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Sample records for access memory cells

  1. Parallel programmable nonvolatile memory using ordinary static random access memory cells

    NASA Astrophysics Data System (ADS)

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

    2017-04-01

    A technique of using an ordinary static random access memory (SRAM) array for a programmable nonvolatile (NV) memory is proposed. The parallel NV writing of the entire array is achieved by simply applying high-voltage stress to the power supply terminal, after storing inverted desired data in the static random access memory (SRAM) array. Successful 2 kbit NV writing is demonstrated using a device-matrix-array (DMA) test element group (TEG) fabricated by 0.18 µm technology.

  2. Priming of transcriptional memory responses via the chromatin accessibility landscape in T cells

    PubMed Central

    Tu, Wen Juan; Hardy, Kristine; Sutton, Christopher R.; McCuaig, Robert; Li, Jasmine; Dunn, Jenny; Tan, Abel; Brezar, Vedran; Morris, Melanie; Denyer, Gareth; Lee, Sau Kuen; Turner, Stephen J.; Seddiki, Nabila; Smith, Corey; Khanna, Rajiv; Rao, Sudha

    2017-01-01

    Memory T cells exhibit transcriptional memory and “remember” their previous pathogenic encounter to increase transcription on re-infection. However, how this transcriptional priming response is regulated is unknown. Here we performed global FAIRE-seq profiling of chromatin accessibility in a human T cell transcriptional memory model. Primary activation induced persistent accessibility changes, and secondary activation induced secondary-specific opening of previously less accessible regions associated with enhanced expression of memory-responsive genes. Increased accessibility occurred largely in distal regulatory regions and was associated with increased histone acetylation and relative H3.3 deposition. The enhanced re-stimulation response was linked to the strength of initial PKC-induced signalling, and PKC-sensitive increases in accessibility upon initial stimulation showed higher accessibility on re-stimulation. While accessibility maintenance was associated with ETS-1, accessibility at re-stimulation-specific regions was linked to NFAT, especially in combination with ETS-1, EGR, GATA, NFκB, and NR4A. Furthermore, NFATC1 was directly regulated by ETS-1 at an enhancer region. In contrast to the factors that increased accessibility, signalling from bHLH and ZEB family members enhanced decreased accessibility upon re-stimulation. Interplay between distal regulatory elements, accessibility, and the combined action of sequence-specific transcription factors allows transcriptional memory-responsive genes to “remember” their initial environmental encounter. PMID:28317936

  3. Priming of transcriptional memory responses via the chromatin accessibility landscape in T cells.

    PubMed

    Tu, Wen Juan; Hardy, Kristine; Sutton, Christopher R; McCuaig, Robert; Li, Jasmine; Dunn, Jenny; Tan, Abel; Brezar, Vedran; Morris, Melanie; Denyer, Gareth; Lee, Sau Kuen; Turner, Stephen J; Seddiki, Nabila; Smith, Corey; Khanna, Rajiv; Rao, Sudha

    2017-03-20

    Memory T cells exhibit transcriptional memory and "remember" their previous pathogenic encounter to increase transcription on re-infection. However, how this transcriptional priming response is regulated is unknown. Here we performed global FAIRE-seq profiling of chromatin accessibility in a human T cell transcriptional memory model. Primary activation induced persistent accessibility changes, and secondary activation induced secondary-specific opening of previously less accessible regions associated with enhanced expression of memory-responsive genes. Increased accessibility occurred largely in distal regulatory regions and was associated with increased histone acetylation and relative H3.3 deposition. The enhanced re-stimulation response was linked to the strength of initial PKC-induced signalling, and PKC-sensitive increases in accessibility upon initial stimulation showed higher accessibility on re-stimulation. While accessibility maintenance was associated with ETS-1, accessibility at re-stimulation-specific regions was linked to NFAT, especially in combination with ETS-1, EGR, GATA, NFκB, and NR4A. Furthermore, NFATC1 was directly regulated by ETS-1 at an enhancer region. In contrast to the factors that increased accessibility, signalling from bHLH and ZEB family members enhanced decreased accessibility upon re-stimulation. Interplay between distal regulatory elements, accessibility, and the combined action of sequence-specific transcription factors allows transcriptional memory-responsive genes to "remember" their initial environmental encounter.

  4. 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.

  5. FeTRAM. An organic ferroelectric material based novel random access memory cell.

    PubMed

    Das, Saptarshi; Appenzeller, Joerg

    2011-09-14

    Science and technology in the electronics area have always been driven by the development of materials with unique properties and their integration into novel device concepts with the ultimate goal to enable new functionalities in innovative circuit architectures. In particular, a shift in paradigm requires a synergistic approach that combines materials, devices and circuit aspects simultaneously. Here we report the experimental implementation of a novel nonvolatile memory cell that combines silicon nanowires with an organic ferroelectric polymer-PVDF-TrFE-into a new ferroelectric transistor architecture. Our new cell, the ferroelectric transistor random access memory (FeTRAM) exhibits similarities with state-of-the-art ferroelectric random access memories (FeRAMs) in that it utilizes a ferroelectric material to store information in a nonvolatile (NV) fashion but with the added advantage of allowing for nondestructive readout. This nondestructive readout is a result of information being stored in our cell using a ferroelectric transistor instead of a capacitor-the scheme commonly employed in conventional FeRAMs.

  6. Statistical analysis of the correlations between cell performance and its initial states in contact resistive random access memory cells

    NASA Astrophysics Data System (ADS)

    Kao, Yun Feng; Hsieh, Wei Ting; Che Chen, Chun; King, Ya-Chin; Lin, Chrong Jung

    2017-04-01

    Variability has been one of the critical challenges in the implementation of large resistive random access memory (RRAM) arrays. Wide variations in set/reset, read and cycling characteristics can significantly reduce the design margin and feasibility of a memory array. Predicting the characteristics of RRAM cells is constructive to provide insights and to adjust the memory operations accordingly. In this study, a strong correlation between the cell performance and its initial state is found in contact RRAM (CRRAM) cells by 28 nm CMOS logic technology. Furthermore, a verify-reset operation is proposed to identify the type of conductive filament (CF) in a cell. Distinctive CRRAM characteristics are found to be linked directly to initial CFs, enabling preliminary screening and adaptive resets to address the large variability problems in sizable CRRAM arrays.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Remote direct memory access

    DOEpatents

    Archer, Charles J.; Blocksome, Michael A.

    2012-12-11

    Methods, parallel computers, and computer program products are disclosed for remote direct memory access. Embodiments include transmitting, from an origin DMA engine on an origin compute node to a plurality target DMA engines on target compute nodes, a request to send message, the request to send message specifying a data to be transferred from the origin DMA engine to data storage on each target compute node; receiving, by each target DMA engine on each target compute node, the request to send message; preparing, by each target DMA engine, to store data according to the data storage reference and the data length, including assigning a base storage address for the data storage reference; sending, by one or more of the target DMA engines, an acknowledgment message acknowledging that all the target DMA engines are prepared to receive a data transmission from the origin DMA engine; receiving, by the origin DMA engine, the acknowledgement message from the one or more of the target DMA engines; and transferring, by the origin DMA engine, data to data storage on each of the target compute nodes according to the data storage reference using a single direct put operation.

  12. Magnetic Analog Random-Access Memory

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

    Proposed integrated, solid-state, analog random-access memory base on principle of magnetic writing and magnetoresistive reading. Current in writing conductor magnetizes storage layer. Remanent magnetization in storage layer penetrates readout layer and detected by magnetoresistive effect or Hall effect. Memory cells are part of integrated circuit including associated reading and writing transistors. Intended to provide high storage density and rapid access, nonvolatile, consumes little power, and relatively invulnerable to ionizing radiation.

  13. 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.

  14. 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

  15. Effect of embedded metal nanocrystals on the resistive switching characteristics in NiN-based resistive random access memory cells

    SciTech Connect

    Yun, Min Ju; Kim, Hee-Dong; Man Hong, Seok; Hyun Park, Ju; Su Jeon, Dong; Geun Kim, Tae

    2014-03-07

    The metal nanocrystals (NCs) embedded-NiN-based resistive random access memory cells are demonstrated using several metal NCs (i.e., Pt, Ni, and Ti) with different physical parameters in order to investigate the metal NC's dependence on resistive switching (RS) characteristics. First, depending on the electronegativity of metal, the size of metal NCs is determined and this affects the operating current of memory cells. If metal NCs with high electronegativity are incorporated, the size of the NCs is reduced; hence, the operating current is reduced owing to the reduced density of the electric field around the metal NCs. Second, the potential wells are formed by the difference of work function between the metal NCs and active layer, and the barrier height of the potential wells affects the level of operating voltage as well as the conduction mechanism of metal NCs embedded memory cells. Therefore, by understanding these correlations between the active layer and embedded metal NCs, we can optimize the RS properties of metal NCs embedded memory cells as well as predict their conduction mechanisms.

  16. 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.

  17. 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.

  18. Source-Bias Dependent Charge Accumulation in P+-Poly Gate SOI Dynamic Random Access Memory Cell Transistors

    NASA Astrophysics Data System (ADS)

    Sim, Jai-hoon; Kim, Kinam

    1998-03-01

    In this paper, we report the dynamic data retention problems caused by the transient leakage current in a cell transistor during the bit-line pull down operation in p+-poly gate fully depleted silicon-on-insulator (FD-SOI) dynamic random access memories (DRAMs) due to the source-induced charge accumulation (SICA) effect in the silicon thin film. Due to the inherent floating body effect in the FD-SOI transistor, charge accumulation in the silicon thin film becomes inevitable when the gate-to-source voltage (VGS) is smaller than the flat-band voltage (VFB). In order to eliminate the transient leakage current problem in p+-poly gate FD-SOI cell transistor, the ground-precharged bit-line (GPB) sensing method is introduced.

  19. Memory access in shared virtual memory

    SciTech Connect

    Berrendorf, R. )

    1992-01-01

    Shared virtual memory (SVM) is a virtual memory layer with a single address space on top of a distributed real memory on parallel computers. We examine the behavior and performance of SVM running a parallel program with medium-grained, loop-level parallelism on top of it. A simulator for the underlying parallel architecture can be used to examine the behavior of SVM more deeply. The influence of several parameters, such as the number of processors, page size, cold or warm start, and restricted page replication, is studied.

  20. Memory access in shared virtual memory

    SciTech Connect

    Berrendorf, R.

    1992-09-01

    Shared virtual memory (SVM) is a virtual memory layer with a single address space on top of a distributed real memory on parallel computers. We examine the behavior and performance of SVM running a parallel program with medium-grained, loop-level parallelism on top of it. A simulator for the underlying parallel architecture can be used to examine the behavior of SVM more deeply. The influence of several parameters, such as the number of processors, page size, cold or warm start, and restricted page replication, is studied.

  1. Direct access to working memory contents.

    PubMed

    Bialkova, Svetlana; Oberauer, Klaus

    2010-01-01

    In two experiments participants held in working memory (WM) three digits in three different colors, and updated individual digits with the results of arithmetic equations presented in one of the colors. In the memory-access condition, a digit from WM had to be used as the first number in the equation; in the no-access condition, complete equations were presented so that no information from WM had to be accessed for the computation. Updating a digit not updated in the preceding step took longer than updating the same digit as in the preceding step, a time difference referred to as object-switch costs. Object-switch costs were equal in access and no-access equations, implying that they did not reflect the time to retrieve a new digit from WM. Access equations were completed as fast as no-access equations, implying that access to information in WM is as fast as reading the same information. No-access equations were slowed by a mismatch between the first digit of the presented equation and the to-be-updated digit in WM, showing that this digit is automatically accessed even when not needed. It is concluded that contents and their contexts form composites in WM that are necessarily accessed together.

  2. Innate Memory T cells

    PubMed Central

    Jameson, Stephen C.; Lee, You Jeong; Hogquist, Kristin A.

    2015-01-01

    Memory T cells are usually considered to be a feature of a successful immune response against a foreign antigen, and such cells can mediate potent immunity. However, in mice, alternative pathways have been described, through which naïve T cells can acquire the characteristics and functions of memory T cells without encountering specific foreign antigen or the typical signals required for conventional T cell differentiation. Such cells reflect a response to the internal rather the external environment, and hence such cells are called innate memory T cells. In this review, we describe how innate memory subsets were identified, the signals that induce their generation and their functional properties and potential role in the normal immune response. The existence of innate memory T cells in mice raises questions about whether parallel populations exist in humans, and we discuss the evidence for such populations during human T cell development and differentiation. PMID:25727290

  3. Regulatory T cell memory

    PubMed Central

    Rosenblum, Michael D.; Way, Sing Sing; Abbas, Abul K.

    2016-01-01

    Memory for antigen is a defining feature of adaptive immunity. Antigen-specific lymphocyte populations show an increase in number and function after antigen encounter and more rapidly re-expand upon subsequent antigen exposure. Studies of immune memory have primarily focused on effector B cells and T cells with microbial specificity, using prime challenge models of infection. However, recent work has also identified persistently expanded populations of antigen-specific regulatory T cells that protect against aberrant immune responses. In this Review, we consider the parallels between memory effector T cells and memory regulatory T cells, along with the functional implications of regulatory memory in autoimmunity, antimicrobial host defence and maternal fetal tolerance. In addition, we discuss emerging evidence for regulatory T cell memory in humans and key unanswered questions in this rapidly evolving field. PMID:26688349

  4. Low latency memory access and synchronization

    DOEpatents

    Blumrich, Matthias A.; Chen, Dong; Coteus, Paul W.; Gara, Alan G.; Giampapa, Mark E.; Heidelberger, Philip; Hoenicke, Dirk; Ohmacht, Martin; Steinmacher-Burow, Burkhard D.; Takken, Todd E.; Vranas, Pavlos M.

    2007-02-06

    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 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.

  5. Low latency memory access and synchronization

    DOEpatents

    Blumrich, Matthias A.; Chen, Dong; Coteus, Paul W.; Gara, Alan G.; Giampapa, Mark E.; Heidelberger, Philip; Hoenicke, Dirk; Ohmacht, Martin; Steinmacher-Burow, Burkhard D.; Takken, Todd E. , Vranas; Pavlos M.

    2010-10-19

    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 processor 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.

  6. 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…

  7. Memory B cells.

    PubMed

    Kurosaki, Tomohiro; Kometani, Kohei; Ise, Wataru

    2015-03-01

    The immune system can remember a previously experienced pathogen and can evoke an enhanced response to reinfection that depends on memory lymphocyte populations. Recent advances in tracking antigen-experienced memory B cells have revealed the existence of distinct classes of cells that have considerable functional differences. Some of these differences seem to be determined by the stimulation history during memory cell formation. To induce rapid recall antibody responses, the contributions of other types of cells, such as memory T follicular helper cells, have also now begun to be appreciated. In this Review, we discuss these and other recent advances in our understanding of memory B cells, focusing on the underlying mechanisms that are required for rapid and effective recall antibody responses.

  8. Purely antiferromagnetic magnetoelectric random access memory.

    PubMed

    Kosub, Tobias; Kopte, Martin; Hühne, Ruben; Appel, Patrick; Shields, Brendan; Maletinsky, Patrick; Hübner, René; Liedke, Maciej Oskar; Fassbender, Jürgen; Schmidt, Oliver G; Makarov, Denys

    2017-01-03

    Magnetic random access memory schemes employing magnetoelectric coupling to write binary information promise outstanding energy efficiency. We propose and demonstrate a purely antiferromagnetic magnetoelectric random access memory (AF-MERAM) that offers a remarkable 50-fold reduction of the writing threshold compared with ferromagnet-based counterparts, is robust against magnetic disturbances and exhibits no ferromagnetic hysteresis losses. Using the magnetoelectric antiferromagnet Cr2O3, we demonstrate reliable isothermal switching via gate voltage pulses and all-electric readout at room temperature. As no ferromagnetic component is present in the system, the writing magnetic field does not need to be pulsed for readout, allowing permanent magnets to be used. Based on our prototypes, we construct a comprehensive model of the magnetoelectric selection mechanisms in thin films of magnetoelectric antiferromagnets, revealing misfit induced ferrimagnetism as an important factor. Beyond memory applications, the AF-MERAM concept introduces a general all-electric interface for antiferromagnets and should find wide applicability in antiferromagnetic spintronics.

  9. Purely antiferromagnetic magnetoelectric random access memory

    NASA Astrophysics Data System (ADS)

    Kosub, Tobias; Kopte, Martin; Hühne, Ruben; Appel, Patrick; Shields, Brendan; Maletinsky, Patrick; Hübner, René; Liedke, Maciej Oskar; Fassbender, Jürgen; Schmidt, Oliver G.; Makarov, Denys

    2017-01-01

    Magnetic random access memory schemes employing magnetoelectric coupling to write binary information promise outstanding energy efficiency. We propose and demonstrate a purely antiferromagnetic magnetoelectric random access memory (AF-MERAM) that offers a remarkable 50-fold reduction of the writing threshold compared with ferromagnet-based counterparts, is robust against magnetic disturbances and exhibits no ferromagnetic hysteresis losses. Using the magnetoelectric antiferromagnet Cr2O3, we demonstrate reliable isothermal switching via gate voltage pulses and all-electric readout at room temperature. As no ferromagnetic component is present in the system, the writing magnetic field does not need to be pulsed for readout, allowing permanent magnets to be used. Based on our prototypes, we construct a comprehensive model of the magnetoelectric selection mechanisms in thin films of magnetoelectric antiferromagnets, revealing misfit induced ferrimagnetism as an important factor. Beyond memory applications, the AF-MERAM concept introduces a general all-electric interface for antiferromagnets and should find wide applicability in antiferromagnetic spintronics.

  10. Investigation of parasitic resistance and capacitance effects in nanoscaled FinFETs and their impact on static random-access memory cells

    NASA Astrophysics Data System (ADS)

    Huang, Bo-Rong; Meng, Fan-Hsuan; King, Ya-Chin; Lin, Chrong Jung

    2017-04-01

    A thorough investigation of the parasitic resistance and capacitance (RC) effects of a single-fin FinFET on logic CMOS devices and circuits is presented. As parasitic RC effects become increasingly prominent in nanoscaled FinFET technologies, they are critical to the overall device and circuit performance. In addition, the effects of dummy patterns as well as multifin structures are analyzed and modeled in detailed. By incorporating parasitic resistance and capacitance extracted by both measurement and simulation, the static and dynamic performance characteristics of standard six transistor static random-access memory (6T-SRAM) cells are comprehensively evaluated as an example of parasitic RC effects in this investigation.

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

    SciTech Connect

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

    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 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.

  12. Natural Killer Cell Memory.

    PubMed

    O'Sullivan, Timothy E; Sun, Joseph C; Lanier, Lewis L

    2015-10-20

    Natural killer (NK) cells have historically been considered short-lived cytolytic cells that can rapidly respond against pathogens and tumors in an antigen-independent manner and then undergo cell death. Recently, however, NK cells have been shown to possess traits of adaptive immunity and can acquire immunological memory in a manner similar to that of T and B cells. In this review, we discuss evidence of NK cell memory and the mechanisms involved in the generation and survival of these innate lymphocytes.

  13. Evaluation of in-plane local stress distribution in stacked IC chip using dynamic random access memory cell array for highly reliable three-dimensional IC

    NASA Astrophysics Data System (ADS)

    Tanikawa, Seiya; Kino, Hisashi; Fukushima, Takafumi; Koyanagi, Mitsumasa; Tanaka, Tetsu

    2016-04-01

    As three-dimensional (3D) ICs have many advantages, IC performances can be enhanced without scaling down of transistor size. However, 3D IC has mechanical stresses inside Si substrates owing to its 3D stacking structure, which induces negative effects on transistor performances such as carrier mobility changes. One of the mechanical stresses is local bending stress due to organic adhesive shrinkage among stacked IC chips. In this paper, we have proposed an evaluation method for in-plane local stress distribution in the stacked IC chips using retention time modulation of a dynamic random access memory (DRAM) cell array. We fabricated a test structure composed of a DRAM chip bonded on a Si interposer with dummy Cu/Sn microbumps. As a result, we clarified that the DRAM cell array can precisely evaluate the in-plane local stress distribution in the stacked IC chips.

  14. Purely antiferromagnetic magnetoelectric random access memory

    PubMed Central

    Kosub, Tobias; Kopte, Martin; Hühne, Ruben; Appel, Patrick; Shields, Brendan; Maletinsky, Patrick; Hübner, René; Liedke, Maciej Oskar; Fassbender, Jürgen; Schmidt, Oliver G.; Makarov, Denys

    2017-01-01

    Magnetic random access memory schemes employing magnetoelectric coupling to write binary information promise outstanding energy efficiency. We propose and demonstrate a purely antiferromagnetic magnetoelectric random access memory (AF-MERAM) that offers a remarkable 50-fold reduction of the writing threshold compared with ferromagnet-based counterparts, is robust against magnetic disturbances and exhibits no ferromagnetic hysteresis losses. Using the magnetoelectric antiferromagnet Cr2O3, we demonstrate reliable isothermal switching via gate voltage pulses and all-electric readout at room temperature. As no ferromagnetic component is present in the system, the writing magnetic field does not need to be pulsed for readout, allowing permanent magnets to be used. Based on our prototypes, we construct a comprehensive model of the magnetoelectric selection mechanisms in thin films of magnetoelectric antiferromagnets, revealing misfit induced ferrimagnetism as an important factor. Beyond memory applications, the AF-MERAM concept introduces a general all-electric interface for antiferromagnets and should find wide applicability in antiferromagnetic spintronics. PMID:28045029

  15. High Speed Oblivious Random Access Memory (HS-ORAM)

    DTIC Science & Technology

    2015-09-01

    HIGH SPEED OBLIVIOUS RANDOM ACCESS MEMORY (HS-ORAM) PRIVATE MACHINES, INC. SEPTEMBER 2015 FINAL TECHNICAL REPORT...REPORT 3. DATES COVERED (From - To) OCT 2013 – MAY 2015 4. TITLE AND SUBTITLE HIGH SPEED OBLIVIOUS RANDOM ACCESS MEMORY (HS-ORAM) 5a. CONTRACT NUMBER...query policies beyond simple access control. 15. SUBJECT TERMS Oblivious Random Access Memory , Hardware-based Security, Embedded Hardware Roots of

  16. Parallel Optical Random Access Memory (PORAM)

    NASA Technical Reports Server (NTRS)

    Alphonse, G. A.

    1989-01-01

    It is shown that the need to minimize component count, power and size, and to maximize packing density require a parallel optical random access memory to be designed in a two-level hierarchy: a modular level and an interconnect level. Three module designs are proposed, in the order of research and development requirements. The first uses state-of-the-art components, including individually addressed laser diode arrays, acousto-optic (AO) deflectors and magneto-optic (MO) storage medium, aimed at moderate size, moderate power, and high packing density. The next design level uses an electron-trapping (ET) medium to reduce optical power requirements. The third design uses a beam-steering grating surface emitter (GSE) array to reduce size further and minimize the number of components.

  17. Remote direct memory access over datagrams

    DOEpatents

    Grant, Ryan Eric; Rashti, Mohammad Javad; Balaji, Pavan; Afsahi, Ahmad

    2014-12-02

    A communication stack for providing remote direct memory access (RDMA) over a datagram network is disclosed. The communication stack has a user level interface configured to accept datagram related input and communicate with an RDMA enabled network interface card (NIC) via an NIC driver. The communication stack also has an RDMA protocol layer configured to supply one or more data transfer primitives for the datagram related input of the user level. The communication stack further has a direct data placement (DDP) layer configured to transfer the datagram related input from a user storage to a transport layer based on the one or more data transfer primitives by way of a lower layer protocol (LLP) over the datagram network.

  18. Parallel Optical Random Access Memory (PORAM)

    NASA Astrophysics Data System (ADS)

    Alphonse, G. A.

    1989-06-01

    It is shown that the need to minimize component count, power and size, and to maximize packing density require a parallel optical random access memory to be designed in a two-level hierarchy: a modular level and an interconnect level. Three module designs are proposed, in the order of research and development requirements. The first uses state-of-the-art components, including individually addressed laser diode arrays, acousto-optic (AO) deflectors and magneto-optic (MO) storage medium, aimed at moderate size, moderate power, and high packing density. The next design level uses an electron-trapping (ET) medium to reduce optical power requirements. The third design uses a beam-steering grating surface emitter (GSE) array to reduce size further and minimize the number of components.

  19. Direct memory access transfer completion notification

    DOEpatents

    Chen, Dong; Giampapa, Mark E.; Heidelberger, Philip; Kumar, Sameer; Parker, Jeffrey J.; Steinmacher-Burow, Burkhard D.; Vranas, Pavlos

    2010-07-27

    Methods, compute nodes, and computer program products are provided for direct memory access (`DMA`) transfer completion notification. Embodiments include determining, by an origin DMA engine on an origin compute node, whether a data descriptor for an application message to be sent to a target compute node is currently in an injection first-in-first-out (`FIFO`) buffer in dependence upon a sequence number previously associated with the data descriptor, the total number of descriptors currently in the injection FIFO buffer, and the current sequence number for the newest data descriptor stored in the injection FIFO buffer; and notifying a processor core on the origin DMA engine that the message has been sent if the data descriptor for the message is not currently in the injection FIFO buffer.

  20. Conductance Quantization in Resistive Random Access Memory

    NASA Astrophysics Data System (ADS)

    Li, Yang; Long, Shibing; Liu, Yang; Hu, Chen; Teng, Jiao; Liu, Qi; Lv, Hangbing; Suñé, Jordi; Liu, Ming

    2015-10-01

    The intrinsic scaling-down ability, simple metal-insulator-metal (MIM) sandwich structure, excellent performances, and complementary metal-oxide-semiconductor (CMOS) technology-compatible fabrication processes make resistive random access memory (RRAM) one of the most promising candidates for the next-generation memory. The RRAM device also exhibits rich electrical, thermal, magnetic, and optical effects, in close correlation with the abundant resistive switching (RS) materials, metal-oxide interface, and multiple RS mechanisms including the formation/rupture of nanoscale to atomic-sized conductive filament (CF) incorporated in RS layer. Conductance quantization effect has been observed in the atomic-sized CF in RRAM, which provides a good opportunity to deeply investigate the RS mechanism in mesoscopic dimension. In this review paper, the operating principles of RRAM are introduced first, followed by the summarization of the basic conductance quantization phenomenon in RRAM and the related RS mechanisms, device structures, and material system. Then, we discuss the theory and modeling of quantum transport in RRAM. Finally, we present the opportunities and challenges in quantized RRAM devices and our views on the future prospects.

  1. 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

    ... COMMISSION In the Matter of Certain Dynamic Random Access Memory and Nand Flash Memory Devices and Products... States after importation of certain dynamic random access memory and NAND flash memory devices and... the sale within the United States after importation of certain dynamic random access memory and...

  2. 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.

  3. 75 FR 44989 - In the Matter of Certain Semiconductor Chips Having Synchronous Dynamic Random Access Memory...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-30

    ... Certain Semiconductor Chips Having Synchronous Dynamic Random Access Memory Controllers and Products... chips having synchronous dynamic random access memory controllers and product containing the same by... importing certain semiconductor chips having synchronous dynamic random access memory controllers...

  4. Magnetic Random Access Memory based non-volatile asynchronous Muller cell for ultra-low power autonomous applications

    SciTech Connect

    Di Pendina, G. E-mail: eldar.zianbetov@cea.fr Zianbetov, E. E-mail: eldar.zianbetov@cea.fr; Beigne, E. E-mail: eldar.zianbetov@cea.fr

    2015-05-07

    Micro and nano electronic integrated circuit domain is today mainly driven by the advent of the Internet of Things for which the constraints are strong, especially in terms of power consumption and autonomy, not only during the computing phases but also during the standby or idle phases. In such ultra-low power applications, the circuit has to meet new constraints mainly linked to its changing energetic environment: long idle phases, automatic wake up, data back-up when the circuit is sporadically turned off, and ultra-low voltage power supply operation. Such circuits have to be completely autonomous regarding their unstable environment, while remaining in an optimum energetic configuration. Therefore, we propose in this paper the first MRAM-based non-volatile asynchronous Muller cell. This cell has been simulated and characterized in a very advanced 28 nm CMOS fully depleted silicon-on-insulator technology, presenting good power performance results due to an extremely efficient body biasing control together with ultra-wide supply voltage range from 160 mV up to 920 mV. The leakage current can be reduced to 154 pA thanks to reverse body biasing. We also propose an efficient standard CMOS bulk version of this cell in order to be compatible with different fabrication processes.

  5. Magnetic Random Access Memory based non-volatile asynchronous Muller cell for ultra-low power autonomous applications

    NASA Astrophysics Data System (ADS)

    Di Pendina, G.; Zianbetov, E.; Beigne, E.

    2015-05-01

    Micro and nano electronic integrated circuit domain is today mainly driven by the advent of the Internet of Things for which the constraints are strong, especially in terms of power consumption and autonomy, not only during the computing phases but also during the standby or idle phases. In such ultra-low power applications, the circuit has to meet new constraints mainly linked to its changing energetic environment: long idle phases, automatic wake up, data back-up when the circuit is sporadically turned off, and ultra-low voltage power supply operation. Such circuits have to be completely autonomous regarding their unstable environment, while remaining in an optimum energetic configuration. Therefore, we propose in this paper the first MRAM-based non-volatile asynchronous Muller cell. This cell has been simulated and characterized in a very advanced 28 nm CMOS fully depleted silicon-on-insulator technology, presenting good power performance results due to an extremely efficient body biasing control together with ultra-wide supply voltage range from 160 mV up to 920 mV. The leakage current can be reduced to 154 pA thanks to reverse body biasing. We also propose an efficient standard CMOS bulk version of this cell in order to be compatible with different fabrication processes.

  6. Memory B cells: total recall.

    PubMed

    Phan, Tri Giang; Tangye, Stuart G

    2017-03-28

    Immunological memory is a cornerstone of adaptive immune responses in higher vertebrates. The remarkable ability to generate memory cells following Ag exposure, in the context of natural infection or immunization, provides long-lived protection against infectious diseases, often for the hosts' lifetime. Indeed, the generation of memory B cells and long-lived plasma cells underpins the success of most vaccines. The concept of immunological memory is not new-it was first proposed nearly 2500 years ago. While our understanding of the complexities of humoral and cell-mediated memory continues to evolve, important aspects of this process remain unresolved. Here, we will provide an overview of recent advances in B-cell memory in mice and humans, and in health and disease.

  7. 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.

  8. 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.

  9. 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…

  10. Empirical Memory-Access Cost Models in Multicore NUMA Architectures

    SciTech Connect

    McCormick, Patrick S.; Braithwaite, Ryan Karl; Feng, Wu-chun

    2011-01-01

    Data location is of prime importance when scheduling tasks in a non-uniform memory access (NUMA) architecture. The characteristics of the NUMA architecture must be understood so tasks can be scheduled onto processors that are close to the task's data. However, in modern NUMA architectures, such as AMD Magny-Cours and Intel Nehalem, there may be a relatively large number of memory controllers with sockets that are connected in a non-intuitive manner, leading to performance degradation due to uninformed task-scheduling decisions. In this paper, we provide a method for experimentally characterizing memory-access costs for modern NUMA architectures via memory latency and bandwidth microbenchmarks. Using the results of these benchmarks, we propose a memory-access cost model to improve task-scheduling decisions by scheduling tasks near the data they need. Simple task-scheduling experiments using the memory-access cost models validate the use of empirical memory-access cost models to significantly improve program performance.

  11. Memory for Recently Accessed Visual Attributes

    ERIC Educational Resources Information Center

    Jiang, Yuhong V.; Shupe, Joshua M.; Swallow, Khena M.; Tan, Deborah H.

    2016-01-01

    Recent reports have suggested that the attended features of an item may be rapidly forgotten once they are no longer relevant for an ongoing task (attribute amnesia). This finding relies on a surprise memory procedure that places high demands on declarative memory. We used intertrial priming to examine whether the representation of an item's…

  12. Direct access inter-process shared memory

    DOEpatents

    Brightwell, Ronald B; Pedretti, Kevin; Hudson, Trammell B

    2013-10-22

    A technique for directly sharing physical memory between processes executing on processor cores is described. The technique includes loading a plurality of processes into the physical memory for execution on a corresponding plurality of processor cores sharing the physical memory. An address space is mapped to each of the processes by populating a first entry in a top level virtual address table for each of the processes. The address space of each of the processes is cross-mapped into each of the processes by populating one or more subsequent entries of the top level virtual address table with the first entry in the top level virtual address table from other processes.

  13. 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.

  14. Memory cell operation based on small Josephson junctions arrays

    NASA Astrophysics Data System (ADS)

    Braiman, Y.; Nair, N.; Rezac, J.; Imam, N.

    2016-12-01

    In this paper we analyze a cryogenic memory cell circuit based on a small coupled array of Josephson junctions. All the basic memory operations (e.g., write, read, and reset) are implemented on the same circuit and different junctions in the array can in principle be utilized for these operations. The presented memory operation paradigm is fundamentally different from conventional single quantum flux operation logics (SFQ). As an example, we demonstrate memory operation driven by a SFQ pulse employing an inductively coupled array of three Josephson junctions. We have chosen realistic Josephson junction parameters based on state-of-the-art fabrication capabilities and have calculated access times and access energies for basic memory cell operations. We also implemented an optimization procedure based on the simulated annealing algorithm to calculate the optimized and typical values of access times and access energies.

  15. Memory B cells in Transplantation

    PubMed Central

    Chong, Anita S.; Sciammas, Roger

    2014-01-01

    Much of the research on the humoral response to allografts has focused on circulating serum antibodies and the long-lived plasma cells that produce these antibodies. In contrast, the interrogation of the quiescent memory B cell compartment is technically more challenging and thus has not been incorporated into the clinical diagnostic or prognostic toolkit. In this review, we discuss new technologies that have allowed this heretofore enigmatic subset of B cells to be identified at quiescence and during a recall response. These technologies in experimental models are providing new insights into memory B cell heterogeneity with respect to their phenotype, cellular function and the antibodies they produce. Similar technologies are also allowing for the identification of comparable memory alloreactive B cells in transplant recipients. While much of the focus in transplant immunology has been on controlling the alloreactive B cell population, long-term transplant patient survival is critically dependent on protection by pathogen-specific memory B cells. Techniques are also available that allow the interrogation of memory B cell response to pathogen re-encounter. Thus we are poised in our ability toinvestigate how immunosuppression affects allo- as well as pathogen-specific memory B cells, and reason that these investigation can yield new insights that will be beneficial for graft as well as patient survival. PMID:25525921

  16. 75 FR 16507 - In the Matter of Certain Semiconductor Chips Having Synchronous Dynamic Random Access Memory...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-01

    ... COMMISSION In the Matter of Certain Semiconductor Chips Having Synchronous Dynamic Random Access Memory... certain semiconductor chips having synchronous dynamic random access memory controllers and products... section 337 by importing certain semiconductor chips having synchronous dynamic random access...

  17. An Investigation of Unified Memory Access Performance in CUDA.

    PubMed

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

    2014-09-01

    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.

  18. High Performance Remote Memory Access Communication: The ARMCI Approach

    SciTech Connect

    Nieplocha, Jarek; Tipparaju, Vinod; Krishnan, Manoj Kumar; Panda, Dhabaleswar K.

    2006-07-01

    This paper describes the Aggregate Remote Memory Copy Interface (ARMCI), a portable high performance remote memory access (RMA) communication interface, developed originally under the DoE-2000 ACTS Toolkit project and currently used as a part of the run-time layer of the DoE project Programming Models for Scalable Parallel Computing. The paper discusses the model, portable implementation, and performance of ARMCI. Special emphasis is placed on the latency hiding mechanisms and ability to optimize noncontiguous data transfers.

  19. 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.

  20. Cell memory-based therapy

    PubMed Central

    Anjamrooz, Seyed Hadi

    2015-01-01

    Current cell therapies, despite all of the progress in this field, still faces major ethical, technical and regulatory hurdles. Because these issues possibly stem from the current, restricted, stereotypical view of cell ultrastructure and function, we must think radically about the nature of the cell. In this regard, the author's theory of the cell memory disc offers ‘memory-based therapy’, which, with the help of immune system rejuvenation, nervous system control and microparticle-based biodrugs, may have substantial therapeutic potential. In addition to its potential value in the study and prevention of premature cell aging, age-related diseases and cell death, memory therapy may improve the treatment of diseases that are currently limited by genetic disorders, risk of tumour formation and the availability and immunocompatibility of tissue transplants. PMID:26256679

  1. Direct memory access transfer completion notification

    DOEpatents

    Archer, Charles J.; Blocksome, Michael A.; Parker, Jeffrey J.

    2011-02-15

    DMA transfer completion notification includes: inserting, by an origin DMA engine on an origin node in an injection first-in-first-out (`FIFO`) buffer, a data descriptor for an application message to be transferred to a target node on behalf of an application on the origin node; inserting, by the origin DMA engine, a completion notification descriptor in the injection FIFO buffer after the data descriptor for the message, the completion notification descriptor specifying a packet header for a completion notification packet; transferring, by the origin DMA engine to the target node, the message in dependence upon the data descriptor; sending, by the origin DMA engine, the completion notification packet to a local reception FIFO buffer using a local memory FIFO transfer operation; and notifying, by the origin DMA engine, the application that transfer of the message is complete in response to receiving the completion notification packet in the local reception FIFO buffer.

  2. Exploiting Nonblocking Remote Memory Access Communication in Scientific Benchmarks

    SciTech Connect

    Tipparaju, Vinod; Krishnan, Manoj Kumar; Nieplocha, Jarek; Santhanaraman, Gopalakrishnan; Panda, Dhabaleswar K.

    2004-12-07

    In the last decade message passing has become the predominant programming model for scientific applications. The current paper attempts to answer the question to what degree performance of well tuned application benchmarks coded in MPI can be improved by using another related programming model, remote memory access (RMA) communication.

  3. Kokkos: Enabling manycore performance portability through polymorphic memory access patterns

    SciTech Connect

    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 diverse 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.

  4. 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

  5. 77 FR 74222 - Certain Dynamic Random Access Memory and NAND Flash Memory Devices and Products Containing Same...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-13

    ... COMMISSION Certain Dynamic Random Access Memory and NAND Flash Memory Devices and Products Containing Same... Bentonville, Arkansas (collectively, ``the remaining respondents''); Elpida Memory, Inc. of Tokyo, Japan and Elpida Memory (USA) of Sunnyvale, California (collectively, ``Elpida''); and SK Hynix Inc. (f/k/a...

  6. Ferroelectric symmetry-protected multibit memory cell

    PubMed Central

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

    2017-01-01

    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. PMID:28176866

  7. 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.

  8. 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.

  9. 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.

  10. 75 FR 14467 - In the Matter of: Certain Dynamic Random Access Memory Semiconductors and Products Containing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-25

    ... COMMISSION In the Matter of: Certain Dynamic Random Access Memory Semiconductors and Products Containing Same, Including Memory Modules; Notice of Investigation AGENCY: U.S. International Trade Commission. ACTION... random access memory semiconductors and products containing same, including memory modules, by reason...

  11. 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.

  12. 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.

  13. Magnetic Random Access Memory; Integrated Passive Components

    DTIC Science & Technology

    2010-06-02

    Donohoe University of Idaho Electrical and Computer Engineering BEL 210, POB 441023 Moscow, ID 83844-1023 2 June 2010 Final Report...University of Idaho Electrical and Computer Engineering BEL 210, POB 441023 Moscow, ID 83844-1023 MRAM-III INTPASS-I Final 9...and  diced. In the  lab , the MTJ cells are deposited, and the upper metal traces completed.                                    Figure 13 shows the

  14. 76 FR 73676 - Certain Dynamic Random Access Memory Devices, and Products Containing Same; Receipt of Complaint...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-29

    ... COMMISSION Certain Dynamic Random Access Memory Devices, and Products Containing Same; Receipt of Complaint... complaint entitled In Re Certain Dynamic Random Access Memory Devices, and Products Containing Same, DN 2859... within the United States after importation of certain dynamic random access memory devices, and...

  15. 76 FR 80964 - Certain Dynamic Random Access Memory Devices, and Products Containing Same; Institution of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-27

    ... COMMISSION Certain Dynamic Random Access Memory Devices, and Products Containing Same; Institution of... States after importation of certain dynamic random access memory devices, and products containing same by... dynamic random access memory devices, and products containing same that infringe one or more of claims...

  16. 76 FR 2336 - Dynamic Random Access Memory Semiconductors From the Republic of Korea: Final Results of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-13

    ... International Trade Administration Dynamic Random Access Memory Semiconductors From the Republic of Korea: Final... on dynamic random access memory semiconductors from the Republic of Korea for the period January 1... publication of the preliminary results of this review. See Dynamic Random Access Memory Semiconductors...

  17. 75 FR 55764 - Dynamic Random Access Memory Semiconductors From the Republic of Korea: Preliminary Results of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-14

    ... International Trade Administration Dynamic Random Access Memory Semiconductors From the Republic of Korea... administrative review of the countervailing duty order on dynamic random access memory semiconductors from the... countervailing duty order on dynamic random access memory semiconductors (``DRAMS'') From the Republic of...

  18. 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

    SciTech Connect

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

    2014-02-07

    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 Cu{sub 0.6}Te{sub 0.4} 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/Cu{sub 0.6}Te{sub 0.4}-C/Al{sub 2}O{sub 3}/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 Al{sub 2}O{sub 3} 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 Al{sub 2}O{sub 3} before and after annealing, showing a higher Cu, Te, and C migration for high carbon contents.

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

    NASA Technical Reports Server (NTRS)

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

  20. 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.

  1. 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.

  2. A random access memory immune to single event upset using a T-Resistor

    DOEpatents

    Ochoa, A. Jr.

    1987-10-28

    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. 4 figs.

  3. Memory B cells in mouse models.

    PubMed

    Bergmann, B; Grimsholm, O; Thorarinsdottir, K; Ren, W; Jirholt, P; Gjertsson, I; Mårtensson, I-L

    2013-08-01

    One of the principles behind vaccination, as shown by Edward Jenner in 1796, and host protection is immunological memory, and one of the cells central to this is the antigen-experienced memory B cell that responds rapidly upon re-exposure to the initiating antigen. Classically, memory B cells have been defined as progenies of germinal centre (GC) B cells expressing isotype-switched and substantially mutated B cell receptors (BCRs), that is, membrane-bound antibodies. However, it has become apparent over the last decade that this is not the only pathway to B cell memory. Here, we will discuss memory B cells in mice, as defined by (1) cell surface markers; (2) multiple layers; (3) formation in a T cell-dependent and either GC-dependent or GC-independent manner; (4) formation in a T cell-independent fashion. Lastly, we will touch upon memory B cells in; (5) mouse models of autoimmune diseases.

  4. A new laterally conductive bridge random access memory by fully CMOS logic compatible process

    NASA Astrophysics Data System (ADS)

    Hsieh, Min-Che; Chin, Yung-Wen; Lin, Yu-Cheng; Chih, Yu-Der; Tsai, Kan-Hsueh; Tsai, Ming-Jinn; King, Ya-Chin; Lin, Chrong Jung

    2014-01-01

    This paper proposes a novel laterally conductive bridge random access memory (L-CBRAM) module using a fully CMOS logic compatible process. A contact buffer layer between the poly-Si and contact plug enables the lateral Ti-based atomic layer to provide on/off resistance ratio via bipolar operations. The proposed device reached more than 100 pulse cycles with an on/off ratio over 10 and very stable data retention under high temperature operations. These results make this Ti-based L-CBRAM cell a promising solution for advanced embedded multi-time programmable (MTP) memory applications.

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

    SciTech Connect

    Song, Kyungmi; Lee, Kyung-Jin

    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 for the optimization of STT-MRAM.

  6. Immune signatures of protective spleen memory CD8 T cells

    PubMed Central

    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

    2016-01-01

    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. PMID:27883012

  7. Administering an epoch initiated for remote memory access

    DOEpatents

    Blocksome, Michael A; Miller, Douglas R

    2014-03-18

    Methods, systems, and products are disclosed for administering an epoch initiated for remote memory access that include: initiating, by an origin application messaging module on an origin compute node, one or more data transfers to a target compute node for the epoch; initiating, by the origin application messaging module after initiating the data transfers, a closing stage for the epoch, including rejecting any new data transfers after initiating the closing stage for the epoch; determining, by the origin application messaging module, whether the data transfers have completed; and closing, by the origin application messaging module, the epoch if the data transfers have completed.

  8. Administering an epoch initiated for remote memory access

    DOEpatents

    Blocksome, Michael A; Miller, Douglas R

    2012-10-23

    Methods, systems, and products are disclosed for administering an epoch initiated for remote memory access that include: initiating, by an origin application messaging module on an origin compute node, one or more data transfers to a target compute node for the epoch; initiating, by the origin application messaging module after initiating the data transfers, a closing stage for the epoch, including rejecting any new data transfers after initiating the closing stage for the epoch; determining, by the origin application messaging module, whether the data transfers have completed; and closing, by the origin application messaging module, the epoch if the data transfers have completed.

  9. Administering an epoch initiated for remote memory access

    DOEpatents

    Blocksome, Michael A.; Miller, Douglas R.

    2013-01-01

    Methods, systems, and products are disclosed for administering an epoch initiated for remote memory access that include: initiating, by an origin application messaging module on an origin compute node, one or more data transfers to a target compute node for the epoch; initiating, by the origin application messaging module after initiating the data transfers, a closing stage for the epoch, including rejecting any new data transfers after initiating the closing stage for the epoch; determining, by the origin application messaging module, whether the data transfers have completed; and closing, by the origin application messaging module, the epoch if the data transfers have completed.

  10. Memory B cells contribute to rapid Bcl6 expression by memory follicular helper T cells.

    PubMed

    Ise, Wataru; Inoue, Takeshi; McLachlan, James B; Kometani, Kohei; Kubo, Masato; Okada, Takaharu; Kurosaki, Tomohiro

    2014-08-12

    In primary humoral responses, B-cell lymphoma 6 (Bcl6) is a master regulator of follicular helper T (TFH) cell differentiation; however, its activation mechanisms and role in memory responses remain unclear. Here we demonstrate that survival of CXCR5(+) TFH memory cells, and thus subsequent recall antibody response, require Bcl6 expression. Furthermore, we show that, upon rechallenge with soluble antigen Bcl6 in memory TFH cells is rapidly induced in a dendritic cell-independent manner and that peptide:class II complexes (pMHC) on cognate memory B cells significantly contribute to this induction. Given the previous evidence that antigen-specific B cells residing in the follicles acquire antigens within minutes of injection, our results suggest that memory B cells present antigens to the cognate TFH memory cells, thereby contributing to rapid Bcl6 reexpression and differentiation of the TFH memory cells during humoral memory responses.

  11. Resistive random access memory enabled by carbon nanotube crossbar electrodes.

    PubMed

    Tsai, Cheng-Lin; Xiong, Feng; Pop, Eric; Shim, Moonsub

    2013-06-25

    We use single-walled carbon nanotube (CNT) crossbar electrodes to probe sub-5 nm memory domains of thin AlOx films. Both metallic and semiconducting CNTs effectively switch AlOx bits between memory states with high and low resistance. The low-resistance state scales linearly with CNT series resistance down to ∼10 MΩ, at which point the ON-state resistance of the AlOx filament becomes the limiting factor. Dependence of switching behavior on the number of cross-points suggests a single channel to dominate the overall characteristics in multi-crossbar devices. We demonstrate ON/OFF ratios up to 5 × 10(5) and programming currents of 1 to 100 nA with few-volt set/reset voltages. Remarkably low reset currents enable a switching power of 10-100 nW and estimated switching energy as low as 0.1-10 fJ per bit. These results are essential for understanding the ultimate scaling limits of resistive random access memory at single-nanometer bit dimensions.

  12. Efficient Memory Access with NumPy Global Arrays using Local Memory Access

    SciTech Connect

    Daily, Jeffrey A.; Berghofer, Dan C.

    2013-08-03

    This paper discusses the work completed working with Global Arrays of data on distributed multi-computer systems and improving their performance. The tasks completed were done at Pacific Northwest National Laboratory in the Science Undergrad Laboratory Internship program in the summer of 2013 for the Data Intensive Computing Group in the Fundamental and Computational Sciences DIrectorate. This work was done on the Global Arrays Toolkit developed by this group. This toolkit is an interface for programmers to more easily create arrays of data on networks of computers. This is useful because scientific computation is often done on large amounts of data sometimes so large that individual computers cannot hold all of it. This data is held in array form and can best be processed on supercomputers which often consist of a network of individual computers doing their computation in parallel. One major challenge for this sort of programming is that operations on arrays on multiple computers is very complex and an interface is needed so that these arrays seem like they are on a single computer. This is what global arrays does. The work done here is to use more efficient operations on that data that requires less copying of data to be completed. This saves a lot of time because copying data on many different computers is time intensive. The way this challenge was solved is when data to be operated on with binary operations are on the same computer, they are not copied when they are accessed. When they are on separate computers, only one set is copied when accessed. This saves time because of less copying done although more data access operations were done.

  13. TCR Signaling in T Cell Memory.

    PubMed

    Daniels, Mark A; Teixeiro, Emma

    2015-01-01

    T cell memory plays a critical role in our protection against pathogens and tumors. The antigen and its interaction with the T cell receptor (TCR) is one of the initiating elements that shape T cell memory together with inflammation and costimulation. Over the last decade, several transcription factors and signaling pathways that support memory programing have been identified. However, how TCR signals regulate them is still poorly understood. Recent studies have shown that the biochemical rules that govern T cell memory, strikingly, change depending on the TCR signal strength. Furthermore, TCR signal strength regulates the input of cytokine signaling, including pro-inflammatory cytokines. These highlight how tailoring antigenic signals can improve immune therapeutics. In this review, we focus on how TCR signaling regulates T cell memory and how the quantity and quality of TCR-peptide-MHC interactions impact the multiple fates a T cell can adopt in the memory pool.

  14. TCR Signaling in T Cell Memory

    PubMed Central

    Daniels, Mark A.; Teixeiro, Emma

    2015-01-01

    T cell memory plays a critical role in our protection against pathogens and tumors. The antigen and its interaction with the T cell receptor (TCR) is one of the initiating elements that shape T cell memory together with inflammation and costimulation. Over the last decade, several transcription factors and signaling pathways that support memory programing have been identified. However, how TCR signals regulate them is still poorly understood. Recent studies have shown that the biochemical rules that govern T cell memory, strikingly, change depending on the TCR signal strength. Furthermore, TCR signal strength regulates the input of cytokine signaling, including pro-inflammatory cytokines. These highlight how tailoring antigenic signals can improve immune therapeutics. In this review, we focus on how TCR signaling regulates T cell memory and how the quantity and quality of TCR–peptide–MHC interactions impact the multiple fates a T cell can adopt in the memory pool. PMID:26697013

  15. Size effect of nano scale phase change random access memory.

    PubMed

    Son, Ji Hoon; Choi, HongKyw; Jang, Nakwon; Kim, Hong Seung; Yi, Dong Young; Lee, Seong Hwan

    2010-05-01

    In this paper, we have investigated the size effect of nano scale PRAM using three-dimensional finite element analysis tool. The reset current and temperature profile of PRAM cells with top and bottom electrode contact hole size were calculated by the numerical method. And temperature profile of PRAM unit cell with size and thickness of GST thin film was simulated. As top electrode contact size was smaller, reset current decreased. But these variations couldn't affect to operate memory. On the other hand, as bottom electrode contact size was smaller, reset current abruptly decreased.

  16. 9. ENGINE TEST CELL BUILDING INTERIOR. CELL ACCESS ELEVATOR, CELLS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. ENGINE TEST CELL BUILDING INTERIOR. CELL ACCESS ELEVATOR, CELLS 2 AND 4, BASEMENT LEVEL. LOOKING SOUTHEAST. - Fairchild Air Force Base, Engine Test Cell Building, Near intersection of Arnold Street & George Avenue, Spokane, Spokane County, WA

  17. Using epigenetics to define vaccine-induced memory T cells

    PubMed Central

    Youngblood, Ben; Hale, J Scott; Akondy, Rama

    2013-01-01

    Memory T cells generated from acute infection or vaccination have the potential to provide the host with life-long immunity against re-infection. Protection by memory T cells is achieved through their acquired ability to persist at anatomical sites of the primary infection as well as maintaining a heightened ability to recall effector functions. The maintenance of CD8 and CD4 T cell function in a state of readiness is key to life-long immunity and manifest through changes in transcriptional regulation. Yet, the ability to identify poised transcriptional programs at the maintenance stage of the response is lacking from most transcriptional profiling studies of memory T cells. Epigenetic profiling allows for the assessment of transcriptionally poised (promoters that are readily accessible for transcription) states of antigen-specific T cells without manipulation of the activation state of the cell. Here we review recent studies that have examined epigenetic programs of effector and memory T cell subsets. These reports demonstrate that acquisition of epigenetic programs during memory T cell differentiation to acute and chronic infections is coupled to, and potentially regulate, the cell’s recall response. We discuss the usefulness of epigenetic profiling in characterizing T cell differentiation state and function for preclinical evaluation of vaccines and the current methodologies for single locus versus genome-wide epigenetic profiling. PMID:23747121

  18. One electron-controlled multiple-valued dynamic random-access-memory

    NASA Astrophysics Data System (ADS)

    Kye, H. W.; Song, B. N.; Lee, S. E.; Kim, J. S.; Shin, S. J.; Choi, J. B.; Yu, Y.-S.; Takahashi, Y.

    2016-02-01

    We propose a new architecture for a dynamic random-access-memory (DRAM) capable of storing multiple values by using a single-electron transistor (SET). The gate of a SET is designed to be connected to a plurality of DRAM unit cells that are arrayed at intersections of word lines and bitlines. In this SET-DRAM hybrid scheme, the multiple switching characteristics of SET enables multiple value data stored in a DRAM unit cell, and this increases the storage functionality of the device. Moreover, since refreshing data requires only a small amount of SET driving current, this enables device operating with low standby power consumption.

  19. The cellular memory disc of reprogrammed cells.

    PubMed

    Anjamrooz, Seyed Hadi

    2013-04-01

    The crucial facts underlying the low efficiency of cellular reprogramming are poorly understood. Cellular reprogramming occurs in nuclear transfer, induced pluripotent stem cell (iPSC) formation, cell fusion, and lineage-switching experiments. Despite these advances, there are three fundamental problems to be addressed: (1) the majority of cells cannot be reprogrammed, (2) the efficiency of reprogramming cells is usually low, and (3) the reprogrammed cells developed from a patient's own cells activate immune responses. These shortcomings present major obstacles for using reprogramming approaches in customised cell therapy. In this Perspective, the author synthesises past and present observations in the field of cellular reprogramming to propose a theoretical picture of the cellular memory disc. The current hypothesis is that all cells undergo an endogenous and exogenous holographic memorisation such that parts of the cellular memory dramatically decrease the efficiency of reprogramming cells, act like a barrier against reprogramming in the majority of cells, and activate immune responses. Accordingly, the focus of this review is mainly to describe the cellular memory disc (CMD). Based on the present theory, cellular memory includes three parts: a reprogramming-resistance memory (RRM), a switch-promoting memory (SPM) and a culture-induced memory (CIM). The cellular memory arises genetically, epigenetically and non-genetically and affects cellular behaviours. [corrected].

  20. Ultrafast switching in nanoscale phase-change random access memory with superlattice-like structures.

    PubMed

    Loke, Desmond; Shi, Luping; Wang, Weijie; Zhao, Rong; Yang, Hongxin; Ng, Lung-Tat; Lim, Kian-Guan; Chong, Tow-Chong; Yeo, Yee-Chia

    2011-06-24

    Phase-change random access memory cells with superlattice-like (SLL) GeTe/Sb(2)Te(3) were demonstrated to have excellent scaling performance in terms of switching speed and operating voltage. In this study, the correlations between the cell size, switching speed and operating voltage of the SLL cells were identified and investigated. We found that small SLL cells can achieve faster switching speed and lower operating voltage compared to the large SLL cells. Fast amorphization and crystallization of 300 ps and 1 ns were achieved in the 40 nm SLL cells, respectively, both significantly faster than those observed in the Ge(2)Sb(2)Te(5) (GST) cells of the same cell size. 40 nm SLL cells were found to switch with low amorphization voltage of 0.9 V when pulse-widths of 5 ns were employed, which is much lower than the 1.6 V required by the GST cells of the same cell size. These effects can be attributed to the fast heterogeneous crystallization, low thermal conductivity and high resistivity of the SLL structures. Nanoscale PCRAM with SLL structure promises applications in high speed and low power memory devices.

  1. Materials selection for oxide-based resistive random access memories

    SciTech Connect

    Guo, Yuzheng; Robertson, John

    2014-12-01

    The energies of atomic processes in resistive random access memories (RRAMs) are calculated for four typical oxides, HfO{sub 2}, TiO{sub 2}, Ta{sub 2}O{sub 5}, and Al{sub 2}O{sub 3}, to define a materials selection process. O vacancies have the lowest defect formation energy in the O-poor limit and dominate the processes. A band diagram defines the operating Fermi energy and O chemical potential range. It is shown how the scavenger metal can be used to vary the O vacancy formation energy, via controlling the O chemical potential, and the mean Fermi energy. The high endurance of Ta{sub 2}O{sub 5} RRAM is related to its more stable amorphous phase and the adaptive lattice rearrangements of its O vacancy.

  2. 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.

  3. SiCOH-based resistive random access memory for backend of line compatible nonvolatile memory application

    NASA Astrophysics Data System (ADS)

    Zheng, Liang; Dai, Ya-Wei; Yu, Lin-Jie; Chen, Lin; Sun, Qing-Qing; Zhang, David Wei

    2017-04-01

    We investigated the resistive switching characteristics of a SiCOH low-k-material-based resistive random access memory (RRAM) in this study. This SiCOH-based RRAM is fully compatible with backend CMOS technology, which is extremely important for its applicability. The device demonstrated here had higher performance characteristics than a conventional SiO2-based RRAM, such as a higher ON/OFF ratio (around 102), and a higher cycling endurance in an ambient environment. Taken together, these characteristics make the device a promising candidate for next-generation nonvolatile applications.

  4. 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.

  5. 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…

  6. Associative memory cells: Formation, function and perspective

    PubMed Central

    Wang, Jin-Hui; Cui, Shan

    2017-01-01

    Associative learning and memory are common activities in life, and their cellular infrastructures constitute the basis of cognitive processes. Although neuronal plasticity emerges after memory formation, basic units and their working principles for the storage and retrieval of associated signals remain to be revealed. Current reports indicate that associative memory cells, through their mutual synapse innervations among the co-activated sensory cortices, are recruited to fulfill the integration, storage and retrieval of multiple associated signals, and serve associative thinking and logical reasoning. In this review, we aim to summarize associative memory cells in their formation, features and functional impacts.

  7. SONOS Nonvolatile Memory Cell Programming Characteristics

    NASA Technical Reports Server (NTRS)

    MacLeod, Todd C.; Phillips, Thomas A.; Ho, Fat D.

    2010-01-01

    Silicon-oxide-nitride-oxide-silicon (SONOS) nonvolatile memory is gaining favor over conventional EEPROM FLASH memory technology. This paper characterizes the SONOS write operation using a nonquasi-static MOSFET model. This includes floating gate charge and voltage characteristics as well as tunneling current, voltage threshold and drain current characterization. The characterization of the SONOS memory cell predicted by the model closely agrees with experimental data obtained from actual SONOS memory cells. The tunnel current, drain current, threshold voltage and read drain current all closely agreed with empirical data.

