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.

A self-resetting spiking phase-change neuron

NASA Astrophysics Data System (ADS)

Cobley, R. A.; Hayat, H.; Wright, C. D.

2018-05-01

Neuromorphic, or brain-inspired, computing applications of phase-change devices have to date concentrated primarily on the implementation of phase-change synapses. However, the so-called accumulation mode of operation inherent in phase-change materials and devices can also be used to mimic the integrative properties of a biological neuron. Here we demonstrate, using physical modelling of nanoscale devices and SPICE modelling of associated circuits, that a single phase-change memory cell integrated into a comparator type circuit can deliver a basic hardware mimic of an integrate-and-fire spiking neuron with self-resetting capabilities. Such phase-change neurons, in combination with phase-change synapses, can potentially open a new route for the realisation of all-phase-change neuromorphic computing.

A self-resetting spiking phase-change neuron.

PubMed

Cobley, R A; Hayat, H; Wright, C D

2018-05-11

Neuromorphic, or brain-inspired, computing applications of phase-change devices have to date concentrated primarily on the implementation of phase-change synapses. However, the so-called accumulation mode of operation inherent in phase-change materials and devices can also be used to mimic the integrative properties of a biological neuron. Here we demonstrate, using physical modelling of nanoscale devices and SPICE modelling of associated circuits, that a single phase-change memory cell integrated into a comparator type circuit can deliver a basic hardware mimic of an integrate-and-fire spiking neuron with self-resetting capabilities. Such phase-change neurons, in combination with phase-change synapses, can potentially open a new route for the realisation of all-phase-change neuromorphic computing.

Controllable SET process in O-Ti-Sb-Te based phase change memory for synaptic application

NASA Astrophysics Data System (ADS)

Ren, Kun; Li, Ruiheng; Chen, Xin; Wang, Yong; Shen, Jiabin; Xia, Mengjiao; Lv, Shilong; Ji, Zhenguo; Song, Zhitang

2018-02-01

The nonlinear resistance change and small bit resolution of phase change memory (PCM) under identical operation pulses will limit its performance as a synaptic device. The octahedral Ti-Te units in Ti-Sb-Te, regarded as nucleation seeds, are degenerated when Ti is bonded with O, causing a slower crystallization and a controllable SET process in PCM cells. A linear resistance change under identical pulses, a resolution of ˜8 bits, and an ON/OFF ratio of ˜102 has been achieved in O-Ti-Sb-Te based PCM, showing its potential application as a synaptic device to improve recognition performance of the neural network.

Multi-level storage and ultra-high speed of superlattice-like Ge50Te50/Ge8Sb92 thin film for phase-change memory application.

PubMed

Wu, Weihua; Chen, Shiyu; Zhai, Jiwei; Liu, Xinyi; Lai, Tianshu; Song, Sannian; Song, Zhitang

2017-10-06

Superlattice-like Ge 50 Te 50 /Ge 8 Sb 92 (SLL GT/GS) thin film was systematically investigated for multi-level storage and ultra-fast switching phase-change memory application. In situ resistance measurement indicates that SLL GT/GS thin film exhibits two distinct resistance steps with elevated temperature. The thermal stability of the amorphous state and intermediate state were evaluated with the Kissinger and Arrhenius plots. The phase-structure evolution revealed that the amorphous SLL GT/GS thin film crystallized into rhombohedral Sb phase first, then the rhombohedral GeTe phase. The microstructure, layered structure, and interface stability of SLL GT/GS thin film was confirmed by using transmission electron microscopy. The transition speed of crystallization and amorphization was measured by the picosecond laser pump-probe system. The volume variation during the crystallization was obtained from x-ray reflectivity. Phase-change memory (PCM) cells based on SLL GT/GS thin film were fabricated to verify the multi-level switching under an electrical pulse as short as 30 ns. These results illustrate that the SLL GT/GS thin film has great potentiality in high-density and high-speed PCM applications.

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

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

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

2015-02-14

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

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

NASA Astrophysics Data System (ADS)

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

2015-02-01

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

Application of long-term cultured interferon-gamma enzyme-linked immunospot assay for assessing effector and memory T cell responses in cattle

USDA-ARS?s Scientific Manuscript database

Effector and memory T cells are generated through developmental programing of naïve cells following antigen recognition. If the infection is controlled, up to 95% of the T cells generated during the expansion phase are eliminated (i.e., contraction phase) and memory T cells remain, sometimes for a l...

Nanoscale phase change memory materials.

PubMed

Caldwell, Marissa A; Jeyasingh, Rakesh Gnana David; Wong, H-S Philip; Milliron, Delia J

2012-08-07

Phase change memory materials store information through their reversible transitions between crystalline and amorphous states. For typical metal chalcogenide compounds, their phase transition properties directly impact critical memory characteristics and the manipulation of these is a major focus in the field. Here, we discuss recent work that explores the tuning of such properties by scaling the materials to nanoscale dimensions, including fabrication and synthetic strategies used to produce nanoscale phase change memory materials. The trends that emerge are relevant to understanding how such memory technologies will function as they scale to ever smaller dimensions and also suggest new approaches to designing materials for phase change applications. Finally, the challenges and opportunities raised by integrating nanoscale phase change materials into switching devices are discussed.

Ti-Sb-Te alloy: a candidate for fast and long-life phase-change memory.

PubMed

Xia, Mengjiao; Zhu, Min; Wang, Yuchan; Song, Zhitang; Rao, Feng; Wu, Liangcai; Cheng, Yan; Song, Sannian

2015-04-15

Phase-change memory (PCM) has great potential for numerous attractive applications on the premise of its high-device performances, which still need to be improved by employing a material with good overall phase-change properties. In respect to fast speed and high endurance, the Ti-Sb-Te alloy seems to be a promising candidate. Here, Ti-doped Sb2Te3 (TST) materials with different Ti concentrations have been systematically studied with the goal of finding the most suitable composition for PCM applications. The thermal stability of TST is improved dramatically with increasing Ti content. The small density change of T0.32Sb2Te3 (2.24%), further reduced to 1.37% for T0.56Sb2Te3, would greatly avoid the voids generated at phase-change layer/electrode interface in a PCM device. Meanwhile, the exponentially diminished grain size (from ∼200 nm to ∼12 nm), resulting from doping more and more Ti, enhances the adhesion between phase-change film and substrate. Tests of TST-based PCM cells have demonstrated a fast switching rate of ∼10 ns. Furthermore, because of the lower thermal conductivities of TST materials, compared with Sb2Te3-based PCM cells, T0.32Sb2Te3-based ones exhibit lower required pulse voltages for Reset operation, which largely decreases by ∼50% for T0.43Sb2Te3-based ones. Nevertheless, the operation voltages for T0.56Sb2Te3-based cells dramatically increase, which may be due to the phase separation after doping excessive Ti. Finally, considering the decreased resistance ratio, TixSb2Te3 alloy with x around 0.43 is proved to be a highly promising candidate for fast and long-life PCM applications.

Contact resistance change memory using N-doped Cr2Ge2Te6 phase-change material showing non-bulk resistance change

NASA Astrophysics Data System (ADS)

Shuang, Y.; Sutou, Y.; Hatayama, S.; Shindo, S.; Song, Y. H.; Ando, D.; Koike, J.

2018-04-01

Phase-change random access memory (PCRAM) is enabled by a large resistance contrast between amorphous and crystalline phases upon reversible switching between the two states. Thus, great efforts have been devoted to identifying potential phase-change materials (PCMs) with large electrical contrast to realize a more accurate reading operation. In contrast, although the truly dominant resistance in a scaled PCRAM cell is contact resistance, less attention has been paid toward the investigation of the contact property between PCMs and electrode metals. This study aims to propose a non-bulk-resistance-dominant PCRAM whose resistance is modulated only by contact. The contact-resistance-dominated PCM exploited here is N-doped Cr2Ge2Te6 (NCrGT), which exhibits almost no electrical resistivity difference between the two phases but exhibits a typical switching behavior involving a three-order-of-magnitude SET/RESET resistance ratio owing to its large contact resistance contrast. The conduction mechanism was discussed on the basis of current-voltage characteristics of the interface between the NCrGT and the W electrode.

Mind bomb-1 is an essential modulator of long-term memory and synaptic plasticity via the Notch signaling pathway

PubMed Central

2012-01-01

Background Notch signaling is well recognized as a key regulator of the neuronal fate during embryonic development, but its function in the adult brain is still largely unknown. Mind bomb-1 (Mib1) is an essential positive regulator in the Notch pathway, acting non-autonomously in the signal-sending cells. Therefore, genetic ablation of Mib1 in mature neuron would give valuable insight to understand the cell-to-cell interaction between neurons via Notch signaling for their proper function. Results Here we show that the inactivation of Mib1 in mature neurons in forebrain results in impaired hippocampal dependent spatial memory and contextual fear memory. Consistently, hippocampal slices from Mib1-deficient mice show impaired late-phase, but not early-phase, long-term potentiation and long-term depression without change in basal synaptic transmission at SC-CA1 synapses. Conclusions These data suggest that Mib1-mediated Notch signaling is essential for long-lasting synaptic plasticity and memory formation in the rodent hippocampus. PMID:23111145

Production of IL-10 by CD4+ regulatory T cells during the resolution of infection promotes the maturation of memory CD8+ T cells

PubMed Central

Laidlaw, Brian J; Cui, Weiguo; Amezquita, Robert A; Gray, Simon M; Guan, Tianxia; Lu, Yisi; Kobayashi, Yasushi; Flavell, Richard A; Kleinstein, Steven H; Craft, Joe; Kaech, Susan M

2016-01-01

Memory CD8+ T cells are critical for host defense upon reexposure to intracellular pathogens. We found that interleukin 10 (IL-10) derived from CD4+ regulatory T cells (Treg cells) was necessary for the maturation of memory CD8+ T cells following acute infection with lymphocytic choriomeningitis virus (LCMV). Treg cell–derived IL-10 was most important during the resolution phase, calming inflammation and the activation state of dendritic cells. Adoptive transfer of IL-10-sufficient Treg cells during the resolution phase ‘restored’ the maturation of memory CD8+ T cells in IL-10-deficient mice. Our data indicate that Treg cell–derived IL-10 is needed to insulate CD8+ T cells from inflammatory signals, and reveal that the resolution phase of infection is a critical period that influences the quality and function of developing memory CD8+ T cells. PMID:26147684

Phase-change memory: A continuous multilevel compact model of subthreshold conduction and threshold switching

NASA Astrophysics Data System (ADS)

Pigot, Corentin; Gilibert, Fabien; Reyboz, Marina; Bocquet, Marc; Zuliani, Paola; Portal, Jean-Michel

2018-04-01

Phase-change memory (PCM) compact modeling of the threshold switching based on a thermal runaway in Poole–Frenkel conduction is proposed. Although this approach is often used in physical models, this is the first time it is implemented in a compact model. The model accuracy is validated by a good correlation between simulations and experimental data collected on a PCM cell embedded in a 90 nm technology. A wide range of intermediate states is measured and accurately modeled with a single set of parameters, allowing multilevel programing. A good convergence is exhibited even in snapback simulation owing to this fully continuous approach. Moreover, threshold properties extraction indicates a thermally enhanced switching, which validates the basic hypothesis of the model. Finally, it is shown that this model is compliant with a new drift-resilient cell-state metric. Once enriched with a phase transition module, this compact model is ready to be implemented in circuit simulators.

Towards a drift-free multi-level Phase Change Memory

NASA Astrophysics Data System (ADS)

Cinar, Ibrahim; Ozdemir, Servet; Cogulu, Egecan; Gokce, Aisha; Stipe, Barry; Katine, Jordan; Aktas, Gulen; Ozatay, Ozhan

For ultra-high density data storage applications, Phase Change Memory (PCM) is considered a potentially disruptive technology. Yet, the long-term reliability of the logic levels corresponding to the resistance states of a PCM device is an important issue for a stable device operation since the resistance levels drift uncontrollably in time. The underlying mechanism for the resistance drift is considered as the structural relaxation and spontaneous crystallization at elevated temperatures. We fabricated a nanoscale single active layer-phase change memory cell with three resistance levels corresponding to crystalline, amorphous and intermediate states by controlling the current injection site geometry. For the intermediate state and the reset state, the activation energies and the trap distances have been found to be 0.021 eV and 0.235 eV, 1.31 nm and 7.56 nm, respectively. We attribute the ultra-low and weakly temperature dependent drift coefficient of the intermediate state (ν = 0.0016) as opposed to that of the reset state (ν = 0.077) as being due to the dominant contribution of the interfacial defects in electrical transport in the case of the mixed phase. Our results indicate that the engineering of interfacial defects will enable a drift-free multi-level PCM device design.

Messier: A Detailed NVM-Based DIMM Model for the SST Simulation Framework.

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

Awad, Amro; Voskuilen, Gwendolyn Renae; Rodrigues, Arun F.

2017-02-01

DRAM technology is the main building block of main memory, however, DRAM scaling is becoming very challenging. The main issues for DRAM scaling are the increasing error rates with each new generation, the geometric and physical constraints of scaling the capacitor part of the DRAM cells, and the high power consumption caused by the continuous need for refreshing cell values. At the same time, emerging Non- Volatile Memory (NVM) technologies, such as Phase-Change Memory (PCM), are emerging as promising replacements for DRAM. NVMs, when compared to current technologies e.g., NAND-based ash, have latencies comparable to DRAM. Additionally, NVMs are non-volatile,more » which eliminates the need for refresh power and enables persistent memory applications. Finally, NVMs have promising densities and the potential for multi-level cell (MLC) storage.« less

The distinctive germinal center phase of IgE+ B lymphocytes limits their contribution to the classical memory response

USDA-ARS?s Scientific Manuscript database

The mechanisms involved in the maintenance of memory IgE responses are poorly understood, and the role played by germinal center (GC) IgE+ cells in memory responses is particularly unclear. IgE B cell differentiation is characterized by a transient GC phase, a bias towards the plasma cell (PC) fate,...

New developments in optical phase-change memory

NASA Astrophysics Data System (ADS)

Ovshinsky, Stanford R.; Czubatyj, Wolodymyr

2001-02-01

Phase change technology has progressed from the original invention of Ovshinsky to become the leading choice for rewritable optical disks. ECD's early work in phase change materials and methods for operating in a direct overwrite fashion were crucial to the successes that have been achieved. Since the introduction of the first rewritable phase change products in 1991, the market has expanded from CD-RW into rewritable DVD with creative work going on worldwide. Phase change technology is ideally suited to address the continuous demand for increased storage capacity. First, laser beams can be focused to ever-smaller spot sizes using shorter wavelength lasers and higher performance optics. Blue lasers are now commercially viable and high numerical aperture and near field lenses have been demonstrated. Second, multilevel approaches can be used to increase capacity by a factor of three or more with concomitant increases in data transfer rate. In addition, ECD has decreased manufacturing costs through the use of innovative production technology. These factors combine to accelerate the widespread use of phase change technology. As in all our technologies, such as thin film photovoltaics, nickel metal hydride batteries, hydrogen storage systems, fuel cells, electrical memory, etc., we have invented the materials, the products, the production machines and the production processes for high rate, low-cost manufacture.

Self-assembled phase-change nanowire for nonvolatile electronic memory

NASA Astrophysics Data System (ADS)

Jung, Yeonwoong

One of the most important subjects in nanosciences is to identify and exploit the relationship between size and structural/physical properties of materials and to explore novel material properties at a small-length scale. Scale-down of materials is not only advantageous in realizing miniaturized devices but nanometer-sized materials often exhibit intriguing physical/chemical properties that greatly differ from their bulk counterparts. This dissertation studies self-assembled phase-change nanowires for future nonvolatile electronic memories, mainly focusing on their size-dependent memory switching properties. Owing to the one-dimensional, unique geometry coupled with the small and tunable sizes, bottom-designed nanowires offer great opportunities in terms for both fundamental science and practical engineering perspectives, which would be difficult to realize in conventional top-down based approaches. We synthesized chalcogenide phase-change nanowires of different compositions and sizes, and studied their electronic memory switching owing to the structural change between crystalline and amorphous phases. In particular, we investigated nanowire size-dependent memory switching parameters, including writing current, power consumption, and data retention times, as well as studying composition-dependent electronic properties. The observed size and composition-dependent switching and recrystallization kinetics are explained based on the heat transport model and heterogeneous nucleation theories, which help to design phase-change materials with better properties. Moreover, we configured unconventional heterostructured phase-change nanowire memories and studied their multiple memory states in single nanowire devices. Finally, by combining in-situ/ex-situ electron microscopy techniques and electrical measurements, we characterized the structural states involved in electrically-driven phase-change in order to understand the atomistic mechanism that governs the electronic memory switching through phase-change.

Evidence for thermally assisted threshold switching behavior in nanoscale phase-change memory cells

NASA Astrophysics Data System (ADS)

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

2016-01-01

In spite of decades of research, the details of electrical transport in phase-change materials are still debated. In particular, the so-called threshold switching phenomenon that allows the current density to increase steeply when a sufficiently high voltage is applied is still not well understood, even though there is wide consensus that threshold switching is solely of electronic origin. However, the high thermal efficiency and fast thermal dynamics associated with nanoscale phase-change memory (PCM) devices motivate us to reassess a thermally assisted threshold switching mechanism, at least in these devices. The time/temperature dependence of the threshold switching voltage and current in doped Ge2Sb2Te5 nanoscale PCM cells was measured over 6 decades in time at temperatures ranging from 40 °C to 160 °C. We observe a nearly constant threshold switching power across this wide range of operating conditions. We also measured the transient dynamics associated with threshold switching as a function of the applied voltage. By using a field- and temperature-dependent description of the electrical transport combined with a thermal feedback, quantitative agreement with experimental data of the threshold switching dynamics was obtained using realistic physical parameters.

Redefining the Speed Limit of Phase Change Memory Revealed by Time-resolved Steep Threshold-Switching Dynamics of AgInSbTe Devices

NASA Astrophysics Data System (ADS)

Shukla, Krishna Dayal; Saxena, Nishant; Durai, Suresh; Manivannan, Anbarasu

2016-11-01

Although phase-change memory (PCM) offers promising features for a ‘universal memory’ owing to high-speed and non-volatility, achieving fast electrical switching remains a key challenge. In this work, a correlation between the rate of applied voltage and the dynamics of threshold-switching is investigated at picosecond-timescale. A distinct characteristic feature of enabling a rapid threshold-switching at a critical voltage known as the threshold voltage as validated by an instantaneous response of steep current rise from an amorphous off to on state is achieved within 250 picoseconds and this is followed by a slower current rise leading to crystallization. Also, we demonstrate that the extraordinary nature of threshold-switching dynamics in AgInSbTe cells is independent to the rate of applied voltage unlike other chalcogenide-based phase change materials exhibiting the voltage dependent transient switching characteristics. Furthermore, numerical solutions of time-dependent conduction process validate the experimental results, which reveal the electronic nature of threshold-switching. These findings of steep threshold-switching of ‘sub-50 ps delay time’, opens up a new way for achieving high-speed non-volatile memory for mainstream computing.

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

NASA Astrophysics Data System (ADS)

Chen, An

2016-11-01

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

Strain-Detecting Composite Materials

NASA Technical Reports Server (NTRS)

Wallace, Terryl A. (Inventor); Smith, Stephen W. (Inventor); Piascik, Robert S. (Inventor); Horne, Michael R. (Inventor); Messick, Peter L. (Inventor); Alexa, Joel A. (Inventor); Glaessgen, Edward H. (Inventor); Hailer, Benjamin T. (Inventor)

2016-01-01

A composite material includes a structural material and a shape-memory alloy embedded in the structural material. The shape-memory alloy changes crystallographic phase from austenite to martensite in response to a predefined critical macroscopic average strain of the composite material. In a second embodiment, the composite material includes a plurality of particles of a ferromagnetic shape-memory alloy embedded in the structural material. The ferromagnetic shape-memory alloy changes crystallographic phase from austenite to martensite and changes magnetic phase in response to the predefined critical macroscopic average strain of the composite material. A method of forming a composite material for sensing the predefined critical macroscopic average strain includes providing the shape-memory alloy having an austenite crystallographic phase, changing a size and shape of the shape-memory alloy to thereby form a plurality of particles, and combining the structural material and the particles at a temperature of from about 100-700.degree. C. to form the composite material.

Enabling universal memory by overcoming the contradictory speed and stability nature of phase-change materials.

PubMed

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

2012-01-01

The quest for universal memory is driving the rapid development of memories with superior all-round capabilities in non-volatility, high speed, high endurance and low power. Phase-change materials are highly promising in this respect. However, their contradictory speed and stability properties present a key challenge towards this ambition. We reveal that as the device size decreases, the phase-change mechanism changes from the material inherent crystallization mechanism (either nucleation- or growth-dominated), to the hetero-crystallization mechanism, which resulted in a significant increase in PCRAM speeds. Reducing the grain size can further increase the speed of phase-change. Such grain size effect on speed becomes increasingly significant at smaller device sizes. Together with the nano-thermal and electrical effects, fast phase-change, good stability and high endurance can be achieved. These findings lead to a feasible solution to achieve a universal memory.

Enabling Universal Memory by Overcoming the Contradictory Speed and Stability Nature of Phase-Change Materials

PubMed Central

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

2012-01-01

The quest for universal memory is driving the rapid development of memories with superior all-round capabilities in non-volatility, high speed, high endurance and low power. Phase-change materials are highly promising in this respect. However, their contradictory speed and stability properties present a key challenge towards this ambition. We reveal that as the device size decreases, the phase-change mechanism changes from the material inherent crystallization mechanism (either nucleation- or growth-dominated), to the hetero-crystallization mechanism, which resulted in a significant increase in PCRAM speeds. Reducing the grain size can further increase the speed of phase-change. Such grain size effect on speed becomes increasingly significant at smaller device sizes. Together with the nano-thermal and electrical effects, fast phase-change, good stability and high endurance can be achieved. These findings lead to a feasible solution to achieve a universal memory. PMID:22496956

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

Oxygen Tuned Local Structure and Phase-Change Performance of Germanium Telluride.

PubMed

Zhou, Xilin; Du, Yonghua; Behera, Jitendra K; Wu, Liangcai; Song, Zhitang; Simpson, Robert E

2016-08-10

The effect of oxygen on the local structure of Ge atoms in GeTe-O materials has been investigated. Oxygen leads to a significant modification to the vibrational modes of Ge octahedra, which results from a decrease in its coordination. We find that a defective octahedral Ge network is the crucial fingerprint for rapid and reversible structural transitions in GeTe-based phase change materials. The appearance of oxide Raman modes confirms phase separation into GeO and TeO at high level O doping. Counterintuitively, despite the increase in crystallization temperature of oxygen doped GeTe-O phase change materials, when GeTe-O materials are used in electrical phase change memory cells, the electrical switching energy is lower than the pure GeTe material. This switching energy reduction is ascribed to the smaller change in volume, and therefore smaller enthalpy change, for the oxygen doped GeTe materials.

