)

1989-01-01

Three papers are presented on the following topics: (1) a cerebellar-model associative memory as a generalized random-access memory; (2) theories of the cerebellum - two early models of associative memory; and (3) intelligent network management and functional cerebellum synthesis.

The dynamics of sensory buffers: geometric, spatial, and experience-dependent shaping of iconic memory.

PubMed

Graziano, Martin; Sigman, Mariano

2008-05-23

When a stimulus is presented, its sensory trace decays rapidly, lasting for approximately 1000 ms. This brief and labile memory, referred as iconic memory, serves as a buffer before information is transferred to working memory and executive control. Here we explored the effect of different factors--geometric, spatial, and experience--with respect to the access and the maintenance of information in iconic memory and the progressive distortion of this memory. We studied performance in a partial report paradigm, a design wherein recall of only part of a stimulus array is required. Subjects had to report the identity of a letter in a location that was cued in a variable delay after the stimulus onset. Performance decayed exponentially with time, and we studied the different parameters (time constant, zero-delay value, and decay amplitude) as a function of the different factors. We observed that experience (determined by letter frequency) affected the access to iconic memory but not the temporal decay constant. On the contrary, spatial position affected the temporal course of delay. The entropy of the error distribution increased with time reflecting a progressive morphological distortion of the iconic buffer. We discuss our results on the context of a model of information access to executive control and how it is affected by learning and attention.

Oscillatory mechanisms of process binding in memory.

PubMed

Klimesch, Wolfgang; Freunberger, Roman; Sauseng, Paul

2010-06-01

A central topic in cognitive neuroscience is the question, which processes underlie large scale communication within and between different neural networks. The basic assumption is that oscillatory phase synchronization plays an important role for process binding--the transient linking of different cognitive processes--which may be considered a special type of large scale communication. We investigate this question for memory processes on the basis of different types of oscillatory synchronization mechanisms. The reviewed findings suggest that theta and alpha phase coupling (and phase reorganization) reflect control processes in two large memory systems, a working memory and a complex knowledge system that comprises semantic long-term memory. It is suggested that alpha phase synchronization may be interpreted in terms of processes that coordinate top-down control (a process guided by expectancy to focus on relevant search areas) and access to memory traces (a process leading to the activation of a memory trace). An analogous interpretation is suggested for theta oscillations and the controlled access to episodic memories. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Dual operation characteristics of resistance random access memory in indium-gallium-zinc-oxide thin film transistors

NASA Astrophysics Data System (ADS)

Yang, Jyun-Bao; Chang, Ting-Chang; Huang, Jheng-Jie; Chen, Yu-Chun; Chen, Yu-Ting; Tseng, Hsueh-Chih; Chu, Ann-Kuo; Sze, Simon M.

2014-04-01

In this study, indium-gallium-zinc-oxide thin film transistors can be operated either as transistors or resistance random access memory devices. Before the forming process, current-voltage curve transfer characteristics are observed, and resistance switching characteristics are measured after a forming process. These resistance switching characteristics exhibit two behaviors, and are dominated by different mechanisms. The mode 1 resistance switching behavior is due to oxygen vacancies, while mode 2 is dominated by the formation of an oxygen-rich layer. Furthermore, an easy approach is proposed to reduce power consumption when using these resistance random access memory devices with the amorphous indium-gallium-zinc-oxide thin film transistor.

Magnet/Hall-Effect Random-Access Memory

NASA Technical Reports Server (NTRS)

Wu, Jiin-Chuan; Stadler, Henry L.; Katti, Romney R.

1991-01-01

In proposed magnet/Hall-effect random-access memory (MHRAM), bits of data stored magnetically in Perm-alloy (or equivalent)-film memory elements and read out by using Hall-effect sensors to detect magnetization. Value of each bit represented by polarity of magnetization. Retains data for indefinite time or until data rewritten. Speed of Hall-effect sensors in MHRAM results in readout times of about 100 nanoseconds. Other characteristics include high immunity to ionizing radiation and storage densities of order 10(Sup6)bits/cm(Sup 2) or more.

Investigation of multilayer magnetic domain lattice file

NASA Technical Reports Server (NTRS)

Torok, E. J.; Kamin, M.; Tolman, C. H.

1980-01-01

The feasibility of the self structured multilayered bubble domain memory as a mass memory medium for satellite applications is examined. Theoretical considerations of multilayer bubble supporting materials are presented, in addition to the experimental evaluation of current accessed circuitry for various memory functions. The design, fabrication, and test of four device designs is described, and a recommended memory storage area configuration is presented. Memory functions which were demonstrated include the current accessed propagation of bubble domains and stripe domains, pinning of stripe domain ends, generation of single and double bubbles, generation of arrays of coexisting strip and bubble domains in a single garnet layer, and demonstration of different values of the strip out field for single and double bubbles indicating adequate margins for data detection. All functions necessary to develop a multilayer self structured bubble memory device were demonstrated in individual experiments.

Spin-transfer torque magnetoresistive random-access memory technologies for normally off computing (invited)

NASA Astrophysics Data System (ADS)

Ando, K.; Fujita, S.; Ito, J.; Yuasa, S.; Suzuki, Y.; Nakatani, Y.; Miyazaki, T.; Yoda, H.

2014-05-01

Most parts of present computer systems are made of volatile devices, and the power to supply them to avoid information loss causes huge energy losses. We can eliminate this meaningless energy loss by utilizing the non-volatile function of advanced spin-transfer torque magnetoresistive random-access memory (STT-MRAM) technology and create a new type of computer, i.e., normally off computers. Critical tasks to achieve normally off computers are implementations of STT-MRAM technologies in the main memory and low-level cache memories. STT-MRAM technology for applications to the main memory has been successfully developed by using perpendicular STT-MRAMs, and faster STT-MRAM technologies for applications to the cache memory are now being developed. The present status of STT-MRAMs and challenges that remain for normally off computers are discussed.

Mutation in the Fas Pathway Impairs CD8+ T Cell Memory1

PubMed Central

Dudani, Renu; Russell, Marsha; van Faassen, Henk; Krishnan, Lakshmi; Sad, Subash

2014-01-01

Fas death pathway is important for lymphocyte homeostasis, but the role of Fas pathway in T cell memory development is not clear. We show that whereas the expansion and contraction of CD8+ T cell response against Listeria monocytogenes were similar for wild-type (WT) and Fas ligand (FasL) mutant mice, the majority of memory CD8+ T cells in FasL mutant mice displayed an effector memory phenotype in the long-term in comparison with the mainly central memory phenotype displayed by memory CD8+ T cells in WT mice. Memory CD8+ T cells in FasL mutant mice expressed reduced levels of IFN-γ and displayed poor homeostatic and Ag-induced proliferation. Impairment in CD8+ T cell memory in FasL mutant hosts was not due to defective programming or the expression of mutant FasL on CD8+ T cells, but was caused by perturbed cytokine environment in FasL mutant mice. Although adoptively transferred WT memory CD8+ T cells mediated protection against L. monocytogenes in either the WT or FasL mutant hosts, FasL mutant memory CD8+ T cells failed to mediate protection even in WT hosts. Thus, in individuals with mutation in Fas pathway, impairment in the function of the memory CD8+ T cells may increase their susceptibility to recurrent/latent infections. PMID:18292515

IgG1 memory B cells keep the memory of IgE responses.

PubMed

He, Jin-Shu; Subramaniam, Sharrada; Narang, Vipin; Srinivasan, Kandhadayar; Saunders, Sean P; Carbajo, Daniel; Wen-Shan, Tsao; Hidayah Hamadee, Nur; Lum, Josephine; Lee, Andrea; Chen, Jinmiao; Poidinger, Michael; Zolezzi, Francesca; Lafaille, Juan J; Curotto de Lafaille, Maria A

2017-09-21

The unique differentiation of IgE cells suggests unconventional mechanisms of IgE memory. IgE germinal centre cells are transient, most IgE cells are plasma cells, and high affinity IgE is produced by the switching of IgG1 cells to IgE. Here we investigate the function of subsets of IgG1 memory B cells in IgE production and find that two subsets of IgG1 memory B cells, CD80 + CD73 + and CD80 - CD73 - , contribute distinctively to the repertoires of high affinity pathogenic IgE and low affinity non-pathogenic IgE. Furthermore, repertoire analysis indicates that high affinity IgE and IgG1 plasma cells differentiate from rare CD80 + CD73 + high affinity memory clones without undergoing further mutagenesis. By identifying the cellular origin of high affinity IgE and the clonal selection of high affinity memory B cells into the plasma cell fate, our findings provide fundamental insights into the pathogenesis of allergies, and on the mechanisms of antibody production in memory B cell responses.IgE is an important mediator of protective immunity as well as allergic reaction, but how high affinity IgE antibodies are produced in memory responses is not clear. Here the authors show that IgE can be generated via class-switch recombination in IgG1 memory B cells without additional somatic hypermutation.

The CD8+ memory T-cell state of readiness is actively maintained and reversible

PubMed Central

Allam, Atef; Conze, Dietrich B.; Giardino Torchia, Maria Letizia; Munitic, Ivana; Yagita, Hideo; Sowell, Ryan T.; Marzo, Amanda L.

2009-01-01

The ability of the adaptive immune system to respond rapidly and robustly upon repeated antigen exposure is known as immunologic memory, and it is thought that acquisition of memory T-cell function is an irreversible differentiation event. In this study, we report that many phenotypic and functional characteristics of antigen-specific CD8 memory T cells are lost when they are deprived of contact with dendritic cells. Under these circumstances, memory T cells reverted from G1 to the G0 cell-cycle state and responded to stimulation like naive T cells, as assessed by proliferation, dependence upon costimulation, and interferon-γ production, without losing cell surface markers associated with memory. The memory state was maintained by signaling via members of the tumor necrosis factor receptor superfamily, CD27 and 4-1BB. Foxo1, a transcription factor involved in T-cell quiescence, was reduced in memory cells, and stimulation of naive CD8 cells via CD27 caused Foxo1 to be phosphorylated and emigrate from the nucleus in a phosphatidylinositol-3 kinase–dependent manner. Consistent with these results, maintenance of G1 in vivo was compromised in antigen-specific memory T cells in vesicular stomatitis virus-infected CD27-deficient mice. Therefore, sustaining the functional phenotype of T memory cells requires active signaling and maintenance. PMID:19617575

Regulation of humoral immunity by complement.

PubMed

Carroll, Michael C; Isenman, David E

2012-08-24

The complement system of innate immunity is important in regulating humoral immunity largely through the complement receptor CR2, which forms a coreceptor on B cells during antigen-induced activation. However, CR2 also retains antigens on follicular dendritic cells (FDCs). Display of antigen on FDCs is critical for clonal selection and affinity maturation of activated B cells. This review will discuss the role of complement in adaptive immunity in general with a focus on the interplay between CR2-associated antigen on B cells with CR2 expressed on FDCs. This latter interaction provides an opportunity for memory B cells to sample antigen over prolonged periods. The cocrystal structure of CR2 with its ligand C3d provides insight into how the complement system regulates access of antigen by B cells with implications for therapeutic manipulations to modulate aberrant B cell responses in the case of autoimmunity. Copyright © 2012 Elsevier Inc. All rights reserved.

Fencing direct memory access data transfers in a parallel active messaging interface of a parallel computer

DOEpatents

Blocksome, Michael A.; Mamidala, Amith R.

2013-09-03

Fencing direct memory access (`DMA`) data transfers in a parallel active messaging interface (`PAMI`) of a parallel computer, the PAMI including data communications endpoints, each endpoint including specifications of a client, a context, and a task, the endpoints coupled for data communications through the PAMI and through DMA controllers operatively coupled to segments of shared random access memory through which the DMA controllers deliver data communications deterministically, including initiating execution through the PAMI of an ordered sequence of active DMA instructions for DMA data transfers between two endpoints, effecting deterministic DMA data transfers through a DMA controller and a segment of shared memory; and executing through the PAMI, with no FENCE accounting for DMA data transfers, an active FENCE instruction, the FENCE instruction completing execution only after completion of all DMA instructions initiated prior to execution of the FENCE instruction for DMA data transfers between the two endpoints.

Fencing direct memory access data transfers in a parallel active messaging interface of a parallel computer

DOEpatents

Blocksome, Michael A; Mamidala, Amith R

2014-02-11

Fencing direct memory access (`DMA`) data transfers in a parallel active messaging interface (`PAMI`) of a parallel computer, the PAMI including data communications endpoints, each endpoint including specifications of a client, a context, and a task, the endpoints coupled for data communications through the PAMI and through DMA controllers operatively coupled to segments of shared random access memory through which the DMA controllers deliver data communications deterministically, including initiating execution through the PAMI of an ordered sequence of active DMA instructions for DMA data transfers between two endpoints, effecting deterministic DMA data transfers through a DMA controller and a segment of shared memory; and executing through the PAMI, with no FENCE accounting for DMA data transfers, an active FENCE instruction, the FENCE instruction completing execution only after completion of all DMA instructions initiated prior to execution of the FENCE instruction for DMA data transfers between the two endpoints.

The role of cytokines in T-cell memory in health and disease.

PubMed

Raeber, Miro E; Zurbuchen, Yves; Impellizzieri, Daniela; Boyman, Onur

2018-05-01

Upon stimulation with their cognate antigen, naive T cells undergo proliferation and differentiation into effector cells, followed by apoptosis or survival as precursors of long-lived memory cells. These phases of a T-cell response and the ensuing maintenance of memory T cells are shaped by cytokines, most notably interleukin-2 (IL-2), IL-7, and IL-15 that share the common γ chain (γ c ) cytokine receptor. Steady-state production of IL-7 and IL-15 is necessary for background proliferation and homeostatic survival of CD4 + and CD8 + memory T cells. During immune responses, augmented levels of IL-2, IL-15, IL-21, IL-12, IL-18, and type-I interferons determine the memory potential of antigen-specific effector CD8 + cells, while increased IL-2 and IL-15 cause bystander proliferation of heterologous CD4 + and CD8 + memory T cells. Limiting availability of γ c cytokines, reduction in regulatory T cells or IL-10, and persistence of inflammation or cognate antigen can result in memory T cells, which fail to become cytokine-dependent long-lived cells. Conversely, increased IL-7 and IL-15 can expand memory T cells, including pathogenic tissue-resident memory T cells, as seen in lymphopenia and certain chronic-inflammatory disorders and malignancies. These abovementioned factors impact immunotherapy and vaccines directed at memory T cells in cancer and chronic infection. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Akt signaling is critical for memory CD8+ T-cell development and tumor immune surveillance.

PubMed

Rogel, Anne; Willoughby, Jane E; Buchan, Sarah L; Leonard, Henry J; Thirdborough, Stephen M; Al-Shamkhani, Aymen

2017-02-14

Memory CD8 + T cells confer long-term immunity against tumors, and anticancer vaccines therefore should maximize their generation. Multiple memory CD8 + T-cell subsets with distinct functional and homing characteristics exist, but the signaling pathways that regulate their development are ill defined. Here we examined the role of the serine/threonine kinase Akt in the generation of protective immunity by CD8 + T cells. Akt is known to be activated by the T-cell antigen receptor and the cytokine IL-2, but its role in T-cell immunity in vivo has not been explored. Using CD8 + T cells from pdk1 K465E/K465E knockin mice, we found that decreased Akt activity inhibited the survival of T cells during the effector-to-memory cell transition and abolished their differentiation into C-X-C chemokine receptor 3 (CXCR3) lo CD43 lo effector-like memory cells. Consequently, antitumor immunity by CD8 + T cells that display defective Akt signaling was substantially diminished during the memory phase. Reduced memory T-cell survival and altered memory cell differentiation were associated with up-regulation of the proapoptotic protein Bim and the T-box transcription factor eomesodermin, respectively. These findings suggest an important role for effector-like memory CD8 + T cells in tumor immune surveillance and identify Akt as a key signaling node in the development of protective memory CD8 + T-cell responses.

Akt signaling is critical for memory CD8+ T-cell development and tumor immune surveillance

PubMed Central

Rogel, Anne; Willoughby, Jane E.; Buchan, Sarah L.; Leonard, Henry J.; Thirdborough, Stephen M.; Al-Shamkhani, Aymen

2017-01-01

Memory CD8+ T cells confer long-term immunity against tumors, and anticancer vaccines therefore should maximize their generation. Multiple memory CD8+ T-cell subsets with distinct functional and homing characteristics exist, but the signaling pathways that regulate their development are ill defined. Here we examined the role of the serine/threonine kinase Akt in the generation of protective immunity by CD8+ T cells. Akt is known to be activated by the T-cell antigen receptor and the cytokine IL-2, but its role in T-cell immunity in vivo has not been explored. Using CD8+ T cells from pdk1K465E/K465E knockin mice, we found that decreased Akt activity inhibited the survival of T cells during the effector-to-memory cell transition and abolished their differentiation into C-X-C chemokine receptor 3 (CXCR3)loCD43lo effector-like memory cells. Consequently, antitumor immunity by CD8+ T cells that display defective Akt signaling was substantially diminished during the memory phase. Reduced memory T-cell survival and altered memory cell differentiation were associated with up-regulation of the proapoptotic protein Bim and the T-box transcription factor eomesodermin, respectively. These findings suggest an important role for effector-like memory CD8+ T cells in tumor immune surveillance and identify Akt as a key signaling node in the development of protective memory CD8+ T-cell responses. PMID:28137869

Memory vs memory-like: The different facets of CD8+ T-cell memory in HCV infection.

PubMed

Hofmann, Maike; Wieland, Dominik; Pircher, Hanspeter; Thimme, Robert

2018-05-01

Memory CD8 + T cells are essential in orchestrating protection from re-infection. Hallmarks of virus-specific memory CD8 + T cells are the capacity to mount recall responses with rapid induction of effector cell function and antigen-independent survival. Growing evidence reveals that even chronic infection does not preclude virus-specific CD8 + T-cell memory formation. However, whether this kind of CD8 + T-cell memory that is established during chronic infection is indeed functional and provides protection from re-infection is still unclear. Human chronic hepatitis C virus infection represents a unique model system to study virus-specific CD8 + T-cell memory formation during and after cessation of persisting antigen stimulation. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Staging memory for massively parallel processor

NASA Technical Reports Server (NTRS)

Batcher, Kenneth E. (Inventor)

1988-01-01

The invention herein relates to a computer organization capable of rapidly processing extremely large volumes of data. A staging memory is provided having a main stager portion consisting of a large number of memory banks which are accessed in parallel to receive, store, and transfer data words simultaneous with each other. Substager portions interconnect with the main stager portion to match input and output data formats with the data format of the main stager portion. An address generator is coded for accessing the data banks for receiving or transferring the appropriate words. Input and output permutation networks arrange the lineal order of data into and out of the memory banks.

Development of highly reliable static random access memory for 40-nm embedded split gate-MONOS flash memory

NASA Astrophysics Data System (ADS)

Okamoto, Shin-ichi; Maekawa, Kei-ichi; Kawashima, Yoshiyuki; Shiba, Kazutoshi; Sugiyama, Hideki; Inoue, Masao; Nishida, Akio

2015-04-01

High quality static random access memory (SRAM) for 40-nm embedded MONOS flash memory with split gate (SG-MONOS) was developed. Marginal failure, which results in threshold voltage/drain current tailing and outliers of SRAM transistors, occurs when using a conventional SRAM structure. These phenomena can be explained by not only gate depletion but also partial depletion and percolation path formation in the MOS channel. A stacked poly-Si gate structure can suppress these phenomena and achieve high quality SRAM without any defects in the 6σ level and with high affinity to the 40-nm SG-MONOS process was developed.

Method for prefetching non-contiguous data structures

DOEpatents

Blumrich, Matthias A [Ridgefield, CT; Chen, Dong [Croton On Hudson, NY; Coteus, Paul W [Yorktown Heights, NY; Gara, Alan G [Mount Kisco, NY; Giampapa, Mark E [Irvington, NY; Heidelberger, Philip [Cortlandt Manor, NY; Hoenicke, Dirk [Ossining, NY; Ohmacht, Martin [Brewster, NY; Steinmacher-Burow, Burkhard D [Mount Kisco, NY; Takken, Todd E [Mount Kisco, NY; Vranas, Pavlos M [Bedford Hills, NY

2009-05-05

A low latency memory system access is provided in association with a weakly-ordered multiprocessor system. Each processor in the multiprocessor shares resources, and each shared resource has an associated lock within a locking device that provides support for synchronization between the multiple processors in the multiprocessor and the orderly sharing of the resources. A processor only has permission to access a resource when it owns the lock associated with that resource, and an attempt by a processor to own a lock requires only a single load operation, rather than a traditional atomic load followed by store, such that the processor only performs a read operation and the hardware locking device performs a subsequent write operation rather than the processor. A simple perfecting for non-contiguous data structures is also disclosed. A memory line is redefined so that in addition to the normal physical memory data, every line includes a pointer that is large enough to point to any other line in the memory, wherein the pointers to determine which memory line to prefect rather than some other predictive algorithm. This enables hardware to effectively prefect memory access patterns that are non-contiguous, but repetitive.

Human memory CD8 T cell effector potential is epigenetically preserved during in vivo homeostasis.

PubMed

Abdelsamed, Hossam A; Moustaki, Ardiana; Fan, Yiping; Dogra, Pranay; Ghoneim, Hazem E; Zebley, Caitlin C; Triplett, Brandon M; Sekaly, Rafick-Pierre; Youngblood, Ben

2017-06-05

Antigen-independent homeostasis of memory CD8 T cells is vital for sustaining long-lived T cell-mediated immunity. In this study, we report that maintenance of human memory CD8 T cell effector potential during in vitro and in vivo homeostatic proliferation is coupled to preservation of acquired DNA methylation programs. Whole-genome bisulfite sequencing of primary human naive, short-lived effector memory (T EM ), and longer-lived central memory (T CM ) and stem cell memory (T SCM ) CD8 T cells identified effector molecules with demethylated promoters and poised for expression. Effector-loci demethylation was heritably preserved during IL-7- and IL-15-mediated in vitro cell proliferation. Conversely, cytokine-driven proliferation of T CM and T SCM memory cells resulted in phenotypic conversion into T EM cells and was coupled to increased methylation of the CCR7 and Tcf7 loci. Furthermore, haploidentical donor memory CD8 T cells undergoing in vivo proliferation in lymphodepleted recipients also maintained their effector-associated demethylated status but acquired T EM -associated programs. These data demonstrate that effector-associated epigenetic programs are preserved during cytokine-driven subset interconversion of human memory CD8 T cells. © 2017 Abdelsamed et al.

CD4 T-Cell Memory Generation and Maintenance

PubMed Central

Gasper, David J.; Tejera, Melba Marie; Suresh, M.

2014-01-01

Immunologic memory is the adaptive immune system's powerful ability to remember a previous antigen encounter and react with accelerated vigor upon antigen re-exposure. It provides durable protection against reinfection with pathogens and is the foundation for vaccine-induced immunity. Unlike the relatively restricted immunologic purview of memory B cells and CD8 T cells, the field of CD4 T-cell memory must account for multiple distinct lineages with diverse effector functions, the issue of lineage commitment and plasticity, and the variable distribution of memory cells within each lineage. Here, we discuss the evidence for lineage-specific CD4 T-cell memory and summarize the known factors contributing to memory-cell generation, plasticity, and long-term maintenance. PMID:24940912

Making Physical Activity Accessible to Older Adults with Memory Loss: A Feasibility Study

ERIC Educational Resources Information Center

Logsdon, Rebecca G.; McCurry, Susan M.; Pike, Kenneth C.; Teri, Linda

2009-01-01

Purpose: For individuals with mild cognitive impairment (MCI), memory loss may prevent successful engagement in exercise, a key factor in preventing additional disability. The Resources and Activities for Life Long Independence (RALLI) program uses behavioral principles to make exercise more accessible for these individuals. Exercises are broken…

IL-15 regulates memory CD8+ T cell O-glycan synthesis and affects trafficking

PubMed Central

Nolz, Jeffrey C.; Harty, John T.

2014-01-01

Memory and naive CD8+ T cells exhibit distinct trafficking patterns. Specifically, memory but not naive CD8+ T cells are recruited to inflamed tissues in an antigen-independent manner. However, the molecular mechanisms that regulate memory CD8+ T cell trafficking are largely unknown. Here, using murine models of infection and T cell transfer, we found that memory but not naive CD8+ T cells dynamically regulate expression of core 2 O-glycans, which interact with P- and E-selectins to modulate trafficking to inflamed tissues. Following infection, antigen-specific effector CD8+ T cells strongly expressed core 2 O-glycans, but this glycosylation pattern was lost by most memory CD8+ T cells. After unrelated infection or inflammatory challenge, memory CD8+ T cells synthesized core 2 O-glycans independently of antigen restimulation. The presence of core 2 O-glycans subsequently directed these cells to inflamed tissue. Memory and naive CD8+ T cells exhibited the opposite pattern of epigenetic modifications at the Gcnt1 locus, which encodes the enzyme that initiates core 2 O-glycan synthesis. The open chromatin configuration in memory CD8+ T cells permitted de novo generation of core 2 O-glycans in a TCR-independent, but IL-15–dependent, manner. Thus, IL-15 stimulation promotes antigen-experienced memory CD8+ T cells to generate core 2 O-glycans, which subsequently localize them to inflamed tissues. These findings suggest that CD8+ memory T cell trafficking potentially can be manipulated to improve host defense and immunotherapy. PMID:24509081

Improving the performance of heterogeneous multi-core processors by modifying the cache coherence protocol

NASA Astrophysics Data System (ADS)

Fang, Juan; Hao, Xiaoting; Fan, Qingwen; Chang, Zeqing; Song, Shuying

2017-05-01

In the Heterogeneous multi-core architecture, CPU and GPU processor are integrated on the same chip, which poses a new challenge to the last-level cache management. In this architecture, the CPU application and the GPU application execute concurrently, accessing the last-level cache. CPU and GPU have different memory access characteristics, so that they have differences in the sensitivity of last-level cache (LLC) capacity. For many CPU applications, a reduced share of the LLC could lead to significant performance degradation. On the contrary, GPU applications can tolerate increase in memory access latency when there is sufficient thread-level parallelism. Taking into account the GPU program memory latency tolerance characteristics, this paper presents a method that let GPU applications can access to memory directly, leaving lots of LLC space for CPU applications, in improving the performance of CPU applications and does not affect the performance of GPU applications. When the CPU application is cache sensitive, and the GPU application is insensitive to the cache, the overall performance of the system is improved significantly.

A diary after dinner: How the time of event recording influences later accessibility of diary events.

PubMed

Szőllősi, Ágnes; Keresztes, Attila; Conway, Martin A; Racsmány, Mihály

2015-01-01

Recording the events of a day in a diary may help improve their later accessibility. An interesting question is whether improvements in long-term accessibility will be greater if the diary is completed at the end of the day, or after a period of sleep, the following morning. We investigated this question using an internet-based diary method. On each of five days, participants (n = 109) recorded autobiographical memories for that day or for the previous day. Recording took place either in the morning or in the evening. Following a 30-day retention interval, the diary events were free recalled. We found that participants who recorded their memories in the evening before sleep had best memory performance. These results suggest that the time of reactivation and recording of recent autobiographical events has a significant effect on the later accessibility of those diary events. We discuss our results in the light of related findings that show a beneficial effect of reduced interference during sleep on memory consolidation and reconsolidation.

Facial Expression Influences Face Identity Recognition During the Attentional Blink

PubMed Central

2014-01-01

Emotional stimuli (e.g., negative facial expressions) enjoy prioritized memory access when task relevant, consistent with their ability to capture attention. Whether emotional expression also impacts on memory access when task-irrelevant is important for arbitrating between feature-based and object-based attentional capture. Here, the authors address this question in 3 experiments using an attentional blink task with face photographs as first and second target (T1, T2). They demonstrate reduced neutral T2 identity recognition after angry or happy T1 expression, compared to neutral T1, and this supports attentional capture by a task-irrelevant feature. Crucially, after neutral T1, T2 identity recognition was enhanced and not suppressed when T2 was angry—suggesting that attentional capture by this task-irrelevant feature may be object-based and not feature-based. As an unexpected finding, both angry and happy facial expressions suppress memory access for competing objects, but only angry facial expression enjoyed privileged memory access. This could imply that these 2 processes are relatively independent from one another. PMID:25286076

Facial expression influences face identity recognition during the attentional blink.

PubMed

Bach, Dominik R; Schmidt-Daffy, Martin; Dolan, Raymond J

2014-12-01

Emotional stimuli (e.g., negative facial expressions) enjoy prioritized memory access when task relevant, consistent with their ability to capture attention. Whether emotional expression also impacts on memory access when task-irrelevant is important for arbitrating between feature-based and object-based attentional capture. Here, the authors address this question in 3 experiments using an attentional blink task with face photographs as first and second target (T1, T2). They demonstrate reduced neutral T2 identity recognition after angry or happy T1 expression, compared to neutral T1, and this supports attentional capture by a task-irrelevant feature. Crucially, after neutral T1, T2 identity recognition was enhanced and not suppressed when T2 was angry-suggesting that attentional capture by this task-irrelevant feature may be object-based and not feature-based. As an unexpected finding, both angry and happy facial expressions suppress memory access for competing objects, but only angry facial expression enjoyed privileged memory access. This could imply that these 2 processes are relatively independent from one another.

Event memory and moving in a well-known environment.

PubMed

Tamplin, Andrea K; Krawietz, Sabine A; Radvansky, Gabriel A; Copeland, David E

2013-11-01

Research in narrative comprehension has repeatedly shown that when people read about characters moving in well-known environments, the accessibility of object information follows a spatial gradient. That is, the accessibility of objects is best when they are in the same room as the protagonist, and it becomes worse the farther away they are see, e.g., Morrow, Greenspan, & Bower, (Journal of Memory and Language, 26, 165-187, 1987). In the present study, we assessed this finding using an interactive environment in which we had people memorize a map and navigate a virtual simulation of the area. During navigation, people were probed with pairs of object names and indicated whether both objects were in the same room. In contrast to the narrative studies described above, several experiments showed no evidence of a clear spatial gradient. Instead, memory for objects in currently occupied locations (e.g., the location room) was more accessible, especially after a small delay, but no clear decline was evident in the accessibility of information in memory with increased distance. Also, memory for objects along the pathway of movement (i.e., rooms that a person only passed through) showed a transitory suppression effect that was present immediately after movement, but attenuated over time. These results were interpreted in light of the event horizon model of event cognition.

The special role of item-context associations in the direct-access region of working memory.

PubMed

Campoy, Guillermo

2017-09-01

The three-embedded-component model of working memory (WM) distinguishes three representational states corresponding to three WM regions: activated long-term memory, direct-access region (DAR), and focus of attention. Recent neuroimaging research has revealed that access to the DAR is associated with enhanced hippocampal activity. Because the hippocampus mediates the encoding and retrieval of item-context associations, it has been suggested that this hippocampal activation is a consequence of the fact that item-context associations are particularly strong and accessible in the DAR. This study provides behavioral evidence for this view using an item-recognition task to assess the effect of non-intentional encoding and maintenance of item-location associations across WM regions. Five pictures of human faces were sequentially presented in different screen locations followed by a recognition probe. Visual cues immediately preceding the probe indicated the location thereof. When probe stimuli appeared in the same location that they had been presented within the memory set, the presentation of the cue was expected to elicit the activation of the corresponding WM representation through the just-established item-location association, resulting in faster recognition. Results showed this same-location effect, but only for items that, according to their serial position within the memory set, were held in the DAR.

A Calendar Savant with Episodic Memory Impairments

PubMed Central

Olson, Ingrid R.; Berryhill, Marian E.; Drowos, David B.; Brown, Lawrence; Chatterjee, Anjan

2010-01-01

Patients with memory disorders have severely restricted learning and memory. For instance, patients with anterograde amnesia can learn motor procedures as well as retaining some restricted ability to learn new words and factual information. However, such learning is inflexible and frequently inaccessible to conscious awareness. Here we present a case of patient AC596, a 25-year old male with severe episodic memory impairments, presumably due to anoxia during a preterm birth. In contrast to his poor episodic memory, he exhibits savant-like memory for calendar information that can be flexibly accessed by day, month, and year cues. He also has the ability to recollect the exact date of a wide range of personal experiences over the past 20 years. The patient appears to supplement his generally poor episodic memory by using memorized calendar information as a retrieval cue for autobiographical events. These findings indicate that islands of preserved memory functioning, such as a highly developed semantic memory system, can exist in individuals with severely impaired episodic memory systems. In this particular case, our patient’s memory for dates far outstripped that of normal individuals and served as a keen retrieval cue, allowing him to access information that was otherwise unavailable. PMID:20104390

Neural Correlates of Conceptual Implicit Memory and Their Contamination of Putative Neural Correlates of Explicit Memory

ERIC Educational Resources Information Center

Voss, Joel L.; Paller, Ken A.