  8. Optimizing NEURON Simulation Environment Using Remote Memory Access with Recursive Doubling on Distributed Memory Systems.

    PubMed

    Shehzad, Danish; Bozkuş, Zeki

    2016-01-01

    Increase in complexity of neuronal network models escalated the efforts to make NEURON simulation environment efficient. The computational neuroscientists divided the equations into subnets amongst multiple processors for achieving better hardware performance. On parallel machines for neuronal networks, interprocessor spikes exchange consumes large section of overall simulation time. In NEURON for communication between processors Message Passing Interface (MPI) is used. MPI_Allgather collective is exercised for spikes exchange after each interval across distributed memory systems. The increase in number of processors though results in achieving concurrency and better performance but it inversely affects MPI_Allgather which increases communication time between processors. This necessitates improving communication methodology to decrease the spikes exchange time over distributed memory systems. This work has improved MPI_Allgather method using Remote Memory Access (RMA) by moving two-sided communication to one-sided communication, and use of recursive doubling mechanism facilitates achieving efficient communication between the processors in precise steps. This approach enhanced communication concurrency and has improved overall runtime making NEURON more efficient for simulation of large neuronal network models.

  9. Optimizing NEURON Simulation Environment Using Remote Memory Access with Recursive Doubling on Distributed Memory Systems

    PubMed Central

    Bozkuş, Zeki

    2016-01-01

    Increase in complexity of neuronal network models escalated the efforts to make NEURON simulation environment efficient. The computational neuroscientists divided the equations into subnets amongst multiple processors for achieving better hardware performance. On parallel machines for neuronal networks, interprocessor spikes exchange consumes large section of overall simulation time. In NEURON for communication between processors Message Passing Interface (MPI) is used. MPI_Allgather collective is exercised for spikes exchange after each interval across distributed memory systems. The increase in number of processors though results in achieving concurrency and better performance but it inversely affects MPI_Allgather which increases communication time between processors. This necessitates improving communication methodology to decrease the spikes exchange time over distributed memory systems. This work has improved MPI_Allgather method using Remote Memory Access (RMA) by moving two-sided communication to one-sided communication, and use of recursive doubling mechanism facilitates achieving efficient communication between the processors in precise steps. This approach enhanced communication concurrency and has improved overall runtime making NEURON more efficient for simulation of large neuronal network models. PMID:27413363

  10. 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

  11. 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.

  12. The Evolving Roles of Memory Immune Cells in Transplantation.

    PubMed

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

    2015-10-01

    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.

  13. Microstructural Characterization in Reliability Measurement of Phase Change Random Access Memory

    NASA Astrophysics Data System (ADS)

    Bae, Junsoo; Hwang, Kyuman; Park, Kwangho; Jeon, Seongbu; Kang, Dae-hwan; Park, Soonoh; Ahn, Juhyeon; Kim, Seoksik; Jeong, Gitae; Chung, Chilhee

    2011-04-01

    The cell failures after cycling endurance in phase-change random access memory (PRAM) have been classified into three groups, which have been analyzed by transmission electron microscopy (TEM). Both stuck reset of the set state (D0) and stuck set of the reset state (D1) are due to a void created inside GeSbTe (GST) film or thereby lowering density of GST film. The decrease of the both set and reset resistances that leads to the tails from the reset distribution are induced from the Sb increase with cycles.

  14. 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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF COMMERCE International Trade Administration Dynamic Random Access Memory Semiconductors from the Republic of Korea... administrative review of the countervailing duty order on dynamic random access memory semiconductors from...

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

    DOEpatents

    Gala, Alan; Ohmacht, Martin

    2014-09-02

    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 memory 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.

  16. Modeling of SONOS Memory Cell Erase Cycle

    NASA Technical Reports Server (NTRS)

    Phillips, Thomas A.; MacLeod, Todd C.; Ho, Fat H.

    2011-01-01

    Utilization of Silicon-Oxide-Nitride-Oxide-Silicon (SONOS) nonvolatile semiconductor memories as a flash memory has many advantages. These electrically erasable programmable read-only memories (EEPROMs) utilize low programming voltages, have a high erase/write cycle lifetime, are radiation hardened, and are compatible with high-density scaled CMOS for low power, portable electronics. In this paper, the SONOS memory cell erase cycle was investigated using a nonquasi-static (NQS) MOSFET model. Comparisons were made between the model predictions and experimental data.

  17. Modeling of Sonos Memory Cell Erase Cycle

    NASA Technical Reports Server (NTRS)

    Phillips, Thomas A.; MacLeond, Todd C.; Ho, Fat D.

    2010-01-01

    Silicon-oxide-nitride-oxide-silicon (SONOS) nonvolatile semiconductor memories (NVSMS) have many advantages. These memories are electrically erasable programmable read-only memories (EEPROMs). They utilize low programming voltages, endure extended erase/write cycles, are inherently resistant to radiation, and are compatible with high-density scaled CMOS for low power, portable electronics. The SONOS memory cell erase cycle was investigated using a nonquasi-static (NQS) MOSFET model. The SONOS floating gate charge and voltage, tunneling current, threshold voltage, and drain current were characterized during an erase cycle. Comparisons were made between the model predictions and experimental device data.

  18. Viable chemical approach for patterning nanoscale magnetoresistive random access memory

    SciTech Connect

    Kim, Taeseung; Kim, Younghee; Chen, Jack Kun-Chieh; Chang, Jane P.

    2015-03-15

    A reactive ion etching process with alternating Cl{sub 2} and H{sub 2} exposures has been shown to chemically etch CoFe film that is an integral component in magnetoresistive random access memory (MRAM). Starting with systematic thermodynamic calculations assessing various chemistries and reaction pathways leading to the highest possible vapor pressure of the etch products reactions, the potential chemical combinations were verified by etch rate investigation and surface chemistry analysis in plasma treated CoFe films. An ∼20% enhancement in etch rate was observed with the alternating use of Cl{sub 2} and H{sub 2} plasmas, in comparison with the use of only Cl{sub 2} plasma. This chemical combination was effective in removing metal chloride layers, thus maintaining the desired magnetic properties of the CoFe films. Scanning electron microscopy equipped with energy-dispersive x-ray spectroscopy showed visually and spectroscopically that the metal chloride layers generated by Cl{sub 2} plasma were eliminated with H{sub 2} plasma to yield a clean etch profile. This work suggests that the selected chemistries can be used to etch magnetic metal alloys with a smooth etch profile and this general strategy can be applied to design chemically based etch processes to enable the fabrication of highly integrated nanoscale MRAM devices.

  19. Radiation dosimetry using three-dimensional optical random access memories

    NASA Technical Reports Server (NTRS)

    Moscovitch, M.; Phillips, G. W.

    2001-01-01

    Three-dimensional optical random access memories (3D ORAMs) are a new generation of high-density data storage devices. Binary information is stored and retrieved via a light induced reversible transformation of an ensemble of bistable photochromic molecules embedded in a polymer matrix. This paper describes the application of 3D ORAM materials to radiation dosimetry. It is shown both theoretically and experimentally, that ionizing radiation in the form of heavy charged particles is capable of changing the information originally stored on the ORAM material. The magnitude and spatial distribution of these changes are used as a measure of the absorbed dose, particle type and energy. The effects of exposure on 3D ORAM materials have been investigated for a variety of particle types and energies, including protons, alpha particles and 12C ions. The exposed materials are observed to fluoresce when exposed to laser light. The intensity and the depth of the fluorescence is dependent on the type and energy of the particle to which the materials were exposed. It is shown that these effects can be modeled using Monte Carlo calculations. The model provides a better understanding of the properties of these materials. which should prove useful for developing systems for charged particle and neutron dosimetry/detector applications. c2001 Published by Elsevier Science B.V.

  20. Human T Cell Memory: A Dynamic View

    PubMed Central

    Macallan, Derek C.; Borghans, José A. M.; Asquith, Becca

    2017-01-01

    Long-term T cell-mediated protection depends upon the formation of a pool of memory cells to protect against future pathogen challenge. In this review we argue that looking at T cell memory from a dynamic viewpoint can help in understanding how memory populations are maintained following pathogen exposure or vaccination. For example, a dynamic view resolves the apparent paradox between the relatively short lifespans of individual memory cells and very long-lived immunological memory by focussing on the persistence of clonal populations, rather than individual cells. Clonal survival is achieved by balancing proliferation, death and differentiation rates within and between identifiable phenotypic pools; such pools correspond broadly to sequential stages in the linear differentiation pathway. Each pool has its own characteristic kinetics, but only when considered as a population; single cells exhibit considerable heterogeneity. In humans, we tend to concentrate on circulating cells, but memory T cells in non-lymphoid tissues and bone marrow are increasingly recognised as critical for immune defence; their kinetics, however, remain largely unexplored. Considering vaccination from this viewpoint shifts the focus from the size of the primary response to the survival of the clone and enables identification of critical system pinch-points and opportunities to improve vaccine efficacy. PMID:28165397

  1. Human T Cell Memory: A Dynamic View.

    PubMed

    Macallan, Derek C; Borghans, José A M; Asquith, Becca

    2017-02-04

    Long-term T cell-mediated protection depends upon the formation of a pool of memory cells to protect against future pathogen challenge. In this review we argue that looking at T cell memory from a dynamic viewpoint can help in understanding how memory populations are maintained following pathogen exposure or vaccination. For example, a dynamic view resolves the apparent paradox between the relatively short lifespans of individual memory cells and very long-lived immunological memory by focussing on the persistence of clonal populations, rather than individual cells. Clonal survival is achieved by balancing proliferation, death and differentiation rates within and between identifiable phenotypic pools; such pools correspond broadly to sequential stages in the linear differentiation pathway. Each pool has its own characteristic kinetics, but only when considered as a population; single cells exhibit considerable heterogeneity. In humans, we tend to concentrate on circulating cells, but memory T cells in non-lymphoid tissues and bone marrow are increasingly recognised as critical for immune defence; their kinetics, however, remain largely unexplored. Considering vaccination from this viewpoint shifts the focus from the size of the primary response to the survival of the clone and enables identification of critical system pinch-points and opportunities to improve vaccine efficacy.

  2. 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.…

  3. Correlation between static random access memory power-up state and transistor variation

    NASA Astrophysics Data System (ADS)

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

    2017-04-01

    The correlation between the static random access memory (SRAM) power-up state (i.e., state 0 or 1 immediately after the power supply is turned on) and cell transistor variation is systematically studied by circuit simulations and mismatch space partitioning. It is revealed that, while both the mismatches of pFETs (pull-up) and nFETs (pull-down and access) contribute, their relative importance changes depending on the voltage ramping speed. The static retention noise margin well correlates with the power-up state only if the ramping speed is sufficiently low. Otherwise, pull-up transistor mismatch dominates the power-up state determination owing to the interference of capacitive current and asymmetrical capacitive coupling of the storage nodes to the ground and power supply.

  4. Direct Access by Spatial Position in Visual Memory. 1. Synopsis of Principal Findings.

    DTIC Science & Technology

    1986-01-20

    AiQi 218 DIRECT ACCESS BY SPATIAL POSITION IN VISUAL MEMORY 1 1/1 SYNOPSIS OF PRINCIPAL FINDINGS(U) PENNSYLVANIA UNIV PPHILADELPHIA S STERNBERG ET...IRR04204 RR04206-01 11 TITLE (Include SecuriY Claw ficat,@n) Direct Access by Spatial Position in Visual Memory: 1. Synopsis of Principal Findings 12...034 -amJanuary 20. 1986 , ? ’ I~ Direct Access by Spatial Position In Visual Memory: 1. Synopsis of Principal gfdings 1. Introduction In recent years

  5. Remote Memory Access Protocol Target Node Intellectual Property

    NASA Technical Reports Server (NTRS)

    Haddad, Omar

    2013-01-01

    The MagnetoSpheric Multiscale (MMS) mission had a requirement to use the Remote Memory Access Protocol (RMAP) over its SpaceWire network. At the time, no known intellectual property (IP) cores were available for purchase. Additionally, MMS preferred to implement the RMAP functionality with control over the low-level details of the design. For example, not all the RMAP standard functionality was needed, and it was desired to implement only the portions of the RMAP protocol that were needed. RMAP functionality had been previously implemented in commercial off-the-shelf (COTS) products, but the IP core was not available for purchase. The RMAP Target IP core is a VHDL (VHSIC Hardware Description Language description of a digital logic design suitable for implementation in an FPGA (field-programmable gate array) or ASIC (application-specific integrated circuit) that parses SpaceWire packets that conform to the RMAP standard. The RMAP packet protocol allows a network host to access and control a target device using address mapping. This capability allows SpaceWire devices to be managed in a standardized way that simplifies the hardware design of the device, as well as the development of the software that controls the device. The RMAP Target IP core has some features that are unique and not specified in the RMAP standard. One such feature is the ability to automatically abort transactions if the back-end logic does not respond to read/write requests within a predefined time. When a request times out, the RMAP Target IP core automatically retracts the request and returns a command response with an appropriate status in the response packet s header. Another such feature is the ability to control the SpaceWire node or router using RMAP transactions in the extended address range. This allows the SpaceWire network host to manage the SpaceWire network elements using RMAP packets, which reduces the number of protocols that the network host needs to support.

  6. RAPID: A random access picture digitizer, display, and memory system

    NASA Technical Reports Server (NTRS)

    Yakimovsky, Y.; Rayfield, M.; Eskenazi, R.

    1976-01-01

    RAPID is a system capable of providing convenient digital analysis of video data in real-time. It has two modes of operation. The first allows for continuous digitization of an EIA RS-170 video signal. Each frame in the video signal is digitized and written in 1/30 of a second into RAPID's internal memory. The second mode leaves the content of the internal memory independent of the current input video. In both modes of operation the image contained in the memory is used to generate an EIA RS-170 composite video output signal representing the digitized image in the memory so that it can be displayed on a monitor.

  7. Peripheral tissue homing receptors enable T cell entry into lymph nodes and affect the anatomical distribution of memory cells

    PubMed Central

    Brinkman, C. Colin; Rouhani, Sherin J.; Srinivasan, Nithya; Engelhard, Victor H.

    2013-01-01

    Peripheral tissue homing receptors enable T cells to access inflamed non-lymphoid tissues. Here we show that two such molecules, E-selectin ligand and α4β1 integrin, enable activated and memory T cells to enter lymph nodes as well. This affects the quantitative and qualitative distribution of these cells among regional lymph node beds. CD8 memory T cells in lymph nodes that express these molecules were mostly CD62Llo, and would normally be classified as effector memory cells. However, similar to central memory cells, they expanded upon antigen re-encounter. This led to differences in the magnitude of the recall response that depended on the route of immunization. These novel cells share properties of both central and effector memory cells, and reside in lymph nodes based on previously undescribed mechanisms of entry. PMID:23926324

  8. Gate contact resistive random access memory in nano scaled FinFET logic technologies

    NASA Astrophysics Data System (ADS)

    Hsu, Meng-Yin; Shih, Yi-Hong; Chih, Yue-Der; Lin, Chrong Jung; King, Ya-Chin

    2017-04-01

    A full logic-compatible embedded gate contact resistive random access memory (GC-RRAM) cell in the CMOS FinFET logic process without extra mask or processing steps has been successfully demonstrated for high-density and low-cost logic nonvolatile memory (NVM) applications. This novel GC-RRAM cell is composed of a transition metal oxide from the gate contact plug and interlayer dielectric (ILD) in the middle, and a gate contact and an n-type epitaxial drain terminal as the top and bottom electrodes, respectively. It features low-voltage operation and reset current, compact cell size, and a stable read window. As a promising embedded NVM solution, the compact one transistor and one resistor (1T1R) cell is highly scalable as the technology node progresses. Excellent data retention and cycling capability have also been demonstrated by the reliability testing results. These superior characteristics make GC-RRAM one of a few viable candidates for logic NVM for future FinFET circuits.

  9. 77 FR 26789 - Certain Semiconductor Chips Having Synchronous Dynamic Random Access Memory Controllers and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-07

    ... From the Federal Register Online via the Government Publishing Office ] INTERNATIONAL TRADE COMMISSION Certain Semiconductor Chips Having Synchronous Dynamic Random Access Memory Controllers and Products Containing Same; Determination Rescinding the Exclusion Order and Cease and Desist Orders...

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

    PubMed

    Sheldon, Signy; Donahue, Julia

    2017-02-27

    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.

  11. 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.

  12. Hybrid Josephson-CMOS Random Access Memory with Interfacing to Josephson Digital Circuits

    DTIC Science & Technology

    2013-10-16

    as reliable high-speed Josephson voltage drivers, Superconductor Science and Technology, (01 2013): 1. doi: TOTAL: 4 (b) Papers published in non...Theodore Van Duzer, ISEC, Washington, DC 2011 "Hybrid Josephson-CMOS Random Access Memory, T. Van Duzer, US Workshop on Superconductor Electronics: Devices...Proceeding publications (other than abstracts): Received Paper 08/22/2013 2.00 Thomas Ortlepp. Vortex transitional superconductor random access memory

  13. Hippocampal place cells, context, and episodic memory.

    PubMed

    Smith, David M; Mizumori, Sheri J Y

    2006-01-01

    Although most observers agree that the hippocampus has a critical role in learning and memory, there remains considerable debate about the precise functional contribution of the hippocampus to these processes. Two of the most influential accounts hold that the primary function of the hippocampus is to generate cognitive maps and to mediate episodic memory processes. The well-documented spatial firing patterns (place fields) of hippocampal neurons in rodents, along with the spatial learning impairments observed with hippocampal damage support the cognitive mapping hypothesis. The amnesia for personally experienced events seen in humans with hippocampal damage and the data of animal models, which show severe memory deficits associated with hippocampal lesions, support the episodic memory account. Although an extensive literature supports each of these hypotheses, a specific contribution of place cells to episodic memory has not been clearly demonstrated. Recent data from our laboratory, together with previous findings, indicate that hippocampal place fields and neuronal responses to task-relevant stimuli are highly sensitive to the context, even when the contexts are defined by abstract task demands rather than the spatial geometry of the environment. On the basis of these findings, it is proposed that place fields reflect a more general context processing function of the hippocampus. Hippocampal context representations could serve to differentiate contexts and prime the relevant memories and behaviors. Since episodic memories, by definition, include information about the time and place where the episode occurred, contextual information is a necessary prerequisite for any episodic memory. Thus, place fields contribute importantly to episodic memory as part of the needed context representations. Additionally, recent findings indicate that hippocampal neurons differentiate contexts at progressively finer levels of detail, suggesting a hierarchical coding scheme which

  14. 75 FR 44283 - In the Matter of Certain Dynamic Random Access Memory Semiconductors and Products Containing Same...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-28

    ... COMMISSION In the Matter of Certain Dynamic Random Access Memory Semiconductors and Products Containing Same, Including Memory Modules; Notice of a Commission Determination Not To Review an Initial Determination... within the United States after importation of certain dynamic random access memory semiconductors...

  15. 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…

  16. Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates.

    PubMed

    Berger, Carolina; Jensen, Michael C; Lansdorp, Peter M; Gough, Mike; Elliott, Carole; Riddell, Stanley R

    2008-01-01

    The adoptive transfer of antigen-specific T cells that have been expanded ex vivo is being actively pursued to treat infections and malignancy in humans. The T cell populations that are available for adoptive immunotherapy include both effector memory and central memory cells, and these differ in phenotype, function, and homing. The efficacy of adoptive immunotherapy requires that transferred T cells persist in vivo, but identifying T cells that can reproducibly survive in vivo after they have been numerically expanded by in vitro culture has proven difficult. Here we show that in macaques, antigen-specific CD8(+) T cell clones derived from central memory T cells, but not effector memory T cells, persisted long-term in vivo, reacquired phenotypic and functional properties of memory T cells, and occupied memory T cell niches. These results demonstrate that clonally derived CD8+ T cells isolated from central memory T cells are distinct from those derived from effector memory T cells and retain an intrinsic capacity that enables them to survive after adoptive transfer and revert to the memory cell pool. These results could have significant implications for the selection of T cells to expand or to engineer for adoptive immunotherapy of human infections or malignancy.

  17. Voltage induced magnetostrictive switching of nanomagnets: Strain assisted strain transfer torque random access memory

    SciTech Connect

    Khan, Asif Nikonov, Dmitri E.; Manipatruni, Sasikanth; Ghani, Tahir; Young, Ian A.

    2014-06-30

    A spintronic device, called the “strain assisted spin transfer torque (STT) random access memory (RAM),” is proposed by combining the magnetostriction effect and the spin transfer torque effect which can result in a dramatic improvement in the energy dissipation relative to a conventional STT-RAM. Magnetization switching in the device which is a piezoelectric-ferromagnetic heterostructure via the combined magnetostriction and STT effect is simulated by solving the Landau-Lifshitz-Gilbert equation incorporating the influence of thermal noise. The simulations show that, in such a device, each of these two mechanisms (magnetostriction and spin transfer torque) provides in a 90° rotation of the magnetization leading a deterministic 180° switching with a critical current significantly smaller than that required for spin torque alone. Such a scheme is an attractive option for writing magnetic RAM cells.

  18. High speed magneto-resistive random access memory

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

    A high speed read MRAM memory element is configured from a sandwich of magnetizable, ferromagnetic film surrounding a magneto-resistive film which may be ferromagnetic or not. One outer ferromagnetic film has a higher coercive force than the other and therefore remains magnetized in one sense while the other may be switched in sense by a switching magnetic field. The magneto-resistive film is therefore sensitive to the amplitude of the resultant field between the outer ferromagnetic films and may be constructed of a high resistivity, high magneto-resistive material capable of higher sensing currents. This permits higher read voltages and therefore faster read operations. Alternate embodiments with perpendicular anisotropy, and in-plane anisotropy are shown, including an embodiment which uses high permeability guides to direct the closing flux path through the magneto-resistive material. High density, high speed, radiation hard, memory matrices may be constructed from these memory elements.

  19. A radiation-hardened two transistor memory cell for monolithic active pixel sensors in STAR experiment

    NASA Astrophysics Data System (ADS)

    Wei, X.; Gao, D.; Dorokhov, A.; Hu, Y.

    2011-01-01

    Radiation tolerance of Monolithic Active Pixel Sensors (MAPS) is dramatically decreased when intellectual property (IP) memories are integrated for fast readout application. This paper presents a new solution to improve radiation hardness and avoid latch-up for memory cell design. The tradeoffs among radiation tolerance, area and speed are significantly considered and analyzed. The cell designed in 0.35 μm process satisfies the radiation tolerance requirements of STAR experiment. The cell size is 4.55 × 5.45 μm2. This cell is smaller than the IP memory cell based on the same process and is only 26% of a radiation tolerant 6T SRAM cell used in previous contribution. The write access time of the cell is less than 2 ns, while the read access time is 80 ns.

  20. Hybrid Flexible Resistive Random Access Memory-Gated Transistor for Novel Nonvolatile Data Storage.

    PubMed

    Han, Su-Ting; Zhou, Ye; Chen, Bo; Wang, Chundong; Zhou, Li; Yan, Yan; Zhuang, Jiaqing; Sun, Qijun; Zhang, Hua; Roy, V A L

    2016-01-20

    Here, a single-device demonstration of novel hybrid architecture is reported to achieve programmable transistor nodes which have analogies to flash memory by incorporating a resistive switching random access memory (RRAM) device as a resistive switch gate for field effect transistor (FET) on a flexible substrate. A high performance flexible RRAM with a three-layered structure is fabricated by utilizing solution-processed MoS2 nanosheets sandwiched between poly(methyl methacrylate) polymer layers. Gate coupling with the pentacene-based transistor can be controlled by the RRAM memory state to produce a nonprogrammed state (inactive) and a programmed state (active) with a well-defined memory window. Compared to the reference flash memory device based on the MoS2 floating gate, the hybrid device presents robust access speed and retention ability. Furthermore, the hybrid RRAM-gated FET is used to build an integrated logic circuit and a wide logic window in inverter logic is achieved. The controllable, well-defined memory window, long retention time, and fast access speed of this novel hybrid device may open up new possibilities of realizing fully functional nonvolatile memory for high-performance flexible electronics.

  1. Asymmetrical access to color and location in visual working memory.

    PubMed

    Rajsic, Jason; Wilson, Daryl E

    2014-10-01

    Models of visual working memory (VWM) have benefitted greatly from the use of the delayed-matching paradigm. However, in this task, the ability to recall a probed feature is confounded with the ability to maintain the proper binding between the feature that is to be reported and the feature (typically location) that is used to cue a particular item for report. Given that location is typically used as a cue-feature, we used the delayed-estimation paradigm to compare memory for location to memory for color, rotating which feature was used as a cue and which was reported. Our results revealed several novel findings: 1) the likelihood of reporting a probed object's feature was superior when reporting location with a color cue than when reporting color with a location cue; 2) location report errors were composed entirely of swap errors, with little to no random location reports; and 3) both colour and location reports greatly benefitted from the presence of nonprobed items at test. This last finding suggests that it is uncertainty over the bindings between locations and colors at memory retrieval that drive swap errors, not at encoding. We interpret our findings as consistent with a representational architecture that nests remembered object features within remembered locations.

  2. Radioactive hot cell access hole decontamination machine

    DOEpatents

    Simpson, William E.

    1982-01-01

    Radioactive hot cell access hole decontamination machine. A mobile housing has an opening large enough to encircle the access hole and has a shielding door, with a door opening and closing mechanism, for uncovering and covering the opening. The housing contains a shaft which has an apparatus for rotating the shaft and a device for independently translating the shaft from the housing through the opening and access hole into the hot cell chamber. A properly sized cylindrical pig containing wire brushes and cloth or other disks, with an arrangement for releasably attaching it to the end of the shaft, circumferentially cleans the access hole wall of radioactive contamination and thereafter detaches from the shaft to fall into the hot cell chamber.

  3. Production of RANKL by Memory B Cells

    PubMed Central

    Meednu, Nida; Zhang, Hengwei; Owen, Teresa; Sun, Wen; Wang, Victor; Cistrone, Christopher; Rangel-Moreno, Javier; Xing, Lianping; Anolik, Jennifer H.

    2016-01-01

    Objective Rheumatoid arthritis (RA) is a systemic autoimmune disease that often leads to joint damage. The mechanisms of bone damage in RA are complex, involving activation of bone-resorbing osteoclasts (OCs) by synoviocytes and Th17 cells. This study was undertaken to investigate whether B cells play a direct role in osteoclastogenesis through the production of RANKL, the essential cytokine for OC development. Methods RANKL production by total B cells or sorted B cell subpopulations in the peripheral blood and synovial tissue from healthy donors or anti–cyclic citrullinated peptide–positive patients with RA was examined by flow cytometry, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical analysis. To define direct effects on osteoclastogenesis, B cells were cocultured with CD14+ monocytes, and OCs were enumerated by tartrate-resistant acid phosphatase staining. Results Healthy donor peripheral blood B cells were capable of expressing RANKL upon stimulation, with switched memory B cells (CD27+IgD−) having the highest propensity for RANKL production. Notably, switched memory B cells in the peripheral blood from RA patients expressed significantly more RANKL compared to healthy controls. In RA synovial fluid and tissue, memory B cells were enriched and spontaneously expressed RANKL, with some of these cells visualized adjacent to RANK+ OC precursors. Critically, B cells supported OC differentiation in vitro in a RANKL-dependent manner, and the number of OCs was higher in cultures with RA B cells than in those derived from healthy controls. Conclusion These findings reveal the critical importance of B cells in bone homeostasis and their likely contribution to joint destruction in RA. PMID:26554541

  4. Memory B cell subpopulations in the aged.

    PubMed

    Colonna-Romano, Giuseppina; Aquino, Alessandra; Bulati, Matteo; Di Lorenzo, Gabriele; Listì, Florinda; Vitello, Salvatore; Lio, Domenico; Candore, Giuseppina; Clesi, Gioacchino; Caruso, Calogero

    2006-01-01

    The literature on immunosenescence has focused mainly on T cell impairment. With the aim of gaining insight into B cell immunosenescence, the authors investigated the serum IgD levels in 24 young and 21 old people and analyzed their relationship with the number of CD19+CD27+ memory cells. Serum IgD were quantified by the use of radial immunodiffusion and the lymphocyte population CD19+CD27+ was identified by a FACScan flow cytometer. Serum IgD levels were significantly lower (p < 0.0001) in old subjects, and the percentage of CD19+CD27+ lymphocytes were significantly increased (p = 0.01) in old subjects. Finally, a significant negative correlation was found (p = 0.01) between serum concentrations of IgD and CD19+CD27+. The present results show that the levels of IgD are negatively age-related to the amount of B memory cells. This suggests that the B repertoire available to respond to new antigenic challenges is decreased in the elderly. In fact, many memory IgD- B cells fill immunologic space, and the number of naïve IgD+ B cells is dramatically decreased. Therefore, these preliminary results suggest that a decrease of naïve IgD+CD27- B cells and a concomitant increase of memory IgD-CD27+ B cells could represent hallmarks of B immunosenescence, might provide biomarkers related to the lifespan of humans, and could be useful for the evaluation of antiaging treatments.

  5. A hybrid ferroelectric-flash memory cells

    NASA Astrophysics Data System (ADS)

    Park, Jae Hyo; Byun, Chang Woo; Seok, Ki Hwan; Kim, Hyung Yoon; Chae, Hee Jae; Lee, Sol Kyu; Son, Se Wan; Ahn, Donghwan; Joo, Seung Ki

    2014-09-01

    A ferroelectric-flash (F-flash) memory cells having a metal-ferroelectric-nitride-oxynitride-silicon structure are demonstrated, and the ferroelectric materials were perovskite-dominated Pb(Zr,Ti)O3 (PZT) crystallized by Pt gate electrode. The PZT thin-film as a blocking layer improves electrical and memorial performance where programming and erasing mechanism are different from the metal-ferroelectric-insulator-semiconductor device or the conventional silicon-oxide-nitride-oxide-silicon device. F-flash cells exhibit not only the excellent electrical transistor performance, having 442.7 cm2 V-1 s-1 of field-effect mobility, 190 mV dec-1 of substhreshold slope, and 8 × 105 on/off drain current ratio, but also a high reliable memory characteristics, having a large memory window (6.5 V), low-operating voltage (0 to -5 V), faster P/E switching speed (50/500 μs), long retention time (>10 years), and excellent fatigue P/E cycle (>105) due to the boosting effect, amplification effect, and energy band distortion of nitride from the large polarization. All these characteristics correspond to the best performances among conventional flash cells reported so far.

  6. Shape-memory surfaces for cell mechanobiology

    PubMed Central

    Ebara, Mitsuhiro

    2015-01-01

    Shape-memory polymers (SMPs) are a new class of smart materials, which have the capability to change from a temporary shape ‘A’ to a memorized permanent shape ‘B’ upon application of an external stimulus. In recent years, SMPs have attracted much attention from basic and fundamental research to industrial and practical applications due to the cheap and efficient alternative to well-known metallic shape-memory alloys. Since the shape-memory effect in SMPs is not related to a specific material property of single polymers, the control of nanoarchitecture of polymer networks is particularly important for the smart functions of SMPs. Such nanoarchitectonic approaches have enabled us to further create shape-memory surfaces (SMSs) with tunable surface topography at nano scale. The present review aims to bring together the exciting design of SMSs and the ever-expanding range of their uses as tools to control cell functions. The goal for these endeavors is to mimic the surrounding mechanical cues of extracellular environments which have been considered as critical parameters in cell fate determination. The untapped potential of SMSs makes them one of the most exciting interfaces of materials science and cell mechanobiology. PMID:27877747

  7. Shape-memory surfaces for cell mechanobiology

    NASA Astrophysics Data System (ADS)

    Ebara, Mitsuhiro

    2015-02-01

    Shape-memory polymers (SMPs) are a new class of smart materials, which have the capability to change from a temporary shape ‘A’ to a memorized permanent shape ‘B’ upon application of an external stimulus. In recent years, SMPs have attracted much attention from basic and fundamental research to industrial and practical applications due to the cheap and efficient alternative to well-known metallic shape-memory alloys. Since the shape-memory effect in SMPs is not related to a specific material property of single polymers, the control of nanoarchitecture of polymer networks is particularly important for the smart functions of SMPs. Such nanoarchitectonic approaches have enabled us to further create shape-memory surfaces (SMSs) with tunable surface topography at nano scale. The present review aims to bring together the exciting design of SMSs and the ever-expanding range of their uses as tools to control cell functions. The goal for these endeavors is to mimic the surrounding mechanical cues of extracellular environments which have been considered as critical parameters in cell fate determination. The untapped potential of SMSs makes them one of the most exciting interfaces of materials science and cell mechanobiology.

  8. Shape-memory surfaces for cell mechanobiology.

    PubMed

    Ebara, Mitsuhiro

    2015-02-01

    Shape-memory polymers (SMPs) are a new class of smart materials, which have the capability to change from a temporary shape 'A' to a memorized permanent shape 'B' upon application of an external stimulus. In recent years, SMPs have attracted much attention from basic and fundamental research to industrial and practical applications due to the cheap and efficient alternative to well-known metallic shape-memory alloys. Since the shape-memory effect in SMPs is not related to a specific material property of single polymers, the control of nanoarchitecture of polymer networks is particularly important for the smart functions of SMPs. Such nanoarchitectonic approaches have enabled us to further create shape-memory surfaces (SMSs) with tunable surface topography at nano scale. The present review aims to bring together the exciting design of SMSs and the ever-expanding range of their uses as tools to control cell functions. The goal for these endeavors is to mimic the surrounding mechanical cues of extracellular environments which have been considered as critical parameters in cell fate determination. The untapped potential of SMSs makes them one of the most exciting interfaces of materials science and cell mechanobiology.

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

    SciTech Connect

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

    2014-05-07

    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.

  10. Effector and memory T cell subsets in the response to bovine tuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long-term (i.e., 14 days) cultured IFN-gamma ELISPOT assays of peripheral blood mononuclear cells (PBMC) are used to access T cell central memory (Tcm) responses in both cattle and humans. With bovine tuberculosis, vaccine-elicited long-term IFN-gamma ELISPOT response correlates with protection; how...

  11. Symmetric Data Objects and Remote Memory Access Communication for Fortran 95-Applications.

    SciTech Connect

    Nieplocha, Jarek; Baxter, Douglas J.; Tipparaju, Vinod; Rasmussen, Craig; Numrich, Robert W.

    2005-08-01

    Symmetric data objects have been introduced by Cray Inc. in context of SHMEM remote memory access communication on Cray T3D/E systems and later adopted by SGI for their Origin servers. Symmetric data objects greatly simplify parallel programming by allowing to reference remote instance of a data structure by specifying address of the local counterpart. The current paper describes how symmetric data objects and remote memory access communication could be implemented in Fortran-95 without requiring specialized hardware or compiler support. NAS Multi-Grid parallel benchmark was used as an application example and demonstrated competitive performance to the standard MPI implementation

  12. Gallium Arsenide Dynamic Random Access Memory Support Circuitry

    DTIC Science & Technology

    1993-03-01

    several reasons for this. the first and foremost is cost. Millions of dollars are required to "tool up" to fabricate ICs. While Si ICs are in tremendous...disadvantages to GaAs digital IC fabrication. First , the present density of the commercially available GaAs ICs is much less than those produced in Si...is accomplished is a similar but slightly different manner. Writing requires data so the first step (given the correct status of the memory busy signal

  13. 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.

  14. 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…

  15. 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.

  16. 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.

  17. Shared direct memory access on the Explorer 2-LX

    NASA Technical Reports Server (NTRS)

    Musgrave, Jeffrey L.

    1990-01-01

    Advances in Expert System technology and Artificial Intelligence have provided a framework for applying automated Intelligence to the solution of problems which were generally perceived as intractable using more classical approaches. As a result, hybrid architectures and parallel processing capability have become more common in computing environments. The Texas Instruments Explorer II-LX is an example of a machine which combines a symbolic processing environment, and a computationally oriented environment in a single chassis for integrated problem solutions. This user's manual is an attempt to make these capabilities more accessible to a wider range of engineers and programmers with problems well suited to solution in such an environment.

  18. Role of memory T cell subsets for adoptive immunotherapy.

    PubMed

    Busch, Dirk H; Fräßle, Simon P; Sommermeyer, Daniel; Buchholz, Veit R; Riddell, Stanley R

    2016-02-01

    Adoptive transfer of primary (unmodified) or genetically engineered antigen-specific T cells has demonstrated astonishing clinical results in the treatment of infections and some malignancies. Besides the definition of optimal targets and antigen receptors, the differentiation status of transferred T cells is emerging as a crucial parameter for generating cell products with optimal efficacy and safety profiles. Long-living memory T cells subdivide into phenotypically as well as functionally different subsets (e.g. central memory, effector memory, tissue-resident memory T cells). This diversification process is crucial for effective immune protection, with probably distinct dependencies on the presence of individual subsets dependent on the disease to which the immune response is directed as well as its organ location. Adoptive T cell therapy intends to therapeutically transfer defined T cell immunity into patients. Efficacy of this approach often requires long-term maintenance of transferred cells, which depends on the presence and persistence of memory T cells. However, engraftment and survival of highly differentiated memory T cell subsets upon adoptive transfer is still difficult to achieve. Therefore, the recent observation that a distinct subset of weakly differentiated memory T cells shows all characteristics of adult tissue stem cells and can reconstitute all types of effector and memory T cell subsets, became highly relevant. We here review our current understanding of memory subset formation and T cell subset purification, and its implications for adoptive immunotherapy.

  19. 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.

  20. 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.

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

    SciTech Connect

    Zhang, Meiyun; Long, Shibing Wang, Guoming; Xu, Xiaoxin; Li, Yang; Liu, Qi; Lv, Hangbing; Liu, Ming; Lian, Xiaojuan; Miranda, Enrique; Suñé, Jordi

    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 electron transport model. Our work provides indications for the improvement of the switching uniformity.

  2. Memory B Cells of Mice and Humans.

    PubMed

    Weisel, Florian; Shlomchik, Mark

    2017-01-30

    Wecomprehensively review memory B cells (MBCs), covering the definition of MBC and their identities and subsets, how MBCs are generated, where they are localized, how they are maintained, and how they are reactivated. Whereas naive B cells adopt multiple fates upon stimulation, MBCs are more restricted in their responses. Evolving work reveals that the MBC compartment in mice and humans consists of distinct subpopulations with differing effector functions. We discuss the various approaches to define subsets and subset-specific roles. A major theme is the need to both deliver faster effector function upon reexposure and readapt to antigenically variant pathogens while avoiding burnout, which would be the result if all MBCs generated only terminal effector function. We discuss cell-intrinsic differences in gene expression and signaling that underlie differences in function between MBCs and naive B cells and among MBC subsets and how this leads to memory responses. Expected final online publication date for the Annual Review of Immunology Volume 35 is April 26, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  3. Effects of erbium doping of indium tin oxide electrode in resistive random access memory

    NASA Astrophysics Data System (ADS)

    Chen, Po-Hsun; Chang, Kuan-Chang; Chang, Ting-Chang; Tsai, Tsung-Ming; Pan, Chih-Hung; Lin, Chih-Yang; Jin, Fu-Yuan; Chen, Min-Chen; Huang, Hui-Chun; Lo, Ikai; Zheng, Jin-Cheng; Sze, Simon M.

    2016-03-01

    Identical insulators and bottom electrodes were fabricated and capped by an indium tin oxide (ITO) film, either undoped or doped with erbium (Er), as a top electrode. This distinctive top electrode dramatically altered the resistive random access memory (RRAM) characteristics, for example, lowering the operation current and enlarging the memory window. In addition, the RESET voltage increased, whereas the SET voltage remained almost the same. A conduction model of Er-doped ITO is proposed through current-voltage (I-V) measurement and current fitting to explain the resistance switching mechanism of Er-doped ITO RRAM and is confirmed by material analysis and reliability tests.

  4. Nonvolatile transtance change random access memory based on magnetoelectric P(VDF-TrFE)/Metglas heterostructures

    NASA Astrophysics Data System (ADS)

    Lu, Peipei; Shang, Dashan; Shen, Jianxin; Chai, Yisheng; Yang, Chuansen; Zhai, Kun; Cong, Junzhuang; Shen, Shipeng; Sun, Young

    2016-12-01

    Transtance change random access memory (TCRAM) is a type of nonvolatile memory based on the nonlinear magnetoelectric coupling effects of multiferroics. In this work, ferroelectric P(VDF-TrFE) thin films were prepared on Metglas foil substrates by the sol-gel technique to form multiferroic heterostructures. The magnetoelectric voltage coefficient of the heterostructure can be switched reproducibly to different levels between positive and negative values by applying selective electric-field pulses. Compared with bulk multiferroic heterostructures, the polarization switching voltage was reduced to 7 V. Our facile technological approach enables this organic magnetoelectric heterostructure as a promising candidate for the applications in multilevel TCRAM devices.

  5. Multiple number and letter comparison: directionality and accessibility in numeric and alphabetic memories.

    PubMed

    Jou, Jerwen

    2003-01-01

    In 3 experiments, subjects made comparativejudgments on a set of 2 numbers or letters, 3 numbers or letters, or 5 numbers or letters. Numeric and alphabetic serial order memories were contrasted. Three aspects of serial order memory processes were identified: computational complexity, directionality, and accessibility. Computational complexity is the number of algorithmic steps involved in identifying a target. Directional bias is measured as the speed differences in identifying serial targets of equal computational complexity in a stimulus array. Memory accessibility is measured as the numeric and alphabetic serial position effects. Subjects had a slight directional bias favoring backward ordering for single digits but no bias in 2-digit number ordering, in contrast to a strong forward directional advantage in letter ordering. The speed of number access was found to steadily and evenly decrease along the numeric scale, in contrast to a systematic pattern of variations in alphabet access along the alphabetic scale. Finally, the middle item effect (the middle item in a multi-item array is identified most slowly) found in Jou's (1997) multiple-letter comparison study was generalized to numbers.

  6. CD4 T-cell memory generation and maintenance.

    PubMed

    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.

  7. Viral inoculum dose impacts memory T-cell inflation.

    PubMed

    Redeker, Anke; Welten, Suzanne P M; Arens, Ramon

    2014-04-01

    Memory T-cell inflation develops during certain persistent viral infections and is characterized by the accumulation and maintenance of large numbers of effector-memory T cells, albeit with varying degrees in size and phenotype among infected hosts. The underlying mechanisms that control memory T-cell inflation are not yet fully understood. Here, we dissected CMV-specific memory T-cell formation and its connection to the initial infectious dose by varying the inoculum size. After low dose inoculum with mouse CMV, the accumulation of inflationary memory T cells was severely hampered and correlated with reduced reservoirs of latent virus in nonhematopoietic cells and diminished antigen-driven T-cell proliferation. Moreover, lowering of the initial viral dose turned the characteristic effector memory-like inflationary T cells into more central memory-like cells as evidenced by the cell-surface phenotype of CD27(high) , CD62L(+) , CD127(+) , and KLRG1(-) , and by improved secondary expansion potential. These data show the impact of the viral inoculum on the degree of memory T-cell inflation and provide a rationale for the observed variation of human CMV-specific T-cell responses in terms of magnitude and phenotype.

  8. Shape memory alloy fixator system for suturing tissue in minimal access surgery.

    PubMed

    Xu, W; Frank, T G; Stockham, G; Cuschieri, A

    1999-01-01

    A new technique for suturing human tissue is described in which tissue closure is achieved by means of small fixators made from shape memory alloy. The aim of the development is to provide an alternative to thread suturing in minimal access surgery, which is quicker and requires less skill to achieve the required suturing quality. The design of the fixators is described in terms of the thermal shape recovery of shape memory alloy and a novel form of finite element analysis, which uses a nonlinear elastic element for the material property. Thermal analysis of the fixators and surrounding tissue is used to predict the temperature distribution during and after the application of electric current heating. This was checked in an in vitro experiment, which confirmed that deployment caused no detectable collateral damage to surrounding tissue. In vivo animal studies on the use of the shape memory alloy fixator for suturing tissue are ongoing to establish safety and healing effects.

  9. 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.

  10. Heterogeneity within T Cell Memory: Implications for Transplant Tolerance

    PubMed Central

    Krummey, Scott M.; Ford, Mandy L.

    2012-01-01

    Adaptive immunity in both mouse and man results in the generation of immunological memory. Memory T cells are both friend and foe to transplant recipients, as they are intimately involved and in many cases absolutely required for the maintenance of protective immunity in the face immunosuppression, yet from the evidence presented herein they clearly constitute a formidable barrier for the successful implementation of tolerance induction strategies in transplantation. This review describes the experimental evidence demonstrating the increased resistance of memory T cells to many distinct tolerance induction strategies, and outlines recent advances in our knowledge of the ways in which alloreactive memory T cells arise in previously untransplanted individuals. Understanding the impact of alloreactive memory T cell specificity, frequency, and quality might allow for better donor selection in order to minimize the donor-reactive memory T cell barrier in an individual transplant recipient, thus allowing stratification of relative risk of alloreactive memory T cell mediated rejection, and conversely increase the likelihood of successful establishment of tolerance. However, further research into the molecular and cellular pathways involved in alloreactive memory T cell-mediated rejection is required in order to design new strategies to overcome the memory T cell barrier, without critically impairing protective immunity. PMID:22566919

  11. Electrical Evaluation of RCA MWS5001D Random Access Memory, Volume 4, Appendix C

    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. Statistical analysis data is supplied along with write pulse width, read cycle time, write cycle time, and chip enable time data.

  12. Improved Writing-Conductor Designs For Magnetic Memory

    NASA Technical Reports Server (NTRS)

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

    1994-01-01

    Writing currents reduced to practical levels. Improved conceptual designs for writing conductors in micromagnet/Hall-effect random-access integrated-circuit memory reduces electrical current needed to magnetize micromagnet in each memory cell. Basic concept of micromagnet/Hall-effect random-access memory presented in "Magnetic Analog Random-Access Memory" (NPO-17999).

  13. Multiple layers of B cell memory with different effector functions.

    PubMed

    Dogan, Ismail; Bertocci, Barbara; Vilmont, Valérie; Delbos, Frédéric; Mégret, Jérome; Storck, Sébastien; Reynaud, Claude-Agnès; Weill, Jean-Claude

    2009-12-01

    Memory B cells are at the center of longstanding controversies regarding the presence of antigen for their survival and their re-engagement in germinal centers after secondary challenge. Using a new mouse model of memory B cell labeling dependent on the cytidine deaminase AID, we show that after immunization with a particulate antigen, B cell memory appeared in several subsets, comprising clusters of immunoglobulin M-positive (IgM(+)) and IgG1(+) B cells in germinal center-like structures that persisted up to 8 months after immunization, as well as IgM(+) and IgG1(+) B cells with a memory phenotype outside of B cell follicles. After challenge, the IgG subset differentiated into plasmocytes, whereas the IgM subset reinitiated a germinal center reaction. This model, in which B cell memory appears in several layers with different functions, reconciles previous conflicting propositions.

  14. Immigration, language proficiency, and autobiographical memories: Lifespan distribution and second-language access.

    PubMed

    Esposito, Alena G; Baker-Ward, Lynne

    2016-08-01

    This investigation examined two controversies in the autobiographical literature: how cross-language immigration affects the distribution of autobiographical memories across the lifespan and under what circumstances language-dependent recall is observed. Both Spanish/English bilingual immigrants and English monolingual non-immigrants participated in a cue word study, with the bilingual sample taking part in a within-subject language manipulation. The expected bump in the number of memories from early life was observed for non-immigrants but not immigrants, who reported more memories for events surrounding immigration. Aspects of the methodology addressed possible reasons for past discrepant findings. Language-dependent recall was influenced by second-language proficiency. Results were interpreted as evidence that bilinguals with high second-language proficiency, in contrast to those with lower second-language proficiency, access a single conceptual store through either language. The final multi-level model predicting language-dependent recall, including second-language proficiency, age of immigration, internal language, and cue word language, explained ¾ of the between-person variance and (1)/5 of the within-person variance. We arrive at two conclusions. First, major life transitions influence the distribution of memories. Second, concept representation across multiple languages follows a developmental model. In addition, the results underscore the importance of considering language experience in research involving memory reports.

  15. Novel therapies for memory cells in autoimmune diseases.

    PubMed

    Bhargava, P; Calabresi, P A

    2015-06-01

    Autoimmune diseases are a major cause of morbidity, and their incidence and prevalence continue to rise. Treatments for these diseases are non-specific and result in significant adverse effects. Targeted therapies may help in improving the risk : benefit ratio associated with treatment. Immunological memory is an important feature of the vertebrate immune system that results in the production of cells that are long-lived and able to respond to antigens in a more robust manner. In the setting of autoimmunity this characteristic becomes detrimental due to the ongoing response to a self-antigen(s). These memory cells have been shown to play key roles in various autoimmune diseases such as type 1 diabetes, multiple sclerosis and psoriasis. Memory T cells and B cells can be identified based on various molecules expressed on their surface. Memory T cells can be divided into three main categories - central memory, effector memory and resident memory cells. These subsets have different proliferative potential and cytokine-producing abilities. Utilizing differentially expressed surface molecules or downstream signalling pathway proteins in these cells it is now possible to target memory cells while sparing naive cells. We will discuss the various available options for such a strategy and several potential strategies that may yield successful therapies in the future.

  16. Probing cell activity in random access modality

    NASA Astrophysics Data System (ADS)

    Sacconi, L.; Crocini, C.; Lotti, J.; Coppini, R.; Ferrantini, C.; Tesi, C.; Yan, P.; Loew, L. M.; Cerbai, E.; Poggesi, C.; Pavone, F. S.

    2013-06-01

    We combined the advantage of an ultrafast random access microscope with novel labelling technologies to study the intra- and inter-cellular action potential propagation in neurons and cardiac myocytes with sub-millisecond time resolution. The random accesses microscopy was used in combination with a new fluorinated voltage sensitive dye with improved photostability to record membrane potential from multiple Purkinje cells with near simultaneous sampling. The RAMP system rapidly scanned between lines drawn in the membranes of neurons to perform multiplex measurements of the TPF signal. This recording was achieved by rapidly positioning the laser excitation with the AOD to sample a patch of membrane from each cell in <100 μs for recording from five cells, multiplexing permits a temporal resolution of 400 μs sufficient to capture every spike. The system is capable to record spontaneous activity over 800 ms from five neighbouring cells simultaneously, showing that spiking is not temporally correlated. The system was also used to investigate the electrical properties of tubular system (TATS) in isolated rat ventricular myocytes.

  17. Retraction: High uniformity and improved nonlinearity by embedding nanocrystals in selector-less resistive random access memory

    NASA Astrophysics Data System (ADS)

    Banerjee, Writam; Lu, Nianduan; Li, Ling; Sun, Pengxiao; Liu, Qi; Lv, Hangbing; Long, Shibing; Liu, Ming

    2015-03-01

    Retraction of `High uniformity and improved nonlinearity by embedding nanocrystals in selector-less resistive random access memory' by Writam Banerjee et al., Nanoscale, 2014, advance article (C4NR05077K)

  18. T-cell identity and epigenetic memory

    PubMed Central

    Rothenberg, Ellen V.; Zhang, Jingli

    2013-01-01

    Summary T cell development endows cells with a flexible range of effector differentiation options, superimposed on a stable core of lineage-specific gene expression that is maintained while access to alternative hematopoietic lineages is permanently renounced. This combination of features could be explained by environmentally responsive transcription factor mobilization overlaying an epigenetically stabilized base gene expression state. For example, “poising” of promoters could offer preferential access to T-cell genes, while repressive histone modifications and DNA methylation of non-T regulatory genes could be responsible for keeping non-T developmental options closed. Here we critically review the evidence for the actual deployment of epigenetic marking to support the stable aspects of T-cell identity. Much of epigenetic marking is dynamically maintained or subject to rapid modification by local action of transcription factors. Repressive histone marks are used in gene-specific ways that do not fit a simple, developmental lineage-exclusion hierarchy. We argue that epigenetic analysis may achieve its greatest impact for illuminating regulatory biology when it is used to locate cis-regulatory elements by catching them in the act of mediating regulatory change. PMID:21833836

  19. Role of Memory T Cells in Allograft Rejection and Tolerance

    PubMed Central

    Benichou, Gilles; Gonzalez, Bruno; Marino, Jose; Ayasoufi, Katayoun; Valujskikh, Anna

    2017-01-01

    Memory T cells are characterized by their low activation threshold, robust effector functions, and resistance to conventional immunosuppression and costimulation blockade. Unlike their naïve counterparts, memory T cells reside in and recirculate through peripheral non-lymphoid tissues. Alloreactive memory T cells are subdivided into different categories based on their origins, phenotypes, and functions. Recipients whose immune systems have been directly exposed to allogeneic major histocompatibility complex (MHC) molecules display high affinity alloreactive memory T cells. In the absence of any prior exposure to allogeneic MHC molecules, endogenous alloreactive memory T cells are regularly generated through microbial infections (heterologous immunity). Regardless of their origin, alloreactive memory T cells represent an essential element of the allograft rejection process and a major barrier to tolerance induction in clinical transplantation. This article describes the different subsets of alloreactive memory T cells involved in transplant rejection and examine their generation, functional properties, and mechanisms of action. In addition, we discuss strategies developed to target deleterious allospecific memory T cells in experimental animal models and clinical settings. PMID:28293238

  20. Memory NK Cells Take Out the (Mitochondrial) Garbage.

    PubMed

    Wagner, Julia A; Fehniger, Todd A

    2015-08-18

    The molecular mechanisms important to generate innate natural killer cell "memory" are poorly understood. In this issue of Immunity, O'Sullivan et al. (2015) demonstrate that mitophagy plays a critical role in natural killer cell memory formation following viral infection.

  1. 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.…

  2. 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…

  3. Yeast cells can access distinct quiescent states.

    PubMed

    Klosinska, Maja M; Crutchfield, Christopher A; Bradley, Patrick H; Rabinowitz, Joshua D; Broach, James R

    2011-02-15

    We conducted a phenotypic, transcriptional, metabolic, and genetic analysis of quiescence in yeast induced by starvation of prototrophic cells for one of three essential nutrients (glucose, nitrogen, or phosphate) and compared those results with those obtained with cells growing slowly due to nutrient limitation. These studies address two related questions: (1) Is quiescence a state distinct from any attained during mitotic growth, and (2) does the nature of quiescence differ depending on the means by which it is induced? We found that either limitation or starvation for any of the three nutrients elicits all of the physiological properties associated with quiescence, such as enhanced cell wall integrity and resistance to heat shock and oxidative stress. Moreover, the starvations result in a common transcriptional program, which is in large part a direct extrapolation of the changes that occur during slow growth. In contrast, the metabolic changes that occur upon starvation and the genetic requirements for surviving starvation differ significantly depending on the nutrient for which the cell is starved. The genes needed by cells to survive starvation do not overlap the genes that are induced upon starvation. We conclude that cells do not access a unique and discrete G(0) state, but rather are programmed, when nutrients are scarce, to prepare for a range of possible future stressors. Moreover, these survival strategies are not unique to quiescence, but are engaged by the cell in proportion to nutrient scarcity.

  4. 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

  5. Recombinant azurin-CdSe/ZnS hybrid structures for nanoscale resistive random access memory device.

    PubMed

    Yagati, Ajay Kumar; Kim, Sang-Uk; Lee, Taek; Min, Junhong; Choi, Jeong-Woo

    2017-04-15

    In the present study, we developed a biohybrid material composed of recombinant azurin and CdSe-ZnS quantum dot to perform as a resistive random access memory (ReRAM) device. Site specific amino acid sequences were introduced in azurin to bind with the surface of CdSe-ZnS nanoparticle allowing the formation of a hybrid and voltage-driven switching enabled to develop a resistive random access memory (ReRAM) device. The analytical measurements confirmed that the azurin and CdSe-ZnS nanoparticles were well conjugated and formed into a single hybrid. Further, reversible, bistable switching along with repeatable writing-reading-erasing processes on individual azurin/CdSe-ZnS hybrid at nanoscale was achieved on the hybrid device. The device was programmed tested for 50 cycles with an ON/OFF ratio and measured to be of three orders of magnitude. The developed device shown good stability and repeatability and operates at low voltages thus makes it promising candidate for future memory device applications.

  6. Spin-transfer torque switched magnetic tunnel junctions in magnetic random access memory

    NASA Astrophysics Data System (ADS)

    Sun, Jonathan Z.

    2016-10-01

    Spin-transfer torque (or spin-torque, or STT) based magnetic tunnel junction (MTJ) is at the heart of a new generation of magnetism-based solid-state memory, the so-called spin-transfer-torque magnetic random access memory, or STT-MRAM. Over the past decades, STT-based switchable magnetic tunnel junction has seen progress on many fronts, including the discovery of (001) MgO as the most favored tunnel barrier, which together with (bcc) Fe or FeCo alloy are yielding best demonstrated tunnel magneto-resistance (TMR); the development of perpendicularly magnetized ultrathin CoFeB-type of thin films sufficient to support high density memories with junction sizes demonstrated down to 11nm in diameter; and record-low spin-torque switching threshold current, giving best reported switching efficiency over 5 kBT/μA. Here we review the basic device properties focusing on the perpendicularly magnetized MTJs, both in terms of switching efficiency as measured by sub-threshold, quasi-static methods, and of switching speed at super-threshold, forced switching. We focus on device behaviors important for memory applications that are rooted in fundamental device physics, which highlights the trade-off of device parameters for best suitable system integration.

  7. 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.

  8. Phenotype and functions of memory Tfh cells in human blood.

    PubMed

    Schmitt, Nathalie; Bentebibel, Salah-Eddine; Ueno, Hideki

    2014-09-01

    Our understanding of the origin and functions of human blood CXCR5(+) CD4(+) T cells found in human blood has changed dramatically in the past years. These cells are currently considered to represent a circulating memory compartment of T follicular helper (Tfh) lineage cells. Recent studies have shown that blood memory Tfh cells are composed of phenotypically and functionally distinct subsets. Here, we review the current understanding of human blood memory Tfh cells and the subsets within this compartment. We present a strategy to define these subsets based on cell surface profiles. Finally, we discuss how increased understanding of the biology of blood memory Tfh cells may contribute insight into the pathogenesis of autoimmune diseases and the mode of action of vaccines.

  9. Bipolar resistive switching characteristics in tantalum nitride-based resistive random access memory devices

    SciTech Connect

    Kim, Myung Ju; Jeon, Dong Su; Park, Ju Hyun; Kim, Tae Geun

    2015-05-18

    This paper reports the bipolar resistive switching characteristics of TaN{sub x}-based resistive random access memory (ReRAM). The conduction mechanism is explained by formation and rupture of conductive filaments caused by migration of nitrogen ions and vacancies; this mechanism is in good agreement with either Ohmic conduction or the Poole-Frenkel emission model. The devices exhibit that the reset voltage varies from −0.82 V to −0.62 V, whereas the set voltage ranges from 1.01 V to 1.30 V for 120 DC sweep cycles. In terms of reliability, the devices exhibit good retention (>10{sup 5 }s) and pulse-switching endurance (>10{sup 6} cycles) properties. These results indicate that TaN{sub x}-based ReRAM devices have a potential for future nonvolatile memory devices.

  10. Self-assembled tin dioxide for forming-free resistive random-access memory application

    NASA Astrophysics Data System (ADS)

    Hong, Ying-Jhan; Wang, Tsang-Hsuan; Wei, Shih-Yuan; Chang, Pin; Yew, Tri-Rung

    2016-06-01

    A novel resistive switching structure, tin-doped indium oxide (ITO)/SnO2- x (defined as SnO2 with oxygen vacancies)/SnS was demonstrated with a set voltage of 0.38 V, a reset voltage of -0.15 V, a ratio of high resistance to low resistance of 544, and forming-free and nonlinear current-voltage (I-V) characteristics. The interface of the ITO and the self-assembled SnO2- x contributed to the resistive switching behavior. This device showed great potential for resistive random access memory (RRAM) application and solving the sneak path problem in cross-bar memory arrays. Furthermore, a nanostructured resistive switching device was demonstrated successfully.