Evidence for thermally assisted threshold switching behavior in nanoscale phase-change memory cells

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

Le Gallo, Manuel; Athmanathan, Aravinthan; Krebs, Daniel

2016-01-14

In spite of decades of research, the details of electrical transport in phase-change materials are still debated. In particular, the so-called threshold switching phenomenon that allows the current density to increase steeply when a sufficiently high voltage is applied is still not well understood, even though there is wide consensus that threshold switching is solely of electronic origin. However, the high thermal efficiency and fast thermal dynamics associated with nanoscale phase-change memory (PCM) devices motivate us to reassess a thermally assisted threshold switching mechanism, at least in these devices. The time/temperature dependence of the threshold switching voltage and current inmore » doped Ge{sub 2}Sb{sub 2}Te{sub 5} nanoscale PCM cells was measured over 6 decades in time at temperatures ranging from 40 °C to 160 °C. We observe a nearly constant threshold switching power across this wide range of operating conditions. We also measured the transient dynamics associated with threshold switching as a function of the applied voltage. By using a field- and temperature-dependent description of the electrical transport combined with a thermal feedback, quantitative agreement with experimental data of the threshold switching dynamics was obtained using realistic physical parameters.« less

A transcriptome-based model of central memory CD4 T cell death in HIV infection.

PubMed

Olvera-García, Gustavo; Aguilar-García, Tania; Gutiérrez-Jasso, Fany; Imaz-Rosshandler, Iván; Rangel-Escareño, Claudia; Orozco, Lorena; Aguilar-Delfín, Irma; Vázquez-Pérez, Joel A; Zúñiga, Joaquín; Pérez-Patrigeon, Santiago; Espinosa, Enrique

2016-11-22

Human central memory CD4 T cells are characterized by their capacity of proliferation and differentiation into effector memory CD4 T cells. Homeostasis of central memory CD4 T cells is considered a key factor sustaining the asymptomatic stage of Human Immunodeficiency Virus type 1 (HIV-1) infection, while progression to acquired immunodeficiency syndrome is imputed to central memory CD4 T cells homeostatic failure. We investigated if central memory CD4 T cells from patients with HIV-1 infection have a gene expression profile impeding proliferation and survival, despite their activated state. Using gene expression microarrays, we analyzed mRNA expression patterns in naive, central memory, and effector memory CD4 T cells from healthy controls, and naive and central memory CD4 T cells from patients with HIV-1 infection. Differentially expressed genes, defined by Log 2 Fold Change (FC) ≥ |0.5| and Log (odds) > 0, were used in pathway enrichment analyses. Central memory CD4 T cells from patients and controls showed comparable expression of differentiation-related genes, ruling out an effector-like differentiation of central memory CD4 T cells in HIV infection. However, 210 genes were differentially expressed in central memory CD4 T cells from patients compared with those from controls. Expression of 75 of these genes was validated by semi quantitative RT-PCR, and independently reproduced enrichment results from this gene expression signature. The results of functional enrichment analysis indicated movement to cell cycle phases G1 and S (increased CCNE1, MKI67, IL12RB2, ADAM9, decreased FGF9, etc.), but also arrest in G2/M (increased CHK1, RBBP8, KIF11, etc.). Unexpectedly, the results also suggested decreased apoptosis (increased CSTA, NFKBIA, decreased RNASEL, etc.). Results also suggested increased IL-1β, IFN-γ, TNF, and RANTES (CCR5) activity upstream of the central memory CD4 T cells signature, consistent with the demonstrated milieu in HIV infection. Our findings support a model where progressive loss of central memory CD4 T cells in chronic HIV-1 infection is driven by increased cell cycle entry followed by mitotic arrest, leading to a non-apoptotic death pathway without actual proliferation, possibly contributing to increased turnover.

Using the two-way shape memory effect of NiTi to control surface texture for cellular mechanotransduction

NASA Astrophysics Data System (ADS)

Liang, Yuan; Qin, Haifeng; Hou, Xiaoning; Doll, Gary L.; Ye, Chang; Dong, Yalin

2018-07-01

Mechanical force can crucially affect form and function of cells, and play critical roles in many diseases. While techniques to conveniently apply mechanical force to cells are limited, we fabricate a surface actuator prototype for cellular mechanotransduction by imparting severe plastic deformation into the surface of shape memory alloy (SMA). Using ultrasonic nanocrystal surface modification (UNSM), a deformation-based surface engineering technique with high controllability, micro surface patterns can be generated on the surface of SMA so that the micro-size cell can conform to the pattern; meanwhile, phase transformation can be induced in the subsurface by severe plastic deformation. By controlling plastic deformation and phase transformation, it is possible to establish a quantitative relation between deformation and temperature. When cells are cultured on the UNSM-treated surface, such surface can dynamically deform in response to external temperature change, and therefore apply controllable mechanical force to cells. Through this study, we demonstrate a novel way to fabricate a low-cost surface actuator that has the potential to be used for high-throughput cellular mechanotransduction.

Acute Infection with Epstein-Barr Virus Targets and Overwhelms the Peripheral Memory B-Cell Compartment with Resting, Latently Infected Cells

PubMed Central

Hochberg, Donna; Souza, Tatyana; Catalina, Michelle; Sullivan, John L.; Luzuriaga, Katherine; Thorley-Lawson, David A.

2004-01-01

In this paper we demonstrate that during acute infection with Epstein-Barr virus (EBV), the peripheral blood fills up with latently infected, resting memory B cells to the point where up to 50% of all the memory cells may carry EBV. Despite this massive invasion of the memory compartment, the virus remains tightly restricted to memory cells, such that, in one donor, fewer than 1 in 104 infected cells were found in the naive compartment. We conclude that, even during acute infection, EBV persistence is tightly regulated. This result confirms the prediction that during the early phase of infection, before cellular immunity is effective, there is nothing to prevent amplification of the viral cycle of infection, differentiation, and reactivation, causing the peripheral memory compartment to fill up with latently infected cells. Subsequently, there is a rapid decline in infected cells for the first few weeks that approximates the decay in the cytotoxic-T-cell responses to viral replicative antigens. This phase is followed by a slower decline that, even by 1 year, had not reached a steady state. Therefore, EBV may approach but never reach a stable equilibrium. PMID:15113901

Vibration damping and heat transfer using material phase changes

NASA Technical Reports Server (NTRS)

Kloucek, Petr (Inventor); Reynolds, Daniel R. (Inventor)

2009-01-01

A method and apparatus wherein phase changes in a material can dampen vibrational energy, dampen noise and facilitate heat transfer. One embodiment includes a method for damping vibrational energy in a body. The method comprises attaching a material to the body, wherein the material comprises a substrate, a shape memory alloy layer, and a plurality of temperature change elements. The method further comprises sensing vibrations in the body. In addition, the method comprises indicating to at least a portion of the temperature change elements to provide a temperature change in the shape memory alloy layer, wherein the temperature change is sufficient to provide a phase change in at least a portion of the shape memory alloy layer, and further wherein the phase change consumes a sufficient amount of kinetic energy to dampen at least a portion of the vibrational energy in the body. In other embodiments, the shape memory alloy layer is a thin film. Additional embodiments include a sensor connected to the material.

Vibration damping and heat transfer using material phase changes

DOEpatents

Kloucek, Petr [Houston, TX; Reynolds, Daniel R [Oakland, CA

2009-03-24

A method and apparatus wherein phase changes in a material can dampen vibrational energy, dampen noise and facilitate heat transfer. One embodiment includes a method for damping vibrational energy in a body. The method comprises attaching a material to the body, wherein the material comprises a substrate, a shape memory alloy layer, and a plurality of temperature change elements. The method further comprises sensing vibrations in the body. In addition, the method comprises indicating to at least a portion of the temperature change elements to provide a temperature change in the shape memory alloy layer, wherein the temperature change is sufficient to provide a phase change in at least a portion of the shape memory alloy layer, and further wherein the phase change consumes a sufficient amount of kinetic energy to dampen at least a portion of the vibrational energy in the body. In other embodiments, the shape memory alloy layer is a thin film. Additional embodiments include a sensor connected to the material.

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

PubMed

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

2015-10-01

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

Forced Ion Migration for Chalcogenide Phase Change Memory Device

NASA Technical Reports Server (NTRS)

Campbell, Kristy A (Inventor)

2013-01-01

Non-volatile memory devices with two stacked layers of chalcogenide materials comprising the active memory device have been investigated for their potential as phase-change memories. The devices tested included GeTe/SnTe, Ge2Se3/SnTe, and Ge2Se3/SnSe stacks. All devices exhibited resistance switching behavior. The polarity of the applied voltage with respect to the SnTe or SnSe layer was critical to the memory switching properties, due to the electric field induced movement of either Sn or Te into the Ge-chalcogenide layer. One embodiment of the invention is a device comprising a stack of chalcogenide-containing layers which exhibit phase-change switching only after a reverse polarity voltage potential is applied across the stack causing ion movement into an adjacent layer and thus "activating" the device to act as a phase-change random access memory device or a reconfigurable electronics device when the applied voltage potential is returned to the normal polarity. Another embodiment of the invention is a device that is capable of exhibiting more than two data states.

Forced ion migration for chalcogenide phase change memory device

NASA Technical Reports Server (NTRS)

Campbell, Kristy A. (Inventor)

2011-01-01

Non-volatile memory devices with two stacked layers of chalcogenide materials comprising the active memory device have been investigated for their potential as phase change memories. The devices tested included GeTe/SnTe, Ge.sub.2Se.sub.3/SnTe, and Ge.sub.2Se.sub.3/SnSe stacks. All devices exhibited resistance switching behavior. The polarity of the applied voltage with respect to the SnTe or SnSe layer was critical to the memory switching properties, due to the electric field induced movement of either Sn or Te into the Ge-chalcogenide layer. One embodiment of the invention is a device comprising a stack of chalcogenide-containing layers which exhibit phase change switching only after a reverse polarity voltage potential is applied across the stack causing ion movement into an adjacent layer and thus "activating" the device to act as a phase change random access memory device or a reconfigurable electronics device when the applied voltage potential is returned to the normal polarity. Another embodiment of the invention is a device that is capable of exhibiting more that two data states.

Forced ion migration for chalcogenide phase change memory device

NASA Technical Reports Server (NTRS)

Campbell, Kristy A. (Inventor)

2012-01-01

Non-volatile memory devices with two stacked layers of chalcogenide materials comprising the active memory device have been investigated for their potential as phase-change memories. The devices tested included GeTe/SnTe, Ge.sub.2Se.sub.3/SnTe, and Ge.sub.2Se.sub.3/SnSe stacks. All devices exhibited resistance switching behavior. The polarity of the applied voltage with respect to the SnTe or SnSe layer was critical to the memory switching properties, due to the electric field induced movement of either Sn or Te into the Ge-chalcogenide layer. One embodiment of the invention is a device comprising a stack of chalcogenide-containing layers which exhibit phase-change switching only after a reverse polarity voltage potential is applied across the stack causing ion movement into an adjacent layer and thus "activating" the device to act as a phase-change random access memory device or a reconfigurable electronics device when the applied voltage potential is returned to the normal polarity. Another embodiment of the invention is a device that is capable of exhibiting more than two data states.

Deconvoluting Post-Transplant Immunity: Cell Subset-Specific Mapping Reveals Pathways for Activation and Expansion of Memory T, Monocytes and B Cells

PubMed Central

Grigoryev, Yevgeniy A.; Kurian, Sunil M.; Avnur, Zafi; Borie, Dominic; Deng, Jun; Campbell, Daniel; Sung, Joanna; Nikolcheva, Tania; Quinn, Anthony; Schulman, Howard; Peng, Stanford L.; Schaffer, Randolph; Fisher, Jonathan; Mondala, Tony; Head, Steven; Flechner, Stuart M.; Kantor, Aaron B.; Marsh, Christopher; Salomon, Daniel R.

2010-01-01

A major challenge for the field of transplantation is the lack of understanding of genomic and molecular drivers of early post-transplant immunity. The early immune response creates a complex milieu that determines the course of ensuing immune events and the ultimate outcome of the transplant. The objective of the current study was to mechanistically deconvolute the early immune response by purifying and profiling the constituent cell subsets of the peripheral blood. We employed genome-wide profiling of whole blood and purified CD4, CD8, B cells and monocytes in tandem with high-throughput laser-scanning cytometry in 10 kidney transplants sampled serially pre-transplant, 1, 2, 4, 8 and 12 weeks. Cytometry confirmed early cell subset depletion by antibody induction and immunosuppression. Multiple markers revealed the activation and proliferative expansion of CD45RO+CD62L− effector memory CD4/CD8 T cells as well as progressive activation of monocytes and B cells. Next, we mechanistically deconvoluted early post-transplant immunity by serial monitoring of whole blood using DNA microarrays. Parallel analysis of cell subset-specific gene expression revealed a unique spectrum of time-dependent changes and functional pathways. Gene expression profiling results were validated with 157 different probesets matching all 65 antigens detected by cytometry. Thus, serial blood cell monitoring reflects the profound changes in blood cell composition and immune activation early post-transplant. Each cell subset reveals distinct pathways and functional programs. These changes illuminate a complex, early phase of immunity and inflammation that includes activation and proliferative expansion of the memory effector and regulatory cells that may determine the phenotype and outcome of the kidney transplant. PMID:20976225

Deconvoluting post-transplant immunity: cell subset-specific mapping reveals pathways for activation and expansion of memory T, monocytes and B cells.

PubMed

Grigoryev, Yevgeniy A; Kurian, Sunil M; Avnur, Zafi; Borie, Dominic; Deng, Jun; Campbell, Daniel; Sung, Joanna; Nikolcheva, Tania; Quinn, Anthony; Schulman, Howard; Peng, Stanford L; Schaffer, Randolph; Fisher, Jonathan; Mondala, Tony; Head, Steven; Flechner, Stuart M; Kantor, Aaron B; Marsh, Christopher; Salomon, Daniel R

2010-10-14

A major challenge for the field of transplantation is the lack of understanding of genomic and molecular drivers of early post-transplant immunity. The early immune response creates a complex milieu that determines the course of ensuing immune events and the ultimate outcome of the transplant. The objective of the current study was to mechanistically deconvolute the early immune response by purifying and profiling the constituent cell subsets of the peripheral blood. We employed genome-wide profiling of whole blood and purified CD4, CD8, B cells and monocytes in tandem with high-throughput laser-scanning cytometry in 10 kidney transplants sampled serially pre-transplant, 1, 2, 4, 8 and 12 weeks. Cytometry confirmed early cell subset depletion by antibody induction and immunosuppression. Multiple markers revealed the activation and proliferative expansion of CD45RO(+)CD62L(-) effector memory CD4/CD8 T cells as well as progressive activation of monocytes and B cells. Next, we mechanistically deconvoluted early post-transplant immunity by serial monitoring of whole blood using DNA microarrays. Parallel analysis of cell subset-specific gene expression revealed a unique spectrum of time-dependent changes and functional pathways. Gene expression profiling results were validated with 157 different probesets matching all 65 antigens detected by cytometry. Thus, serial blood cell monitoring reflects the profound changes in blood cell composition and immune activation early post-transplant. Each cell subset reveals distinct pathways and functional programs. These changes illuminate a complex, early phase of immunity and inflammation that includes activation and proliferative expansion of the memory effector and regulatory cells that may determine the phenotype and outcome of the kidney transplant.

Progressive CD4+ central–memory T cell decline results in CD4+ effector–memory insufficiency and overt disease in chronic SIV infection

PubMed Central

Okoye, Afam; Meier-Schellersheim, Martin; Brenchley, Jason M.; Hagen, Shoko I.; Walker, Joshua M.; Rohankhedkar, Mukta; Lum, Richard; Edgar, John B.; Planer, Shannon L.; Legasse, Alfred; Sylwester, Andrew W.; Piatak, Michael; Lifson, Jeffrey D.; Maino, Vernon C.; Sodora, Donald L.; Douek, Daniel C.; Axthelm, Michael K.; Grossman, Zvi; Picker, Louis J.

2007-01-01

Primary simian immunodeficiency virus (SIV) infections of rhesus macaques result in the dramatic depletion of CD4+ CCR5+ effector–memory T (TEM) cells from extra-lymphoid effector sites, but in most infections, an increased rate of CD4+ memory T cell proliferation appears to prevent collapse of effector site CD4+ TEM cell populations and acute-phase AIDS. Eventually, persistent SIV replication results in chronic-phase AIDS, but the responsible mechanisms remain controversial. Here, we demonstrate that in the chronic phase of progressive SIV infection, effector site CD4+ TEM cell populations manifest a slow, continuous decline, and that the degree of this depletion remains a highly significant correlate of late-onset AIDS. We further show that due to persistent immune activation, effector site CD4+ TEM cells are predominantly short-lived, and that their homeostasis is strikingly dependent on the production of new CD4+ TEM cells from central–memory T (TCM) cell precursors. The instability of effector site CD4+ TEM cell populations over time was not explained by increasing destruction of these cells, but rather was attributable to progressive reduction in their production, secondary to decreasing numbers of CCR5− CD4+ TCM cells. These data suggest that although CD4+ TEM cell depletion is a proximate mechanism of immunodeficiency, the tempo of this depletion and the timing of disease onset are largely determined by destruction, failing production, and gradual decline of CD4+ TCM cells. PMID:17724130

Progressive CD4+ central memory T cell decline results in CD4+ effector memory insufficiency and overt disease in chronic SIV infection.

PubMed

Okoye, Afam; Meier-Schellersheim, Martin; Brenchley, Jason M; Hagen, Shoko I; Walker, Joshua M; Rohankhedkar, Mukta; Lum, Richard; Edgar, John B; Planer, Shannon L; Legasse, Alfred; Sylwester, Andrew W; Piatak, Michael; Lifson, Jeffrey D; Maino, Vernon C; Sodora, Donald L; Douek, Daniel C; Axthelm, Michael K; Grossman, Zvi; Picker, Louis J

2007-09-03

Primary simian immunodeficiency virus (SIV) infections of rhesus macaques result in the dramatic depletion of CD4(+) CCR5(+) effector-memory T (T(EM)) cells from extra-lymphoid effector sites, but in most infections, an increased rate of CD4(+) memory T cell proliferation appears to prevent collapse of effector site CD4(+) T(EM) cell populations and acute-phase AIDS. Eventually, persistent SIV replication results in chronic-phase AIDS, but the responsible mechanisms remain controversial. Here, we demonstrate that in the chronic phase of progressive SIV infection, effector site CD4(+) T(EM) cell populations manifest a slow, continuous decline, and that the degree of this depletion remains a highly significant correlate of late-onset AIDS. We further show that due to persistent immune activation, effector site CD4(+) T(EM) cells are predominantly short-lived, and that their homeostasis is strikingly dependent on the production of new CD4(+) T(EM) cells from central-memory T (T(CM)) cell precursors. The instability of effector site CD4(+) T(EM) cell populations over time was not explained by increasing destruction of these cells, but rather was attributable to progressive reduction in their production, secondary to decreasing numbers of CCR5(-) CD4(+) T(CM) cells. These data suggest that although CD4(+) T(EM) cell depletion is a proximate mechanism of immunodeficiency, the tempo of this depletion and the timing of disease onset are largely determined by destruction, failing production, and gradual decline of CD4(+) T(CM) cells.

Neutron imaging integrated circuit and method for detecting neutrons

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

Nagarkar, Vivek V.; More, Mitali J.

The present disclosure provides a neutron imaging detector and a method for detecting neutrons. In one example, a method includes providing a neutron imaging detector including plurality of memory cells and a conversion layer on the memory cells, setting one or more of the memory cells to a first charge state, positioning the neutron imaging detector in a neutron environment for a predetermined time period, and reading a state change at one of the memory cells, and measuring a charge state change at one of the plurality of memory cells from the first charge state to a second charge statemore » less than the first charge state, where the charge state change indicates detection of neutrons at said one of the memory cells.« less

Preparation and characterization of triple shape memory composite foams.

PubMed

Nejad, Hossein Birjandi; Baker, Richard M; Mather, Patrick T

2014-10-28

Foams prepared from shape memory polymers (SMPs) offer the potential for low density materials that can be triggered to deploy with a large volume change, unlike their solid counterparts that do so at near-constant volume. While examples of shape memory foams have been reported in the past, they have been limited to dual SMPs: those polymers featuring one switching transition between an arbitrarily programmed shape and a single permanent shape established by constituent crosslinks. Meanwhile, advances by SMP researchers have led to several approaches toward triple- or multi-shape polymers that feature more than one switching phase and thus a multitude of temporary shapes allowing for a complex sequence of shape deployments. Here, we report the design, preparation, and characterization of a triple shape memory polymeric foam that is open cell in nature and features a two phase, crosslinked SMP with a glass transition temperature of one phase at a temperature lower than a melting transition of the second phase. The soft materials were observed to feature high fidelity, repeatable triple shape behavior, characterized in compression and demonstrated for complex deployment by fixing a combination of foam compression and bending. We further explored the wettability of the foams, revealing composition-dependent behavior favorable for future work in biomedical investigations.

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.

Requirement for CD4 T Cell Help in Generating Functional CD8 T Cell Memory

NASA Astrophysics Data System (ADS)

Shedlock, Devon J.; Shen, Hao

2003-04-01

Although primary CD8 responses to acute infections are independent of CD4 help, it is unknown whether a similar situation applies to secondary responses. We show that depletion of CD4 cells during the recall response has minimal effect, whereas depletion during the priming phase leads to reduced responses by memory CD8 cells to reinfection. Memory CD8 cells generated in CD4+/+ mice responded normally when transferred into CD4-/- hosts, whereas memory CD8 cells generated in CD4-/- mice mounted defective recall responses in CD4+/+ adoptive hosts. These results demonstrate a previously undescribed role for CD4 help in the development of functional CD8 memory.

Logic computation in phase change materials by threshold and memory switching.

PubMed

Cassinerio, M; Ciocchini, N; Ielmini, D

2013-11-06

Memristors, namely hysteretic devices capable of changing their resistance in response to applied electrical stimuli, may provide new opportunities for future memory and computation, thanks to their scalable size, low switching energy and nonvolatile nature. We have developed a functionally complete set of logic functions including NOR, NAND and NOT gates, each utilizing a single phase-change memristor (PCM) where resistance switching is due to the phase transformation of an active chalcogenide material. The logic operations are enabled by the high functionality of nanoscale phase change, featuring voltage comparison, additive crystallization and pulse-induced amorphization. The nonvolatile nature of memristive states provides the basis for developing reconfigurable hybrid logic/memory circuits featuring low-power and high-speed switching. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phase Change Characteristics of InxSb40-xTe60 Chalcogenide Alloy for Phase Change Random Access Memory

NASA Astrophysics Data System (ADS)

Yun, Jae-Jin; Lee, Won-Jong

2011-07-01

The InxSb40-xTe60 alloy was selected as a new alternative phase change material for Ge2Sb2Te5 (GST) for phase change random access memory (PRAM). The crystal structure of InxSb40-xTe60 was an α(Sb2Te3) rhombohedral (a=b=c, α=β=γ≠90°) single phase with identical lattice parameters in a wide composition range of In (0-28 at. %). The crystallization temperature and melting point of InxSb40-xTe60 were in the ranges of 149-219 °C and 608-614 °C, respectively, and similar to those of GST. The electric properties of InxSb40-xTe60 with a wide composition range of In contents showed the typical PRAM properties such as current-voltage (I-V), resistance-voltage (R-V), and switching behavior. The reset current of InxSb40-xTe60 decreased with increasing In content and the low power consumption and good retention can be realized by controlling In content. The ratio of the cell resistance and sheet resistance of amorphous InxSb40-xTe60 to those crystalline InxSb40-xTe60 were almost the same as or larger than those of GST. The cycling endurance test of InxSb40-xTe60 with a wide range of In contents showed the comparable results to GST. InxSb40-xTe60 was concluded to be a very promising phase change material for PRAM.