2007-01-01

During episodic recognition tests, meaningful stimuli such as words can engender both conscious retrieval (explicit memory) and facilitated access to meaning that is distinct from the awareness of remembering (conceptual implicit memory). Neuroimaging investigations of one type of memory are frequently subject to the confounding influence of the…

Improving memory after interruption: exploiting soft constraints and manipulating information access cost.

PubMed

Morgan, Phillip L; Patrick, John; Waldron, Samuel M; King, Sophia L; Patrick, Tanya

2009-12-01

Forgetting what one was doing prior to interruption is an everyday problem. The recent soft constraints hypothesis (Gray, Sims, Fu, & Schoelles, 2006) emphasizes the strategic adaptation of information processing strategy to the task environment. It predicts that increasing information access cost (IAC: the time, and physical and mental effort involved in accessing information) encourages a more memory-intensive strategy. Like interruptions, access costs are also intrinsic to most work environments, such as when opening documents and e-mails. Three experiments investigated whether increasing IAC during a simple copying task can be an effective method for reducing forgetting following interruption. IAC was designated Low (all information permanently visible), Medium (a mouse movement to uncover target information), or High (an additional few seconds to uncover such information). Experiment 1 found that recall improved across all three levels of IAC. Subsequent experiments found that High IAC facilitated resumption after interruption, particularly when interruption occurred on half of all trials (Experiment 2), and improved prospective memory following two different interrupting tasks, even when one involved the disruptive effect of using the same type of resource as the primary task (Experiment 3). The improvement of memory after interruption with increased IAC supports the prediction of the soft constraints hypothesis. The main disadvantage of a high access cost was a reduction in speed of task completion. The practicality of manipulating IAC as a design method for inducing a memory-intensive strategy to protect against forgetting is discussed. Copyright 2009 APA

Electrical Evaluation of RCA MWS5501D Random Access Memory, Volume 2, Appendix a

NASA Technical Reports Server (NTRS)

Klute, A.

1979-01-01

The electrical characterization and qualification test results are presented for the RCA MWS5001D random access memory. The tests included functional tests, AC and DC parametric tests, AC parametric worst-case pattern selection test, determination of worst-case transition for setup and hold times, and a series of schmoo plots. The address access time, address readout time, the data hold time, and the data setup time are some of the results surveyed.

An Account of Performance in Accessing Information Stored in Long-Term Memory. A Fixed-Links Model Approach

ERIC Educational Resources Information Center

Altmeyer, Michael; Schweizer, Karl; Reiss, Siegbert; Ren, Xuezhu; Schreiner, Michael

2013-01-01

Performance in working memory and short-term memory tasks was employed for predicting performance in a long-term memory task in order to find out about the underlying processes. The types of memory were represented by versions of the Posner Task, the Backward Counting Task and the Sternberg Task serving as measures of long-term memory, working…

A new non-destructive readout by using photo-recovered surface potential contrast

NASA Astrophysics Data System (ADS)

Wang, Le; Jin, Kui-Juan; Gu, Jun-Xing; Ma, Chao; He, Xu; Zhang, Jiandi; Wang, Can; Feng, Yu; Wan, Qian; Shi, Jin-An; Gu, Lin; He, Meng; Lu, Hui-Bin; Yang, Guo-Zhen

2014-11-01

Ferroelectric random access memory is still challenging in the feature of combination of room temperature stability, non-destructive readout and high intensity storage. As a non-contact and non-destructive information readout method, surface potential has never been paid enough attention because of the unavoidable decay of the surface potential contrast between oppositely polarized domains. That is mainly due to the recombination of the surface movable charges around the domain walls. Here, by introducing a laser beam into the combination of piezoresponse force microscopy and Kelvin probe force microscopy, we demonstrate that the surface potential contrast of BiFeO3 films can be recovered under light illumination. The recovering mechanism is understood based on the redistribution of the photo-induced charges driven by the internal electric field. Furthermore, we have created a 12-cell memory pattern based on BiFeO3 films to show the feasibility of such photo-assisted non-volatile and non-destructive readout of the ferroelectric memory.

Tracing the time course of picture--word processing.

PubMed

Smith, M C; Magee, L E

1980-12-01

A number of independent lines of research have suggested that semantic and articulatory information become available differentially from pictures and words. The first of the experiments reported here sought to clarify the time course by which information about pictures and words becomes available by considering the pattern of interference generated when incongruent pictures and words are presented simultaneously in a Stroop-like situation. Previous investigators report that picture naming is easily disrupted by the presence of a distracting word but that word naming is relatively immune to interference from an incongruent picture. Under the assumption that information available from a completed process may disrupt an ongoing process, these results suggest that words access articulatory information more rapidly than do pictures. Experiment 1 extended this paradigm by requiring subjects to verify the category of the target stimulus. In accordance with the hypothesis that picture access the semantic code more rapidly than words, there was a reversal in the interference pattern: Word categorization suffered considerable disruption, whereas picture categorization was minimally affected by the presence of an incongruent word. Experiment 2 sought to further test the hypothesis that access to semantic and articulatory codes is different for pictures and words by examining memory for those items following naming or categorization. Categorized words were better recognized than named words, whereas the reverse was true for pictures, a result which suggests that picture naming involves more extensive processing than picture categorization. Experiment 3 replicated this result under conditions in which viewing time was held constant. The last experiment extended the investigation of memory differences to a situation in which subjects were required to generate the superordinate category name. Here, memory for categorized pictures was as good as memory for named pictures. Category generation also influenced memory for words, memory performance being superior to that following a yes--no verification of category membership. These experiments suggest a model of information access whereby pictures access semantic information were readily than name information, with the reverse being true for words. Memory for both pictures and words was a function of the amount of processing required to access a particular type of information as well as the extent of response differentiation necessitated by the task.

Enhancement of Immune Memory Responses to Respiratory Infection

DTIC Science & Technology

2017-08-01

induction of highly specific B and T cell responses against viral infections. Despite recent progress in vaccine development, the molecular mechanisms...highly expressed in memory B cells in mice, and Atg7 is required for maintenance of long-term memory B cells needed to protect against influenza...infection. Human influenza-specific memory B cells also have high levels of autophagy, but whether autophagy protects memory B cell survival in humans

Allograft dendritic cell p40 homodimers activate donor-reactive memory CD8+ T cells

PubMed Central

Tsuda, Hidetoshi; Su, Charles A.; Tanaka, Toshiaki; Ayasoufi, Katayoun; Min, Booki; Valujskikh, Anna; Fairchild, Robert L.

2018-01-01

Recipient endogenous memory T cells with donor reactivity pose an important barrier to successful transplantation and costimulatory blockade–induced graft tolerance. Longer ischemic storage times prior to organ transplantation increase early posttransplant inflammation and negatively impact early graft function and long-term graft outcome. Little is known about the mechanisms enhancing endogenous memory T cell activation to mediate tissue injury within the increased inflammatory environment of allografts subjected to prolonged cold ischemic storage (CIS). Endogenous memory CD4+ and CD8+ T cell activation is markedly increased within complete MHC-mismatched cardiac allografts subjected to prolonged versus minimal CIS, and the memory CD8+ T cells directly mediate CTLA-4Ig–resistant allograft rejection. Memory CD8+ T cell activation within allografts subjected to prolonged CIS requires memory CD4+ T cell stimulation of graft DCs to produce p40 homodimers, but not IL-12 p40/p35 heterodimers. Targeting p40 abrogates memory CD8+ T cell proliferation within the allografts and their ability to mediate CTLA-4Ig–resistant allograft rejection. These findings indicate a critical role for memory CD4+ T cell–graft DC interactions to increase the intensity of endogenous memory CD8+ T cell activation needed to mediate rejection of higher-risk allografts subjected to increased CIS. PMID:29467328

Pregnancy persistently affects memory T cell populations.

PubMed

Kieffer, Tom E C; Faas, Marijke M; Scherjon, Sicco A; Prins, Jelmer R

2017-02-01

Pregnancy is an immune challenge to the maternal immune system. The effects of pregnancy on maternal immunity and particularly on memory T cells during and after pregnancy are not fully known. This observational study aims to show the short term and the long term effects of pregnancy on the constitution, size and activation status of peripheral human memory T-lymphocyte populations. Effector memory (EM) and central memory (CM) T-lymphocytes were analyzed using flow cytometry of peripheral blood from 14 nulligravid, 12 primigravid and 15 parous women that were on average 18 months postpartum. The short term effects were shown by the significantly higher CD4+ EM cell and activated CD4+ memory cell proportions in primigravid women compared to nulligravid women. The persistent effects found in this study were the significantly higher proportions of CD4+ EM, CD4+ CM and activated memory T cells in parous women compared to nulligravid women. In contrast to CD4+ cells, activation status of CD8+ memory cells did not differ between the groups. This study shows that pregnancy persistently affects the pre-pregnancy CD4+ memory cell pool in human peripheral blood. During pregnancy, CD4+ T-lymphocytes might differentiate into EM cells followed by persistent higher proportions of CD4+ CM and EM cells postpartum. The persistent effects of pregnancy on memory T cells found in this study support the hypothesis that memory T cells are generated during pregnancy and that these cells could be involved in the lower complication risks in multiparous pregnancies in humans. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Development of memory CD8+ T cells and their recall responses during blood-stage infection with Plasmodium berghei ANKA.

PubMed

Miyakoda, Mana; Kimura, Daisuke; Honma, Kiri; Kimura, Kazumi; Yuda, Masao; Yui, Katsuyuki

2012-11-01

Conditions required for establishing protective immune memory vary depending on the infecting microbe. Although the memory immune response against malaria infection is generally thought to be relatively slow to develop and can be lost rapidly, experimental evidence is insufficient. In this report, we investigated the generation, maintenance, and recall responses of Ag-specific memory CD8(+) T cells using Plasmodium berghei ANKA expressing OVA (PbA-OVA) as a model system. Mice were transferred with OVA-specific CD8(+) T (OT-I) cells and infected with PbA-OVA or control Listeria monocytogenes expressing OVA (LM-OVA). Central memory type OT-I cells were maintained for >2 mo postinfection and recovery from PbA-OVA. Memory OT-I cells produced IFN-γ as well as TNF-α upon activation and were protective against challenge with a tumor expressing OVA, indicating that functional memory CD8(+) T cells can be generated and maintained postinfection with P. berghei ANKA. Cotransfer of memory OT-I cells with naive OT-I cells to mice followed by infection with PbA-OVA or LM-OVA revealed that clonal expansion of memory OT-I cells was limited during PbA-OVA infection compared with expansion of naive OT-I cells, whereas it was more rapid during LM-OVA infection. The expression of inhibitory receptors programmed cell death-1 and LAG-3 was higher in memory-derived OT-I cells than naive-derived OT-I cells during infection with PbA-OVA. These results suggest that memory CD8(+) T cells can be established postinfection with P. berghei ANKA, but their recall responses during reinfection are more profoundly inhibited than responses of naive CD8(+) T cells.

Hoxb4 overexpression in CD4 memory phenotype T cells increases the central memory population upon homeostatic proliferation.

PubMed

Frison, Héloïse; Giono, Gloria; Thébault, Paméla; Fournier, Marilaine; Labrecque, Nathalie; Bijl, Janet J

2013-01-01

Memory T cell populations allow a rapid immune response to pathogens that have been previously encountered and thus form the basis of success in vaccinations. However, the molecular pathways underlying the development and maintenance of these cells are only starting to be unveiled. Memory T cells have the capacity to self renew as do hematopoietic stem cells, and overlapping gene expression profiles suggested that these cells might use the same self-renewal pathways. The transcription factor Hoxb4 has been shown to promote self-renewal divisions of hematopoietic stem cells resulting in an expansion of these cells. In this study we investigated whether overexpression of Hoxb4 could provide an advantage to CD4 memory phenotype T cells in engrafting the niche of T cell deficient mice following adoptive transfer. Competitive transplantation experiments demonstrated that CD4 memory phenotype T cells derived from mice transgenic for Hoxb4 contributed overall less to the repopulation of the lymphoid organs than wild type CD4 memory phenotype T cells after two months. These proportions were relatively maintained following serial transplantation in secondary and tertiary mice. Interestingly, a significantly higher percentage of the Hoxb4 CD4 memory phenotype T cell population expressed the CD62L and Ly6C surface markers, characteristic for central memory T cells, after homeostatic proliferation. Thus Hoxb4 favours the maintenance and increase of the CD4 central memory phenotype T cell population. These cells are more stem cell like and might eventually lead to an advantage of Hoxb4 T cells after subjecting the cells to additional rounds of proliferation.

Silent memory engrams as the basis for retrograde amnesia

PubMed Central

Roy, Dheeraj S.; Muralidhar, Shruti; Smith, Lillian M.

2017-01-01

Recent studies identified neuronal ensembles and circuits that hold specific memory information (memory engrams). Memory engrams are retained under protein synthesis inhibition-induced retrograde amnesia. These engram cells can be activated by optogenetic stimulation for full-fledged recall, but not by stimulation using natural recall cues (thus, amnesia). We call this state of engrams “silent engrams” and the cells bearing them “silent engram cells.” The retention of memory information under amnesia suggests that the time-limited protein synthesis following learning is dispensable for memory storage, but may be necessary for effective memory retrieval processes. Here, we show that the full-fledged optogenetic recall persists at least 8 d after learning under protein synthesis inhibition-induced amnesia. This long-term retention of memory information correlates with equally persistent retention of functional engram cell-to-engram cell connectivity. Furthermore, inactivation of the connectivity of engram cell ensembles with its downstream counterparts, but not upstream ones, prevents optogenetic memory recall. Consistent with the previously reported lack of retention of augmented synaptic strength and reduced spine density in silent engram cells, optogenetic memory recall under amnesia is stimulation strength-dependent, with low-power stimulation eliciting only partial recall. Finally, the silent engram cells can be converted to active engram cells by overexpression of α-p-21–activated kinase 1, which increases spine density in engram cells. These results indicate that memory information is retained in a form of silent engram under protein synthesis inhibition-induced retrograde amnesia and support the hypothesis that memory is stored as the specific connectivity between engram cells. PMID:29078397

Silent memory engrams as the basis for retrograde amnesia.

PubMed

Roy, Dheeraj S; Muralidhar, Shruti; Smith, Lillian M; Tonegawa, Susumu

2017-11-14

Recent studies identified neuronal ensembles and circuits that hold specific memory information (memory engrams). Memory engrams are retained under protein synthesis inhibition-induced retrograde amnesia. These engram cells can be activated by optogenetic stimulation for full-fledged recall, but not by stimulation using natural recall cues (thus, amnesia). We call this state of engrams "silent engrams" and the cells bearing them "silent engram cells." The retention of memory information under amnesia suggests that the time-limited protein synthesis following learning is dispensable for memory storage, but may be necessary for effective memory retrieval processes. Here, we show that the full-fledged optogenetic recall persists at least 8 d after learning under protein synthesis inhibition-induced amnesia. This long-term retention of memory information correlates with equally persistent retention of functional engram cell-to-engram cell connectivity. Furthermore, inactivation of the connectivity of engram cell ensembles with its downstream counterparts, but not upstream ones, prevents optogenetic memory recall. Consistent with the previously reported lack of retention of augmented synaptic strength and reduced spine density in silent engram cells, optogenetic memory recall under amnesia is stimulation strength-dependent, with low-power stimulation eliciting only partial recall. Finally, the silent engram cells can be converted to active engram cells by overexpression of α-p-21-activated kinase 1, which increases spine density in engram cells. These results indicate that memory information is retained in a form of silent engram under protein synthesis inhibition-induced retrograde amnesia and support the hypothesis that memory is stored as the specific connectivity between engram cells.

Pathogen stimulation history impacts donor-specific CD8+ T cell susceptibility to costimulation/integrin blockade-based therapy

PubMed Central

Badell, IR; Kitchens, WH; Wagener, ME; Lukacher, AE; Larsen, CP; Ford, ML

2017-01-01

Recent studies have shown that the quantity of donor-reactive memory T cells is an important factor in determining the relative heterologous immunity barrier posed during transplantation. Here, we hypothesized that the quality of T cell memory also potently influences the response to costimulation blockade-based immunosuppression. Using a murine skin graft model of CD8+ memory T cell-mediated costimulation blockade resistance, we elicited donor-reactive memory T cells using three distinct types of pathogen infections. Strikingly, we observed differential efficacy of a costimulation and integrin blockade regimen based on the type of pathogen used to elicit the donor-reactive memory T cell response. Intriguingly, the most immunosuppression-sensitive memory T cell populations were composed primarily of central memory cells that possessed greater recall potential, exhibited a less differentiated phenotype, and contained more multi-cytokine producers. These data therefore demonstrate that the memory T cell barrier is dependent on the specific type of pathogen infection via which the donor-reactive memory T cells are elicited, and suggest that the immune stimulation history of a given transplant patient may profoundly influence the relative barrier posed by heterologous immunity during transplantation. PMID:26228897

A Memory B Cell Crossmatch Assay for Quantification of Donor-Specific Memory B Cells in the Peripheral Blood of HLA-Immunized Individuals.

PubMed

Karahan, G E; de Vaal, Y J H; Krop, J; Wehmeier, C; Roelen, D L; Claas, F H J; Heidt, S

2017-10-01

Humoral responses against mismatched donor HLA are routinely measured as serum HLA antibodies, which are mainly produced by bone marrow-residing plasma cells. Individuals with a history of alloimmunization but lacking serum antibodies may harbor circulating dormant memory B cells, which may rapidly become plasma cells on antigen reencounter. Currently available methods to detect HLA-specific memory B cells are scarce and insufficient in quantifying the complete donor-specific memory B cell response due to their dependence on synthetic HLA molecules. We present a highly sensitive and specific tool for quantifying donor-specific memory B cells in peripheral blood of individuals using cell lysates covering the complete HLA class I and class II repertoire of an individual. Using this enzyme-linked immunospot (ELISpot) assay, we found a median frequency of 31 HLA class I and 89 HLA class II-specific memory B cells per million IgG-producing cells directed at paternal HLA in peripheral blood samples from women (n = 22) with a history of pregnancy, using cell lysates from spouses. The donor-specific memory B cell ELISpot can be used in HLA diagnostic laboratories as a cross-match assay to quantify donor-specific memory B cells in patients with a history of sensitizing events. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

A ketogenic diet rescues hippocampal memory defects in a mouse model of Kabuki syndrome.

PubMed

Benjamin, Joel S; Pilarowski, Genay O; Carosso, Giovanni A; Zhang, Li; Huso, David L; Goff, Loyal A; Vernon, Hilary J; Hansen, Kasper D; Bjornsson, Hans T

2017-01-03

Kabuki syndrome is a Mendelian intellectual disability syndrome caused by mutations in either of two genes (KMT2D and KDM6A) involved in chromatin accessibility. We previously showed that an agent that promotes chromatin opening, the histone deacetylase inhibitor (HDACi) AR-42, ameliorates the deficiency of adult neurogenesis in the granule cell layer of the dentate gyrus and rescues hippocampal memory defects in a mouse model of Kabuki syndrome (Kmt2d +/βGeo ). Unlike a drug, a dietary intervention could be quickly transitioned to the clinic. Therefore, we have explored whether treatment with a ketogenic diet could lead to a similar rescue through increased amounts of beta-hydroxybutyrate, an endogenous HDACi. Here, we report that a ketogenic diet in Kmt2d +/βGeo mice modulates H3ac and H3K4me3 in the granule cell layer, with concomitant rescue of both the neurogenesis defect and hippocampal memory abnormalities seen in Kmt2d +/βGeo mice; similar effects on neurogenesis were observed on exogenous administration of beta-hydroxybutyrate. These data suggest that dietary modulation of epigenetic modifications through elevation of beta-hydroxybutyrate may provide a feasible strategy to treat the intellectual disability seen in Kabuki syndrome and related disorders.

Protective Capacity of Memory CD8+ T Cells is Dictated by Antigen Exposure History and Nature of the Infection

PubMed Central

Nolz, Jeffrey C.; Harty, John T.

2011-01-01

SUMMARY Infection or vaccination confers heightened resistance to pathogen re-challenge due to quantitative and qualitative differences between naïve and primary memory T cells. Herein, we show that secondary (boosted) memory CD8+ T cells were better than primary memory CD8+ T cells in controlling some, but not all acute infections with diverse pathogens. However, secondary memory CD8+ T cells were less efficient than an equal number of primary memory cells at preventing chronic LCMV infection and are more susceptible to functional exhaustion. Importantly, localization of memory CD8+ T cells within lymph nodes, which is reduced by antigen re-stimulation, was critical for both viral control in lymph nodes and for the sustained CD8+ T cell response required to prevent chronic LCMV infection. Thus, repeated antigen-stimulation shapes memory CD8+ T cell populations to either enhance or decrease per cell protective immunity in a pathogen-specific manner, a concept of importance in vaccine design against specific diseases. PMID:21549619

Induction and Maintenance of CX3CR1-Intermediate Peripheral Memory CD8+ T Cells by Persistent Viruses and Vaccines.

PubMed

Gordon, Claire Louse; Lee, Lian Ni; Swadling, Leo; Hutchings, Claire; Zinser, Madeleine; Highton, Andrew John; Capone, Stefania; Folgori, Antonella; Barnes, Eleanor; Klenerman, Paul

2018-04-17

The induction and maintenance of T cell memory is critical to the success of vaccines. A recently described subset of memory CD8 + T cells defined by intermediate expression of the chemokine receptor CX3CR1 was shown to have self-renewal, proliferative, and tissue-surveillance properties relevant to vaccine-induced memory. We tracked these cells when memory is sustained at high levels: memory inflation induced by cytomegalovirus (CMV) and adenovirus-vectored vaccines. In mice, both CMV and vaccine-induced inflationary T cells showed sustained high levels of CX3R1 int cells exhibiting an effector-memory phenotype, characteristic of inflationary pools, in early memory. In humans, CX3CR1 int CD8 + T cells were strongly induced following adenovirus-vectored vaccination for hepatitis C virus (HCV) (ChAd3-NSmut) and during natural CMV infection and were associated with a memory phenotype similar to that in mice. These data indicate that CX3CR1 int cells form an important component of the memory pool in response to persistent viruses and vaccines in both mice and humans. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Identification of Nascent Memory CD8 T Cells and Modeling of Their Ontogeny.

PubMed

Crauste, Fabien; Mafille, Julien; Boucinha, Lilia; Djebali, Sophia; Gandrillon, Olivier; Marvel, Jacqueline; Arpin, Christophe

2017-03-22

Primary immune responses generate short-term effectors and long-term protective memory cells. The delineation of the genealogy linking naive, effector, and memory cells has been complicated by the lack of phenotypes discriminating effector from memory differentiation stages. Using transcriptomics and phenotypic analyses, we identify Bcl2 and Mki67 as a marker combination that enables the tracking of nascent memory cells within the effector phase. We then use a formal approach based on mathematical models describing the dynamics of population size evolution to test potential progeny links and demonstrate that most cells follow a linear naive→early effector→late effector→memory pathway. Moreover, our mathematical model allows long-term prediction of memory cell numbers from a few early experimental measurements. Our work thus provides a phenotypic means to identify effector and memory cells, as well as a mathematical framework to investigate their genealogy and to predict the outcome of immunization regimens in terms of memory cell numbers generated. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Studies on B-cell memory. III. T-dependent aspect of B memory generation in mice immunized with T-independent type-2(TI-2) antigen.

PubMed

Hosokawa, T; Tanaka, Y; Aoike, A; Kawai, K; Muramatsu, S

1984-09-01

The time course of B-cell memory development to a dinitrophenyl (DNP) T-independent type-2 (TI-2) antigen was investigated by adoptive cell transfer. Strong IgM and IgG memory developed in BALB/c mice after immunization with DNP-dextran, to be recalled by challenge with either T-dependent (TD) antigen or TI-2 antigen. However, only weak IgM memory and very feeble IgG memory were detected in athymic nude mice receiving the same immunization as euthymic mice. Once memory was established under probable T cell influence, its recall by TI-2 antigen challenge seemed independent of T cell help and did not require sharing of carriers between priming and challenge antigens. The following may be concluded. (i) Long-term IgM and IgG memory is induced by TI-2 antigen priming in the presence of functional T cells. (ii) The class switch from IgM to IgG in the memory B cell pool is driven effectively by TI-2 antigen and is probably T cell-dependent.

Review of optical memory technologies

NASA Technical Reports Server (NTRS)

Chen, D.

1972-01-01

Optical technologies for meeting the demands of large capacity fast access time memory are discussed in terms of optical phenomena and laser applications. The magneto-optic and electro-optic approaches are considered to be the most promising memory approaches.

Optical interconnection network for parallel access to multi-rank memory in future computing systems.

PubMed

Wang, Kang; Gu, Huaxi; Yang, Yintang; Wang, Kun

2015-08-10

With the number of cores increasing, there is an emerging need for a high-bandwidth low-latency interconnection network, serving core-to-memory communication. In this paper, aiming at the goal of simultaneous access to multi-rank memory, we propose an optical interconnection network for core-to-memory communication. In the proposed network, the wavelength usage is delicately arranged so that cores can communicate with different ranks at the same time and broadcast for flow control can be achieved. A distributed memory controller architecture that works in a pipeline mode is also designed for efficient optical communication and transaction address processes. The scaling method and wavelength assignment for the proposed network are investigated. Compared with traditional electronic bus-based core-to-memory communication, the simulation results based on the PARSEC benchmark show that the bandwidth enhancement and latency reduction are apparent.

Three-dimensional magnetic bubble memory system

NASA Technical Reports Server (NTRS)

Stadler, Henry L. (Inventor); Katti, Romney R. (Inventor); Wu, Jiin-Chuan (Inventor)

1994-01-01

A compact memory uses magnetic bubble technology for providing data storage. A three-dimensional arrangement, in the form of stacks of magnetic bubble layers, is used to achieve high volumetric storage density. Output tracks are used within each layer to allow data to be accessed uniquely and unambiguously. Storage can be achieved using either current access or field access magnetic bubble technology. Optical sensing via the Faraday effect is used to detect data. Optical sensing facilitates the accessing of data from within the three-dimensional package and lends itself to parallel operation for supporting high data rates and vector and parallel processing.

Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory

PubMed Central

Kaji, Tomohiro; Ishige, Akiko; Hikida, Masaki; Taka, Junko; Hijikata, Atsushi; Kubo, Masato; Nagashima, Takeshi; Takahashi, Yoshimasa; Kurosaki, Tomohiro; Okada, Mariko; Ohara, Osamu

2012-01-01

One component of memory in the antibody system is long-lived memory B cells selected for the expression of somatically mutated, high-affinity antibodies in the T cell–dependent germinal center (GC) reaction. A puzzling observation has been that the memory B cell compartment also contains cells expressing unmutated, low-affinity antibodies. Using conditional Bcl6 ablation, we demonstrate that these cells are generated through proliferative expansion early after immunization in a T cell–dependent but GC-independent manner. They soon become resting and long-lived and display a novel distinct gene expression signature which distinguishes memory B cells from other classes of B cells. GC-independent memory B cells are later joined by somatically mutated GC descendants at roughly equal proportions and these two types of memory cells efficiently generate adoptive secondary antibody responses. Deletion of T follicular helper (Tfh) cells significantly reduces the generation of mutated, but not unmutated, memory cells early on in the response. Thus, B cell memory is generated along two fundamentally distinct cellular differentiation pathways. One pathway is dedicated to the generation of high-affinity somatic antibody mutants, whereas the other preserves germ line antibody specificities and may prepare the organism for rapid responses to antigenic variants of the invading pathogen. PMID:23027924

Is There Natural Killer Cell Memory and Can It Be Harnessed by Vaccination? Vaccination Strategies Based on NK Cell and ILC Memory.

PubMed

Cooper, Megan A; Fehniger, Todd A; Colonna, Marco

2017-12-18

Studies over the last decade have decisively shown that innate immune natural killer (NK) cells exhibit enhanced long-lasting functional responses following a single activation event. With the increased recognition of memory and memory-like properties of NK cells, questions have arisen with regard to their ability to effectively mediate vaccination responses in humans. Moreover, recently discovered innate lymphoid cells (ILCs) could also potentially exhibit memory-like functions. Here, we review different forms of NK cell memory, and speculate about the ability of these cells and ILCs to meaningfully contribute to vaccination responses. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

An engram found? Evaluating the evidence from fruit flies.

PubMed

Gerber, Bertram; Tanimoto, Hiromu; Heisenberg, Martin

2004-12-01

Is it possible to localize a memory trace to a subset of cells in the brain? If so, it should be possible to show: first, that neuronal plasticity occurs in these cells. Second, that neuronal plasticity in these cells is sufficient for memory. Third, that neuronal plasticity in these cells is necessary for memory. Fourth, that memory is abolished if these cells cannot provide output during testing. And fifth, that memory is abolished if these cells cannot receive input during training. With regard to olfactory learning in flies, we argue that the notion of the olfactory memory trace being localized to the Kenyon cells of the mushroom bodies is a reasonable working hypothesis.

Perpetual Model Validation

DTIC Science & Technology

2017-03-01

models of software execution, for example memory access patterns, to check for security intrusions. Additional research was performed to tackle the...considered using indirect models of software execution, for example memory access patterns, to check for security intrusions. Additional research ...deterioration for example , no longer corresponds to the model used during verification time. Finally, the research looked at ways to combine hybrid systems

Design of Unstructured Adaptive (UA) NAS Parallel Benchmark Featuring Irregular, Dynamic Memory Accesses

NASA Technical Reports Server (NTRS)

Feng, Hui-Yu; VanderWijngaart, Rob; Biswas, Rupak; Biegel, Bryan (Technical Monitor)

2001-01-01

We describe the design of a new method for the measurement of the performance of modern computer systems when solving scientific problems featuring irregular, dynamic memory accesses. The method involves the solution of a stylized heat transfer problem on an unstructured, adaptive grid. A Spectral Element Method (SEM) with an adaptive, nonconforming mesh is selected to discretize the transport equation. The relatively high order of the SEM lowers the fraction of wall clock time spent on inter-processor communication, which eases the load balancing task and allows us to concentrate on the memory accesses. The benchmark is designed to be three-dimensional. Parallelization and load balance issues of a reference implementation will be described in detail in future reports.

Ventromedial prefrontal cortex pyramidal cells have a temporal dynamic role in recall and extinction of cocaine-associated memory.

PubMed

Van den Oever, Michel C; Rotaru, Diana C; Heinsbroek, Jasper A; Gouwenberg, Yvonne; Deisseroth, Karl; Stuber, Garret D; Mansvelder, Huibert D; Smit, August B

2013-11-13

In addicts, associative memories related to the rewarding effects of drugs of abuse can evoke powerful craving and drug seeking urges, but effective treatment to suppress these memories is not available. Detailed insight into the neural circuitry that mediates expression of drug-associated memory is therefore of crucial importance. Substantial evidence from rodent models of addictive behavior points to the involvement of the ventromedial prefrontal cortex (vmPFC) in conditioned drug seeking, but specific knowledge of the temporal role of vmPFC pyramidal cells is lacking. To this end, we used an optogenetics approach to probe the involvement of vmPFC pyramidal cells in expression of a recent and remote conditioned cocaine memory. In mice, we expressed Channelrhodopsin-2 (ChR2) or Halorhodopsin (eNpHR3.0) in pyramidal cells of the vmPFC and studied the effect of activation or inhibition of these cells during expression of a cocaine-contextual memory on days 1-2 (recent) and ∼3 weeks (remote) after conditioning. Whereas optical activation of pyramidal cells facilitated extinction of remote memory, without affecting recent memory, inhibition of pyramidal cells acutely impaired recall of recent cocaine memory, without affecting recall of remote memory. In addition, we found that silencing pyramidal cells blocked extinction learning at the remote memory time-point. We provide causal evidence of a critical time-dependent switch in the contribution of vmPFC pyramidal cells to recall and extinction of cocaine-associated memory, indicating that the circuitry that controls expression of cocaine memories reorganizes over time.