  11. High-density magnetoresistive random access memory operating at ultralow voltage at room temperature

    PubMed Central

    Hu, Jia-Mian; Li, Zheng; Chen, Long-Qing; Nan, Ce-Wen

    2011-01-01

    The main bottlenecks limiting the practical applications of current magnetoresistive random access memory (MRAM) technology are its low storage density and high writing energy consumption. Although a number of proposals have been reported for voltage-controlled memory device in recent years, none of them simultaneously satisfy the important device attributes: high storage capacity, low power consumption and room temperature operation. Here we present, using phase-field simulations, a simple and new pathway towards high-performance MRAMs that display significant improvements over existing MRAM technologies or proposed concepts. The proposed nanoscale MRAM device simultaneously exhibits ultrahigh storage capacity of up to 88 Gb inch−2, ultralow power dissipation as low as 0.16 fJ per bit and room temperature high-speed operation below 10 ns. PMID:22109527

  12. Soft errors in commercial off-the-shelf static random access memories

    NASA Astrophysics Data System (ADS)

    Dilillo, L.; Tsiligiannis, G.; Gupta, V.; Bosser, A.; Saigne, F.; Wrobel, F.

    2017-01-01

    This article reviews state-of-the-art techniques for the evaluation of the effect of radiation on static random access memory (SRAM). We detailed irradiation test techniques and results from irradiation experiments with several types of particles. Two commercial SRAMs, in 90 and 65 nm technology nodes, were considered as case studies. Besides the basic static and dynamic test modes, advanced stimuli for the irradiation tests were introduced, as well as statistical post-processing techniques allowing for deeper analysis of the correlations between bit-flip cross-sections and design/architectural characteristics of the memory device. Further insight is provided on the response of irradiated stacked layer devices and on the use of characterized SRAM devices as particle detectors.

  13. 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.

  14. Molecular signatures distinguish human central memory from effector memory CD8 T cell subsets.

    PubMed

    Willinger, Tim; Freeman, Tom; Hasegawa, Hitoshi; McMichael, Andrew J; Callan, Margaret F C

    2005-11-01

    Memory T cells are heterogeneous in terms of their phenotype and functional properties. We investigated the molecular profiles of human CD8 naive central memory (T(CM)), effector memory (T(EM)), and effector memory RA (T(EMRA)) T cells using gene expression microarrays and phospho-protein-specific intracellular flow cytometry. We demonstrate that T(CM) have a gene expression and cytokine signaling signature that lies between that of naive and T(EM) or T(EMRA) cells, whereas T(EM) and T(EMRA) are closely related. Our data define the molecular basis for the different functional properties of central and effector memory subsets. We show that T(EM) and T(EMRA) cells strongly express genes with known importance in CD8 T cell effector function. In contrast, T(CM) are characterized by high basal and cytokine-induced STAT5 phosphorylation, reflecting their capacity for self-renewal. Altogether, our results distinguish T(CM) and T(EM)/T(EMRA) at the molecular level and are consistent with the concept that T(CM) represent memory stem cells.

  15. Hidden memories: Front line memory T cells and early pathogen interception

    PubMed Central

    Masopust, David; Picker, Louis J.

    2012-01-01

    Immunologic memory reflects the ability of a host to more effectively respond to a re-encounter with a particular pathogen than the first encounter, and when a vaccine mimics the first encounter, comprises the basis of vaccine efficacy. For T cells, memory is often equated with the anamnestic response, the ability of secondary lymphoid tissue (SLT)-based(central) memory T cells to respond to pathogen exposure with a more rapid and higher magnitude production and infection-site delivery of pathogen-specific effector cells than observed in naïve hosts. However, increasing evidence supports a fundamentally different kind of T cell memory in which differentiated, long-lived effector memory T cells (TEM), pre-positioned in sites of potential pathogen invasion or rapidly mobilized to such sites from blood and marginated pools, intercept and potentially control/eliminate pathogen within hours of infection. Here, we review the evidence for this “hidden” T cell memory, and its implication for vaccine development. PMID:22675215

  16. Hydrogen doping in HfO{sub 2} resistance change random access memory

    SciTech Connect

    Duncan, D.; Magyari-Köpe, B.; Nishi, Y.

    2016-01-25

    The structures and energies of hydrogen-doped monoclinic hafnium dioxide were calculated using density-functional theory. The electronic interactions are described within the LDA + U formalism, where on-site Coulomb corrections are applied to the 5d orbital electrons of Hf atoms and 2p orbital electrons of the O atoms. The effects of charge state, defect-defect interactions, and hydrogenation are investigated and compared with experiment. It is found that hydrogenation of HfO{sub 2} resistance-change random access memory devices energetically stabilizes the formation of oxygen vacancies and conductive vacancy filaments through multiple mechanisms, leading to improved switching characteristic and device yield.

  17. Development and process control of magnetic tunnel junctions for magnetic random access memory devices

    NASA Astrophysics Data System (ADS)

    Kula, Witold; Wolfman, Jerome; Ounadjela, Kamel; Chen, Eugene; Koutny, William

    2003-05-01

    We report on the development and process control of magnetic tunnel junctions (MTJs) for magnetic random access memory (MRAM) devices. It is demonstrated that MTJs with high magnetoresistance ˜40% at 300 mV, resistance-area product (RA) ˜1-3 kΩ μm2, low intrinsic interlayer coupling (Hin) ˜2-3 Oe, and excellent bit switching characteristics can be developed and fully integrated with complementary metal-oxide-semiconductor circuitry into MRAM devices. MTJ uniformity and repeatability level suitable for mass production has been demonstrated with the advanced processing and monitoring techniques.

  18. Temperature effects on failure and annealing behavior in dynamic random access memories

    NASA Astrophysics Data System (ADS)

    Wilkin, N. D.; Self, C. T.

    1982-12-01

    Total dose failure levels and long time anneal characteristics of dynamic random access memories are measured while the devices are exercised under actual use conditions. These measurements were performed over the temperature range of -60 C to +70 C. The total dose failure levels are shown to decrease with increasing temperature. The anneal characteristics are shown to result in both an increase and decrease in the measured number of errors as a function of time. Finally a description of the test instrumentation and irradiation procedures are given.

  19. A stochastic simulation method for the assessment of resistive random access memory retention reliability

    SciTech Connect

    Berco, Dan Tseng, Tseung-Yuen

    2015-12-21

    This study presents an evaluation method for resistive random access memory retention reliability based on the Metropolis Monte Carlo algorithm and Gibbs free energy. The method, which does not rely on a time evolution, provides an extremely efficient way to compare the relative retention properties of metal-insulator-metal structures. It requires a small number of iterations and may be used for statistical analysis. The presented approach is used to compare the relative robustness of a single layer ZrO{sub 2} device with a double layer ZnO/ZrO{sub 2} one, and obtain results which are in good agreement with experimental data.

  20. Low power consumption resistance random access memory with Pt/InOx/TiN structure

    NASA Astrophysics Data System (ADS)

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

    2013-09-01

    In this study, the resistance switching characteristics of a resistive random access memory device with Pt/InOx/TiN structure is investigated. Unstable bipolar switching behavior is observed during the initial switching cycle, which then stabilizes after several switching cycles. Analyses indicate that the current conduction mechanism in the resistance state is dominated by Ohmic conduction. The decrease in electrical conductance can be attributed to the reduction of the cross-sectional area of the conduction path. Furthermore, the device exhibits low operation voltage and power consumption.

  1. TiO2 thin film based transparent flexible resistive switching random access memory

    NASA Astrophysics Data System (ADS)

    Pham, Kim Ngoc; Dung Hoang, Van; Tran, Cao Vinh; Thang Phan, Bach

    2016-03-01

    In our work we have fabricated TiO2 based resistive switching devices both on transparent substrates (ITO, IGZO/glass) and transparent flexible substrate (ITO/PET). All devices demonstrate the reproducibility of forming free bipolar resistive switching with high transparency in the visible light range (∼80% at the wavelength of 550 nm). Particularly, transparent and flexible device exhibits stable resistive switching performance at the initial state (flat) and even after bending state up to 500 times with curvature radius of 10% compared to flat state. The achieved characteristics of resistive switching of TiO2 thin films seem to be promising for transparent flexible random access memory.

  2. Single-cell chromatin accessibility reveals principles of regulatory variation.

    PubMed

    Buenrostro, Jason D; Wu, Beijing; Litzenburger, Ulrike M; Ruff, Dave; Gonzales, Michael L; Snyder, Michael P; Chang, Howard Y; Greenleaf, William J

    2015-07-23

    Cell-to-cell variation is a universal feature of life that affects a wide range of biological phenomena, from developmental plasticity to tumour heterogeneity. Although recent advances have improved our ability to document cellular phenotypic variation, the fundamental mechanisms that generate variability from identical DNA sequences remain elusive. Here we reveal the landscape and principles of mammalian DNA regulatory variation by developing a robust method for mapping the accessible genome of individual cells by assay for transposase-accessible chromatin using sequencing (ATAC-seq) integrated into a programmable microfluidics platform. Single-cell ATAC-seq (scATAC-seq) maps from hundreds of single cells in aggregate closely resemble accessibility profiles from tens of millions of cells and provide insights into cell-to-cell variation. Accessibility variance is systematically associated with specific trans-factors and cis-elements, and we discover combinations of trans-factors associated with either induction or suppression of cell-to-cell variability. We further identify sets of trans-factors associated with cell-type-specific accessibility variance across eight cell types. Targeted perturbations of cell cycle or transcription factor signalling evoke stimulus-specific changes in this observed variability. The pattern of accessibility variation in cis across the genome recapitulates chromosome compartments de novo, linking single-cell accessibility variation to three-dimensional genome organization. Single-cell analysis of DNA accessibility provides new insight into cellular variation of the 'regulome'.

  3. Virtual fabrication using directed self-assembly for process optimization in a 14-nm dynamic random access memory

    NASA Astrophysics Data System (ADS)

    Kamon, Mattan; Akbulut, Mustafa; Yan, Yiguang; Faken, Daniel; Pap, Andras; Allampalli, Vasanth; Greiner, Ken; Fried, David

    2016-07-01

    For directed self-assembly (DSA) to be deployed in advanced semiconductor technologies, it must reliably integrate into a full process flow. We present a methodology for using virtual fabrication software, including predictive DSA process models, to develop and analyze the replacement of self-aligned quadruple patterning with Liu-Nealey chemoepitaxy on a 14-nm dynamic random access memory (DRAM) process. To quantify the impact of this module replacement, we investigated a key process yield metric for DRAM, interface area between the capacitor contacts and transistor source/drain. Additionally, we demonstrate virtual fabrication of the DRAM cell's hexagonally packed capacitors patterned with an array of diblock copolymer cylinders in place of fourfold litho-etch (LE4) patterning.

  4. Autoimmune effector memory T cells: the bad and the good

    PubMed Central

    Devarajan, Priyadharshini; Chen, Zhibin

    2014-01-01

    Immunological memory is a hallmark of adaptive immunity, a defense mechanism endowed to vertebrates during evolution. However, an autoimmune pathogenic role of memory lymphocytes is also emerging with accumulating evidence, despite reasonable skepticism on their existence in a chronic setting of autoimmune damage. It is conceivable that autoimmune memory would be particularly harmful since memory cells would constantly “remember” and attack the body's healthy tissues. It is even more detrimental given the resistance of memory T cells to immunomodulatory therapies. In this review, we focus on self-antigen-reactive CD4+ effector memory T (TEM) cells, surveying the evidence for the role of the TEM compartment in autoimmune pathogenesis. We will also discuss the role of TEM cells in chronic and acute infectious disease settings and how they compare to their counterparts in autoimmune diseases. With their long-lasting potency, the autoimmune TEM cells could also play a critical role in anti-tumor immunity, which may be largely based on their reactivity to self-antigens. Therefore, although autoimmune TEM cells are “bad” due to their role in relentless perpetration of tissue damage in autoimmune disease settings, they are unlikely a by-product of industrial development along the modern surge of autoimmune disease prevalence. Rather, they may be a product of evolution for their “good” in clearing damaged host cells in chronic infections and malignant cells in cancer settings. PMID:24203440

  5. KLRG1 restricts memory T cell antitumor immunity

    PubMed Central

    Li, Lei; Wan, Shanshan; Tao, Kaixiong; Wang, Guobin; Zhao, Ende

    2016-01-01

    Killer cell lectin-like receptor subfamily G member 1 (KLRG1) has been found on human memory T lymphocytes. However, the roles of KLRG1 on human T cells especially in tumor microenvironment have not been fully understood. Our results showed KLRG1 expression on T cells significantly increased in tumor microenvironment. KLRG1+ T cells exhibited poor proliferative capacity with decreased effector cytokine production. Meanwhile, KLRG1+ T cells expressed abundant pro-inflammatory cytokines and demonstrated high level of Foxp3 expression. KLRG1+ T cells showed decreased expression of miRNA-101 and higher expression of CtBP2. Our results indicated KLRG1 might contribute to the impaired antitumor immunity of memory T cells in tumor microenvironment. Thus, repressing KLRG1 on human memory T cells might be a novel therapeutics against cancer. PMID:27557510

  6. Analyzing the Energy and Power Consumption of Remote Memory Accesses in the OpenSHMEM Model

    SciTech Connect

    Jana, Siddhartha; Hernandez, Oscar R; Poole, Stephen W; Hsu, Chung-Hsing; Chapman, Barbara

    2014-01-01

    PGAS models like OpenSHMEM provide interfaces to explicitly initiate one-sided remote memory accesses among processes. In addition, the model also provides synchronizing barriers to ensure a consistent view of the distributed memory at different phases of an application. The incorrect use of such interfaces affects the scalability achievable while using a parallel programming model. This study aims at understanding the effects of these constructs on the energy and power consumption behavior of OpenSHMEM applications. Our experiments show that cost incurred in terms of the total energy and power consumed depends on multiple factors across the software and hardware stack. We conclude that there is a significant impact on the power consumed by the CPU and DRAM due to multiple factors including the design of the data transfer patterns within an application, the design of the communication protocols within a middleware, the architectural constraints laid by the interconnect solutions, and also the levels of memory hierarchy within a compute node. This work motivates treating energy and power consumption as important factors while designing compute solutions for current and future distributed systems.

  7. Targeting memory T cells in type 1 diabetes.

    PubMed

    Ehlers, Mario R; Rigby, Mark R

    2015-11-01

    Type 1 diabetes (T1D) is a chronic autoimmune disease that leads to progressive destruction of pancreatic beta cells. Compared to healthy controls, a characteristic feature of patients with T1D is the presence of self-reactive T cells with a memory phenotype. These autoreactive memory T cells in both the CD4(+) and CD8(+) compartments are likely to be long-lived, strongly responsive to antigenic stimulation with less dependence on costimulation for activation and clonal expansion, and comparatively resistant to suppression by regulatory T cells (Tregs) or downregulation by immune-modulating agents. Persistence of autoreactive memory T cells likely contributes to the difficulty in preventing disease progression in new-onset T1D and maintaining allogeneic islet transplants by regular immunosuppressive regimens. The majority of immune interventions that have demonstrated some success in preserving beta cell function in the new-onset period have been shown to deplete or modulate memory T cells. Based on these and other considerations, preservation of residual beta cells early after diagnosis or restoration of beta cell mass by use of stem cell or transplantation technology will require a successful strategy to control the autoreactive memory T cell compartment, which could include depletion, inhibition of homeostatic cytokines, induction of hyporesponsiveness, or a combination of these approaches.

  8. Accessibility of observable and unobservable characteristics in autobiographical memories of recent and distant past.

    PubMed

    Karylowski, Jerzy J; Mrozinski, Blazej

    2017-02-01

    Self-reports regarding how people visualise themselves during events that occurred in the past show that for events from the distant past individuals report assuming a more external perspective than for events from the recent past [Nigro, G., & Neisser, U. (1983). Point of view in personal memories. Cognitive Psychology, 15, 467-482; Pronin, E., & Ross, L. (2006). Temporal differences in trait self-ascription. Journal of Personality & Social Psychology, 90, 197-209]. Thus it appears that, with the passage of time, representations of self embodied in memories of past events lose their position of an insider and assume a more ordinary position of self as an object seen from the perspective of an outside observer. The purpose of the present experiment was to examine this shift using a performance-based measure of accessibility. Results showed that self-judgements regarding unobservable, covert characteristics were faster for recent-compared to more distant-autobiographical events. However, self-judgements regarding observable, overt characteristics were faster for more distant events. This suggests an accessibility-based mechanism underlying the shift from internal to the relatively more external perspective in forming self-images related to the distant past.

  9. 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

  10. Memory B Cells and Pneumococcal Antibody After Splenectomy1

    PubMed Central

    Wasserstrom, Heather; Bussel, James; Lim, Lony C.-L.; Cunningham-Rundles, Charlotte

    2010-01-01

    Splenectomized patients are susceptible to bloodstream infections with encapsulated bacteria, potentially due to loss of blood filtering but also defective production of anticarbohydrate Ab. Recent studies propose that a lack of Ab is related to reduced numbers of IgM+ CD27+ memory B cells found after splenectomy. To test this, we analyzed CD27+ memory B cell subsets, IgG, and IgM pneumococcal Ab responses in 26 vaccinated splenectomized subjects in comparison to memory B cell subsets and Ab responses in healthy controls. As shown previously, the splenectomized autoimmune subjects had fewer total, isotype switched, and IgM+ CD27+ memory B cells as compared with controls, but there was no difference in memory B cells subsets between controls and splenectomized subjects with spherocytosis. There was no difference between the geometric mean IgG Ab response between normal controls and splenectomized subjects (p = 0.51; p = 0.81). Control subjects produced more IgM Ab than splenectomized autoimmune subjects (p = 0.01) but the same levels as subjects with spherocytosis (p = 0.15.) There was no correlation between memory B cell subsets and IgG or IgM Ab responses for controls or splenectomized subjects. These data suggest that splenectomy alone may not be the sole reason for loss of memory B cells and reduced IgM antipneumococcal Ab. Because subjects with autoimmunity had splenectomy at a significantly older age than participants with spherocytosis, these data suggest that an age-related loss of extra splenic sites necessary for the maintenance or function of memory B cells may lead to impaired immunity in these subjects. PMID:18714044

  11. Resistive Switching of Plasma–Treated Zinc Oxide Nanowires for Resistive Random Access Memory

    PubMed Central

    Lai, Yunfeng; Qiu, Wenbiao; Zeng, Zecun; Cheng, Shuying; Yu, Jinling; Zheng, Qiao

    2016-01-01

    ZnO nanowires (NWs) were grown on Si(100) substrates at 975 °C by a vapor-liquid-solid method with ~2 nm and ~4 nm gold thin films as catalysts, followed by an argon plasma treatment for the as-grown ZnO NWs. A single ZnO NW–based memory cell with a Ti/ZnO/Ti structure was then fabricated to investigate the effects of plasma treatment on the resistive switching. The plasma treatment improves the homogeneity and reproducibility of the resistive switching of the ZnO NWs, and it also reduces the switching (set and reset) voltages with less fluctuations, which would be associated with the increased density of oxygen vacancies to facilitate the resistive switching as well as to average out the stochastic movement of individual oxygen vacancies. Additionally, a single ZnO NW–based memory cell with self-rectification could also be obtained, if the inhomogeneous plasma treatment is applied to the two Ti/ZnO contacts. The plasma-induced oxygen vacancy disabling the rectification capability at one of the Ti/ZnO contacts is believed to be responsible for the self-rectification in the memory cell.

  12. Response of the Ubiquitin-Proteasome System to Memory Retrieval After Extended-Access Cocaine or Saline Self-Administration.

    PubMed

    Werner, Craig T; Milovanovic, Mike; Christian, Daniel T; Loweth, Jessica A; Wolf, Marina E

    2015-12-01

    The ubiquitin-proteasome system (UPS) has been implicated in the retrieval-induced destabilization of cocaine- and fear-related memories in Pavlovian paradigms. However, nothing is known about its role in memory retrieval after self-administration of cocaine, an operant paradigm, or how the length of withdrawal from cocaine may influence retrieval mechanisms. Here, we examined UPS activity after an extended-access cocaine self-administration regimen that leads to withdrawal-dependent incubation of cue-induced cocaine craving. Controls self-administered saline. In initial experiments, memory retrieval was elicited via a cue-induced seeking/retrieval test on withdrawal day (WD) 50-60, when craving has incubated. We found that retrieval of cocaine- and saline-associated memories produced similar increases in polyubiquitinated proteins in the nucleus accumbens (NAc), compared with rats that did not undergo a seeking/retrieval test. Measures of proteasome catalytic activity confirmed similar activation of the UPS after retrieval of saline and cocaine memories. However, in a subsequent experiment in which testing was conducted on WD1, proteasome activity in the NAc was greater after retrieval of cocaine memory than saline memory. Analysis of other brain regions confirmed that effects of cocaine memory retrieval on proteasome activity, relative to saline memory retrieval, depend on withdrawal time. These results, combined with prior studies, suggest that the relationship between UPS activity and memory retrieval depends on training paradigm, brain region, and time elapsed between training and retrieval. The observation that mechanisms underlying cocaine memory retrieval change depending on the age of the memory has implications for development of memory destabilization therapies for cue-induced relapse in cocaine addicts.

  13. Memory improves precision of cell sensing in fluctuating environments

    NASA Astrophysics Data System (ADS)

    Aquino, Gerardo; Tweedy, Luke; Heinrich, Doris; Endres, Robert G.

    2014-07-01

    Biological cells are often found to sense their chemical environment near the single-molecule detection limit. Surprisingly, this precision is higher than simple estimates of the fundamental physical limit, hinting towards active sensing strategies. In this work, we analyse the effect of cell memory, e.g. from slow biochemical processes, on the precision of sensing by cell-surface receptors. We derive analytical formulas, which show that memory significantly improves sensing in weakly fluctuating environments. However, surprisingly when memory is adjusted dynamically, the precision is always improved, even in strongly fluctuating environments. In support of this prediction we quantify the directional biases in chemotactic Dictyostelium discoideum cells in a flow chamber with alternating chemical gradients. The strong similarities between cell sensing and control engineering suggest universal problem-solving strategies of living matter.

  14. Memory improves precision of cell sensing in fluctuating environments

    PubMed Central

    Aquino, Gerardo; Tweedy, Luke; Heinrich, Doris; Endres, Robert G.

    2014-01-01

    Biological cells are often found to sense their chemical environment near the single-molecule detection limit. Surprisingly, this precision is higher than simple estimates of the fundamental physical limit, hinting towards active sensing strategies. In this work, we analyse the effect of cell memory, e.g. from slow biochemical processes, on the precision of sensing by cell-surface receptors. We derive analytical formulas, which show that memory significantly improves sensing in weakly fluctuating environments. However, surprisingly when memory is adjusted dynamically, the precision is always improved, even in strongly fluctuating environments. In support of this prediction we quantify the directional biases in chemotactic Dictyostelium discoideum cells in a flow chamber with alternating chemical gradients. The strong similarities between cell sensing and control engineering suggest universal problem-solving strategies of living matter. PMID:25023459

  15. Controllable quantized conductance for multilevel data storage applications using conductive bridge random access memory.

    PubMed

    Aga, Fekadu Gochole; Woo, Jiyong; Song, Jeonghwan; Park, Jaehyuk; Lim, Seokjae; Sung, Changhyuck; Hwang, Hyunsang

    2017-03-17

    In this paper, we investigate the quantized conduction behavior of conductive bridge random access memory (CBRAM) with varied materials and ramping rates. We report stable and reproducible quantized conductance states with integer multiples of fundamental conductance obtained by optimizing the voltage ramping rate and the Ti-diffusion barrier (DB) at the Cu/HfO2 interface. Owing to controlled diffusion of Cu ions by the Ti-DB and the optimized ramping rate, through which it was possible to control the time delay of Cu ion reduction, more than seven levels of discrete conductance states were clearly observed. Analytical modeling was performed to determine the rate-limiting step in filament growth based on an electrochemical redox reaction. Our understanding of the fundamental mechanisms of quantized conductance behaviors provide a promising future for the multi-bit CBRAM device.

  16. Low-energy Resistive Random Access Memory Devices with No Need for a Compliance Current

    PubMed Central

    Xu, Zedong; Yu, Lina; Wu, Yong; Dong, Chang; Deng, Ning; Xu, Xiaoguang; Miao, J.; Jiang, Yong

    2015-01-01

    A novel resistive random access memory device is designed with SrTiO3/ La2/3Sr1/3MnO3 (LSMO)/MgAl2O4 (MAO)/Cu structure, in which metallic epitaxial LSMO is employed as the bottom electrode rather than traditional metal materials. In this device, the critical external compliance current is no longer necessary due to the high self-resistance of LSMO. The LMSO bottom electrode can act as a series resistor to offer a compliance current during the set process. Besides, the device also has excellent switching features which are originated in the formation of Cu filaments under external voltage. Therefore it provides the possibility of reducing power consumption and accelerating the commercialization of resistive switching devices. PMID:25982101

  17. Characteristics and mechanism study of cerium oxide based random access memories

    SciTech Connect

    Hsieh, Cheng-Chih; Roy, Anupam; Rai, Amritesh; Chang, Yao-Feng; Banerjee, Sanjay K.

    2015-04-27

    In this work, low operating voltage and high resistance ratio of different resistance states of binary transition metal oxide based resistive random access memories (RRAMs) are demonstrated. Binary transition metal oxides with high dielectric constant have been explored for RRAM application for years. However, CeO{sub x} is considered as a relatively new material to other dielectrics. Since research on CeO{sub x} based RRAM is still at preliminary stage, fundamental characteristics of RRAM such as scalability and mechanism studies need to be done before moving further. Here, we show very high operation window and low switching voltage of CeO{sub x} RRAMs and also compare electrical performance of Al/CeO{sub x}/Au system between different thin film deposition methods and discuss characteristics and resistive switching mechanism.

  18. Controllable quantized conductance for multilevel data storage applications using conductive bridge random access memory

    NASA Astrophysics Data System (ADS)

    Gochole Aga, Fekadu; Woo, Jiyong; Song, Jeonghwan; Park, Jaehyuk; Lim, Seokjae; Sung, Changhyuck; Hwang, Hyunsang

    2017-03-01

    In this paper, we investigate the quantized conduction behavior of conductive bridge random access memory (CBRAM) with varied materials and ramping rates. We report stable and reproducible quantized conductance states with integer multiples of fundamental conductance obtained by optimizing the voltage ramping rate and the Ti-diffusion barrier (DB) at the Cu/HfO2 interface. Owing to controlled diffusion of Cu ions by the Ti-DB and the optimized ramping rate, through which it was possible to control the time delay of Cu ion reduction, more than seven levels of discrete conductance states were clearly observed. Analytical modeling was performed to determine the rate-limiting step in filament growth based on an electrochemical redox reaction. Our understanding of the fundamental mechanisms of quantized conductance behaviors provide a promising future for the multi-bit CBRAM device.

  19. Electrical Characterization of the RCA CDP1822SD Random Access Memory, Volume 1, Appendix a

    NASA Technical Reports Server (NTRS)

    Klute, A.

    1979-01-01

    Electrical characteristization tests were performed on 35 RCA CDP1822SD, 256-by-4-bit, CMOS, random access memories. The tests included three functional tests, AC and DC parametric tests, a series of schmoo plots, rise/fall time screening, and a data retention test. All tests were performed on an automated IC test system with temperatures controlled by a thermal airstream unit. All the functional tests, the data retention test, and the AC and DC parametric tests were performed at ambient temperatures of 25 C, -20 C, -55 C, 85 C, and 125 C. The schmoo plots were performed at ambient temperatures of 25 C, -55 C, and 125 C. The data retention test was performed at 25 C. Five devices failed one or more functional tests and four of these devices failed to meet the expected limits of a number of AC parametric tests. Some of the schmoo plots indicated a small degree of interaction between parameters.

  20. Band alignment between Ta2O5 and metals for resistive random access memory electrodes engineering

    NASA Astrophysics Data System (ADS)

    Zhuo, V. Y.-Q.; Jiang, Y.; Li, M. H.; Chua, E. K.; Zhang, Z.; Pan, J. S.; Zhao, R.; Shi, L. P.; Chong, T. C.; Robertson, J.

    2013-02-01

    Band alignment of resistive random access memory (RRAM) switching material Ta2O5 and different metal electrode materials was examined using high-resolution X-ray photoelectron spectroscopy. Schottky and hole barrier heights at the interface between electrode and Ta2O5 were obtained, where the electrodes consist of materials with low to high work function (Φm ,vac from 4.06 to 5.93 eV). Effective metal work functions were extracted to study the Fermi level pinning effect and to discuss the dominant conduction mechanism. An accurate band alignment between electrodes and Ta2O5 is obtained and can be used for RRAM electrode engineering and conduction mechanism study.

  1. Understanding Electrical Conduction States in WO3 Thin Films Applied for Resistive Random-Access Memory

    NASA Astrophysics Data System (ADS)

    Ta, Thi Kieu Hanh; Pham, Kim Ngoc; Dao, Thi Bang Tam; Tran, Dai Lam; Phan, Bach Thang

    2016-05-01

    The electrical conduction and associated resistance switching mechanism of top electrode/WO3/bottom electrode devices [top electrode (TE): Ag, Ti; bottom electrode (BE): Pt, fluorine-doped tin oxide] have been investigated. The direction of switching and switching ability depended on both the top and bottom electrode material. Multiple electrical conduction mechanisms control the leakage current of such switching devices, including trap-controlled space-charge, ballistic, Ohmic, and Fowler-Nordheim tunneling effects. The transition between electrical conduction states is also linked to the switching (SET-RESET) process. This is the first report of ballistic conduction in research into resistive random-access memory. The associated resistive switching mechanisms are also discussed.

  2. Microstructural transitions in resistive random access memory composed of molybdenum oxide with copper during switching cycles.

    PubMed

    Arita, Masashi; Ohno, Yuuki; Murakami, Yosuke; Takamizawa, Keisuke; Tsurumaki-Fukuchi, Atsushi; Takahashi, Yasuo

    2016-08-21

    The switching operation of a Cu/MoOx/TiN resistive random access memory (ReRAM) device was investigated using in situ transmission electron microscopy (TEM), where the TiN surface was slightly oxidized (ox-TiN). The relationship between the switching properties and the dynamics of the ReRAM microstructure was confirmed experimentally. The growth and/or shrinkage of the conductive filament (CF) can be classified into two set modes and two reset modes. These switching modes depend on the device's switching history, factors such as the amount of Cu inclusions in the MoOx layer and the CF geometry. High currents are needed to produce an observable change in the CF. However, sharp and stable switching behaviour can be achieved without requiring such a major change. The local region around the CF is thought to contribute to the ReRAM switching process.

  3. Role of an encapsulating layer for reducing resistance drift in phase change random access memory

    NASA Astrophysics Data System (ADS)

    Jin, Bo; Kim, Jungsik; Pi, Dong-Hai; Kim, Hyoung Seop; Meyyappan, M.; Lee, Jeong-Soo

    2014-12-01

    Phase change random access memory (PCRAM) devices exhibit a steady increase in resistance in the amorphous phase upon aging and this resistance drift phenomenon directly affects the device reliability. A stress relaxation model is used here to study the effect of a device encapsulating layer material in addressing the resistance drift phenomenon in PCRAM. The resistance drift can be increased or decreased depending on the biaxial moduli of the phase change material (YPCM) and the encapsulating layer material (YELM) according to the stress relationship between them in the drift regime. The proposed model suggests that the resistance drift can be effectively reduced by selecting a proper material as an encapsulating layer. Moreover, our model explains that reducing the size of the phase change material (PCM) while fully reset and reducing the amorphous/crystalline ratio in PCM help to improve the resistance drift, and thus opens an avenue for highly reliable multilevel PCRAM applications.

  4. PD-1 blockade expands intratumoral T memory cells

    PubMed Central

    Ribas, Antoni; Shin, Daniel Sanghoon; Zaretsky, Jesse; Frederiksen, Juliet; Cornish, Andrew; Avramis, Earl; Seja, Elizabeth; Kivork, Christine; Siebert, Janet; Kaplan-Lefko, Paula; Wang, Xiaoyan; Chmielowski, Bartosz; Glaspy, John A.; Tumeh, Paul C.; Chodon, Thinle; Pe’er, Dana; Comin-Anduix, Begoña

    2016-01-01

    Tumor responses to PD-1 blockade therapy are mediated by T cells, which we characterized in 102 tumor biopsies obtained from 53 patients treated with pembrolizumab, an antibody to PD-1. Biopsies were dissociated and single cell infiltrates were analyzed by multicolor flow cytometry using two computational approaches to resolve the leukocyte phenotypes at the single cell level. There was a statistically significant increase in the frequency of T cells in patients who responded to therapy. The frequency of intratumoral B cells and monocytic myeloid-derived suppressor cells (moMDSCs) significantly increased in patients’ biopsies taken on treatment. The percentage of cells with a T regulatory phenotype, monocytes, and NK cells did not change while on PD-1 blockade therapy. CD8+ T memory cells were the most prominent phenotype that expanded intratumorally on therapy. However, the frequency of CD4+ T effector memory cells significantly decreased on treatment, whereas CD4+ T effector cells significantly increased in nonresponding tumors on therapy. In peripheral blood, an unusual population of blood cells expressing CD56 were detected in two patients with regressing melanoma. In conclusion, PD-1 blockade increases the frequency of T cells, B cells, and MDSCs in tumors, with the CD8+ T effector memory subset being the major T-cell phenotype expanded in patients with a response to therapy. PMID:26787823

  5. Structure for common access and support of fuel cell stacks

    DOEpatents

    Walsh, Michael M.

    2000-01-01

    A structure provides common support and access to multiple fuel cells externally mounted thereto. The structure has openings leading to passages defined therein for providing the access. Various other fuel cell power system components are connected at the openings, such as reactant and coolant sources.

  6. Metal oxide resistive random access memory based synaptic devices for brain-inspired computing

    NASA Astrophysics Data System (ADS)

    Gao, Bin; Kang, Jinfeng; Zhou, Zheng; Chen, Zhe; Huang, Peng; Liu, Lifeng; Liu, Xiaoyan

    2016-04-01

    The traditional Boolean computing paradigm based on the von Neumann architecture is facing great challenges for future information technology applications such as big data, the Internet of Things (IoT), and wearable devices, due to the limited processing capability issues such as binary data storage and computing, non-parallel data processing, and the buses requirement between memory units and logic units. The brain-inspired neuromorphic computing paradigm is believed to be one of the promising solutions for realizing more complex functions with a lower cost. To perform such brain-inspired computing with a low cost and low power consumption, novel devices for use as electronic synapses are needed. Metal oxide resistive random access memory (ReRAM) devices have emerged as the leading candidate for electronic synapses. This paper comprehensively addresses the recent work on the design and optimization of metal oxide ReRAM-based synaptic devices. A performance enhancement methodology and optimized operation scheme to achieve analog resistive switching and low-energy training behavior are provided. A three-dimensional vertical synapse network architecture is proposed for high-density integration and low-cost fabrication. The impacts of the ReRAM synaptic device features on the performances of neuromorphic systems are also discussed on the basis of a constructed neuromorphic visual system with a pattern recognition function. Possible solutions to achieve the high recognition accuracy and efficiency of neuromorphic systems are presented.

  7. Microstructural transitions in resistive random access memory composed of molybdenum oxide with copper during switching cycles

    NASA Astrophysics Data System (ADS)

    Arita, Masashi; Ohno, Yuuki; Murakami, Yosuke; Takamizawa, Keisuke; Tsurumaki-Fukuchi, Atsushi; Takahashi, Yasuo

    2016-08-01

    The switching operation of a Cu/MoOx/TiN resistive random access memory (ReRAM) device was investigated using in situ transmission electron microscopy (TEM), where the TiN surface was slightly oxidized (ox-TiN). The relationship between the switching properties and the dynamics of the ReRAM microstructure was confirmed experimentally. The growth and/or shrinkage of the conductive filament (CF) can be classified into two set modes and two reset modes. These switching modes depend on the device's switching history, factors such as the amount of Cu inclusions in the MoOx layer and the CF geometry. High currents are needed to produce an observable change in the CF. However, sharp and stable switching behaviour can be achieved without requiring such a major change. The local region around the CF is thought to contribute to the ReRAM switching process.The switching operation of a Cu/MoOx/TiN resistive random access memory (ReRAM) device was investigated using in situ transmission electron microscopy (TEM), where the TiN surface was slightly oxidized (ox-TiN). The relationship between the switching properties and the dynamics of the ReRAM microstructure was confirmed experimentally. The growth and/or shrinkage of the conductive filament (CF) can be classified into two set modes and two reset modes. These switching modes depend on the device's switching history, factors such as the amount of Cu inclusions in the MoOx layer and the CF geometry. High currents are needed to produce an observable change in the CF. However, sharp and stable switching behaviour can be achieved without requiring such a major change. The local region around the CF is thought to contribute to the ReRAM switching process. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr02602h

  8. Synthetic circuits integrating logic and memory in living cells.

    PubMed

    Siuti, Piro; Yazbek, John; Lu, Timothy K

    2013-05-01

    Logic and memory are essential functions of circuits that generate complex, state-dependent responses. Here we describe a strategy for efficiently assembling synthetic genetic circuits that use recombinases to implement Boolean logic functions with stable DNA-encoded memory of events. Application of this strategy allowed us to create all 16 two-input Boolean logic functions in living Escherichia coli cells without requiring cascades comprising multiple logic gates. We demonstrate long-term maintenance of memory for at least 90 cell generations and the ability to interrogate the states of these synthetic devices with fluorescent reporters and PCR. Using this approach we created two-bit digital-to-analog converters, which should be useful in biotechnology applications for encoding multiple stable gene expression outputs using transient inputs of inducers. We envision that this integrated logic and memory system will enable the implementation of complex cellular state machines, behaviors and pathways for therapeutic, diagnostic and basic science applications.

  9. Memory

    MedlinePlus

    ... it has to decide what is worth remembering. Memory is the process of storing and then remembering this information. There are different types of memory. Short-term memory stores information for a few ...

  10. Context controls access to working and reference memory in the pigeon (Columba livia).

    PubMed

    Roberts, William A; Macpherson, Krista; Strang, Caroline

    2016-01-01

    The interaction between working and reference memory systems was examined under conditions in which salient contextual cues were presented during memory retrieval. Ambient colored lights (red or green) bathed the operant chamber during the presentation of comparison stimuli in delayed matching-to-sample training (working memory) and during the presentation of the comparison stimuli as S+ and S- cues in discrimination training (reference memory). Strong competition between memory systems appeared when the same contextual cue appeared during working and reference memory training. When different contextual cues were used, however, working memory was completely protected from reference memory interference.

  11. Granzyme B production distinguishes recently activated CD8+ memory cells from resting memory cells

    PubMed Central

    Nowacki, Tobias M.; Kuerten, Stefanie; Zhang, Wenji; Shive, Carey L.; Kreher, Christian R.; Boehm, Bernhard O.; Lehmann, Paul V.; Tary-Lehmann, Magdalena

    2007-01-01

    For immune diagnostic purposes it would be critical to be able to distinguish between ongoing immune processes, such as active infections, and long-term immune memory, for example imprinted by infections that have been cleared a long time ago or by vaccinations. We tested the hypothesis that the secretion of Granzyme B, as detected in ex vivo ELISPOT assays, permits this distinction. We studied EBV-, flu- and CMV-specific CD8+ cells in healthy individuals, Vaccinia virus-reactive CD8+ cells in the course of vaccination, and HIV-specific CD8+ cells in HIV-infected individuals. Antigen-specific ex vivo GzB production was detected only transiently after Vaccinia immunization, and in HIV-infected individuals. Our data suggest that ex vivo ELISPOT measurements of granzyme B permit the identification of actively ongoing CD8+ cell responses – a notion that is pertinent to the immune diagnostic of infections, transplantation, allergies, autoimmune diseases, tumors, and vaccine development. PMID:17825804

  12. Histone Acetylation Facilitates Rapid and Robust Memory CD8 T Cell Response through Differential Expression of Effector Molecules (Eomesodermin and Its Targets: Perforin and Granzyme B)1

    PubMed Central

    Araki, Yasuto; Fann, Monchou; Wersto, Robert; Weng, Nan-ping

    2008-01-01

    To understand the mechanism regulating the effector function of memory CD8 T cells, we examined expression and chromatin state of a key transcription factor (eomesodermin, EOMES) and two of its targets: perforin (PRF1) and granzyme B (GZMB). Accessible chromatin associated histone 3 lysine 9 acetylation (H3K9Ac) was found significantly higher at the proximal promoter and the first exon region of all three genes in memory CD8 T cells than in naive CD8 T cells. Correspondingly, EOMES and PRF1 were constitutively higher expressed in memory CD8 T cells than in naive CD8 T cells at resting and activated states. In contrast, higher expression of GZMB was induced in memory CD8 T cells than in naive CD8 T cells only after activation. Regardless of their constitutive or inducible expression, decreased H3K9Ac levels after treatment with a histone acetyl-transferase inhibitor (Curcumin) led to decreased expression of all three genes in activated memory CD8 T cells. These findings suggest that H3K9Ac associated accessible chromatin state serves as a corner stone for the differentially high expression of these effector genes in memory CD8 T cells. Thus, epigenetic changes mediated via histone acetylation may provide a chromatin “memory” for the rapid and robust transcriptional response of memory CD8 T cells. PMID:18523274

  13. Epigenomics of T cell activation, differentiation and memory

    PubMed Central

    Cuddapah, Suresh; Barski, Artem; Zhao, Keji

    2010-01-01

    Activation of T cells is an essential step in the immunological response to infection. While activation of naïve T cells results in proliferation and slow differentiation into cytokine-producing effector cells, antigen engagement with memory cells leads to cytokine production immediately. Even though the cell surface signaling events are similar in both the cases, the outcome is different, suggesting that distinct regulatory mechanisms may exist downstream of the activation signals. Recent advances in the understanding of global epigenetic patterns in T cells have resulted in the appreciation of the role of epigenetic mechanisms in processes such as activation and differentiation. In this review we discuss recent data suggesting that naïve T cell activation, differentiation and lineage commitment results in epigenetic changes and a fine balance between different histone modifications is required. On the other hand, memory T cells are poised and do not require epigenetic changes for short-term activation. PMID:20226645

  14. Epigenetic memory and cell fate reprogramming in plants

    PubMed Central

    Roudier, François

    2017-01-01

    Abstract Plants have a high intrinsic capacity to regenerate from adult tissues, with the ability to reprogram adult cell fates. In contrast, epigenetic mechanisms have the potential to stabilize cell identity and maintain tissue organization. The question is whether epigenetic memory creates a barrier to reprogramming that needs to be erased or circumvented in plant regeneration. Early evidence suggests that, while chromatin dynamics impact gene expression in the meristem, a lasting constraint on cell fate is not established until late stages of plant cell differentiation. It is not yet clear whether the plasticity of plant cells arises from the ability of cells to erase identity memory or to deploy cells that may exhibit cellular specialization but still lack an epigenetic restriction on cell fate alteration. PMID:28316791

  15. Epigenetic memory and cell fate reprogramming in plants.

    PubMed

    Birnbaum, Kenneth D; Roudier, François

    2017-02-01

    Plants have a high intrinsic capacity to regenerate from adult tissues, with the ability to reprogram adult cell fates. In contrast, epigenetic mechanisms have the potential to stabilize cell identity and maintain tissue organization. The question is whether epigenetic memory creates a barrier to reprogramming that needs to be erased or circumvented in plant regeneration. Early evidence suggests that, while chromatin dynamics impact gene expression in the meristem, a lasting constraint on cell fate is not established until late stages of plant cell differentiation. It is not yet clear whether the plasticity of plant cells arises from the ability of cells to erase identity memory or to deploy cells that may exhibit cellular specialization but still lack an epigenetic restriction on cell fate alteration.

  16. Innate and virtual memory T cells in man.

    PubMed

    Van Kaer, Luc

    2015-07-01

    A hallmark of the antigen-specific B and T lymphocytes of the adaptive immune system is their capacity to "remember" pathogens long after they are first encountered, a property that forms the basis for effective vaccine development. However, studies in mice have provided strong evidence that some naive T cells can develop characteristics of memory T cells in the absence of foreign antigen encounters. Such innate memory T cells may develop in response to lymphopenia or the presence of high levels of the cytokine IL-4, and have also been identified in unmanipulated animals, a phenomenal referred to as "virtual memory." While the presence of innate memory T cells in mice is now widely accepted, their presence in humans has not yet been fully validated. In this issue of the European Journal of Immunology, Jacomet et al. [Eur. J. Immunol. 2015. 45:1926-1933] provide the best evidence to date for innate memory T cells in humans. These findings may contribute significantly to our understanding of human immunity to microbial pathogens and tumors.

  17. Frontal activations associated with accessing and evaluating information in working memory: an fMRI study.

    PubMed

    Zhang, John X; Leung, Hoi-Chung; Johnson, Marcia K

    2003-11-01

    To investigate the involvement of frontal cortex in accessing and evaluating information in working memory, we used a variant of a Sternberg paradigm and compared brain activations between positive and negative responses (known to differentially tax access/evaluation processes). Participants remembered two trigrams in each trial and were then cued to discard one of them and maintain the other one as the target set. After a delay, a probe letter was presented and participants made decisions about whether or not it was in the target set. Several frontal areas--anterior cingulate (BA32), middle frontal gyrus (bilateral BA9, right BA10, and right BA46), and left inferior frontal gyrus (BA44/45)--showed increased activity when participants made correct negative responses relative to when they made correct positive responses. No areas activated significantly more for the positive responses than for the negative responses. It is suggested that the multiple frontal areas involved in the test phase of this task may reflect several component processes that underlie more general frontal functions.

  18. Three-Year-Old Children Can Access Their Own Memory to Guide Responses on a Visual Matching Task

    ERIC Educational Resources Information Center

    Balcomb, Frances K.; Gerken, LouAnn

    2008-01-01

    Many models of learning rely on accessing internal knowledge states. Yet, although infants and young children are recognized to be proficient learners, the ability to act on metacognitive information is not thought to develop until early school years. In the experiments reported here, 3.5-year-olds demonstrated memory-monitoring skills by…

  19. Dendritic cells drive memory CD8 T-cell homeostasis via IL-15 transpresentation

    PubMed Central

    Stonier, Spencer W.; Ma, Lisa J.; Castillo, Eliseo F.

    2008-01-01

    Interleukin-15 (IL-15) is crucial for the development of naive and memory CD8 T cells and is delivered through a mechanism called transpresentation. Previous studies showed that memory CD8 T cells require IL-15 transpresentation by an as yet unknown cell of hematopoietic origin. We hypothesized that dendritic cells (DCs) transpresent IL-15 to CD8 T cells, and we examined this by developing a transgenic model that limits IL-15 transpresentation to DCs. In this study, IL-15 transpresentation by DCs had little effect on restoring naive CD8 T cells but contributed to the development of memory-phenotype CD8 T cells. The generation of virus-specific, memory CD8 T cells was partially supported by IL-15Rα+ DCs through the preferential enhancement of a subset of KLRG-1+CD27− CD8 T cells. In contrast, these DCs were largely sufficient in driving normal homeostatic proliferation of established memory CD8 T cells, suggesting that memory CD8 T cells grow more dependent on IL-15 transpresentation by DCs. Overall, our study clearly supports a role for DCs in memory CD8 T-cell homeostasis but also provides evidence that other hematopoietic cells are involved in this function. The identification of DCs fulfilling this role will enable future studies to better focus on mechanisms regulating T-cell homeostasis. PMID:18812469

  20. Dendritic cells drive memory CD8 T-cell homeostasis via IL-15 transpresentation.

    PubMed

    Stonier, Spencer W; Ma, Lisa J; Castillo, Eliseo F; Schluns, Kimberly S

    2008-12-01

    Interleukin-15 (IL-15) is crucial for the development of naive and memory CD8 T cells and is delivered through a mechanism called transpresentation. Previous studies showed that memory CD8 T cells require IL-15 transpresentation by an as yet unknown cell of hematopoietic origin. We hypothesized that dendritic cells (DCs) transpresent IL-15 to CD8 T cells, and we examined this by developing a transgenic model that limits IL-15 transpresentation to DCs. In this study, IL-15 transpresentation by DCs had little effect on restoring naive CD8 T cells but contributed to the development of memory-phenotype CD8 T cells. The generation of virus-specific, memory CD8 T cells was partially supported by IL-15Ralpha(+) DCs through the preferential enhancement of a subset of KLRG-1(+)CD27(-) CD8 T cells. In contrast, these DCs were largely sufficient in driving normal homeostatic proliferation of established memory CD8 T cells, suggesting that memory CD8 T cells grow more dependent on IL-15 transpresentation by DCs. Overall, our study clearly supports a role for DCs in memory CD8 T-cell homeostasis but also provides evidence that other hematopoietic cells are involved in this function. The identification of DCs fulfilling this role will enable future studies to better focus on mechanisms regulating T-cell homeostasis.

  1. 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.

  2. The Memory Function of the B Cell Antigen Receptor.

    PubMed

    Wienands, Jürgen; Engels, Niklas

    2016-01-01

    Activated B lymphocytes preserve their antigen experience by differentiating into long-lived pools of antibody-secreting plasma cells or various types of memory B cells (MBCs). The former population constantly produces serum immunoglobulins with sufficient specificity and affinity to thwart infections with recurrent pathogens. By contrast, memory B cell populations retain their antigen receptors on the cell surface and hence need pathogen-induced differentiation steps before they can actively contribute to host defense. The terminal differentiation of MBCs into antibody-secreting plasma cells is hallmarked by the absence of the lag phase characteristic for primary antibody responses. Moreover, secondary antibody responses are predominantly driven by MBCs that bear an antigen receptor of the IgG class on their surface although IgM-positive memory populations exist as well. These fundamental principles of B cell memory were enigmatic for decades. Only recently, we have begun to understand the underlying mechanisms. This review summarizes our current understanding of how different subpopulations of MBCs are generated during primary immune responses and how their functional heterogeneity on antigen recall is controlled by different signaling capabilities of B cell antigen receptor (BCR) isotypes and by the nature of the antigen.

  3. Memory.

    ERIC Educational Resources Information Center

    McKean, Kevin

    1983-01-01

    Discusses current research (including that involving amnesiacs and snails) into the nature of the memory process, differentiating between and providing examples of "fact" memory and "skill" memory. Suggests that three brain parts (thalamus, fornix, mammilary body) are involved in the memory process. (JN)

  4. Optimal memory configuration analysis in tri-hybrid solid-state drives with storage class memory and multi-level cell/triple-level cell NAND flash memory

    NASA Astrophysics Data System (ADS)

    Matsui, Chihiro; Yamada, Tomoaki; Sugiyama, Yusuke; Yamaga, Yusuke; Takeuchi, Ken

    2017-04-01

    This paper analyzes the best mix of memories in a tri-hybrid solid-state drive (SSD) with storage class memory (SCM) and multi-level cell (MLC)/triple-level cell (TLC) NAND flash memory. SCM is fast but its cost is high. Although MLC NAND flash memory is slow, it is more cost effective than SCM. For further cost efficiency, TLC NAND flash memory is denser and less expensive than MLC NAND flash. Performance of tri-hybrid SSD is evaluated in various memory configurations. Moreover, the optimum memory configuration is changed according to the application characteristics. If 10% cost increase is allowed compared to the MLC NAND flash only SSD, SCM/MLC NAND flash hybrid SSD provides the best performance with hot/random workload, whereas SCM/MLC/TLC NAND flash tri-hybrid SSD achieves the best for hot/sequential and cold/random workloads. In addition, it is possible to add long latency but low-cost SCM to the tri-hybrid SSD. As a result, tri-hybrid SSD with slow SCM achieves the best performance.

  5. Conditions of steady switching in phase-transition memory cells

    SciTech Connect

    Popov, A. I. Salnikov, S. M.; Anufriev, Yu. V.

    2015-04-15

    Three types of non-volatile memory cells of different designs based on phase transitions are developed and implemented. The effect of the design features of the cells and their active-region sizes on the switching characteristics and normal operation of the cells is considered as a whole. The causes of failure of the cells are analyzed from the obtained series of scanning electron images upon level-by-level etching of the samples. It is shown that the cell design is the most critical factor from the viewpoint of switching to the high-resistance state. The causes of this fact are analyzed and the criterion for providing the steady operation of cells of non-volatile memory based on phase transitions is formulated.

  6. Mechanical memory

    DOEpatents

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

    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.

  7. Mechanical memory

    DOEpatents

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

    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.

  8. The Vast Universe of T Cell Diversity: Subsets of Memory Cells and Their Differentiation.

    PubMed

    Jandus, Camilla; Usatorre, Amaia Martínez; Viganò, Selena; Zhang, Lianjun; Romero, Pedro

    2017-01-01

    The T cell receptor confers specificity for antigen recognition to T cells. By the first encounter with the cognate antigen, reactive T cells initiate a program of expansion and differentiation that will define not only the ultimate quantity of specific cells that will be generated, but more importantly their quality and functional heterogeneity. Recent achievements using mouse model infection systems have helped to shed light into the complex network of factors that dictate and sustain memory T cell differentiation, ranging from antigen load, TCR signal strength, metabolic fitness, transcriptional programs, and proliferative potential. The different models of memory T cell differentiation are discussed in this chapter, and key phenotypic and functional attributes of memory T cell subsets are presented, both for mouse and human cells. Therapeutic manipulation of memory T cell generation is expected to provide novel unique ways to optimize current immunotherapies, both in infection and cancer.

  9. Exploration of perpendicular magnetic anisotropy material system for application in spin transfer torque - Random access memory

    NASA Astrophysics Data System (ADS)

    Natarajarathinam, Anusha

    Perpendicular magnetic anisotropy (PMA) materials have unique advantages when used in magnetic tunnel junctions (MTJ) which are the most critical part of spin-torque transfer random access memory devices (STT-RAMs) that are being researched intensively as future non-volatile memory technology. They have high magnetoresistance which improves their sensitivity. The STT-RAM has several advantages over competing technologies, for instance, low power consumption, non-volatility, ultra-fast read and write speed and high endurance. In personal computers, it can replace SRAM for high-speed applications, Flash for non-volatility, and PSRAM and DRAM for high-speed program execution. The main aim of this research is to identify and optimize the best perpendicular magnetic anisotropy (PMA) material system for application to STT-RAM technology. Preliminary search for perpendicular magnetic anisotropy (PMA) materials for pinned layer for MTJs started with the exploration and optimization of crystalline alloys such as Co50Pd50 alloy, Mn50Al50 and amorphous alloys such as Tb21Fe72Co7 and are first presented in this work. Further optimization includes the study of Co/[Pd/Pt]x multilayers (ML), and the development of perpendicular synthetic antiferromagnets (SAF) utilizing these multilayers. Focused work on capping and seed layers to evaluate interfacial perpendicular anisotropy in free layers for pMTJs is then discussed. Optimization of the full perpendicular magnetic tunnel junction (pMTJ) includes the CoFeB/MgO/CoFeB trilayer coupled to a pinned/pinning layer with perpendicular Co/[Pd/Pt]x SAF and a thin Ta seeded CoFeB free layer. Magnetometry, simulations, annealing studies, transport measurements and TEM analysis on these samples will then be presented.

  10. Differential T cell receptor-mediated signaling in naive and memory CD4 T cells.

    PubMed

    Farber, D L; Acuto, O; Bottomly, K

    1997-08-01

    Naive and memory CD4 T cells differ in cell surface phenotype, function, activation requirements, and modes of regulation. To investigate the molecular bases for the dichotomies between naive and memory CD4 T cells and to understand how the T cell receptor (TCR) directs diverse functional outcomes, we investigated proximal signaling events triggered through the TCR/CD3 complex in naive and memory CD4 T cell subsets isolated on the basis of CD45 isoform expression. Naive CD4 T cells signal through TCR/CD3 similar to unseparated CD4 T cells, producing multiple tyrosine-phosphorylated protein species overall and phosphorylating the T cell-specific ZAP-70 tyrosine kinase which is recruited to the CD3zeta subunit of the TCR. Memory CD4 T cells, however, exhibit a unique pattern of signaling through TCR/CD3. Following stimulation through TCR/CD3, memory CD4 T cells produce fewer species of tyrosine-phosphorylated substrates and fail to phosphorylate ZAP-70, yet unphosphorylated ZAP-70 can associate with the TCR/CD3 complex. Moreover, a 26/28-kDa phosphorylated doublet is associated with CD3zeta in resting and activated memory but not in naive CD4 T cells. Despite these differences in the phosphorylation of ZAP-70 and CD3-associated proteins, the ZAP-70-related kinase, p72syk, exhibits similar phosphorylation in naive and memory T cell subsets, suggesting that this kinase could function in place of ZAP-70 in memory CD4 T cells. These results indicate that proximal signals are differentially coupled to the TCR in naive versus memory CD4 T cells, potentially leading to distinct downstream signaling events and ultimately to the diverse functions elicited by these two CD4 T cell subsets.

  11. A simple device unit consisting of all NiO storage and switch elements for multilevel terabit nonvolatile random access memory.

    PubMed

    Lee, Myoung-Jae; Ahn, Seung-Eon; Lee, Chang Bum; Kim, Chang-Jung; Jeon, Sanghun; Chung, U-In; Yoo, In-Kyeong; Park, Gyeong-Su; Han, Seungwu; Hwang, In Rok; Park, Bae-Ho

    2011-11-01

    Present charge-based silicon memories are unlikely to reach terabit densities because of scaling limits. As the feature size of memory shrinks to just tens of nanometers, there is insufficient volume available to store charge. Also, process temperatures higher than 800 °C make silicon incompatible with three-dimensional (3D) stacking structures. Here we present a device unit consisting of all NiO storage and switch elements for multilevel terabit nonvolatile random access memory using resistance switching. It is demonstrated that NiO films are scalable to around 30 nm and compatible with multilevel cell technology. The device unit can be a building block for 3D stacking structure because of its simple structure and constituent, high performance, and process temperature lower than 300 °C. Memory resistance switching of NiO storage element is accompanied by an increase in density of grain boundary while threshold resistance switching of NiO switch element is controlled by current flowing through NiO film.

  12. Tuning resistance states by thickness control in an electroforming-free nanometallic complementary resistance random access memory

    SciTech Connect

    Yang, Xiang; Lu, Yang; Lee, Jongho; Chen, I-Wei

    2016-01-04

    Tuning low resistance state is crucial for resistance random access memory (RRAM) that aims to achieve optimal read margin and design flexibility. By back-to-back stacking two nanometallic bipolar RRAMs with different thickness into a complementary structure, we have found that its low resistance can be reliably tuned over several orders of magnitude. Such high tunability originates from the exponential thickness dependence of the high resistance state of nanometallic RRAM, in which electron wave localization in a random network gives rise to the unique scaling behavior. The complementary nanometallic RRAM provides electroforming-free, multi-resistance-state, sub-100 ns switching capability with advantageous characteristics for memory arrays.