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

PubMed

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

2017-08-01

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

Phase-change materials for non-volatile memory devices: from technological challenges to materials science issues

NASA Astrophysics Data System (ADS)

Noé, Pierre; Vallée, Christophe; Hippert, Françoise; Fillot, Frédéric; Raty, Jean-Yves

2018-01-01

Chalcogenide phase-change materials (PCMs), such as Ge-Sb-Te alloys, have shown outstanding properties, which has led to their successful use for a long time in optical memories (DVDs) and, recently, in non-volatile resistive memories. The latter, known as PCM memories or phase-change random access memories (PCRAMs), are the most promising candidates among emerging non-volatile memory (NVM) technologies to replace the current FLASH memories at CMOS technology nodes under 28 nm. Chalcogenide PCMs exhibit fast and reversible phase transformations between crystalline and amorphous states with very different transport and optical properties leading to a unique set of features for PCRAMs, such as fast programming, good cyclability, high scalability, multi-level storage capability, and good data retention. Nevertheless, PCM memory technology has to overcome several challenges to definitively invade the NVM market. In this review paper, we examine the main technological challenges that PCM memory technology must face and we illustrate how new memory architecture, innovative deposition methods, and PCM composition optimization can contribute to further improvements of this technology. In particular, we examine how to lower the programming currents and increase data retention. Scaling down PCM memories for large-scale integration means the incorporation of the PCM into more and more confined structures and raises materials science issues in order to understand interface and size effects on crystallization. Other materials science issues are related to the stability and ageing of the amorphous state of PCMs. The stability of the amorphous phase, which determines data retention in memory devices, can be increased by doping the PCM. Ageing of the amorphous phase leads to a large increase of the resistivity with time (resistance drift), which has up to now hindered the development of ultra-high multi-level storage devices. A review of the current understanding of all these issues is provided from a materials science point of view.

Visual search for changes in scenes creates long-term, incidental memory traces.

PubMed

Utochkin, Igor S; Wolfe, Jeremy M

2018-05-01

Humans are very good at remembering large numbers of scenes over substantial periods of time. But how good are they at remembering changes to scenes? In this study, we tested scene memory and change detection two weeks after initial scene learning. In Experiments 1-3, scenes were learned incidentally during visual search for change. In Experiment 4, observers explicitly memorized scenes. At test, after two weeks observers were asked to discriminate old from new scenes, to recall a change that they had detected in the study phase, or to detect a newly introduced change in the memorization experiment. Next, they performed a change detection task, usually looking for the same change as in the study period. Scene recognition memory was found to be similar in all experiments, regardless of the study task. In Experiment 1, more difficult change detection produced better scene memory. Experiments 2 and 3 supported a "depth-of-processing" account for the effects of initial search and change detection on incidental memory for scenes. Of most interest, change detection was faster during the test phase than during the study phase, even when the observer had no explicit memory of having found that change previously. This result was replicated in two of our three change detection experiments. We conclude that scenes can be encoded incidentally as well as explicitly and that changes in those scenes can leave measurable traces even if they are not explicitly recalled.

Nanoscale thermal cross-talk effect on phase-change probe memory.

PubMed

Wang, Lei; Wen, Jing; Xiong, Bangshu

2018-05-14

Phase-change probe memory is considered as one of the most promising means for next-generation mass storage devices. However, the achievable storage density of phase-change probe memory is drastically affected by the resulting thermal cross-talk effect while previously lacking of detailed study. Therefore, a three dimensional model that couples electrical, thermal, and phase-change processes of the Ge2Sb2Te5 media is developed, and subsequently deployed to assess the thermal cross-talk effect based on Si/TiN/ Ge2Sb2Te5/diamond-like carbon structure by appropriately tailoring the electro-thermal and geometrical properties of the storage media stack for a variety of external excitations. The modeling results show that the diamond-like carbon capping with a thin thickness, a high electrical conductivity, and a low thermal conductivity is desired to minimize the thermal cross-talk, while the TiN underlayer has a slight impact on the thermal cross-talk. Combining the modeling findings with the previous film deposition experience, an optimized phase-change probe memory architecture is presented, and its capability of providing ultra-high recording density simultaneously with a sufficiently low thermal cross-talk is demonstrated. . © 2018 IOP Publishing Ltd.

On-chip photonic memory elements employing phase-change materials.

PubMed

Rios, Carlos; Hosseini, Peiman; Wright, C David; Bhaskaran, Harish; Pernice, Wolfram H P

2014-03-05

Phase-change materials integrated into nanophotonic circuits provide a flexible way to realize tunable optical components. Relying on the enormous refractive-index contrast between the amorphous and crystalline states, such materials are promising candidates for on-chip photonic memories. Nonvolatile memory operation employing arrays of microring resonators is demonstrated as a route toward all-photonic chipscale information processing. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Photo-induced optical activity in phase-change memory materials.

PubMed

Borisenko, Konstantin B; Shanmugam, Janaki; Williams, Benjamin A O; Ewart, Paul; Gholipour, Behrad; Hewak, Daniel W; Hussain, Rohanah; Jávorfi, Tamás; Siligardi, Giuliano; Kirkland, Angus I

2015-03-05

We demonstrate that optical activity in amorphous isotropic thin films of pure Ge2Sb2Te5 and N-doped Ge2Sb2Te5N phase-change memory materials can be induced using rapid photo crystallisation with circularly polarised laser light. The new anisotropic phase transition has been confirmed by circular dichroism measurements. This opens up the possibility of controlled induction of optical activity at the nanosecond time scale for exploitation in a new generation of high-density optical memory, fast chiroptical switches and chiral metamaterials.

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

PubMed

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

2017-03-22

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

Giant electroresistance of super-tetragonal BiFeO3-based ferroelectric tunnel junctions.

PubMed

Yamada, Hiroyuki; Garcia, Vincent; Fusil, Stéphane; Boyn, Sören; Marinova, Maya; Gloter, Alexandre; Xavier, Stéphane; Grollier, Julie; Jacquet, Eric; Carrétéro, Cécile; Deranlot, Cyrile; Bibes, Manuel; Barthélémy, Agnès

2013-06-25

Ferroelectric tunnel junctions enable a nondestructive readout of the ferroelectric state via a change of resistance induced by switching the ferroelectric polarization. We fabricated submicrometer solid-state ferroelectric tunnel junctions based on a recently discovered polymorph of BiFeO3 with giant axial ratio ("T-phase"). Applying voltage pulses to the junctions leads to the highest resistance changes (OFF/ON ratio >10,000) ever reported with ferroelectric tunnel junctions. Along with the good retention properties, this giant effect reinforces the interest in nonvolatile memories based on ferroelectric tunnel junctions. We also show that the changes in resistance scale with the nucleation and growth of ferroelectric domains in the ultrathin BiFeO3 (imaged by piezoresponse force microscopy), thereby suggesting potential as multilevel memory cells and memristors.

Threshold-voltage modulated phase change heterojunction for application of high density memory

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

Yan, Baihan; Tong, Hao, E-mail: tonghao@hust.edu.cn; Qian, Hang

2015-09-28

Phase change random access memory is one of the most important candidates for the next generation non-volatile memory technology. However, the ability to reduce its memory size is compromised by the fundamental limitations inherent in the CMOS technology. While 0T1R configuration without any additional access transistor shows great advantages in improving the storage density, the leakage current and small operation window limit its application in large-scale arrays. In this work, phase change heterojunction based on GeTe and n-Si is fabricated to address those problems. The relationship between threshold voltage and doping concentration is investigated, and energy band diagrams and X-raymore » photoelectron spectroscopy measurements are provided to explain the results. The threshold voltage is modulated to provide a large operational window based on this relationship. The switching performance of the heterojunction is also tested, showing a good reverse characteristic, which could effectively decrease the leakage current. Furthermore, a reliable read-write-erase function is achieved during the tests. Phase change heterojunction is proposed for high-density memory, showing some notable advantages, such as modulated threshold voltage, large operational window, and low leakage current.« less

The yellow fever virus vaccine induces a broad and polyfunctional human memory CD8+ T cell response.

PubMed

Akondy, Rama S; Monson, Nathan D; Miller, Joseph D; Edupuganti, Srilatha; Teuwen, Dirk; Wu, Hong; Quyyumi, Farah; Garg, Seema; Altman, John D; Del Rio, Carlos; Keyserling, Harry L; Ploss, Alexander; Rice, Charles M; Orenstein, Walter A; Mulligan, Mark J; Ahmed, Rafi

2009-12-15

The live yellow fever vaccine (YF-17D) offers a unique opportunity to study memory CD8(+) T cell differentiation in humans following an acute viral infection. We have performed a comprehensive analysis of the virus-specific CD8(+) T cell response using overlapping peptides spanning the entire viral genome. Our results showed that the YF-17D vaccine induces a broad CD8(+) T cell response targeting several epitopes within each viral protein. We identified a dominant HLA-A2-restricted epitope in the NS4B protein and used tetramers specific for this epitope to track the CD8(+) T cell response over a 2 year period. This longitudinal analysis showed the following. 1) Memory CD8(+) T cells appear to pass through an effector phase and then gradually down-regulate expression of activation markers and effector molecules. 2) This effector phase was characterized by down-regulation of CD127, Bcl-2, CCR7, and CD45RA and was followed by a substantial contraction resulting in a pool of memory T cells that re-expressed CD127, Bcl-2, and CD45RA. 3) These memory cells were polyfunctional in terms of degranulation and production of the cytokines IFN-gamma, TNF-alpha, IL-2, and MIP-1beta. 4) The YF-17D-specific memory CD8(+) T cells had a phenotype (CCR7(-)CD45RA(+)) that is typically associated with terminally differentiated cells with limited proliferative capacity (T(EMRA)). However, these cells exhibited robust proliferative potential showing that expression of CD45RA may not always associate with terminal differentiation and, in fact, may be an indicator of highly functional memory CD8(+) T cells generated after acute viral infections.

Input Source and Strength Influences Overall Firing Phase of Model Hippocampal CA1 Pyramidal Cells During Theta: Relevance to REM Sleep Reactivation and Memory Consolidation

PubMed Central

Booth, Victoria; Poe, Gina R.

2005-01-01

In simulation studies using a realistic model CA1 pyramidal cell, we accounted for the shift in mean firing phase from theta cycle peaks to theta cycle troughs during REM sleep reactivation of hippocampal CA1 place cells over several days of growing familiarization with an environment (Poe et al., 2000). Changes in the theta drive between proximal and distal dendritic regions of the cell modulated the theta phase of firing when stimuli were presented at proximal and distal dendritic locations. Stimuli at proximal dendritic sites (proximal to 100 μm from the soma) invoked firing with a significant phase preference at the depolarizing theta peaks, while distal stimuli (> 290 μm from the soma) invoked firing at hyperpolarizing theta troughs. The location-related phase preference depended on active dendritic conductances, a sufficient electrotonic separation between input sites and theta-induced subthreshold membrane potential oscillations in the cell. The simulation results predict that the shift in mean theta phase during REM sleep cellular reactivation could occur through potentiation of distal dendritic (temporo-ammonic) synapses and depotentiation of proximal dendritic (Schaffer collateral) synapses over the course of familiarization. PMID:16411243

Oral Challenge with Wild-Type Salmonella Typhi Induces Distinct Changes in B Cell Subsets in Individuals Who Develop Typhoid Disease.

PubMed

Toapanta, Franklin R; Bernal, Paula J; Fresnay, Stephanie; Magder, Laurence S; Darton, Thomas C; Jones, Claire; Waddington, Claire S; Blohmke, Christoph J; Angus, Brian; Levine, Myron M; Pollard, Andrew J; Sztein, Marcelo B

2016-06-01

A novel human oral challenge model with wild-type Salmonella Typhi (S. Typhi) was recently established by the Oxford Vaccine Group. In this model, 104 CFU of Salmonella resulted in 65% of participants developing typhoid fever (referred here as typhoid diagnosis -TD-) 6-9 days post-challenge. TD was diagnosed in participants meeting clinical (oral temperature ≥38°C for ≥12h) and/or microbiological (S. Typhi bacteremia) endpoints. Changes in B cell subpopulations following S. Typhi challenge remain undefined. To address this issue, a subset of volunteers (6 TD and 4 who did not develop TD -NoTD-) was evaluated. Notable changes included reduction in the frequency of B cells (cells/ml) of TD volunteers during disease days and increase in plasmablasts (PB) during the recovery phase (>day 14). Additionally, a portion of PB of TD volunteers showed a significant increase in activation (CD40, CD21) and gut homing (integrin α4β7) molecules. Furthermore, all BM subsets of TD volunteers showed changes induced by S. Typhi infections such as a decrease in CD21 in switched memory (Sm) CD27+ and Sm CD27- cells as well as upregulation of CD40 in unswitched memory (Um) and Naïve cells. Furthermore, changes in the signaling profile of some BM subsets were identified after S. Typhi-LPS stimulation around time of disease. Notably, naïve cells of TD (compared to NoTD) volunteers showed a higher percentage of cells phosphorylating Akt suggesting enhanced survival of these cells. Interestingly, most these changes were temporally associated with disease onset. This is the first study to describe differences in B cell subsets directly related to clinical outcome following oral challenge with wild-type S. Typhi in humans.

Memory Influences on Hippocampal and Striatal Neural Codes: Effects of a Shift Between Task Rules

PubMed Central

Yeshenko, Oxana; Mizumori, Sheri J.Y.

2007-01-01

Interactions with neocortical memory systems may facilitate flexible information processing by hippocampus. We sought direct evidence for such memory influences by recording hippocampal neural responses to a change in cognitive strategy. Well trained rats switched (within a single recording session) between the use of place and response strategies to solve a plus maze task. Maze and extramaze environments were constant throughout testing. Place fields demonstrated (in-field) firing rate and location based reorganization (Leutgeb, Leutgeb, Barnes, Moser, McNaughton, & Moser, 2005) after a task switch, suggesting that hippocampus encoded each phase of testing as a different context, or episode. The task switch also resulted in qualitative and quantitative changes to discharge that were correlated with an animal's velocity or acceleration of movement. Thus, the effects of a strategy switch extended beyond the spatial domain, and the movement correlates were not passive reflections of the current behavioral state. To determine whether hippocampal neural responses were unique, striatal place and movement-correlated neurons were simultaneously recorded with hippocampal neurons. Striatal place and movement cells exhibited a response profile that was similar, but not identical, to that observed for hippocampus after a strategy switch. Thus, retrieval of a different memory led both neural systems to represent a different context. However, hippocampus may play a special (though not exclusive) role in flexible spatial processing since correlated firing amongst cell pairs was highest when rats successfully switched between two spatial tasks. Correlated firing by striatal cell pairs increased following any strategy switch, supporting the view that striatum codes changes in reinforcement contingencies. PMID:17240173

Changes in the modulation of brain activity during context encoding vs. context retrieval across the adult lifespan.

PubMed

Ankudowich, E; Pasvanis, S; Rajah, M N

2016-10-01

Age-related deficits in context memory may arise from neural changes underlying both encoding and retrieval of context information. Although age-related functional changes in the brain regions supporting context memory begin at midlife, little is known about the functional changes with age that support context memory encoding and retrieval across the adult lifespan. We investigated how age-related functional changes support context memory across the adult lifespan by assessing linear changes with age during successful context encoding and retrieval. Using functional magnetic resonance imaging (fMRI), we compared young, middle-aged and older adults during both encoding and retrieval of spatial and temporal details of faces. Multivariate behavioral partial least squares (B-PLS) analysis of fMRI data identified a pattern of whole-brain activity that correlated with a linear age term and a pattern of whole-brain activity that was associated with an age-by-memory phase (encoding vs. retrieval) interaction. Further investigation of this latter effect identified three main findings: 1) reduced phase-related modulation in bilateral fusiform gyrus, left superior/anterior frontal gyrus and right inferior frontal gyrus that started at midlife and continued to older age, 2) reduced phase-related modulation in bilateral inferior parietal lobule that occurred only in older age, and 3) changes in phase-related modulation in older but not younger adults in left middle frontal gyrus and bilateral parahippocampal gyrus that was indicative of age-related over-recruitment. We conclude that age-related reductions in context memory arise in midlife and are related to changes in perceptual recollection and changes in fronto-parietal retrieval monitoring. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

In situ observation of the impact of surface oxidation on the crystallization mechanism of GeTe phase-change thin films by scanning transmission electron microscopy

NASA Astrophysics Data System (ADS)

Berthier, R.; Bernier, N.; Cooper, D.; Sabbione, C.; Hippert, F.; Noé, P.

2017-09-01

The crystallization mechanisms of prototypical GeTe phase-change material thin films have been investigated by in situ scanning transmission electron microscopy annealing experiments. A novel sample preparation method has been developed to improve sample quality and stability during in situ annealing, enabling quantitative analysis and live recording of phase change events. Results show that for an uncapped 100 nm thick GeTe layer, exposure to air after fabrication leads to composition changes which promote heterogeneous nucleation at the oxidized surface. We also demonstrate that protecting the GeTe layer with a 10 nm SiN capping layer prevents nucleation at the surface and allows volume nucleation at a temperature 50 °C higher than the onset of crystallization in the oxidized sample. Our results have important implications regarding the integration of these materials in confined memory cells.

Recent Advances on Neuromorphic Systems Using Phase-Change Materials

NASA Astrophysics Data System (ADS)

Wang, Lei; Lu, Shu-Ren; Wen, Jing

2017-05-01

Realization of brain-like computer has always been human's ultimate dream. Today, the possibility of having this dream come true has been significantly boosted due to the advent of several emerging non-volatile memory devices. Within these innovative technologies, phase-change memory device has been commonly regarded as the most promising candidate to imitate the biological brain, owing to its excellent scalability, fast switching speed, and low energy consumption. In this context, a detailed review concerning the physical principles of the neuromorphic circuit using phase-change materials as well as a comprehensive introduction of the currently available phase-change neuromorphic prototypes becomes imperative for scientists to continuously progress the technology of artificial neural networks. In this paper, we first present the biological mechanism of human brain, followed by a brief discussion about physical properties of phase-change materials that recently receive a widespread application on non-volatile memory field. We then survey recent research on different types of neuromorphic circuits using phase-change materials in terms of their respective geometrical architecture and physical schemes to reproduce the biological events of human brain, in particular for spike-time-dependent plasticity. The relevant virtues and limitations of these devices are also evaluated. Finally, the future prospect of the neuromorphic circuit based on phase-change technologies is envisioned.

Recent Advances on Neuromorphic Systems Using Phase-Change Materials.

PubMed

Wang, Lei; Lu, Shu-Ren; Wen, Jing

2017-12-01

Realization of brain-like computer has always been human's ultimate dream. Today, the possibility of having this dream come true has been significantly boosted due to the advent of several emerging non-volatile memory devices. Within these innovative technologies, phase-change memory device has been commonly regarded as the most promising candidate to imitate the biological brain, owing to its excellent scalability, fast switching speed, and low energy consumption. In this context, a detailed review concerning the physical principles of the neuromorphic circuit using phase-change materials as well as a comprehensive introduction of the currently available phase-change neuromorphic prototypes becomes imperative for scientists to continuously progress the technology of artificial neural networks. In this paper, we first present the biological mechanism of human brain, followed by a brief discussion about physical properties of phase-change materials that recently receive a widespread application on non-volatile memory field. We then survey recent research on different types of neuromorphic circuits using phase-change materials in terms of their respective geometrical architecture and physical schemes to reproduce the biological events of human brain, in particular for spike-time-dependent plasticity. The relevant virtues and limitations of these devices are also evaluated. Finally, the future prospect of the neuromorphic circuit based on phase-change technologies is envisioned.

Fabrication of high-density In3Sb1Te2 phase change nanoarray on glass-fabric reinforced flexible substrate

NASA Astrophysics Data System (ADS)

Yoon, Jong Moon; Shin, Dong Ok; Yin, You; Seo, Hyeon Kook; Kim, Daewoon; In Kim, Yong; Jin, Jung Ho; Kim, Yong Tae; Bae, Byeong-Soo; Ouk Kim, Sang; Lee, Jeong Yong

2012-06-01

Mushroom-shaped phase change memory (PCM) consisting of a Cr/In3Sb1Te2 (IST)/TiN (bottom electrode) nanoarray was fabricated via block copolymer lithography and single-step dry etching with a gas mixture of Ar/Cl2. The process was performed on a high performance transparent glass-fabric reinforced composite film (GFR Hybrimer) suitable for use as a novel substrate for flexible devices. The use of GFR Hybrimer with low thermal expansion and flat surfaces enabled successful nanoscale patterning of functional phase change materials on flexible substrates. Block copolymer lithography employing asymmetrical block copolymer blends with hexagonal cylindrical self-assembled morphologies resulted in the creation of hexagonal nanoscale PCM cell arrays with an areal density of approximately 176 Gb/in2.

Bi-Metallic Composite Structures With Designed Internal Residual Stress Field

NASA Technical Reports Server (NTRS)

Brice, Craig A.

2014-01-01

Shape memory alloys (SMA) have a unique ability to recover small amounts of plastic strain through a temperature induced phase change. For these materials, mechanical displacement can be accomplished by heating the structure to induce a phase change, through which some of the plastic strain previously introduced to the structure can be reversed. This paper introduces a concept whereby an SMA phase is incorporated into a conventional alloy matrix in a co-continuous reticulated arrangement forming a bi-metallic composite structure. Through memory activation of the mechanically constrained SMA phase, a controlled residual stress field is developed in the interior of the structure. The presented experimental data show that the memory activation of the SMA composite component significantly changes the residual stress distribution in the overall structure. Designing the structural arrangement of the two phases to produce a controlled residual stress field could be used to create structures that have much improved durability and damage tolerance properties.

Event-induced theta responses as a window on the dynamics of memory.

PubMed

Bastiaansen, Marcel; Hagoort, Peter

2003-01-01

An important, but often ignored distinction in the analysis of EEG signals is that between evoked activity and induced activity. Whereas evoked activity reflects the summation of transient post-synaptic potentials triggered by an event, induced activity, which is mainly oscillatory in nature, is thought to reflect changes in parameters controlling dynamic interactions within and between brain structures. We hypothesize that induced activity may yield information about the dynamics of cell assembly formation, activation and subsequent uncoupling, which may play a prominent role in different types of memory operations. We then describe a number of analysis tools that can be used to study the reactivity of induced rhythmic activity, both in terms of amplitude changes and of phase variability. We briefly discuss how alpha, gamma and theta rhythms are thought to be generated, paying special attention to the hypothesis that the theta rhythm reflects dynamic interactions between the hippocampal system and the neocortex. This hypothesis would imply that studying the reactivity of scalp-recorded theta may provide a window on the contribution of the hippocampus to memory functions. We review studies investigating the reactivity of scalp-recorded theta in paradigms engaging episodic memory, spatial memory and working memory. In addition, we review studies that relate theta reactivity to processes at the interface of memory and language. Despite many unknowns, the experimental evidence largely supports the hypothesis that theta activity plays a functional role in cell assembly formation, a process which may constitute the neural basis of memory formation and retrieval. The available data provide only highly indirect support for the hypothesis that scalp-recorded theta yields information about hippocampal functioning. It is concluded that studying induced rhythmic activity holds promise as an additional important way to study brain function.