A Pilot Memory Café for People with Learning Disabilities and Memory Difficulties

ERIC Educational Resources Information Center

Kiddle, Hannah; Drew, Neil; Crabbe, Paul; Wigmore, Jonathan

2016-01-01

Memory cafés have been found to normalise experiences of dementia and provide access to an accepting social network. People with learning disabilities are at increased risk of developing dementia, but the possible benefits of attending a memory café are not known. This study evaluates a 12-week pilot memory café for people with learning…

Large Capacity of Conscious Access for Incidental Memories in Natural Scenes.

PubMed

Kaunitz, Lisandro N; Rowe, Elise G; Tsuchiya, Naotsugu

2016-09-01

When searching a crowd, people can detect a target face only by direct fixation and attention. Once the target is found, it is consciously experienced and remembered, but what is the perceptual fate of the fixated nontarget faces? Whereas introspection suggests that one may remember nontargets, previous studies have proposed that almost no memory should be retained. Using a gaze-contingent paradigm, we asked subjects to visually search for a target face within a crowded natural scene and then tested their memory for nontarget faces, as well as their confidence in those memories. Subjects remembered up to seven fixated, nontarget faces with more than 70% accuracy. Memory accuracy was correlated with trial-by-trial confidence ratings, which implies that the memory was consciously maintained and accessed. When the search scene was inverted, no more than three nontarget faces were remembered. These findings imply that incidental memory for faces, such as those recalled by eyewitnesses, is more reliable than is usually assumed. © The Author(s) 2016.

Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels

PubMed Central

Gossel, Graeme; Hogan, Thea; Cownden, Daniel

2017-01-01

Characterising the longevity of immunological memory requires establishing the rules underlying the renewal and death of peripheral T cells. However, we lack knowledge of the population structure and how self-renewal and de novo influx contribute to the maintenance of memory compartments. Here, we characterise the kinetics and structure of murine CD4 T cell memory subsets by measuring the rates of influx of new cells and using detailed timecourses of DNA labelling that also distinguish the behaviour of recently divided and quiescent cells. We find that both effector and central memory CD4 T cells comprise subpopulations with highly divergent rates of turnover, and show that inflows of new cells sourced from the naive pool strongly impact estimates of memory cell lifetimes and division rates. We also demonstrate that the maintenance of CD4 T cell memory subsets in healthy mice is unexpectedly and strikingly reliant on this replenishment. DOI: http://dx.doi.org/10.7554/eLife.23013.001 PMID:28282024

Antigen-Induced but Not Innate Memory CD8 T Cells Express NKG2D and Are Recruited to the Lung Parenchyma upon Viral Infection.

PubMed

Grau, Morgan; Valsesia, Séverine; Mafille, Julien; Djebali, Sophia; Tomkowiak, Martine; Mathieu, Anne-Laure; Laubreton, Daphné; de Bernard, Simon; Jouve, Pierre-Emmanuel; Ventre, Erwan; Buffat, Laurent; Walzer, Thierry; Leverrier, Yann; Marvel, Jacqueline

2018-05-15

The pool of memory-phenotype CD8 T cells is composed of Ag-induced (AI) and cytokine-induced innate (IN) cells. IN cells have been described as having properties similar to those of AI memory cells. However, we found that pathogen-induced AI memory cells can be distinguished in mice from naturally generated IN memory cells by surface expression of NKG2D. Using this marker, we described the increased functionalities of AI and IN memory CD8 T cells compared with naive cells, as shown by comprehensive analysis of cytokine secretion and gene expression. However, AI differed from IN memory CD8 T cells by their capacity to migrate to the lung parenchyma upon inflammation or infection, a process dependent on their expression of ITGA1/CD49a and ITGA4/CD49d integrins. Copyright © 2018 by The American Association of Immunologists, Inc.

Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels.

PubMed

Gossel, Graeme; Hogan, Thea; Cownden, Daniel; Seddon, Benedict; Yates, Andrew J

2017-03-10

Characterising the longevity of immunological memory requires establishing the rules underlying the renewal and death of peripheral T cells. However, we lack knowledge of the population structure and how self-renewal and de novo influx contribute to the maintenance of memory compartments. Here, we characterise the kinetics and structure of murine CD4 T cell memory subsets by measuring the rates of influx of new cells and using detailed timecourses of DNA labelling that also distinguish the behaviour of recently divided and quiescent cells. We find that both effector and central memory CD4 T cells comprise subpopulations with highly divergent rates of turnover, and show that inflows of new cells sourced from the naive pool strongly impact estimates of memory cell lifetimes and division rates. We also demonstrate that the maintenance of CD4 T cell memory subsets in healthy mice is unexpectedly and strikingly reliant on this replenishment.

IFN-γ Induces the Erosion of Preexisting CD8 T Cell Memory during Infection with a Heterologous Intracellular Bacterium1

PubMed Central

Dudani, Renu; Murali-Krishna, Kaja; Krishnan, Lakshmi; Sad, Subash

2014-01-01

Memory T cells are critical for the control of intracellular pathogens and require few signals for maintenance; however, erosion of established preexisting memory CD8+ T cells has been shown to occur during infection with heterologous viral infections. We evaluated whether this also occurs during infection with various intracellular bacteria and what mechanisms may be involved. We demonstrate that erosion of established memory is also induced during infection of mice with various intracellular bacteria, such as Listeria monocytogenes, Salmonella typhimurium, and Mycobacterium bovis (bacillus Calmette-Guérin). The extent of erosion of established CD8+ T cell memory was dependent on the virulence of the heterologous pathogen, not persistence. Furthermore, when antibiotics were used to comprehensively eliminate the heterologous pathogen, the numbers of memory CD8+ T cells were not restored, indicating that erosion of preexisting memory CD8+ T cells was irreversible. Irrespective of the initial numbers of memory CD8+ T cells, challenge with the heterologous pathogen resulted in a similar extent of erosion of memory CD8+ T cells, suggesting that cellular competition was not responsible for erosion. After challenge with the heterologous pathogen, effector memory CD8+ T cells were rapidly eliminated. More importantly, erosion of preexisting memory CD8+ T cells was abrogated in the absence of IFN-γ. These studies help reveal the paradoxical role of IFN-γ. Although IFN-γ promotes the control of intracellular bacterial replication during primary infection, this comes at the expense of erosion of preexisting memory CD8+ T cells in the wake of infection with heterologous pathogens. PMID:18641306

Learning about memory from (very) large scale hippocampal networks

NASA Astrophysics Data System (ADS)

Meshulam, Leenoy; Gauthier, Jeffrey; Brody, Carlos; Tank, David; Bialek, William

Recent technological progress has dramatically increased our access to the neural activity underlying memory-related tasks. These complex high-dimensional data call for theories that allow us to identify signatures of collective activity in the networks that are crucial for the emergence of cognitive functions. As an example, we study the neural activity in dorsal hippocampus as a mouse runs along a virtual linear track. One of the dominant features of this data is the activity of place cells, which fire when the animal visits particular locations. During the first stage of our work we used a maximum entropy framework to characterize the probability distribution of the joint activity patterns observed across ensembles of up to 100 cells. These models, which are equivalent to Ising models with competing interactions, make surprisingly accurate predictions for the activity of individual neurons given the state of the rest of the network, and this is true both for place cells and for non-place cells. Additionally, the model captures the high-order structure in the data, which cannot be explained by place-related activity alone. For the second stage of our work we study networks of 2000 neurons. To address this much larger system, we are exploring different methods of coarse graining, in the spirit of the renormalization group, searching for simplified models.

Memory T cells in organ transplantation: progress and challenges

PubMed Central

Espinosa, Jaclyn R.; Samy, Kannan P.; Kirk, Allan D.

2017-01-01

Antigen-experienced T cells, also known as memory T cells, are functionally and phenotypically distinct from naive T cells. Their enhanced expression of adhesion molecules and reduced requirement for co-stimulation enables them to mount potent and rapid recall responses to subsequent antigen encounters. Memory T cells generated in response to prior antigen exposures can cross-react with other nonidentical, but similar, antigens. This heterologous cross-reactivity not only enhances protective immune responses, but also engenders de novo alloimmunity. This latter characteristic is increasingly recognized as a potential barrier to allograft acceptance that is worthy of immunotherapeutic intervention, and several approaches have been investigated. Calcineurin inhibition effectively controls memory T-cell responses to allografts, but this benefit comes at the expense of increased infectious morbidity. Lymphocyte depletion eliminates allospecific T cells but spares memory T cells to some extent, such that patients do not completely lose protective immunity. Co-stimulation blockade is associated with reduced adverse-effect profiles and improved graft function relative to calcineurin inhibition, but lacks efficacy in controlling memory T-cell responses. Targeting the adhesion molecules that are upregulated on memory T cells might offer additional means to control co-stimulation-blockade-resistant memory T-cell responses. PMID:26923209

The Effect of NUMA Tunings on CPU Performance

NASA Astrophysics Data System (ADS)

Hollowell, Christopher; Caramarcu, Costin; Strecker-Kellogg, William; Wong, Antonio; Zaytsev, Alexandr

2015-12-01

Non-Uniform Memory Access (NUMA) is a memory architecture for symmetric multiprocessing (SMP) systems where each processor is directly connected to separate memory. Indirect access to other CPU's (remote) RAM is still possible, but such requests are slower as they must also pass through that memory's controlling CPU. In concert with a NUMA-aware operating system, the NUMA hardware architecture can help eliminate the memory performance reductions generally seen in SMP systems when multiple processors simultaneously attempt to access memory. The x86 CPU architecture has supported NUMA for a number of years. Modern operating systems such as Linux support NUMA-aware scheduling, where the OS attempts to schedule a process to the CPU directly attached to the majority of its RAM. In Linux, it is possible to further manually tune the NUMA subsystem using the numactl utility. With the release of Red Hat Enterprise Linux (RHEL) 6.3, the numad daemon became available in this distribution. This daemon monitors a system's NUMA topology and utilization, and automatically makes adjustments to optimize locality. As the number of cores in x86 servers continues to grow, efficient NUMA mappings of processes to CPUs/memory will become increasingly important. This paper gives a brief overview of NUMA, and discusses the effects of manual tunings and numad on the performance of the HEPSPEC06 benchmark, and ATLAS software.

miR-150 Regulates Memory CD8 T Cell Differentiation via c-Myb.

PubMed

Chen, Zeyu; Stelekati, Erietta; Kurachi, Makoto; Yu, Sixiang; Cai, Zhangying; Manne, Sasikanth; Khan, Omar; Yang, Xiaolu; Wherry, E John

2017-09-12

MicroRNAs play an important role in T cell responses. However, how microRNAs regulate CD8 T cell memory remains poorly defined. Here, we found that miR-150 negatively regulates CD8 T cell memory in vivo. Genetic deletion of miR-150 disrupted the balance between memory precursor and terminal effector CD8 T cells following acute viral infection. Moreover, miR-150-deficient memory CD8 T cells were more protective upon rechallenge. A key circuit whereby miR-150 repressed memory CD8 T cell development through the transcription factor c-Myb was identified. Without miR-150, c-Myb was upregulated and anti-apoptotic targets of c-Myb, such as Bcl-2 and Bcl-xL, were also increased, suggesting a miR-150-c-Myb survival circuit during memory CD8 T cell development. Indeed, overexpression of non-repressible c-Myb rescued the memory CD8 T cell defects caused by overexpression of miR-150. Overall, these results identify a key role for miR-150 in memory CD8 T cells through a c-Myb-controlled enhanced survival circuit. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Scarcity of autoreactive human blood IgA+ memory B cells

PubMed Central

Prigent, Julie; Lorin, Valérie; Kök, Ayrin; Hieu, Thierry; Bourgeau, Salomé

2016-01-01

Class‐switched memory B cells are key components of the “reactive” humoral immunity, which ensures a fast and massive secretion of high‐affinity antigen‐specific antibodies upon antigenic challenge. In humans, IgA class‐switched (IgA+) memory B cells and IgA antibodies are abundant in the blood. Although circulating IgA+ memory B cells and their corresponding secreted immunoglobulins likely possess major protective and/or regulatory immune roles, little is known about their specificity and function. Here, we show that IgA+ and IgG+ memory B‐cell antibodies cloned from the same healthy humans share common immunoglobulin gene features. IgA and IgG memory antibodies have comparable lack of reactivity to vaccines, common mucosa‐tropic viruses and commensal bacteria. However, the IgA+ memory B‐cell compartment contains fewer polyreactive clones and importantly, only rare self‐reactive clones compared to IgG+ memory B cells. Self‐reactivity of IgAs is acquired following B‐cell affinity maturation but not antibody class switching. Together, our data suggest the existence of different regulatory mechanisms for removing autoreactive clones from the IgG+ and IgA+ memory B‐cell repertoires, and/or different maturation pathways potentially reflecting the distinct nature and localization of the cognate antigens recognized by individual B‐cell populations. PMID:27469325

Secondary immunization generates clonally related antigen-specific plasma cells and memory B cells.

PubMed

Frölich, Daniela; Giesecke, Claudia; Mei, Henrik E; Reiter, Karin; Daridon, Capucine; Lipsky, Peter E; Dörner, Thomas

2010-09-01

Rechallenge with T cell-dependent Ags induces memory B cells to re-enter germinal centers (GCs) and undergo further expansion and differentiation into plasma cells (PCs) and secondary memory B cells. It is currently not known whether the expanded population of memory B cells and PCs generated in secondary GCs are clonally related, nor has the extent of proliferation and somatic hypermutation of their precursors been delineated. In this study, after secondary tetanus toxoid (TT) immunization, TT-specific PCs increased 17- to 80-fold on days 6-7, whereas TT-specific memory B cells peaked (delayed) on day 14 with a 2- to 22-fold increase. Molecular analyses of V(H)DJ(H) rearrangements of individual cells revealed no major differences of gene usage and CDR3 length between TT-specific PCs and memory B cells, and both contained extensive evidence of somatic hypermutation with a pattern consistent with GC reactions. This analysis identified clonally related TT-specific memory B cells and PCs. Within clusters of clonally related cells, sequences shared a number of mutations but also could contain additional base pair changes. The data indicate that although following secondary immunization PCs can derive from memory B cells without further somatic hypermutation, in some circumstances, likely within GC reactions, asymmetric mutation can occur. These results suggest that after the fate decision to differentiate into secondary memory B cells or PCs, some committed precursors continue to proliferate and mutate their V(H) genes.

Protecting and rescuing the effectors: roles of differentiation and survival in the control of memory T cell development

PubMed Central

Kurtulus, Sema; Tripathi, Pulak; Hildeman, David A.

2013-01-01

Vaccines, arguably the single most important intervention in improving human health, have exploited the phenomenon of immunological memory. The elicitation of memory T cells is often an essential part of successful long-lived protective immunity. Our understanding of T cell memory has been greatly aided by the development of TCR Tg mice and MHC tetrameric staining reagents that have allowed the precise tracking of antigen-specific T cell responses. Indeed, following acute infection or immunization, naïve T cells undergo a massive expansion culminating in the generation of a robust effector T cell population. This peak effector response is relatively short-lived and, while most effector T cells die by apoptosis, some remain and develop into memory cells. Although the molecular mechanisms underlying this cell fate decision remain incompletely defined, substantial progress has been made, particularly with regards to CD8+ T cells. For example, the effector CD8+ T cells generated during a response are heterogeneous, consisting of cells with more or less potential to develop into full-fledged memory cells. Development of CD8+ T cell memory is regulated by the transcriptional programs that control the differentiation and survival of effector T cells. While the type of antigenic stimulation and level of inflammation control effector CD8+ T cell differentiation, availability of cytokines and their ability to control expression and function of Bcl-2 family members governs their survival. These distinct differentiation and survival programs may allow for finer therapeutic intervention to control both the quality and quantity of CD8+ T cell memory. Effector to memory transition of CD4+ T cells is less well characterized than CD8+ T cells, emerging details will be discussed. This review will focus on the recent progress made in our understanding of the mechanisms underlying the development of T cell memory with an emphasis on factors controlling survival of effector T cells. PMID:23346085

TLR4 ligands lipopolysaccharide and monophosphoryl lipid a differentially regulate effector and memory CD8+ T Cell differentiation.

PubMed

Cui, Weiguo; Joshi, Nikhil S; Liu, Ying; Meng, Hailong; Kleinstein, Steven H; Kaech, Susan M

2014-05-01

Vaccines formulated with nonreplicating pathogens require adjuvants to help bolster immunogenicity. The role of adjuvants in Ab production has been well studied, but how they influence memory CD8(+) T cell differentiation remains poorly defined. In this study we implemented dendritic cell-mediated immunization to study the effects of commonly used adjuvants, TLR ligands, on effector and memory CD8(+) T cell differentiation in mice. Intriguingly, we found that the TLR4 ligand LPS was far more superior to other TLR ligands in generating memory CD8(+) T cells upon immunization. LPS boosted clonal expansion similar to the other adjuvants, but fewer of the activated CD8(+) T cells died during contraction, generating a larger pool of memory cells. Surprisingly, monophosphoryl lipid A (MPLA), another TLR4 ligand, enhanced clonal expansion of effector CD8(+) T cells, but it also promoted their terminal differentiation and contraction; thus, fewer memory CD8(+) T cells formed, and MPLA-primed animals were less protected against secondary infection compared with those primed with LPS. Furthermore, gene expression profiling revealed that LPS-primed effector cells displayed a stronger pro-memory gene expression signature, whereas the gene expression profile of MPLA-primed effector cells aligned closer with terminal effector CD8(+) T cells. Lastly, we demonstrated that the LPS-TLR4-derived "pro-memory" signals were MyD88, but not Toll/IL-1R domain-containing adapter inducing IFN-β, dependent. This study reveals the influential power of adjuvants on the quantity and quality of CD8(+) T cell memory, and that attention to adjuvant selection is crucial because boosting effector cell expansion may not always equate with more memory T cells or greater protection.

Enhancing Memory in Your Students: COMPOSE Yourself!

ERIC Educational Resources Information Center

Rotter, Kathleen M.

2009-01-01

The essence of teaching is, in fact, creating new memories for your students. The teacher's role is to help students store the correct information (memories) in ways that make recall and future access and use likely. Therefore, choosing techniques to enhance memory is possibly the most critical aspect of instructional design. COMPOSE is an acronym…

Engrams and Circuits Crucial for Systems Consolidation of a Memory

PubMed Central

Kitamura, Takashi; Ogawa, Sachie K.; Roy, Dheeraj S.; Okuyama, Teruhiro; Morrissey, Mark D.; Smith, Lillian M.; Redondo, Roger L.; Tonegawa, Susumu

2017-01-01

Episodic memories initially require rapid synaptic plasticity within the hippocampus for their formation and are gradually consolidated in neocortical networks for permanent storage. However, the engrams and circuits that support neocortical memory consolidation remain unknown. We found that neocortical prefrontal memory engram cells, critical for remote contextual fear memory, were rapidly generated during initial learning via inputs from both hippocampal-entorhinal cortex and basolateral amygdala. After their generation, the prefrontal engram cells, with support from hippocampal memory engram cells, became functionally mature with time. Whereas hippocampal engram cells gradually became silent with time, engram cells in the basolateral amygdala, which were necessary for fear memory, are maintained. Our data provide new insights into the functional reorganization of engrams and circuits underlying systems consolidation of memory. PMID:28386011

Interleukin-21 regulates expression of key Epstein-Barr virus oncoproteins, EBNA2 and LMP1, in infected human B cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Konforte, Danijela; Department of Immunology, University of Toronto, Toronto, M5S 1A8; Simard, Nathalie

Epstein-Barr virus (EBV) persists for the life of the host by accessing the long-lived memory B cell pool. It has been proposed that EBV uses different combinations of viral proteins, known as latency types, to drive infected B cells to make the transition from resting B cells to memory cells. This process is normally antigen-driven. A major unresolved question is what factors coordinate expression of EBV latency proteins. We have recently described novel type III latency EBV{sup +} B cell lines (OCI-BCLs) that were induced to differentiate into late plasmablasts/early plasma cells in culture with interleukin-21 (IL-21), mimicking normal Bmore » cell development. The objective of this study was to determine whether IL-21-mediated signals also regulate the expression of key EBV latent proteins during this window of development. Here we show that IL-21-reduced gene and protein expression of growth-transforming EBV nuclear antigen 2 (EBNA2) in OCI-BCLs. By contrast, the expression of CD40-like, latent membrane protein 1 (LMP1) strongly increased in these cells suggesting an EBNA2-independent mode of regulation. Same results were also observed in Burkitt's lymphoma line Jijoye and B95-8 transformed lymphoblastoid cell lines. The effect of IL-21 on EBNA2 and LMP1 expression was attenuated by a pharmacological JAK inhibitor indicating involvement of JAK/STAT signalling in this process. Our study also shows that IL-21 induced transcription of ebna1 from the viral Q promoter (Qp)« less

CMV-Specific CD8 T Cell Differentiation and Localization: Implications for Adoptive Therapies.

PubMed

Smith, Corinne J; Quinn, Michael; Snyder, Christopher M

2016-01-01

Human cytomegalovirus (HCMV) is a ubiquitous virus that causes chronic infection and, thus, is one of the most common infectious complications of immune suppression. Adoptive transfer of HCMV-specific T cells has emerged as an effective method to reduce the risk for HCMV infection and/or reactivation by restoring immunity in transplant recipients. However, the CMV-specific CD8 + T cell response is comprised of a heterogenous mixture of subsets with distinct functions and localization, and it is not clear if current adoptive immunotherapy protocols can reconstitute the full spectrum of CD8 + T cell immunity. The aim of this review is to briefly summarize the role of these T cell subsets in CMV immunity and to describe how current adoptive immunotherapy practices might affect their reconstitution in patients. The bulk of the CMV-specific CD8 + T cell population is made up of terminally differentiated effector T cells with immediate effector function and a short life span. Self-renewing memory T cells within the CMV-specific population retain the capacity to expand and differentiate upon challenge and are important for the long-term persistence of the CD8 + T cell response. Finally, mucosal organs, which are frequent sites of CMV reactivation, are primarily inhabited by tissue-resident memory T cells, which do not recirculate. Future work on adoptive transfer strategies may need to focus on striking a balance between the formation of these subsets to ensure the development of long lasting and protective immune responses that can access the organs affected by CMV disease.

Generation of effector CD8+ T cells and their conversion to memory T cells

PubMed Central

Cui, Weiguo; Kaech, Susan M.

2015-01-01

Summary Immunological memory is a cardinal feature of adaptive immunity. We are now beginning to elucidate the mechanisms that govern the formation of memory T cells and their ability to acquire longevity, survive the effector-to-memory transition, and mature into multipotent, functional memory T cells that self-renew. Here, we discuss the recent findings in this area and highlight extrinsic and intrinsic factors that regulate the cellular fate of activated CD8+ T cells. PMID:20636815

Organic-Inorganic Hybrid Halide Perovskites for Memories, Transistors, and Artificial Synapses.

PubMed

Choi, Jaeho; Han, Ji Su; Hong, Kootak; Kim, Soo Young; Jang, Ho Won

2018-05-30

Fascinating characteristics of halide perovskites (HPs), which cannot be seen in conventional semiconductors and metal oxides, have boosted the application of HPs in electronic devices beyond optoelectronics such as solar cells, photodetectors, and light-emitting diodes. Here, recent advances in HP-based memory and logic devices such as resistive-switching memories (i.e., resistive random access memory (RRAM) or memristors), transistors, and artificial synapses are reviewed, focusing on inherently exotic properties of HPs: i) tunable bandgap, ii) facile majority carrier control, iii) fast ion migration, and iv) superflexibility. Various fabrication techniques of HP thin films from solution-based methods to vacuum processes are introduced. Up-to-date work in the field, emphasizing the compositional flexibility of HPs, suggest that HPs are promising candidates for next-generation electronic devices. Taking advantages of their unique electrical properties, low-cost and low-temperature synthesis, and compositional and mechanical flexibility, HPs have enormous potential to provide a new platform for future electronic devices and explosively intensive studies will pave the way in finding new HP materials beyond conventional silicon-based semiconductors to keep up with "More-than-Moore" times. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quiescence of Memory CD8(+) T Cells Is Mediated by Regulatory T Cells through Inhibitory Receptor CTLA-4.

PubMed

Kalia, Vandana; Penny, Laura Anne; Yuzefpolskiy, Yevgeniy; Baumann, Florian Martin; Sarkar, Surojit

2015-06-16

Immune memory cells are poised to rapidly expand and elaborate effector functions upon reinfection yet exist in a functionally quiescent state. The paradigm is that memory T cells remain inactive due to lack of T cell receptor (TCR) stimuli. Here, we report that regulatory T (Treg) cells orchestrate memory T cell quiescence by suppressing effector and proliferation programs through inhibitory receptor, cytotoxic-T-lymphocyte-associated protein-4 (CTLA-4). Loss of Treg cells resulted in activation of genome-wide transcriptional programs characteristic of effector T cells and drove transitioning as well as established memory CD8(+) T cells toward terminally differentiated KLRG-1(hi)IL-7Rα(lo)GzmB(hi) phenotype, with compromised metabolic fitness, longevity, polyfunctionality, and protective efficacy. CTLA-4 functionally replaced Treg cells in trans to rescue memory T cell defects and restore homeostasis. These studies present the CTLA-4-CD28-CD80/CD86 axis as a potential target to accelerate vaccine-induced immunity and improve T cell memory quality in current cancer immunotherapies proposing transient Treg cell ablation. Copyright © 2015 Elsevier Inc. All rights reserved.

Vaccine-elicited memory CD4+ T cell expansion is impaired in the lungs during tuberculosis.

PubMed

Carpenter, Stephen M; Yang, Jason D; Lee, Jinhee; Barreira-Silva, Palmira; Behar, Samuel M

2017-11-01

Immunological memory is the key biological process that makes vaccines possible. Although tuberculosis vaccines elicit protective immunity in animals, few provide durable protection. To understand why protection is transient, we evaluated the ability of memory CD4+ T cells to expand, differentiate, and control Mycobacterium tuberculosis. Both naïve and memory CD4+ T cells initially proliferated exponentially, and the accumulation of memory T cells in the lung correlated with early bacterial control. However, later during infection, memory CD4+ T cell proliferation was curtailed and no protection was observed. We show that memory CD4+ T cells are first activated in the LN and their recruitment to the lung attenuates bacterial growth. However, their interaction with Mtb-infected macrophages does not promote continued proliferation. We conclude that a lack of sustained expansion by memory-derived T cells in the lung limits the durability of their protection, linking their slower expansion with transient protection in vaccinated mice.

Retention of Ag-specific memory CD4+ T cells in the draining lymph node indicates lymphoid tissue resident memory populations.

PubMed

Marriott, Clare L; Dutton, Emma E; Tomura, Michio; Withers, David R

2017-05-01

Several different memory T-cell populations have now been described based upon surface receptor expression and migratory capabilities. Here we have assessed murine endogenous memory CD4 + T cells generated within a draining lymph node and their subsequent migration to other secondary lymphoid tissues. Having established a model response targeting a specific peripheral lymph node, we temporally labelled all the cells within draining lymph node using photoconversion. Tracking of photoconverted and non-photoconverted Ag-specific CD4 + T cells revealed the rapid establishment of a circulating memory population in all lymph nodes within days of immunisation. Strikingly, a resident memory CD4 + T cell population became established in the draining lymph node and persisted for several months in the absence of detectable migration to other lymphoid tissue. These cells most closely resembled effector memory T cells, usually associated with circulation through non-lymphoid tissue, but here, these cells were retained in the draining lymph node. These data indicate that lymphoid tissue resident memory CD4 + T-cell populations are generated in peripheral lymph nodes following immunisation. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Is There Natural Killer Cell Memory and Can It Be Harnessed by Vaccination? Natural Killer Cells in Vaccination.

PubMed

Neely, Harold R; Mazo, Irina B; Gerlach, Carmen; von Andrian, Ulrich H

2017-12-18

Natural killer (NK) cells have historically been considered to be a part of the innate immune system, exerting a rapid response against pathogens and tumors in an antigen (Ag)-independent manner. However, over the past decade, evidence has accumulated suggesting that at least some NK cells display certain characteristics of adaptive immune cells. Indeed, NK cells can learn and remember encounters with a variety of Ags, including chemical haptens and viruses. Upon rechallenge, memory NK cells mount potent recall responses selectively to those Ags. This phenomenon, traditionally termed "immunological memory," has been reported in mice, nonhuman primates, and even humans and appears to be concentrated in discrete NK cell subsets. Because immunological memory protects against recurrent infections and is the central goal of active vaccination, it is crucial to define the mechanisms and consequences of NK cell memory. Here, we summarize the different kinds of memory responses that have been attributed to specific NK cell subsets and discuss the possibility to harness NK cell memory for vaccination purposes. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Frequent Statement and Dereference Elimination for Imperative and Object-Oriented Distributed Programs

PubMed Central

El-Zawawy, Mohamed A.

2014-01-01

This paper introduces new approaches for the analysis of frequent statement and dereference elimination for imperative and object-oriented distributed programs running on parallel machines equipped with hierarchical memories. The paper uses languages whose address spaces are globally partitioned. Distributed programs allow defining data layout and threads writing to and reading from other thread memories. Three type systems (for imperative distributed programs) are the tools of the proposed techniques. The first type system defines for every program point a set of calculated (ready) statements and memory accesses. The second type system uses an enriched version of types of the first type system and determines which of the ready statements and memory accesses are used later in the program. The third type system uses the information gather so far to eliminate unnecessary statement computations and memory accesses (the analysis of frequent statement and dereference elimination). Extensions to these type systems are also presented to cover object-oriented distributed programs. Two advantages of our work over related work are the following. The hierarchical style of concurrent parallel computers is similar to the memory model used in this paper. In our approach, each analysis result is assigned a type derivation (serves as a correctness proof). PMID:24892098

A transcriptome-based model of central memory CD4 T cell death in HIV infection.

PubMed

Olvera-García, Gustavo; Aguilar-García, Tania; Gutiérrez-Jasso, Fany; Imaz-Rosshandler, Iván; Rangel-Escareño, Claudia; Orozco, Lorena; Aguilar-Delfín, Irma; Vázquez-Pérez, Joel A; Zúñiga, Joaquín; Pérez-Patrigeon, Santiago; Espinosa, Enrique

2016-11-22

Human central memory CD4 T cells are characterized by their capacity of proliferation and differentiation into effector memory CD4 T cells. Homeostasis of central memory CD4 T cells is considered a key factor sustaining the asymptomatic stage of Human Immunodeficiency Virus type 1 (HIV-1) infection, while progression to acquired immunodeficiency syndrome is imputed to central memory CD4 T cells homeostatic failure. We investigated if central memory CD4 T cells from patients with HIV-1 infection have a gene expression profile impeding proliferation and survival, despite their activated state. Using gene expression microarrays, we analyzed mRNA expression patterns in naive, central memory, and effector memory CD4 T cells from healthy controls, and naive and central memory CD4 T cells from patients with HIV-1 infection. Differentially expressed genes, defined by Log 2 Fold Change (FC) ≥ |0.5| and Log (odds) > 0, were used in pathway enrichment analyses. Central memory CD4 T cells from patients and controls showed comparable expression of differentiation-related genes, ruling out an effector-like differentiation of central memory CD4 T cells in HIV infection. However, 210 genes were differentially expressed in central memory CD4 T cells from patients compared with those from controls. Expression of 75 of these genes was validated by semi quantitative RT-PCR, and independently reproduced enrichment results from this gene expression signature. The results of functional enrichment analysis indicated movement to cell cycle phases G1 and S (increased CCNE1, MKI67, IL12RB2, ADAM9, decreased FGF9, etc.), but also arrest in G2/M (increased CHK1, RBBP8, KIF11, etc.). Unexpectedly, the results also suggested decreased apoptosis (increased CSTA, NFKBIA, decreased RNASEL, etc.). Results also suggested increased IL-1β, IFN-γ, TNF, and RANTES (CCR5) activity upstream of the central memory CD4 T cells signature, consistent with the demonstrated milieu in HIV infection. Our findings support a model where progressive loss of central memory CD4 T cells in chronic HIV-1 infection is driven by increased cell cycle entry followed by mitotic arrest, leading to a non-apoptotic death pathway without actual proliferation, possibly contributing to increased turnover.

Increased memory T cell populations in Pb-exposed children from an e-waste-recycling area.