  13. Hoxb4 Overexpression in CD4 Memory Phenotype T Cells Increases the Central Memory Population upon Homeostatic Proliferation

    PubMed Central

    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. PMID:24324706

  14. Goal-directed access to mental objects in working memory: the role of task-specific feature retrieval.

    PubMed

    Schwager, Sabine; Hagendorf, Herbert

    2009-12-01

    In the present study, we examined the hypothesis of task-specific access to mental objects from verbal working memory. It is currently assumed that a mental object is brought into the focus of attention in working memory by a process of object selection, which provides this object for any upcoming mental operation (Oberauer, 2002). We argue that this view must be extended, since the selection of information for processing is always guided by current intentions and task goals. In our experiments, it was required that two kinds of comparison tasks be executed on digits selected from a set of three digits held in working memory. The tasks differed in regard to the object features the comparison was based on. Access to a new mental object (object switch) took consistently longer on the semantic comparison task than on the recognition task. This difference is not attributable to object selection difficulty and cannot be fully accounted for by task difficulty or differences in rehearsal processes. The results support our assumptions that (1) mental objects are selected for a given specific task and, so, are accessed with their specific task-relevant object features; (2) verbal mental objects outside the focus of attention are usually not maintained at a full feature level but are refreshed phonologically by subvocal rehearsal; and (3) if more than phonological information is required, access to mental objects involves feature retrieval processes in addition to object selection.

  15. Anomalous random telegraph noise and temporary phenomena in resistive random access memory

    NASA Astrophysics Data System (ADS)

    Puglisi, Francesco Maria; Larcher, Luca; Padovani, Andrea; Pavan, Paolo

    2016-11-01

    In this paper we present a comprehensive examination of the characteristics of complex Random Telegraph Noise (RTN) signals in Resistive Random Access Memory (RRAM) devices with TiN/Ti/HfO2/TiN structure. Initially, the anomalous RTN (aRTN) is investigated through careful systematic experiment, dedicated characterization procedures, and physics-based simulations to gain insights into the physics of this phenomenon. The experimentally observed RTN parameters (amplitude of the current fluctuations, capture and emission times) are analyzed in different operating conditions. Anomalous behaviors are characterized and their statistical characteristics are evaluated. Physics-based simulations considering both the Coulomb interactions among different defects in the device and the possible existence of defects with metastable states are exploited to suggest a possible physical origin of aRTN. The same simulation framework is also shown to be able to predict other temporary phenomena related to RTN, such as the temporary change in RTN stochastic properties or the sudden and iterative random appearing and vanishing of RTN fluctuations always exhibiting the same statistical characteristics. Results highlight the central role of the electrostatic interactions among individual defects and the trapped charge in describing RTN and related phenomena.

  16. Performance improvement of gadolinium oxide resistive random access memory treated by hydrogen plasma immersion ion implantation

    SciTech Connect

    Wang, Jer-Chyi Hsu, Chih-Hsien; Ye, Yu-Ren; Ai, Chi-Fong; Tsai, Wen-Fa

    2014-03-15

    Characteristics improvement of gadolinium oxide (Gd{sub x}O{sub y}) resistive random access memories (RRAMs) treated by hydrogen plasma immersion ion implantation (PIII) was investigated. With the hydrogen PIII treatment, the Gd{sub x}O{sub y} RRAMs exhibited low set/reset voltages and a high resistance ratio, which were attributed to the enhanced movement of oxygen ions within the Gd{sub x}O{sub y} films and the increased Schottky barrier height at Pt/Gd{sub x}O{sub y} interface, respectively. The resistive switching mechanism of Gd{sub x}O{sub y} RRAMs was dominated by Schottky emission, as proved by the area dependence of the resistance in the low resistance state. After the hydrogen PIII treatment, a retention time of more than 10{sup 4} s was achieved at an elevated measurement temperature. In addition, a stable cycling endurance with the resistance ratio of more than three orders of magnitude of the Gd{sub x}O{sub y} RRAMs can be obtained.

  17. High-Speed Optical Library System Using Digital Versatile Disk Random Access Memory

    NASA Astrophysics Data System (ADS)

    Tanabe, Takaya; Ura, Tetsu; Yamamoto, Manabu

    2000-02-01

    A high-data-transfer-rate optical storage system using a redundant array of inexpensive libraries (RAIL) has been developed and tested. It incorporates multiple libraries, where each library consists of dual digital versatile disk (DVD) random access memory (RAM) drives and a single robotic hand and holds 2.6 GB DVD disks. To increase the reliability of data storage and at the same time to eliminate the need for read-after-write verification, which doubles the recording time, a redundant array of inexpensive drives (RAID) 4 algorithm is implemented in the control unit of the storage system. Data sent by the host is transferred to a control unit, which stripes the data into five data groups plus one parity unit. The striped and parity data is sent to individual libraries and written to the DVD disks. This system writes and retrieves data with a transfer rate of approximately 6 MB/s, using write and read control methods that minimize the data striping overhead. This reliable library system can be used for networked multimedia applications.

  18. Single-crystalline CuO nanowires for resistive random access memory applications

    SciTech Connect

    Hong, Yi-Siang; Chen, Jui-Yuan; Huang, Chun-Wei; Chiu, Chung-Hua; Huang, Yu-Ting; Huang, Ting Kai; He, Ruo Shiuan; Wu, Wen-Wei

    2015-04-27

    Recently, the mechanism of resistive random access memory (RRAM) has been partly clarified and determined to be controlled by the forming and erasing of conducting filaments (CF). However, the size of the CF may restrict the application and development as devices are scaled down. In this work, we synthesized CuO nanowires (NW) (∼150 nm in diameter) to fabricate a CuO NW RRAM nanodevice that was much smaller than the filament (∼2 μm) observed in a bulk CuO RRAM device in a previous study. HRTEM indicated that the Cu{sub 2}O phase was generated after operation, which demonstrated that the filament could be minimize to as small as 3.8 nm when the device is scaled down. In addition, energy dispersive spectroscopy (EDS) and electron energy loss spectroscopy (EELS) show the resistive switching of the dielectric layer resulted from the aggregated oxygen vacancies, which also match with the I-V fitting results. Those results not only verify the switching mechanism of CuO RRAM but also show RRAM has the potential to shrink in size, which will be beneficial to the practical application of RRAM devices.

  19. Cu impurity in insulators and in metal-insulator-metal structures: Implications for resistance-switching random access memories

    SciTech Connect

    Pandey, Sumeet C. Meade, Roy; Sandhu, Gurtej S.

    2015-02-07

    We present numerical results from atomistic simulations of Cu in SiO{sub 2} and Al{sub 2}O{sub 3}, with an emphasis on the thermodynamic, kinetic, and electronic properties. The calculated properties of Cu impurity at various concentrations (9.91 × 10{sup 20 }cm{sup −3} and 3.41 × 10{sup 22 }cm{sup −3}) in bulk oxides are presented. The metal-insulator interfaces result in up to a ∼4 eV reduction in the formation energies relative to the crystalline bulk. Additionally, the importance of Cu-Cu interaction in lowering the chemical potential is introduced. These concepts are then discussed in the context of formation and stability of localized conductive paths in resistance-switching Random Access Memories (RRAM-M). The electronic density of states and non-equilibrium transmission through these localized paths are studied, confirming conduction by showing three orders of magnitude increase in the electron transmission. The dynamic behavior of the conductive paths is investigated with atomistic drift-diffusion calculations. Finally, the paper concludes with a molecular dynamics simulation of a RRAM-M cell that attempts to combine the aforementioned phenomena in one self-consistent model.

  20. Cu impurity in insulators and in metal-insulator-metal structures: Implications for resistance-switching random access memories

    NASA Astrophysics Data System (ADS)

    Pandey, Sumeet C.; Meade, Roy; Sandhu, Gurtej S.

    2015-02-01

    We present numerical results from atomistic simulations of Cu in SiO2 and Al2O3, with an emphasis on the thermodynamic, kinetic, and electronic properties. The calculated properties of Cu impurity at various concentrations (9.91 × 1020 cm-3 and 3.41 × 1022 cm-3) in bulk oxides are presented. The metal-insulator interfaces result in up to a ˜4 eV reduction in the formation energies relative to the crystalline bulk. Additionally, the importance of Cu-Cu interaction in lowering the chemical potential is introduced. These concepts are then discussed in the context of formation and stability of localized conductive paths in resistance-switching Random Access Memories (RRAM-M). The electronic density of states and non-equilibrium transmission through these localized paths are studied, confirming conduction by showing three orders of magnitude increase in the electron transmission. The dynamic behavior of the conductive paths is investigated with atomistic drift-diffusion calculations. Finally, the paper concludes with a molecular dynamics simulation of a RRAM-M cell that attempts to combine the aforementioned phenomena in one self-consistent model.

  1. Regulation and Maintenance of an Adoptive T-Cell Dependent Memory B Cell Pool

    PubMed Central

    Anson, Marie; Amado, Inês; Mailhé, Marie-Pierre; Donnadieu, Emmanuel; Garcia, Sylvie; Huetz, François; Freitas, Antonio A.

    2016-01-01

    We investigated the ability of monoclonal B cells to restore primary and secondary T-cell dependent antibody responses in adoptive immune-deficient hosts. Priming induced B cell activation and expansion, AID expression, antibody production and the generation of IgM+IgG- and IgM-IgG+ antigen-experienced B-cell subsets that persisted in the lymphopenic environment by cell division. Upon secondary transfer and recall the IgM-IgG+ cells responded by the production of antigen-specific IgG while the IgM+ memory cells secreted mainly IgM and little IgG, but generated new B cells expressing germinal center markers. The recall responses were more efficient if the antigenic boost was delayed suggesting that a period of adaptation is necessary before the transferred cells are able to respond. Overall these findings indicate that reconstitution of a functional and complete memory pool requires transfer of all different antigen-experienced B cell subsets. We also found that the size of the memory B cell pool did not rely on the number of the responding naïve B cells, suggesting autonomous homeostatic controls for naïve and memory B cells. By reconstituting a stable memory B cell pool in immune-deficient hosts using a monoclonal high-affinity B cell population we demonstrate the potential value of B cell adoptive immunotherapy. PMID:27880797

  2. Scalable Wordline Shielding Scheme using Dummy Cell beyond 40 nm NAND Flash Memory for Eliminating Abnormal Disturb of Edge Memory Cell

    NASA Astrophysics Data System (ADS)

    Park, Ki-Tae; Lee, SeungChul; Sel, Jong-Sun; Choi, Jungdal; Kim, Kinam

    2007-04-01

    A scalable wordline shielding scheme using dummy cell in NAND flash memory is presented to eliminate abnormal disturb of edge memory cell which causes to degradation of NAND flash performance. The proposed NAND flash is also able to improve more NAND scaling compared to conventional NAND string beyond sub-40 nm technology node. By using a proposed program scheme which includes an optimized bias voltage and adjusted Vth of dummy cell, almost abnormal disturbance of edge memory cell is removed and over 58% capacitive coupling noise between select transistor and edge memory cell can be reduced from both simulation and experimental results which used 63 nm NAND flash technology. The proposed NAND flash also improves Vth distribution of memory cell by providing almost equal operation conditions for all memory cells in NAND string.

  3. Human Memory B Cells in Healthy Gingiva, Gingivitis, and Periodontitis.

    PubMed

    Mahanonda, Rangsini; Champaiboon, Chantrakorn; Subbalekha, Keskanya; Sa-Ard-Iam, Noppadol; Rattanathammatada, Warattaya; Thawanaphong, Saranya; Rerkyen, Pimprapa; Yoshimura, Fuminobu; Nagano, Keiji; Lang, Niklaus P; Pichyangkul, Sathit

    2016-08-01

    The presence of inflammatory infiltrates with B cells, specifically plasma cells, is the hallmark of periodontitis lesions. The composition of these infiltrates in various stages of homeostasis and disease development is not well documented. Human tissue biopsies from sites with gingival health (n = 29), gingivitis (n = 8), and periodontitis (n = 21) as well as gingival tissue after treated periodontitis (n = 6) were obtained and analyzed for their composition of B cell subsets. Ag specificity, Ig secretion, and expression of receptor activator of NF-κB ligand and granzyme B were performed. Although most of the B cell subsets in healthy gingiva and gingivitis tissues were CD19(+)CD27(+)CD38(-) memory B cells, the major B cell component in periodontitis was CD19(+)CD27(+)CD38(+)CD138(+)HLA-DR(low) plasma cells, not plasmablasts. Plasma cell aggregates were observed at the base of the periodontal pocket and scattered throughout the gingiva, especially apically toward the advancing front of the lesion. High expression of CXCL12, a proliferation-inducing ligand, B cell-activating factor, IL-10, IL-6, and IL-21 molecules involved in local B cell responses was detected in both gingivitis and periodontitis tissues. Periodontitis tissue plasma cells mainly secreted IgG specific to periodontal pathogens and also expressed receptor activator of NF-κB ligand, a bone resorption cytokine. Memory B cells resided in the connective tissue subjacent to the junctional epithelium in healthy gingiva. This suggested a role of memory B cells in maintaining periodontal homeostasis.

  4. 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

  5. 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.

  6. Switched-memory B cells remodel B cell receptors within secondary germinal centers

    PubMed Central

    Okitsu, Shinji L.; McHeyzer-Williams, Michael G.

    2015-01-01

    Effective vaccines induce high-affinity memory B cells and durable antibody responses through accelerated mechanisms of natural selection. Secondary changes in antibody repertoires after vaccine boosts suggest progressive B cell receptor (BCR) re-diversification, but underlying mechanisms remain unresolved. Here integrated specificity and function of individual memory B cell progeny reveal ongoing evolution of polyclonal antibody specificities through germinal center (GC) specific transcriptional activity. At the clonal and sub-clonal levels, single cell expression of Cd83 and Pol□ segregates the secondary GC transcriptional program into 4 stages that regulate divergent mechanisms of memory BCR evolution. These studies demonstrate that vaccine boosts re-activate a cyclic program of GC function in switched-memory B cells to remodel existing antibody specificities and enhance durable immune protection. PMID:25642821

  7. Analysis of self-heating of thermally assisted spin-transfer torque magnetic random access memory.

    PubMed

    Deschenes, Austin; Muneer, Sadid; Akbulut, Mustafa; Gokirmak, Ali; Silva, Helena

    2016-01-01

    Thermal assistance has been shown to significantly reduce the required operation power for spin torque transfer magnetic random access memory (STT-MRAM). Proposed heating methods include modified material stack compositions that result in increased self-heating or external heat sources. In this work we analyze the self-heating process of a standard perpendicular magnetic anisotropy STT-MRAM device through numerical simulations in order to understand the relative contributions of Joule, thermoelectric Peltier and Thomson, and tunneling junction heating. A 2D rotationally symmetric numerical model is used to solve the coupled electro-thermal equations including thermoelectric effects and heat absorbed or released at the tunneling junction. We compare self-heating for different common passivation materials, positive and negative electrical current polarity, and different device thermal anchoring and boundaries resistance configurations. The variations considered are found to result in significant differences in maximum temperatures reached. Average increases of 3 K, 10 K, and 100 K for different passivation materials, positive and negative polarity, and different thermal anchoring configurations, respectively, are observed. The highest temperatures, up to 424 K, are obtained for silicon dioxide as the passivation material, positive polarity, and low thermal anchoring with thermal boundary resistance configurations. Interestingly it is also found that due to the tunneling heat, Peltier effect, device geometry, and numerous interfacial layers around the magnetic tunnel junction (MTJ), most of the heat is dissipated on the lower potential side of the magnetic junction. This asymmetry in heating, which has also been observed experimentally, is important as thermally assisted switching requires heating of the free layer specifically and this will be significantly different for the two polarity operations, set and reset.

  8. Analysis of self-heating of thermally assisted spin-transfer torque magnetic random access memory

    PubMed Central

    Muneer, Sadid; Akbulut, Mustafa; Gokirmak, Ali; Silva, Helena

    2016-01-01

    Thermal assistance has been shown to significantly reduce the required operation power for spin torque transfer magnetic random access memory (STT-MRAM). Proposed heating methods include modified material stack compositions that result in increased self-heating or external heat sources. In this work we analyze the self-heating process of a standard perpendicular magnetic anisotropy STT-MRAM device through numerical simulations in order to understand the relative contributions of Joule, thermoelectric Peltier and Thomson, and tunneling junction heating. A 2D rotationally symmetric numerical model is used to solve the coupled electro-thermal equations including thermoelectric effects and heat absorbed or released at the tunneling junction. We compare self-heating for different common passivation materials, positive and negative electrical current polarity, and different device thermal anchoring and boundaries resistance configurations. The variations considered are found to result in significant differences in maximum temperatures reached. Average increases of 3 K, 10 K, and 100 K for different passivation materials, positive and negative polarity, and different thermal anchoring configurations, respectively, are observed. The highest temperatures, up to 424 K, are obtained for silicon dioxide as the passivation material, positive polarity, and low thermal anchoring with thermal boundary resistance configurations. Interestingly it is also found that due to the tunneling heat, Peltier effect, device geometry, and numerous interfacial layers around the magnetic tunnel junction (MTJ), most of the heat is dissipated on the lower potential side of the magnetic junction. This asymmetry in heating, which has also been observed experimentally, is important as thermally assisted switching requires heating of the free layer specifically and this will be significantly different for the two polarity operations, set and reset. PMID:28144517

  9. Evaluating OpenSHMEM Explicit Remote Memory Access Operations and Merged Requests

    SciTech Connect

    Boehm, Swen; Pophale, Swaroop S; Gorentla Venkata, Manjunath

    2016-01-01

    The OpenSHMEM Library Specification has evolved consid- erably since version 1.0. Recently, non-blocking implicit Remote Memory Access (RMA) operations were introduced in OpenSHMEM 1.3. These provide a way to achieve better overlap between communication and computation. However, the implicit non-blocking operations do not pro- vide a separate handle to track and complete the individual RMA opera- tions. They are guaranteed to be completed after either a shmem quiet(), shmem barrier() or a shmem barrier all() is called. These are global com- pletion and synchronization operations. Though this semantic is expected to achieve a higher message rate for the applications, the drawback is that it does not allow fine-grained control over the completion of RMA operations. In this paper, first, we introduce non-blocking RMA operations with requests, where each operation has an explicit request to track and com- plete the operation. Second, we introduce interfaces to merge multiple requests into a single request handle. The merged request tracks multiple user-selected RMA operations, which provides the flexibility of tracking related communication operations with one request handle. Lastly, we explore the implications in terms of performance, productivity, usability and the possibility of defining different patterns of communication via merging of requests. Our experimental results show that a well designed and implemented OpenSHMEM stack can hide the overhead of allocating and managing the requests. The latency of RMA operations with requests is similar to blocking and implicit non-blocking RMA operations. We test our implementation with the Scalable Synthetic Compact Applications (SSCA #1) benchmark and observe that using RMA operations with requests and merging of these requests outperform the implementation using blocking RMA operations and implicit non-blocking operations by 49% and 74% respectively.

  10. Towards developing a compact model for magnetization switching in straintronics magnetic random access memory devices

    NASA Astrophysics Data System (ADS)

    Barangi, Mahmood; Erementchouk, Mikhail; Mazumder, Pinaki

    2016-08-01

    Strain-mediated magnetization switching in a magnetic tunneling junction (MTJ) by exploiting a combination of piezoelectricity and magnetostriction has been proposed as an energy efficient alternative to spin transfer torque (STT) and field induced magnetization switching methods in MTJ-based magnetic random access memories (MRAM). Theoretical studies have shown the inherent advantages of strain-assisted switching, and the dynamic response of the magnetization has been modeled using the Landau-Lifshitz-Gilbert (LLG) equation. However, an attempt to use LLG for simulating dynamics of individual elements in large-scale simulations of multi-megabyte straintronics MRAM leads to extremely time-consuming calculations. Hence, a compact analytical solution, predicting the flipping delay of the magnetization vector in the nanomagnet under stress, combined with a liberal approximation of the LLG dynamics in the straintronics MTJ, can lead to a simplified model of the device suited for fast large-scale simulations of multi-megabyte straintronics MRAMs. In this work, a tensor-based approach is developed to study the dynamic behavior of the stressed nanomagnet. First, using the developed method, the effect of stress on the switching behavior of the magnetization is investigated to realize the margins between the underdamped and overdamped regimes. The latter helps the designer realize the oscillatory behavior of the magnetization when settling along the minor axis, and the dependency of oscillations on the stress level and the damping factor. Next, a theoretical model to predict the flipping delay of the magnetization vector is developed and tested against LLG-based numerical simulations to confirm the accuracy of findings. Lastly, the obtained delay is incorporated into the approximate solutions of the LLG dynamics, in order to create a compact model to liberally and quickly simulate the magnetization dynamics of the MTJ under stress. Using the developed delay equation, the

  11. Inflammasome-Dependent Induction of Adaptive NK Cell Memory.

    PubMed

    van den Boorn, Jasper G; Jakobs, Christopher; Hagen, Christian; Renn, Marcel; Luiten, Rosalie M; Melief, Cornelis J M; Tüting, Thomas; Garbi, Natalio; Hartmann, Gunther; Hornung, Veit

    2016-06-21

    Monobenzone is a pro-hapten that is exclusively metabolized by melanocytes, thereby haptenizing melanocyte-specific antigens, which results in cytotoxic autoimmunity specifically against pigmented cells. Studying monobenzone in a setting of contact hypersensitivity (CHS), we observed that monobenzone induced a long-lasting, melanocyte-specific immune response that was dependent on NK cells, yet fully intact in the absence of T- and B cells. Consistent with the concept of "memory NK cells," monobenzone-induced NK cells resided in the liver and transfer of these cells conferred melanocyte-specific immunity to naive animals. Monobenzone-exposed skin displayed macrophage infiltration and cutaneous lymph nodes showed an inflammasome-dependent influx of macrophages with a tissue-resident phenotype, coinciding with local NK cell activation. Indeed, macrophage depletion or the absence of the NLRP3 inflammasome, the adaptor protein ASC or interleukin-18 (IL-18) abolished monobenzone CHS, thereby establishing a non-redundant role for the NLRP3 inflammasome as a critical proinflammatory checkpoint in the induction of hapten-dependent memory NK cells.

  12. Retrieval practice enhances the accessibility but not the quality of memory.

    PubMed

    Sutterer, David W; Awh, Edward

    2016-06-01

    Numerous studies have demonstrated that retrieval from long-term memory (LTM) can enhance subsequent memory performance, a phenomenon labeled the retrieval practice effect. However, the almost exclusive reliance on categorical stimuli in this literature leaves open a basic question about the nature of this improvement in memory performance. It has not yet been determined whether retrieval practice improves the probability of successful memory retrieval or the quality of the retrieved representation. To answer this question, we conducted three experiments using a mixture modeling approach (Zhang & Luck, 2008) that provides a measure of both the probability of recall and the quality of the recalled memories. Subjects attempted to memorize the color of 400 unique shapes. After every 10 images were presented, subjects either recalled the last 10 colors (the retrieval practice condition) by clicking on a color wheel with each shape as a retrieval cue or they participated in a control condition that involved no further presentations (Experiment 1) or restudy of the 10 shape/color associations (Experiments 2 and 3). Performance in a subsequent delayed recall test revealed a robust retrieval practice effect. Subjects recalled a significantly higher proportion of items that they had previously retrieved relative to items that were untested or that they had restudied. Interestingly, retrieval practice did not elicit any improvement in the precision of the retrieved memories. The same empirical pattern also was observed following delays of greater than 24 hours. Thus, retrieval practice increases the probability of successful memory retrieval but does not improve memory quality.

  13. Contexts and Control Operations Used in Accessing List-Specific, Generalized, and Semantic Memories

    ERIC Educational Resources Information Center

    Humphreys, Michael S.; Murray, Krista L.; Maguire, Angela M.

    2009-01-01

    The human ability to focus memory retrieval operations on a particular list, episode or memory structure has not been fully appreciated or documented. In Experiment 1-3, we make it increasingly difficult for participants to switch between a less recent list (multiple study opportunities), and a more recent list (single study opportunity). Task…

  14. Nuclear PKC-θ facilitates rapid transcriptional responses in human memory CD4+ T cells through p65 and H2B phosphorylation

    PubMed Central

    Li, Jasmine; Hardy, Kristine; Phetsouphanh, Chan; Tu, Wen Juan; Sutcliffe, Elissa L.; McCuaig, Robert; Sutton, Christopher R.; Zafar, Anjum; Munier, C. Mee Ling; Zaunders, John J.; Xu, Yin; Theodoratos, Angelo; Tan, Abel; Lim, Pek Siew; Knaute, Tobias; Masch, Antonia; Zerweck, Johannes; Brezar, Vedran; Milburn, Peter J.; Dunn, Jenny; Casarotto, Marco G.; Turner, Stephen J.; Seddiki, Nabila; Kelleher, Anthony D.

    2016-01-01

    ABSTRACT Memory T cells are characterized by their rapid transcriptional programs upon re-stimulation. This transcriptional memory response is facilitated by permissive chromatin, but exactly how the permissive epigenetic landscape in memory T cells integrates incoming stimulatory signals remains poorly understood. By genome-wide ChIP-sequencing ex vivo human CD4+ T cells, here, we show that the signaling enzyme, protein kinase C theta (PKC-θ) directly relays stimulatory signals to chromatin by binding to transcriptional-memory-responsive genes to induce transcriptional activation. Flanked by permissive histone modifications, these PKC-enriched regions are significantly enriched with NF-κB motifs in ex vivo bulk and vaccinia-responsive human memory CD4+ T cells. Within the nucleus, PKC-θ catalytic activity maintains the Ser536 phosphorylation on the p65 subunit of NF-κB (also known as RelA) and can directly influence chromatin accessibility at transcriptional memory genes by regulating H2B deposition through Ser32 phosphorylation. Furthermore, using a cytoplasm-restricted PKC-θ mutant, we highlight that chromatin-anchored PKC-θ integrates activating signals at the chromatin template to elicit transcriptional memory responses in human memory T cells. PMID:27149922

  15. 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.

  16. Self-compliance Pt/HfO2/Ti/Si one-diode-one-resistor resistive random access memory device and its low temperature characteristics

    NASA Astrophysics Data System (ADS)

    Lu, Chao; Yu, Jue; Chi, Xiao-Wei; Lin, Guang-Yang; Lan, Xiao-Ling; Huang, Wei; Wang, Jian-Yuan; Xu, Jian-Fang; Wang, Chen; Li, Cheng; Chen, Song-Yan; Liu, Chunli; Lai, Hong-Kai

    2016-04-01

    A bipolar one-diode-one-resistor (1D1R) device with a Pt/HfO2/Ti/n-Si(001) structure was demonstrated. The 1D1R resistive random access memory (RRAM) device consists of a Ti/n-Si(001) diode and a Pt/HfO2/Ti resistive switching cell. By using the Ti layer as the shared electrode for both the diode and the resistive switching cell, the 1D1R device exhibits the property of stable self-compliance and the characteristic of robust resistive switching with high uniformity. The high/low resistance ratio reaches 103. The electrical RESET/SET curve does not deteriorate after 68 loops. Low-temperature studies show that the 1D1R RRAM device has a critical working temperature of 250 K, and at temperatures below 250 K, the device fails to switch its resistances.

  17. CMOS Interface Circuits for Spin Tunneling Junction Based Magnetic Random Access Memories

    SciTech Connect

    Saripalli, Ganesh

    2002-01-01

    Magneto resistive memories (MRAM) are non-volatile memories which use magnetic instead of electrical structures to store data. These memories, apart from being non-volatile, offer a possibility to achieve densities better than DRAMs and speeds faster than SRAMs. MRAMs could potentially replace all computer memory RAM technologies in use today, leading to future applications like instan-on computers and longer battery life for pervasive devices. Such rapid development was made possible due to the recent discovery of large magnetoresistance in Spin tunneling junction devices. Spin tunneling junctions (STJ) are composite structures consisting of a thin insulating layer sandwiched between two magnetic layers. This thesis research is targeted towards these spin tunneling junction based Magnetic memories. In any memory, some kind of an interface circuit is needed to read the logic states. In this thesis, four such circuits are proposed and designed for Magnetic memories (MRAM). These circuits interface to the Spin tunneling junctions and act as sense amplifiers to read their magnetic states. The physical structure and functional characteristics of these circuits are discussed in this thesis. Mismatch effects on the circuits and proper design techniques are also presented. To demonstrate the functionality of these interface structures, test circuits were designed and fabricated in TSMC 0.35μ CMOS process. Also circuits to characterize the process mismatches were fabricated and tested. These results were then used in Matlab programs to aid in design process and to predict interface circuit's yields.

  18. Feasibility of a neutron detector-dosemeter based on single-event upsets in dynamic random-access memories.

    PubMed

    Phillips, G W; August, R A; Campbell, A B; Nelson, M E; Price, J L; Guardala, N A; Moscovitch, M

    2002-01-01

    The feasibility was investigated of a solid-state neutron detector/dosemeter based on single-event upset (SEU) effects in dynamic random-access memories (DRAMs), commonly used in computer memories. Such a device, which uses a neutron converter material to produce a charged particle capable of causing an upset, would be light-weight, low-power, and could be read simply by polling the memory for bit flips. It would have significant advantages over standard solid-state neutron dosemeters which require off-line processing for track etching and analysis. Previous efforts at developing an SEU neutron detector/dosemeter have suffered from poor response, which can be greatly enhanced by selecting a modern high-density DRAM chip for SEU sensitivity and by using a thin 10B film as a converter. Past attempts to use 10B were not successful because the average alpha particle energy was insufficient to penetrate to the sensitive region of the memory. This can be overcome by removing the surface passivation layer before depositing the 10B film or by implanting 10B directly into the chip. Previous experimental data show a 10(3) increase in neutron sensitivity by chips containing borosilicate glass, which could be used in an SEU detector. The results are presented of simulations showing that the absolute efficiency of an SEU neutron dosemeter can be increased by at least a factor of 1000 over earlier designs.

  19. Flexible resistive random access memory using NiOx/GaN microdisk arrays fabricated on graphene films.

    PubMed

    Lee, Keundong; Park, Jong-Woo; Tchoe, Youngbin; Yoon, Jiyoung; Chung, Kunook; Yoon, Hosang; Lee, Sangik; Yoon, Chansoo; Park, Bae; Yi, Gyu-Chul

    2017-03-17

    We report on flexible resistive random access memory (ReRAM) arrays fabricated using NiOx/GaN microdisk arrays on graphene films. The ReRAM device was created from discrete GaN microdisk arrays grown on graphene films produced by chemical vapor deposition, followed by deposition of NiOx thin layers and Au metal contacts. The microdisk ReRAM arrays were transferred to flexible plastic substrates by a simple lift-off technique. The electrical and memory characteristics of the ReRAM devices were investigated under bending conditions. Resistive switching characteristics, including cumulative probability, endurance, and retention, were measured. After 1000 bending repetitions, no significant change in the device characteristics was observed. The flexible ReRAM devices, constructed using only inorganic materials, operated reliably at temperatures as high as 180°C.

  20. Effector memory and central memory NY-ESO-1-specific re-directed T cells for treatment of multiple myeloma.

    PubMed

    Schuberth, P C; Jakka, G; Jensen, S M; Wadle, A; Gautschi, F; Haley, D; Haile, S; Mischo, A; Held, G; Thiel, M; Tinguely, M; Bifulco, C B; Fox, B A; Renner, C; Petrausch, U

    2013-04-01

    The cancer-testis antigen NY-ESO-1 is a potential target antigen for immune therapy expressed in a subset of patients with multiple myeloma. We generated chimeric antigen receptors (CARs) recognizing the immunodominant NY-ESO-1 peptide 157-165 in the context of HLA-A*02:01 to re-direct autologous CD8(+) T cells towards NY-ESO-1(+) myeloma cells. These re-directed T cells specifically lysed NY-ESO-1(157-165)/HLA-A*02:01-positive cells and secreted IFNγ. A total of 40% of CCR7(-) re-directed T cells had an effector memory phenotype and 5% a central memory phenotype. Based on CCR7 cell sorting, effector and memory CAR-positive T cells were separated and CCR7(+) memory cells demonstrated after antigen-specific re-stimulation downregulation of CCR7 as sign of differentiation towards effector cells accompanied by an increased secretion of memory signature cytokines such as IL-2. To evaluate NY-ESO-1 as potential target antigen, we screened 78 bone marrow biopsies of multiple myeloma patients where NY-ESO-1 protein was found to be expressed by immunohistochemistry in 9.7% of samples. Adoptively transferred NY-ESO-1-specific re-directed T cells protected mice against challenge with endogenously NY-ESO-1-positive myeloma cells in a xenograft model. In conclusion, re-directed effector- and central memory T cells specifically recognized NY-ESO-1(157-165)/ HLA-A*02:01-positive cells resulting in antigen-specific functionality in vitro and in vivo.

  1. Evidence for grid cells in a human memory network.

    PubMed

    Doeller, Christian F; Barry, Caswell; Burgess, Neil

    2010-02-04

    Grid cells in the entorhinal cortex of freely moving rats provide a strikingly periodic representation of self-location which is indicative of very specific computational mechanisms. However, the existence of grid cells in humans and their distribution throughout the brain are unknown. Here we show that the preferred firing directions of directionally modulated grid cells in rat entorhinal cortex are aligned with the grids, and that the spatial organization of grid-cell firing is more strongly apparent at faster than slower running speeds. Because the grids are also aligned with each other, we predicted a macroscopic signal visible to functional magnetic resonance imaging (fMRI) in humans. We then looked for this signal as participants explored a virtual reality environment, mimicking the rats' foraging task: fMRI activation and adaptation showing a speed-modulated six-fold rotational symmetry in running direction. The signal was found in a network of entorhinal/subicular, posterior and medial parietal, lateral temporal and medial prefrontal areas. The effect was strongest in right entorhinal cortex, and the coherence of the directional signal across entorhinal cortex correlated with spatial memory performance. Our study illustrates the potential power of combining single-unit electrophysiology with fMRI in systems neuroscience. Our results provide evidence for grid-cell-like representations in humans, and implicate a specific type of neural representation in a network of regions which supports spatial cognition and also autobiographical memory.

  2. Learning and memory: an emergent property of cell motility.

    PubMed

    Baudry, Michel; Bi, Xiaoning

    2013-09-01

    In this review, we develop the argument that the molecular/cellular mechanisms underlying learning and memory are an adaptation of the mechanisms used by all cells to regulate cell motility. Neuronal plasticity and more specifically synaptic plasticity are widely recognized as the processes by which information is stored in neuronal networks engaged during the acquisition of information. Evidence accumulated over the last 25 years regarding the molecular events underlying synaptic plasticity at excitatory synapses has shown the remarkable convergence between those events and those taking place in cells undergoing migration in response to extracellular signals. We further develop the thesis that the calcium-dependent protease, calpain, which we postulated over 25 years ago to play a critical role in learning and memory, plays a central role in the regulation of both cell motility and synaptic plasticity. The findings discussed in this review illustrate the general principle that fundamental cell biological processes are used for a wide range of functions at the level of organisms.

  3. Identification of Human Memory-Like NK Cells.

    PubMed

    Kovalenko, Elena I; Streltsova, Maria A; Kanevskiy, Leonid M; Erokhina, Sophia A; Telford, William G

    2017-01-05

    Our understanding of NK biology is increased dramatically, a product of improved flow-cytometric techniques for analyzing these cells. NK cells undergo significant changes in repertoire during differentiation. A repeating stimulus, such as a cytomegalovirus infection, may result in accumulation of certain types of highly differentiated NK cells designated as memory-like, or adaptive NK cells. Adaptive NK cells are capable of rapid expansion and effective response to the recall stimulus. These cells differ significantly from conventional NK cells both functionally and phenotypically. Here we describe an approach for identification and analysis of adaptive NK cells in human peripheral blood. CD57-positive cells with high expression of activating-receptor NKG2C, increased expression of KIR receptors, lack of co-expression with inhibitory receptor NKG2A, and decreased expression of activating receptor NCR3 (NKp30) all characterize this cell type. The flow-cytometric method described below can identify this NK cell subset on a relatively simple flow cytometer. © 2017 by John Wiley & Sons, Inc.

  4. Differential mechanisms of memory CD8 T cell maintenance by individual myeloid cell types

    PubMed Central

    Frasca, Loredana; Stonier, Spencer W.; Overwijk, Willem W.; Schluns, Kimberly S.

    2010-01-01

    This study tested the hypothesis that individual myeloid subsets have a differential ability to maintain memory CD8 T cells via IL-15. Although DCs support IL-15-mediated homeostasis of memory CD8 T cells in vivo, whether various DC subsets and other myeloid cells similarly mediate homeostasis is unknown. Therefore, we studied the ability of different myeloid cells to maintain memory CD8 T cells in vitro. Using an in vitro cocoulture system that recapitulated known roles of DCs and IL-15 on memory CD8 T cells, all in vitro-derived or ex vivo-isolated DCs maintained CD8 T cells better than rIL-15 alone, and FLT-3L-DCs are the most efficient compared with GM-DCs, BM-derived macrophages, or freshly isolated DCs. Although FLT-3L-DCs were the least effective at inducing CD8 T cell proliferation, FLT-3L-DCs promoted better CD8 T cell survival and increased Bcl-2 and MCL-2 expression in CD8 T cells. T cell maintenance correlated only partially with DC expression of IL-15Rα and IL-15, suggesting that DCs provided additional support signals. Indeed, in the absence of IL-15 signals, CD70/CD27 further supported CD8 T cell maintenance. IFN-α enhanced CD70 expression by DCs, resulting in increased proliferation of CD8 T cells. Overall, this study supports our hypothesis by demonstrating that specific DC subtypes had a greater capacity to support memory CD8 T cell maintenance and did so through different mechanisms. Furthermore, this study shows that IL-15 trans-presentation can work in conjunction with other signals, such as CD70/CD27 interactions, to mediate CD8 T cell homeostasis efficiently. PMID:20354106

  5. Memory Stem T Cells in Autoimmune Disease: High Frequency of Circulating CD8+ Memory Stem Cells in Acquired Aplastic Anemia.

    PubMed

    Hosokawa, Kohei; Muranski, Pawel; Feng, Xingmin; Townsley, Danielle M; Liu, Baoying; Knickelbein, Jared; Keyvanfar, Keyvan; Dumitriu, Bogdan; Ito, Sawa; Kajigaya, Sachiko; Taylor, James G; Kaplan, Mariana J; Nussenblatt, Robert B; Barrett, A John; O'Shea, John; Young, Neal S

    2016-02-15

    Memory stem T cells (TSCMs) constitute a long-lived, self-renewing lymphocyte population essential for the maintenance of functional immunity. Hallmarks of autoimmune disease pathogenesis are abnormal CD4(+) and CD8(+) T cell activation. We investigated the TSCM subset in 55, 34, 43, and 5 patients with acquired aplastic anemia (AA), autoimmune uveitis, systemic lupus erythematosus, and sickle cell disease, respectively, as well as in 41 age-matched healthy controls. CD8(+) TSCM frequency was significantly increased in AA compared with healthy controls. An increased CD8(+) TSCM frequency at diagnosis was associated with responsiveness to immunosuppressive therapy, and an elevated CD8(+) TSCM population after immunosuppressive therapy correlated with treatment failure or relapse in AA patients. IFN-γ and IL-2 production was significantly increased in various CD8(+) and CD4(+) T cell subsets in AA patients, including CD8(+) and CD4(+) TSCMs. CD8(+) TSCM frequency was also increased in patients with autoimmune uveitis or sickle cell disease. A positive correlation between CD4(+) and CD8(+) TSCM frequencies was found in AA, autoimmune uveitis, and systemic lupus erythematosus. Evaluation of PD-1, CD160, and CD244 expression revealed that TSCMs were less exhausted compared with other types of memory T cells. Our results suggest that the CD8(+) TSCM subset is a novel biomarker and a potential therapeutic target for AA.

  6. Memory Stem T Cells in Autoimmune Disease: High Frequency of Circulating CD8+ Memory Stem Cells in Acquired Aplastic Anemia

    PubMed Central

    Hosokawa, Kohei; Muranski, Pawel; Feng, Xingmin; Townsley, Danielle M.; Liu, Baoying; Knickelbein, Jared; Keyvanfar, Keyvan; Dumitriu, Bogdan; Ito, Sawa; Kajigaya, Sachiko; Taylor, James G.; Kaplan, Mariana J.; Nussenblatt, Robert B.; Barrett, A. John; O’Shea, John; Young, Neal S.

    2015-01-01

    Memory stem T cells (TSCMs) constitute a long-lived, self-renewing lymphocyte population essential for the maintenance of functional immunity. Hallmarks of autoimmune disease pathogenesis are abnormal CD4+ and CD8+ T cell activation. We investigated the TSCM subset in 55, 34, 43, and 5 patients with acquired aplastic anemia (AA), autoimmune uveitis, systemic lupus erythematosus, and sickle cell disease, respectively, as well as in 41 age-matched healthy controls. CD8+ TSCM frequency was significantly increased in AA compared with healthy controls. An increased CD8+ TSCM frequency at diagnosis was associated with responsiveness to immunosuppressive therapy, and an elevated CD8+ TSCM population after immunosuppressive therapy correlated with treatment failure or relapse in AA patients. IFN-γ and IL-2 production was significantly increased in various CD8+ and CD4+ T cell subsets in AA patients, including CD8+ and CD4+ TSCMs. CD8+ TSCM frequency was also increased in patients with autoimmune uveitis or sickle cell disease. A positive correlation between CD4+ and CD8+ TSCM frequencies was found in AA, autoimmune uveitis, and systemic lupus erythematosus. Evaluation of PD-1, CD160, and CD244 expression revealed that TSCMs were less exhausted compared with other types of memory T cells. Our results suggest that the CD8+ TSCM subset is a novel biomarker and a potential therapeutic target for AA. PMID:26764034

  7. Simultaneous Assessment of Rotavirus-Specific Memory B Cells and Serological Memory after B Cell Depletion Therapy with Rituximab

    PubMed Central

    Herrera, Daniel; Rojas, Olga L.; Duarte-Rey, Carolina; Mantilla, Rubén D.; Ángel, Juana; Franco, Manuel A.

    2014-01-01

    The mechanisms that contribute to the maintenance of serological memory are still unclear. Rotavirus (RV) memory B cells (mBc) are enriched in IgM+ and CD27- subpopulations, which are associated with autoimmune diseases pathogenesis. In patients with autoimmune diseases treated with Rituximab (RTX), some autoantibodies (auto-Abs) decrease after treatment, but other auto-Abs and pathogen-specific IgG Abs remain unchanged. Thus, maintenance of autoimmune and pathogen-specific serological memory may depend on the type of antigen and/or Ab isotype evaluated. Antigen-specific mBc and antigen-specific Abs of different isotypes have not been simultaneously assessed in patients after RTX treatment. To study the relationship between mBc subpopulations and serological memory we characterized total, RV- and tetanus toxoid (TT)-specific mBc by flow cytometry in patients with autoimmune diseases before and after treatment with RTX. We also measured total, RV- and TT-Abs, and some auto-Abs by kinetic nephelometry, ELISA, and EliA tests, respectively. Minor differences were observed between the relative frequencies of RV-mBc in healthy controls and patients with autoimmune disease. After RTX treatment, naïve Bc and total, RV- and TT-specific mBc [IgM+, switched (IgA+/IgG+), IgM+ only, IgD+ only, and CD27- (IgA+/IgG+/IgM+)] were significantly diminished. An important decrease in total plasma IgM and minor decreases in total IgG and IgA levels were also observed. IgM rheumatoid factor, IgG anti-CCP, and IgG anti-dsDNA were significantly diminished. In contrast, RV-IgA, RV-IgG and RV-IgG1, and TT-IgG titers remained stable. In conclusion, in patients with autoimmunity, serological memory against RV and TT seem to be maintained by long-lived plasma cells, unaffected by RTX, and an important proportion of total IgM and serological memory against some auto-antigens seem to be maintained by short-lived plasma cells, dependent on mBc precursors depleted by RTX. PMID:24819618

  8. Simultaneous assessment of rotavirus-specific memory B cells and serological memory after B cell depletion therapy with rituximab.

    PubMed

    Herrera, Daniel; Rojas, Olga L; Duarte-Rey, Carolina; Mantilla, Rubén D; Angel, Juana; Franco, Manuel A

    2014-01-01

    The mechanisms that contribute to the maintenance of serological memory are still unclear. Rotavirus (RV) memory B cells (mBc) are enriched in IgM(+) and CD27- subpopulations, which are associated with autoimmune diseases pathogenesis. In patients with autoimmune diseases treated with Rituximab (RTX), some autoantibodies (auto-Abs) decrease after treatment, but other auto-Abs and pathogen-specific IgG Abs remain unchanged. Thus, maintenance of autoimmune and pathogen-specific serological memory may depend on the type of antigen and/or Ab isotype evaluated. Antigen-specific mBc and antigen-specific Abs of different isotypes have not been simultaneously assessed in patients after RTX treatment. To study the relationship between mBc subpopulations and serological memory we characterized total, RV- and tetanus toxoid (TT)-specific mBc by flow cytometry in patients with autoimmune diseases before and after treatment with RTX. We also measured total, RV- and TT-Abs, and some auto-Abs by kinetic nephelometry, ELISA, and EliA tests, respectively. Minor differences were observed between the relative frequencies of RV-mBc in healthy controls and patients with autoimmune disease. After RTX treatment, naïve Bc and total, RV- and TT-specific mBc [IgM(+), switched (IgA(+)/IgG(+)), IgM(+) only, IgD(+) only, and CD27- (IgA(+)/IgG(+)/IgM(+))] were significantly diminished. An important decrease in total plasma IgM and minor decreases in total IgG and IgA levels were also observed. IgM rheumatoid factor, IgG anti-CCP, and IgG anti-dsDNA were significantly diminished. In contrast, RV-IgA, RV-IgG and RV-IgG1, and TT-IgG titers remained stable. In conclusion, in patients with autoimmunity, serological memory against RV and TT seem to be maintained by long-lived plasma cells, unaffected by RTX, and an important proportion of total IgM and serological memory against some auto-antigens seem to be maintained by short-lived plasma cells, dependent on mBc precursors depleted by RTX.

  9. Market access pathways for cell therapies in France

    PubMed Central

    Rémuzat, Cécile; Toumi, Mondher; Jørgensen, Jesper; Kefalas, Panos

    2015-01-01

    Introduction and objective Cell therapies can be classified into three main categories of products: advanced therapy medicinal products (ATMPs), ATMPs prepared on a non-routine basis (hospital exemptions), and minimally manipulated cells. Despite the benefits that cell therapies can bring to patients, they are subject to complex pathways to reach the market in France. The objective of this study was to identify and describe routes to market access for cell therapies in France and how these vary by regulatory status. Methodology The research was structured following five main steps: (1) identification of the French regulatory framework for cell therapies; (2) identification of the health products categorised as cell therapies in France; (3) mapping of the market access pathways per category of cell therapy; (4) validation of findings by interviewing experts; and (5) development of a roadmap summarising market access pathways for cell therapies in France. The secondary research methodology included a comprehensive literature review conducted on websites of French public health institutions, complemented by a research for peer-reviewed articles, abstracts, and grey literature. Results Different market access pathways are possible depending on the cell therapy category. For ATMPs, market access pathways depend on the licensing status of the therapy. Licensed ATMPs followed the same market access pathways as ‘conventional’ pharmaceuticals, whereas not-yet-licensed ATMPs can be funded via a specific financial allowance under the framework of a Temporary Authorisation for Use procedure or various research programmes. For new ATMPs that are associated with a separate medical device (not considered as ‘combined ATMPs’) or associated with a new medical procedure, additional pathways will apply for the medical device and/or medical procedure to be reimbursed in the ambulatory settings or at hospital. The most likely funding option for ATMPs prepared on a non

  10. Pediatric human immunodeficiency virus infection and circulating IgD+ memory B cells.

    PubMed

    Jacobsen, Marianne C; Thiébaut, Rodolphe; Fisher, Christopher; Sefe, Delali; Clapson, Margaret; Klein, Nigel; Baxendale, Helen E

    2008-08-15

    Levels of circulating naive and memory B cells were measured in human immunodeficiency virus (HIV)-infected children and control subjects to determine whether the irreversible depletion of memory B cells described in HIV-infected adults occurs in children with HIV infection. Depletion of circulating IgD+ memory B cells was seen in HIV-infected children despite control of the HIV load with highly active antiretroviral therapy (HAART) (P =. 04). IgD+ memory B cell percentages did not correlate with CD4+ cell percentages (P =. 027) or disease duration (P =. 026). Naive/transitional and IgD- memory B cell numbers were not affected. Pediatric HIV infection is associated with selective depletion of circulating IgD+ memory B cells despite control of the HIV load with HAART.

  11. Adjustable built-in resistor on oxygen-vacancy-rich electrode-capped resistance random access memory

    NASA Astrophysics Data System (ADS)

    Pan, Chih-Hung; Chang, Ting-Chang; Tsai, Tsung-Ming; Chang, Kuan-Chang; Chu, Tian-Jian; Chen, Po-Hsun; Chen, Min-Chen; Sze, Simon M.

    2016-10-01

    In this study, an adjustable built-in resistor was observed on an indium-tin oxide (ITO)-capped resistance random access memory (RRAM) device, which has the potential to reduce operating power. Quite notably, the high-resistance state (HRS) current of the device decreased with decreasing current compliance, and a special situation, that is, a gradual change in current always appears and climbs slowly to reach the compliance current in the set process even when the compliance current decreases, was observed. Owing to this observed phenomenon, the device is regarded to be equipped with an adjustable built-in resistor, which has the potential for low-power device application.

  12. Immune memory in CD4+ CD45RA+ T cells.

    PubMed Central

    Richards, D; Chapman, M D; Sasama, J; Lee, T H; Kemeny, D M

    1997-01-01

    This study addresses the question of whether human peripheral CD4+ CD45RA+ T cells possess antigen-specific immune memory. CD4+ CD45RA+ T cells were isolated by a combination of positive and negative selection. Putative CD4+ CD45RA+ cells expressed CD45RA (98.9%) and contained < 0.1% CD4+ CD45RO+ and < 0.5% CD4+ CD45RA+ CD45RO+ cells. Putative CD45RO+ cells expressed CD45RO (90%) and contained 9% CD45RA+ CD45RO+ and < 0.1% CD4+ CD45RA+ cells. The responder frequency of Dermatophagoides pteronyssinus-stimulated CD4+ CD45RA+ and CD4+ CD45RO+ T cells was determined in two atopic donors and found to be 1:11,314 and 1:8031 for CD4+ CD45RA+ and 1:1463 and 1:1408 for CD4+ CD45RO+ T cells. The responder frequencies of CD4+ CD45RA+ and CD4+ CD45RO+ T cells from two non-atopic, but exposed, donors were 1:78031 and 1:176,903 for CD4+ CD45RA+ and 1:9136 and 1:13,136 for CD4+ CD45RO+ T cells. T cells specific for D. pteronyssinus were cloned at limiting dilution following 10 days of bulk culture with D. pteronyssinus antigen. Sixty-eight clones were obtained from CD4+ CD45RO+ and 24 from CD4+ CD45RA+ T cells. All clones were CD3+ CD4+ CD45RO+ and proliferated in response to D. pteronyssinus antigens. Of 40 clones tested, none responded to Tubercule bacillus purified protein derivative (PPD). No difference was seen in the pattern of interleukin-4 (IL-4) or interferon-gamma (IFN-gamma) producing clones derived from CD4+ CD45RA+ and CD4+ CD45RO+ precursors, although freshly isolated and polyclonally activated CD4+ CD45RA+ T cells produced 20-30-fold lower levels of IL-4 and IFN-gamma than their CD4+ CD45RO+ counterparts. Sixty per cent of the clones used the same pool of V beta genes. These data support the hypothesis that immune memory resides in CD4+ CD45RA+ as well as CD4+ CD45RO+ T cells during the chronic immune response to inhaled antigen. PMID:9301520

  13. Towards scalable parellelism in Monte Carlo particle transport codes using remote memory access

    SciTech Connect

    Romano, Paul K; Brown, Forrest B; Forget, Benoit

    2010-01-01

    One forthcoming challenge in the area of high-performance computing is having the ability to run large-scale problems while coping with less memory per compute node. In this work, they investigate a novel data decomposition method that would allow Monte Carlo transport calculations to be performed on systems with limited memory per compute node. In this method, each compute node remotely retrieves a small set of geometry and cross-section data as needed and remotely accumulates local tallies when crossing the boundary of the local spatial domain. initial results demonstrate that while the method does allow large problems to be run in a memory-limited environment, achieving scalability may be difficult due to inefficiencies in the current implementation of RMA operations.

  14. Viral particles drive rapid differentiation of memory B cells into secondary plasma cells producing increased levels of antibodies.

    PubMed

    Zabel, Franziska; Mohanan, Deepa; Bessa, Juliana; Link, Alexander; Fettelschoss, Antonia; Saudan, Philippe; Kündig, Thomas M; Bachmann, Martin F

    2014-06-15

    Extensive studies have been undertaken to describe naive B cells differentiating into memory B cells at a cellular and molecular level. However, relatively little is known about the fate of memory B cells upon Ag re-encounter. We have previously established a system based on virus-like particles (VLPs), which allows tracking of VLP-specific B cells by flow cytometry as well as histology. Using allotype markers, it is possible to adoptively transfer memory B cells into a naive mouse and track responses of naive and memory B cells in the same mouse under physiological conditions. We have observed that VLP-specific memory B cells quickly differentiated into plasma cells that drove the early onset of a strong humoral IgG response. However, neither IgM(+) nor IgG(+) memory B cells proliferated extensively or entered germinal centers. Remarkably, plasma cells derived from memory B cells preferentially homed to the bone marrow earlier and secreted increased levels of Abs when compared with primary plasma cells derived from naive B cells. Hence, memory B cells have the unique phenotype to differentiate into highly effective secondary plasma cells.

  15. Rapid Recall Ability of Memory T cells is Encoded in their Epigenome

    PubMed Central

    Barski, Artem; Cuddapah, Suresh; Kartashov, Andrey V.; Liu, Chong; Imamichi, Hiromi; Yang, Wenjing; Peng, Weiqun; Lane, H. Clifford; Zhao, Keji

    2017-01-01

    Even though T-cell receptor (TCR) stimulation together with co-stimulation is sufficient for the activation of both naïve and memory T cells, the memory cells are capable of producing lineage specific cytokines much more rapidly than the naïve cells. The mechanisms behind this rapid recall response of the memory cells are still not completely understood. Here, we performed epigenetic profiling of human resting naïve, central and effector memory T cells using ChIP-Seq and found that unlike the naïve cells, the regulatory elements of the cytokine genes in the memory T cells are marked by activating histone modifications even in the resting state. Therefore, the ability to induce expression of rapid recall genes upon activation is associated with the deposition of positive histone modifications during memory T cell differentiation. We propose a model of T cell memory, in which immunological memory state is encoded epigenetically, through poising and transcriptional memory. PMID:28054639

  16. Quantitative assessment of the functional plasticity of memory CD8(+) T cells.

    PubMed

    Baz, Adriana; Groves, Penny; Buttigieg, Kathy; Apte, Simon H; Kienzle, Norbert; Kelso, Anne

    2016-04-01

    While the functional plasticity of memory CD4(+) T cells has been studied extensively, less is known about this property in memory CD8(+) T cells. Here, we report the direct measurement of plasticity by paired daughter analysis of effector and memory OT-I CD8(+) T cells primed in vivo with ovalbumin. Naïve, effector, and memory OT-I cells were isolated and activated in single-cell culture; then, after the first division, their daughter cells were transferred to new cultures with and without IL-4; expression of IFN-γ and IL-4 mRNAs was measured 5 days later in the resultant subclones. Approximately 40% of clonogenic memory CD8(+) T cells were bipotential in this assay, giving rise to an IL-4(-) subclone in the absence of IL-4 and an IL-4(+) subclone in the presence of IL-4. The frequency of bipotential cells was lower among memory cells than naïve cells but markedly higher than among 8-day effectors. Separation based on high or low expression of CD62L, CD122, CD127, or Ly6C did not identify a phenotypic marker of the bipotential cells. Functional plasticity in memory CD8(+) T-cell populations can therefore reflect modulation at the level of a single memory cell and its progeny.

  17. Overview of emerging nonvolatile memory technologies

    PubMed Central

    2014-01-01

    Nonvolatile memory technologies in Si-based electronics date back to the 1990s. Ferroelectric field-effect transistor (FeFET) was one of the most promising devices replacing the conventional Flash memory facing physical scaling limitations at those times. A variant of charge storage memory referred to as Flash memory is widely used in consumer electronic products such as cell phones and music players while NAND Flash-based solid-state disks (SSDs) are increasingly displacing hard disk drives as the primary storage device in laptops, desktops, and even data centers. The integration limit of Flash memories is approaching, and many new types of memory to replace conventional Flash memories have been proposed. Emerging memory technologies promise new memories to store more data at less cost than the expensive-to-build silicon chips used by popular consumer gadgets including digital cameras, cell phones and portable music players. They are being investigated and lead to the future as potential alternatives to existing memories in future computing systems. Emerging nonvolatile memory technologies such as magnetic random-access memory (MRAM), spin-transfer torque random-access memory (STT-RAM), ferroelectric random-access memory (FeRAM), phase-change memory (PCM), and resistive random-access memory (RRAM) combine the speed of static random-access memory (SRAM), the density of dynamic random-access memory (DRAM), and the nonvolatility of Flash memory and so become very attractive as another possibility for future memory hierarchies. Many other new classes of emerging memory technologies such as transparent and plastic, three-dimensional (3-D), and quantum dot memory technologies have also gained tremendous popularity in recent years. Subsequently, not an exaggeration to say that computer memory could soon earn the ultimate commercial validation for commercial scale-up and production the cheap plastic knockoff. Therefore, this review is devoted to the rapidly developing new

  18. The Aviation Careers Accessibility Program (ACAP) at Florida Memorial College. Final Report.

    ERIC Educational Resources Information Center

    Florida Memorial Coll., Miami.

    This project, referred to as the Aviation Careers Accessibility Program (ACAP) established a model program for inner-city minority high school students that would allow them information and accessibility to careers and opportunities in the aviation industry. The project featured two program components: an academic year component during and a 5- or…

  19. Realization of a reversible switching in TaO{sub 2} polymorphs via Peierls distortion for resistance random access memory

    SciTech Connect

    Zhu, Linggang; Sun, Zhimei; Zhou, Jian; Guo, Zhonglu

    2015-03-02

    Transition-metal-oxide based resistance random access memory (RRAM) is a promising candidate for next-generation universal non-volatile memories. Searching and designing appropriate materials used in the memories becomes an urgent task. Here, a structure with the TaO{sub 2} formula was predicted using evolutionary algorithms in combination with first-principles calculations. This triclinic structure (T-TaO{sub 2}) is both energetically and dynamically more favorable than the commonly believed rutile structure (R-TaO{sub 2}). The metal-insulator transition (MIT) between metallic R-TaO{sub 2} and T-TaO{sub 2} (band gap: 1.0 eV) is via a Peierls distortion, which makes TaO{sub 2} a potential candidate for RRAM. The energy barrier for the reversible phase transition is 0.19 eV/atom and 0.23 eV/atom, respectively, suggesting low power consumption for the resistance switch. The present findings about the MIT as the resistance-switch mechanism in Ta-O system will stimulate experimental work to fabricate tantalum oxides based RRAM.