Atomic structure and pressure-induced phase transformations in a phase-change alloy

NASA Astrophysics Data System (ADS)

Xu, Ming

Phase-change materials exist in at least two phases under the ambient condition. One is the amorphous state and another is crystalline phase. These two phases have vastly different physical properties, such as electrical conductivity, optical reflectivity, mass density, thermal conductivity, etc. The distinct physical properties and the fast transformation between amorphous and crystalline phases render these materials the ability to store information. For example, the DVD and the Blue-ray discs take advantage of the optical reflectivity contrast, and the newly developed solid-state memories make use of the large conductivity difference. In addition, both the amorphous and crystalline phases in phase-change memories (PCMs) are very stable at room temperature, and they are easy to be scaled up in the production of devices with large storage density. All these features make phase-change materials the ideal candidates for the next-generation memories. Despite of the fast development of these new memory materials in industry, many fundamental physics problems underlying these interesting materials are still not fully resolved. This thesis is aiming at solving some of the key issues in phase-change materials. Most of phase-change materials are composed of Ge-Sb-Te constituents. Among all these Ge-Sb-Te based materials, Ge2Sb2Te5 (GST) has the best performance and has been frequently studied as a prototypical phase-change material. The first and foremost issue is the structure of the two functioning phases. In this thesis, we investigate the unique atomic structure and bonding nature of amorphous GST (a-GST) and crystalline GST ( c-GST), using ab initio tools and X-ray diffraction (XRD) methods. Their local structures and bonding scenarios are then analyzed using electronic structure calculations. In order to gain insight into the fast phase transformation mechanism, we also carried out a series of high-pressure experiments on GST. Several new polymorphs and their transformations have been revealed under high pressure via in situ XRD and in situ electrical resistivity measurements. The mechanisms of the structural and property changes have been uncovered via ab initio molecular dynamics simulations.

A light writable microfluidic "flash memory": optically addressed actuator array with latched operation for microfluidic applications.

PubMed

Hua, Zhishan; Pal, Rohit; Srivannavit, Onnop; Burns, Mark A; Gulari, Erdogan

2008-03-01

This paper presents a novel optically addressed microactuator array (microfluidic "flash memory") with latched operation. Analogous to the address-data bus mediated memory address protocol in electronics, the microactuator array consists of individual phase-change based actuators addressed by localized heating through focused light patterns (address bus), which can be provided by a modified projector or high power laser pointer. A common pressure manifold (data bus) for the entire array is used to generate large deflections of the phase change actuators in the molten phase. The use of phase change material as the working media enables latched operation of the actuator array. After the initial light "writing" during which the phase is temporarily changed to molten, the actuated status is self-maintained by the solid phase of the actuator without power and pressure inputs. The microfluidic flash memory can be re-configured by a new light illumination pattern and common pressure signal. The proposed approach can achieve actuation of arbitrary units in a large-scale array without the need for complex external equipment such as solenoid valves and electrical modules, which leads to significantly simplified system implementation and compact system size. The proposed work therefore provides a flexible, energy-efficient, and low cost multiplexing solution for microfluidic applications based on physical displacements. As an example, the use of the latched microactuator array as "normally closed" or "normally open" microvalves is demonstrated. The phase-change wax is fully encapsulated and thus immune from contamination issues in fluidic environments.

The microstructural changes of Ge2Sb2Te5 thin film during crystallization process

NASA Astrophysics Data System (ADS)

Xu, Jingbo; Qi, Chao; Chen, Limin; Zheng, Long; Xie, Qiyun

2018-05-01

Phase change memory is known as the most promising candidate for the next generation nonvolatile memory technology. In this paper, the microstructural changes of Ge2Sb2Te5 film, which is the most common choice of phase change memory material, has been carefully studied by the combination of several characterization techniques. The combination of resistance measurements, X-ray diffraction, Raman spectroscopy and X-ray reflectivity allows us to simultaneously extract the characteristics of microstructural changes during crystallization process. The existence of surface/interface Ge2Sb2Te5 layer has been proposed here based on X-ray reflectivity measurements. Although the total film thickness decreases, as a result of the phase transition from amorphous to metastable crystalline cubic and then to the stable hexagonal phase, the surface/interface thickness increases after crystallization. Moreover, the increase of average grain size, density and surface roughness has been confirmed during thermal annealing process.

Nonvolatile “AND,” “OR,” and “NOT” Boolean logic gates based on phase-change memory

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

Li, Y.; Zhong, Y. P.; Deng, Y. F.

2013-12-21

Electronic devices or circuits that can implement both logic and memory functions are regarded as the building blocks for future massive parallel computing beyond von Neumann architecture. Here we proposed phase-change memory (PCM)-based nonvolatile logic gates capable of AND, OR, and NOT Boolean logic operations verified in SPICE simulations and circuit experiments. The logic operations are parallel computing and results can be stored directly in the states of the logic gates, facilitating the combination of computing and memory in the same circuit. These results are encouraging for ultralow-power and high-speed nonvolatile logic circuit design based on novel memory devices.

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

PubMed

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

2018-05-01

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

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

PubMed

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

2017-02-14

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

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

PubMed Central

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

2017-01-01

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

Shape Memory Alloys and Their Applications in Power Generation and Refrigeration

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

Cui, Jun

The shape memory effect is closely related to the reversible martensitic phase transformation, which is diffusionless and involves shear deformation. The recoverable transformation between the two phases with different crystalline symmetry results in reversible changes in physical properties such as electrical conductivity, magnetization, and elasticity. Accompanying the transformation is a change of entropy. Fascinating applications are developed based on these changes. In this paper, the history, fundamentals and technical challenges of both thermoelastic and ferromagnetic shape memory alloys are briefly reviewed; applications related to energy conversion such as power generation and refrigeration as well as recent developments will be discussed.

Shape Memory Alloys and their Applications in Power Generation and Refrigeration

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

Cui, Jun

The shape memory effect is closely related to the reversible martensitic phase transformation, which is diffusionless and involves shear deformation. The recoverable transformation between the two phases with different crystalline symmetry results in reversible changes in physical properties such as electrical conductivity, magnetization, and elasticity. Accompanying the transformation is a change of entropy. Fascinating applications are developed based on these changes. In this paper, the history, fundamentals and technical challenges of both thermoelastic and ferromagnetic shape memory alloys are briefly reviewed; applications related to energy conversion such as power generation and refrigeration as well as recent developments will be discussed.

Microstructure and electrical properties of Sb2Te phase-change material

NASA Astrophysics Data System (ADS)

Liu, Guangyu; Wu, Liangcai; Li, Tao; Rao, Feng; Song, Sannian; Liu, Bo; Song, Zhitang

2016-10-01

Phase Change Memory (PCM) has great potential for commercial applications of next generation non-volatile memory (NVM) due to its high operation speed, high endurance and low power consumption. Sb2Te (ST) is a common phase-change material and has fast crystallization speed, while thermal stability is relatively poor and its crystallization temperature is about 142°C. According to the Arrhenius law, the extrapolated failure temperature is about 55°C for ten years. When heated above the crystallization temperature while below the melting point, its structure can be transformed from amorphous phase to hexagonal phase. Due to the growth-dominated crystallization mechanism, the grain size of ST film is large and the diameter of about 300 nm is too large compared with Ge2Sb2Te5 (GST), which may deteriorate the device performance. High resolution transmission electron microscopy (HRTEM) and selected area electron diffraction (SAED) were employed to study the microstructures and the results indicate that the crystal plane is {110}. In addition, device cells were manufactured and their current-voltage (I-V) and resistance-voltage characteristics were tested, and the results reveal that the threshold voltage (Vth) of ST film is 0.87 V. By researching the basic properties of ST, we can understand its disadvantages and manage to improve its performance by doping or other proper methods. Finally, the improved ST can be a candidate for optical discs and PCM.

Simultaneous ultra-long data retention and low power based on Ge10Sb90/SiO2 multilayer thin films

NASA Astrophysics Data System (ADS)

You, Haipeng; Hu, Yifeng; Zhu, Xiaoqin; Zou, Hua; Song, Sannian; Song, Zhitang

2018-02-01

In this article, Ge10Sb90/SiO2 multilayer thin films were prepared to improve thermal stability and data retention for phase change memory. Compared with Ge10Sb90 monolayer thin film, Ge10Sb90 (1 nm)/SiO2 (9 nm) multilayer thin film had higher crystallization temperature and resistance contrast between amorphous and crystalline states. Annealed Ge10Sb90 (1 nm)/SiO2 (9 nm) had uniform grain with the size of 15.71 nm. After annealing, the root-mean-square surface roughness for Ge10Sb90 (1 nm)/SiO2 (9 nm) thin film increased slightly from 0.45 to 0.53 nm. The amorphization time for Ge10Sb90 (1 nm)/SiO2 (9 nm) thin film (2.29 ns) is shorter than Ge2Sb2Te5 (3.56 ns). The threshold voltage of a cell based on Ge10Sb90 (1 nm)/SiO2 (9 nm) (3.57 V) was smaller than GST (4.18 V). The results indicated that Ge10Sb90/SiO2 was a promising phase change thin film with high thermal ability and low power consumption for phase change memory application.

The Impact of Sex Work Interruption on Blood-Derived T Cells in Sex Workers from Nairobi, Kenya.

PubMed

Omollo, Kenneth; Boily-Larouche, Geneviève; Lajoie, Julie; Kimani, Makobu; Cheruiyot, Julianna; Kimani, Joshua; Oyugi, Julius; Fowke, Keith Raymond

Unprotected sexual intercourse exposes the female genital tract (FGT) to semen-derived antigens, which leads to a proinflammatory response. Studies have shown that this postcoital inflammatory response can lead to recruitment of activated T cells to the FGT, thereby increasing risk of HIV infection. The purpose of this study was to evaluate the impact of sex work on activation and memory phenotypes of peripheral T cells among female sex workers (FSW) from Nairobi, Kenya. Thirty FSW were recruited from the Pumwani Sex Workers Cohort, 10 in each of the following groups: HIV-exposed seronegative (at least 7 years in active sex work), HIV positive, and New Negative (HIV negative, less than 3 years in active sex work). Blood was obtained at three different phases (active sex work, abstinence from sex work-sex break, and following resumption of sex work). Peripheral blood mononuclear cells were isolated and stained for phenotypic markers (CD3, CD4, CD8, and CD161), memory phenotype markers (CD45RA and CCR7), activation markers (CD69, HLA-DR, and CD95), and the HIV coreceptor (CCR5). T-cell populations were compared between groups. In HIV-positive women, CD8+CCR5+ T cells declined at the sex break period, while CD4+CD161+ T cells increased when returning to sex work. All groups showed no significant changes in systemic T-cell activation markers following the interruption of sex work, however, significant reductions in naive CD8+ T cells were noted. For each of the study points, HIV positives had higher effector memory and CD8+CD95+ T cells and lower naive CD8+ T cells than the HIV-uninfected groups. Interruption of sex work had subtle effects on systemic T-cell memory phenotypes.

Graphene-ferroelectric metadevices for nonvolatile memory and reconfigurable logic-gate operations.

PubMed

Kim, Woo Young; Kim, Hyeon-Don; Kim, Teun-Teun; Park, Hyun-Sung; Lee, Kanghee; Choi, Hyun Joo; Lee, Seung Hoon; Son, Jaehyeon; Park, Namkyoo; Min, Bumki

2016-01-27

Memory metamaterials are artificial media that sustain transformed electromagnetic properties without persistent external stimuli. Previous memory metamaterials were realized with phase-change materials, such as vanadium dioxide or chalcogenide glasses, which exhibit memory behaviour with respect to electrically/optically induced thermal stimuli. However, they require a thermally isolated environment for longer retention or strong optical pump for phase-change. Here we demonstrate electrically programmable nonvolatile memory metadevices realised by the hybridization of graphene, a ferroelectric and meta-atoms/meta-molecules, and extend the concept further to establish reconfigurable logic-gate metadevices. For a memory metadevice having a single electrical input, amplitude, phase and even the polarization multi-states were clearly distinguishable with a retention time of over 10 years at room temperature. Furthermore, logic-gate functionalities were demonstrated with reconfigurable logic-gate metadevices having two electrical inputs, with each connected to separate ferroelectric layers that act as the multi-level controller for the doping level of the sandwiched graphene layer.

Graphene-ferroelectric metadevices for nonvolatile memory and reconfigurable logic-gate operations

NASA Astrophysics Data System (ADS)

Kim, Woo Young; Kim, Hyeon-Don; Kim, Teun-Teun; Park, Hyun-Sung; Lee, Kanghee; Choi, Hyun Joo; Lee, Seung Hoon; Son, Jaehyeon; Park, Namkyoo; Min, Bumki

2016-01-01

Memory metamaterials are artificial media that sustain transformed electromagnetic properties without persistent external stimuli. Previous memory metamaterials were realized with phase-change materials, such as vanadium dioxide or chalcogenide glasses, which exhibit memory behaviour with respect to electrically/optically induced thermal stimuli. However, they require a thermally isolated environment for longer retention or strong optical pump for phase-change. Here we demonstrate electrically programmable nonvolatile memory metadevices realised by the hybridization of graphene, a ferroelectric and meta-atoms/meta-molecules, and extend the concept further to establish reconfigurable logic-gate metadevices. For a memory metadevice having a single electrical input, amplitude, phase and even the polarization multi-states were clearly distinguishable with a retention time of over 10 years at room temperature. Furthermore, logic-gate functionalities were demonstrated with reconfigurable logic-gate metadevices having two electrical inputs, with each connected to separate ferroelectric layers that act as the multi-level controller for the doping level of the sandwiched graphene layer.

FXR1P Limits Long-Term Memory, Long-Lasting Synaptic Potentiation, and de novo GluA2 Translation

PubMed Central

Jones, Emma V.; Altimimi, Haider F.; Farmer, W. Todd; Gandin, Valentina; Hanna, Edith; Zong, Ruiting; Barbon, Alessandro; Nelson, David L.; Topisirovic, Ivan; Rochford, Joseph; Stellwagen, David; Béïque, Jean-Claude; Murai, Keith K.

2014-01-01

SUMMARY Translational control of mRNAs allows for rapid and selective changes in synaptic protein expression, changes that are required for long-lasting plasticity and memory formation in the brain. Fragile X Related Protein 1 (FXR1P) is an RNA-binding protein that controls mRNA translation in non-neuronal cells and co-localizes with translational machinery in neurons. However, its neuronal mRNA targets and role in the brain are unknown. Here, we demonstrate that removal of FXR1P from the forebrain of postnatal mice selectively enhances long-term storage of spatial memories, hippocampal late-phase LTP (L-LTP) and de novo GluA2 synthesis. Furthermore, FXR1P binds specifically to the 5’UTR of GluA2 mRNA to repress translation and limit the amount of GluA2 incorporated at potentiated synapses. This study uncovers a new mechanism for regulating long-lasting synaptic plasticity and spatial memory formation and reveals an unexpected divergent role of FXR1P among Fragile X proteins in brain plasticity. PMID:25456134

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 class of memory technologies and scaling of scientific procedures based on an investigation of recent progress in advanced Flash memory devices. PMID:25278820

Overview of emerging nonvolatile memory technologies.

PubMed

Meena, Jagan Singh; Sze, Simon Min; Chand, Umesh; Tseng, Tseung-Yuen

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 class of memory technologies and scaling of scientific procedures based on an investigation of recent progress in advanced Flash memory devices.

Neural correlates of true and false memory in mild cognitive impairment.

PubMed

Sweeney-Reed, Catherine M; Riddell, Patricia M; Ellis, Judi A; Freeman, Jayne E; Nasuto, Slawomir J

2012-01-01

The goal of this research was to investigate the changes in neural processing in mild cognitive impairment. We measured phase synchrony, amplitudes, and event-related potentials in veridical and false memory to determine whether these differed in participants with mild cognitive impairment compared with typical, age-matched controls. Empirical mode decomposition phase locking analysis was used to assess synchrony, which is the first time this analysis technique has been applied in a complex cognitive task such as memory processing. The technique allowed assessment of changes in frontal and parietal cortex connectivity over time during a memory task, without a priori selection of frequency ranges, which has been shown previously to influence synchrony detection. Phase synchrony differed significantly in its timing and degree between participant groups in the theta and alpha frequency ranges. Timing differences suggested greater dependence on gist memory in the presence of mild cognitive impairment. The group with mild cognitive impairment had significantly more frontal theta phase locking than the controls in the absence of a significant behavioural difference in the task, providing new evidence for compensatory processing in the former group. Both groups showed greater frontal phase locking during false than true memory, suggesting increased searching when no actual memory trace was found. Significant inter-group differences in frontal alpha phase locking provided support for a role for lower and upper alpha oscillations in memory processing. Finally, fronto-parietal interaction was significantly reduced in the group with mild cognitive impairment, supporting the notion that mild cognitive impairment could represent an early stage in Alzheimer's disease, which has been described as a 'disconnection syndrome'.

Release from proactive interference in rat spatial working memory.

PubMed

Roberts, William A; MacDonald, Hayden; Brown, Lyn; Macpherson, Krista

2017-09-01

A three-phase procedure was used to produce proactive interference (PI) in one trial on an eight-arm radial maze. Rats were forced to enter four arms for reward on an initial interference phase, to then enter the four remaining arms on a target phase, and to then choose among all eight arms on a retention test, with only the arms not visited in the target phase containing reward. Control trials involved only the target phase and the retention test. Lower accuracy was found on PI trials than on control trials, but performance on PI trials significantly exceeded chance, showing some retention of target memories. Changes in temporal and reward variables between the interference, target, and retention test phases showed release from PI, but changes in context and pattern of arm entry did not. It is suggested that the release from PI paradigm can be used to understand spatial memory encoding in rats and other species.

On the shape memory of red blood cells

NASA Astrophysics Data System (ADS)

Cordasco, Daniel; Bagchi, Prosenjit

2017-04-01

Red blood cells (RBCs) undergo remarkably large deformations when subjected to external forces but return to their biconcave discoid resting shape as the forces are withdrawn. In many experiments, such as when RBCs are subjected to a shear flow and undergo the tank-treading motion, the membrane elements are also displaced from their original (resting) locations along the cell surface with respect to the cell axis, in addition to the cell being deformed. A shape memory is said to exist if after the flow is stopped the RBC regains its biconcave shape and the membrane elements also return to their original locations. The shape memory of RBCs was demonstrated by Fischer ["Shape memory of human red blood cells," Biophys. J. 86, 3304-3313 (2004)] using shear flow go-and-stop experiments. Optical tweezer and micropipette based stretch-relaxation experiments do not reveal the complete shape memory because while the RBC may be deformed, the membrane elements are not significantly displaced from their original locations with respect to the cell axis. Here we present the first three-dimensional computational study predicting the complete shape memory of RBCs using shear flow go-and-stop simulations. The influence of different parameters, namely, membrane shear elasticity and bending rigidity, membrane viscosity, cytoplasmic and suspending fluid viscosity, as well as different stress-free states of the RBC is studied. For all cases, the RBCs always exhibit shape memory. The complete recovery of the RBC in shear flow go-and-stop simulations occurs over a time that is orders of magnitude longer than that for optical tweezer and micropipette based relaxations. The response is also observed to be more complex and composed of widely disparate time scales as opposed to only one time scale that characterizes the optical tweezer and micropipette based relaxations. We observe that the recovery occurs in three phases: a rapid compression of the RBC immediately after the flow is stopped, followed by a slow recovery to the biconcave shape combined with membrane rotation, and a final rotational return of the membrane elements back to their original locations. A fast time scale on the order of a few hundred milliseconds characterizes the initial compression phase while a slow time scale on the order of tens of seconds is associated with the rotational phase. We observe that the response is strongly dependent on the stress-free state of the cells, that is, the relaxation time decreases significantly and the mode of recovery changes from rotation-driven to deformation-driven as the stress-free state becomes more non-spherical. We show that while membrane shear elasticity and non-spherical stress-free shape are necessary and sufficient for the membrane elements to return to their original locations, bending rigidity is needed for the "global" recovery of the biconcave shape. We also perform a novel relaxation simulation in which the cell axis of revolution is not aligned with the shear plane and show that the shape memory is exhibited even when the membrane elements are displaced normal to the imposed flow direction. The results presented here could motivate new experiments to determine the exact stress-free state of the RBC and also to clearly identify different tank-treading modes.

Sb-Te Phase-change Materials under Nanoscale Confinement

NASA Astrophysics Data System (ADS)

Ihalawela, Chandrasiri A.

Size, speed and efficiency are the major challenges of next generation nonvolatile memory (NVM), and phase-change memory (PCM) has captured a great attention due to its promising features. The key for PCM is rapid and reversible switching between amorphous and crystalline phases with optical or electrical excitation. The structural transition is associated with significant contrast in material properties which can be utilized in optical (CD, DVD, BD) and electronic (PCRAM) memory applications. Importantly, both the functionality and the success of PCM technology significantly depend on the core material and its properties. So investigating PC materials is crucial for the development of PCM technology to realized enhanced solutions. In regards to PC materials, Sb-Te binary plays a significant role as a basis to the well-known Ge-Sb-Te system. Unlike the conventional deposition methods (sputtering, evaporation), electrochemical deposition method is used due to its multiple advantages, such as conformality, via filling capability, etc. First, the controllable synthesis of Sb-Te thin films was studied for a wide range of compositions using this novel deposition method. Secondly, the solid electrolytic nature of stoichiometric Sb2Te3 was studied with respect to precious metals. With the understanding of 2D thin film synthesis, Sb-Te 1D nanowires (18 - 220 nm) were synthesized using templated electrodeposition, where nanoporous anodic aluminum oxide (AAO) was used as a template for the growth of nanowires. In order to gain the controllability over the deposition in high aspect ratio structures, growth mechanisms of both the thin films and nanowires were investigated. Systematic understanding gained thorough previous studies helped to formulate the ultimate goal of this dissertation. In this dissertation, the main objective is to understand the size effect of PC materials on their phase transition properties. The reduction of effective memory cell size in conjunction with multilevel cells could be promising to achieve high data densities. However the size reduction may result in changes in material properties. If phase transition properties of the materials are also tunable with respect to the size, then more attractive solutions could be realized. So we have reported the size effect on crystallization temperature of prototypical Sb2Te3 nanowires synthesized in AAO templates. Moreover, we have found that the reduction of nanowire size can elevate the crystallization temperature, which is crucial for data retention in PCM technology. Energy dispersive X-ray spectroscopy, X-ray diffraction, electron microscopy and electrical resistivity measurements were used to characterize the composition, structure, morphology, and phase transition properties of the materials. We believe that this dissertation will provide new insights into the size effect of PC materials in addition to the controllable synthesis of PC thin films and nanowires through the novel electrochemical method.

Relation between bandgap and resistance drift in amorphous phase change materials

PubMed Central

Rütten, Martin; Kaes, Matthias; Albert, Andreas; Wuttig, Matthias; Salinga, Martin

2015-01-01

Memory based on phase change materials is currently the most promising candidate for bridging the gap in access time between memory and storage in traditional memory hierarchy. However, multilevel storage is still hindered by the so-called resistance drift commonly related to structural relaxation of the amorphous phase. Here, we present the temporal evolution of infrared spectra measured on amorphous thin films of the three phase change materials Ag4In3Sb67Te26, GeTe and the most popular Ge2Sb2Te5. A widening of the bandgap upon annealing accompanied by a decrease of the optical dielectric constant ε∞ is observed for all three materials. Quantitative comparison with experimental data for the apparent activation energy of conduction reveals that the temporal evolution of bandgap and activation energy can be decoupled. The case of Ag4In3Sb67Te26, where the increase of activation energy is significantly smaller than the bandgap widening, demonstrates the possibility to identify new phase change materials with reduced resistance drift. PMID:26621533

Relation between bandgap and resistance drift in amorphous phase change materials.