PubMed

Cao, Junjun; Xu, Xijin; Zhang, Yu; Zeng, Zhijun; Hylkema, Machteld N; Huo, Xia

2018-03-01

Chronic exposure to heavy metals could affect cell-mediated immunity. The aim of this study was to explore the status of memory T cell development in preschool children from an e-waste recycling area. Blood lead (Pb) levels, peripheral T cell subpopulations, and serum levels of cytokines (IL-2/IL-7/IL-15), relevant to generation and homeostasis of memory T cells were evaluated in preschool children from Guiyu (e-waste-exposed group) and Haojiang (reference group). The correlations between blood Pb levels and percentages of memory T cell subpopulations were also evaluated. Guiyu children had higher blood Pb levels and increased percentages of CD4 + central memory T cells and CD8 + central memory T cells than in the Haojiang group. Moreover, blood Pb levels were positively associated with the percentages of CD4 + central memory T cells. In contrast, Pb exposure contributed marginally in the change of percentages of CD8 + central memory T cells in children. There was no significant difference in the serum cytokine levels between the e-waste-exposed and reference children. Taken together, preschool children from an e-waste recycling area suffer from relatively higher levels of Pb exposure, which might facilitate the development of CD4 + central memory T cells in these children. Copyright © 2017. Published by Elsevier B.V.

Stroma: the forgotten cells of innate immune memory.

PubMed

Crowley, Thomas; Buckley, Christopher D; Clark, Andrew R

2018-05-05

All organisms are constantly exposed to a variety of infectious and injurious stimuli. These induce inflammatory responses tailored to the threat posed. Whilst the innate immune system is the front line of response to each stimulant, it has been traditionally considered to lack memory, acting in a generic fashion until the adaptive immune arm can take over. This outmoded simplification of the roles of innate and acquired arms of the immune system has been challenged by evidence of myeloid cells altering their response to subsequent encounters based on earlier exposure. This concept of "innate immune memory" has been known for nearly a century, and is accepted amongst myeloid biologists. In recent years, other innate immune cells, such as natural killer cells, have been shown to display memory, suggesting innate immune memory is a trait common to several cell types. Over the last thirty years, evidence has slowly accumulated in favour of not only haematopoietic cells, but also stromal cells, being imbued with memory following inflammatory episodes. A recent publication showing this also to be true in epithelial cells suggests innate immune memory to be widespread, if underappreciated, in non-haematopoietic cells. In this review, we will examine the evidence supporting the existence of innate immune memory in stromal cells. We will also discuss the ramifications of memory in long-lived tissue-resident cells. Finally, we will pose questions we feel to be important in the understanding of these forgotten cells in the field of innate memory. This article is protected by copyright. All rights reserved. © 2018 British Society for Immunology.

Retention and Fading of Military Skills: Literature Review

DTIC Science & Technology

2000-04-01

distinction between availability and accessibility of human memory ( Tulving & Pearlstone , 1966; Tulving , 1983). Observation of some decrement in performance...Army War College. TULVING , E. (1983). Elements of Episodic Memory. London: Oxford University Press. TULVING , E., & PEARLSTONE , Z. (1966). Availability...store ( Tulving , 1983). To access this knowledge, the individual consciously recalls facts about the task and attempts to use them to guide performance

Access to Attitude-Relevant Information in Memory as a Determinant of Persuasion: The Role of Message and Communicator Attributes.

ERIC Educational Resources Information Center

Wood, Wendy; And Others

Research literature shows that people with access to attitude-relevant information in memory are able to draw on relevant beliefs and prior experiences when analyzing a persuasive message. This suggests that people who can retrieve little attitude-relevant information should be less able to engage in systematic processing. Two experiments were…

76 FR 45295 - In the Matter of Certain Static Random Access Memories and Products Containing Same; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-28

... supplementing the amended complaint was filed on June 28, 2011. A second amended complaint was filed on July 13... of certain static random access memories and products containing same by reason of infringement of... 13 of the `937 patent, and whether an industry in the United States exists as required by subsection...

Multibit Polycristalline Silicon-Oxide-Silicon Nitride-Oxide-Silicon Memory Cells with High Density Designed Utilizing a Separated Control Gate

NASA Astrophysics Data System (ADS)

Rok Kim, Kyeong; You, Joo Hyung; Dal Kwack, Kae; Kim, Tae Whan

2010-10-01

Unique multibit NAND polycrystalline silicon-oxide-silicon nitride-oxide-silicon (SONOS) memory cells utilizing a separated control gate (SCG) were designed to increase memory density. The proposed NAND SONOS memory device based on a SCG structure was operated as two bits, resulting in an increase in the storage density of the NVM devices in comparison with conventional single-bit memories. The electrical properties of the SONOS memory cells with a SCG were investigated to clarify the charging effects in the SONOS memory cells. When the program voltage was supplied to each gate of the NAND SONOS flash memory cells, the electrons were trapped in the nitride region of the oxide-nitride-oxide layer under the gate to supply the program voltage. The electrons were accumulated without affecting the other gate during the programming operation, indicating the absence of cross-talk between two trap charge regions. It is expected that the inference effect will be suppressed by the lower program voltage than the program voltage of the conventional NAND flash memory. The simulation results indicate that the proposed unique NAND SONOS memory cells with a SCG can be used to increase memory density.

B Cell and Antibody Responses in Mice Induced by a Putative Cell Surface Peptidase of Pneumocystis murina Protect against Experimental Infection

PubMed Central

Ruan, Sanbao; Cai, Yang; Ramsay, Alistair J.; Welsh, David A.; Norris, Karen; Shellito, Judd E.

2016-01-01

Rationale Pneumocystis pneumonia is a major cause of morbidity and mortality in HIV-infected subjects, cancer patients undergoing chemotherapy and solid organ transplant recipients. No vaccine is currently available. By chemical labeling coupled with proteomic approach, we have identified a putative surface protein (SPD1, Broad Institute gene accession number PNEG_01848) derived from single suspended P. murina cysts. SPD1 was expressed in an insect cell line and tested for vaccine development. Methods Mice were immunized with SPD1 plus adjuvant MF-59 by subcutaneous injection. Three weeks after the last immunization, CD4+ cells were depleted with anti-CD4 antibody GK1.5. The mice were then challenged with 2 × 105 Pneumocystis organisms. Mice were sacrificed at 4 and 6 weeks after PC challenge. Spleen/lung cells and serum were harvested. B cells and memory B cells were assessed via flow cytometry. Specific Pneumocystis IgG antibody was measured by ELISA before and after challenge. Infection burden was measured as real-time PCR for P. murina rRNA. Results Normal mice infected with Pneumocystis mounted a serum IgG antibody response to SPD1. Serum from rhesus macaques exposed to Pneumocystis showed a similar serum IgG response to purified SPD1. SPD1 immunization increased B cell and memory B cell absolute cell counts in CD4-depleted Balb/c mice post Pneumocystis challenge in spleen and lung. Immunization with SPD1 significantly increased specific Pneumocystis IgG antibody production before and after challenge. Mice immunized with SPD1 showed significantly decreased P. murina copy number compared with mice that did not receive SPD1 at 6 weeks after challenge. Conclusion Immunization with SPD1 provides protective efficacy against P. murina infection. SPD1 protection against Pneumocystis challenge is associated with enhanced memory B cell production and higher anti–Pneumocystis IgG antibody production. SPD1 is a potential vaccine candidate to prevent or treat pulmonary infection with Pneumocystis. PMID:28012778

Implementing a bubble memory hierarchy system

NASA Technical Reports Server (NTRS)

Segura, R.; Nichols, C. D.

1979-01-01

This paper reports on implementation of a magnetic bubble memory in a two-level hierarchial system. The hierarchy used a major-minor loop device and RAM under microprocessor control. Dynamic memory addressing, dual bus primary memory, and hardware data modification detection are incorporated in the system to minimize access time. It is the objective of the system to incorporate the advantages of bipolar memory with that of bubble domain memory to provide a smart, optimal memory system which is easy to interface and independent of user's system.

Integrated Vertical Bloch Line (VBL) memory

NASA Technical Reports Server (NTRS)

Katti, R. R.; Wu, J. C.; Stadler, H. L.

1991-01-01

Vertical Bloch Line (VBL) Memory is a recently conceived, integrated, solid state, block access, VLSI memory which offers the potential of 1 Gbit/sq cm areal storage density, data rates of hundreds of megabits/sec, and submillisecond average access time simultaneously at relatively low mass, volume, and power values when compared to alternative technologies. VBLs are micromagnetic structures within magnetic domain walls which can be manipulated using magnetic fields from integrated conductors. The presence or absence of BVL pairs are used to store binary information. At present, efforts are being directed at developing a single chip memory using 25 Mbit/sq cm technology in magnetic garnet material which integrates, at a single operating point, the writing, storage, reading, and amplification functions needed in a memory. The current design architecture, functional elements, and supercomputer simulation results are described which are used to assist the design process.

Fencing direct memory access data transfers in a parallel active messaging interface of a parallel computer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blocksome, Michael A.; Mamidala, Amith R.

2013-09-03

Fencing direct memory access (`DMA`) data transfers in a parallel active messaging interface (`PAMI`) of a parallel computer, the PAMI including data communications endpoints, each endpoint including specifications of a client, a context, and a task, the endpoints coupled for data communications through the PAMI and through DMA controllers operatively coupled to segments of shared random access memory through which the DMA controllers deliver data communications deterministically, including initiating execution through the PAMI of an ordered sequence of active DMA instructions for DMA data transfers between two endpoints, effecting deterministic DMA data transfers through a DMA controller and a segmentmore » of shared memory; and executing through the PAMI, with no FENCE accounting for DMA data transfers, an active FENCE instruction, the FENCE instruction completing execution only after completion of all DMA instructions initiated prior to execution of the FENCE instruction for DMA data transfers between the two endpoints.« less

Guilt as a Motivator for Moral Judgment: An Autobiographical Memory Study

PubMed Central

Knez, Igor; Nordhall, Ola

2017-01-01

The aim was to investigate the phenomenology of self-defining moral memory and its relations to self-conscious feelings of guilt and willingness to do wrong (moral intention) in social and economic moral situations. We found that people use guilt as a moral motivator for their moral intention. The reparative function of guilt varied, however, with type of situation; that is, participants felt guiltier and were less willing to do wrong in economic compared to social moral situations. The self-defining moral memory was shown to be relatively more easy to access (accessibility), logically structured (coherence), vivid, seen from the first-person perspective (visual perspective), real (sensory detail); but was relatively less positive (valence), emotionally intense, chronologically clear (time perspective), in agreement with the present self (distancing), and shared. Finally, it was indicated that the more guilt people felt the more hidden/denied (less accessible), but more real (more sensory details), the self-defining moral memory. PMID:28539906

CD73 expression identifies a subset of IgM+ antigen-experienced cells with memory attributes that is T cell and CD40 signalling dependent.

PubMed

D'Souza, Lucas; Gupta, Sneh Lata; Bal, Vineeta; Rath, Satyajit; George, Anna

2017-12-01

B-cell memory was long characterized as isotype-switched, somatically mutated and germinal centre (GC)-derived. However, it is now clear that the memory pool is a complex mixture that includes unswitched and unmutated cells. Further, expression of CD73, CD80 and CD273 has allowed the categorization of B-cell memory into multiple subsets, with combinatorial expression of the markers increasing with GC progression, isotype-switching and acquisition of somatic mutations. We have extended these findings to determine whether these markers can be used to identify IgM memory phenotypically as arising from T-dependent versus T-independent responses. We report that CD73 expression identifies a subset of antigen-experienced IgM + cells that share attributes of functional B-cell memory. This subset is reduced in the spleens of T-cell-deficient and CD40-deficient mice and in mixed marrow chimeras made with mutant and wild-type marrow, the proportion of CD73 + IgM memory is restored in the T-cell-deficient donor compartment but not in the CD40-deficient donor compartment, indicating that CD40 ligation is involved in its generation. We also report that CD40 signalling supports optimal expression of CD73 on splenic T cells and age-associated B cells (ABCs), but not on other immune cells such as neutrophils, marginal zone B cells, peritoneal cavity B-1 B cells and regulatory T and B cells. Our data indicate that in addition to promoting GC-associated memory generation during B-cell differentiation, CD40-signalling can influence the composition of the unswitched memory B-cell pool. They also raise the possibility that a fraction of ABCs may represent T-cell-dependent IgM memory. © 2017 John Wiley & Sons Ltd.

Enhanced anti-tumour immunity requires the interplay between resident and circulating memory CD8+ T cells

PubMed Central

Enamorado, Michel; Iborra, Salvador; Priego, Elena; Cueto, Francisco J.; Quintana, Juan A.; Martínez-Cano, Sarai; Mejías-Pérez, Ernesto; Esteban, Mariano; Melero, Ignacio; Hidalgo, Andrés; Sancho, David

2017-01-01

The goal of successful anti-tumoural immunity is the development of long-term protective immunity to prevent relapse. Infiltration of tumours with CD8+ T cells with a resident memory (Trm) phenotype correlates with improved survival. However, the interplay of circulating CD8+ T cells and Trm cells remains poorly explored in tumour immunity. Using different vaccination strategies that fine-tune the generation of Trm cells or circulating memory T cells, here we show that, while both subsets are sufficient for anti-tumour immunity, the presence of Trm cells improves anti-tumour efficacy. Transferred central memory T cells (Tcm) generate Trm cells following viral infection or tumour challenge. Anti-PD-1 treatment promotes infiltration of transferred Tcm cells within tumours, improving anti-tumour immunity. Moreover, Batf3-dependent dendritic cells are essential for reactivation of circulating memory anti-tumour response. Our findings show the plasticity, collaboration and requirements for reactivation of memory CD8+ T cells subsets needed for optimal tumour vaccination and immunotherapy. PMID:28714465

Humans with chronic granulomatous disease maintain humoral immunologic memory despite low frequencies of circulating memory B cells

PubMed Central

Santich, Brian H.; Kim, Jin Young; Posada, Jacqueline G.; Ho, Jason; Buckner, Clarisa M.; Wang, Wei; Kardava, Lela; Garofalo, Mary; Marciano, Beatriz E.; Manischewitz, Jody; King, Lisa R.; Khurana, Surender; Chun, Tae-Wook; Golding, Hana; Fauci, Anthony S.; Malech, Harry L.

2012-01-01

CD27+ memory B cells are reduced in the blood of patients with chronic granulomatous disease (CGD) for reasons and consequences that remain unclear. Here we confirm not only decreased CD27+ but also IgG+ B cells in the blood of CGD patients compared with healthy donors (HDs). However, among IgG+ B cells, the ratio of CD27− to CD27+ was significantly higher in CGD patients compared with HDs. Similar to conventional memory B cells, CD27−IgG+ B cells of CGD patients expressed activation markers and had undergone somatic hypermutation, albeit at levels lower than their CD27+ counterparts. Functional analyses revealed slight reductions in frequencies of total IgG but not influenza-specific memory B-cell responses, as measured by Elispot in CGD patients compared with HDs. Serum IgG levels and influenza-specific antibodies were also normal in these CGD patients. Finally, we provide evidence that influenza-specific memory B cells can be present within the CD27−IgG+ B-cell compartment. Together, these findings show that, despite reduced circulating CD27+ memory B cells, CGD patients maintain an intact humoral immunologic memory, with potential contribution from CD27− B cells. PMID:23074274

Humans with chronic granulomatous disease maintain humoral immunologic memory despite low frequencies of circulating memory B cells.

PubMed

Moir, Susan; De Ravin, Suk See; Santich, Brian H; Kim, Jin Young; Posada, Jacqueline G; Ho, Jason; Buckner, Clarisa M; Wang, Wei; Kardava, Lela; Garofalo, Mary; Marciano, Beatriz E; Manischewitz, Jody; King, Lisa R; Khurana, Surender; Chun, Tae-Wook; Golding, Hana; Fauci, Anthony S; Malech, Harry L

2012-12-06

CD27(+) memory B cells are reduced in the blood of patients with chronic granulomatous disease (CGD) for reasons and consequences that remain unclear. Here we confirm not only decreased CD27(+) but also IgG(+) B cells in the blood of CGD patients compared with healthy donors (HDs). However, among IgG(+) B cells, the ratio of CD27(-) to CD27(+) was significantly higher in CGD patients compared with HDs. Similar to conventional memory B cells, CD27(-)IgG(+) B cells of CGD patients expressed activation markers and had undergone somatic hypermutation, albeit at levels lower than their CD27(+) counterparts. Functional analyses revealed slight reductions in frequencies of total IgG but not influenza-specific memory B-cell responses, as measured by Elispot in CGD patients compared with HDs. Serum IgG levels and influenza-specific antibodies were also normal in these CGD patients. Finally, we provide evidence that influenza-specific memory B cells can be present within the CD27(-)IgG(+) B-cell compartment. Together, these findings show that, despite reduced circulating CD27(+) memory B cells, CGD patients maintain an intact humoral immunologic memory, with potential contribution from CD27(-) B cells.

Synchrotron radiation x-ray photoelectron spectroscopy study on the interface chemistry of high-k PrxAl2-xO3 (x=0-2) dielectrics on TiN for dynamic random access memory applications

NASA Astrophysics Data System (ADS)

Schroeder, T.; Lupina, G.; Sohal, R.; Lippert, G.; Wenger, Ch.; Seifarth, O.; Tallarida, M.; Schmeisser, D.

2007-07-01

Engineered dielectrics combined with compatible metal electrodes are important materials science approaches to scale three-dimensional trench dynamic random access memory (DRAM) cells. Highly insulating dielectrics with high dielectric constants were engineered in this study on TiN metal electrodes by partly substituting Al in the wide band gap insulator Al2O3 by Pr cations. High quality PrAlO3 metal-insulator-metal capacitors were processed with a dielectric constant of 19, three times higher than in the case of Al2O3 reference cells. As a parasitic low dielectric constant interface layer between PrAlO3 and TiN limits the total performance gain, a systematic nondestructive synchrotron x-ray photoelectron spectroscopy study on the interface chemistry of PrxAl2-xO3 (x =0-2) dielectrics on TiN layers was applied to unveil its chemical origin. The interface layer results from the decreasing chemical reactivity of PrxAl2-xO3 dielectrics with increasing Pr content x to reduce native Ti oxide compounds present on unprotected TiN films. Accordingly, PrAlO3 based DRAM capacitors require strict control of the surface chemistry of the TiN electrode, a parameter furthermore of importance to engineer the band offsets of PrxAl2-xO3/TiN heterojunctions.

Programmed Death 1 Regulates Memory Phenotype CD4 T Cell Accumulation, Inhibits Expansion of the Effector Memory Phenotype Subset and Modulates Production of Effector Cytokines

PubMed Central

Charlton, Joanna J.; Tsoukatou, Debbie; Mamalaki, Clio; Chatzidakis, Ioannis

2015-01-01

Memory phenotype CD4 T cells are found in normal mice and arise through response to environmental antigens or homeostatic mechanisms. The factors that regulate the homeostasis of memory phenotype CD4 cells are not clear. In the present study we demonstrate that there is a marked accumulation of memory phenotype CD4 cells, specifically of the effector memory (TEM) phenotype, in lymphoid organs and tissues of mice deficient for the negative co-stimulatory receptor programmed death 1 (PD-1). This can be correlated with decreased apoptosis but not with enhanced homeostatic turnover potential of these cells. PD-1 ablation increased the frequency of memory phenotype CD4 IFN-γ producers but decreased the respective frequency of IL-17A-producing cells. In particular, IFN-γ producers were more abundant but IL-17A producing cells were more scarce among PD-1 KO TEM-phenotype cells relative to WT. Transfer of peripheral naïve CD4 T cells suggested that accumulated PD-1 KO TEM-phenotype cells are of peripheral and not of thymic origin. This accumulation effect was mediated by CD4 cell-intrinsic mechanisms as shown by mixed bone marrow chimera experiments. Naïve PD-1 KO CD4 T cells gave rise to higher numbers of TEM-phenotype lymphopenia-induced proliferation memory cells. In conclusion, we provide evidence that PD-1 has an important role in determining the composition and functional aspects of memory phenotype CD4 T cell pool. PMID:25803808

Low interleukin-2 concentration favors generation of early memory T cells over effector phenotypes during chimeric antigen receptor T-cell expansion.

PubMed

Kaartinen, Tanja; Luostarinen, Annu; Maliniemi, Pilvi; Keto, Joni; Arvas, Mikko; Belt, Heini; Koponen, Jonna; Loskog, Angelica; Mustjoki, Satu; Porkka, Kimmo; Ylä-Herttuala, Seppo; Korhonen, Matti

2017-06-01

Adoptive T-cell therapy offers new options for cancer treatment. Clinical results suggest that T-cell persistence, depending on T-cell memory, improves efficacy. The use of interleukin (IL)-2 for in vitro T-cell expansion is not straightforward because it drives effector T-cell differentiation but does not promote the formation of T-cell memory. We have developed a cost-effective expansion protocol for chimeric antigen receptor (CAR) T cells with an early memory phenotype. Lymphocytes were transduced with third-generation lentiviral vectors and expanded using CD3/CD28 microbeads. The effects of altering the IL-2 supplementation (0-300 IU/mL) and length of expansion (10-20 days) on the phenotype of the T-cell products were analyzed. High IL-2 levels led to a decrease in overall generation of early memory T cells by both decreasing central memory T cells and augmenting effectors. T memory stem cells (T SCM , CD95 + CD45RO - CD45RA + CD27 + ) were present variably during T-cell expansion. However, their presence was not IL-2 dependent but was linked to expansion kinetics. CD19-CAR T cells generated in these conditions displayed in vitro antileukemic activity. In summary, production of CAR T cells without any cytokine supplementation yielded the highest proportion of early memory T cells, provided a 10-fold cell expansion and the cells were functionally potent. The number of early memory T cells in a T-cell preparation can be increased by simply reducing the amount of IL-2 and limiting the length of T-cell expansion, providing cells with potentially higher in vivo performance. These findings are significant for robust and cost-effective T-cell manufacturing. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Towards Terabit Memories

NASA Astrophysics Data System (ADS)

Hoefflinger, Bernd

Memories have been the major yardstick for the continuing validity of Moore's law. In single-transistor-per-Bit dynamic random-access memories (DRAM), the number of bits per chip pretty much gives us the number of transistors. For decades, DRAM's have offered the largest storage capacity per chip. However, DRAM does not scale any longer, both in density and voltage, severely limiting its power efficiency to 10 fJ/b. A differential DRAM would gain four-times in density and eight-times in energy. Static CMOS RAM (SRAM) with its six transistors/cell is gaining in reputation because it scales well in cell size and operating voltage so that its fundamental advantage of speed, non-destructive read-out and low-power standby could lead to just 2.5 electrons/bit in standby and to a dynamic power efficiency of 2aJ/b. With a projected 2020 density of 16 Gb/cm², the SRAM would be as dense as normal DRAM and vastly better in power efficiency, which would mean a major change in the architecture and market scenario for DRAM versus SRAM. Non-volatile Flash memory have seen two quantum jumps in density well beyond the roadmap: Multi-Bit storage per transistor and high-density TSV (through-silicon via) technology. The number of electrons required per Bit on the storage gate has been reduced since their first realization in 1996 by more than an order of magnitude to 400 electrons/Bit in 2010 for a complexity of 32Gbit per chip at the 32 nm node. Chip stacking of eight chips with TSV has produced a 32GByte solid-state drive (SSD). A stack of 32 chips with 2 b/cell at the 16 nm node will reach a density of 2.5 Terabit/cm². Non-volatile memory with a density of 10 × 10 nm²/Bit is the target for widespread development. Phase-change memory (PCM) and resistive memory (RRAM) lead in cell density, and they will reach 20 Gb/cm² in 2D and higher with 3D chip stacking. This is still almost an order-of-magnitude less than Flash. However, their read-out speed is ~10-times faster, with as yet little data on their energy/b. As a read-out memory with unparalleled retention and lifetime, the ROM with electron-beam direct-write-lithography (Chap. 8) should be considered for its projected 2D density of 250 Gb/cm², a very small read energy of 0.1 μW/Gb/s. The lithography write-speed 10 ms/Terabit makes this ROM a serious contentender for the optimum in non-volatile, tamper-proof storage.

Increased numbers of pre-existing memory CD8 T cells and decreased T-bet expression can restrain terminal differentiation of secondary effector and memory CD8 T cells1

PubMed Central

Joshi, Nikhil S.; Cui, Weiguo; Dominguez, Claudia; Chen, Jonathan H.; Hand, Timothy W.; Kaech, Susan M.

2011-01-01

Memory CD8 T cells acquire TEM properties following reinfection, and may reach terminally differentiated, senescent states (“Hayflick limit”) after multiple infections. The signals controlling this process are not well understood, but we found that the degree of 2o effector and memory CD8 T cell differentiation was intimately linked to the amount of T-bet expressed upon reactivation and pre-existing memory CD8 T cell number (i.e., 1o memory CD8 T cell precursor frequency) present during secondary infection. Compared to naïve cells, memory CD8 T cells were predisposed towards terminal effector (TE) cell differentiation because they could immediately respond to IL-12 and induce T-bet, even in the absence of antigen. TE cell formation following 2o or 3o infections was dependent on increased T-bet expression because T-bet+/− cells were resistant to these phenotypic changes. Larger numbers of pre-existing memory CD8 T cells limited the duration of 2o infection and the amount of IL-12 produced, and consequently, this reduced T-bet expression and the proportion of 2o TE CD8 T cells that formed. Together, these data show that, over repeated infections, memory CD8 T cell quality and proliferative fitness is not strictly determined by the number of serial encounters with antigen or cell divisions, but is a function of the CD8 T cell differentiation state, which is genetically controlled in a T-bet-dependent manner. This differentiation state can be modulated by pre-existing memory CD8 T cell number and the intensity of inflammation during reinfection. These results have important implications for vaccinations involving prime-boost strategies. PMID:21930973

CD4+CD25+ regulatory T cells suppress allograft rejection mediated by memory CD8+ T cells via a CD30-dependent mechanism.

PubMed

Dai, Zhenhua; Li, Qi; Wang, Yinong; Gao, Ge; Diggs, Lonnette S; Tellides, George; Lakkis, Fadi G

2004-01-01

CD4(+)CD25(+) regulatory T (Treg) cells suppress naive T cell responses, prevent autoimmunity, and delay allograft rejection. It is not known, however, whether Treg cells suppress allograft rejection mediated by memory T cells, as the latter mount faster and stronger immune responses than their naive counterparts. Here we show that antigen-induced, but not naive, Treg cells suppress allograft rejection mediated by memory CD8(+) T cells. Suppression was allospecific, as Treg cells induced by third-party antigens did not delay allograft rejection. In vivo and in vitro analyses revealed that the apoptosis of allospecific memory CD8(+) T cells is significantly increased in the presence of antigen-induced Treg cells, while their proliferation remains unaffected. Importantly, neither suppression of allograft rejection nor enhanced apoptosis of memory CD8(+) T cells was observed when Treg cells lacked CD30 or when CD30 ligand-CD30 interaction was blocked with anti-CD30 ligand Ab. This study therefore provides direct evidence that pathogenic memory T cells are amenable to suppression in an antigen-specific manner and identifies CD30 as a molecule that is critical for the regulation of memory T cell responses.

CD4+CD25+ regulatory T cells suppress allograft rejection mediated by memory CD8+ T cells via a CD30-dependent mechanism

PubMed Central

Dai, Zhenhua; Li, Qi; Wang, Yinong; Gao, Ge; Diggs, Lonnette S.; Tellides, George; Lakkis, Fadi G.

2004-01-01

CD4+CD25+ regulatory T (Treg) cells suppress naive T cell responses, prevent autoimmunity, and delay allograft rejection. It is not known, however, whether Treg cells suppress allograft rejection mediated by memory T cells, as the latter mount faster and stronger immune responses than their naive counterparts. Here we show that antigen-induced, but not naive, Treg cells suppress allograft rejection mediated by memory CD8+ T cells. Suppression was allospecific, as Treg cells induced by third-party antigens did not delay allograft rejection. In vivo and in vitro analyses revealed that the apoptosis of allospecific memory CD8+ T cells is significantly increased in the presence of antigen-induced Treg cells, while their proliferation remains unaffected. Importantly, neither suppression of allograft rejection nor enhanced apoptosis of memory CD8+ T cells was observed when Treg cells lacked CD30 or when CD30 ligand–CD30 interaction was blocked with anti–CD30 ligand Ab. This study therefore provides direct evidence that pathogenic memory T cells are amenable to suppression in an antigen-specific manner and identifies CD30 as a molecule that is critical for the regulation of memory T cell responses. PMID:14722622

Deciding with the eye: how the visually manipulated accessibility of information in memory influences decision behavior.

PubMed

Platzer, Christine; Bröder, Arndt; Heck, Daniel W

2014-05-01

Decision situations are typically characterized by uncertainty: Individuals do not know the values of different options on a criterion dimension. For example, consumers do not know which is the healthiest of several products. To make a decision, individuals can use information about cues that are probabilistically related to the criterion dimension, such as sugar content or the concentration of natural vitamins. In two experiments, we investigated how the accessibility of cue information in memory affects which decision strategy individuals rely on. The accessibility of cue information was manipulated by means of a newly developed paradigm, the spatial-memory-cueing paradigm, which is based on a combination of the looking-at-nothing phenomenon and the spatial-cueing paradigm. The results indicated that people use different decision strategies, depending on the validity of easily accessible information. If the easily accessible information is valid, people stop information search and decide according to a simple take-the-best heuristic. If, however, information that comes to mind easily has a low predictive validity, people are more likely to integrate all available cue information in a compensatory manner.

The Effect of Retrieval Cues on Visual Preferences and Memory in Infancy: Evidence for a Four-Phase Attention Function.

ERIC Educational Resources Information Center

Bahrick, Lorraine E.; Hernandez-Reif, Maria; Pickens, Jeffrey N.

1997-01-01

Tested hypothesis from Bahrick and Pickens' infant attention model that retrieval cues increase memory accessibility and shift visual preferences toward greater novelty to resemble recent memories. Found that after retention intervals associated with remote or intermediate memory, previous familiarity preferences shifted to null or novelty…

Activation and Binding in Verbal Working Memory: A Dual-Process Model for the Recognition of Nonwords

ERIC Educational Resources Information Center

Oberauer, Klauss; Lange, Elke B.

2009-01-01

The article presents a mathematical model of short-term recognition based on dual-process models and the three-component theory of working memory [Oberauer, K. (2002). Access to information in working memory: Exploring the focus of attention. "Journal of Experimental Psychology: Learning, Memory, and Cognition, 28", 411-421]. Familiarity arises…

Thermal characterization and analysis of phase change random access memory

NASA Astrophysics Data System (ADS)

Giraud, V.; Cluzel, J.; Sousa, V.; Jacquot, A.; Dauscher, A.; Lenoir, B.; Scherrer, H.; Romer, S.

2005-07-01

The cross-plane thermal conductivity of Ge2Sb2Te5, either in its amorphous state or fcc crystallized state, and titanium nitride (TiN) thin films has been measured at room temperature by the 3ω method. These materials are involved in the fabrication of phase change random access memory (PC-RAM), Ge2Sb2Te5 and TiN being the PC and pseudoelectrode materials, respectively. The thermal conductivity of insulating SiO2 and ZnS :SiO2 layers was determined too. Each thermal conductivity measurement was performed by the means of at least two strip widths in order to check both the measurement self-consistency and the measurement accuracy. The performance of PC-RAM cells, i.e., the time needed to reach the melting temperature of the PC material and the cooling speed, has been evaluated as a function of both the measured thermal conductivity of the PC material and the reset current intensity independently of the thermal properties of the pseudoelectrodes by the way of analytical formula. The influence of the thickness and the thermal properties of the pseudoelectrodes on the performances have been determined by numerical simulations.

Breaking the current density threshold in spin-orbit-torque magnetic random access memory

NASA Astrophysics Data System (ADS)

Zhang, Yin; Yuan, H. Y.; Wang, X. S.; Wang, X. R.