  20. Perpendicular spin transfer torque magnetic random access memories with high spin torque efficiency and thermal stability for embedded applications (invited)

    NASA Astrophysics Data System (ADS)

    Thomas, Luc; Jan, Guenole; Zhu, Jian; Liu, Huanlong; Lee, Yuan-Jen; Le, Son; Tong, Ru-Ying; Pi, Keyu; Wang, Yu-Jen; Shen, Dongna; He, Renren; Haq, Jesmin; Teng, Jeffrey; Lam, Vinh; Huang, Kenlin; Zhong, Tom; Torng, Terry; Wang, Po-Kang

    2014-05-01

    Magnetic random access memories based on the spin transfer torque phenomenon (STT-MRAMs) have become one of the leading candidates for next generation memory applications. Among the many attractive features of this technology are its potential for high speed and endurance, read signal margin, low power consumption, scalability, and non-volatility. In this paper, we discuss our recent results on perpendicular STT-MRAM stack designs that show STT efficiency higher than 5 kBT/μA, energy barriers higher than 100 kBT at room temperature for sub-40 nm diameter devices, and tunnel magnetoresistance higher than 150%. We use both single device data and results from 8 Mb array to demonstrate data retention sufficient for automotive applications. Moreover, we also demonstrate for the first time thermal stability up to 400 °C exceeding the requirement of Si CMOS back-end processing, thus opening the realm of non-volatile embedded memory to STT-MRAM technology.

  1. Uncorrelated multiple conductive filament nucleation and rupture in ultra-thin high-κ dielectric based resistive random access memory

    NASA Astrophysics Data System (ADS)

    Wu, Xing; Li, Kun; Raghavan, Nagarajan; Bosman, Michel; Wang, Qing-Xiao; Cha, Dongkyu; Zhang, Xi-Xiang; Pey, Kin-Leong

    2011-08-01

    Resistive switching in transition metal oxides could form the basis for next-generation non-volatile memory (NVM). It has been reported that the current in the high-conductivity state of several technologically relevant oxide materials flows through localized filaments, but these filaments have been characterized only individually, limiting our understanding of the possibility of multiple conductive filaments nucleation and rupture and the correlation kinetics of their evolution. In this study, direct visualization of uncorrelated multiple conductive filaments in ultra-thin HfO2-based high-κ dielectric resistive random access memory (RRAM) device has been achieved by high-resolution transmission electron microscopy (HRTEM), along with electron energy loss spectroscopy (EELS), for nanoscale chemical analysis. The locations of these multiple filaments are found to be spatially uncorrelated. The evolution of these microstructural changes and chemical properties of these filaments will provide a fundamental understanding of the switching mechanism for RRAM in thin oxide films and pave way for the investigation into improving the stability and scalability of switching memory devices.

  2. The role of the local chemical environment of Ag on the resistive switching mechanism of conductive bridging random access memories.

    PubMed

    Souchier, E; D'Acapito, F; Noé, P; Blaise, P; Bernard, M; Jousseaume, V

    2015-10-07

    Conductive bridging random access memories (CBRAMs) are one of the most promising emerging technologies for the next generation of non-volatile memory. However, the lack of understanding of the switching mechanism at the nanoscale level prevents successful transfer to industry. In this paper, Ag/GeSx/W CBRAM devices are analyzed using depth selective X-ray Absorption Spectroscopy before and after switching. The study of the local environment around Ag atoms in such devices reveals that Ag is in two very distinct environments with short Ag-S bonds due to Ag dissolved in the GeSx matrix, and longer Ag-Ag bonds related to an Ag metallic phase. These experiments allow the conclusion that the switching process involves the formation of metallic Ag nano-filaments initiated at the Ag electrode. All these experimental features are well supported by ab initio molecular dynamics simulations showing that Ag favorably bonds to S atoms, and permit the proposal of a model at the microscopic level that can explain the instability of the conductive state in these Ag-GeSx CBRAM devices. Finally, the principle of the nondestructive method described here can be extended to other types of resistive memory concepts.

  3. Dimensional effect of non-polar resistive random access memory (RRAM) for low-power memory application.

    PubMed

    Ryoo, Kyung-Chang; Oh, Jeong-Hoon; Jung, Sunghun; Jeong, Hongsik; Park, Byung-Gook

    2012-07-01

    The relationships between the resistive cell dimension and the related analytical parameters such as the forming voltage, set voltage, and reset current were investigated to implement high-density and low-power unipolar RRAM. It was shown that the formation process in unipolar switching is strongly related to the cell dimension in the sub-nm region, not only in terms of its vertical thickness but also of its horizontal length, using the numerical simulation method. With the optimal cell size having sufficient initial resistance and a low forming voltage, the achievement of the greatest feasibility of the high-density low-power RRAM will be further accelerated. A numerical simulation was performed using a random circuit breaker (RCB) simulation model to investigate the optimal resistive switching condition. The on/off resistance ratio increases as the cell area decreases at the sub-nm level, and these phenomena are explained in terms of the relatively large set resistance change in a very small area due to the conductive defect (CD) amount effect in the RCB network model.

  4. [Co/Ni]-CoFeB hybrid free layer stack materials for high density magnetic random access memory applications

    NASA Astrophysics Data System (ADS)

    Liu, E.; Swerts, J.; Couet, S.; Mertens, S.; Tomczak, Y.; Lin, T.; Spampinato, V.; Franquet, A.; Van Elshocht, S.; Kar, G.; Furnemont, A.; De Boeck, J.

    2016-03-01

    Alternative free layer materials with high perpendicular anisotropy are researched to provide spin-transfer-torque magnetic random access memory stacks' sufficient thermal stability at critical dimensions of 20 nm and below. We demonstrate a high tunnel magetoresistance (TMR) MgO-based magnetic tunnel junction stack with a hybrid free layer design made of a [Co/Ni] multilayer and CoFeB. The seed material on which the [Co/Ni] multilayer is deposited determines its switching characteristics. When deposited on a Pt seed layer, soft magnetic switching behavior with high squareness is obtained. When deposited on a NiCr seed, the perpendicular anisotropy remains high, but the squareness is low and coercivity exceeds 1000 Oe. Interdiffusion of the seed material with the [Co/Ni] multilayers is found to be responsible for the different switching characteristics. In optimized stacks, a TMR of 165% and low resistance-area (RA) product of 7.0 Ω μm2 are attained for free layers with an effective perpendicular magnetic anisotropy energy of 1.25 erg/cm2, which suggests that the hybrid free layer materials may be a viable candidate for high density magnetic random access memory applications.

  5. In situ observation of nickel as an oxidizable electrode material for the solid-electrolyte-based resistive random access memory

    SciTech Connect

    Sun, Jun; Wu, Xing; Xu, Feng; Xu, Tao; Sun, Litao; Liu, Qi; Xie, Hongwei; Long, Shibing; Lv, Hangbing; Li, Yingtao; Liu, Ming

    2013-02-04

    In this letter, we dynamically investigate the resistive switching characteristics and physical mechanism of the Ni/ZrO{sub 2}/Pt device. The device shows stable bipolar resistive switching behaviors after forming process, which is similar to the Ag/ZrO{sub 2}/Pt and Cu/ZrO{sub 2}/Pt devices. Using in situ transmission electron microscopy, we observe in real time that several conductive filaments are formed across the ZrO{sub 2} layer between Ni and Pt electrodes after forming. Energy-dispersive X-ray spectroscopy results confirm that Ni is the main composition of the conductive filaments. The ON-state resistance increases with increasing temperature, exhibiting the feature of metallic conduction. In addition, the calculated resistance temperature coefficient is equal to that of the 10-30 nm diameter Ni nanowire, further indicating that the nanoscale Ni conductive bridge is the physical origin of the observed conductive filaments. The resistive switching characteristics and the conductive filament's component of Ni/ZrO{sub 2}/Pt device are consistent with the characteristics of the typical solid-electrolyte-based resistive random access memory. Therefore, aside from Cu and Ag, Ni can also be used as an oxidizable electrode material for resistive random access memory applications.

  6. Role of Memory T Cells and Perspectives for Intervention in Organ Transplantation

    PubMed Central

    Lin, Kailin; Chen, Song; Chen, Gang

    2015-01-01

    Memory T cells are necessary for protective immunity against invading pathogens, especially under conditions of immunosuppression. However, their presence also threatens transplant survival, making transplantation a great challenge. Significant progress has been achieved in recent years in advancing our understanding of the role that memory T cells play in transplantation. This review focuses on the latest advances in our understanding of the involvement of memory T cells in graft rejection and transplant tolerance and discusses potential strategies for targeting memory T cells in order to minimize allograft rejection and optimize clinical outcomes. PMID:26441978

  7. Rapid erasure of hippocampal memory following inhibition of dentate gyrus granule cells

    PubMed Central

    Madroñal, Noelia; Delgado-García, José M.; Fernández-Guizán, Azahara; Chatterjee, Jayanta; Köhn, Maja; Mattucci, Camilla; Jain, Apar; Tsetsenis, Theodoros; Illarionova, Anna; Grinevich, Valery; Gross, Cornelius T.; Gruart, Agnès

    2016-01-01

    The hippocampus is critical for the acquisition and retrieval of episodic and contextual memories. Lesions of the dentate gyrus, a principal input of the hippocampus, block memory acquisition, but it remains unclear whether this region also plays a role in memory retrieval. Here we combine cell-type specific neural inhibition with electrophysiological measurements of learning-associated plasticity in behaving mice to demonstrate that dentate gyrus granule cells are not required for memory retrieval, but instead have an unexpected role in memory maintenance. Furthermore, we demonstrate the translational potential of our findings by showing that pharmacological activation of an endogenous inhibitory receptor expressed selectively in dentate gyrus granule cells can induce a rapid loss of hippocampal memory. These findings open a new avenue for the targeted erasure of episodic and contextual memories. PMID:26988806

  8. Respecting Relations: Memory Access and Antecedent Retrieval in Incremental Sentence Processing

    ERIC Educational Resources Information Center

    Kush, Dave W.

    2013-01-01

    This dissertation uses the processing of anaphoric relations to probe how linguistic information is encoded in and retrieved from memory during real-time sentence comprehension. More specifically, the dissertation attempts to resolve a tension between the demands of a linguistic processor implemented in a general-purpose cognitive architecture and…

  9. Hyperlink Format, Categorization Abilities and Memory Span as Contributors to Deaf Users Hypertext Access

    ERIC Educational Resources Information Center

    Farjardo, Inmaculada; Arfe, Barbara; Benedetti, Patrizia; Altoe, Gianmarco

    2008-01-01

    Sixty deaf and hearing students were asked to search for goods in a Hypertext Supermarket with either graphical or textual links of high typicality, frequency, and familiarity. Additionally, they performed a picture and word categorization task and two working memory span tasks (spatial and verbal). Results showed that deaf students were faster in…

  10. Memories.

    ERIC Educational Resources Information Center

    Brand, Judith, Ed.

    1998-01-01

    This theme issue of the journal "Exploring" covers the topic of "memories" and describes an exhibition at San Francisco's Exploratorium that ran from May 22, 1998 through January 1999 and that contained over 40 hands-on exhibits, demonstrations, artworks, images, sounds, smells, and tastes that demonstrated and depicted the biological,…

  11. Memory CD4+ T cells are suppressed by CD8+ regulatory T cells in vitro and in vivo

    PubMed Central

    Long, Xin; Cheng, Qi; Liang, Huifang; Zhao, Jianping; Wang, Jian; Wang, Wei; Tomlinson, Stephen; Chen, Lin; Atkinson, Carl; Zhang, Bixiang; Chen, Xiaoping; Zhu, Peng

    2017-01-01

    Background: Acute graft rejection mediated by alloreactive memory CD4+ T cells is a major obstacle to transplantation tolerance. It has been reported that CD8+ T regulatory cells (Tregs) have the ability to induce graft tolerance by restraining the function of activated CD4+ T cells, but not including memory T cells. The aim of this study is to elucidate the effect of CD8+ Tregs on alloreactive memory CD4+ T cells. Methods: We detected Qa-1 expression and performed proliferative assay on memory CD4+ T cells. All memory CD4+ T cells were purified from mice receiving skin allografts. We performed inhibitory and cytotoxic assays on CD8+ Tregs, which were isolated from a T cell vaccination mouse model, and IL-2, IL-4, IL-10 and IFN-γ levels were measured in co-culture supernatants by ELISA. To confirm CD8+ Tregs inhibition of memory CD4+ T cells in-vivo, we utilized a murine model of cardiac allograft transplantation. Results: Memory CD4+ T cells mediated acute allograft rejection, and CD8+ Tregs suppressed the proliferation of memory CD4+ T cells. In vitro, memory CD4+ T cells were inhibited and lysed by CD8+ Tregs. There was a positive correlation between IFN-γ levels, and cell lysis rate induced by CD8+ Tregs. In-vivo studies demonstrated CD8+ Tregs prolonged graft survival times, by inhibiting CD4+ memory T cells, through a Qa-1-peptide-TCR pathway. Conclusions: CD8+ Tregs inhibit CD4+ memory T cell-mediated acute murine cardiac allograft rejection, and further prolong graft survival times. These results provide new insights into immune regulation of organ rejection. PMID:28123634

  12. Accessibility

    EPA Pesticide Factsheets

    Federal laws, including Section 508 of the Rehabilitation Act, mandate that people with disabilities have access to the same information that someone without a disability would have. 508 standards cover electronic and information technology (EIT) products.

  13. The role of OX40 (CD134) in T-cell memory generation.

    PubMed

    Weinberg, Andrew D

    2010-01-01

    Memory T-cell generation is limited by activation-induced cell death during the effector T-cell stage. Cell surface proteins are known to transmit signals that either accentuate or limit T-cell death after activation. This chapter will focus on the TNF-receptor family member OX40, which is expressed on effector T cells and when engaged greatly enhances survival of T cells leading to increased memory T-cell generation. Targeting OX40 in vivo can alter the fate ofT-cell survival. Enhancing OX40 signaling during Ag priming through agonists increases memory T-cell development, while blocking OX40 signaling decreases the memory T-cell pool. These two opposing outcomes provide therapeutic tools for blocking inflammation in autoimmune conditions and enhancing immunity in hosts harboring cancer or chronic pathogens. OX40 agonists and antagonists are in the first stages of human clinical trials and their therapeutic potential will soon be realized.

  14. CXCR5+ CCR7- CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles.

    PubMed

    Quigley, Máire F; Gonzalez, Veronica D; Granath, Anna; Andersson, Jan; Sandberg, Johan K

    2007-12-01

    Naive and central memory CD8 T cells use CCR7 to recirculate through T cell zones of secondary lymphoid organs where they can encounter antigen. Here we describe a subset of human CD8 T cells expressing CXCR5 which enables homing in response to CXCL13 produced within B cell follicles. CXCR5+ CD8 T cells were found in tonsil B cell follicles, and isolated cells migrated towards CXCL13 in vitro. They expressed CD27, CD28, CD45RO, CD69, and were CD7low, and produced IFN-gamma and granzyme A but lacked perforin, a functional profile suggesting that these cells are early effector memory cells in the context of contemporary T cell differentiation models. Receptors important in the interaction with B cells, including CD70, OX40 and ICOS, were induced upon activation, and CXCR5+ CD8 T cells could to some extent support survival and IgG production in tonsil B cells. Furthermore, CXCR5+ CD8 T cells expressed CCR5 but no CCR7, suggesting a migration pattern distinct from that of follicular CD4 T cells. The finding that a subset of early effector memory CD8 T cells use CXCR5 to locate to B cell follicles indicates that MHC class I-restricted CD8 T cells are part of the follicular T cell population.

  15. Gut memories do not fade: epigenetic regulation of lasting gut homing receptor expression in CD4(+) memory T cells.

    PubMed

    Szilagyi, B A; Triebus, J; Kressler, C; de Almeida, M; Tierling, S; Durek, P; Mardahl, M; Szilagyi, A; Floess, S; Huehn, J; Syrbe, U; Walter, J; Polansky, J K; Hamann, A

    2017-02-15

    The concept of a "topographical memory" in lymphocytes implies a stable expression of homing receptors mediating trafficking of lymphocytes back to the tissue of initial activation. However, a significant plasticity of the gut-homing receptor α4β7 was found in CD8(+) T cells, questioning the concept. We now demonstrate that α4β7 expression in murine CD4(+) memory T cells is, in contrast, imprinted and remains stable in the absence of the inducing factor retinoic acid (RA) or other stimuli from mucosal environments. Repetitive rounds of RA treatment enhanced the stability of de novo induced α4β7. A novel enhancer element in the murine Itga4 locus was identified that showed, correlating to stability, selective DNA demethylation in mucosa-seeking memory cells and methylation-dependent transcriptional activity in a reporter gene assay. This implies that epigenetic mechanisms contribute to the stabilization of α4β7 expression. Analogous DNA methylation patterns could be observed in the human ITGA4 locus, suggesting that its epigenetic regulation is conserved between mice and men. These data prove that mucosa-specific homing mediated by α4β7 is imprinted in CD4(+) memory T cells, reinstating the validity of the concept of "topographical memory" for mucosal tissues, and imply a critical role of epigenetic mechanisms.Mucosal Immunology advance online publication 15 February 2017. doi:10.1038/mi.2017.7.

  16. Theoretical study of SET operation in carbon nanotube memory cell

    NASA Astrophysics Data System (ADS)

    Stopa, Michael; Rueckes, Thomas

    2016-04-01

    We present results of self-consistent electronic structure calculations for an electromechanical memory cell consisting of a carbon nanotube (CNT) fabric between titanium leads to elucidate the mechanism whereby the applied bias works to close the current gaps in the CNT fabric. We demonstrate that the asymmetry in the bias conditions required to achieve the “SET” operation of the cell (changing it from a high resistivity to low resistivity) results from the nature of a voltage drop in a compensated semiconducting material and depends sensitively on the background charge as well as on the position of the layer where the conducting gaps occur. The calculations provide insight into the behavior of the material and suggest possible fabrication strategies to modify the functionality.

  17. Influenza and Memory T Cells: How to Awake the Force

    PubMed Central

    Spitaels, Jan; Roose, Kenny; Saelens, Xavier

    2016-01-01

    Annual influenza vaccination is an effective way to prevent human influenza. Current vaccines are mainly focused on eliciting a strain-matched humoral immune response, requiring yearly updates, and do not provide protection for all vaccinated individuals. The past few years, the importance of cellular immunity, and especially memory T cells, in long-lived protection against influenza virus has become clear. To overcome the shortcomings of current influenza vaccines, eliciting both humoral and cellular immunity is imperative. Today, several new vaccines such as infection-permissive and recombinant T cell inducing vaccines, are being developed and show promising results. These vaccines will allow us to stay several steps ahead of the constantly evolving influenza virus. PMID:27754364

  18. Landscape of monoallelic DNA accessibility in mouse embryonic stem cells and neural progenitor cells

    PubMed Central

    Xu, Jin; Carter, Ava C; Gendrel, Anne-Valerie; Attia, Mikael; Loftus, Joshua; Greenleaf, William J; Tibshirani, Robert; Heard, Edith; Chang, Howard Y

    2017-01-01

    We developed an allele-specific assay for transposase-accessible chromatin with high-throughput sequencing (ATAC–seq) to genotype and profile active regulatory DNA across the genome. Using a mouse hybrid F1 system, we found that monoallelic DNA accessibility across autosomes was pervasive, developmentally programmed and composed of several patterns. Genetically determined accessibility was enriched at distal enhancers, but random monoallelically accessible (RAMA) elements were enriched at promoters and may act as gatekeepers of monoallelic mRNA expression. Allelic choice at RAMA elements was stable across cell generations and bookmarked through mitosis. RAMA elements in neural progenitor cells were biallelically accessible in embryonic stem cells but premarked with bivalent histone modifications; one allele was silenced during differentiation. Quantitative analysis indicated that allelic choice at the majority of RAMA elements is consistent with a stochastic process; however, up to 30% of RAMA elements may deviate from the expected pattern, suggesting a regulated or counting mechanism. PMID:28112738

  19. Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease

    PubMed Central

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

    2016-01-01

    Summary Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory decline and subsequent loss of broader cognitive functions1. Memory decline in early stages of Alzheimer’s is mostly limited to episodic memory, for which the hippocampus (HPC) plays a crucial role2. However, it has been uncertain whether the observed amnesia in early stages of Alzheimer’s 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 Alzheimer’s, 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 utilized, revealing a retrieval, rather than a storage impairment. Prior to amyloid plaque deposition, the amnesia in these mice is age-dependent3–5, which correlates with a progressive reduction of spine density of hippocampal dentate gyrus (DG) engram cells. We show that optogenetic induction of long-term potentiation (LTP) at perforant path (PP) synapses of DG engram cells restores both spine density and long-term memory. We also demonstrate that an ablation of DG 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 early stages of Alzheimer’s disease. PMID:26982728

  20. An energy-efficient SIMD DSP with multiple VLIW configurations and an advanced memory access unit for LTE-A modem LSIs

    NASA Astrophysics Data System (ADS)

    Tomono, Mitsuru; Ito, Makiko; Nomura, Yoshitaka; Mouri, Makoto; Hirose, Yoshio

    2015-12-01

    Energy efficiency is the most important factor in the design of wireless modem LSIs for mobile handset systems. We have developed an energy-efficient SIMD DSP for LTE-A modem LSIs. Our DSP has mainly two hardware features in order to reduce energy consumption. The first one is multiple VLIW configurations to minimize accesses to instruction memories. The second one is an advanced memory access unit to realize complex memory accesses required for wireless baseband processing. With these features, performance of our DSP is about 1.7 times faster than a base DSP on average for standard LTE-A Libraries. Our DSP achieves about 20% improvement in energy efficiency compared to a base DSP for LTE-A modem LSIs.

  1. Mcl-1 regulates effector and memory CD8 T-cell differentiation during acute viral infection.

    PubMed

    Kim, Eui Ho; Neldner, Brandon; Gui, Jingang; Craig, Ruth W; Suresh, M

    2016-03-01

    Mcl-1, an anti-apoptotic member of Bcl-2 family maintains cell viability during clonal expansion of CD8 T cells, but the cell intrinsic role of Mcl-1 in contraction of effectors or the number of memory CD8 T cells is unknown. Mcl-1 levels decline during the contraction phase but rebound to high levels in memory CD8 T cells. Therefore, by overexpressing Mcl-1 in CD8 T cells we asked whether limiting levels of Mcl-1 promote contraction of effectors and constrain CD8 T-cell memory. Mcl-1 overexpression failed to affect CD8 T-cell expansion, contraction or the magnitude of CD8 T-cell memory. Strikingly, high Mcl-1 levels enhanced mTOR phosphorylation and augmented the differentiation of terminal effector cells and effector memory CD8 T cells to the detriment of poly-cytokine-producing central memory CD8 T cells. Taken together, these findings provided unexpected insights into the role of Mcl-1 in the differentiation of effector and memory CD8 T cells.

  2. On EMDR: eye movements during retrieval reduce subjective vividness and objective memory accessibility during future recall.

    PubMed

    van den Hout, Marcel A; Bartelski, Nicola; Engelhard, Iris M

    2013-01-01

    In eye movement desensitization and reprocessing (EMDR), a treatment for post-traumatic stress disorder (PTSD), patients make eye movements (EM) during trauma recall. Earlier experimental studies found that EM during recall reduces memory vividness during future recalls, and this was taken as laboratory support for the underlying mechanism of EMDR. However, reduced vividness was assessed with self-reports that may be affected by demand characteristics. We tested whether recall+EM also reduces memory vividness on a behavioural reaction time (RT) task. Undergraduates (N=32) encoded two pictures, recalled them, and rated their vividness. In the EM group, one of the pictures was recalled again while making EM. In the no-EM group one of the pictures was recalled without EM. Then fragments from both the recalled and non-recalled pictures, and new fragments were presented and participants rated whether these were (or were not) seen before. Both pictures were rated again for vividness. In the EM group, self-rated vividness of the recalled+EM picture decreased, relative to the non-recalled picture. In the no-EM group there was no difference between the recalled versus non-recalled picture. The RT task showed the same pattern. Reduction of memory vividness due to recall+EM is also evident from non-self-report data.

  3. 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

  4. 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

  5. IgG-Immune Complexes Promote B Cell Memory by Inducing BAFF.

    PubMed

    Kang, SunAh; Keener, Amanda B; Jones, Shannon Z; Benschop, Robert J; Caro-Maldonado, Alfredo; Rathmell, Jeffrey C; Clarke, Stephen H; Matsushima, Glenn K; Whitmire, Jason K; Vilen, Barbara J

    2016-01-01

    Memory B cell responses are vital for protection against infections but must also be regulated to prevent autoimmunity. Cognate T cell help, somatic hypermutation, and affinity maturation within germinal centers (GCs) are required for high-affinity memory B cell formation; however, the signals that commit GC B cells to the memory pool remain unclear. In this study, we identify a role for IgG-immune complexes (ICs), FcγRs, and BAFF during the formation of memory B cells in mice. We found that early secretion of IgG in response to immunization with a T-dependent Ag leads to IC-FcγR interactions that induce dendritic cells to secrete BAFF, which acts at or upstream of Bcl-6 in activated B cells. Loss of CD16, hematopoietic cell-derived BAFF, or blocking IC:FcγR regions in vivo diminished the expression of Bcl-6, the frequency of GC and memory B cells, and secondary Ab responses. BAFF also contributed to the maintenance and/or expansion of the follicular helper T cell population, although it was dispensable for their formation. Thus, early Ab responses contribute to the optimal formation of B cell memory through IgG-ICs and BAFF. Our work defines a new role for FcγRs in GC and memory B cell responses.

  6. Interleukin-21 Drives Proliferation and Differentiation of Porcine Memory B Cells into Antibody Secreting Cells

    PubMed Central

    Murtaugh, Michael P.

    2017-01-01

    Immunological prevention of infectious disease, especially viral, is based on antigen-specific long-lived memory B cells. To test for cellular proliferation and differentiation factors in swine, an outbred model for humans, CD21+ B cells were activated in vitro with CD40L and stimulated with purported stimulatory cytokines to characterize functional responses. IL-21 induced a 3-fold expansion in total cell numbers with roughly 15% of all B cells differentiating to IgM or IgG antibody secreting cells (ASCs.) However, even with robust proliferation, cellular viability rapidly deteriorated. Therefore, a proliferation inducing ligand (APRIL) and B cell activating factor (BAFF) were evaluated as survival and maintenance factors. BAFF was effective at enhancing the viability of mature B cells as well as ASCs, while APRIL was only effective for ASCs. Both cytokines increased approximately two-fold the amount of IgM and IgG which was secreted by IL-21 differentiated ASCs. Mature B cells from porcine reproductive and respiratory virus (PRRSV) immune and naïve age-matched pigs were activated and treated with IL-21 and then tested for memory cell differentiation using a PRRSV non-structural protein 7 ELISPOT and ELISA. PRRSV immune pigs were positive on both ELISPOT and ELISA while naïve animals were negative on both assays. These results highlight the IL-21-driven expansion and differentiation of memory B cells in vitro without stimulation of the surface immunoglobulin receptor complex, as well as the establishment of a defined memory B cell culture system for characterization of vaccine responses in outbred animals. PMID:28125737

  7. 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…

  8. Bone Marrow T Cells and the Integrated Functions of Recirculating and Tissue-Resident Memory T Cells

    PubMed Central

    Di Rosa, Francesca; Gebhardt, Thomas

    2016-01-01

    Changes in T cell trafficking accompany the naive to memory T cell antigen-driven differentiation, which remains an incompletely defined developmental step. Upon priming, each naive T cell encounters essential signals – i.e., antigen, co-stimuli and cytokines – in a secondary lymphoid organ; nevertheless, its daughter effector and memory T cells recirculate and receive further signals during their migration through various lymphoid and non-lymphoid organs. These additional signals from tissue microenvironments have an impact on immune response features, including T cell effector function, expansion and contraction, memory differentiation, long-term maintenance, and recruitment upon antigenic rechallenge into local and/or systemic responses. The critical role of T cell trafficking in providing efficient T cell memory has long been a focus of interest. It is now well recognized that naive and memory T cells have different migratory pathways, and that memory T cells are heterogeneous with respect to their trafficking. We and others have observed that, long time after priming, memory T cells are preferentially found in certain niches such as the bone marrow (BM) or at the skin/mucosal site of pathogen entry, even in the absence of residual antigen. The different underlying mechanisms and peculiarities of resulting immunity are currently under study. In this review, we summarize key findings on BM and tissue-resident memory (TRM) T cells and revisit some issues in memory T cell maintenance within such niches. Moreover, we discuss BM seeding by memory T cells in the context of migration patterns and protective functions of either recirculating or TRM T cells. PMID:26909081

  9. Control of memory B cell responses by extrinsic and intrinsic mechanisms.

    PubMed

    Wienands, Jürgen; Engels, Niklas

    2016-10-01

    Following primary activation, B lymphocytes generate a long-lived memory compartment to harness the organism for future reinfections by the same pathogen species. Only recently the composition and signaling signature of the scarce memory B cell pool could be explored in more detail. This review highlights current concepts of how B cells preserve their antigen experience at the cellular and molecular level.

  10. A Symptom-Focused Hypnotic Approach to Accessing and Processing Previously Repressed/Dissociated Memories.

    ERIC Educational Resources Information Center

    Ratican, Kathleen L.

    1996-01-01

    The kinesthetic track back technique accesses the origins of current symptoms and may uncover previously repressed/dissociated material, if such material exists in the client's unconscious mind, is relevant to the symptoms, and is ready to be processed consciously. Case examples are given to illustrate proper use of this technique. (LSR)

  11. Improving Memory after Interruption: Exploiting Soft Constraints and Manipulating Information Access Cost

    ERIC Educational Resources Information Center

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

    2009-01-01

    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…

  12. Glprof: A Gprof inspired, Callgraph-oriented Per-Object Disseminating Memory Access Multi-Cache Profiler

    SciTech Connect

    Janjusic, Tommy; Kartsaklis, Christos

    2015-01-01

    Application analysis is facilitated through a number of program profiling tools. The tools vary in their complexity, ease of deployment, design, and profiling detail. Specifically, understand- ing, analyzing, and optimizing is of particular importance for scientific applications where minor changes in code paths and data-structure layout can have profound effects. Understanding how intricate data-structures are accessed and how a given memory system responds is a complex task. In this paper we describe a trace profiling tool, Glprof, specifically aimed to lessen the burden of the programmer to pin-point heavily involved data-structures during an application's run-time, and understand data-structure run-time usage. Moreover, we showcase the tool's modularity using additional cache simulation components. We elaborate on the tool's design, and features. Finally we demonstrate the application of our tool in the context of Spec bench- marks using the Glprof profiler and two concurrently running cache simulators, PPC440 and AMD Interlagos.

  13. Improved characteristics of amorphous indium-gallium-zinc-oxide-based resistive random access memory using hydrogen post-annealing

    NASA Astrophysics Data System (ADS)

    Kang, Dae Yun; Lee, Tae-Ho; Kim, Tae Geun

    2016-08-01

    The authors report an improvement in resistive switching (RS) characteristics of amorphous indium-gallium-zinc-oxide (a-IGZO)-based resistive random access memory devices using hydrogen post-annealing. Because this a-IGZO thin film has oxygen off-stoichiometry in the form of deficient and excessive oxygen sites, the film properties can be improved by introducing hydrogen atoms through the annealing process. After hydrogen post-annealing, the device exhibited a stable bipolar RS, low-voltage set and reset operation, long retention (>105 s), good endurance (>106 cycles), and a narrow distribution in each current state. The effect of hydrogen post-annealing is also investigated by analyzing the sample surface using X-ray photon spectroscopy and atomic force microscopy.

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

    DOEpatents

    Blocksome, Michael A.; Mamidala, Amith R.

    2015-07-14

    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 a deterministic data communications network 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 the deterministic data communications network; 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.

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

    DOEpatents

    Blocksome, Michael A.; Mamidala, Amith R.

    2015-07-07

    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 a deterministic data communications network 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 the deterministic data communications network; 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.

  16. Observation of AlO x material in electrical resistive switching for nonvolatile random access memory application

    NASA Astrophysics Data System (ADS)

    Jung, Kyun-Ho; Song, Seung-Gon; Park, Kyoung-Wan; Sok, Jung-Hyun; Kim, Kyong-Min; Park, Yun-Sun

    2017-03-01

    We fabricated an Al / AlO x / Al device by using a RF magnetron sputter system. The device showed a unipolar resistive switching process. In this study, the switching mechanism of the device followed the conductive filament model. The conduction mechanisms for the conductive filament model were explained by using Ohmic conduction for the low resistance state (LRS) and Schottky emission for the high resistance state (HRS). The average value of the resistance ratio between the HRS and the LRS was about 3.48 × 107 when the reading voltage (0.1 V) was achieved. The electrical property of the endurance was achieved under 50 switching cycles. A low switching voltage could be obtained for a low power consuming device. These results proved that the AlO x material has various possibilities for use in nonvolatile random access memory applications.

  17. A Novel Metal-Ferroelectric-Semiconductor Field-Effect Transistor Memory Cell Design

    NASA Technical Reports Server (NTRS)

    Phillips, Thomas A.; Bailey, Mark; Ho, Fat Duen

    2004-01-01

    The use of a Metal-Ferroelectric-Semiconductor Field-Effect Transistor (MFSFET) in a resistive-load SRAM memory cell has been investigated A typical two-transistor resistive-load SRAM memory cell architecture is modified by replacing one of the NMOS transistors with an n-channel MFSFET. The gate of the MFSFET is connected to a polling voltage pulse instead of the other NMOS transistor drain. The polling voltage pulses are of sufficient magnitude to saturate the ferroelectric gate material and force the MFSFET into a particular logic state. The memory cell circuit is further modified by the addition of a PMOS transistor and a load resistor in order to improve the retention characteristics of the memory cell. The retention characteristics of both the "1" and "0" logic states are simulated. The simulations show that the MFSFET memory cell design can maintain both the "1" and "0" logic states for a long period of time.

  18. Mechanistic insights into the impairment of memory B cells and antibody production in the elderly.

    PubMed

    Aberle, Judith H; Stiasny, Karin; Kundi, Michael; Heinz, Franz X

    2013-04-01

    It is well established that immunologic memory generated early in life can be maintained into old age and mediate robust anamnestic antibody responses. Little is known, however, about the initiation of memory B cells in the elderly. We have conducted a prospective analysis of the quantities and functionalities of antigen-specific B cell responses and its association with the functional helper CD4(+)T cell responses. The ability of naïve B cells from old (60-80 years) and young (20-31 years) humans to establish functional memory was examined following primary and booster vaccination with an inactivated-virus vaccine against tick-borne encephalitis. Our data show that the number of antigen-specific memory B cells generated during primary vaccination was ~3-fold lower in old than in young individuals. The maintenance and booster responsiveness of these memory B cells were not compromised, as evidenced by similar increases in specific memory B cell frequencies upon revaccination in old and young adults. In contrast, the Ab response mediated per memory B cell after revaccination was dramatically diminished in the elderly. Also, antigen-specific IL-2-positive CD4(+)T cell responses were strongly reduced in the elderly and displayed an excellent correlation with Ab titres. The data suggest that the dramatically lower antibody response in the elderly could only partially be accounted for by the reduced B cell numbers and was strongly correlated with profound functional defects in CD4 help.

  19. Defining CD4 T cell memory by the epigenetic landscape of CpG DNA methylation.

    PubMed

    Komori, H Kiyomi; Hart, Traver; LaMere, Sarah A; Chew, Pamela V; Salomon, Daniel R

    2015-02-15

    Memory T cells are primed for rapid responses to Ag; however, the molecular mechanisms responsible for priming remain incompletely defined. CpG methylation in promoters is an epigenetic modification, which regulates gene transcription. Using targeted bisulfite sequencing, we examined methylation of 2100 genes (56,000 CpGs) mapped by deep sequencing of T cell activation in human naive and memory CD4 T cells. Four hundred sixty-six CpGs (132 genes) displayed differential methylation between naive and memory cells. Twenty-one genes exhibited both differential methylation and gene expression before activation, linking promoter DNA methylation states to gene regulation; 6 of 21 genes encode proteins closely studied in T cells, whereas 15 genes represent novel targets for further study. Eighty-four genes demonstrated differential methylation between memory and naive cells that correlated to differential gene expression following activation, of which 39 exhibited reduced methylation in memory cells coupled with increased gene expression upon activation compared with naive cells. These reveal a class of primed genes more rapidly expressed in memory compared with naive cells and putatively regulated by DNA methylation. These findings define a DNA methylation signature unique to memory CD4 T cells that correlates with activation-induced gene expression.

  20. Defining CD4 T Cell Memory by the Epigenetic Landscape of CpG DNA Methylation

    PubMed Central

    Komori, H. Kiyomi; Hart, Traver; LaMere, Sarah A.; Chew, Pamela V.; Salomon, Daniel R.

    2015-01-01

    Memory T cells are primed for rapid responses to antigen; however, the molecular mechanisms responsible for priming remain incompletely defined. CpG methylation in promoters is an epigenetic modification, which regulates gene transcription. Using targeted bisulfite sequencing, we examined methylation of 2100 genes (56,000 CpG) mapped by deep sequencing of T cell activation in human naïve and memory CD4 T cells. 466 CpGs (132 genes) displayed differential methylation between naïve and memory cells. 21 genes exhibited both differential methylation and gene expression before activation, linking promoter DNA methylation states to gene regulation; 6 of 21 genes encode proteins closely studied in T cells, while 15 genes represent novel targets for further study. 84 genes demonstrated differential methylation between memory and naïve cells that correlated to differential gene expression following activation, of which 39 exhibited reduced methylation in memory cells coupled with increased gene expression upon activation compared to naïve cells. These reveal a class of primed genes more rapidly expressed in memory compared to naïve cells and putatively regulated by DNA methylation. These findings define a DNA methylation signature unique to memory CD4 T cells that correlates with activation-induced gene expression. PMID:25576597

  1. Thin Co/Ni-based bottom pinned spin-transfer torque magnetic random access memory stacks with high annealing tolerance

    NASA Astrophysics Data System (ADS)

    Tomczak, Y.; Swerts, J.; Mertens, S.; Lin, T.; Couet, S.; Liu, E.; Sankaran, K.; Pourtois, G.; Kim, W.; Souriau, L.; Van Elshocht, S.; Kar, G.; Furnemont, A.

    2016-01-01

    Spin-transfer torque magnetic random access memory (STT-MRAM) is considered as a replacement for next generation embedded and stand-alone memory applications. One of the main challenges in the STT-MRAM stack development is the compatibility of the stack with CMOS process flows in which thermal budgets up to 400 °C are applied. In this letter, we report on a perpendicularly magnetized MgO-based tunnel junction (p-MTJ) on a thin Co/Ni perpendicular synthetic antiferromagnetic layer with high annealing tolerance. Tunnel magneto resistance (TMR) loss after annealing occurs when the reference layer loses its perpendicular magnetic anisotropy due to reduction of the CoFeB/MgO interfacial anisotropy. A stable Co/Ni based p-MTJ stack with TMR values of 130% at resistance-area products of 9 Ω μm2 after 400 °C anneal is achieved via moment control of the Co/Ta/CoFeB reference layer. Thinning of the CoFeB polarizing layer down to 0.8 nm is the key enabler to achieve 400 °C compatibility with limited TMR loss. Thinning the Co below 0.6 nm leads to a loss of the antiferromagnetic interlayer exchange coupling strength through Ru. Insight into the thickness and moment engineering of the reference layer is displayed to obtain the best magnetic properties and high thermal stability for thin Co/Ni SAF-based STT-MRAM stacks.

  2. Impact of adolescent sucrose access on cognitive control, recognition memory, and parvalbumin immunoreactivity.

    PubMed

    Reichelt, Amy C; Killcross, Simon; Hambly, Luke D; Morris, Margaret J; Westbrook, R Fred

    2015-04-01

    In this study we sought to determine the effect of daily sucrose consumption in young rats on their subsequent performance in tasks that involve the prefrontal cortex and hippocampus. High levels of sugar consumption have been associated with the development of obesity, however less is known about how sugar consumption influences behavioral control and high-order cognitive processes. Of particular concern is the fact that sugar intake is greatest in adolescence, an important neurodevelopmental period. We provided sucrose to rats when they were progressing through puberty and adolescence. Cognitive performance was assessed in adulthood on a task related to executive function, a rodent analog of the Stroop task. We found that sucrose-exposed rats failed to show context-appropriate responding during incongruent stimulus compounds presented at test, indicative of impairments in prefrontal cortex function. Sucrose exposed rats also showed deficits in an on object-in-place recognition memory task, indicating that both prefrontal and hippocampal function was impaired. Analysis of brains showed a reduction in expression of parvalbumin-immunoreactive GABAergic interneurons in the hippocampus and prefrontal cortex, indicating that sucrose consumption during adolescence induced long-term pathology, potentially underpinning the cognitive deficits observed. These results suggest that consumption of high levels of sugar-sweetened beverages by adolescents may also impair neurocognitive functions affecting decision-making and memory, potentially rendering them at risk for developing mental health disorders.

  3. Temperature induced complementary switching in titanium oxide resistive random access memory

    NASA Astrophysics Data System (ADS)

    Panda, D.; Simanjuntak, F. M.; Tseng, T.-Y.

    2016-07-01

    On the way towards high memory density and computer performance, a considerable development in energy efficiency represents the foremost aspiration in future information technology. Complementary resistive switch consists of two antiserial resistive switching memory (RRAM) elements and allows for the construction of large passive crossbar arrays by solving the sneak path problem in combination with a drastic reduction of the power consumption. Here we present a titanium oxide based complementary RRAM (CRRAM) device with Pt top and TiN bottom electrode. A subsequent post metal annealing at 400°C induces CRRAM. Forming voltage of 4.3 V is required for this device to initiate switching process. The same device also exhibiting bipolar switching at lower compliance current, Ic <50 μA. The CRRAM device have high reliabilities. Formation of intermediate titanium oxi-nitride layer is confirmed from the cross-sectional HRTEM analysis. The origin of complementary switching mechanism have been discussed with AES, HRTEM analysis and schematic diagram. This paper provides valuable data along with analysis on the origin of CRRAM for the application in nanoscale devices.

  4. The structure-sensitivity of memory access: evidence from Mandarin Chinese

    PubMed Central

    Dillon, Brian; Chow, Wing-Yee; Wagers, Matthew; Guo, Taomei; Liu, Fengqin; Phillips, Colin

    2014-01-01

    The present study examined the processing of the Mandarin Chinese long-distance reflexive ziji to evaluate the role that syntactic structure plays in the memory retrieval operations that support sentence comprehension. Using the multiple-response speed-accuracy tradeoff (MR-SAT) paradigm, we measured the speed with which comprehenders retrieve an antecedent for ziji. Our experimental materials contrasted sentences where ziji's antecedent was in the local clause with sentences where ziji's antecedent was in a distant clause. Time course results from MR-SAT suggest that ziji dependencies with syntactically distant antecedents are slower to process than syntactically local dependencies. To aid in interpreting the SAT data, we present a formal model of the antecedent retrieval process, and derive quantitative predictions about the time course of antecedent retrieval. The modeling results support the Local Search hypothesis: during syntactic retrieval, comprehenders initially limit memory search to the local syntactic domain. We argue that Local Search hypothesis has important implications for theories of locality effects in sentence comprehension. In particular, our results suggest that not all locality effects may be reduced to the effects of temporal decay and retrieval interference. PMID:25309486

  5. 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.

  6. Crystal growth within a phase change memory cell.

    PubMed

    Sebastian, Abu; Le Gallo, Manuel; Krebs, Daniel

    2014-07-07

    In spite of the prominent role played by phase change materials in information technology, a detailed understanding of the central property of such materials, namely the phase change mechanism, is still lacking mostly because of difficulties associated with experimental measurements. Here, we measure the crystal growth velocity of a phase change material at both the nanometre length and the nanosecond timescale using phase-change memory cells. The material is studied in the technologically relevant melt-quenched phase and directly in the environment in which the phase change material is going to be used in the application. We present a consistent description of the temperature dependence of the crystal growth velocity in the glass and the super-cooled liquid up to the melting temperature.

  7. Increased CD8+ T cell memory to concurrent infection at the expense of increased erosion of pre-existing memory: the paradoxical role of IL-15.

    PubMed

    Chapdelaine, Yvan; Smith, Dean K; Pedras-Vasconcelos, Joao A; Krishnan, Lakshmi; Sad, Subash

    2003-11-15

    The use of cytokines during vaccination, particularly IL-15, is being considered due to the unique ability of IL-15 to enhance the proliferation of memory CD8(+) T cells. However, as homeostatic mechanisms limit excessive lymphocyte expansion, we addressed the consequences of this enhancement of T cell memory by IL-15. Infection of mice with either recombinant Mycobacterium bovis (BCG) expressing IL-15 (BCG-IL-15) or BCG and purified IL-15 resulted in an increased CD44, IL-2Rbeta expression and increased frequency of IFN-gamma-secreting CD8(+) T cells. Surprisingly, the enhancement of memory to concurrent infection by IL-15 exacerbated the attrition of pre-existing memory. Infection of mice with Listeria monocytogenes expressing OVA resulted in potent OVA(257-264)-specific CD8(+) T cell memory, and a challenge of these mice with either BCG-IL-15 or BCG and purified IL-15 resulted in an increased erosion of OVA(257-264)-specific CD8(+) T cell memory, relative to BCG. Enhancement in the erosion of OVA-specific CD8(+) T cell memory by BCG-IL-15 resulted in a consequently greater impairment in protection against a challenge with OVA-expressing tumor cells. We thus raise important questions regarding vaccinations that are aimed at maximizing T cell memory without considering the impact on pre-existing T cell memory.

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

    SciTech Connect

    Jovanović, B. E-mail: lionel.torres@lirmm.fr; Brum, R. M.; Torres, L.

    2014-04-07

    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.

  9. Combination of volatile and non-volatile functions in a single memory cell and its scalability

    NASA Astrophysics Data System (ADS)

    Kim, Hyungjin; Hwang, Sungmin; Lee, Jong-Ho; Park, Byung-Gook

    2017-04-01

    A single memory cell which combines volatile memory and non-volatile memory functions has been demonstrated with an independent asymmetric dual-gate structure. Owing to the second gate whose dielectric is composed of oxide/nitride/oxide layers, floating body effect was observed even on a fully depleted silicon-on-insulator device and the non-volatile memory function was measured. In addition, read retention characteristics of the volatile memory function depending on the non-volatile memory state were evaluated and analyzed. Further scalability in body thickness was also verified through simulation studies. These results indicate that the proposed device is a promising candidate for high-density embedded memory applications.

  10. Interleukin-7 and -15 maintain pathogenic memory Th17 cells in autoimmunity.

    PubMed

    Chen, Yihe; Chauhan, Sunil K; Tan, Xuhua; Dana, Reza

    2017-02-01

    Th17 cells are principal mediators of many autoimmune conditions. Recently, memory Th17 cells have been revealed as crucial in mediating the chronicity of various refractory autoimmune disorders; however, the underlying mechanisms maintaining memory Th17 cells have remained elusive. Here, using a preclinical model of ocular autoimmune disease we show that both IL-7 and IL-15 are critical for maintaining pathogenic memory Th17 cells. Neutralization of these cytokines leads to substantial reduction of memory Th17 cells; both IL-7 and IL-15 provide survival signals via activating STAT5, and IL-15 provides additional proliferation signals via activating both STAT5 and Akt. Topical neutralization of ocular IL-7 or IL-15 effectively reduces memory Th17 cells at the inflammatory site and draining lymphoid tissues, while topical neutralization of IL-17 alone, the major pathogenic cytokine secreted by Th17 cells, does not diminish memory Th17 cells at the draining lymphoid tissues. Our results suggest that the effective removal of pathogenic memory Th17 cells via abolishing environmental IL-7 or IL-15 is likely to be a novel strategy in the treatment of autoimmune diseases.

  11. 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

  12. Nanovesicle-targeted Kv1.3 knockdown in memory T cells suppresses CD40L expression and memory phenotype.

    PubMed

    Chimote, Ameet A; Hajdu, Peter; Kottyan, Leah C; Harley, John B; Yun, Yeoheung; Conforti, Laura

    2016-05-01

    Ca(2+) signaling controls activation and effector functions of T lymphocytes. Ca(2+) levels also regulate NFAT activation and CD40 ligand (CD40L) expression in T cells. CD40L in activated memory T cells binds to its cognate receptor, CD40, on other cell types resulting in the production of antibodies and pro-inflammatory mediators. The CD40L/CD40 interaction is implicated in the pathogenesis of autoimmune disorders and CD40L is widely recognized as a therapeutic target. Ca(2+) signaling in T cells is regulated by Kv1.3 channels. We have developed lipid nanoparticles that deliver Kv1.3 siRNAs (Kv1.3-NPs) selectively to CD45RO(+) memory T cells and reduce the activation-induced Ca(2+) influx. Herein we report that Kv1.3-NPs reduced NFAT activation and CD40L expression exclusively in CD45RO(+) T cells. Furthermore, Kv1.3-NPs suppressed cytokine release and induced a phenotype switch of T cells from predominantly memory to naïve. These findings indicate that Kv1.3-NPs operate as targeted immune suppressive agents with promising therapeutic potentials.

  13. The automatic visual simulation of words: A memory reactivated mask slows down conceptual access.

    PubMed

    Rey, Amandine E; Riou, Benoit; Vallet, Guillaume T; Versace, Rémy

    2017-03-01

    How do we represent the meaning of words? The present study assesses whether access to conceptual knowledge requires the reenactment of the sensory components of a concept. The reenactment-that is, simulation-was tested in a word categorisation task using an innovative masking paradigm. We hypothesised that a meaningless reactivated visual mask should interfere with the simulation of the visual dimension of concrete words. This assumption was tested in a paradigm in which participants were not aware of the link between the visual mask and the words to be processed. In the first phase, participants created a tone-visual mask or tone-control stimulus association. In the test phase, they categorised words that were presented with 1 of the tones. Results showed that words were processed more slowly when they were presented with the reactivated mask. This interference effect was only correlated with and explained by the value of the visual perceptual strength of the words (i.e., our experience with the visual dimensions associated with concepts) and not with other characteristics. We interpret these findings in terms of word access, which may involve the simulation of sensory features associated with the concept, even if participants were not explicitly required to access visual properties. (PsycINFO Database Record

  14. The role of the inserted layer in resistive random access memory device

    NASA Astrophysics Data System (ADS)

    Zhang, Dainan; Ma, Guokun; Zhang, Huaiwu; Tang, Xiaoli; Zhong, Zhiyong; Jie, Li; Su, Hua

    2016-07-01

    NiO resistive switching devices were fabricated by reactive DC magnetron sputtering at room temperature containing different inserted layers. From measurements, we demonstrated the filaments were made up by metal Co rather than the oxygen defect or other metal. A current jumping phenomenon in the SET process was observed, evidencing that the filament generating procedure was changed due to the inserted layers. In this process, we demonstrate the current jumping appeared in higher voltage region when the position of inserted layer was close to the bottom electrode. The I-V curves shifted to the positive direction as the thickness of inserted layer increasing. With the change of the number of inserted layers, SET voltages varied while the RESET voltage kept stable. According to the electrochemical metallization memory mechanism, detailed explanations on all the phenomena were addressed. This discovery is supposed of great potentials in the use of designing multi-layer RRAM devices.

  15. Characterization of Magnetic Tunnel Junctions For Spin Transfer Torque Magnetic Random Access Memory

    NASA Astrophysics Data System (ADS)

    Dill, Joshua Luchay

    This thesis details two experimental methods for quantifying magnetic tunnel junction behavior, namely write error rates and field modulated spin-torque ferromagnetic resonance. The former examines how reliably an applied spin-transfer torque can excite magnetization dynamics that lead to a reversal of magnetization direction while the latter studies steady state dynamics provided by an oscillating spin-transfer torque. These characterization techniques reveal write error rate behavior for a particular composition magnetic tunnel junction that qualitatively deviates from theoretical predictions. Possible origins of this phenomenon are also investigated with the field modulated spin-torque ferromagnetic resonance technique. By understanding the dynamics of magnetic moments predicted by theory, one can experimentally confirm or disprove these theories in order to accurately model and predict tunnel junction behavior. By having a better model for what factors are important in magnetization dynamics, one can optimize these factors in terms of improving magnetic tunnel junctions for their use as computer memory.

  16. Access to long-term optical memories using photon echoes retrieved from semiconductor spins

    NASA Astrophysics Data System (ADS)

    Langer, L.; Poltavtsev, S. V.; Yugova, I. A.; Salewski, M.; Yakovlev, D. R.; Karczewski, G.; Wojtowicz, T.; Akimov, I. A.; Bayer, M.

    2014-11-01

    The ability to store optical information is important for both classical and quantum communication. Achieving this in a comprehensive manner (converting the optical field into material excitation, storing this excitation, and releasing it after a controllable time delay) is greatly complicated by the many, often conflicting, properties of the material. More specifically, optical resonances in semiconductor quantum structures with high oscillator strength are inevitably characterized by short excitation lifetimes (and, therefore, short optical memory). Here, we present a new experimental approach to stimulated photon echoes by transferring the information contained in the optical field into a spin system, where it is decoupled from the optical vacuum field and may persist much longer. We demonstrate this for an n-doped CdTe/(Cd,Mg)Te quantum well, the storage time of which could be increased by more than three orders of magnitude, from the picosecond range up to tens of nanoseconds.

  17. Distribution of nanoscale nuclei in the amorphous dome of a phase change random access memory

    SciTech Connect

    Lee, Bong-Sub Darmawikarta, Kristof; Abelson, John R.; Raoux, Simone; Shih, Yen-Hao; Zhu, Yu

    2014-02-17

    The nanoscale crystal nuclei in an amorphous Ge{sub 2}Sb{sub 2}Te{sub 5} bit in a phase change memory device were evaluated by fluctuation transmission electron microscopy. The quench time in the device (∼10 ns) afforded more and larger nuclei in the melt-quenched state than in the as-deposited state. However, nuclei were even more numerous and larger in a test structure with a longer quench time (∼100 ns), verifying the prediction of nucleation theory that slower cooling produces more nuclei. It also demonstrates that the thermal design of devices will strongly influence the population of nuclei, and thus the speed and data retention characteristics.

  18. Manufacture of gene-modified human T-cells with a memory stem/central memory phenotype.

    PubMed

    Gomez-Eerland, Raquel; Nuijen, Bastiaan; Heemskerk, Bianca; van Rooij, Nienke; van den Berg, Joost H; Beijnen, Jos H; Uckert, Wolfgang; Kvistborg, Pia; Schumacher, Ton N; Haanen, John B A G; Jorritsma, Annelies

    2014-10-01

    Advances in genetic engineering have made it possible to generate human T-cell products that carry desired functionalities, such as the ability to recognize cancer cells. The currently used strategies for the generation of gene-modified T-cell products lead to highly differentiated cells within the infusion product, and on the basis of data obtained in preclinical models, this is likely to impact the efficacy of these products. We set out to develop a good manufacturing practice (GMP) protocol that yields T-cell receptor (TCR) gene-modified T-cells with more favorable properties for clinical application. Here, we show the robust clinical-scale production of human peripheral blood T-cells with an early memory phenotype that express a MART-1-specific TCR. By combining selection and stimulation using anti-CD3/CD28 beads for retroviral transduction, followed by expansion in the presence of IL-7 and IL-15, production of a well-defined clinical-scale TCR gene-modified T-cell product could be achieved. A major fraction of the T-cells generated in this fashion were shown to coexpress CD62L and CD45RA, and express CD27 and CD28, indicating a central memory or memory stemlike phenotype. Furthermore, these cells produced IFNγ, TNFα, and IL-2 and displayed cytolytic activity against target cells expressing the relevant antigen. The T-cell products manufactured by this robust and validated GMP production process are now undergoing testing in a phase I/IIa clinical trial in HLA-A*02:01 MART-1-positive advanced stage melanoma patients. To our knowledge, this is the first clinical trial protocol in which the combination of IL-7 and IL-15 has been applied for the generation of gene-modified T-cell products.

  19. Manufacture of Gene-Modified Human T-Cells with a Memory Stem/Central Memory Phenotype

    PubMed Central

    Gomez-Eerland, Raquel; Nuijen, Bastiaan; Heemskerk, Bianca; van Rooij, Nienke; van den Berg, Joost H.; Beijnen, Jos H.; Uckert, Wolfgang; Kvistborg, Pia; Schumacher, Ton N.; Jorritsma, Annelies

    2014-01-01

    Abstract Advances in genetic engineering have made it possible to generate human T-cell products that carry desired functionalities, such as the ability to recognize cancer cells. The currently used strategies for the generation of gene-modified T-cell products lead to highly differentiated cells within the infusion product, and on the basis of data obtained in preclinical models, this is likely to impact the efficacy of these products. We set out to develop a good manufacturing practice (GMP) protocol that yields T-cell receptor (TCR) gene-modified T-cells with more favorable properties for clinical application. Here, we show the robust clinical-scale production of human peripheral blood T-cells with an early memory phenotype that express a MART-1-specific TCR. By combining selection and stimulation using anti-CD3/CD28 beads for retroviral transduction, followed by expansion in the presence of IL-7 and IL-15, production of a well-defined clinical-scale TCR gene-modified T-cell product could be achieved. A major fraction of the T-cells generated in this fashion were shown to coexpress CD62L and CD45RA, and express CD27 and CD28, indicating a central memory or memory stemlike phenotype. Furthermore, these cells produced IFNγ, TNFα, and IL-2 and displayed cytolytic activity against target cells expressing the relevant antigen. The T-cell products manufactured by this robust and validated GMP production process are now undergoing testing in a phase I/IIa clinical trial in HLA-A*02:01 MART-1-positive advanced stage melanoma patients. To our knowledge, this is the first clinical trial protocol in which the combination of IL-7 and IL-15 has been applied for the generation of gene-modified T-cell products. PMID:25143008

  20. Pharmacologic Induction of CD8+ T Cell Memory: Better Living Through Chemistry

    PubMed Central

    Gattinoni, Luca; Klebanoff, Christopher A.; Restifo, Nicholas P.

    2011-01-01

    The generation of a robust population of memory T cells is critical for effective vaccine and cell-based therapies to prevent and treat infectious diseases and cancer. A series of recent papers have established a new, cell-intrinsic approach in which small molecules target key metabolic and developmental pathways to enhance the formation and maintenance of highly functional CD8+ memory T cells. These findings raise the exciting new possibility of using small molecules, many of which are already approved for human use, for the pharmacologic induction of immunologic memory. PMID:20371454

  1. Effects of abnormal cell-to-cell interference on p-type floating gate and control gate NAND flash memory

    NASA Astrophysics Data System (ADS)

    Kim, Yong Jun; Kang, Jun Geun; Lee, Byungin; Cho, Gyu-Seog; Park, Sung-Kye; Choi, Woo Young

    2014-01-01

    Abnormal cell-to-cell interference occurring in NAND flash memory has been investigated. In the case of extremely downscaled NAND flash memory, cell-to-cell interference increases abnormally. The abnormal cell-to-cell interference has been observed in a p-type floating gate (FG)/control gate (CG) cells for the first time. It has been found that the depletion region variation leads to the abnormal cell-to-cell interference. The depletion region variation of FG and CG is determined by state of neighbor cells. The depletion region variation affects CG-to-FG coupling capacitance and threshold voltage variation (ΔVT). Finally, it is observed that there is a symmetrical relationship between n- and p-type FG/CG NAND flash memory in terms of cell-to-cell interference.

  2. Antigen availability determines CD8+ T cell-dendritic cell interaction kinetics and memory fate decisions

    PubMed Central

    Henrickson, Sarah E.; Stutte, Susanne; Quigley, Michael; Alexe, Gabriela; Iannacone, Matteo; Flynn, Michael P.; Omid, Shaida; Jesneck, Jonathan L.; Imam, Sabrina; Mempel, Thorsten R.; Mazo, Irina B.; Haining, William N.; von Andrian, Ulrich H.