PubMed

Rütten, Martin; Kaes, Matthias; Albert, Andreas; Wuttig, Matthias; Salinga, Martin

2015-12-01

Memory based on phase change materials is currently the most promising candidate for bridging the gap in access time between memory and storage in traditional memory hierarchy. However, multilevel storage is still hindered by the so-called resistance drift commonly related to structural relaxation of the amorphous phase. Here, we present the temporal evolution of infrared spectra measured on amorphous thin films of the three phase change materials Ag4In3Sb67Te26, GeTe and the most popular Ge2Sb2Te5. A widening of the bandgap upon annealing accompanied by a decrease of the optical dielectric constant ε∞ is observed for all three materials. Quantitative comparison with experimental data for the apparent activation energy of conduction reveals that the temporal evolution of bandgap and activation energy can be decoupled. The case of Ag4In3Sb67Te26, where the increase of activation energy is significantly smaller than the bandgap widening, demonstrates the possibility to identify new phase change materials with reduced resistance drift.

Effects of the swimming exercise on the consolidation and persistence of auditory and contextual fear memory.

PubMed

Faria, Rodolfo Souza; Gutierres, Luís Felipe Soares; Sobrinho, Fernando César Faria; Miranda, Iris do Vale; Reis, Júlia Dos; Dias, Elayne Vieira; Sartori, Cesar Renato; Moreira, Dalmo Antonio Ribeiro

2016-08-15

Exposure to negative environmental events triggers defensive behavior and leads to the formation of aversive associative memory. Cellular and molecular changes in the central nervous system underlie this memory formation, as well as the associated behavioral changes. In general, memory process is established in distinct phases such as acquisition, consolidation, evocation, persistence, and extinction of the acquired information. After exposure to a particular event, early changes in involved neural circuits support the memory consolidation, which corresponds to the short-term memory. Re-exposure to previously memorized events evokes the original memory, a process that is considered essential for the reactivation and consequent persistence of memory, ensuring that long-term memory is established. Different environmental stimuli may modulate the memory formation process, as well as their distinct phases. Among the different environmental stimuli able of modulating memory formation is the physical exercise which is a potent modulator of neuronal activity. There are many studies showing that physical exercise modulates learning and memory processes, mainly in the consolidation phase of the explicit memory. However, there are few reports in the literature regarding the role of physical exercise in implicit aversive associative memory, especially at the persistence phase. Thus, the present study aimed to investigate the relationship between swimming exercise and the consolidation and persistence of contextual and auditory-cued fear memory. Male Wistar rats were submitted to sessions of swimming exercise five times a week, over six weeks. After that, the rats were submitted to classical aversive conditioning training by a pairing tone/foot shock paradigm. Finally, rats were evaluated for consolidation and persistence of fear memory to both auditory and contextual cues. Our results demonstrate that classical aversive conditioning with tone/foot shock pairing induced consolidation as well as persistence of conditioned fear memory. In addition, rats submitted to swimming exercise over six weeks showed an improved performance in the test of auditory-cued fear memory persistence, but not in the test of contextual fear memory persistence. Moreover, no significant effect from swimming exercise was observed on consolidation of both contextual and auditory fear memory. So, our study, revealing the effect of the swimming exercise on different stages of implicit memory of tone/foot shock conditioning, contributes to and complements the current knowledge about the environmental modulation of memory process. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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. © 2011 Blackwell Publishing Ltd.

Thrombin-induced microglial activation impairs hippocampal neurogenesis and spatial memory ability in mice.

PubMed

Yang, Yuan; Zhang, Meikui; Kang, Xiaoni; Jiang, Chen; Zhang, Huan; Wang, Pei; Li, Jingjing

2015-09-26

To investigate the effects of microglia/macrophages activation induced by intrastriatal thrombin injection on dentate gyrus neurogenesis and spatial memory ability in mice. The male C57BL/6 mice were divided into 4 groups of 10: sham, intracerebral hemorrhage (ICH), ICH + hirudin (thrombin inhibitor), and ICH + indometacin (Indo, an anti-inflammation drug). ICH model was created by intrastriatal thrombin (1U) injection. BrdU (50 mg/kg) was administrated on the same day after surgery for 6 consecutive days. Motor functions were evaluated with rotarod and beam walking tests. The spatial memory deficit was measured with Morris water maze (MWM). Cell quantification was performed for doublecortin (DCX, immature neuron), BrdU (S-phase proliferating cell population) and CD68 (activated microglia/macrophage) immune-reactive cells. Microglia/macrophages activation induced by intrastriatal thrombin injection reduced hippocampal neurogenesis and impaired spatial memory ability, but did not affect the motor function at 3 and 5 days post-injury. Both hirudin and indometacin reduced microglia/macrophages activation, enhanced hippocampal neurogenesis, and improved spatial memory ability in mice. Microglia/macrophages activation induced by intrastriatal thrombin injection might be responsible for the spatial memory deficit. Targeting both thrombin and inflammation systems in acute phase of ICH might be important in alleviating the significant spatial memory deficits.

Modulation of Autoimmune T-Cell Memory by Stem Cell Educator Therapy: Phase 1/2 Clinical Trial.

PubMed

Delgado, Elias; Perez-Basterrechea, Marcos; Suarez-Alvarez, Beatriz; Zhou, Huimin; Revuelta, Eva Martinez; Garcia-Gala, Jose Maria; Perez, Silvia; Alvarez-Viejo, Maria; Menendez, Edelmiro; Lopez-Larrea, Carlos; Tang, Ruifeng; Zhu, Zhenlong; Hu, Wei; Moss, Thomas; Guindi, Edward; Otero, Jesus; Zhao, Yong

2015-12-01

Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that causes a deficit of pancreatic islet β cells. The complexities of overcoming autoimmunity in T1D have contributed to the challenges the research community faces when devising successful treatments with conventional immune therapies. Overcoming autoimmune T cell memory represents one of the key hurdles. In this open-label, phase 1/phase 2 study, Caucasian T1D patients (N = 15) received two treatments with the Stem Cell Educator (SCE) therapy, an approach that uses human multipotent cord blood-derived multipotent stem cells (CB-SCs). SCE therapy involves a closed-loop system that briefly treats the patient's lymphocytes with CB-SCs in vitro and returns the "educated" lymphocytes (but not the CB-SCs) into the patient's blood circulation. This study is registered with ClinicalTrials.gov, NCT01350219. Clinical data demonstrated that SCE therapy was well tolerated in all subjects. The percentage of naïve CD4(+) T cells was significantly increased at 26 weeks and maintained through the final follow-up at 56 weeks. The percentage of CD4(+) central memory T cells (TCM) was markedly and constantly increased at 18 weeks. Both CD4(+) effector memory T cells (TEM) and CD8(+) TEM cells were considerably decreased at 18 weeks and 26 weeks respectively. Additional clinical data demonstrated the modulation of C-C chemokine receptor 7 (CCR7) expressions on naïve T, TCM, and TEM cells. Following two treatments with SCE therapy, islet β-cell function was improved and maintained in individuals with residual β-cell function, but not in those without residual β-cell function. Current clinical data demonstrated the safety and efficacy of SCE therapy in immune modulation. SCE therapy provides lasting reversal of autoimmune memory that could improve islet β-cell function in Caucasian subjects. Obra Social "La Caixa", Instituto de Salud Carlos III, Red de Investigación Renal, European Union FEDER Funds, Principado de Asturias, FICYT, and Hackensack University Medical Center Foundation.

Modulation of Autoimmune T-Cell Memory by Stem Cell Educator Therapy: Phase 1/2 Clinical Trial

PubMed Central

Delgado, Elias; Perez-Basterrechea, Marcos; Suarez-Alvarez, Beatriz; Zhou, Huimin; Revuelta, Eva Martinez; Garcia-Gala, Jose Maria; Perez, Silvia; Alvarez-Viejo, Maria; Menendez, Edelmiro; Lopez-Larrea, Carlos; Tang, Ruifeng; Zhu, Zhenlong; Hu, Wei; Moss, Thomas; Guindi, Edward; Otero, Jesus; Zhao, Yong

2015-01-01

Background Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that causes a deficit of pancreatic islet β cells. The complexities of overcoming autoimmunity in T1D have contributed to the challenges the research community faces when devising successful treatments with conventional immune therapies. Overcoming autoimmune T cell memory represents one of the key hurdles. Methods In this open-label, phase 1/phase 2 study, Caucasian T1D patients (N = 15) received two treatments with the Stem Cell Educator (SCE) therapy, an approach that uses human multipotent cord blood-derived multipotent stem cells (CB-SCs). SCE therapy involves a closed-loop system that briefly treats the patient's lymphocytes with CB-SCs in vitro and returns the “educated” lymphocytes (but not the CB-SCs) into the patient's blood circulation. This study is registered with ClinicalTrials.gov, NCT01350219. Findings Clinical data demonstrated that SCE therapy was well tolerated in all subjects. The percentage of naïve CD4+ T cells was significantly increased at 26 weeks and maintained through the final follow-up at 56 weeks. The percentage of CD4+ central memory T cells (TCM) was markedly and constantly increased at 18 weeks. Both CD4+ effector memory T cells (TEM) and CD8+ TEM cells were considerably decreased at 18 weeks and 26 weeks respectively. Additional clinical data demonstrated the modulation of C–C chemokine receptor 7 (CCR7) expressions on naïve T, TCM, and TEM cells. Following two treatments with SCE therapy, islet β-cell function was improved and maintained in individuals with residual β-cell function, but not in those without residual β-cell function. Interpretation Current clinical data demonstrated the safety and efficacy of SCE therapy in immune modulation. SCE therapy provides lasting reversal of autoimmune memory that could improve islet β-cell function in Caucasian subjects. Funding Obra Social “La Caixa”, Instituto de Salud Carlos III, Red de Investigación Renal, European Union FEDER Funds, Principado de Asturias, FICYT, and Hackensack University Medical Center Foundation. PMID:26844283

Autophagy is essential for effector CD8 T cell survival and memory formation

PubMed Central

Xu, Xiaojin; Araki, Koichi; Li, Shuzhao; Han, Jin-Hwan; Ye, Lilin; Tan, Wendy G.; Konieczny, Bogumila T.; Bruinsma, Monique W.; Martinez, Jennifer; Pearce, Erika L; Green, Douglas R.; Jones, Dean P.; Virgin, Herbert W.; Ahmed, Rafi

2014-01-01

The importance of autophagy in memory CD8 T cell differentiation in vivo is not well defined. We show here that autophagy is dynamically regulated in virus-specific CD8 T cells during acute lymphocytic choriomeningitis virus infection. Autophagy decreased in activated proliferating T cells, and was then upregulated at the peak of the effector T cell response. Consistent with this model, deletion of the key autophagy genes Atg7 or Atg5 in virus-specific CD8 T cells had minimal effect on generating effector cells but greatly enhanced their death during the contraction phase resulting in compromised memory formation. These findings provide insight into when autophagy is needed during effector and memory T cell differentiation in vivo and also warrant a re-examination of our current concepts about the relationship between T cell activation and autophagy. PMID:25362489

Simian immunodeficiency virus infection induces severe loss of intestinal central memory T cells which impairs CD4+ T-cell restoration during antiretroviral therapy.

PubMed

Verhoeven, D; Sankaran, S; Dandekar, S

2007-08-01

Simian immunodeficiency virus (SIV) infection leads to severe loss of intestinal CD4(+) T cells and, as compared to peripheral blood, restoration of these cells is slow during antiretroviral therapy (ART). Mechanisms for this delay have not been examined in context of which specific CD4(+) memory subsets or lost and fail to regenerate during ART. Fifteen rhesus macaques were infected with SIV, five of which received ART (FTC/PMPA) for 30 weeks. Viral loads were measured by real-time PCR. Flow cytometric analysis determined changes in T-cell subsets and their proliferative state. Changes in proliferative CD4(+) memory subsets during infection accelerated their depletion. This reduced the central memory CD4(+) T-cell pool and contributed to slow CD4(+) T-cell restoration during ART. There was a lack of restoration of the CD4(+) central memory and effector memory T-cell subsets in gut-associated lymphoid tissue during ART, which may contribute to the altered intestinal T-cell homeostasis in SIV infection.

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

NASA Astrophysics Data System (ADS)

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

2010-06-01

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

Optimisation of readout performance of phase-change probe memory in terms of capping layer and probe tip

NASA Astrophysics Data System (ADS)

Wang, Lei; Wright, C. David; Aziz, Mustafa. M.; Yang, Ci Hui; Yang, Guo Wei

2014-11-01

The capping layer and the probe tip that serve as the protective layer and the recording tool, respectively, for phase-change probe memory play an important role on the writing performance of phase-change probe memory, thus receiving considerable attention. On the other hand, their influence on the readout performance of phasechange probe memory has rarely been reported before. A three-dimensional parametric study based on the Laplace equation was therefore conducted to investigate the effect of the capping layer and the probe tip on the resulting reading contrast for the two cases of reading a crystalline bit from an amorphous matrix and reading an amorphous bit from a crystalline matrix. The results indicated that a capping layer with a thickness of 2 nm and an electrical conductivity of 50 Ω-1m-1 is able to provide an appropriate reading contrast for both the cases, while satisfying the previous writing requirement, particularly with the assistance of a platinum silicide probe tip.

Vanadium doped Sb{sub 2}Te{sub 3} material with modified crystallization mechanism for phase-change memory application

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

Ji, Xinglong; Zheng, Yonghui; Zhou, Wangyang

2015-06-15

In this paper, V{sub 0.21}Sb{sub 2}Te{sub 3} (VST) has been proposed for phase-change memory applications. With vanadium incorporating, VST has better thermal stability than Sb{sub 2}Te{sub 3} and can maintain in amorphous phase at room temperature. Two resistance steps were observed in temperature dependent resistance measurements. By real-time observing the temperature dependent lattice structure evolution, VST presents as a homogenous phase throughout the whole thermal process. Combining Hall measurement and transmission electron microscopy results, we can ascribe the two resistance steps to the unique crystallization mechanism of VST material. Then, the amorphous thermal stability enhancement can also be rooted inmore » the suppression of the fast growth crystallization mechanism. Furthermore, the applicability of VST is demonstrated by resistance-voltage measurement, and the phase transition of VST can be triggered by a 15 ns electric pulse. In addition, endurance up to 2.7×10{sup 4} cycles makes VST a promising candidate for phase-change memory applications.« less

Autoreactive T effector memory differentiation mirrors β-cell function in type 1 diabetes.

PubMed

Yeo, Lorraine; Woodwyk, Alyssa; Sood, Sanjana; Lorenc, Anna; Eichmann, Martin; Pujol-Autonell, Irma; Melchiotti, Rossella; Skowera, Ania; Fidanis, Efthymios; Dolton, Garry M; Tungatt, Katie; Sewell, Andrew K; Heck, Susanne; Saxena, Alka; Beam, Craig A; Peakman, Mark

2018-05-31

In type 1 diabetes, cytotoxic CD8 T cells with specificity for β-cell autoantigens are found in the pancreatic islets where they are implicated in the destruction of insulin-secreting β cells. In contrast, the disease relevance of β-cell-reactive CD8 T cells that are detectable in the circulation, and their relationship to β-cell function, are not known. Here, we tracked multiple, circulating β-cell-reactive CD8 T cell subsets and measured β-cell function longitudinally for two years, starting immediately after diagnosis of type 1 diabetes. We found that change in β-cell-specific effector memory CD8 T cells expressing CD57 was positively correlated with C-peptide change in subjects below 12 years of age. Autoreactive CD57+ effector memory CD8 T cells bore the signature of enhanced effector function (higher expression of granzyme B, killer specific protein 37 and CD16, and reduced expression of CD28) compared with their CD57-negative counterparts, and network association modelling indicated that the dynamics of β-cell-reactive CD57+ effector memory CD8 T cell subsets were strongly linked. Thus, coordinated changes in circulating β-cell-specific CD8 T cells within the CD57+ effector memory subset calibrate to functional insulin reserve in type 1 diabetes, providing a tool for immune monitoring and a mechanism-based target for immunotherapy.

Can We Repurpose FDA-Approved Alefacept to Diminish the HIV Reservoir?

PubMed Central

Zaidi, Asifa; Meng, Qinglai; Popkin, Daniel

2016-01-01

Current anti-retroviral treatment (ART) for HIV is effective in maintaining HIV at undetectable levels. However, cessation of ART results in immediate and brisk rebound of viremia to high levels. This rebound is driven by an HIV reservoir mainly enriched in memory CD4+ T cells. In order to provide any form of functional HIV Cure, elimination of this viral reservoir has become the focus of current HIV cure strategies. Alefacept was initially developed for the treatment of chronic plaque psoriasis. Alefacept is a chimeric fusion protein consisting of the CD2-binding portion of human leukocyte function antigen-3 (LFA3) linked to the Fc region of human IgG1 (LFA3-Fc). Alefacept was designed to inhibit memory T cell activation that contributes to the chronic autoimmune disease psoriasis by blocking the CD2 coreceptor. However, it was found to deplete memory T cells that express high levels of CD2 via NK cell-mediated antibody dependent cell cytotoxicity (ADCC) in vivo. Phase II and phase III clinical trials of alefacept with psoriasis patients demonstrated promising results and an excellent safety profile. Subsequently, alefacept has been successfully repurposed for other memory T cell-mediated autoimmune diseases including skin diseases other than psoriasis, organ transplantation and type I diabetes (T1D). Herein, we review our specific strategy to repurpose the FDA approved biologic alefacept to decrease and hopefully someday eliminate the HIV reservoir, for which CD2hi memory CD4+ T cells are a significant contributor. PMID:27110598

Si-Sb-Te materials for phase change memory applications.

PubMed

Rao, Feng; Song, Zhitang; Ren, Kun; Zhou, Xilin; Cheng, Yan; Wu, Liangcai; Liu, Bo

2011-04-08

Si-Sb-Te materials including Te-rich Si₂Sb₂Te₆ and Si(x)Sb₂Te₃ with different Si contents have been systemically studied with the aim of finding the most suitable Si-Sb-Te composition for phase change random access memory (PCRAM) use. Si(x)Sb₂Te₃ shows better thermal stability than Ge₂Sb₂Te₅ or Si₂Sb₂Te₆ in that Si(x)Sb₂Te₃ does not have serious Te separation under high annealing temperature. As Si content increases, the data retention ability of Si(x)Sb₂Te₃ improves. The 10 years retention temperature for Si₃Sb₂Te₃ film is ~393 K, which meets the long-term data storage requirements of automotive electronics. In addition, Si richer Si(x)Sb₂Te₃ films also show improvement on thickness change upon annealing and adhesion on SiO₂ substrate compared to those of Ge₂Sb₂Te₅ or Si₂Sb₂Te₆ films. However, the electrical performance of PCRAM cells based on Si(x)Sb₂Te₃ films with x > 3.5 becomes worse in terms of stable and long-term operations. Si(x)Sb₂Te₃ materials with 3 < x < 3.5 are proved to be suitable for PCRAM use to ensure good overall performance.

Neural Correlates of True and False Memory in Mild Cognitive Impairment

PubMed Central

Sweeney-Reed, Catherine M.; Riddell, Patricia M.; Ellis, Judi A.; Freeman, Jayne E.; Nasuto, Slawomir J.

2012-01-01

The goal of this research was to investigate the changes in neural processing in mild cognitive impairment. We measured phase synchrony, amplitudes, and event-related potentials in veridical and false memory to determine whether these differed in participants with mild cognitive impairment compared with typical, age-matched controls. Empirical mode decomposition phase locking analysis was used to assess synchrony, which is the first time this analysis technique has been applied in a complex cognitive task such as memory processing. The technique allowed assessment of changes in frontal and parietal cortex connectivity over time during a memory task, without a priori selection of frequency ranges, which has been shown previously to influence synchrony detection. Phase synchrony differed significantly in its timing and degree between participant groups in the theta and alpha frequency ranges. Timing differences suggested greater dependence on gist memory in the presence of mild cognitive impairment. The group with mild cognitive impairment had significantly more frontal theta phase locking than the controls in the absence of a significant behavioural difference in the task, providing new evidence for compensatory processing in the former group. Both groups showed greater frontal phase locking during false than true memory, suggesting increased searching when no actual memory trace was found. Significant inter-group differences in frontal alpha phase locking provided support for a role for lower and upper alpha oscillations in memory processing. Finally, fronto-parietal interaction was significantly reduced in the group with mild cognitive impairment, supporting the notion that mild cognitive impairment could represent an early stage in Alzheimer’s disease, which has been described as a ‘disconnection syndrome’. PMID:23118992

Understanding Phase-Change Memory Alloys from a Chemical Perspective

NASA Astrophysics Data System (ADS)

Kolobov, A. V.; Fons, P.; Tominaga, J.

2015-09-01

Phase-change memories (PCM) are associated with reversible ultra-fast low-energy crystal-to-amorphous switching in GeTe-based alloys co-existing with the high stability of the two phases at ambient temperature, a unique property that has been recently explained by the high fragility of the glass-forming liquid phase, where the activation barrier for crystallisation drastically increases as the temperature decreases from the glass-transition to room temperature. At the same time the atomistic dynamics of the phase-change process and the associated changes in the nature of bonding have remained unknown. In this work we demonstrate that key to this behavior is the formation of transient three-center bonds in the excited state that is enabled due to the presence of lone-pair electrons. Our findings additionally reveal previously ignored fundamental similarities between the mechanisms of reversible photoinduced structural changes in chalcogenide glasses and phase-change alloys and offer new insights into the development of efficient PCM materials.

Understanding Phase-Change Memory Alloys from a Chemical Perspective.

PubMed

Kolobov, A V; Fons, P; Tominaga, J

2015-09-01

Phase-change memories (PCM) are associated with reversible ultra-fast low-energy crystal-to-amorphous switching in GeTe-based alloys co-existing with the high stability of the two phases at ambient temperature, a unique property that has been recently explained by the high fragility of the glass-forming liquid phase, where the activation barrier for crystallisation drastically increases as the temperature decreases from the glass-transition to room temperature. At the same time the atomistic dynamics of the phase-change process and the associated changes in the nature of bonding have remained unknown. In this work we demonstrate that key to this behavior is the formation of transient three-center bonds in the excited state that is enabled due to the presence of lone-pair electrons. Our findings additionally reveal previously ignored fundamental similarities between the mechanisms of reversible photoinduced structural changes in chalcogenide glasses and phase-change alloys and offer new insights into the development of efficient PCM materials.

Mixed-Mode Operation of Hybrid Phase-Change Nanophotonic Circuits.