2018-04-01

Spin-orbit-torque magnetic random access memory (SOT-MRAM) is a promising technology for the next generation of data storage devices. The main bottleneck of this technology is the high reversal current density threshold. This outstanding problem is now solved by a new strategy in which the magnitude of the driven current density is fixed while the current direction varies with time. The theoretical limit of minimal reversal current density is only a fraction (the Gilbert damping coefficient) of the threshold current density of the conventional strategy. The Euler-Lagrange equation for the fastest magnetization reversal path and the optimal current pulse is derived for an arbitrary magnetic cell and arbitrary spin-orbit torque. The theoretical limit of minimal reversal current density and current density for a GHz switching rate of the new reversal strategy for CoFeB/Ta SOT-MRAMs are, respectively, of the order of 105 A/cm 2 and 106 A/cm 2 far below 107 A/cm 2 and 108 A/cm 2 in the conventional strategy. Furthermore, no external magnetic field is needed for a deterministic reversal in the new strategy.

Recognition-induced forgetting is not due to category-based set size.

PubMed

Maxcey, Ashleigh M

2016-01-01

What are the consequences of accessing a visual long-term memory representation? Previous work has shown that accessing a long-term memory representation via retrieval improves memory for the targeted item and hurts memory for related items, a phenomenon called retrieval-induced forgetting. Recently we found a similar forgetting phenomenon with recognition of visual objects. Recognition-induced forgetting occurs when practice recognizing an object during a two-alternative forced-choice task, from a group of objects learned at the same time, leads to worse memory for objects from that group that were not practiced. An alternative explanation of this effect is that category-based set size is inducing forgetting, not recognition practice as claimed by some researchers. This alternative explanation is possible because during recognition practice subjects make old-new judgments in a two-alternative forced-choice task, and are thus exposed to more objects from practiced categories, potentially inducing forgetting due to set-size. Herein I pitted the category-based set size hypothesis against the recognition-induced forgetting hypothesis. To this end, I parametrically manipulated the amount of practice objects received in the recognition-induced forgetting paradigm. If forgetting is due to category-based set size, then the magnitude of forgetting of related objects will increase as the number of practice trials increases. If forgetting is recognition induced, the set size of exemplars from any given category should not be predictive of memory for practiced objects. Consistent with this latter hypothesis, additional practice systematically improved memory for practiced objects, but did not systematically affect forgetting of related objects. These results firmly establish that recognition practice induces forgetting of related memories. Future directions and important real-world applications of using recognition to access our visual memories of previously encountered objects are discussed.

A Memory-Based Programmable Logic Device Using Look-Up Table Cascade with Synchronous Static Random Access Memories

NASA Astrophysics Data System (ADS)

Nakamura, Kazuyuki; Sasao, Tsutomu; Matsuura, Munehiro; Tanaka, Katsumasa; Yoshizumi, Kenichi; Nakahara, Hiroki; Iguchi, Yukihiro

2006-04-01

A large-scale memory-technology-based programmable logic device (PLD) using a look-up table (LUT) cascade is developed in the 0.35-μm standard complementary metal oxide semiconductor (CMOS) logic process. Eight 64 K-bit synchronous SRAMs are connected to form an LUT cascade with a few additional circuits. The features of the LUT cascade include: 1) a flexible cascade connection structure, 2) multi phase pseudo asynchronous operations with synchronous static random access memory (SRAM) cores, and 3) LUT-bypass redundancy. This chip operates at 33 MHz in 8-LUT cascades at 122 mW. Benchmark results show that it achieves a comparable performance to field programmable gate array (FPGAs).

Liver-primed memory T cells generated under noninflammatory conditions provide anti-infectious immunity.

PubMed

Böttcher, Jan P; Schanz, Oliver; Wohlleber, Dirk; Abdullah, Zeinab; Debey-Pascher, Svenja; Staratschek-Jox, Andrea; Höchst, Bastian; Hegenbarth, Silke; Grell, Jessica; Limmer, Andreas; Atreya, Imke; Neurath, Markus F; Busch, Dirk H; Schmitt, Edgar; van Endert, Peter; Kolanus, Waldemar; Kurts, Christian; Schultze, Joachim L; Diehl, Linda; Knolle, Percy A

2013-03-28

Development of CD8(+) T cell (CTL) immunity or tolerance is linked to the conditions during T cell priming. Dendritic cells (DCs) matured during inflammation generate effector/memory T cells, whereas immature DCs cause T cell deletion/anergy. We identify a third outcome of T cell priming in absence of inflammation enabled by cross-presenting liver sinusoidal endothelial cells. Such priming generated memory T cells that were spared from deletion by immature DCs. Similar to central memory T cells, liver-primed T cells differentiated into effector CTLs upon antigen re-encounter on matured DCs even after prolonged absence of antigen. Their reactivation required combinatorial signaling through the TCR, CD28, and IL-12R and controlled bacterial and viral infections. Gene expression profiling identified liver-primed T cells as a distinct Neuropilin-1(+) memory population. Generation of liver-primed memory T cells may prevent pathogens that avoid DC maturation by innate immune escape from also escaping adaptive immunity through attrition of the T cell repertoire. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Peripheral B cells latently infected with Epstein–Barr virus display molecular hallmarks of classical antigen-selected memory B cells

PubMed Central

Souza, Tatyana A.; Stollar, B. David; Sullivan, John L.; Luzuriaga, Katherine; Thorley-Lawson, David A.

2005-01-01

Epstein–Barr virus (EBV) establishes a lifelong persistent infection within peripheral blood B cells with the surface phenotype of memory cells. To date there is no proof that these cells have the genotype of true germinal-center-derived memory B cells. It is critical to understand the relative contribution of viral mimicry versus antigen signaling to the production of these cells because EBV encodes proteins that can affect the surface phenotype of infected cells and provide both T cell help and B cell receptor signals in the absence of cognate antigen. To address these questions we have developed a technique to identify single EBV-infected cells in the peripheral blood and examine their expressed Ig genes. The genes were all isotype-switched and somatically mutated. Furthermore, the mutations do not cause stop codons and display the pattern expected for antigen-selected memory cells based on their frequency, type, and location within the Ig gene. We conclude that latently infected peripheral blood B cells display the molecular hallmarks of classical antigen-selected memory B cells. Therefore, EBV does not disrupt the normal processing of latently infected cells into memory, and deviations from normal B cell biology are not tolerated in the infected cells. This article provides definitive evidence that EBV in the peripheral blood persists in true memory B cells. PMID:16330748

Loss of memory B cells impairs maintenance of long-term serologic memory during HIV-1 infection.

PubMed

Titanji, Kehmia; De Milito, Angelo; Cagigi, Alberto; Thorstensson, Rigmor; Grützmeier, Sven; Atlas, Ann; Hejdeman, Bo; Kroon, Frank P; Lopalco, Lucia; Nilsson, Anna; Chiodi, Francesca

2006-09-01

Circulating memory B cells are severely reduced in the peripheral blood of HIV-1-infected patients. We investigated whether dysfunctional serologic memory to non-HIV antigens is related to disease progression by evaluating the frequency of memory B cells, plasma IgG, plasma levels of antibodies to measles, and Streptococcus pneumoniae, and enumerating measles-specific antibody-secreting cells in patients with primary, chronic, and long-term nonprogressive HIV-1 infection. We also evaluated the in vitro production of IgM and IgG antibodies against measles and S pneumoniae antigens following polyclonal activation of peripheral blood mononuclear cells (PBMCs) from patients. The percentage of memory B cells correlated with CD4+ T-cell counts in patients, thus representing a marker of disease progression. While patients with primary and chronic infection had severe defects in serologic memory, long-term nonprogressors had memory B-cell frequency and levels of antigen-specific antibodies comparable with controls. We also evaluated the effect of antiretroviral therapy on these serologic memory defects and found that antiretroviral therapy did not restore serologic memory in primary or in chronic infection. We suggest that HIV infection impairs maintenance of long-term serologic immunity to HIV-1-unrelated antigens and this defect is initiated early in infection. This may have important consequences for the response of HIV-infected patients to immunizations.

NFκB–Pim-1–Eomesodermin axis is critical for maintaining CD8 T-cell memory quality

PubMed Central

Knudson, Karin M.; Saxena, Vikas; Altman, Amnon; Daniels, Mark A.; Teixeiro, Emma

2017-01-01

T-cell memory is critical for long-term immunity. However, the factors involved in maintaining the persistence, function, and phenotype of the memory pool are undefined. Eomesodermin (Eomes) is required for the establishment of the memory pool. Here, we show that in T cells transitioning to memory, the expression of high levels of Eomes is not constitutive but rather requires a continuum of cell-intrinsic NFκB signaling. Failure to maintain NFκB signals after the peak of the response led to impaired Eomes expression and a defect in the maintenance of CD8 T-cell memory. Strikingly, we found that antigen receptor [T-cell receptor (TCR)] signaling regulates this process through expression of the NFκB-dependent kinase proviral integration site for Moloney murine leukemia virus-1 (PIM-1), which in turn regulates NFκB and Eomes. T cells defective in TCR-dependent NFκB signaling were impaired in late expression of Pim-1, Eomes, and CD8 memory. These defects were rescued when TCR-dependent NFκB signaling was restored. We also found that NFκB–Pim-1 signals were required at memory to maintain memory CD8 T-cell longevity, effector function, and Eomes expression. Hence, an NFκB–Pim-1–Eomes axis regulates Eomes levels to maintain memory fitness. PMID:28193872

A Higher Activation Threshold of Memory CD8+ T Cells Has a Fitness Cost That Is Modified by TCR Affinity during Tuberculosis.

PubMed

Carpenter, Stephen M; Nunes-Alves, Cláudio; Booty, Matthew G; Way, Sing Sing; Behar, Samuel M

2016-01-01

T cell vaccines against Mycobacterium tuberculosis (Mtb) and other pathogens are based on the principle that memory T cells rapidly generate effector responses upon challenge, leading to pathogen clearance. Despite eliciting a robust memory CD8+ T cell response to the immunodominant Mtb antigen TB10.4 (EsxH), we find the increased frequency of TB10.4-specific CD8+ T cells conferred by vaccination to be short-lived after Mtb challenge. To compare memory and naïve CD8+ T cell function during their response to Mtb, we track their expansions using TB10.4-specific retrogenic CD8+ T cells. We find that the primary (naïve) response outnumbers the secondary (memory) response during Mtb challenge, an effect moderated by increased TCR affinity. To determine whether the expansion of polyclonal memory T cells is restrained following Mtb challenge, we used TCRβ deep sequencing to track TB10.4-specific CD8+ T cells after vaccination and subsequent challenge in intact mice. Successful memory T cells, defined by their clonal expansion after Mtb challenge, express similar CDR3β sequences suggesting TCR selection by antigen. Thus, both TCR-dependent and -independent factors affect the fitness of memory CD8+ responses. The impaired expansion of the majority of memory T cell clonotypes may explain why some TB vaccines have not provided better protection.

A Higher Activation Threshold of Memory CD8+ T Cells Has a Fitness Cost That Is Modified by TCR Affinity during Tuberculosis

PubMed Central

Carpenter, Stephen M.; Nunes-Alves, Cláudio; Booty, Matthew G.; Way, Sing Sing; Behar, Samuel M.

2016-01-01

T cell vaccines against Mycobacterium tuberculosis (Mtb) and other pathogens are based on the principle that memory T cells rapidly generate effector responses upon challenge, leading to pathogen clearance. Despite eliciting a robust memory CD8+ T cell response to the immunodominant Mtb antigen TB10.4 (EsxH), we find the increased frequency of TB10.4-specific CD8+ T cells conferred by vaccination to be short-lived after Mtb challenge. To compare memory and naïve CD8+ T cell function during their response to Mtb, we track their expansions using TB10.4-specific retrogenic CD8+ T cells. We find that the primary (naïve) response outnumbers the secondary (memory) response during Mtb challenge, an effect moderated by increased TCR affinity. To determine whether the expansion of polyclonal memory T cells is restrained following Mtb challenge, we used TCRβ deep sequencing to track TB10.4-specific CD8+ T cells after vaccination and subsequent challenge in intact mice. Successful memory T cells, defined by their clonal expansion after Mtb challenge, express similar CDR3β sequences suggesting TCR selection by antigen. Thus, both TCR-dependent and -independent factors affect the fitness of memory CD8+ responses. The impaired expansion of the majority of memory T cell clonotypes may explain why some TB vaccines have not provided better protection. PMID:26745507

Diversity in T cell memory: An embarrassment of riches

PubMed Central

Jameson, Stephen C.; Masopust, David

2010-01-01

The adaptive immune response meets the needs of the organism to generate effector cells capable of controlling pathogens, but also leads to production of memory cells, which mediate more effective protection during rechallenge. In this review we focus on the generation, maintenance and function of memory T cells, with a special emphasis on the increasing evidence for great diversity among functional memory T cell subsets. PMID:20064446

Endogenous Memory CD8 T Cells Directly Mediate Cardiac Allograft Rejection

PubMed Central

Su, C. A.; Iida, S.; Abe, T.; Fairchild, R. L.

2014-01-01

Differences in levels of environmentally induced memory T cells that cross-react with donor MHC molecules are postulated to account for the efficacy of allograft tolerance inducing strategies in rodents versus their failure in nonhuman primates and human transplant patients. Strategies to study the impact of donor-reactive memory T cells on allografts in rodents have relied on the pre-transplant induction of memory T cells cross-reactive with donor allogeneic MHC molecules through recipient viral infection, priming directly with donor antigen, or adoptive transfer of donor-antigen primed memory T cells. Each approach accelerates allograft rejection and confers resistance to tolerance induction, but also biases the T cell repertoire to strong donor-reactivity. The ability of endogenous memory T cells within unprimed mice to directly reject an allograft is unknown. Here we show a direct association between increased duration of cold ischemic allograft storage and numbers and enhanced functions of early graft infiltrating endogenous CD8 memory T cells. These T cells directly mediate rejection of allografts subjected to prolonged ischemia and this rejection is resistant to costimulatory blockade. These findings recapitulate the clinically significant impact of endogenous memory T cells with donor reactivity in a mouse transplant model in the absence of prior recipient priming. PMID:24502272

Cell-autonomous CCL5 transcription by memory CD8 T cells is regulated by IL-4.

PubMed

Marçais, Antoine; Coupet, Charles-Antoine; Walzer, Thierry; Tomkowiak, Martine; Ghittoni, Raffaella; Marvel, Jacqueline

2006-10-01

Immunological memory is associated with the display of improved effector functions. The maintenance by CD8 memory cells of high levels of untranslated CCL5 mRNA allows these cells to immediately secrete this chemokine upon Ag stimulation. Untranslated mRNA storage is a newly described process supporting the immediate display of an effector function by memory lymphocytes. We have tested the capacity of different cytokines to regulate the memorization of CCL5 by memory CD8 T cells. We found that IL-4 treatment of murine CD8 T cells impairs immediate CCL5 secretion capacity by inhibiting CCL5 mRNA transcription through a STAT6-dependent pathway. The inhibition by IL-4 is reversible, as memory CD8 T cells reconstitute their CCL5 mRNA stores and reacquire their immediate CCL5 secretion capacity when IL-4 is withdrawn. This recovery is cell autonomous because it proceeds in culture medium in the absence of exogenous growth factors, suggesting that CCL5 expression by memory CD8 T cells is a default process. Overall, these results indicate that the expression of CCL5 is an intrinsic property acquired by memory CD8 T cells that is regulated by environmental factors.

Memory T cells maintain protracted protection against malaria.

PubMed

Krzych, Urszula; Zarling, Stasya; Pichugin, Alexander

2014-10-01

Immunologic memory is one of the cardinal features of antigen-specific immune responses, and the persistence of memory cells contributes to prophylactic immunizations against infectious agents. Adequately maintained memory T and B cell pools assure a fast, effective and specific response against re-infections. However, many aspects of immunologic memory are still poorly understood, particularly immunologic memory inducible by parasites, for example, Plasmodium spp., the causative agents of malaria. For example, memory responses to Plasmodium antigens amongst residents of malaria endemic areas appear to be either inadequately developed or maintained, because persons who survive episodes of childhood malaria remain vulnerable to intermittent malaria infections. By contrast, multiple exposures of humans and laboratory rodents to radiation-attenuated Plasmodium sporozoites (γ-spz) induce sterile and long-lasting protection against experimental sporozoite challenge. Multifactorial immune mechanisms maintain this protracted and sterile protection. While the presence of memory CD4 T cell subsets has been associated with lasting protection in humans exposed to multiple bites from Anopheles mosquitoes infected with attenuated Plasmodium falciparum, memory CD8 T cells maintain protection induced with Plasmodium yoelii and Plasmodium berghei γ-spz in murine models. In this review, we discuss our observations that show memory CD8 T cells specific for antigens expressed by P. berghei liver stage parasites as an indispensable component for the maintenance of protracted protective immunity against experimental malaria infection; moreover, the provision of an Ag-depot assures a quick recall of memory T cells as IFN-γ-producing effector CD8 T cells and IL-4- producing CD4 T cells that collaborate with B cells for an effective antibody response. Published by Elsevier B.V.

TLR4 ligands LPS and MPLA differentially regulate effector and memory CD8+ T cell differentiation

PubMed Central

Cui, Weiguo; Joshi, Nikhil S.; Liu, Ying; Meng, Hailong; Kleinstein, Steven H; Kaech, Susan M.

2014-01-01

Vaccines formulated with non-replicating pathogens require adjuvants to help bolster immunogenicity. The role of adjuvants in antibody production has been well studied, but how they influence memory CD8+ T cell differentiation remains poorly defined. Here we implemented dendritic cell (DC)-mediated immunization to study the effects of commonly used adjuvants, TLR ligands, on effector and memory CD8+ T cell differentiation in mice. Intriguingly, we found that the TLR4 ligand LPS was far more superior to other TLR ligands in generating memory CD8+ T cells upon immunization. LPS boosted clonal expansion similar to the other adjuvants, but fewer of the activated CD8+ T cells died during contraction, generating a larger pool of memory cells. Surprisingly, monophosphoryl lipid A (MPLA), another TLR4 ligand, enhanced clonal expansion of effector CD8+ T cells, but also promoted their terminal differentiation and contraction; thus, fewer memory CD8+ T cells formed and MPLA-primed animals were less protected against secondary infection compared to those primed with LPS. Furthermore, gene expression profiling revealed that LPS-primed effector cells displayed a stronger pro-memory gene expression signature, whereas the gene expression profile of MPLA-primed effector cells aligned closer with terminal effector CD8+ T cells. Lastly, we demonstrated that the LPS-TLR4-derived “pro-memory” signals were MyD88, but not Trif, dependent. This study reveals the influential power of adjuvants on the quantity and quality of CD8+ T cell memory, and that attention to adjuvant selection is crucial because boosting effector cell expansion may not always equate with more memory T cells or greater protection. PMID:24659688

Eight microprocessor-based instrument data systems in the Galileo Orbiter spacecraft

NASA Technical Reports Server (NTRS)

Barry, R. C.

1980-01-01

Instrument data systems consist of a microprocessor, 3K bytes of Read Only Memory and 3K bytes of Random Access Memory. It interfaces with the spacecraft data bus through an isolated user interface with a direct memory access bus adaptor, and/or parallel data from instrument devices such as registers, buffers, analog to digital converters, multiplexers, and solid state sensors. These data systems support the spacecraft hardware and software communication protocol, decode and process instrument commands, generate continuous instrument operating modes, control the instrument mechanisms, acquire, process, format, and output instrument science data.

Write operation study of Co/BTO/LSMO ferroelectric tunnel junction

NASA Astrophysics Data System (ADS)

Wang, Z. H.; Zhao, W. S.; Kang, W.; Bouchenak-Khelladi, A.; Zhang, Y.; Klein, J.-O.; Ravelosona, D.; Chappert, C.

2013-07-01

Recently, a Co/BaTiO3/La0.67Sr0.33MnO3 (Co/BTO/LSMO) ferroelectric tunnel junction (FTJ) has shown the great potential towards non-volatile memory and logic applications due to its excellent performance. Especially, the giant OFF/ON tunnel resistance ratio (e.g., ˜100) assures that FTJ-based random access memory (FTRAM) can achieve lower reading error rate than emerging magnetic RAM. Nevertheless, in this paper, our investigation demonstrated that this FTJ suffered from difficulties in write operation when integrating with current CMOS technology into a FTRAM. Specifically, the write performances of Co/BTO/LSMO 1T1R FTRAM such as cell area, speed, energy dissipation, and thermal fluctuation effect were simulated and evaluated with a compact model and CMOS 40 nm design kit. Simulation results indicate the drawbacks of this FTRAM including significant performance asymmetry between two write orientations, high write voltage, large cell area, and severe thermal fluctuation disturbance. Simultaneously, this research provides several methods of improving write performance of FTRAM from the perspective of device size and process parameters.

A Genome-wide Regulatory Network Identifies Key Transcription Factors for Memory CD8+ T Cell Development

PubMed Central

Hu, Guangan; Chen, Jianzhu

2014-01-01

Memory CD8+ T cell development is defined by the expression of a specific set of memory signature genes (MSGs). Despite recent progress, many components of the transcriptional control of memory CD8+ T cell development are still unknown. To identify transcription factors (TFs) and their interactions in memory CD8+ T cell development, we construct a genome-wide regulatory network and apply it to identify key TFs that regulate MSGs. Most of the known TFs in memory CD8+ T cell development are rediscovered and about a dozen new TFs are also identified. Sox4, Bhlhe40, Bach2 and Runx2 are experimentally verified and Bach2 is further shown to promote both development and recall proliferation of memory CD8+ T cells through Prdm1 and Id3. Gene perturbation study identifies the mode of interactions among the TFs with Sox4 as a hub. The identified TFs and insights into their interactions should facilitate further dissection of molecular mechanisms underlying memory CD8+ T cell development. PMID:24335726

Memory-like Responses of Natural Killer Cells

PubMed Central

Cooper, Megan A.; Yokoyama, Wayne M.

2010-01-01

Summary Natural killer (NK) cells are lymphocytes with the capacity to produce cytokines and kill target cells upon activation. NK cells have long been categorized as members of the innate immune system and as such have been thought to follow the ‘rules’ of innate immunity, including the principle that they have no immunologic memory, a property thought to be strictly limited to adaptive immunity. However, recent studies have suggested that NK cells have the capacity to alter their behavior based on prior activation. This property is analogous to adaptive immune memory; however, some NK cell memory-like functions are not strictly antigen-dependent and can be demonstrated following cytokine stimulation. Here we discuss the recent evidence that NK cells can exhibit properties of immunologic memory, focusing on the ability of cytokines to non-specifically induce memory-like NK cells with enhanced responses to restimulation. PMID:20536571

Interregional synaptic maps among engram cells underlie memory formation.

PubMed

Choi, Jun-Hyeok; Sim, Su-Eon; Kim, Ji-Il; Choi, Dong Il; Oh, Jihae; Ye, Sanghyun; Lee, Jaehyun; Kim, TaeHyun; Ko, Hyoung-Gon; Lim, Chae-Seok; Kaang, Bong-Kiun

2018-04-27

Memory resides in engram cells distributed across the brain. However, the site-specific substrate within these engram cells remains theoretical, even though it is generally accepted that synaptic plasticity encodes memories. We developed the dual-eGRASP (green fluorescent protein reconstitution across synaptic partners) technique to examine synapses between engram cells to identify the specific neuronal site for memory storage. We found an increased number and size of spines on CA1 engram cells receiving input from CA3 engram cells. In contextual fear conditioning, this enhanced connectivity between engram cells encoded memory strength. CA3 engram to CA1 engram projections strongly occluded long-term potentiation. These results indicate that enhanced structural and functional connectivity between engram cells across two directly connected brain regions forms the synaptic correlate for memory formation. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Engrams and circuits crucial for systems consolidation of a memory.

PubMed

Kitamura, Takashi; Ogawa, Sachie K; Roy, Dheeraj S; Okuyama, Teruhiro; Morrissey, Mark D; Smith, Lillian M; Redondo, Roger L; Tonegawa, Susumu

2017-04-07

Episodic memories initially require rapid synaptic plasticity within the hippocampus for their formation and are gradually consolidated in neocortical networks for permanent storage. However, the engrams and circuits that support neocortical memory consolidation have thus far been unknown. We found that neocortical prefrontal memory engram cells, which are critical for remote contextual fear memory, were rapidly generated during initial learning through inputs from both the hippocampal-entorhinal cortex network and the basolateral amygdala. After their generation, the prefrontal engram cells, with support from hippocampal memory engram cells, became functionally mature with time. Whereas hippocampal engram cells gradually became silent with time, engram cells in the basolateral amygdala, which were necessary for fear memory, were maintained. Our data provide new insights into the functional reorganization of engrams and circuits underlying systems consolidation of memory. Copyright © 2017, American Association for the Advancement of Science.

Vertical Launch System Loadout Planner

DTIC Science & Technology

2015-03-01

United States Navy USS United States’ Ship VBA Visual Basic for Applications VLP VLS Loadout Planner VLS Vertical Launch System...with 32 gigabytes of random access memory and eight processors, General Algebraic Modeling System (GAMS) CPLEX version 24 (GAMS, 2015) solves this...problem in ten minutes to an integer tolerance of 10%. The GAMS interpreter and CPLEX solver require 75 Megabytes of random access memory for this

Nonvolatile GaAs Random-Access Memory

NASA Technical Reports Server (NTRS)

Katti, Romney R.; Stadler, Henry L.; Wu, Jiin-Chuan

1994-01-01

Proposed random-access integrated-circuit electronic memory offers nonvolatile magnetic storage. Bits stored magnetically and read out with Hall-effect sensors. Advantages include short reading and writing times and high degree of immunity to both single-event upsets and permanent damage by ionizing radiation. Use of same basic material for both transistors and sensors simplifies fabrication process, with consequent benefits in increased yield and reduced cost.

MemAxes Visualization Software

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hardware advancements such as Intel's PEBS and AMD's IBS, as well as software developments such as the perf_event API in Linux have made available the acquisition of memory access samples with performance information. MemAxes is a visualization and analysis tool for memory access sample data. By mapping the samples to their associated code, variables, node topology, and application dataset, MemAxes provides intuitive views of the data.

Recollection Rejection: How Children Edit Their False Memories.

ERIC Educational Resources Information Center

Brainerd, C. J.; Reyna, V. F.

2002-01-01

Presents new measure of children's use of an editing operation that suppresses false memories by accessing verbatim traces of true events. Application of the methodology showed that false-memory editing increased dramatically between early and middle childhood. Measure reacted appropriately to experimental manipulations. Developmental reductions…

Skin-resident CD4+ T cells protect against Leishmania major by recruiting and activating inflammatory monocytes

PubMed Central

Glennie, Nelson D.; Volk, Susan W.

2017-01-01

Tissue-resident memory T cells are required for establishing protective immunity against a variety of different pathogens, although the mechanisms mediating protection by CD4+ resident memory T cells are still being defined. In this study we addressed this issue with a population of protective skin-resident, IFNγ-producing CD4+ memory T cells generated following Leishmania major infection. We previously found that resident memory T cells recruit circulating effector T cells to enhance immunity. Here we show that resident memory CD4+ T cells mediate the delayed-hypersensitivity response observed in immune mice and provide protection without circulating T cells. This protection occurs rapidly after challenge, and requires the recruitment and activation of inflammatory monocytes, which limit parasites by production of both reactive oxygen species and nitric oxide. Overall, these data highlight a novel role for tissue-resident memory cells in recruiting and activating inflammatory monocytes, and underscore the central role that skin-resident T cells play in immunity to cutaneous leishmaniasis. PMID:28419151

γδ T cells exhibit multifunctional and protective memory in intestinal tissues

PubMed Central

Sheridan, Brian S.; Romagnoli, Pablo A.; Pham, Quynh-Mai; Fu, Han-Hsuan; Alonzo, Francis; Schubert, Wolf-Dieter; Freitag, Nancy E.; Lefrançois, Leo

2013-01-01

Summary The study of T cell memory and the target of vaccine design has focused on memory subsumed by T cells bearing the αβ T cell receptor. Alternatively, γδ T cells are thought to provide rapid immunity particularly at mucosal borders. Here we have shown that a distinct subset of mucosal γδ T cells mounts an immune response to oral Listeria monocytogenes (Lm) infection leading to the development of multifunctional memory T cells in the murine intestinal mucosa that is capable of simultaneously producing interferon-γ and interleukin-17A. Challenge infection with oral Lm, but not oral Salmonella or intravenous Lm, induced rapid expansion of memory γδ T cells suggesting contextual specificity to the priming pathogen. Importantly, memory γδ T cells were able to provide enhanced protection against infection. These findings illustrate a previously unrecognized role for γδ T cells with hallmarks of adaptive immunity in the intestinal mucosa. PMID:23890071

Ezh2 phosphorylation state determines its capacity to maintain CD8+ T memory precursors for antitumor immunity.

PubMed

He, Shan; Liu, Yongnian; Meng, Lijun; Sun, Hongxing; Wang, Ying; Ji, Yun; Purushe, Janaki; Chen, Pan; Li, Changhong; Madzo, Jozef; Issa, Jean-Pierre; Soboloff, Jonathan; Reshef, Ran; Moore, Bethany; Gattinoni, Luca; Zhang, Yi

2017-12-14

Memory T cells sustain effector T-cell production while self-renewing in reaction to persistent antigen; yet, excessive expansion reduces memory potential and impairs antitumor immunity. Epigenetic mechanisms are thought to be important for balancing effector and memory differentiation; however, the epigenetic regulator(s) underpinning this process remains unknown. Herein, we show that the histone methyltransferase Ezh2 controls CD8 + T memory precursor formation and antitumor activity. Ezh2 activates Id3 while silencing Id2, Prdm1 and Eomes, promoting the expansion of memory precursor cells and their differentiation into functional memory cells. Akt activation phosphorylates Ezh2 and decreases its control of these transcriptional programs, causing enhanced effector differentiation at the expense of T memory precursors. Engineering T cells with an Akt-insensitive Ezh2 mutant markedly improves their memory potential and capability of controlling tumor growth compared to transiently inhibiting Akt. These findings establish Akt-mediated phosphorylation of Ezh2 as a critical target to potentiate antitumor immunotherapeutic strategies.

Transcriptional Profiling of Antigen-Dependent Murine B Cell Differentiation and Memory Formation1

PubMed Central

Bhattacharya, Deepta; Cheah, Ming T.; Franco, Christopher B.; Hosen, Naoki; Pin, Christopher L.; Sha, William C.; Weissman, Irving L.

2015-01-01

Humoral immunity is characterized by the generation of Ab-secreting plasma cells and memory B cells that can more rapidly generate specific Abs upon Ag exposure than their naive counterparts. To determine the intrinsic differences that distinguish naive and memory B cells and to identify pathways that allow germinal center B cells to differentiate into memory B cells, we compared the transcriptional profiles of highly purified populations of these three cell types along with plasma cells isolated from mice immunized with a T-dependent Ag. The transcriptional profile of memory B cells is similar to that of naive B cells, yet displays several important differences, including increased expression of activation-induced deaminase and several antiapoptotic genes, chemotactic receptors, and costimulatory molecules. Retroviral expression of either Klf2 or Ski, two transcriptional regulators specifically enriched in memory B cells relative to their germinal center precursors, imparted a competitive advantage to Ag receptor and CD40-engaged B cells in vitro. These data suggest that humoral recall responses are more rapid than primary responses due to the expression of a unique transcriptional program by memory B cells that allows them to both be maintained at high frequencies and to detect and rapidly respond to antigenic re-exposure. PMID:17982071

Microneedle Array Design Determines the Induction of Protective Memory CD8+ T Cell Responses Induced by a Recombinant Live Malaria Vaccine in Mice

PubMed Central

Carey, John B.; Pearson, Frances E.; Vrdoljak, Anto; McGrath, Marie G.; Crean, Abina M.; Walsh, Patrick T.; Doody, Timothy; O'Mahony, Conor; Hill, Adrian V. S.; Moore, Anne C.