    2014-01-01

    Summary T cells are activated by antigen (Ag) bearing dendritic cells (DCs) in lymph nodes in 3 phases. The duration of the initial phase of transient, serial DC-T cell interactions is inversely correlated with Ag dose. The second phase, characterized by stable DC-T cell contacts, is believed to be necessary for full-fledged T cell activation. Here we have shown that this is not the case. CD8+ T cells interacting with DCs presenting low-dose, short-lived Ag did not transition to phase 2, while higher Ag dose yielded phase 2 transition. Both antigenic constellations promoted T cell proliferation and effector differentiation, but yielded different transcriptome signatures at 12h and 24h. T cells that experienced phase 2 developed long-lived memory, whereas conditions without stable contacts yielded immunological amnesia. Thus, T cells make fate decisions within hours after Ag exposure resulting in long-term memory or abortive effector responses, correlating with T cell-DCs interaction kinetics. PMID:24054328

  3. The possible role of virus-specific CD8(+) memory T cells in decidual tissue.

    PubMed

    van Egmond, A; van der Keur, C; Swings, G M J S; Scherjon, S A; Claas, F H J

    2016-02-01

    The most abundant lymphocyte present in decidual tissue is the CD8(+) T cell. It has been shown that most decidual CD8(+) T cells have an effector-memory phenotype, but expressed reduced levels of perforin and granzyme B compared with the peripheral CD8(+) effector-memory T cells. The specificity of these CD8(+) memory T cells has yet to be determined. One hypothesis is that the decidual memory T cells are virus-specific T cells that should protect the fetus against incoming pathogens. As virus-specific CD8(+) memory T cells can cross-react with human leukocyte alloantigens, an alternative, but not mutually exclusive, hypothesis is that these CD8(+) T cells are fetus-specific. Using virus-specific tetramers, we found increased percentages of virus-specific CD8(+) T cells in decidual tissue compared with peripheral blood after uncomplicated pregnancy. So far, no evidence has been obtained for a cross-reactive response of these virus-specific T cells to fetal human leukocyte antigens. These results suggest that the virus-specific memory T cells accumulate in the placenta to protect the fetus from a harmful infection.

  4. Generation of human memory stem T cells after haploidentical T-replete hematopoietic stem cell transplantation.

    PubMed

    Cieri, Nicoletta; Oliveira, Giacomo; Greco, Raffaella; Forcato, Mattia; Taccioli, Cristian; Cianciotti, Beatrice; Valtolina, Veronica; Noviello, Maddalena; Vago, Luca; Bondanza, Attilio; Lunghi, Francesca; Marktel, Sarah; Bellio, Laura; Bordignon, Claudio; Bicciato, Silvio; Peccatori, Jacopo; Ciceri, Fabio; Bonini, Chiara

    2015-04-30

    Memory stem T cells (TSCM) have been proposed as key determinants of immunologic memory. However, their exact contribution to a mounting immune response, as well as the mechanisms and timing of their in vivo generation, are poorly understood. We longitudinally tracked TSCM dynamics in patients undergoing haploidentical hematopoietic stem cell transplantation (HSCT), thereby providing novel hints on the contribution of this subset to posttransplant immune reconstitution in humans. We found that donor-derived TSCM are highly enriched early after HSCT. We showed at the antigen-specific and clonal level that TSCM lymphocytes can differentiate directly from naive precursors infused within the graft and that the extent of TSCM generation might correlate with interleukin 7 serum levels. In vivo fate mapping through T-cell receptor sequencing allowed defining the in vivo differentiation landscapes of human naive T cells, supporting the notion that progenies of single naive cells embrace disparate fates in vivo and highlighting TSCM as relevant novel players in the diversification of immunological memory after allogeneic HSCT.

  5. Inability of memory T cells to induce graft-versus-host disease is a result of an abortive alloresponse

    PubMed Central

    Deoliveira, Divino; Cui, Xiuyu; Le, Ngocdiep T.; Son, Jessica; Whitesides, John F.; Chao, Nelson J.

    2007-01-01

    Several groups, including our own, have independently demonstrated that effector memory T cells from non–alloantigen-primed donors do not cause graft-versus-host disease (GVHD). In the current study, we further investigated whether this approach could be extended to all memory T cells, and we studied the underlying mechanisms. Neither total memory T cells nor purified central memory T cells were able to induce GVHD. Memory T cells were at least 3-log less potent than bulk T cells in mediating GVHD. As expected, memory T cells failed to elicit cytotoxicity and proliferated poorly against alloantigens in standard 5-day mixed-lymphocyte cultures. However, the proliferative responses of memory T cells were more comparable with those of bulk and naive T cells when the culture time was shortened. Moreover, the frequencies of IL-2–secreting cells measured by 42-hour enzyme-linked immunosorbent spot (ELISPOT) assay were similar among naive, memory, and bulk T cells. These data indicated that memory T cells are able to respond to alloantigens initially but fail to develop to full potential. The abortive immune response, which was mediated by non–alloantigen-specific memory T cells in response to alloantigens, may explain why memory T cells from unprimed and non–alloantigen-primed donors could not induce GVHD. PMID:17148592

  6. Epigenomic Profiling of Human CD4(+) T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development.

    PubMed

    Durek, Pawel; Nordström, Karl; Gasparoni, Gilles; Salhab, Abdulrahman; Kressler, Christopher; de Almeida, Melanie; Bassler, Kevin; Ulas, Thomas; Schmidt, Florian; Xiong, Jieyi; Glažar, Petar; Klironomos, Filippos; Sinha, Anupam; Kinkley, Sarah; Yang, Xinyi; Arrigoni, Laura; Amirabad, Azim Dehghani; Ardakani, Fatemeh Behjati; Feuerbach, Lars; Gorka, Oliver; Ebert, Peter; Müller, Fabian; Li, Na; Frischbutter, Stefan; Schlickeiser, Stephan; Cendon, Carla; Fröhler, Sebastian; Felder, Bärbel; Gasparoni, Nina; Imbusch, Charles D; Hutter, Barbara; Zipprich, Gideon; Tauchmann, Yvonne; Reinke, Simon; Wassilew, Georgi; Hoffmann, Ute; Richter, Andreas S; Sieverling, Lina; Chang, Hyun-Dong; Syrbe, Uta; Kalus, Ulrich; Eils, Jürgen; Brors, Benedikt; Manke, Thomas; Ruland, Jürgen; Lengauer, Thomas; Rajewsky, Nikolaus; Chen, Wei; Dong, Jun; Sawitzki, Birgit; Chung, Ho-Ryun; Rosenstiel, Philip; Schulz, Marcel H; Schultze, Joachim L; Radbruch, Andreas; Walter, Jörn; Hamann, Alf; Polansky, Julia K

    2016-11-15

    The impact of epigenetics on the differentiation of memory T (Tmem) cells is poorly defined. We generated deep epigenomes comprising genome-wide profiles of DNA methylation, histone modifications, DNA accessibility, and coding and non-coding RNA expression in naive, central-, effector-, and terminally differentiated CD45RA(+) CD4(+) Tmem cells from blood and CD69(+) Tmem cells from bone marrow (BM-Tmem). We observed a progressive and proliferation-associated global loss of DNA methylation in heterochromatic parts of the genome during Tmem cell differentiation. Furthermore, distinct gradually changing signatures in the epigenome and the transcriptome supported a linear model of memory development in circulating T cells, while tissue-resident BM-Tmem branched off with a unique epigenetic profile. Integrative analyses identified candidate master regulators of Tmem cell differentiation, including the transcription factor FOXP1. This study highlights the importance of epigenomic changes for Tmem cell biology and demonstrates the value of epigenetic data for the identification of lineage regulators.

  7. 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 memorycells remain inactive due to lack of T cell receptor (TCR) stimuli. Here, we report that regulatory T (Treg) cells orchestrate memorycell 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 memorycell 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.

  8. Tissue Distribution of Memory T and B Cells in Rhesus Monkeys following Influenza A Infection

    PubMed Central

    Yongvanitchit, Kosol; Limsalakpetch, Amporn; Kum-Arb, Utaiwan; Im-Erbsin, Rawiwan; Boonnak, Kobporn; Thitithayanont, Arunee; Jongkaewwattana, Anan; Wiboon-ut, Suwimon; Mongkolsirichaikul, Duangrat; Mahanonda, Rangsini; Spring, Michele; Chuang, Ilin; Mason, Carl J.; Saunders, David L.

    2015-01-01

    Studies of influenza-specific immune responses in humans have largely assessed systemic responses involving serum Ab and peripheral blood T cell responses. However, recent evidence indicates that tissue-resident memory T (TRM) cells play an important role in local murine intrapulmonary immunity. Rhesus monkeys were pulmonary exposed to 2009 pandemic H1N1 virus at days 0 and 28 and immune responses in different tissue compartments were measured. All animals were asymptomatic postinfection. Although only minimal memory immune responses were detected in peripheral blood, a high frequency of influenza nucleoprotein–specific memory T cells was detected in the lung at the “contraction phase,” 49–58 d after second virus inoculation. A substantial proportion of lung nucleoprotein-specific memory CD8+ T cells expressed CD103 and CD69, phenotypic markers of TRM cells. Lung CD103+ and CD103- memory CD8+ T cells expressed similar levels of IFN-γ and IL-2. Unlike memory T cells, spontaneous Ab secreting cells and memory B cells specific to influenza hemagglutinin were primarily observed in the mediastinal lymph nodes. Little difference in systemic and local immune responses against influenza was observed between young adult (6–8 y) and old animals (18–28 y). Using a nonhuman primate model, we revealed substantial induction of local T and B cell responses following 2009 pandemic H1N1 infection. Our study identified a subset of influenza-specific lung memory T cells characterized as TRM cells in rhesus monkeys. The rhesus monkey model may be useful to explore the role of TRM cells in local tissue protective immunity after rechallenge and vaccination. PMID:26408671

  9. Pediatric common variable immunodeficiency: immunologic and phenotypic associations with switched memory B cells.

    PubMed

    Yong, Pierre L; Orange, Jordan S; Sullivan, Kathleen E

    2010-08-01

    Recent studies suggest that patients with common variable immunodeficiency (CVID) and low numbers of switched memory B cells have lower IgG levels and higher rates of autoimmune disease, splenomegaly, and granulomatous disease; however, no prior literature has focused exclusively on pediatric cases. We examined the relationship between switched memory B cells and clinical and immunologic manifestations of CVID in a pediatric population. Forty-five patients were evaluated. Patients were categorized as Group I (<5 switched memory B cells/ml, n = 24) or Group II (> or =5 switched memory B cells/mL, n = 21). CD3(+) T-cell counts and CD19(+) B-cell levels were lower among Group I patients. Only those in Group I had meningitis, sepsis, bronchiectasis, granulomatous lung disease, autoimmune cytopenias, or hematologic malignancies. Segregation of pediatric patients into high risk (Group I) and average risk (Group II) may assist in targeting surveillance appropriately.

  10. Immunologic considerations for generating memory CD8 T cells through vaccination.

    PubMed

    Butler, Noah S; Nolz, Jeffrey C; Harty, John T

    2011-07-01

    Following infection or vaccination, naïve CD8 T cells that receive the appropriate integration of antigenic, co-stimulatory and inflammatory signals undergo a programmed series of biological changes that ultimately results in the generation of memory cells. Memory CD8 T cells, in contrast to naïve cells, more effectively limit or prevent pathogen re-infection because of both qualitative and quantitative changes that occur following their induction. Unlike vaccination strategies aimed at generating antibody production, the ability to generate protective memory CD8 T cells has proven more complicated and problematic. However, recent experimental results have revealed important principles regarding the molecular and genetic basis for memory CD8 T cell formation, as well as identified ways to manipulate their development through vaccination, resulting in potential new avenues to enhance protective immunity.

  11. Simulation of phase-change random access memory with 35nm diameter of the TiN bottom electrode by finite element modeling

    NASA Astrophysics Data System (ADS)

    Jin, Qiuxue; Liu, Bo; Liu, Yan; Wang, Heng; Xu, Zhen; Gao, Dan; Wang, Qing; Xia, Yangyang; Wang, Weiwei; Song, Zhitang; Feng, Songlin

    2016-10-01

    A three-dimensional finite element model for Phase-Change Random Access Memory (PCRAM) is established to simulate thermal and electrical distribution during RESET operation. The establishment of the model is highly in accordance with the manufacture of PCRAM cell in the 40nm process and the model is applied to simulate the RESET behaviors of 35 nm diameter of titanium nitride (TiN) bottom electrode in the conventional mushroom structure (MS). By the simulations of thermal and electrical distribution, the highest temperature is observed in TiN bottom electrode contactor and meanwhile the voltage of the TiN bottom electrode accounts for as high as 65 percent of the total voltage. It induces high RESET current which suggests that the thermoelectric conductivity of MS is crucial in improving the heating efficiency in RESET process. Simulation results of RESET current and high resistance distribution during RESET operation are close to the data from the actual measurement. However those two values of low resistance are slightly different, probably due to the interface resistance between Ge2Sb2Te5 (GST) and other materials and the resistance caused by microstructural defects. This work reveals the importance of the thermoelectrical properties of materials in PCRAM cells and improves the quality of PCRAM simulations in industrial application.

  12. Skin vaccination with live virus vectored microneedle arrays induce long lived CD8(+) T cell memory.

    PubMed

    Becker, Pablo D; Hervouet, Catherine; Mason, Gavin M; Kwon, Sung-Yun; Klavinskis, Linda S

    2015-09-08

    A simple dissolvable microneedle array (MA) platform has emerged as a promising technology for vaccine delivery, due to needle-free injection with a formulation that preserves the immunogenicity of live viral vectored vaccines dried in the MA matrix. While recent studies have focused largely on design parameters optimized to induce primary CD8(+) T cell responses, the hallmark of a vaccine is synonymous with engendering long-lasting memory. Here, we address the capacity of dried MA vaccination to programme phenotypic markers indicative of effector/memory CD8(+) T cell subsets and also responsiveness to recall antigen benchmarked against conventional intradermal (ID) injection. We show that despite a slightly lower frequency of dividing T cell receptor transgenic CD8(+) T cells in secondary lymphoid tissue at an early time point, the absolute number of CD8(+) T cells expressing an effector memory (CD62L(-)CD127(+)) and central memory (CD62L(+)CD127(+)) phenotype during peak expansion were comparable after MA and ID vaccination with a recombinant human adenovirus type 5 vector (AdHu5) encoding HIV-1 gag. Similarly, both vaccination routes generated CD8(+) memory T cell subsets detected in draining LNs for at least two years post-vaccination capable of responding to secondary antigen. These data suggest that CD8(+) T cell effector/memory generation and long-term memory is largely unaffected by physical differences in vaccine delivery to the skin via dried MA or ID suspension.

  13. Hyperlink format, categorization abilities and memory span as contributors to deaf users hypertext access.

    PubMed

    Fajardo, Inmaculada; Farjardo, Inmaculada; Arfé, Barbara; Benedetti, Patrizia; Altoé, Gianmarco

    2008-01-01

    Sixty deaf and hearing students were asked to search for goods in a Hypertext Supermarket with either graphical or textual links of high typicality, frequency, and familiarity. Additionally, they performed a picture and word categorization task and two working memory span tasks (spatial and verbal). Results showed that deaf students were faster in graphical than in verbal hypertext when the number of visited pages per search trial was blocked. Regardless of stimuli format, accuracy differences between groups did not appear, although deaf students were slower than hearing students in both Web search and categorization tasks (graphical or verbal). No relation between the two tasks was found. Correlation analyses showed that deaf students with higher spatial span were faster in graphical Web search, but no correlations emerged between verbal span and verbal Web search. A hypothesis of different strategies used by the two groups for searching information in hypertext is formulated. It is suggested that deaf users use a visual-matching strategy more than a semantic approach to make navigation decisions.

  14. Spin-based single-photon transistor, dynamic random access memory, diodes, and routers in semiconductors

    NASA Astrophysics Data System (ADS)

    Hu, C. Y.

    2016-12-01

    The realization of quantum computers and quantum Internet requires not only quantum gates and quantum memories, but also transistors at single-photon levels to control the flow of information encoded on single photons. Single-photon transistor (SPT) is an optical transistor in the quantum limit, which uses a single photon to open or block a photonic channel. In sharp contrast to all previous SPT proposals which are based on single-photon nonlinearities, here I present a design for a high-gain and high-speed (up to THz) SPT based on a linear optical effect: giant circular birefringence induced by a single spin in a double-sided optical microcavity. A gate photon sets the spin state via projective measurement and controls the light propagation in the optical channel. This spin-cavity transistor can be directly configured as diodes, routers, DRAM units, switches, modulators, etc. Due to the duality as quantum gate and transistor, the spin-cavity unit provides a solid-state platform ideal for future Internet: a mixture of all-optical Internet with quantum Internet.

  15. Explicit memory creation during sleep demonstrates a causal role of place cells in navigation.

    PubMed

    de Lavilléon, Gaetan; Lacroix, Marie Masako; Rondi-Reig, Laure; Benchenane, Karim

    2015-04-01

    Hippocampal place cells assemblies are believed to support the cognitive map, and their reactivations during sleep are thought to be involved in spatial memory consolidation. By triggering intracranial rewarding stimulations by place cell spikes during sleep, we induced an explicit memory trace, leading to a goal-directed behavior toward the place field. This demonstrates that place cells' activity during sleep still conveys relevant spatial information and that this activity is functionally significant for navigation.

  16. Directional memory arises from long-lived cytoskeletal asymmetries in polarized chemotactic cells.

    PubMed

    Prentice-Mott, Harrison V; Meroz, Yasmine; Carlson, Andreas; Levine, Michael A; Davidson, Michael W; Irimia, Daniel; Charras, Guillaume T; Mahadevan, L; Shah, Jagesh V

    2016-02-02

    Chemotaxis, the directional migration of cells in a chemical gradient, is robust to fluctuations associated with low chemical concentrations and dynamically changing gradients as well as high saturating chemical concentrations. Although a number of reports have identified cellular behavior consistent with a directional memory that could account for behavior in these complex environments, the quantitative and molecular details of such a memory process remain unknown. Using microfluidics to confine cellular motion to a 1D channel and control chemoattractant exposure, we observed directional memory in chemotactic neutrophil-like cells. We modeled this directional memory as a long-lived intracellular asymmetry that decays slower than observed membrane phospholipid signaling. Measurements of intracellular dynamics revealed that moesin at the cell rear is a long-lived element that when inhibited, results in a reduction of memory. Inhibition of ROCK (Rho-associated protein kinase), downstream of RhoA (Ras homolog gene family, member A), stabilized moesin and directional memory while depolymerization of microtubules (MTs) disoriented moesin deposition and also reduced directional memory. Our study reveals that long-lived polarized cytoskeletal structures, specifically moesin, actomyosin, and MTs, provide a directional memory in neutrophil-like cells even as they respond on short time scales to external chemical cues.

  17. Type I interferons regulate eomesodermin expression and the development of unconventional memory CD8(+) T cells.

    PubMed

    Martinet, Valérie; Tonon, Sandrine; Torres, David; Azouz, Abdulkader; Nguyen, Muriel; Kohler, Arnaud; Flamand, Véronique; Mao, Chai-An; Klein, William H; Leo, Oberdan; Goriely, Stanislas

    2015-05-08

    CD8(+) T-cell memory phenotype and function are acquired after antigen-driven activation. Memory-like cells may also arise in absence of antigenic exposure in the thymus or in the periphery. Eomesodermin (Eomes) is a key transcription factor for the development of these unconventional memory cells. Herein, we show that type I interferon signalling in CD8(+) T cells directly activates Eomes gene expression. Consistent with this observation, the phenotype, function and age-dependent expansion of 'virtual memory' CD8(+) T cells are strongly affected in absence of type I interferon signalling. In addition, type I interferons induce a sustained expansion of 'virtual memory' CD8(+) T cells in an Eomes-dependent fashion. We further show that the development of 'innate thymic' CD8(+) T cells is dependent on the same pathway. In conclusion, we demonstrate that type I interferon signalling in CD8(+) T cells drives Eomes expression and thereby regulates the function and homeostasis of memory-like CD8(+) T cells.

  18. γδ T cells come to stay: Innate skin memory in the Aldara model.

    PubMed

    Prinz, Immo; Sandrock, Inga

    2015-11-01

    The term immunological memory has long been a trademark restricted to adaptive lymphocytes such as memory B cells and plasma cells as well as memory CD8(+) αβ T cells. In recent years, innate lymphocytes such as NK cells have also been shown to adapt to their environment by antigen-specific expansion and selective survival. However, whether γδ T cells mount comparable memory responses to pathogenic stimuli is less well understood. In this issue of European Journal of Immunology, Hartwig et al. [Eur. J. Immunol. 2015. 45: 3022-3033] identify a subset of IL-17-producing γδ T cells that are capable of establishing long-lived memory in the skin of mice exposed to imiquimod in the Aldara psoriasis model. These γδ T cells uniformly express a Vγ4(+) Vδ4(+) TCR. They produce IL-17A/F and persist in the dermis for long periods of time, also at untreated distal sites. Upon secondary challenge, experienced Vγ4(+) Vδ4(+) cells show enhanced effector functions and mediate exacerbated secondary inflammation. These findings showcase innate γδ T-cell memory that uses a single conserved public TCR combination. Furthermore, they provide mechanistic insight to the observed psoriatic relapses in patients in response to topical treatment with imiquimod.

  19. Distribution and compartmentalization of human circulating and tissue-resident memory T cell subsets

    PubMed Central

    Sathaliyawala, Taheri; Kubota, Masaru; Yudanin, Naomi; Turner, Damian; Camp, Philip; Thome, Joseph J. C.; Bickham, Kara L.; Lerner, Harvey; Goldstein, Michael; Sykes, Megan; Kato, Tomoaki; Farber, Donna L.

    2012-01-01

    SUMMARY Knowledge of human T cells derives chiefly from studies of peripheral blood, whereas their distribution and function in tissues remains largely unknown. Here, we present a unique analysis of human T cells in lymphoid and mucosal tissues obtained from individual organ donors, revealing tissue-intrinsic compartmentalization of naive, effector and memory subsets conserved between diverse individuals. Effector-memory CD4+ T cells producing IL-2 predominated in mucosal tissues and accumulated as central-memory subsets in lymphoid tissue, whereas CD8+ T cells were maintained as naïve subsets in lymphoid tissues and IFN-γ-producing effector-memory CD8+ T cells in mucosal sites. The T cell activation marker, CD69, was constitutively expressed by memory T cells in all tissues, distinguishing them from circulating subsets, with mucosal memory T cells exhibiting additional distinct phenotypic and functional properties. Our results provide an assessment of human T cell compartmentalization as a new baseline for understanding human adaptive immunity. PMID:23260195

  20. Mucosal BCG Vaccination Induces Protective Lung-Resident Memory T Cell Populations against Tuberculosis

    PubMed Central

    Perdomo, Carolina; Zedler, Ulrike; Kühl, Anja A.; Lozza, Laura; Saikali, Philippe; Sander, Leif E.; Vogelzang, Alexis; Kupz, Andreas

    2016-01-01

    ABSTRACT Mycobacterium bovis Bacille Calmette-Guérin (BCG) is the only licensed vaccine against tuberculosis (TB), yet its moderate efficacy against pulmonary TB calls for improved vaccination strategies. Mucosal BCG vaccination generates superior protection against TB in animal models; however, the mechanisms of protection remain elusive. Tissue-resident memory T (TRM) cells have been implicated in protective immune responses against viral infections, but the role of TRM cells following mycobacterial infection is unknown. Using a mouse model of TB, we compared protection and lung cellular infiltrates of parenteral and mucosal BCG vaccination. Adoptive transfer and gene expression analyses of lung airway cells were performed to determine the protective capacities and phenotypes of different memory T cell subsets. In comparison to subcutaneous vaccination, intratracheal and intranasal BCG vaccination generated T effector memory and TRM cells in the lung, as defined by surface marker phenotype. Adoptive mucosal transfer of these airway-resident memory T cells into naive mice mediated protection against TB. Whereas airway-resident memory CD4+ T cells displayed a mixture of effector and regulatory phenotype, airway-resident memory CD8+ T cells displayed prototypical TRM features. Our data demonstrate a key role for mucosal vaccination-induced airway-resident T cells in the host defense against pulmonary TB. These results have direct implications for the design of refined vaccination strategies. PMID:27879332

  1. Thin Co/Ni-based bottom pinned spin-transfer torque magnetic random access memory stacks with high annealing tolerance

    SciTech Connect

    Tomczak, Y.; Swerts, J.; Mertens, S.; Lin, T.; Couet, S.; Sankaran, K.; Pourtois, G.; Kim, W.; Souriau, L.; Van Elshocht, S.; Kar, G.; Furnemont, A.; Liu, E.

    2016-01-25

    Spin-transfer torque magnetic random access memory (STT-MRAM) is considered as a replacement for next generation embedded and stand-alone memory applications. One of the main challenges in the STT-MRAM stack development is the compatibility of the stack with CMOS process flows in which thermal budgets up to 400 °C are applied. In this letter, we report on a perpendicularly magnetized MgO-based tunnel junction (p-MTJ) on a thin Co/Ni perpendicular synthetic antiferromagnetic layer with high annealing tolerance. Tunnel magneto resistance (TMR) loss after annealing occurs when the reference layer loses its perpendicular magnetic anisotropy due to reduction of the CoFeB/MgO interfacial anisotropy. A stable Co/Ni based p-MTJ stack with TMR values of 130% at resistance-area products of 9 Ω μm{sup 2} after 400 °C anneal is achieved via moment control of the Co/Ta/CoFeB reference layer. Thinning of the CoFeB polarizing layer down to 0.8 nm is the key enabler to achieve 400 °C compatibility with limited TMR loss. Thinning the Co below 0.6 nm leads to a loss of the antiferromagnetic interlayer exchange coupling strength through Ru. Insight into the thickness and moment engineering of the reference layer is displayed to obtain the best magnetic properties and high thermal stability for thin Co/Ni SAF-based STT-MRAM stacks.

  2. Entorhinal Cortical Ocean Cells Encode Specific Contexts and Drive Context-Specific Fear Memory.

    PubMed

    Kitamura, Takashi; Sun, Chen; Martin, Jared; Kitch, Lacey J; Schnitzer, Mark J; Tonegawa, Susumu

    2015-09-23

    Forming distinct representations and memories of multiple contexts and episodes is thought to be a crucial function of the hippocampal-entorhinal cortical network. The hippocampal dentate gyrus (DG) and CA3 are known to contribute to these functions, but the role of the entorhinal cortex (EC) is poorly understood. Here, we show that Ocean cells, excitatory stellate neurons in the medial EC layer II projecting into DG and CA3, rapidly form a distinct representation of a novel context and drive context-specific activation of downstream CA3 cells as well as context-specific fear memory. In contrast, Island cells, excitatory pyramidal neurons in the medial EC layer II projecting into CA1, are indifferent to context-specific encoding or memory. On the other hand, Ocean cells are dispensable for temporal association learning, for which Island cells are crucial. Together, the two excitatory medial EC layer II inputs to the hippocampus have complementary roles in episodic memory.

  3. ICAM-1-dependent tuning of memory CD8 T-cell responses following acute infection.

    PubMed

    Cox, Maureen A; Barnum, Scott R; Bullard, Daniel C; Zajac, Allan J

    2013-01-22

    CD8 T-cell responses are critical for protection against intracellular pathogens and tumors. The induction and properties of these responses are governed by a series of integrated processes that rely heavily on cell-cell interactions. Intercellular adhesion molecule (ICAM)-1 functions to enhance the strength of antigenic stimulation, extend the duration of contact with antigen-presenting cells, and augment cytokine signals, which are all factors that influence peripheral CD8 T-cell differentiation. Although previous studies suggest that ICAM-1 is essential for establishing memory T-cell populations following peptide immunization, the roles of ICAM-1 in antiviral cellular immunity are less well understood. Here we show that, following a prototypic acute viral infection, the formation and maintenance of memory-phenotype CD127(hi), KLRG-1(lo) CD8 T cells does not require ICAM-1. Nevertheless, ICAM-1 expression on nonlymphocytes dictates the phenotypic and functional attributes of the antiviral CD8 T-cell populations that develop and promotes the gradual attrition of residual effector-like CD127(lo), KLRG-1(hi) CD8 T cells during the memory phase of the response. Although memory T cells do emerge and are maintained if ICAM-1 expression is abolished, the secondary proliferative capacity of these T cells is severely curtailed. Collectively, these studies reveal potential dual roles for ICAM-1 in both promoting the decay of effector responses and programming the sensitivity of memory CD8 T cells to secondary stimuli.

  4. Non-hematopoietic cells in lymph nodes drive memory CD8 T cell inflation during murine cytomegalovirus infection.

    PubMed

    Torti, Nicole; Walton, Senta M; Brocker, Thomas; Rülicke, Thomas; Oxenius, Annette

    2011-10-01

    During human and murine cytomegalovirus (MCMV) infection an exceptionally large virus-specific CD8 T cell pool is maintained in the periphery lifelong. This anomalous response is only seen for specific subsets of MCMV-specific CD8 T cells which are referred to as 'inflationary T cells'. How memory CD8 T cell inflation is induced and maintained is unclear, though their activated phenotype strongly suggests an involvement of persistent antigen encounter during MCMV latency. To dissect the cellular and molecular requirements for memory CD8 T cell inflation, we have generated a transgenic mouse expressing an MHC class I-restricted T cell receptor specific for an immunodominant inflationary epitope of MCMV. Through a series of adoptive transfer experiments we found that memory inflation was completely dependent on antigen presentation by non-hematopoietic cells, which are also the predominant site of MCMV latency. In particular, non-hematopoietic cells selectively induced robust proliferation of inflationary CD8 T cells in lymph nodes, where a majority of the inflationary CD8 T cells exhibit a central-memory phenotype, but not in peripheral tissues, where terminally differentiated inflationary T cells accumulate. These results indicate that continuous restimulation of central memory CD8 T cells in the lymph nodes by infected non-hematopoietic cells ensures the maintenance of a functional effector CD8 T pool in the periphery, providing protection against viral reactivation events.

  5. Organic electrical bistable devices and rewritable memory cells

    NASA Astrophysics Data System (ADS)

    Ma, L. P.; Liu, J.; Yang, Y.

    2002-04-01

    Electrical bistability is a phenomenon in which a device exhibits two states of different conductivities, at the same applied voltage. We report an organic electrical bistable device (OBD) comprising of a thin metal layer embedded within the organic material, as the active medium [L. P. Ma, J. Liu, and Y. Yang, US Patent Pending, (2001)]. The performance of this device makes it attractive for memory-cell type of applications. The two states of the OBD differ in their conductivity by several orders in magnitude and show remarkable stability, i.e., once the device reaches either state, it tends to remain in that state for a prolonged period of time. More importantly, the high and low conductivity states of an OBD can be precisely controlled by the application of a positive voltage pulse (to write) or a negative voltage pulse (to erase), respectively. One million writing-erasing cycles for the OBD have been tested in ambient conditions without significant device degradation. These discoveries pave the way for newer applications, such as low-cost, large-area, flexible, high-density, electrically addressable data storage devices.

  6. Memristive behavior in a junctionless flash memory cell

    SciTech Connect

    Orak, Ikram; Ürel, Mustafa; Dana, Aykutlu; Bakan, Gokhan

    2015-06-08

    We report charge storage based memristive operation of a junctionless thin film flash memory cell when it is operated as a two terminal device by grounding the gate. Unlike memristors based on nanoionics, the presented device mode, which we refer to as the flashristor mode, potentially allows greater control over the memristive properties, allowing rational design. The mode is demonstrated using a depletion type n-channel ZnO transistor grown by atomic layer deposition (ALD), with HfO{sub 2} as the tunnel dielectric, Al{sub 2}O{sub 3} as the control dielectric, and non-stoichiometric silicon nitride as the charge storage layer. The device exhibits the pinched hysteresis of a memristor and in the unoptimized device, R{sub off}/R{sub on} ratios of about 3 are presented with low operating voltages below 5 V. A simplified model predicts R{sub off}/R{sub on} ratios can be improved significantly by adjusting the native threshold voltage of the devices. The repeatability of the resistive switching is excellent and devices exhibit 10{sup 6 }s retention time, which can, in principle, be improved by engineering the gate stack and storage layer properties. The flashristor mode can find use in analog information processing applications, such as neuromorphic computing, where well-behaving and highly repeatable memristive properties are desirable.

  7. Cross-dressed dendritic cells drive memory CD8+ T-cell activation after viral infection.

    PubMed

    Wakim, Linda M; Bevan, Michael J

    2011-03-31

    After an infection, cytotoxic T lymphocyte precursors proliferate and become effector cells by recognizing foreign peptides in the groove of major histocompatibility complex (MHC) class I molecules expressed by antigen-presenting cells (APCs). Professional APCs specialized for T-cell activation acquire viral antigen either by becoming infected themselves (direct presentation) or by phagocytosis of infected cells, followed by transfer of antigen to the cytosol, processing and MHC class I loading in a process referred to as cross-presentation. An alternative way, referred to as 'cross-dressing', by which an uninfected APC could present antigen was postulated to be by the transfer of preformed peptide-MHC complexes from the surface of an infected cell to the APC without the need of further processing. Here we show that this mechanism exists and boosts the antiviral response of mouse memory CD8(+) T cells. A number of publications have demonstrated sharing of peptide-loaded MHC molecules in vitro. Our in vitro experiments demonstrate that cross-dressing APCs do not acquire peptide-MHC complexes in the form of exosomes released by donor cells. Rather, the APCs and donor cells have to contact each other for the transfer to occur. After a viral infection, we could isolate cross-dressed APCs able to present viral antigen in vitro. Furthermore, using the diphtheria toxin system to selectively eliminate APCs that could only acquire viral peptide-MHC complexes by cross-dressing, we show that such presentation can promote the expansion of resting memory T cells. Notably, naive T cells were excluded from taking part in the response. Cross-dressing is a mechanism of antigen presentation used by dendritic cells that may have a significant role in activating previously primed CD8(+) T cells.

  8. Tracking genetically engineered lymphocytes long-term reveals the dynamics of T cell immunological memory.

    PubMed

    Oliveira, Giacomo; Ruggiero, Eliana; Stanghellini, Maria Teresa Lupo; Cieri, Nicoletta; D'Agostino, Mattia; D'Agostino, Mattio; Fronza, Raffaele; Lulay, Christina; Dionisio, Francesca; Mastaglio, Sara; Greco, Raffaella; Peccatori, Jacopo; Aiuti, Alessandro; Ambrosi, Alessandro; Biasco, Luca; Bondanza, Attilio; Lambiase, Antonio; Traversari, Catia; Vago, Luca; von Kalle, Christof; Schmidt, Manfred; Bordignon, Claudio; Ciceri, Fabio; Bonini, Chiara

    2015-12-09

    Long-lasting immune protection from pathogens and cancer requires the generation of memory T cells able to survive long-term. To unravel the immunological requirements for long-term persistence of human memory T cells, we characterized and traced, over several years, T lymphocytes genetically modified to express the thymidine kinase (TK) suicide gene that were infused in 10 patients after haploidentical hematopoietic stem cell transplantation (HSCT). At 2 to 14 years after infusion and in the presence of a broad and resting immune system, we could still detect effectors/effector memory (TEM/EFF), central memory (TCM), and stem memory (TSCM) TK(+) cells, circulating at low but stable levels in all patients. Longitudinal analysis of cytomegalovirus (CMV)- and Flu-specific TK(+) cells indicated that antigen recognition was dominant in driving in vivo expansion and persistence at detectable levels. The amount of infused TSCM cells positively correlated with early expansion and with the absolute counts of long-term persisting gene-marked cells. By combining T cell sorting with sequencing of integration (IS), TCRα and TCRβ clonal markers, we showed that T cells retrieved long-term were enriched in clones originally shared in different memory T cell subsets, whereas dominant long-term clonotypes appeared to preferentially originate from infused TSCM and TCM clones. Together, these results indicate that long-term persistence of gene-modified memory T cells after haploidentical HSCT is influenced by antigen exposure and by the original phenotype of infused cells. Cancer adoptive immunotherapy might thus benefit from cellular products enriched in lymphocytes with an early-differentiated phenotype.

  9. A Novel Read Scheme for Large Size One-Resistor Resistive Random Access Memory Array

    NASA Astrophysics Data System (ADS)

    Zackriya, Mohammed; Kittur, Harish M.; Chin, Albert

    2017-02-01

    The major issue of RRAM is the uneven sneak path that limits the array size. For the first time record large One-Resistor (1R) RRAM array of 128x128 is realized, and the array cells at the worst case still have good Low-/High-Resistive State (LRS/HRS) current difference of 378 nA/16 nA, even without using the selector device. This array has extremely low read current of 9.7 μA due to both low-current RRAM device and circuit interaction, where a novel and simple scheme of a reference point by half selected cell and a differential amplifier (DA) were implemented in the circuit design.

  10. A Novel Read Scheme for Large Size One-Resistor Resistive Random Access Memory Array

    PubMed Central

    Zackriya, Mohammed; Kittur, Harish M.; Chin, Albert

    2017-01-01

    The major issue of RRAM is the uneven sneak path that limits the array size. For the first time record large One-Resistor (1R) RRAM array of 128x128 is realized, and the array cells at the worst case still have good Low-/High-Resistive State (LRS/HRS) current difference of 378 nA/16 nA, even without using the selector device. This array has extremely low read current of 9.7 μA due to both low-current RRAM device and circuit interaction, where a novel and simple scheme of a reference point by half selected cell and a differential amplifier (DA) were implemented in the circuit design. PMID:28186147

  11. Multiplex single cell profiling of chromatin accessibility by combinatorial cellular indexing.

    PubMed

    Cusanovich, Darren A; Daza, Riza; Adey, Andrew; Pliner, Hannah A; Christiansen, Lena; Gunderson, Kevin L; Steemers, Frank J; Trapnell, Cole; Shendure, Jay

    2015-05-22

    Technical advances have enabled the collection of genome and transcriptome data sets with single-cell resolution. However, single-cell characterization of the epigenome has remained challenging. Furthermore, because cells must be physically separated before biochemical processing, conventional single-cell preparatory methods scale linearly. We applied combinatorial cellular indexing to measure chromatin accessibility in thousands of single cells per assay, circumventing the need for compartmentalization of individual cells. We report chromatin accessibility profiles from more than 15,000 single cells and use these data to cluster cells on the basis of chromatin accessibility landscapes. We identify modules of coordinately regulated chromatin accessibility at the level of single cells both between and within cell types, with a scalable method that may accelerate progress toward a human cell atlas.

  12. Multiplex Single Cell Profiling of Chromatin Accessibility by Combinatorial Cellular Indexing

    PubMed Central

    Cusanovich, Darren A.; Daza, Riza; Adey, Andrew; Pliner, Hannah; Christiansen, Lena; Gunderson, Kevin L.; Steemers, Frank J.; Trapnell, Cole

    2016-01-01

    Technical advances have enabled the collection of genome and transcriptome datasets with single-cell resolution. However, single-cell characterization of the epigenome has remained challenging. Furthermore, because cells must be physically separated prior to biochemical processing, conventional single-cell preparatory methods scale linearly. We applied combinatorial cellular indexing to measure chromatin accessibility in thousands of single cells per assay, circumventing the need for compartmentalization of individual cells. We report chromatin accessibility profiles from over 15,000 single cells and use these data to cluster cells on the basis of chromatin accessibility landscapes. We identify modules of coordinately regulated chromatin accessibility at the level of single cells both between and within cell types, with a scalable method that may accelerate progress towards a human cell atlas. PMID:25953818

  13. Interleukin-2-Dependent Allergen-Specific Tissue-Resident Memory Cells Drive Asthma.

    PubMed

    Hondowicz, Brian D; An, Dowon; Schenkel, Jason M; Kim, Karen S; Steach, Holly R; Krishnamurty, Akshay T; Keitany, Gladys J; Garza, Esteban N; Fraser, Kathryn A; Moon, James J; Altemeier, William A; Masopust, David; Pepper, Marion

    2016-01-19

    Exposure to inhaled allergens generates T helper 2 (Th2) CD4(+) T cells that contribute to episodes of inflammation associated with asthma. Little is known about allergen-specific Th2 memory cells and their contribution to airway inflammation. We generated reagents to understand how endogenous CD4(+) T cells specific for a house dust mite (HDM) allergen form and function. After allergen exposure, HDM-specific memory cells persisted as central memory cells in the lymphoid organs and tissue-resident memory cells in the lung. Experimental blockade of lymphocyte migration demonstrated that lung-resident cells were sufficient to induce airway hyper-responsiveness, which depended upon CD4(+) T cells. Investigation into the differentiation of pathogenic Trm cells revealed that interleukin-2 (IL-2) signaling was required for residency and directed a program of tissue homing migrational cues. These studies thus identify IL-2-dependent resident Th2 memory cells as drivers of lung allergic responses.

  14. Calculation of energy-barrier lowering by incoherent switching in spin-transfer torque magnetoresistive random-access memory

    SciTech Connect

    Munira, Kamaram; Visscher, P. B.

    2015-05-07

    To make a useful spin-transfer torque magnetoresistive random-access memory (STT-MRAM) device, it is necessary to be able to calculate switching rates, which determine the error rates of the device. In a single-macrospin model, one can use a Fokker-Planck equation to obtain a low-current thermally activated rate ∝exp(−E{sub eff}/k{sub B}T). Here, the effective energy barrier E{sub eff} scales with the single-macrospin energy barrier KV, where K is the effective anisotropy energy density and V the volume. A long-standing paradox in this field is that the actual energy barrier appears to be much smaller than this. It has been suggested that incoherent motions may lower the barrier, but this has proved difficult to quantify. In the present paper, we show that the coherent precession has a magnetostatic instability, which allows quantitative estimation of the energy barrier and may resolve the paradox.

  15. Switching characteristics in Cu:SiO2 by chemical soak methods for resistive random access memory (ReRAM)

    NASA Astrophysics Data System (ADS)

    Chin, Fun-Tat; Lin, Yu-Hsien; Yang, Wen-Luh; Liao, Chin-Hsuan; Lin, Li-Min; Hsiao, Yu-Ping; Chao, Tien-Sheng

    2015-01-01

    A limited copper (Cu)-source Cu:SiO2 switching layer composed of various Cu concentrations was fabricated using a chemical soaking (CS) technique. The switching layer was then studied for developing applications in resistive random access memory (ReRAM) devices. Observing the resistive switching mechanism exhibited by all the samples suggested that Cu conductive filaments formed and ruptured during the set/reset process. The experimental results indicated that the endurance property failure that occurred was related to the joule heating effect. Moreover, the endurance switching cycle increased as the Cu concentration decreased. In high-temperature tests, the samples demonstrated that the operating (set/reset) voltages decreased as the temperature increased, and an Arrhenius plot was used to calculate the activation energy of the set/reset process. In addition, the samples demonstrated stable data retention properties when baked at 85 °C, but the samples with low Cu concentrations exhibited short retention times in the low-resistance state (LRS) during 125 °C tests. Therefore, Cu concentration is a crucial factor in the trade-off between the endurance and retention properties; furthermore, the Cu concentration can be easily modulated using this CS technique.

  16. Energetics of intrinsic defects in NiO and the consequences for its resistive random access memory performance

    SciTech Connect

    Dawson, J. A. Guo, Y.; Robertson, J.

    2015-09-21

    Energetics for a variety of intrinsic defects in NiO are calculated using state-of-the-art ab initio hybrid density functional theory calculations. At the O-rich limit, Ni vacancies are the lowest cost defect for all Fermi energies within the gap, in agreement with the well-known p-type behaviour of NiO. However, the ability of the metal electrode in a resistive random access memory metal-oxide-metal setup to shift the oxygen chemical potential towards the O-poor limit results in unusual NiO behaviour and O vacancies dominating at lower Fermi energy levels. Calculated band diagrams show that O vacancies in NiO are positively charged at the operating Fermi energy giving it the advantage of not requiring a scavenger metal layer to maximise drift. Ni and O interstitials are generally found to be higher in energy than the respective vacancies suggesting that significant recombination of O vacancies and interstitials does not take place as proposed in some models of switching behaviour.

  17. Material insights of HfO2-based integrated 1-transistor-1-resistor resistive random access memory devices processed by batch atomic layer deposition

    NASA Astrophysics Data System (ADS)

    Niu, Gang; Kim, Hee-Dong; Roelofs, Robin; Perez, Eduardo; Schubert, Markus Andreas; Zaumseil, Peter; Costina, Ioan; Wenger, Christian

    2016-06-01

    With the continuous scaling of resistive random access memory (RRAM) devices, in-depth understanding of the physical mechanism and the material issues, particularly by directly studying integrated cells, become more and more important to further improve the device performances. In this work, HfO2-based integrated 1-transistor-1-resistor (1T1R) RRAM devices were processed in a standard 0.25 μm complementary-metal-oxide-semiconductor (CMOS) process line, using a batch atomic layer deposition (ALD) tool, which is particularly designed for mass production. We demonstrate a systematic study on TiN/Ti/HfO2/TiN/Si RRAM devices to correlate key material factors (nano-crystallites and carbon impurities) with the filament type resistive switching (RS) behaviours. The augmentation of the nano-crystallites density in the film increases the forming voltage of devices and its variation. Carbon residues in HfO2 films turn out to be an even more significant factor strongly impacting the RS behaviour. A relatively higher deposition temperature of 300 °C dramatically reduces the residual carbon concentration, thus leading to enhanced RS performances of devices, including lower power consumption, better endurance and higher reliability. Such thorough understanding on physical mechanism of RS and the correlation between material and device performances will facilitate the realization of high density and reliable embedded RRAM devices with low power consumption.

  18. Material insights of HfO2-based integrated 1-transistor-1-resistor resistive random access memory devices processed by batch atomic layer deposition.

    PubMed

    Niu, Gang; Kim, Hee-Dong; Roelofs, Robin; Perez, Eduardo; Schubert, Markus Andreas; Zaumseil, Peter; Costina, Ioan; Wenger, Christian

    2016-06-17

    With the continuous scaling of resistive random access memory (RRAM) devices, in-depth understanding of the physical mechanism and the material issues, particularly by directly studying integrated cells, become more and more important to further improve the device performances. In this work, HfO2-based integrated 1-transistor-1-resistor (1T1R) RRAM devices were processed in a standard 0.25 μm complementary-metal-oxide-semiconductor (CMOS) process line, using a batch atomic layer deposition (ALD) tool, which is particularly designed for mass production. We demonstrate a systematic study on TiN/Ti/HfO2/TiN/Si RRAM devices to correlate key material factors (nano-crystallites and carbon impurities) with the filament type resistive switching (RS) behaviours. The augmentation of the nano-crystallites density in the film increases the forming voltage of devices and its variation. Carbon residues in HfO2 films turn out to be an even more significant factor strongly impacting the RS behaviour. A relatively higher deposition temperature of 300 °C dramatically reduces the residual carbon concentration, thus leading to enhanced RS performances of devices, including lower power consumption, better endurance and higher reliability. Such thorough understanding on physical mechanism of RS and the correlation between material and device performances will facilitate the realization of high density and reliable embedded RRAM devices with low power consumption.

  19. Material insights of HfO2-based integrated 1-transistor-1-resistor resistive random access memory devices processed by batch atomic layer deposition

    PubMed Central

    Niu, Gang; Kim, Hee-Dong; Roelofs, Robin; Perez, Eduardo; Schubert, Markus Andreas; Zaumseil, Peter; Costina, Ioan; Wenger, Christian

    2016-01-01

    With the continuous scaling of resistive random access memory (RRAM) devices, in-depth understanding of the physical mechanism and the material issues, particularly by directly studying integrated cells, become more and more important to further improve the device performances. In this work, HfO2-based integrated 1-transistor-1-resistor (1T1R) RRAM devices were processed in a standard 0.25 μm complementary-metal-oxide-semiconductor (CMOS) process line, using a batch atomic layer deposition (ALD) tool, which is particularly designed for mass production. We demonstrate a systematic study on TiN/Ti/HfO2/TiN/Si RRAM devices to correlate key material factors (nano-crystallites and carbon impurities) with the filament type resistive switching (RS) behaviours. The augmentation of the nano-crystallites density in the film increases the forming voltage of devices and its variation. Carbon residues in HfO2 films turn out to be an even more significant factor strongly impacting the RS behaviour. A relatively higher deposition temperature of 300 °C dramatically reduces the residual carbon concentration, thus leading to enhanced RS performances of devices, including lower power consumption, better endurance and higher reliability. Such thorough understanding on physical mechanism of RS and the correlation between material and device performances will facilitate the realization of high density and reliable embedded RRAM devices with low power consumption. PMID:27312225

  20. Distinct Effects of Saracatinib on Memory CD8+ T-cell Differentiation

    PubMed Central

    Takai, Shinji; Sabzevari, Helen; Farsaci, Benedetto; Schlom, Jeffrey; Greiner, John W.

    2012-01-01

    Immunologic memory involving CD8+ T-cells is a hallmark of an adaptive antigen-specific immune response and comprises a critical component of protective immunity. Designing approaches that enhance long-term T-cell memory would, for the most part, fortify vaccines and enhance host protection against infectious diseases and, perhaps, cancer immunotherapy. A better understanding of the cellular programs involved in the antigen-specific T-cell response has led to new approaches that target the magnitude and quality of the memory T-cell response. Here we show that T-cells from T-cell receptor transgenic mice for the nucleoprotein of influenza virus NP68 exhibit the distinct phases priming, expansion, contraction, memory - of an antigen-specific T-cell response when exposed in vitro to the cognate peptide. Saracatinib, a specific inhibitor of Src family kinases, administered at low doses during the expansion or contraction phases, increased CD62Lhigh/CD44high central memory CD8+ T-cells and IFN-γ production, while suppressing immunity when added during the priming phase. These effects by saracatinib were not accompanied by the expected decline of Src family kinases, but were accompanied by Akt-mTOR suppression and/or mediated via another pathway. Increased central memory cells by saracatinib were recapitulated in mice using a poxvirus-based influenza vaccine, thus underscoring the importance of dose and timing of the inhibitor in the context of memory T-cell differentiation. Finally, vaccine plus saracatinib treatment showed better protection against tumor challenge. The immune-potentiating effects on CD8+ T-cells by a low dose of saracatinib might afford better protection from pathogen or cancer when combined with vaccine. PMID:22450814

  1. A stochastic model of chromatin modification: cell population coding of winter memory in plants.

    PubMed

    Satake, Akiko; Iwasa, Yoh

    2012-06-07

    Biological memory, a sustained cellular response to a transient stimulus, has been found in many natural systems. The best example in plants is the winter memory by which plants can flower in favorable conditions in spring. For this winter memory, epigenetic regulation of FLOWERING LOCUS C (FLC), which acts as a floral repressor, plays a key role. Exposure to prolonged periods of cold results in the gradual suppression of FLC, which allows plants to measure the length of cold and to flower only after a sufficiently long winter. Although many genes involved in histone modifications have been isolated, molecular mechanisms of winter memory are not well understood. Here, we develop a model for chromatin modification, in which the dynamics of a single nucleosome are aggregated to on/off behavior of FLC expression at the cellular level and further integrated to a change of FLC expression at the whole-plant level. We propose cell-population coding of winter memory: each cell is described as a bistable system that shows heterogeneous timing of the transition from on to off in FLC expression under cold and measures the length of cold as the proportion of cells in the off state. This mechanism well explains robust FLC regulation and stable inheritance of winter memory after cell division in response to noisy signals. Winter memory lasts longer if deposition of the repressive histone mark occurs faster. A difference in deposition speed would discriminate between stable maintenance of FLC repression in annuals and transient expression in perennials.

  2. Atypical and classical memory B cells produce Plasmodium falciparum neutralizing antibodies

    PubMed Central

    Muellenbeck, Matthias F.; Ueberheide, Beatrix; Amulic, Borko; Epp, Alexandra; Fenyo, David; Busse, Christian E.; Esen, Meral; Theisen, Michael; Mordmüller, Benjamin

    2013-01-01

    Antibodies can protect from Plasmodium falciparum (Pf) infection and clinical malaria disease. However, in the absence of constant reexposure, serum immunoglobulin (Ig) levels rapidly decline and full protection from clinical symptoms is lost, suggesting that B cell memory is functionally impaired. We show at the single cell level that natural Pf infection induces the development of classical memory B cells (CM) and atypical memory B cells (AtM) that produce broadly neutralizing antibodies against blood stage Pf parasites. CM and AtM contribute to anti-Pf serum IgG production, but only AtM show signs of active antibody secretion. AtM and CM were also different in their IgG gene repertoire, suggesting that they develop from different precursors. The findings provide direct evidence that natural Pf infection leads to the development of protective memory B cell antibody responses and suggest that constant immune activation rather than impaired memory function leads to the accumulation of AtM in malaria. Understanding the memory B cell response to natural Pf infection may be key to the development of a malaria vaccine that induces long-lived protection. PMID:23319701

  3. Aging promotes acquisition of naive-like CD8+ memory T cell traits and enhanced functionalities.

    PubMed

    Eberlein, Jens; Davenport, Bennett; Nguyen, Tom; Victorino, Francisco; Haist, Kelsey; Jhun, Kevin; Karimpour-Fard, Anis; Hunter, Lawrence; Kedl, Ross; Clambey, Eric T; Homann, Dirk

    2016-10-03

    Protective T cell memory is an acquired trait that is contingent upon the preservation of its constituents and therefore vulnerable to the potentially deleterious effects of organismal aging. Here, however, we have found that long-term T cell memory in a natural murine host-pathogen system can substantially improve over time. Comprehensive molecular, phenotypic, and functional profiling of aging antiviral CD8+ memory T cells (CD8+ TM) revealed a pervasive remodeling process that promotes the gradual acquisition of distinct molecular signatures, of increasingly homogeneous phenotypes, and of diversified functionalities that combine to confer a CD8+ TM-autonomous capacity for enhanced recall responses and immune protection. Notably, the process of CD8+ TM aging is characterized by a progressive harmonization of memory and naive T cell traits, is broadly amenable to experimental acceleration or retardation, and serves as a constitutional component for the "rebound model" of memory T cell maturation. By casting CD8+ TM populations within the temporal framework of their slowly evolving properties, this model establishes a simple ontogenetic perspective on the principal organization of CD8+ T cell memory that may directly inform the development of improved diagnostic, prophylactic, and therapeutic modalities.

  4. Aging promotes acquisition of naive-like CD8+ memory T cell traits and enhanced functionalities

    PubMed Central

    Davenport, Bennett; Nguyen, Tom; Victorino, Francisco; Haist, Kelsey; Jhun, Kevin; Karimpour-Fard, Anis; Hunter, Lawrence; Kedl, Ross; Clambey, Eric T.

    2016-01-01

    Protective T cell memory is an acquired trait that is contingent upon the preservation of its constituents and therefore vulnerable to the potentially deleterious effects of organismal aging. Here, however, we have found that long-term T cell memory in a natural murine host-pathogen system can substantially improve over time. Comprehensive molecular, phenotypic, and functional profiling of aging antiviral CD8+ memory T cells (CD8+ TM) revealed a pervasive remodeling process that promotes the gradual acquisition of distinct molecular signatures, of increasingly homogeneous phenotypes, and of diversified functionalities that combine to confer a CD8+ TM–autonomous capacity for enhanced recall responses and immune protection. Notably, the process of CD8+ TM aging is characterized by a progressive harmonization of memory and naive T cell traits, is broadly amenable to experimental acceleration or retardation, and serves as a constitutional component for the “rebound model” of memory T cell maturation. By casting CD8+ TM populations within the temporal framework of their slowly evolving properties, this model establishes a simple ontogenetic perspective on the principal organization of CD8+ T cell memory that may directly inform the development of improved diagnostic, prophylactic, and therapeutic modalities. PMID:27617858

  5. 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.

  6. Functional classification of memory CD8+ T cells by CX3CR1 expression

    PubMed Central

    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.

    2015-01-01

    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 CD62LhiCX3CR1+ 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. PMID:26404698

  7. Target morphology and cell memory: a model of regenerative pattern formation

    PubMed Central

    Bessonov, Nikolai; Levin, Michael; Morozova, Nadya; Reinberg, Natalia; Tosenberger, Alen; Volpert, Vitaly

    2015-01-01

    Despite the growing body of work on molecular components required for regenerative repair, we still lack a deep understanding of the ability of some animal species to regenerate their appropriate complex anatomical structure following damage. A key question is how regenerating systems know when to stop growth and remodeling – what mechanisms implement recognition of correct morphology that signals a stop condition? In this work, we review two conceptual models of pattern regeneration that implement a kind of pattern memory. In the first one, all cells communicate with each other and keep the value of the total signal received from the other cells. If a part of the pattern is amputated, the signal distribution changes. The difference fromthe original signal distribution stimulates cell proliferation and leads to pattern regeneration, in effect implementing an error minimization process that uses signaling memory to achieve pattern correction. In the second model, we consider a more complex pattern organization with different cell types. Each tissue contains a central (coordinator) cell that controls the tissue and communicates with the other central cells. Each of them keeps memory about the signals received from other central cells. The values of these signals depend on the mutual cell location, and the memory allows regeneration of the structure when it is modified. The purpose of these models is to suggest possible mechanisms of pattern regeneration operating on the basis of cell memory which are compatible with diverse molecular implementation mechanisms within specific organisms. PMID:26889161

  8. Quantifying susceptibility of CD4+ stem memory T-cells to infection by laboratory adapted and clinical HIV-1 strains.

    PubMed

    Flynn, Jacqueline K; Paukovics, Geza; Cashin, Kieran; Borm, Katharina; Ellett, Anne; Roche, Michael; Jakobsen, Martin R; Churchill, Melissa J; Gorry, Paul R

    2014-02-10

    CD4+ T cells are principal targets for human immunodeficiency virus type 1 (HIV-1) infection. CD4+ T cell subsets are heterogeneous cell populations, divided by functional and phenotypic differences into naïve and memory T cells. The memory CD4+ T cells are further segregated into central, effector and transitional memory cell subsets by functional, phenotypic and homeostatic characteristics. Defining the distribution of HIV-1 infection in different T cell subsets is important, as this can play a role in determining the size and composition of the viral reservoir. Both central memory and transitional memory CD4+ T cells have been described as long-lived viral reservoirs for HIV. Recently, the newly described stem memory T cell subset has also been implicated as a long-lived HIV reservoir. Using green fluorescent protein (GFP) reporter strains of HIV-1 and multi parameter flow cytometry, we developed an assay to simultaneously quantify the susceptibility of stem memory (TSCM), central memory, effector memory, transitional memory and naïve CD4+ T cell subsets, to HIV-1 infection in vitro. We show that TSCM are susceptible to infection with laboratory adapted and clinical HIV-1 strains. Our system facilitates the quantitation of HIV-1 infection in alternative T cell subsets by CCR5- and CXCR4-using viruses across different HIV-1 subtypes, and will be useful for studies of HIV-1 pathogenesis and viral reservoirs.

  9. Quantifying Susceptibility of CD4+ Stem Memory T-Cells to Infection by Laboratory Adapted and Clinical HIV-1 Strains

    PubMed Central

    Flynn, Jacqueline K.; Paukovics, Geza; Cashin, Kieran; Borm, Katharina; Ellett, Anne; Roche, Michael; Jakobsen, Martin R.; Churchill, Melissa J.; Gorry, Paul R.