PubMed

Lu, Yegang; Stegmaier, Matthias; Nukala, Pavan; Giambra, Marco A; Ferrari, Simone; Busacca, Alessandro; Pernice, Wolfram H P; Agarwal, Ritesh

2017-01-11

Phase change materials (PCMs) are highly attractive for nonvolatile electrical and all-optical memory applications because of unique features such as ultrafast and reversible phase transitions, long-term endurance, and high scalability to nanoscale dimensions. Understanding their transient characteristics upon phase transition in both the electrical and the optical domains is essential for using PCMs in future multifunctional optoelectronic circuits. Here, we use a PCM nanowire embedded into a nanophotonic circuit to study switching dynamics in mixed-mode operation. Evanescent coupling between light traveling along waveguides and a phase-change nanowire enables reversible phase transition between amorphous and crystalline states. We perform time-resolved measurements of the transient change in both the optical transmission and resistance of the nanowire and show reversible switching operations in both the optical and the electrical domains. Our results pave the way toward on-chip multifunctional optoelectronic integrated devices, waveguide integrated memories, and hybrid processing applications.

Materials and methods for the preparation of nanocomposites

DOEpatents

Nag, Angshuman; Talapin, Dmitri V.

2018-01-30

Disclosed herein is an isolable colloidal particle comprising a nanoparticle and an inorganic capping agent bound to the surface of the nanoparticle, a method for making the same in a biphasic solvent mixture, and the formation of structures and solids from the isolable colloidal particle. The process can yield photovoltaic cells, piezoelectric crystals, thermoelectric layers, optoelectronic layers, light emitting diodes, ferroelectric layers, thin film transistors, floating gate memory devices, phase change layers, and sensor devices.

Induction of long term mucosal immunological memory in humans by an oral inactivated multivalent enterotoxigenic Escherichia coli vaccine.

PubMed

Lundgren, Anna; Jertborn, Marianne; Svennerholm, Ann-Mari

2016-06-08

We have evaluated the capacity of an oral multivalent enterotoxigenic Escherichia coli (ETEC) vaccine (MEV) to induce mucosal immunological memory. MEV consists of four inactivated E. coli strains over-expressing the major colonization factors (CFs) CFA/I, CS3, CS5 and CS6 and the LTB-related toxoid LCTBA. Memory responses were analyzed by comparing the magnitudes and kinetics of intestine-derived antibody-secreting cell responses to a single dose of MEV in three groups of adult Swedish volunteers (n=16-19 subjects per group) in a Phase I trial: non-immunized controls (I) and subjects who in a previous Phase I trial 13-23 months earlier had received two biweekly doses of MEV (II) or MEV+double mutant LT (dmLT) adjuvant (III). Responses against CFs and LTB were analyzed in antibodies in lymphocyte secretions (ALS) of blood mononuclear cells collected before (day 0) and 4/5 and 7 days after immunization. Specific circulating memory B cells present at the time of the single dose vaccination were also studied to determine if such cells may reflect mucosal memory. Considerably higher and significantly more frequent IgA ALS responses against all CFs and LTB were induced by the single vaccine dose in the previously immunized than in non-immunized volunteers. Furthermore, peak IgA ALS responses against all antigens were observed on days 4/5 in most of the previously immunized subjects whereas only a few previously non-vaccinated individuals responded before day 7. Priming with adjuvant did not influence memory responses. Circulating vaccine specific IgA memory B cells were not detected, whereas anti-toxin IgG memory B cells were identified 13-23 months after priming vaccination. We conclude that MEV induces functional mucosal immunological memory which remains at least 1-2 years. Furthermore, our results support that analysis of antibody-secreting cell responses after booster vaccination may be a useful approach to evaluate longstanding mucosal immunological memory in humans. ISRCTN27096290. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Physical principles and current status of emerging non-volatile solid state memories

NASA Astrophysics Data System (ADS)

Wang, L.; Yang, C.-H.; Wen, J.

2015-07-01

Today the influence of non-volatile solid-state memories on persons' lives has become more prominent because of their non-volatility, low data latency, and high robustness. As a pioneering technology that is representative of non-volatile solidstate memories, flash memory has recently seen widespread application in many areas ranging from electronic appliances, such as cell phones and digital cameras, to external storage devices such as universal serial bus (USB) memory. Moreover, owing to its large storage capacity, it is expected that in the near future, flash memory will replace hard-disk drives as a dominant technology in the mass storage market, especially because of recently emerging solid-state drives. However, the rapid growth of the global digital data has led to the need for flash memories to have larger storage capacity, thus requiring a further downscaling of the cell size. Such a miniaturization is expected to be extremely difficult because of the well-known scaling limit of flash memories. It is therefore necessary to either explore innovative technologies that can extend the areal density of flash memories beyond the scaling limits, or to vigorously develop alternative non-volatile solid-state memories including ferroelectric random-access memory, magnetoresistive random-access memory, phase-change random-access memory, and resistive random-access memory. In this paper, we review the physical principles of flash memories and their technical challenges that affect our ability to enhance the storage capacity. We then present a detailed discussion of novel technologies that can extend the storage density of flash memories beyond the commonly accepted limits. In each case, we subsequently discuss the physical principles of these new types of non-volatile solid-state memories as well as their respective merits and weakness when utilized for data storage applications. Finally, we predict the future prospects for the aforementioned solid-state memories for the next generation of data-storage devices based on a comparison of their performance. [Figure not available: see fulltext.

Episodic sequence memory is supported by a theta-gamma phase code.

PubMed

Heusser, Andrew C; Poeppel, David; Ezzyat, Youssef; Davachi, Lila

2016-10-01

The meaning we derive from our experiences is not a simple static extraction of the elements but is largely based on the order in which those elements occur. Models propose that sequence encoding is supported by interactions between high- and low-frequency oscillations, such that elements within an experience are represented by neural cell assemblies firing at higher frequencies (gamma) and sequential order is encoded by the specific timing of firing with respect to a lower frequency oscillation (theta). During episodic sequence memory formation in humans, we provide evidence that items in different sequence positions exhibit greater gamma power along distinct phases of a theta oscillation. Furthermore, this segregation is related to successful temporal order memory. Our results provide compelling evidence that memory for order, a core component of an episodic memory, capitalizes on the ubiquitous physiological mechanism of theta-gamma phase-amplitude coupling.

Artificial cognitive memory—changing from density driven to functionality driven

NASA Astrophysics Data System (ADS)

Shi, L. P.; Yi, K. J.; Ramanathan, K.; Zhao, R.; Ning, N.; Ding, D.; Chong, T. C.

2011-03-01

Increasing density based on bit size reduction is currently a main driving force for the development of data storage technologies. However, it is expected that all of the current available storage technologies might approach their physical limits in around 15 to 20 years due to miniaturization. To further advance the storage technologies, it is required to explore a new development trend that is different from density driven. One possible direction is to derive insights from biological counterparts. Unlike physical memories that have a single function of data storage, human memory is versatile. It contributes to functions of data storage, information processing, and most importantly, cognitive functions such as adaptation, learning, perception, knowledge generation, etc. In this paper, a brief review of current data storage technologies are presented, followed by discussions of future storage technology development trend. We expect that the driving force will evolve from density to functionality, and new memory modules associated with additional functions other than only data storage will appear. As an initial step toward building a future generation memory technology, we propose Artificial Cognitive Memory (ACM), a memory based intelligent system. We also present the characteristics of ACM, new technologies that can be used to develop ACM components such as bioinspired element cells (silicon, memristor, phase change, etc.), and possible methodologies to construct a biologically inspired hierarchical system.

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

NASA Astrophysics Data System (ADS)

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

2014-02-01

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

Projected phase-change memory devices.

PubMed

Koelmans, Wabe W; Sebastian, Abu; Jonnalagadda, Vara Prasad; Krebs, Daniel; Dellmann, Laurent; Eleftheriou, Evangelos

2015-09-03

Nanoscale memory devices, whose resistance depends on the history of the electric signals applied, could become critical building blocks in new computing paradigms, such as brain-inspired computing and memcomputing. However, there are key challenges to overcome, such as the high programming power required, noise and resistance drift. Here, to address these, we present the concept of a projected memory device, whose distinguishing feature is that the physical mechanism of resistance storage is decoupled from the information-retrieval process. We designed and fabricated projected memory devices based on the phase-change storage mechanism and convincingly demonstrate the concept through detailed experimentation, supported by extensive modelling and finite-element simulations. The projected memory devices exhibit remarkably low drift and excellent noise performance. We also demonstrate active control and customization of the programming characteristics of the device that reliably realize a multitude of resistance states.

Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation*

PubMed Central

Borovok, Natalia; Nesher, Elimelech; Levin, Yishai; Reichenstein, Michal; Pinhasov, Albert

2016-01-01

Spatial memory depends on the hippocampus, which is particularly vulnerable to aging. This vulnerability has implications for the impairment of navigation capacities in older people, who may show a marked drop in performance of spatial tasks with advancing age. Contemporary understanding of long-term memory formation relies on molecular mechanisms underlying long-term synaptic plasticity. With memory acquisition, activity-dependent changes occurring in synapses initiate multiple signal transduction pathways enhancing protein turnover. This enhancement facilitates de novo synthesis of plasticity related proteins, crucial factors for establishing persistent long-term synaptic plasticity and forming memory engrams. Extensive studies have been performed to elucidate molecular mechanisms of memory traces formation; however, the identity of plasticity related proteins is still evasive. In this study, we investigated protein turnover in mouse hippocampus during long-term spatial memory formation using the reference memory version of radial arm maze (RAM) paradigm. We identified 1592 proteins, which exhibited a complex picture of expression changes during spatial memory formation. Variable linear decomposition reduced significantly data dimensionality and enriched three principal factors responsible for variance of memory-related protein levels at (1) the initial phase of memory acquisition (165 proteins), (2) during the steep learning improvement (148 proteins), and (3) the final phase of the learning curve (123 proteins). Gene ontology and signaling pathways analysis revealed a clear correlation between memory improvement and learning phase-curbed expression profiles of proteins belonging to specific functional categories. We found differential enrichment of (1) neurotrophic factors signaling pathways, proteins regulating synaptic transmission, and actin microfilament during the first day of the learning curve; (2) transcription and translation machinery, protein trafficking, enhancement of metabolic activity, and Wnt signaling pathway during the steep phase of memory formation; and (3) cytoskeleton organization proteins. Taken together, this study clearly demonstrates dynamic assembly and disassembly of protein-protein interaction networks depending on the stage of memory formation engrams. PMID:26598641

Cell-Type-Specific Transcriptome Analysis in the Drosophila Mushroom Body Reveals Memory-Related Changes in Gene Expression.

PubMed

Crocker, Amanda; Guan, Xiao-Juan; Murphy, Coleen T; Murthy, Mala

2016-05-17

Learning and memory formation in Drosophila rely on a network of neurons in the mushroom bodies (MBs). Whereas numerous studies have delineated roles for individual cell types within this network in aspects of learning or memory, whether or not these cells can also be distinguished by the genes they express remains unresolved. In addition, the changes in gene expression that accompany long-term memory formation within the MBs have not yet been studied by neuron type. Here, we address both issues by performing RNA sequencing on single cell types (harvested via patch pipets) within the MB. We discover that the expression of genes that encode cell surface receptors is sufficient to identify cell types and that a subset of these genes, required for sensory transduction in peripheral sensory neurons, is not only expressed within individual neurons of the MB in the central brain, but is also critical for memory formation. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Electrical properties and transport mechanisms in phase change memory thin films of quasi-binary-line GeTe–Sb{sub 2}Te{sub 3} chalcogenide semiconductors

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

Sherchenkov, A. A.; Kozyukhin, S. A., E-mail: sergkoz@igic.ras.ru; Lazarenko, P. I.

The temperature dependences of the resistivity and current–voltage (I–V) characteristics of phase change memory thin films based on quasi-binary-line GeTe–Sb{sub 2}Te{sub 3} chalcogenide semiconductors Ge{sub 2}Sb{sub 2}Te{sub 5}, GeSb{sub 2}Te{sub 5}, and GeSb{sub 4}Te{sub 7} are investigated. The effect of composition variation along the quasibinary line on the electrical properties and transport mechanisms of the thin films is studied. The existence of three ranges with different I–V characteristics is established. The position and concentration of energy levels controlling carrier transport are estimated. The results obtained show that the electrical properties of the thin films can significantly change during a shiftmore » along the quasi-binary line GeTe–Sb{sub 2}Te{sub 3}, which is important for targeted optimization of the phase change memory technology.« less

AMPA Receptor Endocytosis in Rat Perirhinal Cortex Underlies Retrieval of Object Memory

ERIC Educational Resources Information Center

Cazakoff, Brittany N.; Howland, John G.

2011-01-01

Mechanisms consistent with long-term depression in the perirhinal cortex (PRh) play a fundamental role in object recognition memory; however, whether AMPA receptor endocytosis is involved in distinct phases of recognition memory is not known. To address this question, we used local PRh infusions of the cell membrane-permeable Tat-GluA2[subscript…

Metal-Insulator Transition Driven by Vacancy Ordering in GeSbTe Phase Change Materials.

PubMed

Bragaglia, Valeria; Arciprete, Fabrizio; Zhang, Wei; Mio, Antonio Massimiliano; Zallo, Eugenio; Perumal, Karthick; Giussani, Alessandro; Cecchi, Stefano; Boschker, Jos Emiel; Riechert, Henning; Privitera, Stefania; Rimini, Emanuele; Mazzarello, Riccardo; Calarco, Raffaella

2016-04-01

Phase Change Materials (PCMs) are unique compounds employed in non-volatile random access memory thanks to the rapid and reversible transformation between the amorphous and crystalline state that display large differences in electrical and optical properties. In addition to the amorphous-to-crystalline transition, experimental results on polycrystalline GeSbTe alloys (GST) films evidenced a Metal-Insulator Transition (MIT) attributed to disorder in the crystalline phase. Here we report on a fundamental advance in the fabrication of GST with out-of-plane stacking of ordered vacancy layers by means of three distinct methods: Molecular Beam Epitaxy, thermal annealing and application of femtosecond laser pulses. We assess the degree of vacancy ordering and explicitly correlate it with the MIT. We further tune the ordering in a controlled fashion attaining a large range of resistivity. Employing ordered GST might allow the realization of cells with larger programming windows.

Genetic Dissection of Aversive Associative Olfactory Learning and Memory in Drosophila Larvae

PubMed Central

Widmann, Annekathrin; Artinger, Marc; Biesinger, Lukas; Boepple, Kathrin; Schlechter, Jana; Selcho, Mareike; Thum, Andreas S.

2016-01-01

Memory formation is a highly complex and dynamic process. It consists of different phases, which depend on various neuronal and molecular mechanisms. In adult Drosophila it was shown that memory formation after aversive Pavlovian conditioning includes—besides other forms—a labile short-term component that consolidates within hours to a longer-lasting memory. Accordingly, memory formation requires the timely controlled action of different neuronal circuits, neurotransmitters, neuromodulators and molecules that were initially identified by classical forward genetic approaches. Compared to adult Drosophila, memory formation was only sporadically analyzed at its larval stage. Here we deconstruct the larval mnemonic organization after aversive olfactory conditioning. We show that after odor-high salt conditioning larvae form two parallel memory phases; a short lasting component that depends on cyclic adenosine 3’5’-monophosphate (cAMP) signaling and synapsin gene function. In addition, we show for the first time for Drosophila larvae an anesthesia resistant component, which relies on radish and bruchpilot gene function, protein kinase C activity, requires presynaptic output of mushroom body Kenyon cells and dopamine function. Given the numerical simplicity of the larval nervous system this work offers a unique prospect for studying memory formation of defined specifications, at full-brain scope with single-cell, and single-synapse resolution. PMID:27768692

Genetic Dissection of Aversive Associative Olfactory Learning and Memory in Drosophila Larvae.

PubMed

Widmann, Annekathrin; Artinger, Marc; Biesinger, Lukas; Boepple, Kathrin; Peters, Christina; Schlechter, Jana; Selcho, Mareike; Thum, Andreas S

2016-10-01

Memory formation is a highly complex and dynamic process. It consists of different phases, which depend on various neuronal and molecular mechanisms. In adult Drosophila it was shown that memory formation after aversive Pavlovian conditioning includes-besides other forms-a labile short-term component that consolidates within hours to a longer-lasting memory. Accordingly, memory formation requires the timely controlled action of different neuronal circuits, neurotransmitters, neuromodulators and molecules that were initially identified by classical forward genetic approaches. Compared to adult Drosophila, memory formation was only sporadically analyzed at its larval stage. Here we deconstruct the larval mnemonic organization after aversive olfactory conditioning. We show that after odor-high salt conditioning larvae form two parallel memory phases; a short lasting component that depends on cyclic adenosine 3'5'-monophosphate (cAMP) signaling and synapsin gene function. In addition, we show for the first time for Drosophila larvae an anesthesia resistant component, which relies on radish and bruchpilot gene function, protein kinase C activity, requires presynaptic output of mushroom body Kenyon cells and dopamine function. Given the numerical simplicity of the larval nervous system this work offers a unique prospect for studying memory formation of defined specifications, at full-brain scope with single-cell, and single-synapse resolution.

Abortive T Follicular Helper Development Is Associated with a Defective Humoral Response in Leishmania infantum-Infected Macaques

PubMed Central

Rodrigues, Vasco; Laforge, Mireille; Campillo-Gimenez, Laure; Soundaramourty, Calaiselvy; Correia-de-Oliveira, Ana; Dinis-Oliveira, Ricardo Jorge; Ouaissi, Ali; Cordeiro-da-Silva, Anabela; Silvestre, Ricardo; Estaquier, Jérôme

2014-01-01

Leishmania infantum causes a chronic infectious disease named visceral leishmaniasis (VL). We employed a non-human primate model to monitor immune parameters over time and gain new insights into the disease. Rhesus macaques were infected with L. infantum and the T helper and B cell immunological profiles characterized during acute and chronic phases of infection. Parasite detection in visceral compartments during the acute phase was associated with differentiation of effector memory CD4 T cells and increased levels of Th1 transcripts. At the chronic phase, parasites colonized novel lymphoid niches concomitant with increased expression of IL10. Despite the occurrence of hypergammaglobulinemia, the production of parasite-specific IgG was poor, being confined to the acute phase and positively correlated with the frequency of an activated memory splenic B cell population. We noticed the expansion of a splenic CD4 T cell population expressing CXCR5 and Bcl-6 during acute infection that was associated with the differentiation of the activated memory B cell population. Moreover, the number of splenic germinal centers peaked at one month after infection, hence paralleling the production of specific IgG. However, at chronic infection these populations contracted impacting the production of parasite-specific IgG. Our study provides new insights into the immune events taking place in a physiologically relevant host and a mechanistic basis for the inefficient humoral response during VL. PMID:24763747

ROLE OF NEUROTRANSMITTERS AND PROTEIN SYNTHESIS IN SHORT- AND LONG-TERM MEMORY

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

Bennett, E.L.; Rosenzweig, M.R.; Flood, J.F.

1978-10-01

Anisomycin is an effective inhibitor of cerebral protein synthesis in mice and is also an effective amnestic agent for both passive and active behavioral tasks. From use of anisomycin in combination with a variety of stimulant and depressant drugs, we conclude that the level of arousal following acquisition plays an important role in determining the duration and the rate of the biosynthetic phase of memory formation. While we have interpreted the experiments with anisomycin as evidence for an essential role of protein in memory storage, others have suggested that side effects of inhibitors of protein synthesis on catecholamine metabolism aremore » the main cause of amnesia. Several experiments were therefore done to compare the effects of anisemycin and catecholamine inhibitors on memory. We conclude that anisomycin's principal amnestic mechanism does not involve inhibition of the catecholamine system. The results strengthen our conclusion that protein synthesis is an essential component for longterm memory trace formation. Also, it is suggested that proteins synthesized in the neuronal cell body are used, in conjunction with other molecules, to produce permanent and semi-permanent anatomical changes.« less

Threshold switching in SiGeAsTeN chalcogenide glass prepared by As ion implantation into sputtered SiGeTeN film

NASA Astrophysics Data System (ADS)

Liu, Guangyu; Wu, Liangcai; Song, Zhitang; Liu, Yan; Li, Tao; Zhang, Sifan; Song, Sannian; Feng, Songlin

2017-12-01

A memory cell composed of a selector device and a storage device is the basic unit of phase change memory. The threshold switching effect, main principle of selectors, is a universal phenomenon in chalcogenide glasses. In this work, we put forward a safe and controllable method to prepare a SiGeAsTeN chalcogenide film by implanting As ions into sputtered SiGeTeN films. For the SiGeAsTeN material, the phase structure maintains the amorphous state, even at high temperature, indicating that no phase transition occurs for this chalcogenide-based material. The electrical test results show that the SiGeAsTeN-based devices exhibit good threshold switching characteristics and the switching voltage decreases with the increasing As content. The decrease in valence alternation pairs, reducing trap state density, may be the physical mechanism for lower switch-on voltage, which makes the SiGeAsTeN material more applicable in selector devices through component optimization.

How Polycomb-Mediated Cell Memory Deals With a Changing Environment: Variations in PcG complexes and proteins assortment convey plasticity to epigenetic regulation as a response to environment.

PubMed

Marasca, Federica; Bodega, Beatrice; Orlando, Valerio

2018-04-01

Cells and tissues are continuously exposed to a changing microenvironment, hence the necessity of a flexible modulation of gene expression that in complex organism have been achieved through specialized chromatin mechanisms. Chromatin-based cell memory enables cells to maintain their identity by fixing lineage specific transcriptional programs, ensuring their faithful transmission through cell division; in particular PcG-based memory system evolved to maintain the silenced state of developmental and cell cycle genes. In evolution the complexity of this system have increased, particularly in vertebrates, indicating combinatorial and dynamic properties of Polycomb proteins, in some cases even overflowing outside the cell nucleus. Therefore, their function may not be limited to the imposition of rigid states of genetic programs, but on the ability to recognize signals and allow plastic transcriptional changes in response to different stimuli. Here, we discuss the most novel PcG mediated memory functions in facing and responding to the challenges posed by a fluctuating environment. © 2018 The Authors. BioEssays Published by WILEY Periodicals, Inc.

Anomalous Phase Change in [(GeTe)2/(Sb2Te3)]20 Superlattice Observed by Coherent Phonon Spectroscopy

NASA Astrophysics Data System (ADS)

Makino, K.; Saito, Y.; Mitrofanov, K.; Tominaga, J.; Kolobov, A. V.; Nakano, T.; Fons, P.; Hase, M.

The temperature-dependent ultrafast coherent phonon dynamics of topological (GeTe)2/(Sb2Te3) super lattice phase change memory material was investigated. By comparing with Ge-Sb-Te alloy, a clear contrast suggesting the unique phase change behavior was found.

Multilevel control of the metastable states in a manganite film

NASA Astrophysics Data System (ADS)

Jin, Feng; Feng, Qiyuan; Guo, Zhuang; Lan, Da; Chen, Binbin; Xu, Haoran; Wang, Ze; Wang, Lingfei; Gao, Guanyin; Chen, Feng; Lu, Qingyou; Wu, Wenbin

2017-06-01

For high density memory applications, the dynamic switching between multilevel resistance states per cell is highly desirable, and for oxide-based memory devices, the multistate operation has been actively explored. We have previously shown that for La2/3Ca1/3MnO3 films, the antiferromagnetic charge-ordered-insulator (COI) phase can be induced via the anisotropic epitaxial strain, and it competes with the doping-determined ferromagnetic-metal (FMM) ground state in a wide temperature range. Here, we show that for the phase competitions, in various magnetic fields and/or thermal cycling, the reappearance of the COI phase and thus the resistance and magnetization can be manipulated and quantified in a multilevel manner at lower temperatures. Furthermore, by using a high-field magnetic force microscope, we image the COI/FMM domain structures in accordance with the transport measurements, and find that the evolving domains or the phase fraction ratios do underline the metastability of the reappeared COI droplets, possibly protected by the energy barriers due to accommodation strain. These results may add new insights into the design and fabrication of future multilevel memory cells.