2011-01-01

Background Vaccine delivery into the skin has received renewed interest due to ease of access to the immune system and microvasculature, however the stratum corneum (SC), must be breached for successful vaccination. This has been achieved by removing the SC by abrasion or scarification or by delivering the vaccine intradermally (ID) with traditional needle-and-syringes or with long microneedle devices. Microneedle patch-based transdermal vaccine studies have predominantly focused on antibody induction by inactivated or subunit vaccines. Here, our principal aim is to determine if the design of a microneedle patch affects the CD8+ T cell responses to a malaria antigen induced by a live vaccine. Methodology and Findings Recombinant modified vaccinia virus Ankara (MVA) expressing a malaria antigen was percutaneously administered to mice using a range of silicon microneedle patches, termed ImmuPatch, that differed in microneedle height, density, patch area and total pore volume. We demonstrate that microneedle arrays that have small total pore volumes induce a significantly greater proportion of central memory T cells that vigorously expand to secondary immunization. Microneedle-mediated vaccine priming induced significantly greater T cell immunity post-boost and equivalent protection against malaria challenge compared to ID vaccination. Notably, unlike ID administration, ImmuPatch-mediated vaccination did not induce inflammatory responses at the site of immunization or in draining lymph nodes. Conclusions/Significance This study demonstrates that the design of microneedle patches significantly influences the magnitude and memory of vaccine-induced CD8+ T cell responses and can be optimised for the induction of desired immune responses. Furthermore, ImmuPatch-mediated delivery may be of benefit to reducing unwanted vaccine reactogenicity. In addition to the advantages of low cost and lack of pain, the development of optimised microneedle array designs for the induction of T cell responses by live vaccines aids the development of solutions to current obstacles of immunization programmes. PMID:21799855

FOXO1 opposition of CD8+ T cell effector programming confers early memory properties and phenotypic diversity.

PubMed

Delpoux, Arnaud; Lai, Chen-Yen; Hedrick, Stephen M; Doedens, Andrew L

2017-10-17

The factors and steps controlling postinfection CD8 + T cell terminal effector versus memory differentiation are incompletely understood. Whereas we found that naive TCF7 (alias "Tcf-1") expression is FOXO1 independent, early postinfection we report bimodal, FOXO1-dependent expression of the memory-essential transcription factor TCF7 in pathogen-specific CD8 + T cells. We determined the early postinfection TCF7 high population is marked by low TIM3 expression and bears memory signature hallmarks before the appearance of established memory precursor marker CD127 (IL-7R). These cells exhibit diminished TBET, GZMB, mTOR signaling, and cell cycle progression. Day 5 postinfection, TCF7 high cells express higher memory-associated BCL2 and EOMES, as well as increased accumulation potential and capacity to differentiate into memory phenotype cells. TCF7 retroviral transduction opposes GZMB expression and the formation of KLRG1 pos phenotype cells, demonstrating an active role for TCF7 in extinguishing the effector program and forestalling terminal differentiation. Past the peak of the cellular immune response, we report a gradient of FOXO1 and TCF7 expression, which functions to oppose TBET and orchestrate a continuum of effector-to-memory phenotypes.

Ablation of SLP-76 signaling after T cell priming generates memory CD4 T cells impaired in steady-state and cytokine-driven homeostasis.

PubMed

Bushar, Nicholas D; Corbo, Evann; Schmidt, Michelle; Maltzman, Jonathan S; Farber, Donna L

2010-01-12

The intracellular signaling mechanisms regulating the generation and long-term persistence of memory T cells in vivo remain unclear. In this study, we used mouse models with conditional deletion of the key T cell receptor (TCR)-coupled adaptor molecule SH2-domain-containing phosphoprotein of 76 kDa (SLP-76), to analyze signaling mechanisms for memory CD4 T cell generation, maintenance, and homeostasis. We found that ablation of SLP-76 expression after T cell priming did not inhibit generation of phenotypic effector or memory CD4 T cells; however, the resultant SLP-76-deficient memory CD4 T cells could not produce recall cytokines in response to TCR-mediated stimulation and showed decreased persistence in vivo. In addition, SLP-76-deficient memory CD4 T cells exhibited reduced steady-state homeostasis and were impaired in their ability to homeostatically expand in vivo in response to the gamma(c) cytokine IL-7, despite intact proximal signaling through the IL-7R-coupled JAK3/STAT5 pathway. Direct in vivo deletion of SLP-76 in polyclonal memory CD4 T cells likewise led to impaired steady-state homeostasis as well as impaired homeostatic responses to IL-7. Our findings demonstrate a dominant role for SLP-76-dependent TCR signals in regulating turnover and perpetuation of memory CD4 T cells and their responses to homeostatic cytokines, with implications for the selective survival of memory CD4 T cells following pathogen exposure, vaccination, and aging.

Dynamic phenotypic restructuring of the CD4 and CD8 T-cell subsets with age in healthy humans: a compartmental model analysis.

PubMed

Jackola, D R; Hallgren, H M

1998-11-16

In healthy humans, phenotypic restructuring occurs with age within the CD3+ T-lymphocyte complement. This is characterized by a non-linear decrease of the percentage of 'naive' (CD45RA+) cells and a corresponding non-linear increase of the percentage of 'memory' (CD45R0+) cells among both the CD4+ and CD8+ T-cell subsets. We devised a simple compartmental model to study the age-dependent kinetics of phenotypic restructuring. We also derived differential equations whose parameters determined yearly gains minus losses of the percentage and absolute numbers of circulating naive cells, yearly gains minus losses of the percentage and absolute numbers of circulating memory cells, and the yearly rate of conversion of naive to memory cells. Solutions of these evaluative differential equations demonstrate the following: (1) the memory cell complement 'resides' within its compartment for a longer time than the naive cell complement within its compartment for both CD4 and CD8 cells; (2) the average, annual 'turnover rate' is the same for CD4 and CD8 naive cells. In contrast, the average, annual 'turnover rate' for memory CD8 cells is 1.5 times that of memory CD4 cells; (3) the average, annual conversion rate of CD4 naive cells to memory cells is twice that of the CD8 conversion rate; (4) a transition in dynamic restructuring occurs during the third decade of life that is due to these differences in turnover and conversion rates, between and from naive to memory cells.

Another look at retroactive and proactive interference: a quantitative analysis of conversion processes.

PubMed

Blank, Hartmut

2005-02-01

Traditionally, the causes of interference phenomena were sought in "real" or "hard" memory processes such as unlearning, response competition, or inhibition, which serve to reduce the accessibility of target items. I propose an alternative approach which does not deny the influence of such processes but highlights a second, equally important, source of interference-the conversion (Tulving, 1983) of accessible memory information into memory performance. Conversion is conceived as a problem-solving-like activity in which the rememberer tries to find solutions to a memory task. Conversion-based interference effects are traced to different conversion processes in the experimental and control conditions of interference designs. I present a simple theoretical model that quantitatively predicts the resulting amount of interference. In two paired-associate learning experiments using two different types of memory tests, these predictions were corroborated. Relations of the present approach to traditional accounts of interference phenomena and implications for eyewitness testimony are discussed.

On Using the Volatile Mem-Capacitive Effect of TiO2 Resistive Random Access Memory to Mimic the Synaptic Forgetting Process

NASA Astrophysics Data System (ADS)

Sarkar, Biplab; Mills, Steven; Lee, Bongmook; Pitts, W. Shepherd; Misra, Veena; Franzon, Paul D.

2018-02-01

In this work, we report on mimicking the synaptic forgetting process using the volatile mem-capacitive effect of a resistive random access memory (RRAM). TiO2 dielectric, which is known to show volatile memory operations due to migration of inherent oxygen vacancies, was used to achieve the volatile mem-capacitive effect. By placing the volatile RRAM candidate along with SiO2 at the gate of a MOS capacitor, a volatile capacitance change resembling the forgetting nature of a human brain is demonstrated. Furthermore, the memory operation in the MOS capacitor does not require a current flow through the gate dielectric indicating the feasibility of obtaining low power memory operations. Thus, the mem-capacitive effect of volatile RRAM candidates can be attractive to the future neuromorphic systems for implementing the forgetting process of a human brain.

Marijuana effects on long-term memory assessment and retrieval.

PubMed

Darley, C F; Tinklenberg, J R; Roth, W T; Vernon, S; Kopell, B S

1977-05-09

The ability of 16 college-educated male subjects to recall from long-term memory a series of common facts was tested during intoxication with marijuana extract calibrated to 0.3 mg/kg delta-9-tetrahydrocannabinol and during placebo conditions. The subjects' ability to assess their memory capabilities was then determined by measuring how certain they were about the accuracy of their recall performance and by having them predict their performance on a subsequent recognition test involving the same recall items. Marijuana had no effect on recall or recognition performance. These results do not support the view that marijuana provides access to facts in long-term storage which are inaccessible during non-intoxication. During both marijuana and placebo conditions, subjects could accurately predict their recognition memory performance. Hence, marijuana did not alter the subjects' ability to accurately assess what information resides in long-term memory even though they did not have complete access to that information.

Parameter optimization for transitions between memory states in small arrays of Josephson junctions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rezac, Jacob D.; Imam, Neena; Braiman, Yehuda

Coupled arrays of Josephson junctions possess multiple stable zero voltage states. Such states can store information and consequently can be utilized for cryogenic memory applications. Basic memory operations can be implemented by sending a pulse to one of the junctions and studying transitions between the states. In order to be suitable for memory operations, such transitions between the states have to be fast and energy efficient. Here in this article we employed simulated annealing, a stochastic optimization algorithm, to study parameter optimization of array parameters which minimizes times and energies of transitions between specifically chosen states that can be utilizedmore » for memory operations (Read, Write, and Reset). Simulation results show that such transitions occur with access times on the order of 10–100 ps and access energies on the order of 10 -19–5×10 -18 J. Numerical simulations are validated with approximate analytical results.« less

The contribution of epigenetic memory to immunologic memory.

PubMed

Zediak, Valerie P; Wherry, E John; Berger, Shelley L

2011-04-01

Memory T lymphocytes are distinct from antigen-inexperienced naïve T cells in that memory T cells can respond more rapidly when they re-encounter a pathogen. Work over the past decade has begun to define the epigenetic underpinnings of the transcriptional component of the memory T cell response. An emerging theme is the persistence of an active chromatin signature at relevant gene loci in resting memory T cells, even when those genes are transcriptionally inactive. This gives strength to the concept of gene poising, and has shown that memory T lymphocytes are an ideal model in which to further define various mechanisms of epigenetic poising. Copyright © 2011 Elsevier Ltd. All rights reserved.

Functional classification of memory CD8(+) T cells by CX3CR1 expression.

PubMed

Böttcher, Jan P; Beyer, Marc; Meissner, Felix; Abdullah, Zeinab; Sander, Jil; Höchst, Bastian; Eickhoff, Sarah; Rieckmann, Jan C; Russo, Caroline; Bauer, Tanja; Flecken, Tobias; Giesen, Dominik; Engel, Daniel; Jung, Steffen; Busch, Dirk H; Protzer, Ulrike; Thimme, Robert; Mann, Matthias; Kurts, Christian; Schultze, Joachim L; Kastenmüller, Wolfgang; Knolle, Percy A

2015-09-25

Localization of memory CD8(+) T cells to lymphoid or peripheral tissues is believed to correlate with proliferative capacity or effector function. Here we demonstrate that the fractalkine-receptor/CX3CR1 distinguishes memory CD8(+) T cells with cytotoxic effector function from those with proliferative capacity, independent of tissue-homing properties. CX3CR1-based transcriptome and proteome-profiling defines a core signature of memory CD8(+) T cells with effector function. We find CD62L(hi)CX3CR1(+) memory T cells that reside within lymph nodes. This population shows distinct migration patterns and positioning in proximity to pathogen entry sites. Virus-specific CX3CR1(+) memory CD8(+) T cells are scarce during chronic infection in humans and mice but increase when infection is controlled spontaneously or by therapeutic intervention. This CX3CR1-based functional classification will help to resolve the principles of protective CD8(+) T-cell memory.

Effects of Recording Food Intake Using Cell Phone Camera Pictures on Energy Intake and Food Choice.

PubMed

Doumit, Rita; Long, JoAnn; Kazandjian, Chant; Gharibeh, Nathalie; Karam, Lina; Song, Huaxin; Boswell, Carol; Zeeni, Nadine

2016-06-01

The well-documented increases in obesity and unhealthy dietary practices substantiate the need for evidence-based tools that can help people improve their dietary habits. The current spread of mobile phone-embedded cameras offers new opportunities for recording food intake. Moreover, the act of taking pictures of food consumed may enhance visual consciousness of food choice and quantity. The present study aimed to assess the effect of using cell phone pictures to record food intake on energy intake and food choice in college students. The effectiveness and acceptability of cell phone picture-based diet recording also was assessed. A repeated measures crossover design was used. One group of participants entered their food intake online during 3 days based on their memory, although a second group recorded their food intake using cell phone pictures as their reference. Participants then crossed over to complete 3 more days of diet recording using the alternate method. Focus groups were conducted to obtain feedback on the effectiveness and acceptability of cell phone picture-based diet recording. Intake of meat and vegetable servings were significantly higher in the memory period compared with the cell phone period, regardless of the order. Results from the focus group indicated a positive attitude toward the use of cell phone pictures in recording food intake and an increased awareness of food choice and portion size. Cell phone pictures may be an easy, relevant, and accessible method of diet self-monitoring when aiming at dietary changes. Future trials should combine this technique with healthy eating education. © 2015 Sigma Theta Tau International.

Implications of scaling on static RAM bit cell stability and reliability

NASA Astrophysics Data System (ADS)

Coones, Mary Ann; Herr, Norm; Bormann, Al; Erington, Kent; Soorholtz, Vince; Sweeney, John; Phillips, Michael

1993-01-01

In order to lower manufacturing costs and increase performance, static random access memory (SRAM) bit cells are scaled progressively toward submicron geometries. The reliability of an SRAM is highly dependent on the bit cell stability. Smaller memory cells with less capacitance and restoring current make the array more susceptible to failures from defectivity, alpha hits, and other instabilities and leakage mechanisms. Improving long term reliability while migrating to higher density devices makes the task of building in and improving reliability increasingly difficult. Reliability requirements for high density SRAMs are very demanding with failure rates of less than 100 failures per billion device hours (100 FITs) being a common criteria. Design techniques for increasing bit cell stability and manufacturability must be implemented in order to build in this level of reliability. Several types of analyses are performed to benchmark the performance of the SRAM device. Examples of these analysis techniques which are presented here include DC parametric measurements of test structures, functional bit mapping of the circuit used to characterize the entire distribution of bits, electrical microprobing of weak and/or failing bits, and system and accelerated soft error rate measurements. These tests allow process and design improvements to be evaluated prior to implementation on the final product. These results are used to provide comprehensive bit cell characterization which can then be compared to device models and adjusted accordingly to provide optimized cell stability versus cell size for a particular technology. The result is designed in reliability which can be accomplished during the early stages of product development.

Massive infection and loss of CD4+ T cells occurs in the intestinal tract of neonatal rhesus macaques in acute SIV infection.

PubMed

Wang, Xiaolei; Rasmussen, Terri; Pahar, Bapi; Poonia, Bhawna; Alvarez, Xavier; Lackner, Andrew A; Veazey, Ronald S

2007-02-01

Rapid, profound, and selective depletion of memory CD4+ T cells has now been confirmed to occur in simian immunodeficiency virus (SIV)-infected adult macaques and human immunodeficiency virus (HIV)-infected humans. Within days of infection, marked depletion of memory CD4+ T cells occurs primarily in mucosal tissues, the major reservoir for memory CD4+ T cells in adults. However, HIV infection in neonates often results in higher viral loads and rapid disease progression, despite the paucity of memory CD4+ T cells in the peripheral blood. Here, we examined the immunophenotype of CD4+ T cells in normal and SIV-infected neonatal macaques to determine the distribution of naive and memory T-cell subsets in tissues. We demonstrate that, similar to adults, neonates have abundant memory CD4+ T cells in the intestinal tract and spleen and that these are selectively infected and depleted in primary SIV infection. Within 12 days of SIV infection, activated (CD69+), central memory (CD95+CD28+) CD4+ T cells are marked and persistently depleted in the intestine and other tissues of neonates compared with controls. The results in dicate that "activated" central memory CD4+ T cells are the major target for early SIV infection and CD4+ T cell depletion in neonatal macaques.

Massive infection and loss of CD4+ T cells occurs in the intestinal tract of neonatal rhesus macaques in acute SIV infection

PubMed Central

Wang, Xiaolei; Rasmussen, Terri; Pahar, Bapi; Poonia, Bhawna; Alvarez, Xavier; Lackner, Andrew A.; Veazey, Ronald S.

2007-01-01

Rapid, profound, and selective depletion of memory CD4+ T cells has now been confirmed to occur in simian immunodeficiency virus (SIV)–infected adult macaques and human immunodeficiency virus (HIV)–infected humans. Within days of infection, marked depletion of memory CD4+ T cells occurs primarily in mucosal tissues, the major reservoir for memory CD4+ T cells in adults. However, HIV infection in neonates often results in higher viral loads and rapid disease progression, despite the paucity of memory CD4+ T cells in the peripheral blood. Here, we examined the immunophenotype of CD4+ T cells in normal and SIV-infected neonatal macaques to determine the distribution of naive and memory T-cell subsets in tissues. We demonstrate that, similar to adults, neonates have abundant memory CD4+ T cells in the intestinal tract and spleen and that these are selectively infected and depleted in primary SIV infection. Within 12 days of SIV infection, activated (CD69+), central memory (CD95+CD28+) CD4+ T cells are marked and persistently depleted in the intestine and other tissues of neonates compared with controls. The results in dicate that “activated” central memory CD4+ T cells are the major target for early SIV infection and CD4+ T cell depletion in neonatal macaques. PMID:17047153

Dementia - daily care

MedlinePlus

... pdf . Accessed on June 27, 2016. Budson AE, Solomon PR. Life adjustments for memory loss, Alzheimer's disease, and dementia. In: Budson AE, Solomon PR, eds. Memory Loss, Alzheimer's Disease, and Dementia: ...

Neutron imaging integrated circuit and method for detecting neutrons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagarkar, Vivek V.; More, Mitali J.

The present disclosure provides a neutron imaging detector and a method for detecting neutrons. In one example, a method includes providing a neutron imaging detector including plurality of memory cells and a conversion layer on the memory cells, setting one or more of the memory cells to a first charge state, positioning the neutron imaging detector in a neutron environment for a predetermined time period, and reading a state change at one of the memory cells, and measuring a charge state change at one of the plurality of memory cells from the first charge state to a second charge statemore » less than the first charge state, where the charge state change indicates detection of neutrons at said one of the memory cells.« less

Memory B cells in Guillain-Barré syndrome.

PubMed

Wang, Qian; Xing, Chunye; Hao, Yanlei; Shi, Qiguang; Qi, Ziyou; Lv, Zhanyun; Song, Yan; Xu, Peng; Feng, Xungang; Zhang, Lili; Zhang, Yong; Wang, Yuzhong; Yuki, Nobuhiro

2017-04-15

IgG autoantibodies against gangliosides show the highest titers at the disease onset of axonal Guillain-Barré syndrome (GBS), in which there are no IgM anti-ganglioside antibodies. We hypothesized that memory B cells take part in the development of producing IgG autoantibodies. In this study, we analyzed the memory B cells in patients with GBS using flow cytometry. There was significantly higher percentage of memory B cells in patients with GBS than the healthy controls. The Spearman correlation analysis demonstrated that increased percentage of memory B cells was positively correlated with the clinical severity of the patients with GBS. Our study provides the evidences that memory B cells may be involved in mechanism of GBS. Copyright © 2017 Elsevier B.V. All rights reserved.

De novo alloreactive memory CD8+ T cells develop following allogeneic challenge when CNI immunosuppression is delayed.

PubMed

Hart-Matyas, M; Gareau, A J; Hirsch, G M; Lee, T D G

2015-01-01

Allospecific memory T cells are a recognized threat to the maintenance of solid-organ transplants. Limited information exists regarding the development of alloreactive memory T cells when post-transplant immunosuppression is present. The clinical practice of delaying calcineurin inhibitor (CNI) initiation post-transplant may permit the development of a de novo allospecific memory population. We investigated the development of de novo allospecific memory CD8+ T cells following the introduction of CNI immunosuppression in a murine model using allogeneic cell priming. Recipient mice alloprimed with splenocytes from fully mismatched donors received cyclosporine (CyA), initiated at 0, 2, 6, or 10days post-prime. Splenocytes from recipients were analyzed by flow cytometry or enzyme-linked immunosorbent assay for evidence of memory cell formation. Memory and effector CD8+ T cell development was prevented when CyA was initiated at 0day or 2days post-prime (p<0.001), but not 6days post-prime. Following a boost challenge, these memory CD8+ T cells were capable of producing a similarly sized population of secondary effectors as recipients not treated with CyA (p>0.05). Delaying CyA up to 6days or later post-prime permits the development of functional de novo allospecific memory CD8+ T cells. The development of this potentially detrimental T cell population in patients could be prevented by starting CNI immunosuppression early post-transplant. Copyright © 2014 Elsevier B.V. All rights reserved.

Rapid recovery from transient faults in the fault-tolerant processor with fault-tolerant shared memory

NASA Technical Reports Server (NTRS)

Harper, Richard E.; Butler, Bryan P.

1990-01-01

The Draper fault-tolerant processor with fault-tolerant shared memory (FTP/FTSM), which is designed to allow application tasks to continue execution during the memory alignment process, is described. Processor performance is not affected by memory alignment. In addition, the FTP/FTSM incorporates a hardware scrubber device to perform the memory alignment quickly during unused memory access cycles. The FTP/FTSM architecture is described, followed by an estimate of the time required for channel reintegration.

CLONAL MEMORY

PubMed Central

McMichael, A. J.; Williamson, A. R.

1974-01-01

A single clone of B cells producing anti-DNP antibody recognizable by the isoelectric-focusing spectrum has been used, in a double transfer system, to study clonal memory. Trasnsferable B memory develops between 4 and 7 days after the first transfer with antigen. B-memory cells thus proliferate before or concomitantly with antibody-forming cells. PMID:4545165

The Two Faces of Selective Memory Retrieval: Recall Specificity of the Detrimental but Not the Beneficial Effect

ERIC Educational Resources Information Center

Bäuml, Karl-Heinz T.; Dobler, Ina M.

2015-01-01

Depending on the degree to which the original study context is accessible, selective memory retrieval can be detrimental or beneficial for the recall of other memories (Bäuml & Samenieh, 2012). Prior work has shown that the detrimental effect of memory retrieval is typically recall specific and does not arise after restudy trials, whereas…

Epigenetic Memory Underlies Cell-Autonomous Heterogeneous Behavior of Hematopoietic Stem Cells.

PubMed

Yu, Vionnie W C; Yusuf, Rushdia Z; Oki, Toshihiko; Wu, Juwell; Saez, Borja; Wang, Xin; Cook, Colleen; Baryawno, Ninib; Ziller, Michael J; Lee, Eunjung; Gu, Hongcang; Meissner, Alexander; Lin, Charles P; Kharchenko, Peter V; Scadden, David T

2016-11-17

Stem cells determine homeostasis and repair of many tissues and are increasingly recognized as functionally heterogeneous. To define the extent of-and molecular basis for-heterogeneity, we overlaid functional, transcriptional, and epigenetic attributes of hematopoietic stem cells (HSCs) at a clonal level using endogenous fluorescent tagging. Endogenous HSC had clone-specific functional attributes over time in vivo. The intra-clonal behaviors were highly stereotypic, conserved under the stress of transplantation, inflammation, and genotoxic injury, and associated with distinctive transcriptional, DNA methylation, and chromatin accessibility patterns. Further, HSC function corresponded to epigenetic configuration but not always to transcriptional state. Therefore, hematopoiesis under homeostatic and stress conditions represents the integrated action of highly heterogeneous clones of HSC with epigenetically scripted behaviors. This high degree of epigenetically driven cell autonomy among HSCs implies that refinement of the concepts of stem cell plasticity and of the stem cell niche is warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

Telomerase Is Involved in IL-7-Mediated Differential Survival of Naive and Memory CD4+ T Cells1

PubMed Central

Yang, Yinhua; An, Jie; Weng, Nan-ping

2008-01-01

IL-7 plays an essential role in T cell maintenance and survival. The survival effect of IL-7 is thought to be mediated through regulation of Bcl2 family proteins. After a comparative analysis of IL-7-induced growth and cell death of human naive and memory CD4+ T cells, we observed that more memory CD4+ T cells underwent cell division and proceeded to apoptosis than naive cells in response to IL-7. However, IL-7-induced expressions of Bcl2 family members (Bcl2, Bcl-xL, Bax, and Bad) were similar between naive and memory cells. Instead, we found that IL-7 induced higher levels of telomerase activity in naive cells than in memory cells, and the levels of IL-7-induced telomerase activity had a significant inverse correlation with cell death in CD4+ T cells. Furthermore, we showed that reducing expression of telomerase reverse transcriptase and telomerase activity significantly increased cell death of IL-7-cultured CD4+ T cells. Together, these findings demonstrate that telomerase is involved in IL-7-mediated differential survival of naive and memory CD4+ T cells. PMID:18322183

Friends not foes: CTLA-4 blockade and mTOR inhibition cooperate during CD8+ T cell priming to promote memory formation and metabolic readiness.

PubMed

Pedicord, Virginia A; Cross, Justin R; Montalvo-Ortiz, Welby; Miller, Martin L; Allison, James P

2015-03-01

During primary Ag encounter, T cells receive numerous positive and negative signals that control their proliferation, function, and differentiation, but how these signals are integrated to modulate T cell memory has not been fully characterized. In these studies, we demonstrate that combining seemingly opposite signals, CTLA-4 blockade and rapamycin-mediated mammalian target of rapamycin inhibition, during in vivo T cell priming leads to both an increase in the frequency of memory CD8(+) T cells and improved memory responses to tumors and bacterial challenges. This enhanced efficacy corresponds to increased early expansion and memory precursor differentiation of CD8(+) T cells and increased mitochondrial biogenesis and spare respiratory capacity in memory CD8(+) T cells in mice treated with anti-CTLA-4 and rapamycin during immunization. Collectively, these results reveal that mammalian target of rapamycin inhibition cooperates with rather than antagonizes blockade of CTLA-4, promoting unrestrained effector function and proliferation, and an optimal metabolic program for CD8(+) T cell memory. Copyright © 2015 by The American Association of Immunologists, Inc.

Flexible and twistable non-volatile memory cell array with all-organic one diode-one resistor architecture.

PubMed

Ji, Yongsung; Zeigler, David F; Lee, Dong Su; Choi, Hyejung; Jen, Alex K-Y; Ko, Heung Cho; Kim, Tae-Wook

2013-01-01

Flexible organic memory devices are one of the integral components for future flexible organic electronics. However, high-density all-organic memory cell arrays on malleable substrates without cross-talk have not been demonstrated because of difficulties in their fabrication and relatively poor performances to date. Here we demonstrate the first flexible all-organic 64-bit memory cell array possessing one diode-one resistor architectures. Our all-organic one diode-one resistor cell exhibits excellent rewritable switching characteristics, even during and after harsh physical stresses. The write-read-erase-read output sequence of the cells perfectly correspond to the external pulse signal regardless of substrate deformation. The one diode-one resistor cell array is clearly addressed at the specified cells and encoded letters based on the standard ASCII character code. Our study on integrated organic memory cell arrays suggests that the all-organic one diode-one resistor cell architecture is suitable for high-density flexible organic memory applications in the future.

Humoral Immune Reconstitution Kinetics after Allogeneic Hematopoietic Stem Cell Transplantation in Children: A Maturation Block of IgM Memory B Cells May Lead to Impaired Antibody Immune Reconstitution.

PubMed

Abdel-Azim, Hisham; Elshoury, Amro; Mahadeo, Kris M; Parkman, Robertson; Kapoor, Neena

2017-09-01

Although T cell immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been well studied, long-term B cell immune reconstitution remains less characterized. We evaluated humoral immune reconstitution among 71 pediatric allo-HSCT recipients. Although tetanus toxoid antibody levels were normal at 1 year after allo-HSCT, antipolysaccharide carbohydrate antibodies remained persistently low for up to 5 years. While naive B cell counts normalized by 6 months, IgM memory B cell deficiency persisted for up to 2 years (P = .01); switched memory B cell deficiency normalized by 1 year after allo-HSCT. CD4 + T cell immune reconstitution correlated with that of switched memory B cells as early as 6 months after allo-HSCT (r = .55, P = .002) but did not correlate with IgM memory B cells at any time point after allo-HSCT. Taken together, this suggests that allo-HSCT recipients have impaired antibody immune reconstitution, mainly due to IgM memory B cell maturation block, compared with more prompt T cell-dependent switched memory cell immune reconstitution. We further explored other factors that might affect humoral immune reconstitution. The use of total body irradiation was associated with lower naive B cells counts at 6 months after HSCT (P = .04) and lower IgM (P = .008) and switched (P = .003) memory B cells up to 2 years. Allo-HSCT recipients with extensive chronic graft-versus-host disease had lower IgM memory B cell counts (P = .03) up to 2 years after allo-HSCT. The use of cord blood was associated with better naive (P = .01), IgM (P = .0005), and switched memory (P = .006) B cells immune reconstitution. These findings may inform future prophylaxis and treatment strategies regarding risk of overwhelming infection, graft-versus-host disease, and post-allogeneic HSCT revaccination. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Immune memory: the basics and how to trigger an efficient long-term immune memory.

PubMed

Beverley, P C L

2010-01-01

Immunological memory consists of expanded clones of T and B lymphocytes that show an increased rate of cell division and shortened telomeres compared with naïve cells. However, exhaustion of clones is delayed by kinetic heterogeneity within clones and altered survival and up-regulation of telomerase. Prolonged maintenance of protective B-cell immunity is T-cell dependent and requires a balance between plasma cells and memory B cells. Protective T-cell immunity also requires correct quality of T cells and that they are located appropriately. Copyright 2009 Elsevier Ltd. All rights reserved.

In Vitro-Generated Tc17 Cells Present a Memory Phenotype and Serve As a Reservoir of Tc1 Cells In Vivo

PubMed Central

Flores-Santibáñez, Felipe; Cuadra, Bárbara; Fernández, Dominique; Rosemblatt, Mariana V.; Núñez, Sarah; Cruz, Pablo; Gálvez-Cancino, Felipe; Cárdenas, J. César; Lladser, Alvaro; Rosemblatt, Mario; Bono, María Rosa; Sauma, Daniela

2018-01-01

Memory CD8+ T cells are ideal candidates for cancer immunotherapy because they can mediate long-term protection against tumors. However, the therapeutic potential of different in vitro-generated CD8+ T cell effector subsets to persist and become memory cells has not been fully characterized. Type 1 CD8+ T (Tc1) cells produce interferon-γ and are endowed with high cytotoxic capacity, whereas IL-17-producing CD8+ T (Tc17) cells are less cytotoxic but display enhanced self-renewal capacity. We sought to evaluate the functional properties of in vitro-generated Tc17 cells and elucidate their potential to become long lasting memory cells. Our results show that in vitro-generated Tc17 cells display a greater in vivo persistence and expansion in response to secondary antigen stimulation compared to Tc1 cells. When transferred into recipient mice, Tc17 cells persist in secondary lymphoid organs, present a recirculation behavior consistent with central memory T cells, and can shift to a Tc1 phenotype. Accordingly, Tc17 cells are endowed with a higher mitochondrial spare respiratory capacity than Tc1 cells and express higher levels of memory-related molecules than Tc1 cells. Together, these results demonstrate that in vitro-generated Tc17 cells acquire a central memory program and provide a lasting reservoir of Tc1 cells in vivo, thus supporting the use of Tc17 lymphocytes in the design of novel and more effective therapies. PMID:29472932

Temporal entrainment of cognitive functions: musical mnemonics induce brain plasticity and oscillatory synchrony in neural networks underlying memory.

PubMed

Thaut, Michael H; Peterson, David A; McIntosh, Gerald C

2005-12-01

In a series of experiments, we have begun to investigate the effect of music as a mnemonic device on learning and memory and the underlying plasticity of oscillatory neural networks. We used verbal learning and memory tests (standardized word lists, AVLT) in conjunction with electroencephalographic analysis to determine differences between verbal learning in either a spoken or musical (verbal materials as song lyrics) modality. In healthy adults, learning in both the spoken and music condition was associated with significant increases in oscillatory synchrony across all frequency bands. A significant difference between the spoken and music condition emerged in the cortical topography of the learning-related synchronization. When using EEG measures as predictors during learning for subsequent successful memory recall, significantly increased coherence (phase-locked synchronization) within and between oscillatory brain networks emerged for music in alpha and gamma bands. In a similar study with multiple sclerosis patients, superior learning and memory was shown in the music condition when controlled for word order recall, and subjects were instructed to sing back the word lists. Also, the music condition was associated with a significant power increase in the low-alpha band in bilateral frontal networks, indicating increased neuronal synchronization. Musical learning may access compensatory pathways for memory functions during compromised PFC functions associated with learning and recall. Music learning may also confer a neurophysiological advantage through the stronger synchronization of the neuronal cell assemblies underlying verbal learning and memory. Collectively our data provide evidence that melodic-rhythmic templates as temporal structures in music may drive internal rhythm formation in recurrent cortical networks involved in learning and memory.