    2014-01-01

    CD4+ T cells are principal targets for human immunodeficiency virus type 1 (HIV-1) infection. CD4+ T cell subsets are heterogeneous cell populations, divided by functional and phenotypic differences into naïve and memory T cells. The memory CD4+ T cells are further segregated into central, effector and transitional memory cell subsets by functional, phenotypic and homeostatic characteristics. Defining the distribution of HIV-1 infection in different T cell subsets is important, as this can play a role in determining the size and composition of the viral reservoir. Both central memory and transitional memory CD4+ T cells have been described as long-lived viral reservoirs for HIV. Recently, the newly described stem memory T cell subset has also been implicated as a long-lived HIV reservoir. Using green fluorescent protein (GFP) reporter strains of HIV-1 and multi parameter flow cytometry, we developed an assay to simultaneously quantify the susceptibility of stem memory (TSCM), central memory, effector memory, transitional memory and naïve CD4+ T cell subsets, to HIV-1 infection in vitro. We show that TSCM are susceptible to infection with laboratory adapted and clinical HIV-1 strains. Our system facilitates the quantitation of HIV-1 infection in alternative T cell subsets by CCR5- and CXCR4-using viruses across different HIV-1 subtypes, and will be useful for studies of HIV-1 pathogenesis and viral reservoirs. PMID:24517971

  10. Limited clonal relatedness between gut IgA plasma cells and memory B cells after oral immunization

    PubMed Central

    Bemark, Mats; Hazanov, Helena; Strömberg, Anneli; Komban, Rathan; Holmqvist, Joel; Köster, Sofia; Mattsson, Johan; Sikora, Per; Mehr, Ramit; Lycke, Nils Y.

    2016-01-01

    Understanding how memory B cells are induced and relate to long-lived plasma cells is important for vaccine development. Immunity to oral vaccines has been considered short-lived because of a poor ability to develop IgA B-cell memory. Here we demonstrate that long-lived mucosal IgA memory is readily achieved by oral but not systemic immunization in mouse models with NP hapten conjugated with cholera toxin and transfer of B1-8high/GFP+ NP-specific B cells. Unexpectedly, memory B cells are poorly related to long-lived plasma cells and less affinity-matured. They are α4β7-integrin+CD73+PD-L2+CD80+ and at systemic sites mostly IgM+, while 80% are IgA+ in Peyer's patches. On reactivation, most memory B cells in Peyer's patches are GL7−, but expand in germinal centres and acquire higher affinity and more mutations, demonstrating strong clonal selection. CCR9 expression is found only in Peyer's patches and appears critical for gut homing. Thus, gut mucosal memory possesses unique features not seen after systemic immunization. PMID:27596266

  11. Distinct effects of saracatinib on memory CD8+ T cell differentiation.

    PubMed

    Takai, Shinji; Sabzevari, Helen; Farsaci, Benedetto; Schlom, Jeffrey; Greiner, John W

    2012-05-01

    Immunologic memory involving CD8(+) T cells is a hallmark of an adaptive Ag-specific immune response and constitutes a critical component of protective immunity. Designing approaches that enhance long-term T cell memory would, for the most part, fortify vaccines and enhance host protection against infectious diseases and, perhaps, cancer immunotherapy. A better understanding of the cellular programs involved in the Ag-specific T cell response has led to new approaches that target the magnitude and quality of the memory T cell response. In this article, we show that T cells from TCR transgenic mice for the nucleoprotein of influenza virus NP68 exhibit the distinct phases--priming, expansion, contraction, and memory--of an Ag-specific T cell response when exposed in vitro to the cognate peptide. Saracatinib, a specific inhibitor of Src family kinases, administered at low doses during the expansion or contraction phases, increased CD62L(high)/CD44(high) central memory CD8(+) T cells and IFN-γ production but suppressed immunity when added during the priming phase. These effects by saracatinib were not accompanied by the expected decline of Src family kinases but were accompanied by Akt-mammalian target of rapamycin suppression and/or mediated via another pathway. Increased central memory cells by saracatinib were recapitulated in mice using a poxvirus-based influenza vaccine, thus underscoring the importance of dose and timing of the inhibitor in the context of memory T cell differentiation. Finally, vaccine plus saracatinib treatment showed better protection against tumor challenge. The immune-potentiating effects on CD8(+) T cells by a low dose of saracatinib might afford better protection from pathogens or cancer when combined with vaccine.

  12. Invariant NKT cells induce plasmacytoid dendritic cell (DC) cross-talk with conventional DCs for efficient memory CD8+ T cell induction.

    PubMed

    Shimizu, Kanako; Asakura, Miki; Shinga, Jun; Sato, Yusuke; Kitahara, Shuji; Hoshino, Katsuaki; Kaisho, Tsuneyasu; Schoenberger, Stephen P; Ezaki, Taichi; Fujii, Shin-ichiro

    2013-06-01

    A key goal of vaccine immunotherapy is the generation of long-term memory CD8(+) T cells capable of mediating immune surveillance. We discovered a novel intercellular pathway governing the development of potent memory CD8(+) T cell responses against cell-associated Ags that is mediated through cross-presentation by XCR1(+) dendritic cells (DCs). Generation of CD8(+) memory T cells against tumor cells pulsed with an invariant NKT cell ligand depended on cross-talk between XCR1(+) and plasmacytoid DCs that was regulated by IFN-α/IFN-αR signals. IFN-α production by plasmacytoid DCs was stimulated by an OX40 signal from the invariant NKT cells, as well as an HMGB1 signal from the dying tumor cells. These findings reveal a previously unknown pathway of intercellular collaboration for the generation of tumor-specific CD8(+) memory T cells that can be exploited for strategic vaccination in the setting of tumor immunotherapy.

  13. Leishmania infantum antigens modulate memory cell subsets of liver resident T lymphocyte.

    PubMed

    Rodrigues, A; Claro, M; Alexandre-Pires, G; Santos-Mateus, D; Martins, C; Valério-Bolas, A; Rafael-Fernandes, M; Pereira, M A; Pereira da Fonseca, I; Tomás, A M; Santos-Gomes, G

    2017-02-01

    In the recent years, the liver has been recognized as an important immune organ with major regulatory functions and immune memory, adding to the well-described vital metabolic functions. There are evidences from experimental infections performed with visceral Leishmania species that immune responses to parasite infection can be organ-specific. The liver is the compartment of acute resolving infection, with minimal tissue damage and resistance to reinfection, whereas the spleen is the compartment of parasite persistence. Control of hepatic infection in mice requires a coordinated immune response that involves the development of inflammatory granulomas. It is also described that the liver harbors populations of resident lymphocytes, which may exhibit memory characteristics. Therefore, the present study aims to address the role of the liver as an immune memory organ in the context of Leishmania infantum infection, by characterizing phenotypically resident liver T lymphocytes. The dynamics of memory T cells in L. infantum infected BALB/c mice and the effect of anti-leishmanial treatment in the differentiation of memory cell subsets were analyzed. The potential of recognition, differentiation and selection of memory lymphocytes by three L. infantum recombinant proteins were also explored. L. infantum infection generates effector and central memory T cells, but the cells did not expand when recalled, demonstrating a possible parasite silencing effect. The treatment with a leishmanicidal drug (antimoniate meglumine) increases the levels of memory and effector T cells, eliciting a more robust hepatic immune response. L. infantum parasites with a decreased sensitivity to the leishmanicidal drug favor the expansion of memory CD8(+) T cell subset, but inhibit the proliferation of CD8(+) T effector cells, possibly assuring their own survival. The recombinant proteins LirCyp1 and LirSOD are strongly recognized by memory cells of treated mice, indicating that these proteins

  14. Total ionizing dose effect of γ-ray radiation on the switching characteristics and filament stability of HfOx resistive random access memory

    SciTech Connect

    Fang, Runchen; Yu, Shimeng; Gonzalez Velo, Yago; Chen, Wenhao; Holbert, Keith E.; Kozicki, Michael N.; Barnaby, Hugh

    2014-05-05

    The total ionizing dose (TID) effect of gamma-ray (γ-ray) irradiation on HfOx based resistive random access memory was investigated by electrical and material characterizations. The memory states can sustain TID level ∼5.2 Mrad (HfO{sub 2}) without significant change in the functionality or the switching characteristics under pulse cycling. However, the stability of the filament is weakened after irradiation as memory states are more vulnerable to flipping under the electrical stress. X-ray photoelectron spectroscopy was performed to ascertain the physical mechanism of the stability degradation, which is attributed to the Hf-O bond breaking by the high-energy γ-ray exposure.

  15. Fabrication and properties of nanoscale multiferroic heterostructures for application in magneto-electric random access memory (MERAM) devices

    NASA Astrophysics Data System (ADS)

    Kim, Gunwoo

    Magnetoelectric random access memory (MERAM) has emerged as a promising new class of non-volatile solid-state memory device. It offers nondestructive reading along with low power consumption during the write operation. A common implementation of MERAM involves use of multiferroic tunneling junctions (MFTJs), which besides offering non-volatility are both electrically and magnetically tunable. Fundamentally, a MFTJ consists of a heterostructure of an ultrathin multiferroic or ferroelectric material as the active tunneling barrier sandwiched between ferromagnetic electrodes. Thereby, the MFTJ exhibits both tunnel electroresistance (TER) and tunnel magnetoresistance (TMR) effects with application of an electric and magnetic field, respectively. In this thesis work, we have developed two-dimensional (2D) thin-film multiferroic heterostructure METJ prototypes consisting of ultrathin ferroelectric BaTiO3 (BTO) layer and a conducting ferromagnetic La0.67Sr 0.33MnO3 (LSMO) electrode. The heteroepitaxial films are grown using the pulsed laser deposition (PLD) technique. This oxide heterostructure offers the opportunity to study the nano-scale details of the tunnel electroresistance (TER) effect using scanning probe microscopy techniques. We performed the measurements using the MFP-3D (Asylum Research) scanning probe microscope. The ultrathin BTO films (1.2-2.0 nm) grown on LSMO electrodes display both ferro- and piezo-electric properties and exhibit large tunnel resistance effect. We have explored the growth and properties of one-dimensional (1D) heterostructures, referred to as multiferoric nanowire (NW) heterostructures. The ferromagnetic/ferroelectric composite heterostructures are grown as sheath layers using PLD on lattice-matched template NWs, e.g. MgO, that are deposited by chemical vapor deposition utilizing the vapor-liquid-solid (VLS) mechanism. The one-dimensional geometry can substantially overcome the clamping effect of the substrate present in two

  16. CD22 is required for formation of memory B cell precursors within germinal centers

    PubMed Central

    Chappell, Craig P.; Draves, Kevin E.

    2017-01-01

    CD22 is a BCR co-receptor that regulates B cell signaling, proliferation and survival and is required for T cell-independent Ab responses. To investigate the role of CD22 during T cell-dependent (TD) Ab responses and memory B cell formation, we analyzed Ag-specific B cell responses generated by wild-type (WT) or CD22-/- B cells following immunization with a TD Ag. CD22-/- B cells mounted normal early Ab responses yet failed to generate either memory B cells or long-lived plasma cells, whereas WT B cells formed both populations. Surprisingly, B cell expansion and germinal center (GC) differentiation were comparable between WT and CD22-/- B cells. CD22-/- B cells, however, were significantly less capable of generating a population of CXCR4hiCD38hi GC B cells, which we propose represent memory B cell precursors within GCs. These results demonstrate a novel role for CD22 during TD humoral responses evident during primary GC formation and underscore that CD22 functions not only during B cell maturation but also during responses to both TD and T cell-independent antigens. PMID:28346517

  17. 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

    2017-03-15

    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.

  18. A New Differential Logic-Compatible Multiple-Time Programmable Memory Cell

    NASA Astrophysics Data System (ADS)

    Tsai, Yi-Hung; Yang, Hsiao-Lan; Lin, Wun-Jie; Lin, Chrong Jung; King, Ya-Chin

    2010-04-01

    This work presents a novel differential n-channel logic-compatible multiple-time programmable (MTP) memory cell. This cell features double sensing window by a differential pair of floating gates, and therefore increases the retention lifetime of the nonvolatile memory effectively. Also, a self-selective programming (SSP) method is innovated in writing one pair differential data by a single cell without increasing any design or process complexity in peripheral circuit. The differential cell is a promising MTP solution to challenge thin floating gate oxide below 70 Å for 90 nm complementary metal-oxide-semiconductor (CMOS) node and beyond.

  19. Chromaffin cell grafts to rat cerebral cortex reverse lesion-induced memory deficits.

    PubMed

    Welner, S A; Koty, Z C; Boksa, P

    1990-09-10

    Adrenal chromaffin cells were isolated from donor adult rats and transplanted to the cerebral cortex of bilaterally nucleus basalis magnocellularis-lesioned rats. Chromaffin cell grafts to lesioned animals completely reversed the spatial memory deficit seen in lesioned alone animals on a T-maze alternation task. Although chromaffin cell grafts have been used previously to reverse motor abnormalities arising from defective nigro-striatal aminergic transmission, the present report is the first evidence that chromaffin cell transplants can reverse deficits in memory function. Grafts also enhanced cortical acetylcholinesterase staining.

  20. Sustained CD8+ T cell memory inflation after infection with a single-cycle cytomegalovirus.

    PubMed

    Snyder, Christopher M; Cho, Kathy S; Bonnett, Elizabeth L; Allan, Jane E; Hill, Ann B

    2011-10-01

    Cytomegalovirus (CMV) is a β-herpesvirus that establishes a lifelong latent or persistent infection. A hallmark of chronic CMV infection is the lifelong persistence of large numbers of virus-specific CD8+ effector/effector memory T cells, a phenomenon called "memory inflation". How the virus continuously stimulates these T cells without being eradicated remains an enigma. The prevailing view is that CMV establishes a low grade "smoldering" infection characterized by tiny bursts of productive infection which are rapidly extinguished, leaving no detectable virus but replenishing the latent pool and leaving the immune system in a highly charged state. However, since abortive reactivation with limited viral gene expression is known to occur commonly, we investigated the necessity for virus reproduction in maintaining the inflationary T cell pool. We inhibited viral replication or spread in vivo using two different mutants of murine CMV (MCMV). First, famcyclovir blocked the replication of MCMV encoding the HSV Thymidine Kinase gene, but had no impact on the CD8+ T cell memory inflation once the infection was established. Second, MCMV that lacks the essential glycoprotein L, and thus is completely unable to spread from cell to cell, also drove memory inflation if the virus was administered systemically. Our data suggest that CMV which cannot spread from the cells it initially infects can repeatedly generate viral antigens to drive memory inflation without suffering eradication of the latent genome pool.

  1. Regulation of Antigen-Experienced T Cells: Lessons from the Quintessential Memory Marker CD44

    PubMed Central

    Baaten, Bas J. G.; Tinoco, Roberto; Chen, Alex T.; Bradley, Linda M.

    2011-01-01

    Despite the widespread use of the cell-surface receptor CD44 as a marker for antigen (Ag)-experienced, effector and memory T cells, surprisingly little is known regarding its function on these cells. The best-established function of CD44 is the regulation of cell adhesion and migration. As such, the interactions of CD44, primarily with its major ligand, the extracellular matrix (ECM) component hyaluronic acid (HA), can be crucial for the recruitment and function of effector and memory T cells into/within inflamed tissues. However, little is known about the signaling events following engagement of CD44 on T cells and how cooperative interactions of CD44 with other surface receptors affect T cell responses. Recent evidence suggests that the CD44 signaling pathway(s) may be shared with those of other adhesion receptors, and that these provide contextual signals at different anatomical sites to ensure the correct T cell effector responses. Furthermore, CD44 ligation may augment T cell activation after Ag encounter and promote T cell survival, as well as contribute to regulation of the contraction phase of an immune response and the maintenance of tolerance. Once the memory phase is established, CD44 may have a role in ensuring the functional fitness of memory T cells. Thus, the summation of potential signals after CD44 ligation on T cells highlights that migration and adhesion to the ECM can critically impact the development and homeostasis of memory T cells, and may differentially affect subsets of T cells. These aspects of CD44 biology on T cells and how they might be modulated for translational purposes are discussed. PMID:22566907

  2. Brain-resident memory T cells represent an autonomous cytotoxic barrier to viral infection

    PubMed Central

    Vincenti, Ilena; Wagner, Ingrid; Pinschewer, Daniel

    2016-01-01

    Tissue-resident memory T cells (TRM) persist at sites of prior infection and have been shown to enhance pathogen clearance by recruiting circulating immune cells and providing bystander activation. Here, we characterize the functioning of brain-resident memory T cells (bTRM) in an animal model of viral infection. bTRM were subject to spontaneous homeostatic proliferation and were largely refractory to systemic immune cell depletion. After viral reinfection in mice, bTRM rapidly acquired cytotoxic effector function and prevented fatal brain infection, even in the absence of circulating CD8+ memory T cells. Presentation of cognate antigen on MHC-I was essential for bTRM-mediated protective immunity, which involved perforin- and IFN-γ–dependent effector mechanisms. These findings identify bTRM as an organ-autonomous defense system serving as a paradigm for TRM functioning as a self-sufficient first line of adaptive immunity. PMID:27377586

  3. Dynamic T cell migration program provides resident memory within intestinal epithelium

    PubMed Central

    Choo, Daniel; Vezys, Vaiva; Wherry, E. John; Duraiswamy, Jaikumar; Akondy, Rama; Wang, Jun; Casey, Kerry A.; Barber, Daniel L.; Kawamura, Kim S.; Fraser, Kathryn A.; Webby, Richard J.; Brinkmann, Volker; Butcher, Eugene C.; Newell, Kenneth A.

    2010-01-01

    Migration to intestinal mucosa putatively depends on local activation because gastrointestinal lymphoid tissue induces expression of intestinal homing molecules, whereas skin-draining lymph nodes do not. This paradigm is difficult to reconcile with reports of intestinal T cell responses after alternative routes of immunization. We reconcile this discrepancy by demonstrating that activation within spleen results in intermediate induction of homing potential to the intestinal mucosa. We further demonstrate that memory T cells within small intestine epithelium do not routinely recirculate with memory T cells in other tissues, and we provide evidence that homing is similarly dynamic in humans after subcutaneous live yellow fever vaccine immunization. These data explain why systemic immunization routes induce local cell-mediated immunity within the intestine and indicate that this tissue must be seeded with memory T cell precursors shortly after activation. PMID:20156972

  4. Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells

    PubMed Central

    Hurton, Lenka V.; Singh, Harjeet; Najjar, Amer M.; Switzer, Kirsten C.; Mi, Tiejuan; Maiti, Sourindra; Olivares, Simon; Rabinovich, Brian; Huls, Helen; Forget, Marie-Andrée; Datar, Vrushali; Kebriaei, Partow; Lee, Dean A.; Champlin, Richard E.; Cooper, Laurence J. N.

    2016-01-01

    Adoptive immunotherapy retargeting T cells to CD19 via a chimeric antigen receptor (CAR) is an investigational treatment capable of inducing complete tumor regression of B-cell malignancies when there is sustained survival of infused cells. T-memory stem cells (TSCM) retain superior potential for long-lived persistence, but challenges exist in manufacturing this T-cell subset because they are rare among circulating lymphocytes. We report a clinically relevant approach to generating CAR+ T cells with preserved TSCM potential using the Sleeping Beauty platform. Because IL-15 is fundamental to T-cell memory, we incorporated its costimulatory properties by coexpressing CAR with a membrane-bound chimeric IL-15 (mbIL15). The mbIL15-CAR T cells signaled through signal transducer and activator of transcription 5 to yield improved T-cell persistence independent of CAR signaling, without apparent autonomous growth or transformation, and achieved potent rejection of CD19+ leukemia. Long-lived T cells were CD45ROnegCCR7+CD95+, phenotypically most similar to TSCM, and possessed a memory-like transcriptional profile. Overall, these results demonstrate that CAR+ T cells can develop long-term persistence with a memory stem-cell phenotype sustained by signaling through mbIL15. This observation warrants evaluation in clinical trials. PMID:27849617

  5. Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells.

    PubMed

    Hurton, Lenka V; Singh, Harjeet; Najjar, Amer M; Switzer, Kirsten C; Mi, Tiejuan; Maiti, Sourindra; Olivares, Simon; Rabinovich, Brian; Huls, Helen; Forget, Marie-Andrée; Datar, Vrushali; Kebriaei, Partow; Lee, Dean A; Champlin, Richard E; Cooper, Laurence J N

    2016-11-29

    Adoptive immunotherapy retargeting T cells to CD19 via a chimeric antigen receptor (CAR) is an investigational treatment capable of inducing complete tumor regression of B-cell malignancies when there is sustained survival of infused cells. T-memory stem cells (TSCM) retain superior potential for long-lived persistence, but challenges exist in manufacturing this T-cell subset because they are rare among circulating lymphocytes. We report a clinically relevant approach to generating CAR(+) T cells with preserved TSCM potential using the Sleeping Beauty platform. Because IL-15 is fundamental to T-cell memory, we incorporated its costimulatory properties by coexpressing CAR with a membrane-bound chimeric IL-15 (mbIL15). The mbIL15-CAR T cells signaled through signal transducer and activator of transcription 5 to yield improved T-cell persistence independent of CAR signaling, without apparent autonomous growth or transformation, and achieved potent rejection of CD19(+) leukemia. Long-lived T cells were CD45RO(neg)CCR7(+)CD95(+), phenotypically most similar to TSCM, and possessed a memory-like transcriptional profile. Overall, these results demonstrate that CAR(+) T cells can develop long-term persistence with a memory stem-cell phenotype sustained by signaling through mbIL15. This observation warrants evaluation in clinical trials.

  6. Oct1 and OCA-B are selectively required for CD4 memory T cell function.

    PubMed

    Shakya, Arvind; Goren, Alon; Shalek, Alex; German, Cody N; Snook, Jeremy; Kuchroo, Vijay K; Yosef, Nir; Chan, Raymond C; Regev, Aviv; Williams, Matthew A; Tantin, Dean

    2015-11-16

    Epigenetic changes are crucial for the generation of immunological memory. Failure to generate or maintain these changes will result in poor memory responses. Similarly, augmenting or stabilizing the correct epigenetic states offers a potential method of enhancing memory. Yet the transcription factors that regulate these processes are poorly defined. We find that the transcription factor Oct1 and its cofactor OCA-B are selectively required for the in vivo generation of CD4(+) memory T cells. More importantly, the memory cells that are formed do not respond properly to antigen reencounter. In vitro, both proteins are required to maintain a poised state at the Il2 target locus in resting but previously stimulated CD4(+) T cells. OCA-B is also required for the robust reexpression of multiple other genes including Ifng. ChIPseq identifies ∼50 differentially expressed direct Oct1 and OCA-B targets. We identify an underlying mechanism involving OCA-B recruitment of the histone lysine demethylase Jmjd1a to targets such as Il2, Ifng, and Zbtb32. The findings pinpoint Oct1 and OCA-B as central mediators of CD4(+) T cell memory.

  7. Atomic Layer Deposited Oxide-Based Nanocomposite Structures with Embedded CoPtx Nanocrystals for Resistive Random Access Memory Applications.

    PubMed

    Wang, Lai-Guo; Cao, Zheng-Yi; Qian, Xu; Zhu, Lin; Cui, Da-Peng; Li, Ai-Dong; Wu, Di

    2017-02-22

    Al2O3- or HfO2-based nanocomposite structures with embedded CoPtx nanocrystals (NCs) on TiN-coated Si substrates have been prepared by combination of thermal atomic layer deposition (ALD) and plasma-enhanced ALD for resistive random access memory (RRAM) applications. The impact of CoPtx NCs and their average size/density on the resistive switching properties has been explored. Compared to the control sample without CoPtx NCs, ALD-derived Pt/oxide/100 cycle-CoPtx NCs/TiN/SiO2/Si exhibits a typical bipolar, reliable, and reproducible resistive switching behavior, such as sharp distribution of RRAM parameters, smaller set/reset voltages, stable resistance ratio (≥10(2)) of OFF/ON states, better switching endurance up to 10(4) cycles, and longer data retention over 10(5) s. The possible resistive switching mechanism based on nanocomposite structures of oxide/CoPtx NCs has been proposed. The dominant conduction mechanisms in low- and high-resistance states of oxide-based device units with embedded CoPtx NCs are Ohmic behavior and space-charge-limited current, respectively. The insertion of CoPtx NCs can effectively improve the formation of conducting filaments due to the CoPtx NC-enhanced electric field intensity. Besides excellent resistive switching performances, the nanocomposite structures also simultaneously present ferromagnetic property. This work provides a flexible pathway by combining PEALD and TALD compatible with state-of-the-art Si-based technology for multifunctional electronic devices applications containing RRAM.

  8. Circulating herpes simplex type 1 (HSV-1)-specific CD8+ T cells do not access HSV-1 latently infected trigeminal ganglia

    PubMed Central

    2011-01-01

    Background Therapeutic vaccines can be designed to enhance existing T cell memory populations for increased protection against re-infection. In the case of herpes simplex virus type 1, recurrent disease results from reactivation of latent virus in sensory ganglia, which is controlled in part by a ganglia-resident HSV-specific memory CD8+ T cell population. Thus, an important goal of a therapeutic HSV-1 vaccine would be to enhance this population. Methods HSV-1-infected mice were treated with TAK-779 to block CCR5- and CXCR3-mediated CD8+ T cell migration during both acute and latent infections. Additionally, HSV-1-specific CD8+ T cells were transferred into HSV-1 latently infected mice to mimic the effect of a therapeutic vaccine, and their migration into trigeminal ganglia (TG) was traced during steady-state latency, or during recovery of the TG-resident memory CD8+ T cell population following stress-, and corticosterone-induced depletion and HSV-1 reactivation from latency. Bromodeoxy uridine (BrdU) incorporation measured cell proliferation in vivo. Results TAK-779 treatment during acute HSV-1 infection reduced the number of infiltrating CD8+ T cells but did not alter the number of viral genome copies. TAK-779 treatment during HSV latency did not affect the size of the TG-resident memory CD8+ T cell population. Transferred HSV-specific CD8+ T cells failed to access latently infected TG during steady-state latency, or during recovery of the TG resident HSV-specific CD8+ T cell population following exposure of latently infected mice to stress and corticosterone. Recovery of the HSV-specific CD8+ T cell population after stress and corticosterone treatment occurred with homeostatic levels of cell division and did not require CD4+ T cell help. Conclusions Our findings are consistent with the notion that the CD8+ T cells in latently infected TG are a tissue-resident memory (Trm) population that is maintained without replenishment from the periphery, and that when this

  9. Mass cytometry analysis shows that a novel memory phenotype B cell is expanded in multiple myeloma

    PubMed Central

    Hansmann, Leo; Blum, Lisa; Ju, Chia-Hsin; Liedtke, Michaela; Robinson, William H.; Davis, Mark M.

    2015-01-01

    It would be very beneficial if the status of cancers could be determined from a blood specimen. However, peripheral blood leukocytes are very heterogeneous between individuals and thus high resolution technologies are likely required. We used cytometry by time-of-flight (CyTOF) and next generation sequencing to ask whether a plasma cell cancer (multiple myeloma) and related pre-cancerous states had any consistent effect on the peripheral blood mononuclear cell phenotypes of patients. Analysis of peripheral blood samples from 13 cancer patients, 9 pre-cancer patients, and 9 healthy individuals revealed significant differences in the frequencies of the T, B, and natural killer cell compartments. Most strikingly, we identified a novel B-cell population that normally accounts for 4.0±0.7% (mean±SD) of total B cells and is up to 13-fold expanded in multiple myeloma patients with active disease. This population expressed markers previously associated with both memory (CD27+) and naïve (CD24loCD38+) phenotypes. Single-cell immunoglobulin gene sequencing showed polyclonality, indicating that these cells are not precursors to the myeloma, and somatic mutations, a characteristic of memory cells. SYK, ERK, and p38 phosphorylation responses, and the fact that most of these cells expressed isotypes other than IgM or IgD, confirmed the memory character of this population, defining it as a novel type of memory B cells. PMID:25711758

  10. Reduced numbers of switched memory B cells with high terminal differentiation potential in Down syndrome.

    PubMed

    Carsetti, Rita; Valentini, Diletta; Marcellini, Valentina; Scarsella, Marco; Marasco, Emiliano; Giustini, Ferruccio; Bartuli, Andrea; Villani, Alberto; Ugazio, Alberto G

    2015-03-01

    Children with Down syndrome (DS) have increased susceptibility to infections and a high frequency of leukemia and autoimmune disorders, suggesting that immunodeficiency and immune dysfunction are integral parts of the syndrome. A reduction in B-cell numbers has been reported, associated with moderate immunodeficiency and normal immunoglobulin levels. Here, we compared B-cell populations of 19 children with DS with those in healthy age-matched controls. We found that all steps of peripheral B-cell development are altered in DS, with a more severe defect during the later stages of B-cell development. Transitional and mature-naïve B-cell numbers are reduced by 50% whereas switched memory B cells represent 10-15% of the numbers in age-matched controls. Serum IgM levels were slightly reduced, but all other immunoglobulin isotypes were in the normal range. The frequency of switched memory B cells specific for vaccine antigens was significantly lower in affected children than in their equivalently vaccinated siblings. In vitro switched memory B cells of patients with DS have an increased ability to differentiate into antibody-forming cells in response to TLR9 signals. Tailored vaccination schedules increasing the number of switched memory B cells may improve protection and reduce the risk of death from infection in DS.

  11. Dopaminergic neurons write and update memories with cell-type-specific rules

    PubMed Central

    Aso, Yoshinori; Rubin, Gerald M

    2016-01-01

    Associative learning is thought to involve parallel and distributed mechanisms of memory formation and storage. In Drosophila, the mushroom body (MB) is the major site of associative odor memory formation. Previously we described the anatomy of the adult MB and defined 20 types of dopaminergic neurons (DANs) that each innervate distinct MB compartments (Aso et al., 2014a, 2014b). Here we compare the properties of memories formed by optogenetic activation of individual DAN cell types. We found extensive differences in training requirements for memory formation, decay dynamics, storage capacity and flexibility to learn new associations. Even a single DAN cell type can either write or reduce an aversive memory, or write an appetitive memory, depending on when it is activated relative to odor delivery. Our results show that different learning rules are executed in seemingly parallel memory systems, providing multiple distinct circuit-based strategies to predict future events from past experiences. DOI: http://dx.doi.org/10.7554/eLife.16135.001 PMID:27441388

  12. Lung airway-surveilling CXCR3(hi) memory CD8(+) T cells are critical for protection against influenza A virus.

    PubMed

    Slütter, Bram; Pewe, Lecia L; Kaech, Susan M; Harty, John T

    2013-11-14

    Inducing memory CD8(+) T cells specific for conserved antigens from influenza A virus (IAV) is a potential strategy for broadly protective vaccines. Here we show that memory CD8(+) T cells in the airways played an important role in early control of IAV. Expression of the chemokine receptor CXCR3 was critical for memory CD8(+) T cells to populate the airways during the steady state and vaccination approaches were designed to favor the establishment of memory CD8(+) T cells in the airways. Specifically, we found that interleukin-12 (IL-12) signaling shortly after immunization limited CXCR3 expression on memory CD8(+) T cells. Neutralization of IL-12 or adjuvants that did not induce high amounts of IL-12 enhanced CXCR3 expression, sustained airway localization of memory CD8(+) T cells, and resulted in superior protection against IAV.

  13. Tracing the development of single memory-lineage B cells in a highly defined immune response

    PubMed Central

    1996-01-01

    To study the development of B lymphocyte memory, we identified and isolated splenic B cells expressing a highly defined antibody variable region that constitutes a reproducible and predominant component of the memory antibody response to p-azophenylarsonate (Ars). Isolation was achieved during the primary immune response by surface staining and flow cytometry using a specific anti-idiotypic antibody called E4, which recognizes this canonical V region, encoded by one set of V gene segments. The isolated E4+ cells displayed all of the phenotypic characteristics of germinal center centrocytes, including a low level of surface Ig, a lack of surface IgD, a high level of receptor for peanut agglutinin, and expression of mutated antibody V genes. E4+ B cells were first detected in the spleen 7-8 d after primary immunization, reached peak numbers from days 10-13, and waned by day 16. Surprisingly, at their peak, E4+ cells comprised only 40,000 of all splenocytes, and half of these failed to bind Ars. Using this number, we estimate the total number of Ars-specific memory-lineage cells in the spleen to be no more than 50,000 (0.1%) at any one time, and presumably far fewer that are committed to the memory pool. Chromosomal copies of rearranged V genes from single E4+ cells were amplified by nested PCR, and the amplified products were sequenced directly without cloning, using standardized conditions that disclose virtually no Taq polymerase errors. V gene sequence analyses of E4+ cells isolated from single mice confirmed their canonical nature and revealed that they were derived from few precursors. In the average mouse, the E4+ pool was derived from fewer than five canonical precursors. Somatic mutations were found within the V genes of almost all cell isolates. At day 13, a significant fraction of E4+ cells had mutations known to increase antibody affinity for Ars, suggesting they were products of at least one cycle of post-mutational antigen-driven selection. However, the

  14. VACCINES. A mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells.

    PubMed

    Stary, Georg; Olive, Andrew; Radovic-Moreno, Aleksandar F; Gondek, David; Alvarez, David; Basto, Pamela A; Perro, Mario; Vrbanac, Vladimir D; Tager, Andrew M; Shi, Jinjun; Yethon, Jeremy A; Farokhzad, Omid C; Langer, Robert; Starnbach, Michael N; von Andrian, Ulrich H

    2015-06-19

    Genital Chlamydia trachomatis (Ct) infection induces protective immunity that depends on interferon-γ-producing CD4 T cells. By contrast, we report that mucosal exposure to ultraviolet light (UV)-inactivated Ct (UV-Ct) generated regulatory T cells that exacerbated subsequent Ct infection. We show that mucosal immunization with UV-Ct complexed with charge-switching synthetic adjuvant particles (cSAPs) elicited long-lived protection in conventional and humanized mice. UV-Ct-cSAP targeted immunogenic uterine CD11b(+)CD103(-) dendritic cells (DCs), whereas UV-Ct accumulated in tolerogenic CD11b(-)CD103(+) DCs. Regardless of vaccination route, UV-Ct-cSAP induced systemic memory T cells, but only mucosal vaccination induced effector T cells that rapidly seeded uterine mucosa with resident memory T cells (T(RM) cells). Optimal Ct clearance required both T(RM) seeding and subsequent infection-induced recruitment of circulating memory T cells. Thus, UV-Ct-cSAP vaccination generated two synergistic memory T cell subsets with distinct migratory properties.

  15. Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis

    PubMed Central

    Wojciechowski, Sara; Tripathi, Pulak; Bourdeau, Tristan; Acero, Luis; Grimes, H. Leighton; Katz, Jonathan D.; Finkelman, Fred D.; Hildeman, David A.

    2007-01-01

    We examined the role of the antiapoptotic molecule Bcl-2 in combating the proapoptotic molecule Bim in control of naive and memory T cell homeostasis using Bcl-2−/− mice that were additionally deficient in one or both alleles of Bim. Naive T cells were significantly decreased in Bim+/−Bcl-2−/− mice, but were largely restored in Bim−/−Bcl-2−/− mice. Similarly, a synthetic Bcl-2 inhibitor killed wild-type, but not Bim−/−, T cells. Further, T cells from Bim+/−Bcl-2−/− mice died rapidly ex vivo and were refractory to cytokine-driven survival in vitro. In vivo, naive CD8+ T cells required Bcl-2 to combat Bim to maintain peripheral survival, whereas naive CD4+ T cells did not. In contrast, Bim+/−Bcl-2−/− mice generated relatively normal numbers of memory T cells after lymphocytic choriomeningitis virus infection. Accumulation of memory T cells in Bim+/−Bcl-2−/− mice was likely caused by their increased proliferative renewal because of the lymphopenic environment of the mice. Collectively, these data demonstrate a critical role for a balance between Bim and Bcl-2 in controlling homeostasis of naive and memory T cells. PMID:17591857

  16. Autoimmune memory T helper 17 cell function and expansion are dependent on interleukin-23.

    PubMed

    Haines, Christopher J; Chen, Yi; Blumenschein, Wendy M; Jain, Renu; Chang, Charlie; Joyce-Shaikh, Barbara; Porth, Katherine; Boniface, Katia; Mattson, Jeanine; Basham, Beth; Anderton, Stephen M; McClanahan, Terrill K; Sadekova, Svetlana; Cua, Daniel J; McGeachy, Mandy J

    2013-05-30

    Interleukin-23 (IL-23) is essential for the differentiation of pathogenic effector T helper 17 (Th17) cells, but its role in memory Th17 cell responses is unclear. Using the experimental autoimmune encephalomyelitis (EAE) model, we report that memory Th17 cells rapidly expanded in response to rechallenge and migrated to the CNS in high numbers, resulting in earlier onset and increased severity of clinical disease. Memory Th17 cells were generated from IL-17+ and RORγt+ precursors, and the stability of the Th17 cell phenotype depended on the amount of time allowed for the primary response. IL-23 was required for this enhanced recall response. IL-23 receptor blockade did not directly impact IL-17 production, but did impair the subsequent proliferation and generation of effectors coexpressing the Th1 cell-specific transcription factor T-bet. In addition, many genes required for cell-cycle progression were downregulated in Th17 cells that lacked IL-23 signaling, showing that a major mechanism for IL-23 in primary and memory Th17 cell responses operates via regulation of proliferation-associated pathways.

  17. Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis.

    PubMed

    Wojciechowski, Sara; Tripathi, Pulak; Bourdeau, Tristan; Acero, Luis; Grimes, H Leighton; Katz, Jonathan D; Finkelman, Fred D; Hildeman, David A

    2007-07-09

    We examined the role of the antiapoptotic molecule Bcl-2 in combating the proapoptotic molecule Bim in control of naive and memory T cell homeostasis using Bcl-2(-/-) mice that were additionally deficient in one or both alleles of Bim. Naive T cells were significantly decreased in Bim(+/-)Bcl-2(-/-) mice, but were largely restored in Bim(-/-)Bcl-2(-/-) mice. Similarly, a synthetic Bcl-2 inhibitor killed wild-type, but not Bim(-/-), T cells. Further, T cells from Bim(+/-)Bcl-2(-/-) mice died rapidly ex vivo and were refractory to cytokine-driven survival in vitro. In vivo, naive CD8(+) T cells required Bcl-2 to combat Bim to maintain peripheral survival, whereas naive CD4(+) T cells did not. In contrast, Bim(+/-)Bcl-2(-/-) mice generated relatively normal numbers of memory T cells after lymphocytic choriomeningitis virus infection. Accumulation of memory T cells in Bim(+/-)Bcl-2(-/-) mice was likely caused by their increased proliferative renewal because of the lymphopenic environment of the mice. Collectively, these data demonstrate a critical role for a balance between Bim and Bcl-2 in controlling homeostasis of naive and memory T cells.

  18. Circulating Tumor Cells: Clinically Relevant Molecular Access Based on a Novel CTC Flow Cell

    PubMed Central

    Winer-Jones, Jessamine P.; Vahidi, Behrad; Arquilevich, Norma; Fang, Cong; Ferguson, Samuel; Harkins, Darren; Hill, Cory; Klem, Erich; Pagano, Paul C.; Peasley, Chrissy; Romero, Juan; Shartle, Robert; Vasko, Robert C.; Strauss, William M.; Dempsey, Paul W.

    2014-01-01

    Background Contemporary cancer diagnostics are becoming increasing reliant upon sophisticated new molecular methods for analyzing genetic information. Limiting the scope of these new technologies is the lack of adequate solid tumor tissue samples. Patients may present with tumors that are not accessible to biopsy or adequate for longitudinal monitoring. One attractive alternate source is cancer cells in the peripheral blood. These rare circulating tumor cells (CTC) require enrichment and isolation before molecular analysis can be performed. Current CTC platforms lack either the throughput or reliability to use in a clinical setting or they provide CTC samples at purities that restrict molecular access by limiting the molecular tools available. Methodology/Principal Findings Recent advances in magetophoresis and microfluidics have been employed to produce an automated platform called LiquidBiopsy®. This platform uses high throughput sheath flow microfluidics for the positive selection of CTC populations. Furthermore the platform quantitatively isolates cells useful for molecular methods such as detection of mutations. CTC recovery was characterized and validated with an accuracy (<20% error) and a precision (CV<25%) down to at least 9 CTC/ml. Using anti-EpCAM antibodies as the capture agent, the platform recovers 78% of MCF7 cells within the linear range. Non specific recovery of background cells is independent of target cell density and averages 55 cells/mL. 10% purity can be achieved with as low as 6 CTCs/mL and better than 1% purity can be achieved with 1 CTC/mL. Conclusions/Significance The LiquidBiopsy platform is an automated validated platform that provides high throughput molecular access to the CTC population. It can be validated and integrated into the lab flow enabling CTC enumeration as well as recovery of consistently high purity samples for molecular analysis such as quantitative PCR and Next Generation Sequencing. This tool opens the way for

  19. Role of germinal centers for the induction of broadly-reactive memory B cells.

    PubMed

    Takahashi, Yoshimasa; Kelsoe, Garnett

    2017-03-27

    Virus-specific memory B cells (Bmem) play a crucial role in protecting against variant viruses. The ability to recognize these variant viruses, defined as antibody breadth, is achieved in Bmem populations by two very different pathways, germline-encoded cross-reactivity and affinity-driven, somatic evolution in germinal centers (GCs) for conserved viral epitopes. The latter class of broadly-reactive Bmem cells are not cross-reactive per se, but bind epitopes crucial for viral fitness. Although these conserved epitopes are often weakly immunogenic, the GC reaction is surprisingly permissive for the continued survival/proliferation of B cells that bind with low affinity or react to cryptic epitopes, increasing their chance of memory recruitment. In this review, we discuss the adaptive strategies of B-cell memory to viral antigenic variations.

  20. Real-time tracking of cell cycle progression during CD8+ effector and memory T-cell differentiation

    PubMed Central

    Kinjyo, Ichiko; Qin, Jim; Tan, Sioh-Yang; Wellard, Cameron J.; Mrass, Paulus; Ritchie, William; Doi, Atsushi; Cavanagh, Lois L.; Tomura, Michio; Sakaue-Sawano, Asako; Kanagawa, Osami; Miyawaki, Atsushi; Hodgkin, Philip D.; Weninger, Wolfgang

    2015-01-01

    The precise pathways of memory T-cell differentiation are incompletely understood. Here we exploit transgenic mice expressing fluorescent cell cycle indicators to longitudinally track the division dynamics of individual CD8+ T cells. During influenza virus infection in vivo, naive T cells enter a CD62Lintermediate state of fast proliferation, which continues for at least nine generations. At the peak of the anti-viral immune response, a subpopulation of these cells markedly reduces their cycling speed and acquires a CD62Lhi central memory cell phenotype. Construction of T-cell family division trees in vitro reveals two patterns of proliferation dynamics. While cells initially divide rapidly with moderate stochastic variations of cycling times after each generation, a slow-cycling subpopulation displaying a CD62Lhi memory phenotype appears after eight divisions. Phenotype and cell cycle duration are inherited by the progeny of slow cyclers. We propose that memory precursors cell-intrinsically modulate their proliferative activity to diversify differentiation pathways. PMID:25709008

  1. B cells expressing IL-10 mRNA modulate memory T cells after DNA-Hsp65 immunization

    PubMed Central

    Fontoura, I. C.; Trombone, A.P.F.; Almeida, L. P.; Lorenzi, J. C. C.; Rossetti, R. A. M.; Malardo, T.; Padilha, E.; Schluchting, W.; Silva, R. L. L.; Gembre, A. F.; Fiuza, J. E. C.; Silva, C. L.; Panunto-Castelo, A.; Coelho-Castelo, A. A. M.

    2015-01-01

    In DNA vaccines, the gene of interest is cloned into a bacterial plasmid that is engineered to induce protein production for long periods in eukaryotic cells. Previous research has shown that the intramuscular immunization of BALB/c mice with a naked plasmid DNA fragment encoding the Mycobacterium leprae 65-kDa heat-shock protein (pcDNA3-Hsp65) induces protection against M. tuberculosis challenge. A key stage in the protective immune response after immunization is the generation of memory T cells. Previously, we have shown that B cells capture plasmid DNA-Hsp65 and thereby modulate the formation of CD8+ memory T cells after M. tuberculosis challenge in mice. Therefore, clarifying how B cells act as part of the protective immune response after DNA immunization is important for the development of more-effective vaccines. The aim of this study was to investigate the mechanisms by which B cells modulate memory T cells after DNA-Hsp65 immunization. C57BL/6 and BKO mice were injected three times, at 15-day intervals, with 100 µg naked pcDNA-Hsp65 per mouse. Thirty days after immunization, the percentages of effector memory T (TEM) cells (CD4+ and CD8+/CD44high/CD62Llow) and memory CD8+ T cells (CD8+/CD44high/CD62Llow/CD127+) were measured with flow cytometry. Interferon γ, interleukin 12 (IL-12), and IL-10 mRNAs were also quantified in whole spleen cells and purified B cells (CD43−) with real-time qPCR. Our data suggest that a B-cell subpopulation expressing IL-10 downregulated proinflammatory cytokine expression in the spleen, increasing the survival of CD4+ TEM cells and CD8+ TEM/CD127+ cells. PMID:26397973

  2. 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.

  3. Rescue of CD8+ T cell vaccine memory following sublethal γ irradiation

    PubMed Central

    McFarland, Hugh I.; Berkson, Julia D.; Lee, Jay P.; Elkahloun, Abdel G.; Mason, Karen P.; Rosenberg, Amy S.

    2015-01-01

    Sublethal γ irradiation eliminates CD8+ T cell mediated memory responses. In this work, we explored how these memory responses could be rescued in the aftermath of such exposure. We utilized two models of CD8+ T cell mediated immunity: a mouse model of Listeria monocytogenes (LM) infection in which CD8+ T cells specific for LM expressed antigens (Listeriolysin O, LLO) can be tracked, and a murine skin graft model in which CD8+ T cells mediate rejection across a MHC class I (Dd) disparity. In the LM immunized mice, LL0 specific CD8+ T memory cells were lost on irradiation, preserved with rapid revaccination with an attenuated strain 1-3 days post-irradiation (PI), and these mice survived a subsequent wild type LM challenge. A genetic “signature of rescue” identified a group of immune-associated mRNA maintained or upregulated following irradiation and rescue. A number of these factors, including IL-36γ, dectin-2 (Clec4n), and mir101c are upregulated rapidly after exposure of mice to sublethal γ radiation alone and are sustained by early, but not later rescue. Such factors will be evaluated as potential therapeutics to replace individual vaccines for global rescue of CD8+ T memory cell responses following sublethal γ irradiation. The skin allograft model mirrored that of the LM model in that the accelerated Dd skin allograft rejection response was lost in mice exposed to sublethal γ radiation, but infusion of allogeneic Dd expressing bone marrow cells 1-4 days PI preserved the CD8+ T memory mediated accelerated rejection response, further suggesting that innate immune responses may not always be essential to rescue of CD8+ memory T cells following γ irradiation. PMID:26122582

  4. Bovine central memory T cells are highly proliferative in response to bovine tuberculosis infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long-term (i.e., 14 days) cultured IFN-gamma responses of peripheral blood mononuclear cells are used as a correlate of T cell central memory (Tcm) responses in both humans and cattle. With bovine tuberculosis, vaccine-elicited long-term IFN-gamma ELISPOT assays are a correlate of protection. Recent...

  5. Persistence of skin-resident memory T cells within an epidermal niche

    PubMed Central

    Zaid, Ali; Mackay, Laura K.; Rahimpour, Azad; Braun, Asolina; Veldhoen, Marc; Carbone, Francis R.; Manton, Jonathan H.; Heath, William R.; Mueller, Scott N.

    2014-01-01

    Barrier tissues such as the skin contain various populations of immune cells that contribute to protection from infections. These include recently identified tissue-resident memory T cells (TRM). In the skin, these memory CD8+ T cells reside in the epidermis after being recruited to this site by infection or inflammation. In this study, we demonstrate prolonged persistence of epidermal TRM preferentially at the site of prior infection despite sustained migration. Computational simulation of TRM migration within the skin over long periods revealed that the slow rate of random migration effectively constrains these memory cells within the region of skin in which they form. Notably, formation of TRM involved a concomitant local reduction in dendritic epidermal γδ T-cell numbers in the epidermis, indicating that these populations persist in mutual exclusion and may compete for local survival signals. Accordingly, we show that expression of the aryl hydrocarbon receptor, a transcription factor important for dendritic epidermal γδ T-cell maintenance in skin, also contributes to the persistence of skin TRM. Together, these data suggest that skin tissue-resident memory T cells persist within a tightly regulated epidermal T-cell niche. PMID:24706879

  6. The majority of human memory B cells recognizing RhD and tetanus resides in IgM+ B cells.

    PubMed

    Della Valle, Luciana; Dohmen, Serge E; Verhagen, Onno J H M; Berkowska, Magdalena A; Vidarsson, Gestur; Ellen van der Schoot, C

    2014-08-01

    B cell memory to T cell-dependent (TD) Ags are considered to largely reside in class-switched CD27(+) cells. However, we previously observed that anti-RhD (D) Igs cloned from two donors, hyperimmunized with D(+) erythrocytes, were predominantly of the IgM isotype. We therefore analyzed in this study the phenotype and frequency of D- and tetanus toxoid-specific B cells by culturing B cells in limiting dilution upon irradiated CD40L-expressing EL4.B5 cells and testing the culture supernatant. Most Ag-specific B cells for both TD Ags were found to reside in the IgM-expressing B cells, including CD27(-) B cells, in both hyperimmunized donors and nonhyperimmunized volunteers. Only shortly after immunization a sharp increase in Ag-specific CD27(+)IgG(+) B cells was observed. Next, B cells were enriched with D(+) erythrocyte ghosts and sorted as single cells. Sequencing of IGHV, IGLV, IGKV, and BCL6 genes from these D-specific B cell clones demonstrated that both CD27(-)IgM(+) and CD27(+)IgM(+) B cells harbored somatic mutations, documenting their Ag-selected nature. Furthermore, sequencing revealed a clonal relationship between the CD27(-)IgM(+), CD27(+)IgM(+), and CD27(+)IgG(+) B cell subsets. These data strongly support the recently described multiple layers of memory B cells to TD Ags in mice, where IgM(+) B cells represent a memory reservoir which can re-enter the germinal center and ensure replenishment of class-switched memory CD27(+) B cells from Ag-experienced precursors.

  7. Plasmodium vivax infection induces expansion of activated naïve/memorycells and differentiation into a central memory profile.

    PubMed

    Silva, Ana Luiza Teixeira; Lacerda, Marcus Vinícius; Fujiwara, Ricardo Toshio; Bueno, Lilian Lacerda; Braga, Erika Martins

    2013-11-01

    Immunity to malaria is widely believed to wane in the absence of reinfection, but direct evidence for the presence or absence of durable immunological memory to malaria is limited. Here, we characterized the profile of circulating naïve and memory (including central and effector) CD4⁺ T cells responses of individuals naturally infected by Plasmodium vivax. In the current study, we demonstrated that acute P. vivax infection induces a significant increase in the absolute number of both naïve and memory cells, which were responsible for the production of anti-inflammatory (IL-10) and pro-inflammatory (IFN-γ) cytokines. Finally, we described the profile of memory cell subtypes (T(CM)-CD45RO(high)CCR7⁺ and T(EM)-CD45RO(high)CCR7⁻), as well as the pattern of cell migration based on CD62L selectin expression, demonstrating that P. vivax-infected donors presented with a predominantly central memory cell profile. Our results indicate that the expansion of both naïve and memory T cells, responsible for the production of both pro-inflammatory and regulatory cytokines, which might also contribute to the modulation of immune responses during P. vivax infection.

  8. Retention modeling for ultra-thin density of Cu-based conductive bridge random access memory (CBRAM)

    SciTech Connect

    Aga, Fekadu Gochole; Woo, Jiyong; Lee, Sangheon; Song, Jeonghwan; Park, Jaesung; Park, Jaehyuk; Lim, Seokjae; Sung, Changhyuck; Hwang, Hyunsang

    2016-02-15

    We investigate the effect of Cu concentration On-state resistance retention characteristics of W/Cu/Ti/HfO{sub 2}/Pt memory cell. The development of RRAM device for application depends on the understanding of the failure mechanism and the key parameters for device optimization. In this study, we develop analytical expression for cations (Cu{sup +}) diffusion model using Gaussian distribution for detailed analysis of data retention time at high temperature. It is found that the improvement of data retention time depends not only on the conductive filament (CF) size but also on Cu atoms concentration density in the CF. Based on the simulation result, better data retention time is observed for electron wave function associated with Cu{sup +} overlap and an extended state formation. This can be verified by analytical calculation of Cu atom defects inside the filament, based on Cu{sup +} diffusion model. The importance of Cu diffusion for the device reliability and the corresponding local temperature of the filament were analyzed by COMSOL Multiphysics simulation.

  9. Abacavir-Reactive Memory T Cells Are Present in Drug Naïve Individuals

    PubMed Central

    Lucas, Andrew; Lucas, Michaela; Strhyn, Anette; Keane, Niamh M.; McKinnon, Elizabeth; Pavlos, Rebecca; Moran, Ellen M.; Meyer-Pannwitt, Viola; Gaudieri, Silvana; D’Orsogna, Lloyd; Kalams, Spyros; Ostrov, David A.; Buus, Søren; Peters, Bjoern; Mallal, Simon; Phillips, Elizabeth

    2015-01-01

    Background Fifty-five percent of individuals with HLA-B*57:01 exposed to the antiretroviral drug abacavir develop a hypersensitivity reaction (HSR) that has been attributed to naïve T-cell responses to neo-antigen generated by the drug. Immunologically confirmed abacavir HSR can manifest clinically in less than 48 hours following first exposure suggesting that, at least in some cases, abacavir HSR is due to re-stimulation of a pre-existing memory T-cell population rather than priming of a high frequency naïve T-cell population. Methods To determine whether a pre-existing abacavir reactive memory T-cell population contributes to early abacavir HSR symptoms, we studied the abacavir specific naïve or memory T-cell response using HLA-B*57:01 positive HSR patients or healthy controls using ELISpot assay, intra-cellular cytokine staining and tetramer labelling. Results Abacavir reactive CD8+ T-cell responses were detected in vitro in one hundred percent of abacavir unexposed HLA-B*57:01 positive healthy donors. Abacavir-specific CD8+ T cells from such donors can be expanded from sorted memory, and sorted naïve, CD8+ T cells without need for autologous CD4+ T cells. Conclusions We propose that these pre-existing abacavir-reactive memory CD8+ T-cell responses must have been primed by earlier exposure to another foreign antigen and that these T cells cross-react with an abacavir-HLA-B*57:01-endogenous peptide ligand complex, in keeping with the model of heterologous immunity proposed in transplant rejection. PMID:25674793

  10. Defective T Memory Cell Differentiation after Varicella Zoster Vaccination in Older Individuals

    PubMed Central

    Wagar, Lisa E.; Mackey, Sally; Hu, Jinyu; Maecker, Holden; Davis, Mark M.; Dekker, Cornelia L.; Tian, Lu; Weyand, Cornelia M.; Goronzy, Jörg J.

    2016-01-01

    Vaccination with attenuated live varicella zoster virus (VZV) can prevent zoster reactivation, but protection is incomplete especially in an older population. To decipher the molecular mechanisms underlying variable vaccine responses, T- and B-cell responses to VZV vaccination were examined in individuals of different ages including identical twin pairs. Contrary to the induction of VZV-specific antibodies, antigen-specific T cell responses were significantly influenced by inherited factors. Diminished generation of long-lived memory T cells in older individuals was mainly caused by increased T cell loss after the peak response while the expansion of antigen-specific T cells was not affected by age. Gene expression in activated CD4 T cells at the time of the peak response identified gene modules related to cell cycle regulation and DNA repair that correlated with the contraction phase of the T cell response and consequently the generation of long-lived memory cells. These data identify cell cycle regulatory mechanisms as targets to reduce T cell attrition in a vaccine response and to improve the generation of antigen-specific T cell memory, in particular in an older population. PMID:27764254

  11. Tumor cells and memory T cells converge at glycolysis: therapeutic implications.

    PubMed

    Karthikeyan, Swathi; Geschwind, Jean-Francois; Ganapathy-Kanniappan, Shanmugasundaram

    2014-05-01

    In the immune system, activation of naïve T (Tn) cells into effector T cells (Teff) involves a metabolic switch to glycolysis to promote rapid proliferation and differentiation. In the October issue of The Journal of Clinical Investigation, Sukumar et al. have demonstrated that in CD8(+) memory T (Tems) cells glycolytic phenotype contributes to the shortened lifespan of Tems. Conversely, inhibition of glycolysis in Tems not only extended their viability but also augmented desirable properties. Notably, they also demonstrate that glycolytic inhibition during the ex vivo clonal expansion of tumor-specific Tems enhanced their antitumor function. Overall, the data suggest that an antiglycolytic strategy targeting the Tems could enhance antitumor immune response. On the other hand, cancer cells have long been known to exhibit metabolic reprogramming which involves a shift toward glycolysis (the conversion of glucose into lactate) to facilitate uninterrupted growth. Interestingly, antiglycolytic treatment of cancer cells has been known to trigger antitumor immune response as well. Taken together, it is probable that a strategy involving concurrent inhibition of glycolysis in tumor cells and Tems could promote a dual attack on cancer by inducing an effective antitumor immune response and an immunogenic chemotherapy.

  12. Cellular resolution optical access to brain regions in fissures: imaging medial prefrontal cortex and grid cells in entorhinal cortex.

    PubMed

    Low, Ryan J; Gu, Yi; Tank, David W

    2014-12-30

    In vivo two-photon microscopy provides the foundation for an array of powerful techniques for optically measuring and perturbing neural circuits. However, challenging tissue properties and geometry have prevented high-resolution optical access to regions situated within deep fissures. These regions include the medial prefrontal and medial entorhinal cortex (mPFC and MEC), which are of broad scientific and clinical interest. Here, we present a method for in vivo, subcellular resolution optical access to the mPFC and MEC using microprisms inserted into the fissures. We chronically imaged the mPFC and MEC in mice running on a spherical treadmill, using two-photon laser-scanning microscopy and genetically encoded calcium indicators to measure network activity. In the MEC, we imaged grid cells, a widely studied cell type essential to memory and spatial information processing. These cells exhibited spatially modulated activity during navigation in a virtual reality environment. This method should be extendable to other brain regions situated within deep fissures, and opens up these regions for study at cellular resolution in behaving animals using a rapidly expanding palette of optical tools for perturbing and measuring network structure and function.