A phase code for memory could arise from circuit mechanisms in entorhinal cortex

PubMed Central

Hasselmo, Michael E.; Brandon, Mark P.; Yoshida, Motoharu; Giocomo, Lisa M.; Heys, James G.; Fransen, Erik; Newman, Ehren L.; Zilli, Eric A.

2009-01-01

Neurophysiological data reveals intrinsic cellular properties that suggest how entorhinal cortical neurons could code memory by the phase of their firing. Potential cellular mechanisms for this phase coding in models of entorhinal function are reviewed. This mechanism for phase coding provides a substrate for modeling the responses of entorhinal grid cells, as well as the replay of neural spiking activity during waking and sleep. Efforts to implement these abstract models in more detailed biophysical compartmental simulations raise specific issues that could be addressed in larger scale population models incorporating mechanisms of inhibition. PMID:19656654

Memory for environmental sounds in sighted, congenitally blind and late blind adults: evidence for cross-modal compensation.

PubMed

Röder, Brigitte; Rösler, Frank

2003-10-01

Several recent reports suggest compensatory performance changes in blind individuals. It has, however, been argued that the lack of visual input leads to impoverished semantic networks resulting in the use of data-driven rather than conceptual encoding strategies on memory tasks. To test this hypothesis, congenitally blind and sighted participants encoded environmental sounds either physically or semantically. In the recognition phase, both conceptually as well as physically distinct and physically distinct but conceptually highly related lures were intermixed with the environmental sounds encountered during study. Participants indicated whether or not they had heard a sound in the study phase. Congenitally blind adults showed elevated memory both after physical and semantic encoding. After physical encoding blind participants had lower false memory rates than sighted participants, whereas the false memory rates of sighted and blind participants did not differ after semantic encoding. In order to address the question if compensatory changes in memory skills are restricted to critical periods during early childhood, late blind adults were tested with the same paradigm. When matched for age, they showed similarly high memory scores as the congenitally blind. These results demonstrate compensatory performance changes in long-term memory functions due to the loss of a sensory system and provide evidence for high adaptive capabilities of the human cognitive system.

Thermomechanical behavior of shape memory elastomeric composites

NASA Astrophysics Data System (ADS)

Ge, Qi; Luo, Xiaofan; Rodriguez, Erika D.; Zhang, Xiao; Mather, Patrick T.; Dunn, Martin L.; Qi, H. Jerry

2012-01-01

Shape memory polymers (SMPs) can fix a temporary shape and recover their permanent shape in response to environmental stimuli such as heat, electricity, or irradiation. Most thermally activated SMPs use the macromolecular chain mobility change around the glass transition temperature ( Tg) to achieve the shape memory (SM) effects. During this process, the stiffness of the material typically changes by three orders of magnitude. Recently, a composite materials approach was developed to achieve thermally activated shape memory effect where the material exhibits elastomeric response in both the temporary and the recovered configurations. These shape memory elastomeric composites (SMECs) consist of an elastomeric matrix reinforced by a semicrystalline polymer fiber network. The matrix provides background rubber elasticity while the fiber network can transform between solid crystals and melt phases over the operative temperature range. As such it serves as a reversible "switching phase" that enables shape fixing and recovery. Shape memory elastomeric composites provide a new paradigm for the development of a wide array of active polymer composites that utilize the melt-crystal transition to achieve the shape memory effect. This potentially allows for material systems with much simpler chemistries than most shape memory polymers and thus can facilitate more rapid material development and insertion. It is therefore important to understand the thermomechanical behavior and to develop corresponding material models. In this paper, a 3D finite-deformation constitutive modeling framework was developed to describe the thermomechanical behavior of SMEC. The model is phenomenological, although inspired by micromechanical considerations of load transfer between the matrix and fiber phases of a composite system. It treats the matrix as an elastomer and the fibers as a complex solid that itself is an aggregate of melt and crystal phases that evolve from one to the other during a temperature change. As such, the composite consists of an elastomer reinforced by a soft liquid at high temperature and a stiff solid at low temperature. The model includes a kinetic description of the non-isothermal crystallization and melting of the fibers during a temperature change. As the fibers transform from melt to crystal during cooling it is assumed that new crystals are formed in an undeformed state, which requires careful tracking of the kinematics of the evolving phases which comes at a significant computational cost. In order to improve the computational efficiency, an effective phase model (EPM) is adopted to treat the evolving crystal phases as an effective medium. A suite of careful thermomechanical experiments with a SMEC was carried out to calibrate various model parameters, and then to demonstrate the ability of the model to accurately capture the shape memory behavior of the SMEC system during complex thermomechanical loading scenarios. The model also identifies the effects of microstructural design parameters such as the fiber volume fraction.

Motor cortical encoding of serial order in a context-recall task.

PubMed

Carpenter, A F; Georgopoulos, A P; Pellizzer, G

1999-03-12

The neural encoding of serial order was studied in the motor cortex of monkeys performing a context-recall memory scanning task. Up to five visual stimuli were presented successively on a circle (list presentation phase), and then one of them (test stimulus) changed color; the monkeys had to make a single motor response toward the stimulus that immediately followed the test stimulus in the list. Correct performance in this task depends on memorization of the serial order of the stimuli during their presentation. It was found that changes in neural activity during the list presentation phase reflected the serial order of the stimuli; the effect on cell activity of the serial order of stimuli during their presentation was at least as strong as the effect of motor direction on cell activity during the execution of the motor response. This establishes the serial order of stimuli in a motor task as an important determinant of motor cortical activity during stimulus presentation and in the absence of changes in peripheral motor events, in contrast to the commonly held view of the motor cortex as just an "upper motor neuron."

Changes in heart rate variability are associated with expression of short-term and long-term contextual and cued fear memories.

PubMed

Liu, Jun; Wei, Wei; Kuang, Hui; Zhao, Fang; Tsien, Joe Z

2013-01-01

Heart physiology is a highly useful indicator for measuring not only physical states, but also emotional changes in animals. Yet changes of heart rate variability during fear conditioning have not been systematically studied in mice. Here, we investigated changes in heart rate and heart rate variability in both short-term and long-term contextual and cued fear conditioning. We found that while fear conditioning could increase heart rate, the most significant change was the reduction in heart rate variability which could be further divided into two distinct stages: a highly rhythmic phase (stage-I) and a more variable phase (stage-II). We showed that the time duration of the stage-I rhythmic phase were sensitive enough to reflect the transition from short-term to long-term fear memories. Moreover, it could also detect fear extinction effect during the repeated tone recall. These results suggest that heart rate variability is a valuable physiological indicator for sensitively measuring the consolidation and expression of fear memories in mice.

Chronic Dry Eye Disease is Principally Mediated by Effector Memory Th17 Cells

PubMed Central

Chen, Yihe; Chauhan, Sunil K.; Lee, Hyun Soo; Saban, Daniel R.; Dana, Reza

2013-01-01

Recent experimental and clinical data suggest that there is a link between dry eye disease (DED) and T cell-mediated immunity. However, whether these immune responses are a consequence or cause of ocular surface inflammation remains to be determined. Thus far, only models of acute DED have been used to derive experimental data. This is in contrast to clinical DED which usually presents as a chronic disease. In the present study, using a murine model of chronic DED, it was established that the chronic phase of the disease is accompanied by Th17 responses at the ocular surface, and that a significant memory T cell population can be recovered from chronic DED. This memory response is predominantly mediated by Th17 cells. Moreover, adoptive transfer of this memory T cell population was shown to induce more severe and rapidly progressing DED than did the adoptive transfer of its effector or naïve counterparts. Not only do these results clearly demonstrate that effector memory Th17 cells are primarily responsible for maintaining the chronic and relapsing course of DED, but they also highlight a potentially novel therapeutic strategy for targeting memory immune responses in patients with DED. PMID:23571503

A Combined Omics Approach to Generate the Surface Atlas of Human Naive CD4+ T Cells during Early T-Cell Receptor Activation*

PubMed Central

Graessel, Anke; Hauck, Stefanie M.; von Toerne, Christine; Kloppmann, Edda; Goldberg, Tatyana; Koppensteiner, Herwig; Schindler, Michael; Knapp, Bettina; Krause, Linda; Dietz, Katharina; Schmidt-Weber, Carsten B.; Suttner, Kathrin

2015-01-01

Naive CD4+ T cells are the common precursors of multiple effector and memory T-cell subsets and possess a high plasticity in terms of differentiation potential. This stem-cell-like character is important for cell therapies aiming at regeneration of specific immunity. Cell surface proteins are crucial for recognition and response to signals mediated by other cells or environmental changes. Knowledge of cell surface proteins of human naive CD4+ T cells and their changes during the early phase of T-cell activation is urgently needed for a guided differentiation of naive T cells and may support the selection of pluripotent cells for cell therapy. Periodate oxidation and aniline-catalyzed oxime ligation technology was applied with subsequent quantitative liquid chromatography-tandem MS to generate a data set describing the surface proteome of primary human naive CD4+ T cells and to monitor dynamic changes during the early phase of activation. This led to the identification of 173 N-glycosylated surface proteins. To independently confirm the proteomic data set and to analyze the cell surface by an alternative technique a systematic phenotypic expression analysis of surface antigens via flow cytometry was performed. This screening expanded the previous data set, resulting in 229 surface proteins, which were expressed on naive unstimulated and activated CD4+ T cells. Furthermore, we generated a surface expression atlas based on transcriptome data, experimental annotation, and predicted subcellular localization, and correlated the proteomics result with this transcriptional data set. This extensive surface atlas provides an overall naive CD4+ T cell surface resource and will enable future studies aiming at a deeper understanding of mechanisms of T-cell biology allowing the identification of novel immune targets usable for the development of therapeutic treatments. PMID:25991687

Advances in memory research: single-neuron recordings from the human medial temporal lobe aid our understanding of declarative memory.

PubMed

Viskontas, Indre V

2008-12-01

To gain a complete understanding of how the brain functions, both in illness and good health, data from multiple levels of analysis must be integrated. Technical advances have made direct recordings of neuronal activity deep inside the human brain tractable, providing a rare glimpse into cellular processes during long-term memory formation. Recent findings using intracranial recordings in the medial temporal lobe inform current neural network models of memory, and may lead to a more comprehensive understanding of the neural basis of memory-related processes. These recordings have shown that cells in the hippocampus appear to support declarative learning by distinguishing novel and familiar stimuli via changes in firing patterns. Some cells with highly selective and invariant responses have also been described, and these responses seem to represent abstract concepts such as identity, rather than superficial perceptual features of items. Importantly, however, both selective and globally responsive cells are capable of changing their preferred stimulus depending on the conscious demands of the task. Firing patterns of human medial temporal lobe neurons indicate that cells can be both plastic and stable in terms of the information that they code; although some cells show highly selective and reproducible excitatory responses when presented with a familiar object, other cells change their receptive fields in line with changes in experience and the cognitive environment.

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. © 2015 Shakya et al.

Oct1 and OCA-B are selectively required for CD4 memory T cell function

PubMed Central

Shakya, Arvind; Goren, Alon; Shalek, Alex; German, Cody N.; Snook, Jeremy; Kuchroo, Vijay K.; Yosef, Nir; Chan, Raymond C.; Regev, Aviv

2015-01-01

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. PMID:26481684

Sex and menstrual cycle phase at encoding influence emotional memory for gist and detail

PubMed Central

Nielsen, Shawn E.; Ahmed, Imran; Cahill, Larry

2013-01-01

Sex influences on emotional memory have received increasing interest over the past decade. However, only a subset of this previous work explored the influence of sex on memory for central information (gist) and peripheral detail in emotional versus neutral contexts. Here we examined the influence of sex and menstrual cycle phase at encoding on memory for either an emotional or neutral story, specifically with respect to the retention of gist and peripheral detail. Healthy naturally cycling women and men viewed a brief, narrated, three-phase story containing neutral or emotionally arousing elements. One week later, participants received a surprise free recall test for story elements. The results indicate that naturally cycling women in the luteal (high hormone) phase of the menstrual cycle at encoding show enhanced memory for peripheral details, but not gist, when in the emotional compared with neutral stories (p<.05). In contrast, naturally cycling women in the follicular (low hormone) phase of the menstrual cycle at encoding did not show enhanced memory for gist or peripheral details in the emotional compared with neutral stories. Men show enhanced memory for gist, but not peripheral details, in the emotional versus neutral stories (p<.05). In addition, these sex influences on memory cannot be attributed to differences in attention or arousal; luteal women, follicular women, and men performed similarly on measures of attention (fixation time percentage) and arousal (pupil diameter changes) during the most arousing phase of the emotional story. These findings suggest that sex and menstrual cycle phase at encoding influence long term memory for different types of emotional information. PMID:23891713

Theoretical potential for low energy consumption phase change memory utilizing electrostatically-induced structural phase transitions in 2D materials

NASA Astrophysics Data System (ADS)

Rehn, Daniel A.; Li, Yao; Pop, Eric; Reed, Evan J.

2018-01-01

Structural phase-change materials are of great importance for applications in information storage devices. Thermally driven structural phase transitions are employed in phase-change memory to achieve lower programming voltages and potentially lower energy consumption than mainstream nonvolatile memory technologies. However, the waste heat generated by such thermal mechanisms is often not optimized, and could present a limiting factor to widespread use. The potential for electrostatically driven structural phase transitions has recently been predicted and subsequently reported in some two-dimensional materials, providing an athermal mechanism to dynamically control properties of these materials in a nonvolatile fashion while achieving potentially lower energy consumption. In this work, we employ DFT-based calculations to make theoretical comparisons of the energy required to drive electrostatically-induced and thermally-induced phase transitions. Determining theoretical limits in monolayer MoTe2 and thin films of Ge2Sb2Te5, we find that the energy consumption per unit volume of the electrostatically driven phase transition in monolayer MoTe2 at room temperature is 9% of the adiabatic lower limit of the thermally driven phase transition in Ge2Sb2Te5. Furthermore, experimentally reported phase change energy consumption of Ge2Sb2Te5 is 100-10,000 times larger than the adiabatic lower limit due to waste heat flow out of the material, leaving the possibility for energy consumption in monolayer MoTe2-based devices to be orders of magnitude smaller than Ge2Sb2Te5-based devices.

Hierarchically Self-Assembled Block Copolymer Blends for Templating Hollow Phase-Change Nanostructures with an Extremely Low Switching Current

DOE PAGES

Park, Woon Ik; Kim, Jong Min; Jeong, Jae Won; ...

2015-03-17

Phase change memory (PCM) is one of the most promising candidates for next-generation nonvolatile memory devices because of its high speed, excellent reliability, and outstanding scalability. But, the high switching current of PCM devices has been a critical hurdle to realize low-power operation. Although one solution is to reduce the switching volume of the memory, the resolution limit of photolithography hinders further miniaturization of device dimensions. Here, we employed unconventional self-assembly geometries obtained from blends of block copolymers (BCPs) to form ring-shaped hollow PCM nanostructures with an ultrasmall contact area between a phase-change material (Ge 2Sb 2Te 5) and amore » heater (TiN) electrode. The high-density (approximately 0.1 terabits per square inch) PCM nanoring arrays showed extremely small switching current of 2-3 mu A. Furthermore, the relatively small reset current of the ring-shaped PCM compared to the pillar-shaped devices is attributed to smaller switching volume, which is well supported by electro-thermal simulation results. Our approach may also be extended to other nonvolatile memory device applications such as resistive switching memory and magnetic storage devices, where the control of nanoscale geometry can significantly affect device performances.« less

Identification and Manipulation of Memory Engram Cells.

PubMed

Liu, Xu; Ramirez, Steve; Redondo, Roger L; Tonegawa, Susumu

2014-01-01

How memories are formed and stored in the brain remains a fascinating question in neuroscience. Here we discuss the memory engram theory, our recent attempt to identify and manipulate memory engram cells in the brain with optogenetics, and how these methods are used to address questions such as how false memory is formed and how the valence of a memory can be changed in the brain. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

The Respiratory Environment Diverts the Development of Antiviral Memory CD8 T Cells.

PubMed

Shane, Hillary L; Reagin, Katie L; Klonowski, Kimberly D

2018-06-01

Our understanding of memory CD8 + T cells has been largely derived from acute, systemic infection models. However, memory CD8 + T cells generated from mucosal infection exhibit unique properties and, following respiratory infection, are not maintained in the lung long term. To better understand how infection route modifies memory differentiation, we compared murine CD8 + T cell responses to a vesicular stomatitis virus (VSV) challenge generated intranasally (i.n.) or i.v. The i.n. infection resulted in greater peak expansion of VSV-specific CD8 + T cells. However, this numerical advantage was rapidly lost during the contraction phase of the immune response, resulting in memory CD8 + T cell numerical deficiencies when compared with i.v. infection. Interestingly, the antiviral CD8 + T cells generated in response to i.n. VSV exhibited a biased and sustained proportion of early effector cells (CD127 lo KLRG1 lo ) akin to the developmental program favored after i.n. influenza infection, suggesting that respiratory infection broadly favors an incomplete memory differentiation program. Correspondingly, i.n. VSV infection resulted in lower CD122 expression and eomesodermin levels by VSV-specific CD8 + T cells, further indicative of an inferior transition to bona fide memory. These results may be due to distinct (CD103 + CD11b + ) dendritic cell subsets in the i.n. versus i.v. T cell priming environments, which express molecules that regulate T cell signaling and the balance between tolerance and immunity. Therefore, we propose that distinct immunization routes modulate both the quality and quantity of antiviral effector and memory CD8 + T cells in response to an identical pathogen and should be considered in CD8 + T cell-based vaccine design. Copyright © 2018 by The American Association of Immunologists, Inc.

GABAergic contributions to gating, timing, and phase precession of hippocampal neuronal activity during theta oscillations.

PubMed

Cutsuridis, Vassilis; Hasselmo, Michael

2012-07-01

Successful spatial exploration requires gating, storage, and retrieval of spatial memories in the correct order. The hippocampus is known to play an important role in the temporal organization of spatial information. Temporally ordered spatial memories are encoded and retrieved by the firing rate and phase of hippocampal pyramidal cells and inhibitory interneurons with respect to ongoing network theta oscillations paced by intra- and extrahippocampal areas. Much is known about the anatomical, physiological, and molecular characteristics as well as the connectivity and synaptic properties of various cell types in the hippocampal microcircuits, but how these detailed properties of individual neurons give rise to temporal organization of spatial memories remains unclear. We present a model of the hippocampal CA1 microcircuit based on observed biophysical properties of pyramidal cells and six types of inhibitory interneurons: axo-axonic, basket, bistratistified, neurogliaform, ivy, and oriens lacunosum-moleculare cells. The model simulates a virtual rat running on a linear track. Excitatory transient inputs come from the entorhinal cortex (EC) and the CA3 Schaffer collaterals and impinge on both the pyramidal cells and inhibitory interneurons, whereas inhibitory inputs from the medial septum impinge only on the inhibitory interneurons. Dopamine operates as a gate-keeper modulating the spatial memory flow to the PC distal dendrites in a frequency-dependent manner. A mechanism for spike-timing-dependent plasticity in distal and proximal PC dendrites consisting of three calcium detectors, which responds to the instantaneous calcium level and its time course in the dendrite, is used to model the plasticity effects. The model simulates the timing of firing of different hippocampal cell types relative to theta oscillations, and proposes functional roles for the different classes of the hippocampal and septal inhibitory interneurons in the correct ordering of spatial memories as well as in the generation and maintenance of theta phase precession of pyramidal cells (place cells) in CA1. The model leads to a number of experimentally testable predictions that may lead to a better understanding of the biophysical computations in the hippocampus and medial septum. Copyright © 2011 Wiley Periodicals, Inc.

Materials and methods for the preparation of nanocomposites

DOEpatents

Talapin, Dmitri V.; Kovalenko, Maksym V.; Lee, Jong-Soo; Jiang, Chengyang

2016-05-24

Disclosed herein is an isolable colloidal particle comprising a nanoparticle and an inorganic capping agent bound to the surface of the nanoparticle, a solution of the same, a method for making the same from a biphasic solvent mixture, and the formation of structures and solids from the isolable colloidal particle. The process can yield photovoltaic cells, piezoelectric crystals, thermoelectric layers, optoelectronic layers, light emitting diodes, ferroelectric layers, thin film transistors, floating gate memory devices, imaging devices, phase change layers, and sensor devices.

Role of mechanical stress in the resistance drift of Ge2Sb2Te5 films and phase change memories

NASA Astrophysics Data System (ADS)

Rizzi, M.; Spessot, A.; Fantini, P.; Ielmini, D.

2011-11-01

In a phase change memory (PCM), the device resistance increases slowly with time after the formation of the amorphous phase, thus affecting the stability of stored data. This work investigates the resistance drift in thin films of amorphous Ge2Sb2Te5 and in PCMs, demonstrating a common kinetic of drift in stressed/unstressed films and in the nanometer-size active volume of a PCM with different stress levels developed via stressor layers. It is concluded that stress is not the root cause of PCM drift, which is instead attributed to intrinsic structural relaxation due to the disordered, metastable nature of the amorphous chalcogenide phase.

Low-Energy Amorphization of Ti1Sb2Te5 Phase Change Alloy Induced by TiTe2 Nano-Lamellae

PubMed Central

Ding, Keyuan; Rao, Feng; Lv, Shilong; Cheng, Yan; Wu, Liangcai; Song, Zhitang

2016-01-01

Increasing SET operation speed and reducing RESET operation energy have always been the innovation direction of phase change memory (PCM) technology. Here, we demonstrate that ∼87% and ∼42% reductions of RESET operation energy can be achieved on PCM cell based on stoichiometric Ti1Sb2Te5 alloy, compared with Ge2Sb2Te5 and non-stoichiometric Ti0.4Sb2Te3 based PCM cells at the same size, respectively. The Ti1Sb2Te5 based PCM cell also shows one order of magnitude faster SET operation speed compared to that of the Ge2Sb2Te5 based one. The enhancements may be caused by substantially increased concentration of TiTe2 nano-lamellae in crystalline Ti1Sb2Te5 phase. The highly electrical conduction and lowly thermal dissipation of the TiTe2 nano-lamellae play a major role in enhancing the thermal efficiency of the amorphization, prompting the low-energy RESET operation. Our work may inspire the interests to more thorough understanding and tailoring of the nature of the (TiTe2)n(Sb2Te3)m pseudobinary system which will be advantageous to realize high-speed and low-energy PCM applications. PMID:27469931

Low-Energy Amorphization of Ti1Sb2Te5 Phase Change Alloy Induced by TiTe2 Nano-Lamellae.

PubMed

Ding, Keyuan; Rao, Feng; Lv, Shilong; Cheng, Yan; Wu, Liangcai; Song, Zhitang

2016-07-29

Increasing SET operation speed and reducing RESET operation energy have always been the innovation direction of phase change memory (PCM) technology. Here, we demonstrate that ∼87% and ∼42% reductions of RESET operation energy can be achieved on PCM cell based on stoichiometric Ti1Sb2Te5 alloy, compared with Ge2Sb2Te5 and non-stoichiometric Ti0.4Sb2Te3 based PCM cells at the same size, respectively. The Ti1Sb2Te5 based PCM cell also shows one order of magnitude faster SET operation speed compared to that of the Ge2Sb2Te5 based one. The enhancements may be caused by substantially increased concentration of TiTe2 nano-lamellae in crystalline Ti1Sb2Te5 phase. The highly electrical conduction and lowly thermal dissipation of the TiTe2 nano-lamellae play a major role in enhancing the thermal efficiency of the amorphization, prompting the low-energy RESET operation. Our work may inspire the interests to more thorough understanding and tailoring of the nature of the (TiTe2)n(Sb2Te3)m pseudobinary system which will be advantageous to realize high-speed and low-energy PCM applications.