Neurophysiological bases of exponential sensory decay and top-down memory retrieval: a model.

PubMed

Zylberberg, Ariel; Dehaene, Stanislas; Mindlin, Gabriel B; Sigman, Mariano

2009-01-01

Behavioral observations suggest that multiple sensory elements can be maintained for a short time, forming a perceptual buffer which fades after a few hundred milliseconds. Only a subset of this perceptual buffer can be accessed under top-down control and broadcasted to working memory and consciousness. In turn, single-cell studies in awake-behaving monkeys have identified two distinct waves of response to a sensory stimulus: a first transient response largely determined by stimulus properties and a second wave dependent on behavioral relevance, context and learning. Here we propose a simple biophysical scheme which bridges these observations and establishes concrete predictions for neurophsyiological experiments in which the temporal interval between stimulus presentation and top-down allocation is controlled experimentally. Inspired in single-cell observations, the model involves a first transient response and a second stage of amplification and retrieval, which are implemented biophysically by distinct operational modes of the same circuit, regulated by external currents. We explicitly investigated the neuronal dynamics, the memory trace of a presented stimulus and the probability of correct retrieval, when these two stages were bracketed by a temporal gap. The model predicts correctly the dependence of performance with response times in interference experiments suggesting that sensory buffering does not require a specific dedicated mechanism and establishing a direct link between biophysical manipulations and behavioral observations leading to concrete predictions.

Memory hierarchy using row-based compression

DOEpatents

Loh, Gabriel H.; O'Connor, James M.

2016-10-25

A system includes a first memory and a device coupleable to the first memory. The device includes a second memory to cache data from the first memory. The second memory includes a plurality of rows, each row including a corresponding set of compressed data blocks of non-uniform sizes and a corresponding set of tag blocks. Each tag block represents a corresponding compressed data block of the row. The device further includes decompression logic to decompress data blocks accessed from the second memory. The device further includes compression logic to compress data blocks to be stored in the second memory.

CXCR4 is critical for CD8+ memory T cell homeostatic self-renewal but not rechallenge self-renewal1

PubMed Central

Chaix, Julie; Nish, Simone A.; Lin, Wen-Hsuan W.; Rothman, Nyanza J.; Ding, Lei; Wherry, E. John; Reiner, Steven L.

2014-01-01

Central memory (CM) CD8+ T cells “remember” prior encounters because they maintain themselves through cell division in the absence of ongoing challenge (homeostatic self-renewal) as well as reproduce the central memory fate while manufacturing effector cells during secondary antigen encounters (rechallenge self-renewal). We tested the consequence of conditional deletion of the bone marrow (BM) homing receptor CXCR4 on antiviral T cell responses. CXCR4-deficient CD8+ T cells have impaired memory cell maintenance due to defective homeostatic proliferation. Upon rechallenge, however, CXCR4-deficient T cells can re-expand and renew the central memory pool while producing secondary effector cells. The critical BM-derived signals essential for CD8+ T cell homeostatic self-renewal appear to be dispensable to yield self-renewing, functionally asymmetric cell fates during rechallenge. PMID:24973450

CD4+CD62L+ Central Memory T Cells Can Be Converted to Foxp3+ T Cells

PubMed Central

Zhang, Xiaolong; Chang Li, Xian; Xiao, Xiang; Sun, Rui; Tian, Zhigang; Wei, Haiming

2013-01-01

The peripheral Foxp3+ Treg pool consists of naturally arising Treg (nTreg) and adaptive Treg cells (iTreg). It is well known that naive CD4+ T cells can be readily converted to Foxp3+ iTreg in vitro, and memory CD4+ T cells are resistant to conversion. In this study, we investigated the induction of Foxp3+ T cells from various CD4+ T-cell subsets in human peripheral blood. Though naive CD4+ T cells were readily converted to Foxp3+ T cells with TGF-β and IL-2 treatment in vitro, such Foxp3+ T cells did not express the memory marker CD45RO as do Foxp3+ T cells induced in the peripheral blood of Hepatitis B Virus (HBV) patients. Interestingly, a subset of human memory CD4+ T cells, defined as CD62L+ central memory T cells, could be induced by TGF-β to differentiate into Foxp3+ T cells. It is well known that Foxp3+ T cells derived from human CD4+CD25- T cells in vitro are lack suppressive functions. Our data about the suppressive functions of CD4+CD62L+ central memory T cell-derived Foxp3+ T cells support this conception, and an epigenetic analysis of these cells showed a similar methylation pattern in the FOXP3 Treg-specific demethylated region as the naive CD4+ T cell-derived Foxp3+ T cells. But further research showed that mouse CD4+ central memory T cells also could be induced to differentiate into Foxp3+ T cells, such Foxp3+ T cells could suppress the proliferation of effector T cells. Thus, our study identified CD4+CD62L+ central memory T cells as a novel potential source of iTreg. PMID:24155942

Hippocampal awake replay in fear memory retrieval

PubMed Central

Wu, Chun-Ting; Haggerty, Daniel; Kemere, Caleb; Ji, Daoyun

2017-01-01

Hippocampal place cells are key to episodic memories. How these cells participate in memory retrieval remains unclear. Here, after rats acquired a fear memory by receiving mild foot-shocks at a shock zone of a track, we analyzed place cells when the animals were placed back to the track and displayed an apparent memory retrieval behavior: avoidance of the shock zone. We found that place cells representing the shock zone were reactivated, despite the fact that the animals did not enter the shock zone. This reactivation occurred in ripple-associated awake replay of place cell sequences encoding the paths from the animal’s current positions to the shock zone, but not in place cell sequences within individual cycles of theta oscillation. The result reveals a specific place cell pattern underlying the inhibitory avoidance behavior and provides strong evidence for the involvement of awake replay in fear memory retrieval. PMID:28218916

Origin and Function of Circulating Plasmablasts during Acute Viral Infections.

PubMed

Fink, Katja

2012-01-01

Activated B cells proliferate and differentiate into antibody-producing cells, long-lived plasma cells, and memory B cells after immunization or infection. Repeated encounter of the same antigen triggers the rapid re-activation of pre-existing specific memory B cells, which then potentially enter new germinal center reactions and differentiate into short-lived plasmablasts or remain in the system as memory B cells. Short-lived class-switched IgG and IgA plasmablasts appear in the circulation transiently and the frequency of these cells can be remarkably high. The specificities and affinities of single plasmablasts in humans have been reported for several viral infections, so far most extensively for influenza and HIV. In general, the immunoglobulin variable regions of plasmablasts are highly mutated and diverse, suggesting that plasmablasts are derived from memory B cells, yet it is unclear which memory B cell subsets are activated and whether activated memory B cells adapt or mature before differentiation. This review summarizes what is known about the phenotype and the origin of human plasmablasts in the context of viral infections and whether these cells can be predictors of long-lived immunity.

Bcl-2 Allows Effector and Memory CD8+ T Cells To Tolerate Higher Expression of Bim

PubMed Central

Kurtulus, Sema; Tripathi, Pulak; Moreno-Fernandez, Maria E.; Sholl, Allyson; Katz, Jonathan D.; Grimes, H. Leighton; Hildeman, David A.

2014-01-01

As acute infections resolve, most effector CD8+ T cells die, whereas some persist and become memory T cells. Recent work showed that subsets of effector CD8+ T cells, identified by reciprocal expression of killer cell lectin-like receptor G1 (KLRG1) and CD127, have different lifespans. Similar to previous reports, we found that effector CD8+ T cells reported to have a longer lifespan (i.e., KLRG1lowCD127high) have increased levels of Bcl-2 compared with their shorter-lived KLRG1highCD127low counterparts. Surprisingly, we found that these effector KLRG1lowCD127high CD8+ T cells also had increased levels of Bim compared with KLRG1highCD127low cells. Similar effects were observed in memory cells, in which CD8+ central memory T cells expressed higher levels of Bim and Bcl-2 than did CD8+ effector memory T cells. Using both pharmacologic and genetic approaches, we found that survival of both subsets of effector and memory CD8+ T cells required Bcl-2 to combat the proapoptotic activity of Bim. Interestingly, inhibition or absence of Bcl-2 led to significantly decreased expression of Bim in surviving effector and memory T cells. In addition, manipulation of Bcl-2 levels by IL-7 or IL-15 also affected expression of Bim in effector CD8+ T cells. Finally, we found that Bim levels were significantly increased in effector CD8+ T cells lacking Bax and Bak. Together, these data indicate that cells having the highest levels of Bim are selected against during contraction of the response and that Bcl-2 determines the level of Bim that effector and memory T cells can tolerate. PMID:21451108

Cytokine-Induced Memory-Like Differentiation Enhances Unlicensed Natural Killer Cell Antileukemia and FcγRIIIa-Triggered Responses.

PubMed

Wagner, Julia A; Berrien-Elliott, Melissa M; Rosario, Maximillian; Leong, Jeffrey W; Jewell, Brea A; Schappe, Timothy; Abdel-Latif, Sara; Fehniger, Todd A

2017-03-01

Cytokine-induced memory-like natural killer (NK) cells differentiate after short-term preactivation with IL-12, IL-15, and IL-18 and display enhanced effector function in response to cytokines or tumor targets for weeks after the initial preactivation. Conventional NK cell function depends on a licensing signal, classically delivered by an inhibitory receptor engaging its cognate MHC class I ligand. How licensing status integrates with cytokine-induced memory-like NK cell responses is unknown. We investigated this interaction using killer cell immunoglobulin-like receptor- and HLA-genotyped primary human NK cells. Memory-like differentiation resulted in enhanced IFN-γ production triggered by leukemia targets or FcγRIIIa ligation within licensed NK cells, which exhibited the highest functionality of the NK cell subsets interrogated. IFN-γ production by unlicensed memory-like NK cells was also enhanced to a level comparable with that of licensed control NK cells. Mechanistically, differences in responses to FcγRIIIa-based triggering were not explained by alterations in key signaling intermediates, indicating that the underlying biology of memory-like NK cells is distinct from that of adaptive NK cells in human cytomegalovirus-positive individuals. Additionally, memory-like NK cells responded robustly to cytokine receptor restimulation with no impact of licensing status. These results demonstrate that both licensed and unlicensed memory-like NK cell populations have enhanced functionality, which may be translated to improve leukemia immunotherapy. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

A PARP1-ERK2 synergism is required for the induction of LTP

PubMed Central

Visochek, L.; Grigoryan, G.; Kalal, A.; Milshtein-Parush, H.; Gazit, N.; Slutsky, I.; Yeheskel, A.; Shainberg, A.; Castiel, A.; Seger, R.; Langelier, M. F.; Dantzer, F.; Pascal, J. M.; Segal, M.; Cohen-Armon, M.

2016-01-01

Unexpectedly, a post-translational modification of DNA-binding proteins, initiating the cell response to single-strand DNA damage, was also required for long-term memory acquisition in a variety of learning paradigms. Our findings disclose a molecular mechanism based on PARP1-Erk synergism, which may underlie this phenomenon. A stimulation induced PARP1 binding to phosphorylated Erk2 in the chromatin of cerebral neurons caused Erk-induced PARP1 activation, rendering transcription factors and promoters of immediate early genes (IEG) accessible to PARP1-bound phosphorylated Erk2. Thus, Erk-induced PARP1 activation mediated IEG expression implicated in long-term memory. PARP1 inhibition, silencing, or genetic deletion abrogated stimulation-induced Erk-recruitment to IEG promoters, gene expression and LTP generation in hippocampal CA3-CA1-connections. Moreover, a predominant binding of PARP1 to single-strand DNA breaks, occluding its Erk binding sites, suppressed IEG expression and prevented the generation of LTP. These findings outline a PARP1-dependent mechanism required for LTP generation, which may be implicated in long-term memory acquisition and in its deterioration in senescence. PMID:27121568

A PARP1-ERK2 synergism is required for the induction of LTP.

PubMed

Visochek, L; Grigoryan, G; Kalal, A; Milshtein-Parush, H; Gazit, N; Slutsky, I; Yeheskel, A; Shainberg, A; Castiel, A; Seger, R; Langelier, M F; Dantzer, F; Pascal, J M; Segal, M; Cohen-Armon, M

2016-04-28

Unexpectedly, a post-translational modification of DNA-binding proteins, initiating the cell response to single-strand DNA damage, was also required for long-term memory acquisition in a variety of learning paradigms. Our findings disclose a molecular mechanism based on PARP1-Erk synergism, which may underlie this phenomenon. A stimulation induced PARP1 binding to phosphorylated Erk2 in the chromatin of cerebral neurons caused Erk-induced PARP1 activation, rendering transcription factors and promoters of immediate early genes (IEG) accessible to PARP1-bound phosphorylated Erk2. Thus, Erk-induced PARP1 activation mediated IEG expression implicated in long-term memory. PARP1 inhibition, silencing, or genetic deletion abrogated stimulation-induced Erk-recruitment to IEG promoters, gene expression and LTP generation in hippocampal CA3-CA1-connections. Moreover, a predominant binding of PARP1 to single-strand DNA breaks, occluding its Erk binding sites, suppressed IEG expression and prevented the generation of LTP. These findings outline a PARP1-dependent mechanism required for LTP generation, which may be implicated in long-term memory acquisition and in its deterioration in senescence.

Neem leaf glycoprotein promotes dual generation of central and effector memory CD8(+) T cells against sarcoma antigen vaccine to induce protective anti-tumor immunity.

PubMed

Ghosh, Sarbari; Sarkar, Madhurima; Ghosh, Tithi; Guha, Ipsita; Bhuniya, Avishek; Saha, Akata; Dasgupta, Shayani; Barik, Subhasis; Bose, Anamika; Baral, Rathindranath

2016-03-01

We have previously shown that Neem Leaf Glycoprotein (NLGP) mediates sustained tumor protection by activating host immune response. Now we report that adjuvant help from NLGP predominantly generates CD44(+)CD62L(high)CCR7(high) central memory (TCM; in lymph node) and CD44(+)CD62L(low)CCR7(low) effector memory (TEM; in spleen) CD8(+) T cells of Swiss mice after vaccination with sarcoma antigen (SarAg). Generated TCM and TEM participated either to replenish memory cell pool for sustained disease free states or in rapid tumor eradication respectively. TCM generated after SarAg+NLGP vaccination underwent significant proliferation and IL-2 secretion following SarAg re-stimulation. Furthermore, SarAg+NLGP vaccination helps in greater survival of the memory precursor effector cells at the peak of the effector response and their maintenance as mature memory cells, in comparison to single modality treatment. Such response is corroborated with the reduced phosphorylation of FOXO in the cytosol and increased KLF2 in the nucleus associated with enhanced CD62L, CCR7 expression of lymph node-resident CD8(+) T cells. However, spleen-resident CD8(+) T memory cells show superior efficacy for immediate memory-to-effector cell conversion. The data support in all aspects that SarAg+NLGP demonstrate superiority than SarAg vaccination alone that benefits the host by rapid effector functions whenever required, whereas, central-memory cells are thought to replenish the memory cell pool for ultimate sustained disease free survival till 60 days following post-vaccination tumor inoculation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Schedulers with load-store queue awareness

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Tong; Eichenberger, Alexandre E.; Jacob, Arpith C.

2017-02-07

In one embodiment, a computer-implemented method includes tracking a size of a load-store queue (LSQ) during compile time of a program. The size of the LSQ is time-varying and indicates how many memory access instructions of the program are on the LSQ. The method further includes scheduling, by a computer processor, a plurality of memory access instructions of the program based on the size of the LSQ.

Schedulers with load-store queue awareness

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Tong; Eichenberger, Alexandre E.; Jacob, Arpith C.

2017-01-24

In one embodiment, a computer-implemented method includes tracking a size of a load-store queue (LSQ) during compile time of a program. The size of the LSQ is time-varying and indicates how many memory access instructions of the program are on the LSQ. The method further includes scheduling, by a computer processor, a plurality of memory access instructions of the program based on the size of the LSQ.

Temperature dependent characteristics of the random telegraph noise on contact resistive random access memory

NASA Astrophysics Data System (ADS)

Chang, Liang-Shun; Lin, Chrong Jung; King, Ya-Chin

2014-01-01

The temperature dependent characteristics of the random telegraphic noise (RTN) on contact resistive random access memory (CRRAM) are studied in this work. In addition to the bi-level switching, the occurrences of the middle states in the RTN signal are investigated. Based on the unique its temperature dependent characteristics, a new temperature sensing scheme is proposed for applications in ultra-low power sensor modules.

Generation of memory B cells and their reactivation.

PubMed

Inoue, Takeshi; Moran, Imogen; Shinnakasu, Ryo; Phan, Tri Giang; Kurosaki, Tomohiro

2018-05-01

The successful establishment of humoral memory response depends on at least two layers of defense. Pre-existing protective antibodies secreted by long-lived plasma cells act as a first line of defense against reinfection ("constitutive humoral memory"). Previously, a second line of defense in which pathogen-experienced memory B cells are rapidly reactivated to produce antibodies ("reactive humoral memory"), was considered as simply a back-up system for the first line (particularly for re-infection with homologous viruses). However, in the case of re-infection with similar but different strains of viruses, or in response to viral escape mutants, the reactive humoral memory plays a crucial role. Here, we review recent progress in our understanding of how memory B cells are generated in the pre-GC stage and during the GC reaction, and how these memory B cells are robustly reactivated with the help of memory Tfh cells to generate the secondary antibody response. In addition, we discuss how these advances may be relevant to the quest for a vaccine that can induce broadly reactive antibodies against influenza and HIV. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Induction of CD4 T cell memory by local cellular collectivity.

PubMed

Polonsky, Michal; Rimer, Jacob; Kern-Perets, Amos; Zaretsky, Irina; Miller, Stav; Bornstein, Chamutal; David, Eyal; Kopelman, Naama Meira; Stelzer, Gil; Porat, Ziv; Chain, Benjamin; Friedman, Nir

2018-06-15

Cell differentiation is directed by signals driving progenitors into specialized cell types. This process can involve collective decision-making, when differentiating cells determine their lineage choice by interacting with each other. We used live-cell imaging in microwell arrays to study collective processes affecting differentiation of naïve CD4 + T cells into memory precursors. We found that differentiation of precursor memory T cells sharply increases above a threshold number of locally interacting cells. These homotypic interactions involve the cytokines interleukin-2 (IL-2) and IL-6, which affect memory differentiation orthogonal to their effect on proliferation and survival. Mathematical modeling suggests that the differentiation rate is continuously modulated by the instantaneous number of locally interacting cells. This cellular collectivity can prioritize allocation of immune memory to stronger responses. Copyright © 2018, American Association for the Advancement of Science.

Requirement for CD4 T Cell Help in Generating Functional CD8 T Cell Memory

NASA Astrophysics Data System (ADS)

Shedlock, Devon J.; Shen, Hao

2003-04-01

Although primary CD8 responses to acute infections are independent of CD4 help, it is unknown whether a similar situation applies to secondary responses. We show that depletion of CD4 cells during the recall response has minimal effect, whereas depletion during the priming phase leads to reduced responses by memory CD8 cells to reinfection. Memory CD8 cells generated in CD4+/+ mice responded normally when transferred into CD4-/- hosts, whereas memory CD8 cells generated in CD4-/- mice mounted defective recall responses in CD4+/+ adoptive hosts. These results demonstrate a previously undescribed role for CD4 help in the development of functional CD8 memory.

A simple GPU-accelerated two-dimensional MUSCL-Hancock solver for ideal magnetohydrodynamics

NASA Astrophysics Data System (ADS)

Bard, Christopher M.; Dorelli, John C.

2014-02-01

We describe our experience using NVIDIA's CUDA (Compute Unified Device Architecture) C programming environment to implement a two-dimensional second-order MUSCL-Hancock ideal magnetohydrodynamics (MHD) solver on a GTX 480 Graphics Processing Unit (GPU). Taking a simple approach in which the MHD variables are stored exclusively in the global memory of the GTX 480 and accessed in a cache-friendly manner (without further optimizing memory access by, for example, staging data in the GPU's faster shared memory), we achieved a maximum speed-up of ≈126 for a 10242 grid relative to the sequential C code running on a single Intel Nehalem (2.8 GHz) core. This speedup is consistent with simple estimates based on the known floating point performance, memory throughput and parallel processing capacity of the GTX 480.

Thy1+IL-7+ lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation

PubMed Central

Shinoda, Kenta; Hirahara, Kiyoshi; Iinuma, Tomohisa; Ichikawa, Tomomi; Suzuki, Akane S.; Sugaya, Kaoru; Tumes, Damon J.; Yamamoto, Heizaburo; Hara, Takahiro; Tani-ichi, Shizue; Ikuta, Koichi; Okamoto, Yoshitaka; Nakayama, Toshinori

2016-01-01

Memory CD4+ T helper (Th) cells are central to long-term protection against pathogens, but they can also be pathogenic and drive chronic inflammatory disorders. How these pathogenic memory Th cells are maintained, particularly at sites of local inflammation, remains unclear. We found that ectopic lymphoid-like structures called inducible bronchus-associated lymphoid tissue (iBALT) are formed during chronic allergic inflammation in the lung, and that memory-type pathogenic Th2 (Tpath2) cells capable of driving allergic inflammation are maintained within the iBALT structures. The maintenance of memory Th2 cells within iBALT is supported by Thy1+IL-7–producing lymphatic endothelial cells (LECs). The Thy1+IL-7–producing LECs express IL-33 and T-cell–attracting chemokines CCL21 and CCL19. Moreover, ectopic lymphoid structures consisting of memory CD4+ T cells and IL-7+IL-33+ LECs were found in nasal polyps of patients with eosinophilic chronic rhinosinusitis. Thus, Thy1+IL-7–producing LECs control chronic allergic airway inflammation by providing a survival niche for memory-type Tpath2 cells. PMID:27140620

Comprehensive Approach for Identifying the T Cell Subset Origin of CD3 and CD28 Antibody-Activated Chimeric Antigen Receptor-Modified T Cells.

PubMed

Schmueck-Henneresse, Michael; Omer, Bilal; Shum, Thomas; Tashiro, Haruko; Mamonkin, Maksim; Lapteva, Natalia; Sharma, Sandhya; Rollins, Lisa; Dotti, Gianpietro; Reinke, Petra; Volk, Hans-Dieter; Rooney, Cliona M

2017-07-01

The outcome of therapy with chimeric Ag receptor (CAR)-modified T cells is strongly influenced by the subset origin of the infused T cells. However, because polyclonally activated T cells acquire a largely CD45RO + CCR7 - effector memory phenotype after expansion, regardless of subset origin, it is impossible to know which subsets contribute to the final T cell product. To determine the contribution of naive T cell, memory stem T cell, central memory T cell, effector memory T cell, and terminally differentiated effector T cell populations to the CD3 and CD28-activated CAR-modified T cells that we use for therapy, we followed the fate and function of individually sorted CAR-modified T cell subsets after activation with CD3 and CD28 Abs (CD3/28), transduction and culture alone, or after reconstitution into the relevant subset-depleted population. We show that all subsets are sensitive to CAR transduction, and each developed a distinct T cell functional profile during culture. Naive-derived T cells showed the greatest rate of proliferation but had more limited effector functions and reduced killing compared with memory-derived populations. When cultured in the presence of memory T cells, naive-derived T cells show increased differentiation, reduced effector cytokine production, and a reduced reproliferative response to CAR stimulation. CD3/28-activated T cells expanded in IL-7 and IL-15 produced greater expansion of memory stem T cells and central memory T cell-derived T cells compared with IL-2. Our strategy provides a powerful tool to elucidate the characteristics of CAR-modified T cells, regardless of the protocol used for expansion, reveals the functional properties of each expanded T cell subset, and paves the way for a more detailed evaluation of the effects of manufacturing changes on the subset contribution to in vitro-expanded T cells. Copyright © 2017 by The American Association of Immunologists, Inc.

Memory retrieval by activating engram cells in mouse models of early Alzheimer's disease.

PubMed

Roy, Dheeraj S; Arons, Autumn; Mitchell, Teryn I; Pignatelli, Michele; Ryan, Tomás J; Tonegawa, Susumu

2016-03-24

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory decline and subsequent loss of broader cognitive functions. Memory decline in the early stages of AD is mostly limited to episodic memory, for which the hippocampus has a crucial role. However, it has been uncertain whether the observed amnesia in the early stages of AD is due to disrupted encoding and consolidation of episodic information, or an impairment in the retrieval of stored memory information. Here we show that in transgenic mouse models of early AD, direct optogenetic activation of hippocampal memory engram cells results in memory retrieval despite the fact that these mice are amnesic in long-term memory tests when natural recall cues are used, revealing a retrieval, rather than a storage impairment. Before amyloid plaque deposition, the amnesia in these mice is age-dependent, which correlates with a progressive reduction in spine density of hippocampal dentate gyrus engram cells. We show that optogenetic induction of long-term potentiation at perforant path synapses of dentate gyrus engram cells restores both spine density and long-term memory. We also demonstrate that an ablation of dentate gyrus engram cells containing restored spine density prevents the rescue of long-term memory. Thus, selective rescue of spine density in engram cells may lead to an effective strategy for treating memory loss in the early stages of AD.

Diet-induced obesity does not impact the generation and maintenance of primary memory CD8 T cells.

PubMed

Khan, Shaniya H; Hemann, Emily A; Legge, Kevin L; Norian, Lyse A; Badovinac, Vladimir P

2014-12-15

The extent to which obesity compromises the differentiation and maintenance of protective memory CD8 T cell responses and renders obese individuals susceptible to infection remains unknown. In this study, we show that diet-induced obesity did not impact the maintenance of pre-existing memory CD8 T cells, including acquisition of a long-term memory phenotype (i.e., CD27(hi), CD62L(hi), KLRG1(lo)) and function (i.e., cytokine production, secondary expansion, and memory CD8 T cell-mediated protection). Additionally, obesity did not influence the differentiation and maintenance of newly evoked memory CD8 T cell responses in inbred and outbred hosts generated in response to different types of systemic (LCMV, L. monocytogenes) and/or localized (influenza virus) infections. Interestingly, the rate of naive-to-memory CD8 T cell differentiation after a peptide-coated dendritic cell immunization was similar in lean and obese hosts, suggesting that obesity-associated inflammation, unlike pathogen- or adjuvant-induced inflammation, did not influence the development of endogenous memory CD8 T cell responses. Therefore, our studies reveal that the obese environment does not influence the development or maintenance of memory CD8 T cell responses that are either primed before or after obesity is established, a surprising notion with important implications for future studies aiming to elucidate the role obesity plays in host susceptibility to infections. Copyright © 2014 by The American Association of Immunologists, Inc.

Overgeneral Autobiographical Memory and Traumatic Events: An Evaluative Review

ERIC Educational Resources Information Center

Moore, Sally A.; Zoellner, Lori A.

2007-01-01

Does trauma exposure impair retrieval of autobiographical memories? Many theorists have suggested that the reduced ability to access specific memories of life events, termed overgenerality, is a protective mechanism helping attenuate painful emotions associated with trauma. The authors addressed this question by reviewing 24 studies that assessed…

Working Memory Underpins Cognitive Development, Learning, and Education

ERIC Educational Resources Information Center

Cowan, Nelson

2014-01-01

Working memory is the retention of a small amount of information in a readily accessible form. It facilitates planning, comprehension, reasoning, and problem solving. I examine the historical roots and conceptual development of the concept and the theoretical and practical implications of current debates about working memory mechanisms. Then, I…

Tolerance induction of IgG+ memory B cells by T cell-independent type II antigens.

PubMed

Haniuda, Kei; Nojima, Takuya; Ohyama, Kyosuke; Kitamura, Daisuke

2011-05-15

Memory B cells generated during a T cell-dependent immune response rapidly respond to a secondary immunization by producing abundant IgG Abs that bind cognate Ag with high affinity. It is currently unclear whether this heightened recall response by memory B cells is due to augmented IgG-BCR signaling, which has only been demonstrated in the context of naive transgenic B cells. To address this question, we examined whether memory B cells can respond in vivo to Ags that stimulate only through BCR, namely T cell-independent type II (TI-II) Ags. In this study, we show that the TI-II Ag (4-hydroxy-3-nitrophenyl) acetyl (NP)-Ficoll cannot elicit the recall response in mice first immunized with the T cell-dependent Ag NP-chicken γ-globulin. Moreover, the NP-Ficoll challenge in vivo as well as in vitro significantly inhibits a subsequent recall response to NP-chicken γ-globulin in a B cell-intrinsic manner. This NP-Ficoll-mediated tolerance is caused by the preferential elimination of IgG(+) memory B cells binding to NP with high affinity. These data indicate that BCR cross-linking with a TI-II Ag does not activate IgG(+) memory B cells, but rather tolerizes them, identifying a terminal checkpoint of memory B cell differentiation that may prevent autoimmunity.

Memory CD8+ T Cells Protect Dendritic Cells from CTL Killing1

PubMed Central

Watchmaker, Payal B.; Urban, Julie A.; Berk, Erik; Nakamura, Yutaro; Mailliard, Robbie B.; Watkins, Simon C.; van Ham, S. Marieke; Kalinski, Pawel

2010-01-01

CD8+ T cells have been shown to be capable of either suppressing or promoting immune responses. To reconcile these contrasting regulatory functions, we compared the ability of human effector and memory CD8+ T cells to regulate survival and functions of dendritic cells (DC). We report that, in sharp contrast to the effector cells (CTLs) that kill DCs in a granzyme B- and perforin-dependent mechanism, memory CD8+ T cells enhance the ability of DCs to produce IL-12 and to induce functional Th1 and CTL responses in naive CD4+ and CD8+ T cell populations. Moreover, memory CD8+ T cells that release the DC-activating factor TNF-α before the release of cytotoxic granules induce DC expression of an endogenous granzyme B inhibitor PI-9 and protect DCs from CTL killing with similar efficacy as CD4+ Th cells. The currently identified DC-protective function of memory CD8+ T cells helps to explain the phenomenon of CD8+ T cell memory, reduced dependence of recall responses on CD4+ T cell help, and the importance of delayed administration of booster doses of vaccines for the optimal outcome of immunization. PMID:18322193

CD4+ virtual memory: Antigen-inexperienced T cells reside in the naïve, regulatory, and memory T cell compartments at similar frequencies, implications for autoimmunity.

PubMed

Marusina, Alina I; Ono, Yoko; Merleev, Alexander A; Shimoda, Michiko; Ogawa, Hiromi; Wang, Elizabeth A; Kondo, Kayo; Olney, Laura; Luxardi, Guillaume; Miyamura, Yoshinori; Yilma, Tilahun D; Villalobos, Itzel Bustos; Bergstrom, Jennifer W; Kronenberg, Daniel G; Soulika, Athena M; Adamopoulos, Iannis E; Maverakis, Emanual

2017-02-01

It is widely accepted that central and effector memory CD4 + T cells originate from naïve T cells after they have encountered their cognate antigen in the setting of appropriate co-stimulation. However, if this were true the diversity of T cell receptor (TCR) sequences within the naïve T cell compartment should be far greater than that of the memory T cell compartment, which is not supported by TCR sequencing data. Here we demonstrate that aged mice with far fewer naïve T cells, respond to the model antigen, hen eggwhite lysozyme (HEL), by utilizing the same TCR sequence as their younger counterparts. CD4 + T cell repertoire analysis of highly purified T cell populations from naive animals revealed that the HEL-specific clones displayed effector and central "memory" cell surface phenotypes even prior to having encountered their cognate antigen. Furthermore, HEL-inexperienced CD4 + T cells were found to reside within the naïve, regulatory, central memory, and effector memory T cell populations at similar frequencies and the majority of the CD4 + T cells within the regulatory and memory populations were unexpanded. These findings support a new paradigm for CD4 + T cell maturation in which a specific clone can undergo a differentiation process to exhibit a "memory" or regulatory phenotype without having undergone a clonal expansion event. It also demonstrates that a foreign-specific T cell is just as likely to reside within the regulatory T cell compartment as it would the naïve compartment, arguing against the specificity of the regulatory T cell compartment being skewed towards self-reactive T cell clones. Finally, we demonstrate that the same set of foreign and autoreactive CD4 + T cell clones are repetitively generated throughout adulthood. The latter observation argues against T cell-depleting strategies or autologous stem cell transplantation as therapies for autoimmunity-as the immune system has the ability to regenerate pathogenic clones. Published by Elsevier Ltd.