  13. IgM+ Memory B Cell Expression Predicts HIV-Associated Cryptococcosis Status

    PubMed Central

    Subramaniam, Krishanthi; Metzger, Brian; Hanau, Lawrence H.; Guh, Alice; Rucker, Lisa; Badri, Sheila; Pirofski, Liise-anne

    2009-01-01

    Background The role of B cells in resistance to Cryptococcus neoformans disease (i.e., cryptococcosis) is unknown. Given evidence that IgM+ memory B cells are required for immunity to other encapsulated pathogens, we hypothesized that these cells might contribute to resistance to cryptococcosis. Methods We compared levels of IgM expression on memory B cells in 29 HIV-infected individuals who had a history of cryptococcosis (the HIV+CN+ group) with levels in 30 human immunodeficiency virus (HIV)–infected subjects who had no history of cryptococcosis (the HIV+CN− group) and 20 HIV-uninfected subjects who had no history of cryptococcosis (the HIV− group) (cohort 1). We also determined levels of IgM expression on memory B cells in banked samples obtained before cryptococcosis onset from 31 participants in the Multicenter AIDS Cohort Study, of whom 8 had HIV infection and subsequently developed cryptococcosis (the HIV+CN+ group), 8 had HIV infection and did not develop cryptococcosis (the HIV+CN− group), and 15 did not have HIV infection and did not develop cryptococcosis (the HIV− group) (cohort 2). Results In cohort 1, the percentage of memory B cells that expressed IgM was lower among HIV+CN+ subjects, compared with HIV+CN− subjects (P < .01) and HIV− subjects (P <.05); expression of IgM on ≤50% of memory B cells was a significant predictor of C. neoformans disease status (odds ratio, 5.5; P = .03). In cohort 2, the percentage of memory B cells that expressed IgM was lower in HIV+CN+ subjects than in HIV+CN− subjects (P = .02) and HIV− subjects (P < .01); an IgM+ memory B cell percentage of ≤38.5% was a significant predictor of future development of cryptococcosis (odds ratio, 14; P = .02). Conclusions These findings suggest that HIV-infected persons in whom the percentage of memory B cells that express IgM is decreased might be at greater risk for the development of cryptococcosis. PMID:19527168

  14. Influence of cooling rate in planar thermally assisted magnetic random access memory: Improved writeability due to spin-transfer-torque influence

    SciTech Connect

    Chavent, A.; Ducruet, C.; Portemont, C.; Creuzet, C.; Alvarez-Hérault, J.; Vila, L.; Sousa, R. C.; Prejbeanu, I. L.; Dieny, B.

    2015-09-14

    This paper investigates the effect of a controlled cooling rate on magnetic field reversal assisted by spin transfer torque (STT) in thermally assisted magnetic random access memory. By using a gradual linear decrease of the voltage at the end of the write pulse, the STT decays more slowly or at least at the same rate as the temperature. This condition is necessary to make sure that the storage layer magnetization remains in the desired written direction during cooling of the cell. The influence of the write current pulse decay rate was investigated on two exchange biased synthetic ferrimagnet (SyF) electrodes. For a NiFe based electrode, a significant improvement in writing reproducibility was observed using a gradual linear voltage transition. The write error rate decreases by a factor of 10 when increasing the write pulse fall-time from ∼3 ns to 70 ns. For comparison, a second CoFe/NiFe based electrode was also reversed by magnetic field assisted by STT. In this case, no difference between sharp and linear write pulse fall shape was observed. We attribute this observation to the higher thermal stability of the CoFe/NiFe electrode during cooling. In real-time measurements of the magnetization reversal, it was found that Ruderman-Kittel-Kasuya-Yosida (RKKY) coupling in the SyF electrode vanishes for the highest pulse voltages that were used due to the high temperature reached during write. As a result, during the cooling phase, the final state is reached through a spin-flop transition of the SyF storage layer.

  15. Memory protection

    NASA Technical Reports Server (NTRS)

    Denning, Peter J.

    1988-01-01

    Accidental overwriting of files or of memory regions belonging to other programs, browsing of personal files by superusers, Trojan horses, and viruses are examples of breakdowns in workstations and personal computers that would be significantly reduced by memory protection. Memory protection is the capability of an operating system and supporting hardware to delimit segments of memory, to control whether segments can be read from or written into, and to confine accesses of a program to its segments alone. The absence of memory protection in many operating systems today is the result of a bias toward a narrow definition of performance as maximum instruction-execution rate. A broader definition, including the time to get the job done, makes clear that cost of recovery from memory interference errors reduces expected performance. The mechanisms of memory protection are well understood, powerful, efficient, and elegant. They add to performance in the broad sense without reducing instruction execution rate.

  16. Persistent expansion of CD4+ effector memory T cells in Wegener's granulomatosis.

    PubMed

    Abdulahad, W H; van der Geld, Y M; Stegeman, C A; Kallenberg, C G M

    2006-09-01

    In order to test the hypothesis that Wegener's granulomatosis (WG) is associated with an ongoing immune effector response, even in remission, we examined the distribution of peripheral naive and memory T-lymphocytes in this disease, and analyzed the function-related phenotypes of the memory T-cell population. Peripheral blood mononuclear cells (PBMCs) were freshly isolated from WG-patients in remission (R-WG, n=40), active WG-patients (A-WG, n=17), and age-matched healthy controls (HCs, n=21). Expression of CD4, CD8, CD45RO, CCR7, interleukin (IL)-18Ralpha, ST2L, and FoxP3 were determined by four-color flow cytometric analysis. CD45RO and CCR7 were used for distinction between naive and memory T cells, IL-18Ralpha, ST2L, and FoxP3 for the assessment of Type1, Type2, and regulatory T-cells, respectively. In R-WG, the CD4+CD45RO+CCR7- effector memory T-cell subpopulation (TEM) was relatively increased, whereas the CD4+CD45RO-CCR7+ naive T-cell population (TNaive) was decreased as compared to HC. The distribution of naive and memory CD8+T cells did not differ between R-WG, A-WG, and HC, nor did CD4+CD45RO+CCR7+ central memory T cells (TCM). In contrast to HC, the percentage of CD4+TNaive cells in R-WG correlated negatively with age, whereas CD4+TEM cells showed a positive correlation. In R-WG, a skewing towards Type2 T cells was observed in CD4+TEM cells. No differences were detected in FoxP3+CD4+TEM cells between R-WG and A-WG, whereas the FoxP3-CD4+TEM cells were increased in R-WG and decreased in A-WG as compared to HC. Collectively, peripheral blood homeostasis of CD4+T cells is disturbed in R-WG with the persistent expansion of non-regulatory CD4+TEM cells. These cells might be involved in relapse and may constitute a target for therapy.

  17. Foxp3+ T cells inhibit antitumor immune memory modulated by mTOR inhibition.

    PubMed

    Wang, Yanping; Sparwasser, Tim; Figlin, Robert; Kim, Hyung L

    2014-04-15

    Inhibition of mTOR signaling enhances antitumor memory lymphocytes. However, pharmacologic mTOR inhibition also enhances regulatory T-cell (Treg) activity. To counter this effect, Treg control was added to mTOR inhibition in preclinical models. Tregs were controlled with CD4-depleting antibodies because CD4 depletion has high translational potential and already has a well-established safety profile in patients. The antitumor activity of the combination therapy was CD8 dependent and controlled growth of syngeneic tumors even when an adoptive immunotherapy was not used. Lymphocytes resulting from the combination therapy could be transferred into naïve mice to inhibit aggressive growth of lung metastases. The combination therapy enhanced CD8 memory formation as determined by memory markers and functional studies of immune recall. Removal of FoxP3-expressing T lymphocytes was the mechanism underlying immunologic memory formation following CD4 depletion. This was confirmed using transgenic DEREG (depletion of regulatory T cells) mice to specifically remove Foxp3(+) T cells. It was further confirmed with reciprocal studies where stimulation of immunologic memory because of CD4 depletion was completely neutralized by adoptively transferring tumor-specific Foxp3(+) T cells. Also contributing to tumor control, Tregs that eventually recovered following CD4 depletion were less immunosuppressive. These results provide a rationale for further study of mTOR inhibition and CD4 depletion in patients.

  18. Antigen independent differentiation and maintenance of effector-like resident memory T cells in tissues

    PubMed Central

    Casey, Kerry A; Fraser, Kathryn A; Schenkel, Jason M; Moran, Amy; Abt, Michael C; Beura, Lalit K; Lucas, Philip J; Artis, David; Wherry, E John; Hogquist, Kristin; Vezys, Vaiva; Masopust, David

    2012-01-01

    Differentiation and maintenance of recirculating effector memory CD8 T cells (TEM) depends on prolonged cognate antigen stimulation. Whether similar pathways of differentiation exist for recently identified tissue-resident effector memory T cells (TRM), which contribute to rapid local protection upon pathogen re-exposure, is unknown. Memory CD8αβ+ T cells within small intestine epithelium are well-characterized examples of TRM and they maintain a long-lived effector-like phenotype that is highly suggestive of persistent antigen stimulation. This study sought to define the sources and requirements for prolonged Ag-stimulation in programming this differentiation state, including local stimulation via cognate or cross-reactive antigens derived from pathogens, microbial flora, or dietary proteins. Contrary to expectations, we found that prolonged cognate Ag-stimulation was dispensable for intestinal TRM ontogeny. In fact, chronic antigenic stimulation skewed differentiation away from the canonical intestinal T cell phenotype. Resident memory signatures, CD69 and CD103, were expressed in many non-lymphoid tissues including intestine, stomach, kidney, reproductive tract, pancreas, brain, heart, and salivary gland, and could be driven by cytokines. Moreover, TGFβ driven CD103 expression was required for TRM maintenance within intestinal epithelium in vivo. Thus, induction and maintenance of long-lived effector-like intestinal TRM differed from classic models of TEM ontogeny, and were programmed through a novel location-dependent pathway that was required for the persistence of local immunological memory. PMID:22504644

  19. Medial entorhinal cortex lesions only partially disrupt hippocampal place cells and hippocampus-dependent place memory

    PubMed Central

    Hales, Jena B; Schlesiger, Magdalene I; Leutgeb, Jill K; Squire, Larry R; Leutgeb, Stefan; Clark, Robert E

    2014-01-01

    SUMMARY Entorhinal cortex provides the primary cortical projections to the hippocampus, a brain structure critical for memory. However, it remains unclear how the precise firing patterns of medial entorhinal cortex (MEC) cells influence hippocampal physiology and hippocampus-dependent behavior. We found that complete bilateral lesions of MEC resulted in a lower proportion of active hippocampal cells. The remaining active cells had place fields, but with decreased spatial precision and decreased long-term spatial stability. In addition, MEC rats were as impaired at acquiring the watermaze as hippocampus rats, while rats with combined MEC and hippocampal lesions had an even greater deficit. However, MEC rats were not impaired on other hippocampus-dependent tasks, including those in which an object location or context was remembered. Thus, MEC is not necessary for all types of spatial coding, nor for all types of hippocampus-dependent memory, but is necessary for the normal acquisition of place memory. PMID:25437546

  20. Cosmic ray-induced soft errors in static MOS memory cells

    NASA Technical Reports Server (NTRS)

    Sivo, L. L.; Peden, J. C.; Brettschneider, M.; Price, W.; Pentecost, P.

    1979-01-01

    Previous analytical models were extended to predict cosmic ray-induced soft error rates in static MOS memory devices. The effect is due to ionization and can be introduced by high energy, heavy ion components of the galactic environment. The results indicate that the sensitivity of memory cells is directly related to the density of the particular MOS technology which determines the node capacitance values. Hence, CMOS is less sensitive than e.g., PMOS. In addition, static MOS memory cells are less sensitive than dynamic ones due to differences in the mechanisms of storing bits. The flip-flop of a static cell is inherently stable against cosmic ray-induced bit flips. Predicted error rates on a CMOS RAM and a PMOS shift register are in general agreement with previous spacecraft flight data.

  1. Different Subsets of T Cells, Memory, Effector Functions, and CAR-T Immunotherapy.

    PubMed

    Golubovskaya, Vita; Wu, Lijun

    2016-03-15

    This review is focused on different subsets of T cells: CD4 and CD8, memory and effector functions, and their role in CAR-T therapy--a cellular adoptive immunotherapy with T cells expressing chimeric antigen receptor. The CAR-T cells recognize tumor antigens and induce cytotoxic activities against tumor cells. Recently, differences in T cell functions and the role of memory and effector T cells were shown to be important in CAR-T cell immunotherapy. The CD4⁺ subsets (Th1, Th2, Th9, Th17, Th22, Treg, and Tfh) and CD8⁺ memory and effector subsets differ in extra-cellular (CD25, CD45RO, CD45RA, CCR-7, L-Selectin [CD62L], etc.); intracellular markers (FOXP3); epigenetic and genetic programs; and metabolic pathways (catabolic or anabolic); and these differences can be modulated to improve CAR-T therapy. In addition, CD4⁺ Treg cells suppress the efficacy of CAR-T cell therapy, and different approaches to overcome this suppression are discussed in this review. Thus, next-generation CAR-T immunotherapy can be improved, based on our knowledge of T cell subsets functions, differentiation, proliferation, and signaling pathways to generate more active CAR-T cells against tumors.

  2. Detrimental effect of interfacial Dzyaloshinskii-Moriya interaction on perpendicular spin-transfer-torque magnetic random access memory

    SciTech Connect

    Jang, Peong-Hwa; Lee, Seo-Won E-mail: kj-lee@korea.ac.kr; Song, Kyungmi; Lee, Seung-Jae; Lee, Kyung-Jin E-mail: kj-lee@korea.ac.kr

    2015-11-16

    Interfacial Dzyaloshinskii-Moriya interaction in ferromagnet/heavy metal bilayers is recently of considerable interest as it offers an efficient control of domain walls and the stabilization of magnetic skyrmions. However, its effect on the performance of perpendicular spin transfer torque memory has not been explored yet. We show based on numerical studies that the interfacial Dzyaloshinskii-Moriya interaction decreases the thermal energy barrier while increases the switching current. As high thermal energy barrier as well as low switching current is required for the commercialization of spin torque memory, our results suggest that the interfacial Dzyaloshinskii-Moriya interaction should be minimized for spin torque memory applications.

  3. Sustained interactions between T cell receptors and antigens promote the differentiation of CD4⁺ memory T cells.

    PubMed

    Kim, Chulwoo; Wilson, Theodore; Fischer, Kael F; Williams, Matthew A

    2013-09-19

    During CD4⁺ T cell activation, T cell receptor (TCR) signals impact T cell fate, including recruitment, expansion, differentiation, trafficking, and survival. To determine the impact of TCR signals on the fate decision of activated CD4⁺ T cells to become end-stage effector or long-lived memory T helper 1 (Th1) cells, we devised a deep-sequencing-based approach that allowed us to track the evolution of TCR repertoires after acute infection. The transition of effector Th1 cells into the memory pool was associated with a significant decrease in repertoire diversity, and the major histocompatibility complex (MHC) class II tetramer off rate, but not tetramer avidity, was a key predictive factor in the representation of individual clonal T cell populations at the memory stage. We conclude that stable and sustained interactions with antigens during the development of Th1 responses to acute infection are a determinative factor in promoting the differentiation of Th1 memory cells.

  4. CD27 costimulation contributes substantially to the expansion of functional memory CD8(+) T cells after peptide immunization.

    PubMed

    Taraban, Vadim Y; Rowley, Tania F; Kerr, Jonathan P; Willoughby, Jane E; Johnson, Peter M W; Al-Shamkhani, Aymen; Buchan, Sarah L

    2013-12-01

    Naive T cells require signals from multiple costimulatory receptors to acquire full effector function and differentiate to long-lived memory cells. The costimulatory receptor, CD27, is essential for optimal T-cell priming and memory differentiation in a variety of settings, although whether CD27 is similarly required during memory CD8(+) T-cell reactivation remains controversial. We have used OVA and anti-CD40 to establish a memory CD8(+) T-cell population and report here that their secondary expansion, driven by peptide and anti-CD40, polyI:C, or LPS, requires CD27. Furthermore, antigenic peptide and a soluble form of the CD27 ligand, CD70 (soluble recombinant CD70 (sCD70)), is sufficient for secondary memory CD8(+) T-cell accumulation at multiple anatomical sites, dependent on CD80/86. Prior to boost, resting effector- and central-memory CD8(+) T cells both expressed CD27 with greater expression on central memory cells. Nonetheless, both populations upregulated CD27 after TCR engagement and accumulated in proportion after boosting with Ag and sCD70. Mechanistically, sCD70 increased the frequency of divided and cytolytic memory T cells, conferred resistance to apoptosis and enabled retardation of tumor growth in vivo. These data demonstrate the central role played by CD27/70 during secondary CD8(+) T-cell activation to a peptide Ag, and identify sCD70 as an immunotherapeutic adjuvant for antitumor immunity.

  5. Human memory, but not naive, CD4+ T cells expressing transcription factor T-bet might drive rapid cytokine production.

    PubMed

    Yu, Si-fei; Zhang, Yan-nan; Yang, Bin-yan; Wu, Chang-you

    2014-12-19

    We found that after stimulation for a few hours, memory but not naive CD4(+) T cells produced a large amount of IFN-γ; however, the mechanism of rapid response of memory CD4(+) T cells remains undefined. We compared the expression of transcription factors in resting or activated naive and memory CD4(+) T cells and found that T-bet, but not pSTAT-1 or pSTAT-4, was highly expressed in resting memory CD4(+) T cells and that phenotypic characteristics of T-bet(+)CD4(+) T cells were CD45RA(low)CD62L(low) CCR7(low). After short-term stimulation, purified memory CD4(+) T cells rapidly produced effector cytokines that were closely associated with the pre-existence of T-bet. By contrast, resting naive CD4(+) T cells did not express T-bet, and they produced cytokines only after sustained stimulation. Our further studies indicated that T-bet was expressed in the nuclei of resting memory CD4(+) T cells, which might have important implications for rapid IFN-γ production. Our results indicate that the pre-existence and nuclear mobilization of T-bet in resting memory CD4(+) T cells might be a possible transcriptional mechanism for rapid production of cytokines by human memory CD4(+) T cells.

  6. 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.

  7. Memory B cell compartment constitution and susceptibility to recurrent lower respiratory tract infections in young children.

    PubMed

    Siebert, Johan N; L'huillier, Arnaud G; Grillet, Stéphane; Delhumeau, Cécile; Siegrist, Claire-Anne; Posfay-Barbe, Klara M

    2013-06-01

    A proportion of children have recurrent LRTIs, mostly as a result of Spn, which persist after 2 years of age. Here, we investigate, by flow cytofluorometry, the constitution of the memory B cell compartment in 90 healthy children and 49 children with recurrent LRTIs to determine if an increased susceptibility to recurrent LRTIs results from a delayed or abnormal ontogeny with poor antibody-mediated protection. Total IgA, IgM, IgG, and IgG subclasses were measured by nephelometry, as well as antipneumococcal antibodies by ELISA. Pneumococcal vaccination status was obtained. We show that the memory B cells increase between birth and 2 years of age (1.6% vs. 21.1%, P<0.001) without further significant increase noted per additional years (3-4 years old: 23.3%; 4-5 years old: 22.2%, P>0.40) to reach adult-like values (31.8±11.8%, P=0.08). Proportions of switched and IgM memory B cells were similar in children and adults. Comparatively, LRTI children had no delay in the constitution of their memory B cell compartment (2-3 years old: 26.9%; 3-4 years old: 18.2%; 4-5 years old: 26.8%, P>0.05). Their switched and IgM memory B cells were similar among age categories, and the distribution was overall similar to that of healthy controls. LRTI children had normal total and pneumococcal serotype-specific antibody values but showed a rapid waning of antipneumococcal antibody levels after vaccination. In summary, our results show that the memory B cell compartment is already similarly constituted at 2 years of age in healthy and LRTI children and thus, cannot explain the increased susceptibility to bacterial pneumonia. However, the waning of antibodies might predispose children to recurrent infections in the absence of revaccination.

  8. NFκB-Pim-1-Eomesodermin axis is critical for maintaining CD8 T-cell memory quality.

    PubMed

    Knudson, Karin M; Pritzl, Curtis J; Saxena, Vikas; Altman, Amnon; Daniels, Mark A; Teixeiro, Emma

    2017-02-28

    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.

  9. Rapid and Continued T-Cell Differentiation into Long-term Effector and Memory Stem Cells in Vaccinated Melanoma Patients.

    PubMed

    Gannon, Philippe O; Baumgaertner, Petra; Huber, Alexandre; Iancu, Emanuela M; Cagnon, Laurène; Abed Maillard, Samia; Maby-El Hajjami, Hélène; Speiser, Daniel E; Rufer, Nathalie

    2016-11-21

    Purpose: Patients with cancer benefit increasingly from T-cell-based therapies, such as adoptive T-cell transfer, checkpoint blockade, or vaccination. We have previously shown that serial vaccinations with Melan-A(MART-1)26-35 peptide, CpG-B, and incomplete Freund adjuvant (IFA) generated robust tumor-specific CD8 T-cell responses in patients with melanoma. Here, we describe the detailed kinetics of early- and long-term establishment of T-cell frequency, differentiation (into memory and effector cells), polyfunctionality, and clonotype repertoire induced by vaccination.Experimental Design: Twenty-nine patients with melanoma were treated with multiple monthly subcutaneous vaccinations consisting of CpG-B, and either the native/EAA (n = 13) or the analogue/ELA (n = 16) Melan-A(MART-1)26-35 peptide emulsified in IFA. Phenotypes and functionality of circulating Melan-A-specific CD8 T cells were assessed directly ex vivo by multiparameter flow cytometry, and TCR clonotypes were determined ex vivo by mRNA transcript analyses of individually sorted cells.Results: Our results highlight the determining impact of the initial vaccine injections on the rapid and strong induction of differentiated effector T cells in both patient cohorts. Moreover, long-term polyfunctional effector T-cell responses were associated with expansion of stem cell-like memory T cells over time along vaccination. Dominant TCR clonotypes emerged early and persisted throughout the entire period of observation. Interestingly, one highly dominant clonotype was found shared between memory and effector subsets.Conclusions: Peptide/CpG-B/IFA vaccination induced powerful long-term T-cell responses with robust effector cells and stem cell-like memory cells. These results support the further development of CpG-B-based cancer vaccines, either alone or as specific component of combination therapies. Clin Cancer Res; 1-12. ©2016 AACR.

  10. Quantifying data retention of perpendicular spin-transfer-torque magnetic random access memory chips using an effective thermal stability factor method

    SciTech Connect

    Thomas, Luc Jan, Guenole; Le, Son; Wang, Po-Kang

    2015-04-20

    The thermal stability of perpendicular Spin-Transfer-Torque Magnetic Random Access Memory (STT-MRAM) devices is investigated at chip level. Experimental data are analyzed in the framework of the Néel-Brown model including distributions of the thermal stability factor Δ. We show that in the low error rate regime important for applications, the effect of distributions of Δ can be described by a single quantity, the effective thermal stability factor Δ{sub eff}, which encompasses both the median and the standard deviation of the distributions. Data retention of memory chips can be assessed accurately by measuring Δ{sub eff} as a function of device diameter and temperature. We apply this method to show that 54 nm devices based on our perpendicular STT-MRAM design meet our 10 year data retention target up to 120 °C.

  11. Investigation of thermal resistance and power consumption in Ga-doped indium oxide (In{sub 2}O{sub 3}) nanowire phase change random access memory

    SciTech Connect

    Jin, Bo; Lee, Jeong-Soo E-mail: ljs6951@postech.ac.kr; Lim, Taekyung; Ju, Sanghyun; Latypov, Marat I.; Pi, Dong-Hai; Seop Kim, Hyoung; Meyyappan, M. E-mail: ljs6951@postech.ac.kr

    2014-03-10

    The resistance stability and thermal resistance of phase change memory devices using ∼40 nm diameter Ga-doped In{sub 2}O{sub 3} nanowires (Ga:In{sub 2}O{sub 3} NW) with different Ga-doping concentrations have been investigated. The estimated resistance stability (R(t)/R{sub 0} ratio) improves with higher Ga concentration and is dependent on annealing temperature. The extracted thermal resistance (R{sub th}) increases with higher Ga-concentration and thus the power consumption can be reduced by ∼90% for the 11.5% Ga:In{sub 2}O{sub 3} NW, compared to the 2.1% Ga:In{sub 2}O{sub 3} NW. The excellent characteristics of Ga-doped In{sub 2}O{sub 3} nanowire devices offer an avenue to develop low power and reliable phase change random access memory applications.

  12. Virus-specific CD4+ memory phenotype T cells are abundant in unexposed adults

    PubMed Central

    Su, Laura F.; Kidd, Brian A.; Han, Arnold; Kotzin, Jonathan J.; Davis, Mark M.

    2013-01-01

    While T cell memory is generally thought to require direct antigen exposure, we find an abundance of memory phenotype cells (20–90%, averaging over 50%) of CD4+ T cells specific for viral antigens in adults that have never been infected. These cells express the appropriate memory markers and genes, rapidly produce cytokines, and have clonally expanded. This contrasts with newborns where the same T cell receptor (TCR) specificities are almost entirely naïve, which may explain the vulnerability of young children to infections. One mechanism for this phenomenon is TCR cross-reactivity to environmental antigens and in support of this we find extensive cross-recognition by HIV-1 and influenza-reactive T lymphocytes to other microbial peptides and the expansion of one of these following influenza vaccination. Thus the presence of these memory phenotype T cells has significant implications for immunity to novel pathogens, child and adult health, and the influence of pathogen-rich versus hygienic environments. PMID:23395677

  13. Endotoxemia contributes to CD27+ memory B-cell apoptosis via enhanced sensitivity to Fas ligation in patients with Cirrhosis

    PubMed Central

    Chang, Li-Yuan; Li, Yonghai; Kaplan, David E.

    2016-01-01

    Peripheral CD27+ memory B-cells become quantitatively reduced and dysfunctional in patients with cirrhosis through poorly characterized mechanisms. We hypothesized that the disappearance of CD27+ memory B-cells results from enhanced sensitivity to apoptosis caused by exposure to gut microbial translocation products. Using isolated naïve and memory B-cells from patients with cirrhosis and age-matched controls, ex vivo and activation-induced sensitivity to Fas-mediated apoptosis was assessed under relevant experimental conditions. We observed differential expression of CD95(Fas) in CD27+ B-cells from cirrhotic patients that was inversely correlated with peripheral CD27+ B-cell frequency. While memory B-cells from cirrhotic patients were resistant to Fas-mediated apoptosis ex vivo, Toll-like receptor 4(TLR4)-ligation restored Fas-sensitivity. Sensitivity to Fas-mediated apoptosis could be transferred to healthy donor memory B-cells by co-culturing these cells with plasma from cirrhotic patients, a sensitivity partially mediated by Fas and TLR4 signaling, and partially rescued via B-cell receptor crosslinking. We conclude that peripheral CD27+ memory B-cells in cirrhosis exhibit increased sensitivity to Fas-induced apoptosis in an activation-dependent manner to which endotoxin contributes, associated with reduced frequency of circulating memory B-cells. Destruction of this critical cell subset may contribute to the cirrhotic immunodeficiency state and heightened risk of systemic infections in advanced liver disease. PMID:27857173

  14. Genetic Regulation of Fate Decisions in Therapeutic T Cells to Enhance Tumor Protection and Memory Formation.

    PubMed

    Veliça, Pedro; Zech, Mathias; Henson, Sian; Holler, Angelika; Manzo, Teresa; Pike, Rebecca; Santos E Sousa, Pedro; Zhang, Lei; Heinz, Niels; Schiedlmeier, Bernhard; Pule, Martin; Stauss, Hans; Chakraverty, Ronjon

    2015-07-01

    A key challenge in the field of T-cell immunotherapy for cancer is creating a suitable platform for promoting differentiation of effector cells while at the same time enabling self-renewal needed for long-term memory. Although transfer of less differentiated memory T cells increases efficacy through greater expansion and persistence in vivo, the capacity of such cells to sustain effector functions within immunosuppressive tumor microenvironments may still be limiting. We have therefore directly compared the impact of effector versus memory differentiation of therapeutic T cells in tumor-bearing mice by introducing molecular switches that regulate cell fate decisions via mTOR. Ectopic expression of RAS homolog enriched in brain (RHEB) increased mTORC1 signaling, promoted a switch to aerobic glycolysis, and increased expansion of effector T cells. By rapidly infiltrating tumors, RHEB-transduced T cells significantly reduced the emergence of immunoedited escape variants. In contrast, expression of proline-rich Akt substrate of 40 kDa (PRAS40) inhibited mTORC1, promoted quiescence, and blocked tumor infiltration. Fate mapping studies following transient expression of PRAS40 demonstrated that mTORC1(low) T cells made no contribution to initial tumor control but instead survived to become memory cells proficient in generating recall immunity. Our data support the design of translational strategies for generating heterogeneous T-cell immunity against cancer, with the appropriate balance between promoting effector differentiation and self-renewal. Unlike pharmacologic inhibitors, the genetic approach described here allows for upregulation as well as inhibition of the mTORC1 pathway and is highly selective for the therapeutic T cells without affecting systemic mTORC1 functions.

  15. Modulation of Memory T Cells to Control Acquired Bone Marrow Failure

    DTIC Science & Technology

    2016-01-01

    function of T-bet, which is a transcription factor key to the generation of Th1 cells. However, transcription factors are difficult drug targets.55 Thus...reference-37). Fig. 6. In the absence of Ezh2, LN cells are defective in mediating AA in mice. To assess whether conditionally deleting Ezh2 in...new perspective to study how Notch and Notch ligands may interact with epigenetic regulators to control memory T cell development and subsequent

  16. Therapeutic effect of mesenchymal multipotent stromal cells on memory in animals with Alzheimer-type neurodegeneration.

    PubMed

    Bobkova, N V; Poltavtseva, R A; Samokhin, A N; Sukhikh, G T

    2013-11-01

    Transplantation of human mesenchymal multipotent stromal cells improved spatial memory in bulbectomized mice with Alzheimer-type neurodegeneration. The positive effect was observed in 1 month after intracerebral transplantation and in 3 months after systemic injection of mesenchymal multipotent stromal cells. No cases of malignant transformation were noted. These findings indicate prospects of using mesenchymal multipotent stromal cells for the therapy of Alzheimer disease and the possibility of their systemic administration for attaining the therapeutic effect.

  17. Activating Autophagy in Hippocampal Cells Alleviates the Morphine-Induced Memory Impairment.

    PubMed

    Pan, Jingrui; He, Lei; Li, Xiangpen; Li, Mei; Zhang, Xiaoni; Venesky, Jacob; Li, Yi; Peng, Ying

    2017-04-01

    Morphine abuse in treating severe and chronic pain has become a worldwide problem. But, chronic morphine exposure can cause memory impairment with its mechanisms not fully elucidated by past research sstudies which all focused on the harmful effects of morphine. Autophagy is an important pathway for cells to maintain survival. Here we showed that repeated morphine injection into C57BL/6 mice at a dose of 15 mg/kg per day for 7 days activated autophagic flux mainly in the hippocampi, especially in neurons of hippocampal CA1 region and microglia, with spatial memory impairment confirmed by Morris water maze test. Autophagy inhibition by 3-methyladenine obviously aggravates this morphine-induced memory impairment, accompanied with increased cell deaths in stratum pyramidale of hippocampal CA1, CA3, and DG regions and the activation of microglia to induce inflammation in hippocampus, such as upregulated expression of TNF-α, IL-1β, IL-6, and iNOS, as well as NF-κB' s activation, while morphine alone promoted microglial immunosuppression in hippocampus with autophagy activation which was also confirmed in primary microglia. Taken together, our data indicates that autophagy activating in hippocampal cells can alleviate the memory impairment caused by morphine, by decreasing neuronal deaths in hippocampus and suppressing inflammation in hippocampal microglia, implying that modulating the activation of autophagy might be a promising method to prevent or treat the memory impairment caused by morphine.

  18. Effects of Asiatic Acid on Spatial Working Memory and Cell Proliferation in the Adult Rat Hippocampus.

    PubMed

    Sirichoat, Apiwat; Chaijaroonkhanarak, Wunnee; Prachaney, Parichat; Pannangrong, Wanassanan; Leksomboon, Ratana; Chaichun, Amnart; Wigmore, Peter; Welbat, Jariya Umka

    2015-10-05

    Asiatic acid is a pentacyclic triterpene from Centella asiatica. Previous studies have reported that asiatic acid exhibits antioxidant and neuroprotective activities in cell culture. It also prevents memory deficits in animal models. The objective of this study was to investigate the relationship between spatial working memory and changes in cell proliferation within the hippocampus after administration of asiatic acid to male Spraque-Dawley rats. Control rats received vehicle (propylene glycol) while treated rats received asiatic acid (30 mg/kg) orally for 14 or 28 days. Spatial memory was determined using the novel object location (NOL) test. In animals administered asiatic acid for both 14 and 28 days, the number of Ki-67 positive cells in the subgranular zone of the dentate gyrus was significantly higher than in control animals. This was associated with a significant increase in their ability to discriminate between novel and familiar object locations in a novel object discrimination task, a hippocampus-dependent spatial memory test. Administration of asiatic acid also significantly increased doublecortin (DCX) and Notch1 protein levels in the hippocampus. These findings demonstrate that asiatic acid treatment may be a potent cognitive enhancer which improves hippocampal-dependent spatial memory, likely by increasing hippocampal neurogenesis.

  19. Effects of Asiatic Acid on Spatial Working Memory and Cell Proliferation in the Adult Rat Hippocampus

    PubMed Central

    Sirichoat, Apiwat; Chaijaroonkhanarak, Wunnee; Prachaney, Parichat; Pannangrong, Wanassanan; Leksomboon, Ratana; Chaichun, Amnart; Wigmore, Peter; Umka Welbat, Jariya

    2015-01-01

    Asiatic acid is a pentacyclic triterpene from Centella asiatica. Previous studies have reported that asiatic acid exhibits antioxidant and neuroprotective activities in cell culture. It also prevents memory deficits in animal models. The objective of this study was to investigate the relationship between spatial working memory and changes in cell proliferation within the hippocampus after administration of asiatic acid to male Spraque-Dawley rats. Control rats received vehicle (propylene glycol) while treated rats received asiatic acid (30 mg/kg) orally for 14 or 28 days. Spatial memory was determined using the novel object location (NOL) test. In animals administered asiatic acid for both 14 and 28 days, the number of Ki-67 positive cells in the subgranular zone of the dentate gyrus was significantly higher than in control animals. This was associated with a significant increase in their ability to discriminate between novel and familiar object locations in a novel object discrimination task, a hippocampus-dependent spatial memory test. Administration of asiatic acid also significantly increased doublecortin (DCX) and Notch1 protein levels in the hippocampus. These findings demonstrate that asiatic acid treatment may be a potent cognitive enhancer which improves hippocampal-dependent spatial memory, likely by increasing hippocampal neurogenesis. PMID:26445061

  20. The Memory Metal Minimal Access Cage: A New Concept in Lumbar Interbody Fusion—A Prospective, Noncomparative Study to Evaluate the Safety and Performance

    PubMed Central

    Kok, D.; Donk, R. D.; Wapstra, F. H.; Veldhuizen, A. G.

    2012-01-01

    Study Design/Objective. A single-centre, prospective, non-comparative study of 25 patients to evaluate the performance and safety of the Memory Metal Minimal Access Cage (MAC) in Lumbar Interbody Fusion. Summary of Background Data. Interbody fusion cages in general are designed to withstand high axial loads and in the meantime to allow ingrowth of new bone for bony fusion. In many cages the contact area with the endplate is rather large leaving a relatively small contact area for the bone graft with the adjacent host bone. MAC is constructed from the memory metal Nitinol and builds on the concept of sufficient axial support in combination with a large contact area of the graft facilitating bony ingrowth and ease in minimal access implantation due to its high deformability. Methods. Twenty five subjects with a primary diagnosis of disabling back and radicular leg pain from a single level degenerative lumbar disc underwent an interbody fusion using MAC and pedicle screws. Clinical performance was evaluated prospectively over 2 years using the Oswestry Disability Index (ODI), Short Form 36 questionnaire (SF-36) and pain visual analogue scale (VAS) scores. The interbody fusion status was assessed using conventional radiographs and CT scan. Safety of the device was studied by registration of intra- and post-operative adverse effects. Results. Clinical performance improved significantly (P < .0018), CT scan confirmed solid fusion in all 25 patients at two year follow-up. In two patients migration of the cage occurred, which was resolved uneventfully by placing a larger size at the subsequent revision. Conclusions. We conclude that the Memory Metal Minimal Access Cage (MAC) resulted in 100% solid fusions in 2 years and proved to be safe, although two patients required revision surgery in order to achieve solid fusion. PMID:22567409

  1. Human embryonic stem cell research, justice, and the problem of unequal biological access.

    PubMed

    Moller, Mark S

    2008-09-29

    In 2003, Ruth Faden and eighteen other colleagues argued that a "problem of unequal biological access" is likely to arise in access to therapies resulting from human embryonic stem cell research. They showed that unless deliberate steps are taken in the United States to ensure that the human embryonic stem cell lines available to researchers mirrors the genetic diversity of the general population, white Americans will likely receive the benefits of these therapies to the relative exclusion of minority ethnic groups. Over the past five years the problem of unequal biological access has not received much attention from politicians, bioethicists and even many researchers in the United States, in spite of the widely held belief in the country that there is an obligation to prevent and correct ethnic disparities in access to medical care. The purpose of this paper is to increase awareness of the problem of unequal biological access and of the need to do more than is currently being done to ensure that ethnic disparities in access to human embryonic stem cell-based therapies do not arise. Specifically, this paper explains why the problem of unequal biological access will likely arise in the United States in such a way that white Americans will disproportionately receive most of the benefits of the therapies resulting from human embryonic stem cell research. It also argues for why there is an obligation to prevent these ethnic disparities in access from happening and outlines four steps that need to be taken towards meeting this obligation.

  2. Human embryonic stem cell research, justice, and the problem of unequal biological access

    PubMed Central

    Moller, Mark S

    2008-01-01

    In 2003, Ruth Faden and eighteen other colleagues argued that a "problem of unequal biological access" is likely to arise in access to therapies resulting from human embryonic stem cell research. They showed that unless deliberate steps are taken in the United States to ensure that the human embryonic stem cell lines available to researchers mirrors the genetic diversity of the general population, white Americans will likely receive the benefits of these therapies to the relative exclusion of minority ethnic groups. Over the past five years the problem of unequal biological access has not received much attention from politicians, bioethicists and even many researchers in the United States, in spite of the widely held belief in the country that there is an obligation to prevent and correct ethnic disparities in access to medical care. The purpose of this paper is to increase awareness of the problem of unequal biological access and of the need to do more than is currently being done to ensure that ethnic disparities in access to human embryonic stem cell-based therapies do not arise. Specifically, this paper explains why the problem of unequal biological access will likely arise in the United States in such a way that white Americans will disproportionately receive most of the benefits of the therapies resulting from human embryonic stem cell research. It also argues for why there is an obligation to prevent these ethnic disparities in access from happening and outlines four steps that need to be taken towards meeting this obligation. PMID:18823539

  3. 39% access time improvement, 11% energy reduction, 32 kbit 1-read/1-write 2-port static random-access memory using two-stage read boost and write-boost after read sensing scheme

    NASA Astrophysics Data System (ADS)

    Yamamoto, Yasue; Moriwaki, Shinichi; Kawasumi, Atsushi; Miyano, Shinji; Shinohara, Hirofumi

    2016-04-01

    We propose novel circuit techniques for 1 clock (1CLK) 1 read/1 write (1R/1W) 2-port static random-access memories (SRAMs) to improve read access time (tAC) and write margins at low voltages. Two-stage read boost (TSR-BST) and write word line boost (WWL-BST) after the read sensing schemes have been proposed. TSR-BST reduces the worst read bit line (RBL) delay by 61% and RBL amplitude by 10% at V DD = 0.5 V, which improves tAC by 39% and reduces energy dissipation by 11% at V DD = 0.55 V. WWL-BST after read sensing scheme improves minimum operating voltage (V min) by 140 mV. A 32 kbit 1CLK 1R/1W 2-port SRAM with TSR-BST and WWL-BST has been developed using a 40 nm CMOS.

  4. Mechanism of power consumption inhibitive multi-layer Zn:SiO{sub 2}/SiO{sub 2} structure resistance random access memory

    SciTech Connect

    Zhang, Rui; Lou, Jen-Chung; Tsai, Tsung-Ming E-mail: tcchang@mail.phys.nsysu.edu.tw; Chang, Kuan-Chang; Huang, Syuan-Yong; Shih, Chih-Cheng; Pan, Jhih-Hong; Tung, Cheng-Wei; Chang, Ting-Chang E-mail: tcchang@mail.phys.nsysu.edu.tw; Chen, Kai-Huang; Young, Tai-Fa; Chen, Hsin-Lu; Chen, Jung-Hui; Chen, Min-Chen; Syu, Yong-En; Sze, Simon M.

    2013-12-21

    In this paper, multi-layer Zn:SiO{sub 2}/SiO{sub 2} structure is introduced to reduce the operation power consumption of resistive random access memory (RRAM) device by modifying the filament formation process. And the configuration of multi-layer Zn:SiO{sub 2}/SiO{sub 2} structure is confirmed and demonstrated by auger electron spectrum. Material analysis together with conduction current fitting is applied to qualitatively evaluate the carrier conduction mechanism on both low resistance state and high resistance state. Finally, single layer and multilayer conduction models are proposed, respectively, to clarify the corresponding conduction characteristics of two types of RRAM devices.

  5. Reducing operation voltages by introducing a low-k switching layer in indium-tin-oxide-based resistance random access memory

    NASA Astrophysics Data System (ADS)

    Jin, Fu-Yuan; Chang, Kuan-Chang; Chang, Ting-Chang; Tsai, Tsung-Ming; Pan, Chih-Hung; Lin, Chih-Yang; Chen, Po-Hsun; Chen, Min-Chen; Huang, Hui-Chun; Lo, Ikai; Zheng, Jin-Cheng; Sze, Simon M.

    2016-06-01

    In this letter, we inserted a low dielectric constant (low-k) or high dielectric constant (high-k) material as a switching layer in indium-tin-oxide-based resistive random-access memory. After measuring the two samples, we found that the low-k material device has very low operating voltages (-80 and 110 mV for SET and RESET operations, respectively). Current fitting results were then used with the COMSOL software package to simulate electric field distribution in the layers. After combining the electrical measurement results with simulations, a conduction model was proposed to explain resistance switching behaviors in the two structures.

  6. Suppression of endurance degradation by applying constant voltage stress in one-transistor and one-resistor resistive random access memory

    NASA Astrophysics Data System (ADS)

    Su, Yu-Ting; Chang, Ting-Chang; Tsai, Tsung-Ming; Chang, Kuan-Chang; Chu, Tian-Jian; Chen, Hsin-Lu; Chen, Min-Chen; Yang, Chih-Cheng; Huang, Hui-Chun; Lo, Ikai; Zheng, Jin-Cheng; Sze, Simon M.

    2017-01-01

    In this letter we demonstrate an operation method that effectively suppresses endurance degradation. After many operations, the off-state of resistance random access memory (RRAM) degrades. This degradation is caused by reduction of active oxygen ions participating in the set process, as determined by current fitting of current-voltage (I-V) curves obtained from the endurance test between the interval of seventy to one hundred million operations. To address this problem, we propose the application of constant voltage stress after every five million operations during the endurance test. The experimental result shows that this method can maintain oxygen ions at the proper depth in the electrode and improve RRAM reliability.

  7. Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis.

    PubMed

    Cheuk, Stanley; Wikén, Maria; Blomqvist, Lennart; Nylén, Susanne; Talme, Toomas; Ståhle, Mona; Eidsmo, Liv

    2014-04-01

    Psoriasis is a common and chronic inflammatory skin disease in which T cells play a key role. Effective treatment heals the skin without scarring, but typically psoriasis recurs in previously affected areas. A pathogenic memory within the skin has been proposed, but the nature of such site-specific disease memory is unknown. Tissue-resident memory T (TRM) cells have been ascribed a role in immunity after resolved viral skin infections. Because of their localization in the epidermal compartment of the skin, TRM may contribute to tissue pathology during psoriasis. In this study, we investigated whether resolved psoriasis lesions contain TRM cells with the ability to maintain and potentially drive recurrent disease. Three common and effective therapies, narrowband-UVB treatment and long-term biologic treatment systemically inhibiting TNF-α or IL-12/23 signaling were studied. Epidermal T cells were highly activated in psoriasis and a high proportion of CD8 T cells expressed TRM markers. In resolved psoriasis, a population of cutaneous lymphocyte-associated Ag, CCR6, CD103, and IL-23R expressing epidermal CD8 T cells was highly enriched. Epidermal CD8 T cells expressing the TRM marker CD103 responded to ex vivo stimulation with IL-17A production and epidermal CD4 T cells responded with IL-22 production after as long as 6 y of TNF-α inhibition. Our data suggest that epidermal TRM cells are retained in resolved psoriasis and that these cells are capable of producing cytokines with a critical role in psoriasis pathogenesis. We provide a potential mechanism for a site-specific T cell-driven disease memory in psoriasis.

  8. Allograft rejection mediated by memory T cells is resistant to regulation.

    PubMed

    Yang, Jaeseok; Brook, Matthew O; Carvalho-Gaspar, Manuela; Zhang, Jidong; Ramon, Hilda E; Sayegh, Mohamed H; Wood, Kathryn J; Turka, Laurence A; Jones, Nick D

    2007-12-11

    Alloreactive memory T cells may be refractory to many of the tolerance-inducing strategies that are effective against naive T cells and thus present a significant barrier to long-term allograft survival. Because CD4(+)CD25(+) regulatory T cells (Tregs) are critical elements of many approaches to successful induction/maintenance of transplantation tolerance, we used MHC class I and II alloreactive TCR-transgenic models to explore the ability of antigen-specific Tregs to control antigen-specific memory T cell responses. Upon coadoptive transfer into RAG-1(-/-) mice, we found that Tregs effectively suppressed the ability of naive T cells to reject skin grafts, but neither antigen-unprimed nor antigen-primed Tregs suppressed rejection by memory T cells. Interestingly, different mechanisms appeared to be active in the ability of Tregs to control naive T cell-mediated graft rejection in the class II versus class I alloreactive models. In the former case, we observed decreased early expansion of effector cells in lymphoid tissue. In contrast, in the class I model, an effect of Tregs on early proliferation and expansion was not observed. However, at a late time point, significant differences in cell numbers were seen, suggesting effects on responding T cell survival. Overall, these data indicate that the relative resistance of both CD4(+) and CD8(+) alloreactive memory T cells to regulation may mediate resistance to tolerance induction seen in hosts with preexisting alloantigen-specific immunity and further indicate the multiplicity of mechanisms by which Tregs may control alloimmune responses in vivo.

  9. Restricted specificity of peripheral alloreactive memory B cells in HLA-sensitized patients awaiting a kidney transplant.

    PubMed

    Snanoudj, Renaud; Claas, Frans H J; Heidt, Sebastiaan; Legendre, Christophe; Chatenoud, Lucienne; Candon, Sophie

    2015-06-01

    The contribution of memory B cells in alloreactive humoral responses remains poorly understood. Here we tested the presence of circulating alloreactive memory B cells in 69 patients with end-stage renal disease under renal replacement therapy, using an in vitro memory B cell-stimulation assay combined with identification of IgG human leukocyte antigen (HLA) antibodies in culture supernatant. HLA antibody-producing memory B cells were evidenced only in patients carrying serum HLA antibodies following multiple classical HLA-immunizing events. In patients with a previous renal allograft, alloreactive memory B cells could be detected ranging from 6 to 32 years (mean 13.2 years) after transplantation. HLA antibodies produced by memory B cells were also detected in the corresponding sera and showed a restricted reactivity, targeting only a few epitopes shared by several HLA antigens. In contrast, serum HLA antibodies, not associated with the detection of specific memory B cells, showed a broader pattern of specificities. Thus, expansion and survival of alloreactive memory B cells is alloantigen driven, and their frequency is related to the 'strength' of HLA immunization.

  10. Evaluation of EBV transformation of human memory B-cells isolated by FACS and MACS techniques.

    PubMed

    Sadreddini, Sanam; Jadidi-Niaragh, Farhad; Younesi, Vahid; Pourlak, Tala; Afkham, Amir; Shokri, Fazel; Yousefi, Mehdi

    2016-07-01

    Several studies have been performed to develop effective neutralizing monoclonal antibodies. The Epstein-Barr virus (EBV) can efficiently immortalize B-cells to establish lymphoblastoid cell lines (LCL) and so it has been used extensively for transformation of B-cells to produce and secrete immunoglobulin. The present study addressed the effect of TLR7/8 agonist (R848), feeder cells layer and fluorescence-activated cell sorting (FACS) and magnetic-activated cell sorting (MACS) cell separation methods on the transformation efficiency of antibody-producing memory B-cells. For these studies, the antigen used for analyses of antibody formation was the tetanus neurotoxin (TeNT) derived from Clostridium tetani. The results here showed that employing an HFFF.PI6 feeder cell layer, R848 agonist and FACS-mediated purification of memory B-cells led to increased transformation efficiency. Altogether, the effects of the R848 and the feeder cells provided an efficient method for EBV transformation of human B-cells. Moreover, there was an advantage in using FACS sorting of B-cells over the MACS method in the context of EBV transformation and immortalization of precursors of antigen-specific B-cells.

  11. 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.

  12. About Training and Memory: NK-Cell Adaptation to Viral Infections.

    PubMed

    Hammer, Q; Romagnani, C

    2017-01-01

    Viral infections continuously challenge and shape our immune system. Due to their fine antigen recognition ability, adaptive lymphocytes protect against pathogen reencounter by generating specific immunological memory. Innate cells such as macrophages also adapt to pathogen challenge and mount resistance to reinfection, a phenomenon termed trained immunity. As part of the innate immunity, natural killer (NK) cells can display rapid effector functions and play a crucial role in the control of viral infections, especially by the β-herpesvirus cytomegalovirus (CMV). CMV activates the NK-cell pool by inducing proinflammatory signals, which prime NK cells, paralleling macrophage training. In addition, CMV dramatically shapes the NK-cell repertoire due to its ability to trigger specific NK cell-activating receptors, and enables the expansion and persistence of a specific NK-cell subset displaying adaptive and memory features. In this chapter, we will discuss how different signals during CMV infection contribute to NK-cell training and acquisition of classical memory properties and how these events can impact on reinfection and cross-resistance.

  13. Stiffness-Controlled Thermoresponsive Hydrogels for Cell Harvesting with Sustained Mechanical Memory.

    PubMed

    Fan, Xingliang; Zhu, Lu; Wang, Ke; Wang, Bingjie; Wu, Yaozu; Xie, Wei; Huang, Chengyu; Chan, Barbara Pui; Du, Yanan

    2017-03-01

    Most mechanobiological investigations focused on in situ mechanical regulation of cells on stiffness-controlled substrates with few downstream applications, as it is still challenging to harvest and expand mechanically primed cells by enzymatic digestion (e.g., trypsin) without interrupting cellular mechanical memory between passages. This study develops thermoresponsive hydrogels with controllable stiffness to generate mechanically primed cells with intact mechanical memory for augmented wound healing. No significant cellular property alteration of the fibroblasts primed on thermoresponsive hydrogels with varied stiffness has been observed through thermoresponsive harvesting. When reseeding the harvested cells for further evaluation, softer hydrogels are proven to better sustain the mechanical priming effects compared to rigid tissue culture plate, which indicates that both the stiffness-controlled substrate and thermoresponsive harvesting are required to sustain cellular mechanical memory between passages. Moreover, epigenetics analysis reveals that thermoresponsive harvesting could reduce the rearrangement and loss of chromatin proteins compared to that of trypsinization. In vivo wound healing using mechanically primed fibroblasts shows featured epithelium and sebaceous glands, which indicates augmented skin recovery compared with trypsinized fibroblasts. Thus, the thermoresponsive hydrogel-based cell harvesting system offers a powerful tool to investigate mechanobiology between cell passages and produces abundant cells with tailored mechanical priming properties for cell-based applications.

  14. Reversible Reprogramming of Circulating Memory T Follicular Helper Cell Function during Chronic HIV Infection

    PubMed Central

    Cubas, Rafael; van Grevenynghe, Julien; Wills, Saintedym; Kardava, Lela; Santich, Brian H.; Buckner, Clarisa M.; Muir, Roshell; Tardif, Virginie; Nichols, Carmen; Procopio, Francesco; He, Zhong; Metcalf, Talibah; Ghneim, Khader; Locci, Michela; Ancuta, Petronella; Routy, Jean-Pierre; Trautmann, Lydie; Li, Yuxing; McDermott, Adrian B.; Koup, Rick A.; Petrovas, Constantinos; Migueles, Steven A.; Connors, Mark; Tomaras, Georgia D.; Moir, Susan; Crotty, Shane

    2015-01-01

    Despite the overwhelming benefits of antiretroviral therapy (ART) in curtailing viral load in HIV-infected individuals, ART does not fully restore cellular and humoral immunity. HIV-infected individuals under ART show reduced responses to vaccination and infections and are unable to mount an effective antiviral immune response upon ART cessation. Many factors contribute to these defects, including persistent inflammation, especially in lymphoid tissues, where T follicular helper (Tfh) cells instruct and help B cells launch an effective humoral immune response. In this study we investigated the phenotype and function of circulating memory Tfh cells as a surrogate of Tfh cells in lymph nodes and found significant impairment of this cell population in chronically HIV-infected individuals, leading to reduced B cell responses. We further show that these aberrant memory Tfh cells exhibit an IL-2–responsive gene signature and are more polarized toward a Th1 phenotype. Treatment of functional memory Tfh cells with IL-2 was able to recapitulate the detrimental reprogramming. Importantly, this defect was reversible, as interfering with the IL-2 signaling pathway helped reverse the abnormal differentiation and improved Ab responses. Thus, reversible reprogramming of memory Tfh cells in HIV-infected individuals could be used to enhance Ab responses. Altered microenvironmental conditions in lymphoid tissues leading to altered Tfh cell differentiation could provide one explanation for the poor responsiveness of HIV-infected individuals to new Ags. This explanation has important implications for the development of therapeutic interventions to enhance HIV- and vaccine-mediated Ab responses in patients under ART. PMID:26546609

  15. Reversible Reprogramming of Circulating Memory T Follicular Helper Cell Function during Chronic HIV Infection.

    PubMed

    Cubas, Rafael; van Grevenynghe, Julien; Wills, Saintedym; Kardava, Lela; Santich, Brian H; Buckner, Clarisa M; Muir, Roshell; Tardif, Virginie; Nichols, Carmen; Procopio, Francesco; He, Zhong; Metcalf, Talibah; Ghneim, Khader; Locci, Michela; Ancuta, Petronella; Routy, Jean-Pierre; Trautmann, Lydie; Li, Yuxing; McDermott, Adrian B; Koup, Rick A; Petrovas, Constantinos; Migueles, Steven A; Connors, Mark; Tomaras, Georgia D; Moir, Susan; Crotty, Shane; Haddad, Elias K

    2015-12-15

    Despite the overwhelming benefits of antiretroviral therapy (ART) in curtailing viral load in HIV-infected individuals, ART does not fully restore cellular and humoral immunity. HIV-infected individuals under ART show reduced responses to vaccination and infections and are unable to mount an effective antiviral immune response upon ART cessation. Many factors contribute to these defects, including persistent inflammation, especially in lymphoid tissues, where T follicular helper (Tfh) cells instruct and help B cells launch an effective humoral immune response. In this study we investigated the phenotype and function of circulating memory Tfh cells as a surrogate of Tfh cells in lymph nodes and found significant impairment of this cell population in chronically HIV-infected individuals, leading to reduced B cell responses. We further show that these aberrant memory Tfh cells exhibit an IL-2-responsive gene signature and are more polarized toward a Th1 phenotype. Treatment of functional memory Tfh cells with IL-2 was able to recapitulate the detrimental reprogramming. Importantly, this defect was reversible, as interfering with the IL-2 signaling pathway helped reverse the abnormal differentiation and improved Ab responses. Thus, reversible reprogramming of memory Tfh cells in HIV-infected individuals could be used to enhance Ab responses. Altered microenvironmental conditions in lymphoid tissues leading to altered Tfh cell differentiation could provide one explanation for the poor responsiveness of HIV-infected individuals to new Ags. This explanation has important implications for the development of therapeutic interventions to enhance HIV- and vaccine-mediated Ab responses in patients under ART.

  16. Prolonged antigen presentation by immune complex-binding dendritic cells programs the proliferative capacity of memory CD8 T cells.

    PubMed

    León, Beatriz; Ballesteros-Tato, André; Randall, Troy D; Lund, Frances E

    2014-07-28

    The commitment of naive CD8 T cells to effector or memory cell fates can occur after a single day of antigenic stimulation even though virus-derived antigens (Ags) are still presented by DCs long after acute infection is resolved. However, the effects of extended Ag presentation on CD8 T cells are undefined and the mechanisms that regulate prolonged Ag presentation are unknown. We showed that the sustained presentation of two different epitopes from influenza virus by DCs prevented the premature contraction of the primary virus-specific CD8 T cell response. Although prolonged Ag presentation did not alter the number of memory CD8 T cells that developed, it was essential for programming the capacity of these cells to proliferate, produce cytokines, and protect the host after secondary challenge. Importantly, prolonged Ag presentation by DCs was dependent on virus-specific, isotype-switched antibodies (Abs) that facilitated the capture and cross-presentation of viral Ags by FcγR-expressing DCs. Collectively, our results demonstrate that B cells and Abs can regulate the quality and functionality of a subset of antiviral CD8 T cell memory responses and do so by promoting sustained Ag presentation by DCs during the contraction phase of the primary T cell response.

  17. Role of naive-derived T memory stem cells in T-cell reconstitution following allogeneic transplantation

    PubMed Central

    Roberto, Alessandra; Castagna, Luca; Zanon, Veronica; Bramanti, Stefania; Crocchiolo, Roberto; McLaren, James E.; Gandolfi, Sara; Tentorio, Paolo; Sarina, Barbara; Timofeeva, Inna; Santoro, Armando; Carlo-Stella, Carmelo; Bruno, Benedetto; Carniti, Cristiana; Corradini, Paolo; Gostick, Emma; Ladell, Kristin; Price, David A.; Roederer, Mario; Mavilio, Domenico

    2015-01-01

    Early T-cell reconstitution following allogeneic transplantation depends on the persistence and function of T cells that are adoptively transferred with the graft. Posttransplant cyclophosphamide (pt-Cy) effectively prevents alloreactive responses from unmanipulated grafts, but its effect on subsequent immune reconstitution remains undetermined. Here, we show that T memory stem cells (TSCM), which demonstrated superior reconstitution capacity in preclinical models, are the most abundant circulating T-cell population in the early days following haploidentical transplantation combined with pt-Cy and precede the expansion of effector cells. Transferred naive, but not TSCM or conventional memory cells preferentially survive cyclophosphamide, thus suggesting that posttransplant TSCM originate from naive precursors. Moreover, donor naive T cells specific for exogenous and self/tumor antigens persist in the host and contribute to peripheral reconstitution by differentiating into effectors. Similarly, pathogen-specific memory T cells generate detectable recall responses, but only in the presence of the cognate antigen. We thus define the cellular basis of T-cell reconstitution following pt-Cy at the antigen-specific level and propose to explore naive-derived TSCM in the clinical setting to overcome immunodeficiency. These trials were registered at www.clinicaltrials.gov as #NCT02049424 and #NCT02049580. PMID:25742699

  18. 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.

  19. Effector and memory T cell subsets in the response to bovine tuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long-term (i.e., 14d) cultured IFN-gamma ELISPOT assays of PBMC are used as a correlate of T cell central memory (Tcm) responses in cattle and humans. With bovine tuberculosis, vaccine-elicited Tcm responses correlate with protection against experimental Mycobacterium bovis infection. The objective ...

  20. The Memories of NK Cells: Innate-Adaptive Immune Intrinsic Crosstalk

    PubMed Central

    Ortolani, Claudio; del Zotto, Genny; Luchetti, Francesca; Canonico, Barbara; Artico, Marco; Papa, Stefano

    2016-01-01

    Although NK cells are considered part of the innate immune system, a series of evidences has demonstrated that they possess characteristics typical of the adaptive immune system. These NK adaptive features, in particular their memory-like functions, are discussed from an ontogenetic and evolutionary point of view. PMID:28078307