Library API for Z-Order Memory Layout

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bethel, E. Wes

This library provides a simple-to-use API for implementing an altnerative to traditional row-major order in-memory layout, one based on a Morton- order space filling curve (SFC) , specifically, a Z-order variant of the Morton order curve. The library enables programmers to, after a simple initialization step, to convert a multidimensional array from row-major to Z- order layouts, then use a single, generic API call to access data from any arbitrary (i,j,k) location from within the array, whether it it be stored in row- major or z-order format. The motivation for using a SFC in-memory layout is for improved spatial locality,more » which results in increased use of local high speed cache memory. The basic idea is that with row-major order layouts, a data access to some location that is nearby in index space is likely far away in physical memory, resulting in poor spatial locality and slow runtime. On the other hand, with a SFC-based layout, accesses that are nearby in index space are much more likely to also be nearby in physical memory, resulting in much better spatial locality, and better runtime performance. Numerous studies over the years have shown significant runtime performance gains are realized by using a SFC-based memory layout compared to a row-major layout, sometimes by as much as 50%, which result from the better use of the memory and cache hierarchy that are attendant with a SFC-based layout (see, for example, [Beth2012]). This library implementation is intended for use with codes that work with structured, array-based data in 2 or 3 dimensions. It is not appropriate for use with unstructured or point-based data.« less

Characterization of a CD44/CD122int memory CD8 T cell subset generated under sterile inflammatory conditions.

PubMed

Mbitikon-Kobo, Florentin-Martial; Vocanson, Marc; Michallet, Marie-Cécile; Tomkowiak, Martine; Cottalorda, Anne; Angelov, Georgi S; Coupet, Charles-Antoine; Djebali, Sophia; Marçais, Antoine; Dubois, Bertrand; Bonnefoy-Bérard, Nathalie; Nicolas, Jean-François; Arpin, Christophe; Marvel, Jacqueline

2009-03-15

Most memory CD8 T cell subsets that have been hitherto defined are generated in response to infectious pathogens. In this study, we have characterized the CD8 T cells that survive priming conditions, devoid of pathogen-derived danger signals. In both a TCR-transgenic model and a model of contact hypersensitivity, we show that the priming of naive CD8 T cells under sterile inflammatory conditions generates memory. The corresponding memory CD8 T cells can be identified by their intermediate expression levels of CD44 and CD122. We also show that CD44/122(int) memory CD8 T cells spontaneously develop in wild type mice and that they display intermediate levels of several other memory traits including functional (IFN-gamma secretion capacity, CCL5 messenger stores), phenotypic, and molecular (T-bet and eomesodermin expression levels) features. We finally show that they correspond to an early differentiation stage and can further differentiate in CD44/122(high) memory T cells. Altogether, our results identify a new memory CD8 T cell subset that is generated under sterile inflammatory conditions and involved in the recall contact hypersensitivity reactions that are responsible for allergic contact dermatitis.

White Adipose Tissue Is a Reservoir for Memory T Cells and Promotes Protective Memory Responses to Infection.

PubMed

Han, Seong-Ji; Glatman Zaretsky, Arielle; Andrade-Oliveira, Vinicius; Collins, Nicholas; Dzutsev, Amiran; Shaik, Jahangheer; Morais da Fonseca, Denise; Harrison, Oliver J; Tamoutounour, Samira; Byrd, Allyson L; Smelkinson, Margery; Bouladoux, Nicolas; Bliska, James B; Brenchley, Jason M; Brodsky, Igor E; Belkaid, Yasmine

2017-12-19

White adipose tissue bridges body organs and plays a fundamental role in host metabolism. To what extent adipose tissue also contributes to immune surveillance and long-term protective defense remains largely unknown. Here, we have shown that at steady state, white adipose tissue contained abundant memory lymphocyte populations. After infection, white adipose tissue accumulated large numbers of pathogen-specific memory T cells, including tissue-resident cells. Memory T cells in white adipose tissue expressed a distinct metabolic profile, and white adipose tissue from previously infected mice was sufficient to protect uninfected mice from lethal pathogen challenge. Induction of recall responses within white adipose tissue was associated with the collapse of lipid metabolism in favor of antimicrobial responses. Our results suggest that white adipose tissue represents a memory T cell reservoir that provides potent and rapid effector memory responses, positioning this compartment as a potential major contributor to immunological memory. Published by Elsevier Inc.

Dementia - what to ask your doctor

MedlinePlus

... recs.pdf . Accessed December 8, 2016. Budson AE, Solomon PR. Life adjustments for memory loss, Alzheimer's disease, and dementia. In: Budson AE, Solomon PR, eds. Memory Loss, Alzheimer's Disease, and Dementia: ...

Dementia - keeping safe in the home

MedlinePlus

... recs.pdf . Accessed June 27, 2016. Budson AE, Solomon PR. Life adjustments for memory loss, Alzheimer's disease, and dementia. In: Budson AE, Solomon PR, eds. Memory Loss, Alzheimer's Disease, and Dementia: ...

Origin of the OFF state variability in ReRAM cells

NASA Astrophysics Data System (ADS)

Salaoru, Iulia; Khiat, Ali; Li, Qingjiang; Berdan, Radu; Papavassiliou, Christos; Prodromakis, Themistoklis

2014-04-01

This work exploits the switching dynamics of nanoscale resistive random access memory (ReRAM) cells with particular emphasis on the origin of the observed variability when cells are consecutively cycled/programmed at distinct memory states. It is demonstrated that this variance is a common feature of all ReRAM elements and is ascribed to the formation and rupture of conductive filaments that expand across the active core, independently of the material employed as the active switching core, the causal physical switching mechanism, the switching mode (bipolar/unipolar) or even the unit cells' dimensions. Our hypothesis is supported through both experimental and theoretical studies on TiO2 and In2O3 : SnO2 (ITO) based ReRAM cells programmed at three distinct resistive states. Our prototypes employed TiO2 or ITO active cores over 5 × 5 µm2 and 100 × 100 µm2 cell areas, with all tested devices demonstrating both unipolar and bipolar switching modalities. In the case of TiO2-based cells, the underlying switching mechanism is based on the non-uniform displacement of ionic species that foster the formation of conductive filaments. On the other hand, the resistive switching observed in the ITO-based devices is considered to be due to a phase change mechanism. The selected experimental parameters allowed us to demonstrate that the observed programming variance is a common feature of all ReRAM devices, proving that its origin is dependent upon randomly oriented local disorders within the active core that have a substantial impact on the overall state variance, particularly for high-resistive states.

Enhanced clonal burst size corrects an otherwise defective memory response by CD8+ recent thymic emigrants

PubMed Central

Deets, Katherine A.; Berkley, Amy M.; Bergsbaken, Tessa; Fink, Pamela J.

2016-01-01

The youngest peripheral T cells (recent thymic emigrants or RTEs) are functionally distinct from naïve T cells that have completed post-thymic maturation. We now assess the RTE memory response, and find that RTEs produced less granzyme B than their mature counterparts during infection, but proliferated more and therefore generated equivalent target killing in vivo. After infection, RTE numbers contracted less dramatically than those of mature T cells, but RTEs were delayed in their transition to central memory, displaying impaired expression of CD62L, IL-2, Eomesodermin, and CXCR4, which resulted in impaired bone marrow localization. RTE-derived and mature memory cells expanded equivalently during rechallenge, indicating the robust proliferative capacity of RTEs was maintained independently of central memory phenotype. Thus, the diminished effector function and delayed central memory differentiation of RTE-derived memory cells are counterbalanced by their increased proliferative capacity, driving the efficacy of the RTE response to that of mature T cells. PMID:26873989

Cutting Edge: Enhanced Clonal Burst Size Corrects an Otherwise Defective Memory Response by CD8+ Recent Thymic Emigrants.

PubMed

Deets, Katherine A; Berkley, Amy M; Bergsbaken, Tessa; Fink, Pamela J

2016-03-15

The youngest peripheral T cells (recent thymic emigrants [RTEs]) are functionally distinct from naive T cells that have completed postthymic maturation. We assessed the RTE memory response and found that RTEs produced less granzyme B than their mature counterparts during infection but proliferated more and, therefore, generated equivalent target killing in vivo. Postinfection, RTE numbers contracted less dramatically than those of mature T cells, but RTEs were delayed in their transition to central memory, displaying impaired expression of CD62L, IL-2, Eomesodermin, and CXCR4, which resulted in impaired bone marrow localization. RTE-derived and mature memory cells expanded equivalently during rechallenge, indicating that the robust proliferative capacity of RTEs was maintained independently of central memory phenotype. Thus, the diminished effector function and delayed central memory differentiation of RTE-derived memory cells are counterbalanced by their increased proliferative capacity, driving the efficacy of the RTE response to that of mature T cells. Copyright © 2016 by The American Association of Immunologists, Inc.

Associative memory cells and their working principle in the brain

PubMed Central

Wang, Jin-Hui; Cui, Shan

2018-01-01

The acquisition, integration and storage of exogenous associated signals are termed as associative learning and memory. The consequences and processes of associative thinking and logical reasoning based on these stored exogenous signals can be memorized as endogenous signals, which are essential for decision making, intention, and planning. Associative memory cells recruited in these primary and secondary associative memories are presumably the foundation for the brain to fulfill cognition events and emotional reactions in life, though the plasticity of synaptic connectivity and neuronal activity has been believed to be involved in learning and memory. Current reports indicate that associative memory cells are recruited by their mutual synapse innervations among co-activated brain regions to fulfill the integration, storage and retrieval of associated signals. The activation of these associative memory cells initiates information recall in the mind, and the successful activation of their downstream neurons endorses memory presentations through behaviors and emotion reactions. In this review, we aim to draw a comprehensive diagram for associative memory cells, working principle and modulation, as well as propose their roles in cognition, emotion and behaviors. PMID:29487741

Insights from child development on the relationship between episodic and semantic memory.

PubMed

Robertson, Erin K; Köhler, Stefan

2007-11-05

The present study was motivated by a recent controversy in the neuropsychological literature on semantic dementia as to whether episodic encoding requires semantic processing or whether it can proceed solely based on perceptual processing. We addressed this issue by examining the effect of age-related limitations in semantic competency on episodic memory in 4-6-year-old children (n=67). We administered three different forced-choice recognition memory tests for pictures previously encountered in a single study episode. The tests varied in the degree to which access to semantically encoded information was required at retrieval. Semantic competency predicted recognition performance regardless of whether access to semantic information was required. A direct relation between picture naming at encoding and subsequent recognition was also found for all tests. Our findings emphasize the importance of semantic encoding processes even in retrieval situations that purportedly do not require access to semantic information. They also highlight the importance of testing neuropsychological models of memory in different populations, healthy and brain damaged, at both ends of the developmental continuum.

How Distinctive Processing Enhances Hits and Reduces False Alarms

PubMed Central

Hunt, R. Reed; Smith, Rebekah E.

2015-01-01

Distinctive processing is a concept designed to account for precision in memory, both correct responses and avoidance of errors. The principal question addressed in two experiments is how distinctive processing of studied material reduces false alarms to familiar distractors. Jacoby (Jacoby, Kelley, & McElree, 1999) has used the metaphors early selection and late correction to describe two different types of control processes. Early selection refers to limitations on access whereas late correction describes controlled monitoring of accessed information. The two types of processes are not mutually exclusive, and previous research has provided evidence for the operation of both. The data reported here extend previous work to a criterial recollection paradigm and to a recognition memory test. The results of both experiments show that variables that reduce false memory for highly familiar distracters continue to exert their effect under conditions of minimal post-access monitoring. Level of monitoring was reduced in the first experiment through test instructions and in the second experiment through speeded test responding. The results were consistent with the conclusion that both early selection and late correction operate to control accuracy in memory. PMID:26034343

Memory inhibition as a critical factor preventing creative problem solving.

PubMed

Gómez-Ariza, Carlos J; Del Prete, Francesco; Prieto Del Val, Laura; Valle, Tania; Bajo, M Teresa; Fernandez, Angel

2017-06-01

The hypothesis that reduced accessibility to relevant information can negatively affect problem solving in a remote associate test (RAT) was tested by using, immediately before the RAT, a retrieval practice procedure to hinder access to target solutions. The results of 2 experiments clearly showed that, relative to baseline, target words that had been competitors during selective retrieval were much less likely to be provided as solutions in the RAT, demonstrating that performance in the problem-solving task was strongly influenced by the predetermined accessibility status of the solutions in memory. Importantly, this was so even when participants were unaware of the relationship between the memory and the problem-solving procedures in the experiments. This finding is consistent with an inhibitory account of retrieval-induced forgetting effects and, more generally, constitutes support for the idea that the activation status of mental representations originating in a given task (e.g., episodic memory) can unwittingly have significant consequences for a different, unrelated task (e.g., problem solving). (PsycINFO Database Record (c) 2017 APA, all rights reserved).

In Vitro Measles Virus Infection of Human Lymphocyte Subsets Demonstrates High Susceptibility and Permissiveness of both Naive and Memory B Cells.

PubMed

Laksono, Brigitta M; Grosserichter-Wagener, Christina; de Vries, Rory D; Langeveld, Simone A G; Brem, Maarten D; van Dongen, Jacques J M; Katsikis, Peter D; Koopmans, Marion P G; van Zelm, Menno C; de Swart, Rik L

2018-04-15

Measles is characterized by a transient immune suppression, leading to an increased risk of opportunistic infections. Measles virus (MV) infection of immune cells is mediated by the cellular receptor CD150, expressed by subsets of lymphocytes, dendritic cells, macrophages, and thymocytes. Previous studies showed that human and nonhuman primate memory T cells express higher levels of CD150 than naive cells and are more susceptible to MV infection. However, limited information is available about the CD150 expression and relative susceptibility to MV infection of B-cell subsets. In this study, we assessed the susceptibility and permissiveness of naive and memory T- and B-cell subsets from human peripheral blood or tonsils to in vitro MV infection. Our study demonstrates that naive and memory B cells express CD150, but at lower frequencies than memory T cells. Nevertheless, both naive and memory B cells proved to be highly permissive to MV infection. Furthermore, we assessed the susceptibility and permissiveness of various functionally distinct T and B cells, such as helper T (T H ) cell subsets and IgG- and IgA-positive memory B cells, in peripheral blood and tonsils. We demonstrated that T H 1T H 17 cells and plasma and germinal center B cells were the subsets most susceptible and permissive to MV infection. Our study suggests that both naive and memory B cells, along with several other antigen-experienced lymphocytes, are important target cells of MV infection. Depletion of these cells potentially contributes to the pathogenesis of measles immune suppression. IMPORTANCE Measles is associated with immune suppression and is often complicated by bacterial pneumonia, otitis media, or gastroenteritis. Measles virus infects antigen-presenting cells and T and B cells, and depletion of these cells may contribute to lymphopenia and immune suppression. Measles has been associated with follicular exhaustion in lymphoid tissues in humans and nonhuman primates, emphasizing the importance of MV infection of B cells in vivo However, information on the relative susceptibility of B-cell subsets is scarce. Here, we compared the susceptibility and permissiveness to in vitro MV infection of human naive and memory T- and B-cell subsets isolated from peripheral blood or tonsils. Our results demonstrate that both naive and memory B cells are more permissive to MV infection than T cells. The highest infection levels were detected in plasma cells and germinal center B cells, suggesting that infection and depletion of these populations contribute to reduced host resistance. Copyright © 2018 Laksono et al.

In Vitro Measles Virus Infection of Human Lymphocyte Subsets Demonstrates High Susceptibility and Permissiveness of both Naive and Memory B Cells

PubMed Central

Laksono, Brigitta M.; Grosserichter-Wagener, Christina; de Vries, Rory D.; Langeveld, Simone A. G.; Brem, Maarten D.; van Dongen, Jacques J. M.; Koopmans, Marion P. G.

2018-01-01

ABSTRACT Measles is characterized by a transient immune suppression, leading to an increased risk of opportunistic infections. Measles virus (MV) infection of immune cells is mediated by the cellular receptor CD150, expressed by subsets of lymphocytes, dendritic cells, macrophages, and thymocytes. Previous studies showed that human and nonhuman primate memory T cells express higher levels of CD150 than naive cells and are more susceptible to MV infection. However, limited information is available about the CD150 expression and relative susceptibility to MV infection of B-cell subsets. In this study, we assessed the susceptibility and permissiveness of naive and memory T- and B-cell subsets from human peripheral blood or tonsils to in vitro MV infection. Our study demonstrates that naive and memory B cells express CD150, but at lower frequencies than memory T cells. Nevertheless, both naive and memory B cells proved to be highly permissive to MV infection. Furthermore, we assessed the susceptibility and permissiveness of various functionally distinct T and B cells, such as helper T (TH) cell subsets and IgG- and IgA-positive memory B cells, in peripheral blood and tonsils. We demonstrated that TH1TH17 cells and plasma and germinal center B cells were the subsets most susceptible and permissive to MV infection. Our study suggests that both naive and memory B cells, along with several other antigen-experienced lymphocytes, are important target cells of MV infection. Depletion of these cells potentially contributes to the pathogenesis of measles immune suppression. IMPORTANCE Measles is associated with immune suppression and is often complicated by bacterial pneumonia, otitis media, or gastroenteritis. Measles virus infects antigen-presenting cells and T and B cells, and depletion of these cells may contribute to lymphopenia and immune suppression. Measles has been associated with follicular exhaustion in lymphoid tissues in humans and nonhuman primates, emphasizing the importance of MV infection of B cells in vivo. However, information on the relative susceptibility of B-cell subsets is scarce. Here, we compared the susceptibility and permissiveness to in vitro MV infection of human naive and memory T- and B-cell subsets isolated from peripheral blood or tonsils. Our results demonstrate that both naive and memory B cells are more permissive to MV infection than T cells. The highest infection levels were detected in plasma cells and germinal center B cells, suggesting that infection and depletion of these populations contribute to reduced host resistance. PMID:29437964

If It Is Stored in My Memory I Will Surely Retrieve It: Anatomy of a Metacognitive Belief

ERIC Educational Resources Information Center

Kornell, Nate

2015-01-01

Retrieval failures--moments when a memory will not come to mind--are a universal human experience. Yet many laypeople believe human memory is a reliable storage system in which a stored memory should be accessible. I predicted that people would see retrieval failures as aberrations and predict that fewer retrieval failures would happen in the…

Synesthetic experiences enhance unconscious learning.

PubMed

Rothen, Nicolas; Scott, Ryan B; Mealor, Andy D; Coolbear, Daniel J; Burckhardt, Vera; Ward, Jamie

2013-01-01

Synesthesia  is characterized  by consistent extra perceptual experiences in response to normal sensory input. Recent studies provide evidence for a specific profile of enhanced memory performance in synesthesia, but focus exclusively on explicit memory paradigms for which the learned content is consciously accessible. In this study, for the first time, we demonstrate with an implicit memory paradigm that synesthetic experiences also enhance memory performance relating to unconscious knowledge.

Unstructured Adaptive Meshes: Bad for Your Memory?

NASA Technical Reports Server (NTRS)

Biswas, Rupak; Feng, Hui-Yu; VanderWijngaart, Rob

2003-01-01

This viewgraph presentation explores the need for a NASA Advanced Supercomputing (NAS) parallel benchmark for problems with irregular dynamical memory access. This benchmark is important and necessary because: 1) Problems with localized error source benefit from adaptive nonuniform meshes; 2) Certain machines perform poorly on such problems; 3) Parallel implementation may provide further performance improvement but is difficult. Some examples of problems which use irregular dynamical memory access include: 1) Heat transfer problem; 2) Heat source term; 3) Spectral element method; 4) Base functions; 5) Elemental discrete equations; 6) Global discrete equations. Nonconforming Mesh and Mortar Element Method are covered in greater detail in this presentation.

Integrated, nonvolatile, high-speed analog random access memory

NASA Technical Reports Server (NTRS)

Katti, Romney R. (Inventor); Wu, Jiin-Chuan (Inventor); Stadler, Henry L. (Inventor)

1994-01-01

This invention provides an integrated, non-volatile, high-speed random access memory. A magnetically switchable ferromagnetic or ferrimagnetic layer is sandwiched between an electrical conductor which provides the ability to magnetize the magnetically switchable layer and a magneto resistive or Hall effect material which allows sensing the magnetic field which emanates from the magnetization of the magnetically switchable layer. By using this integrated three-layer form, the writing process, which is controlled by the conductor, is separated from the storage medium in the magnetic layer and from the readback process which is controlled by the magnetoresistive layer. A circuit for implementing the memory in CMOS or the like is disclosed.

Optical memory development. Volume 2: Gain-assisted holographic storage media

NASA Technical Reports Server (NTRS)

Gange, R. A.; Mezrich, R. S.

1972-01-01

Thin deformable films were investigated for use as the storage medium in a holographic optical memory. The research was directed toward solving the problems of material fatigue, selective heat addressing, electrical charging of the film surface and charge patterning by light. A number of solutions to these problems were found but the main conclusion to be drawn from the work is that deformable media which employ heat in the recording process are not satisfactory for use in a high-speed random-access read/write holographic memory. They are, however, a viable approach in applications where either high speed or random-access is not required.

Ferroelectric tunneling element and memory applications which utilize the tunneling element

DOEpatents

Kalinin, Sergei V [Knoxville, TN; Christen, Hans M [Knoxville, TN; Baddorf, Arthur P [Knoxville, TN; Meunier, Vincent [Knoxville, TN; Lee, Ho Nyung [Oak Ridge, TN

2010-07-20

A tunneling element includes a thin film layer of ferroelectric material and a pair of dissimilar electrically-conductive layers disposed on opposite sides of the ferroelectric layer. Because of the dissimilarity in composition or construction between the electrically-conductive layers, the electron transport behavior of the electrically-conductive layers is polarization dependent when the tunneling element is below the Curie temperature of the layer of ferroelectric material. The element can be used as a basis of compact 1R type non-volatile random access memory (RAM). The advantages include extremely simple architecture, ultimate scalability and fast access times generic for all ferroelectric memories.

Cost aware cache replacement policy in shared last-level cache for hybrid memory based fog computing

NASA Astrophysics Data System (ADS)

Jia, Gangyong; Han, Guangjie; Wang, Hao; Wang, Feng

2018-04-01

Fog computing requires a large main memory capacity to decrease latency and increase the Quality of Service (QoS). However, dynamic random access memory (DRAM), the commonly used random access memory, cannot be included into a fog computing system due to its high consumption of power. In recent years, non-volatile memories (NVM) such as Phase-Change Memory (PCM) and Spin-transfer torque RAM (STT-RAM) with their low power consumption have emerged to replace DRAM. Moreover, the currently proposed hybrid main memory, consisting of both DRAM and NVM, have shown promising advantages in terms of scalability and power consumption. However, the drawbacks of NVM, such as long read/write latency give rise to potential problems leading to asymmetric cache misses in the hybrid main memory. Current last level cache (LLC) policies are based on the unified miss cost, and result in poor performance in LLC and add to the cost of using NVM. In order to minimize the cache miss cost in the hybrid main memory, we propose a cost aware cache replacement policy (CACRP) that reduces the number of cache misses from NVM and improves the cache performance for a hybrid memory system. Experimental results show that our CACRP behaves better in LLC performance, improving performance up to 43.6% (15.5% on average) compared to LRU.

Human Infant Memory B Cell and CD4+ T Cell Responses to HibMenCY-TT Glyco-Conjugate Vaccine

PubMed Central

Fuery, Angela; Richmond, Peter C.; Currie, Andrew J.

2015-01-01

Carrier-specific T cell and polysaccharide-specific B cell memory responses are not well characterised in infants following glyco-conjugate vaccination. We aimed to determine if the number of Meningococcal (Men) C- and Y- specific memory B cells and; number and quality of Tetanus Toxoid (TT) carrier-specific memory CD4+ T cells are associated with polysaccharide-specific IgG post HibMenCY-TT vaccination. Healthy infants received HibMenCY-TT vaccine at 2, 4 and 6 months with a booster at 12 months. Peripheral blood mononuclear cells were isolated and polysaccharide-specific memory B cells enumerated using ELISpot. TT-specific memory CD4+ T cells were detected and phenotyped based on CD154 expression and intracellular TNF-α, IL-2 and IFN-γ expression following stimulation. Functional polysaccharide-specific IgG titres were measured using the serum bactericidal activity (SBA) assay. Polysaccharide-specific Men C- but not Men Y- specific memory B cell frequencies pre-boost (12 months) were significantly associated with post-boost (13 months) SBA titres. Regression analysis showed no association between memory B cell frequencies post-priming (at 6 or 7 months) and SBA at 12 months or 13 months. TT-specific CD4+ T cells were detected at frequencies between 0.001 and 0.112 as a percentage of CD3+ T cells, but their numbers were not associated with SBA titres. There were significant negative associations between SBA titres at M13 and cytokine expression at M7 and M12. Conclusion: Induction of persistent polysaccharide-specific memory B cells prior to boosting is an important determinant of secondary IgG responses in infants. However, polysaccharide-specific functional IgG responses appear to be independent of the number and quality of circulating carrier-specific CD4+ T cells after priming. PMID:26191794

Different Dynamics for IgG and IgA Memory B Cells in Adolescents following a Meningococcal Serogroup C Tetanus Toxoid Conjugate Booster Vaccination Nine Years after Priming: A Role for Priming Age?

PubMed Central

Stoof, Susanne P.; Buisman, Anne-Marie; van Rooijen, Debbie M.; Boonacker, Rianne; van der Klis, Fiona R. M.; Sanders, Elisabeth A. M.; Berbers, Guy A. M.

2015-01-01

Background Antibody levels wane rapidly after Meningococcal serogroup C conjugate (MenCC) vaccination in young children, rendering the need for an adolescent booster dose. It is not clear whether circulating memory B cells are associated with persistence of MenC-specific antibody levels. Methods Measurement of MenC-specific IgG and IgA memory B cells and levels of serum and salivary MenC-specific IgG and IgA in healthy 10-, 12- and 15-year-olds prior to and one month and one year after a MenCC booster vaccination. All participants had received a primary MenCC vaccination nine years earlier. Results The number of circulating MenC-specific IgG memory B cells prior to booster was low and not predictive for MenC-specific IgG responses in serum or saliva post-booster, whereas the number of MenC-specific IgA memory B cells pre-booster positively correlated with MenC-specific IgA levels in saliva post-booster (R = 0.5, P<0.05). The booster induced a clear increase in the number of MenC-specific IgG and IgA memory B cells. The number of MenC-PS-specific IgG memory B cells at 1 month post-booster was highest in the 12-year-olds. The number of MenC-specific memory B cells at one month post-booster showed no correlation with the rate of MenC-specific antibody decay throughout the first year post-booster. Conclusions Circulating MenC-specific IgA memory B cells correlate with IgA responses in saliva, whereas circulating MenC-specific IgG memory B cells are not predictive for MenC-specific IgG responses in serum or saliva. Our results are suggestive for age-dependent differences in pre-existing memory against MenC. PMID:26458006

Different Dynamics for IgG and IgA Memory B Cells in Adolescents following a Meningococcal Serogroup C Tetanus Toxoid Conjugate Booster Vaccination Nine Years after Priming: A Role for Priming Age?

PubMed

Stoof, Susanne P; Buisman, Anne-Marie; van Rooijen, Debbie M; Boonacker, Rianne; van der Klis, Fiona R M; Sanders, Elisabeth A M; Berbers, Guy A M

2015-01-01

Antibody levels wane rapidly after Meningococcal serogroup C conjugate (MenCC) vaccination in young children, rendering the need for an adolescent booster dose. It is not clear whether circulating memory B cells are associated with persistence of MenC-specific antibody levels. Measurement of MenC-specific IgG and IgA memory B cells and levels of serum and salivary MenC-specific IgG and IgA in healthy 10-, 12- and 15-year-olds prior to and one month and one year after a MenCC booster vaccination. All participants had received a primary MenCC vaccination nine years earlier. The number of circulating MenC-specific IgG memory B cells prior to booster was low and not predictive for MenC-specific IgG responses in serum or saliva post-booster, whereas the number of MenC-specific IgA memory B cells pre-booster positively correlated with MenC-specific IgA levels in saliva post-booster (R = 0.5, P<0.05). The booster induced a clear increase in the number of MenC-specific IgG and IgA memory B cells. The number of MenC-PS-specific IgG memory B cells at 1 month post-booster was highest in the 12-year-olds. The number of MenC-specific memory B cells at one month post-booster showed no correlation with the rate of MenC-specific antibody decay throughout the first year post-booster. Circulating MenC-specific IgA memory B cells correlate with IgA responses in saliva, whereas circulating MenC-specific IgG memory B cells are not predictive for MenC-specific IgG responses in serum or saliva. Our results are suggestive for age-dependent differences in pre-existing memory against MenC.

Kanerva's sparse distributed memory: An associative memory algorithm well-suited to the Connection Machine

NASA Technical Reports Server (NTRS)

Rogers, David

1988-01-01

The advent of the Connection Machine profoundly changes the world of supercomputers. The highly nontraditional architecture makes possible the exploration of algorithms that were impractical for standard Von Neumann architectures. Sparse distributed memory (SDM) is an example of such an algorithm. Sparse distributed memory is a particularly simple and elegant formulation for an associative memory. The foundations for sparse distributed memory are described, and some simple examples of using the memory are presented. The relationship of sparse distributed memory to three important computational systems is shown: random-access memory, neural networks, and the cerebellum of the brain. Finally, the implementation of the algorithm for sparse distributed memory on the Connection Machine is discussed.

Histone acetylation is associated with differential gene expression in the rapid and robust memory CD8+ T-cell response

PubMed Central

Fann, Monchou; Godlove, Jason M.; Catalfamo, Marta; Wood, William H.; Chrest, Francis J.; Chun, Nicholas; Granger, Larry; Wersto, Robert; Madara, Karen; Becker, Kevin; Henkart, Pierre A.; Weng, Nan-ping

2006-01-01

To understand the molecular basis for the rapid and robust memory T-cell responses, we examined gene expression and chromatin modification by histone H3 lysine 9 (H3K9) acetylation in resting and activated human naive and memory CD8+ T cells. We found that, although overall gene expression patterns were similar, a number of genes are differentially expressed in either memory or naive cells in their resting and activated states. To further elucidate the basis for differential gene expression, we assessed the role of histone H3K9 acetylation in differential gene expression. Strikingly, higher H3K9 acetylation levels were detected in resting memory cells, prior to their activation, for those genes that were differentially expressed following activation, indicating that hyperacetylation of histone H3K9 may play a role in selective and rapid gene expression of memory CD8+ T cells. Consistent with this model, we showed that inducing high levels of H3K9 acetylation resulted in an increased expression in naive cells of those genes that are normally expressed differentially in memory cells. Together, these findings suggest that differential gene expression mediated at least in part by histone H3K9 hyperacetylation may be responsible for the rapid and robust memory CD8+ T-cell response. PMID:16868257

1T1R Nonvolatile Memory with Al/TiO₂/Au and Sol-Gel-Processed Insulator for Barium Zirconate Nickelate Gate in Pentacene Thin Film Transistor.

PubMed

Lee, Ke-Jing; Chang, Yu-Chi; Lee, Cheng-Jung; Wang, Li-Wen; Wang, Yeong-Her

2017-12-09

A one-transistor and one-resistor (1T1R) architecture with a resistive random access memory (RRAM) cell connected to an organic thin-film transistor (OTFT) device is successfully demonstrated to avoid the cross-talk issues of only one RRAM cell. The OTFT device, which uses barium zirconate nickelate (BZN) as a dielectric layer, exhibits favorable electrical properties, such as a high field-effect mobility of 5 cm²/Vs, low threshold voltage of -1.1 V, and low leakage current of 10 -12 A, for a driver in the 1T1R operation scheme. The 1T1R architecture with a TiO₂-based RRAM cell connected with a BZN OTFT device indicates a low operation current (10 μA) and reliable data retention (over ten years). This favorable performance of the 1T1R device can be attributed to the additional barrier heights introduced by using Ni (II) acetylacetone as a substitute for acetylacetone, and the relatively low leakage current of a BZN dielectric layer. The proposed 1T1R device with low leakage current OTFT and excellent uniform resistance distribution of RRAM exhibits a good potential for use in practical low-power electronic applications.