Preparation and characterization of Sb2Se3 devices for memory applications

NASA Astrophysics Data System (ADS)

Shylashree, N.; Uma B., V.; Dhanush, S.; Abachi, Sagar; Nisarga, A.; Aashith, K.; Sangeetha B., G.

2018-05-01

In this paper, A phase change material of Sb2Se3 was proposed for non volatile memory application. The thin film device preparation and characterization were carried out. The deposition method used was vapor evaporation technique and a thickness of 180nm was deposited. The switching between the SET and RESET state is shown by the I-V characterization. The change of phase was studied using R-V characterization. Different fundamental modes were also identified using Raman spectroscopy.

Liking and Memory for Musical Stimuli as a Function of Exposure

ERIC Educational Resources Information Center

Szpunar, Karl K.; Schellenberg, E. Glenn; Pliner, Patricia

2004-01-01

Three experiments examined changes in liking and memory for music as a function of number of previous exposures, the ecological validity of the music, and whether the exposure phase required focused or incidental listening. After incidental listening, liking ratings were higher for music heard more often in the exposure phase and this association…

Microscopic origin of resistance drift in the amorphous state of the phase-change compound GeTe

NASA Astrophysics Data System (ADS)

Gabardi, S.; Caravati, S.; Sosso, G. C.; Behler, J.; Bernasconi, M.

2015-08-01

Aging is a common feature of the glassy state. In the case of phase-change chalcogenide alloys the aging of the amorphous state is responsible for an increase of the electrical resistance with time. This phenomenon called drift is detrimental in the application of these materials in phase-change nonvolatile memories, which are emerging as promising candidates for storage class memories. By means of combined molecular dynamics and electronic structure calculations based on density functional theory, we have unraveled the atomistic origin of the resistance drift in the prototypical phase-change compound GeTe. The drift results from a widening of the band gap and a reduction of Urbach tails due to structural relaxations leading to the removal of chains of Ge-Ge homopolar bonds. The same structural features are actually responsible for the high mobility above the glass transition which boosts the crystallization speed exploited in the device.

Effects of germanium and nitrogen incorporation on crystallization of N-doped Ge2+xSb2Te5 (x = 0,1) thin films for phase-change memory

NASA Astrophysics Data System (ADS)

Cheng, Limin; Wu, Liangcai; Song, Zhitang; Rao, Feng; Peng, Cheng; Yao, Dongning; Liu, Bo; Xu, Ling

2013-01-01

The phase-change behavior and microstructure changes of N-doped Ge3Sb2Te5 [N-GST(3/2/5)] and Ge2Sb2Te5 [GST(2/2/5)] films during the phase transition from an amorphous to a crystalline phase were studied using in situ temperature-dependent sheet resistance measurements, X-ray diffraction, and transmission electron microscopy. The optical band gaps of N-GST(3/2/5) films are higher than that of GST(2/2/5) film in both the amorphous and face-centered-cubic (fcc) phases. Ge nitride formation by X-ray photoelectron spectroscopy analysis increased the optical band gap and suppressed crystalline grain growth, resulting in an increase in the crystallization temperature and resistance in the fcc phase. As a result, the Ge- and N-doped GST(2/2/5) composite films can be considered as a promising material for phase-change memory application because of improved thermal stability and reduced power consumption.

Thermal characterization and analysis of phase change random access memory

NASA Astrophysics Data System (ADS)

Giraud, V.; Cluzel, J.; Sousa, V.; Jacquot, A.; Dauscher, A.; Lenoir, B.; Scherrer, H.; Romer, S.

2005-07-01

The cross-plane thermal conductivity of Ge2Sb2Te5, either in its amorphous state or fcc crystallized state, and titanium nitride (TiN) thin films has been measured at room temperature by the 3ω method. These materials are involved in the fabrication of phase change random access memory (PC-RAM), Ge2Sb2Te5 and TiN being the PC and pseudoelectrode materials, respectively. The thermal conductivity of insulating SiO2 and ZnS :SiO2 layers was determined too. Each thermal conductivity measurement was performed by the means of at least two strip widths in order to check both the measurement self-consistency and the measurement accuracy. The performance of PC-RAM cells, i.e., the time needed to reach the melting temperature of the PC material and the cooling speed, has been evaluated as a function of both the measured thermal conductivity of the PC material and the reset current intensity independently of the thermal properties of the pseudoelectrodes by the way of analytical formula. The influence of the thickness and the thermal properties of the pseudoelectrodes on the performances have been determined by numerical simulations.

Age-related memory decline is associated with vascular and microglial degeneration in aged rats.

PubMed

Zhang, Rong; Kadar, Tamar; Sirimanne, Ernest; MacGibbon, Alastair; Guan, Jian

2012-12-01

The hippocampus processes memory is an early target of aging-related biological and structural lesions, leading to memory decline. With absent neurodegeneration in the hippocampus, which identified in rodent model of normal aging the pathology underlying age-related memory impairment is not complete. The effective glial-vascular networks are the key for maintaining neuronal functions. The changes of glial cells and cerebral capillaries with age may contribute to memory decline. Thus we examined age associated changes in neurons, glial phenotypes and microvasculature in the hippocampus of aged rats with memory decline. Young adult (6 months) and aged (35 months) male rats (Fisher/Norway-Brown) were used. To evaluate memory, four days of acquisition phase of Morris water maze tasks were carried out in both age groups and followed by a probe trial 2 h after the acquisition. The brains were then collected for analysis using immunochemistry. The aged rats showed a delayed latency (p<0.001) and longer swimming path (p<0.001) to locate a hidden platform. They also spent less time in and made delayed and fewer entries into the correct quadrant during the probe trial. Without seen neuronal degeneration, the aged rats with memory impairments have displayed dopamine depletion, profound vascular and microglial degeneration with reduced vascular endothelial growth factor and elevated GFAP expression in the hippocampus. The data indicate the memory decline with age is associated with neuronal dysfunction, possibly due to impaired glial-vascular-neuronal networks, but not neuronal degeneration. Glial and vascular degeneration found in aged rats may represent early event of aging pathology prior to neuronal degeneration. Copyright © 2012 Elsevier B.V. All rights reserved.

Selective Reduction of AMPA Currents onto Hippocampal Interneurons Impairs Network Oscillatory Activity

PubMed Central

Le Magueresse, Corentin; Monyer, Hannah

2012-01-01

Reduction of excitatory currents onto GABAergic interneurons in the forebrain results in impaired spatial working memory and altered oscillatory network patterns in the hippocampus. Whether this phenotype is caused by an alteration in hippocampal interneurons is not known because most studies employed genetic manipulations affecting several brain regions. Here we performed viral injections in genetically modified mice to ablate the GluA4 subunit of the AMPA receptor in the hippocampus (GluA4HC−/− mice), thereby selectively reducing AMPA receptor-mediated currents onto a subgroup of hippocampal interneurons expressing GluA4. This regionally selective manipulation led to a strong spatial working memory deficit while leaving reference memory unaffected. Ripples (125–250 Hz) in the CA1 region of GluA4HC−/− mice had larger amplitude, slower frequency and reduced rate of occurrence. These changes were associated with an increased firing rate of pyramidal cells during ripples. The spatial selectivity of hippocampal pyramidal cells was comparable to that of controls in many respects when assessed during open field exploration and zigzag maze running. However, GluA4 ablation caused altered modulation of firing rate by theta oscillations in both interneurons and pyramidal cells. Moreover, the correlation between the theta firing phase of pyramidal cells and position was weaker in GluA4HC−/− mice. These results establish the involvement of AMPA receptor-mediated currents onto hippocampal interneurons for ripples and theta oscillations, and highlight potential cellular and network alterations that could account for the altered working memory performance. PMID:22675480

Memory CD8+ T cells are sufficient to alleviate impaired host resistance to influenza A virus infection caused by neonatal oxygen supplementation.

PubMed

Giannandrea, Matthew; Yee, Min; O'Reilly, Michael A; Lawrence, B Paige

2012-09-01

Supplemental oxygen administered to preterm infants is an important clinical intervention, but it is associated with life-long changes in lung development and increased sensitivity to respiratory viral infections. The precise immunological changes caused by neonatal oxygen treatment remain poorly understood. We previously reported that adult mice exposed to supplemental oxygen as neonates display persistent pulmonary inflammation and enhanced mortality after a sublethal influenza A virus infection. These changes suggest that neonatal hyperoxia impairs the cytotoxic CD8(+) T cell response required to clear the virus. In this study, we show that although host resistance to several different strains of influenza A virus is reduced by neonatal hyperoxia, this treatment does not impair viral clearance, nor does it alter the magnitude of the virus-specific CD8(+) T cell response to primary infection. Moreover, memory T cells are sufficient to ameliorate the increased morbidity and mortality and alleviate the excessive lung damage observed in mice exposed to high oxygen levels as neonates, and we attribute this sufficiency principally to virus-specific memory CD8(+) T cells. Thus, we show that neonatal hyperoxia reduces host resistance to influenza virus infection without diminishing the function of cytotoxic T lymphocytes or the generation of virus-specific memory T cells and that CD8(+) memory T cells are sufficient to provide protection from negative consequences of this important life-saving intervention. Our findings suggest that vaccines that generate robust T cell memory may be efficacious at reducing the increased sensitivity to respiratory viral infections in people born prematurely.

On-chip phase-change photonic memory and computing

NASA Astrophysics Data System (ADS)

Cheng, Zengguang; Ríos, Carlos; Youngblood, Nathan; Wright, C. David; Pernice, Wolfram H. P.; Bhaskaran, Harish

2017-08-01

The use of photonics in computing is a hot topic of interest, driven by the need for ever-increasing speed along with reduced power consumption. In existing computing architectures, photonic data storage would dramatically improve the performance by reducing latencies associated with electrical memories. At the same time, the rise of `big data' and `deep learning' is driving the quest for non-von Neumann and brain-inspired computing paradigms. To succeed in both aspects, we have demonstrated non-volatile multi-level photonic memory avoiding the von Neumann bottleneck in the existing computing paradigm and a photonic synapse resembling the biological synapses for brain-inspired computing using phase-change materials (Ge2Sb2Te5).

Epigenetic mechanisms of memory formation and reconsolidation.

PubMed

Jarome, Timothy J; Lubin, Farah D

2014-11-01

Memory consolidation involves transcriptional control of genes in neurons to stabilize a newly formed memory. Following retrieval, a once consolidated memory destabilizes and again requires gene transcription changes in order to restabilize, a process referred to as reconsolidation. Understanding the molecular mechanisms of gene transcription during the consolidation and reconsolidation processes could provide crucial insights into normal memory formation and memory dysfunction associated with psychiatric disorders. In the past decade, modifications of epigenetic markers such as DNA methylation and posttranslational modifications of histone proteins have emerged as critical transcriptional regulators of gene expression during initial memory formation and after retrieval. In light of the rapidly growing literature in this exciting area of research, we here examine the most recent and latest evidence demonstrating how memory acquisition and retrieval trigger epigenetic changes during the consolidation and reconsolidation phases to impact behavior. In particular we focus on the reconsolidation process, where we discuss the already identified epigenetic regulators of gene transcription during memory reconsolidation, while exploring other potential epigenetic modifications that may also be involved, and expand on how these epigenetic modifications may be precisely and temporally controlled by important signaling cascades critical to the reconsolidation process. Finally, we explore the possibility that epigenetic mechanisms may serve to regulate a system or circuit level reconsolidation process and may be involved in retrieval-dependent memory updating. Hence, we propose that epigenetic mechanisms coordinate changes in neuronal gene transcription, not only during the initial memory consolidation phase, but are triggered by retrieval to regulate molecular and cellular processes during memory reconsolidation. Copyright © 2014 Elsevier Inc. All rights reserved.

Epigenetic Mechanisms of Memory Formation and Reconsolidation

PubMed Central

Jarome, Timothy J.; Lubin, Farah D.

2014-01-01

Memory consolidation involves transcriptional control of genes in neurons to stabilize a newly formed memory. Following retrieval, a once consolidated memory destabilizes and again requires gene transcription changes in order to restabilize, a process referred to as reconsolidation. Understanding the molecular mechanisms of gene transcription during the consolidation and reconsolidation processes could provide crucial insights into normal memory formation and memory dysfunction associated with psychiatric disorders. In the past decade, modifications of epigenetic markers such as DNA methylation and posttranslational modifications of histone proteins have emerged as critical transcriptional regulators of gene expression during initial memory formation and after retrieval. In light of the rapidly growing literature in this exciting area of research, we here examine the most recent and latest evidence demonstrating how memory acquisition and retrieval trigger epigenetic changes during the consolidation and reconsolidation phases to impact behavior. In particular we focus on the reconsolidation process, where we discuss the already identified epigenetic regulators of gene transcription during memory reconsolidation, while exploring other potential epigenetic modifications that may also be involved, and expand on how these epigenetic modifications may be precisely and temporally controlled by important signaling cascades critical to the reconsolidation process. Finally, we explore the possibility that epigenetic mechanisms may serve to regulate a system or circuit level reconsolidation process and may be involved in retrieval-dependent memory updating. Hence, we propose that epigenetic mechanisms coordinate changes in neuronal gene transcription, not only during the initial memory consolidation phase, but are triggered by retrieval to regulate molecular and cellular processes during memory reconsolidation. PMID:25130533

Plastic Deformation and Failure Analysis of Phase Change Random Access Memory

NASA Astrophysics Data System (ADS)

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

2009-04-01

Although lateral phase change random access memory (PCRAM) has attracted a lot of interest due to its simpler fabrication process and lower current compared to ovonic unified memory (OUM), it faces a problem of poor lifetime. This paper studied relation between plastic deformation and the failure of PCRAM through both experiment and simulation. OUM and lateral PCRAM incorporating Ge2Sb2Te5 were fabricated and tested. The overwriting test showed that lifetime of OUM exceeded 106 while that of lateral PCRAM was only about 100. Using atomic force microscopy (AFM), it was found that the plastic deformation after 106 overwriting reached several tens of nm for lateral PCRAM while it was negligible for OUM. The thermo-mechanical simulation results confirmed the similar results on larger plastic deformation of lateral PCRAM than that of OUM during overwriting. As plastic deformation involves of atomic bonds breaking and reforming in phase change material, the plastic deformation may be one main reason for the failure of lateral PCRAM.

Resistive switching characteristics of interfacial phase-change memory at elevated temperature

NASA Astrophysics Data System (ADS)

Mitrofanov, Kirill V.; Saito, Yuta; Miyata, Noriyuki; Fons, Paul; Kolobov, Alexander V.; Tominaga, Junji

2018-04-01

Interfacial phase-change memory (iPCM) devices were fabricated using W and TiN for the bottom and top contacts, respectively, and the effect of operation temperature on the resistive switching was examined over the range between room temperature and 200 °C. It was found that the high-resistance (RESET) state in an iPCM device drops sharply at around 150 °C to a low-resistance (SET) state, which differs by ˜400 Ω from the SET state obtained by electric-field-induced switching. The iPCM device SET state resistance recovered during the cooling process and remained at nearly the same value for the RESET state. These resistance characteristics greatly differ from those of the conventional Ge-Sb-Te (GST) alloy phase-change memory device, underscoring the fundamentally different switching nature of iPCM devices. From the thermal stability measurements of iPCM devices, their optimal temperature operation was concluded to be less than 100 °C.

Pupil size reflects successful encoding and recall of memory in humans.

PubMed

Kucewicz, Michal T; Dolezal, Jaromir; Kremen, Vaclav; Berry, Brent M; Miller, Laura R; Magee, Abigail L; Fabian, Vratislav; Worrell, Gregory A

2018-03-21

Pupil responses are known to indicate brain processes involved in perception, attention and decision-making. They can provide an accessible biomarker of human memory performance and cognitive states in general. Here we investigated changes in the pupil size during encoding and recall of word lists. Consistent patterns in the pupil response were found across and within distinct phases of the free recall task. The pupil was most constricted in the initial fixation phase and was gradually more dilated through the subsequent encoding, distractor and recall phases of the task, as the word items were maintained in memory. Within the final recall phase, retrieving memory for individual words was associated with pupil dilation in absence of visual stimulation. Words that were successfully recalled showed significant differences in pupil response during their encoding compared to those that were forgotten - the pupil was more constricted before and more dilated after the onset of word presentation. Our results suggest pupil size as a potential biomarker for probing and modulation of memory processing.

Selective resistance of CD44hi T cells to p53-dependent cell death results in persistence of immunologic memory after total body irradiation.

PubMed

Yao, Zhenyu; Jones, Jennifer; Kohrt, Holbrook; Strober, Samuel

2011-10-15

Our previous studies showed that treatment of mice with total body irradiation (TBI) or total lymphoid tissue irradiation markedly changes the balance of residual T cell subsets to favor CD4(+)CD44(hi) NKT cells because of the differential resistance of the latter subset to cell death. The object of the current study was to further elucidate the changed balance and mechanisms of differential radioresistance of T cell subsets after graded doses of TBI. The experimental results showed that CD4(+) T cells were markedly more resistant than CD8(+) T cells, and CD44(hi) T cells, including NKT cells and memory T cells, were markedly more resistant than CD44(lo) (naive) T cells. The memory T cells immunized to alloantigens persisted even after myeloablative (1000 cGy) TBI and were able to prevent engraftment of bone marrow transplants. Although T cell death after 1000 cGy was prevented in p53(-/-) mice, there was progressive T cell death in p53(-/-) mice at higher doses. Although p53-dependent T cell death changed the balance of subsets, p53-independent T cell death did not. In conclusion, resistance of CD44(hi) T cells to p53-dependent cell death results in the persistence of immunological memory after TBI and can explain the immune-mediated rejection of marrow transplants in sensitized recipients.

Inception of a false memory by optogenetic manipulation of a hippocampal memory engram.

PubMed

Liu, Xu; Ramirez, Steve; Tonegawa, Susumu

2014-01-05

Memories can be easily distorted, and a lack of relevant animal models has largely hindered our understanding of false-memory formation. Here, we first identified a population of cells in the dentate gyrus (DG) of the hippocampus that bear the engrams for a specific context; these cells were naturally activated during the encoding phase of fear conditioning and their artificial reactivation using optogenetics in an unrelated context was sufficient for inducing the fear memory specific to the conditioned context. In a further study, DG or CA1 neurons activated by exposure to a particular context were labelled with channelrhodopsin-2 (ChR2). These neurons were later optically reactivated during fear conditioning in a different context. The DG experimental group showed increased freezing in the original context in which a foot shock was never delivered. The recall of this false memory was context specific, activated similar downstream regions engaged during natural fear-memory recall, and was also capable of driving an active fear response. Together, our data demonstrate that by substituting a natural conditioned stimulus with optogenetically reactivated DG cells that bear contextual memory engrams, it is possible to incept an internally and behaviourally represented false fear memory.

Inception of a false memory by optogenetic manipulation of a hippocampal memory engram

PubMed Central

Liu, Xu; Ramirez, Steve; Tonegawa, Susumu

2014-01-01

Memories can be easily distorted, and a lack of relevant animal models has largely hindered our understanding of false-memory formation. Here, we first identified a population of cells in the dentate gyrus (DG) of the hippocampus that bear the engrams for a specific context; these cells were naturally activated during the encoding phase of fear conditioning and their artificial reactivation using optogenetics in an unrelated context was sufficient for inducing the fear memory specific to the conditioned context. In a further study, DG or CA1 neurons activated by exposure to a particular context were labelled with channelrhodopsin-2 (ChR2). These neurons were later optically reactivated during fear conditioning in a different context. The DG experimental group showed increased freezing in the original context in which a foot shock was never delivered. The recall of this false memory was context specific, activated similar downstream regions engaged during natural fear-memory recall, and was also capable of driving an active fear response. Together, our data demonstrate that by substituting a natural conditioned stimulus with optogenetically reactivated DG cells that bear contextual memory engrams, it is possible to incept an internally and behaviourally represented false fear memory. PMID:24298144

Biocompatibility of austenite and martensite phases in NiTi-based alloys

NASA Astrophysics Data System (ADS)

Danilov, A.; Kapanen, A.; Kujala, S.; Saaranen, J.; Ryhänen, J.; Pramila, A.; Jämsä, T.; Tuukkanen, J.

2003-10-01

The effect of surface phase composition on the biocompatibility of NiTi-based shape memory alloys was studied. The biocompatibility characteristics of parent β-phase (austenite) in binary NiTi and of martensite in ternary NiTiCu alloys after similar surface mechanical treatment were compared. The martensitic phase as a result of surface mechanical treatment (strain-induced martensite) was shown to decrease the biocompatibility of material in comparison to fully austenite state. The cytotoxicity (amount of dead cells / 1000 cells) and cell attachent (paxillin count / frame) were found to be linear functions of structural stresses in austenite.

Intrinsic role of FoxO3a in the development of CD8+ T cell memory

PubMed Central

Tzelepis, Fanny; Joseph, Julie; Haddad, Elias K.; MacLean, Susanne; Dudani, Renu; Agenes, Fabien; Peng, Stanford L.; Sekaly, Rafick-Pierre; Sad, Subash

2013-01-01

CD8+ T cells undergo rapid expansion during infection with intracellular pathogens, which is followed by swift and massive culling of primed CD8+ T cells. The mechanisms that govern the massive contraction and maintenance of primed CD8+ T cells are not clear. We show here that the transcription factor, FoxO3a does not influence antigen-presentation and the consequent expansion of CD8+ T cell response during Listeria monocytogenes (LM) infection, but plays a key role in the maintenance of memory CD8+ T cells. The effector function of primed CD8+ T cells as revealed by cytokine secretion and CD107a degranulation was not influenced by inactivation of FoxO3a. Interestingly, FoxO3a-deficient CD8+ T cells displayed reduced expression of pro-apoptotic molecules BIM and PUMA during the various phases of response, and underwent reduced apoptosis in comparison to WT cells. A higher number of memory precursor effector cells (MPECs) and memory subsets were detectable in FoxO3a-deficient mice compared to WT mice. Furthermore, FoxO3a-deficient memory CD8+ T cells upon transfer into normal or RAG1-deficient mice displayed enhanced survival. These results suggest that FoxO3a acts in a cell intrinsic manner to regulate the survival of primed CD8+ T cells. PMID:23277488

Calculation of optical parameters for covalent binary alloys used in optical memories/solar cells: a modified approach

NASA Astrophysics Data System (ADS)

Bhatnagar, Promod K.; Gupta, Poonam; Singh, Laxman

2001-06-01

Chalcogenide based alloys find applications in a number of devices like optical memories, IR detectors, optical switches, photovoltaics, compound semiconductor heterosrtuctures etc. We have modified the Gurman's statistical thermodynamic model (STM) of binary covalent alloys. In the Gurman's model, entropy calculations are based on the number of structural units present. The need to modify this model arose due to the fact that it gives equal probability for all the tetrahedra present in the alloy. We have modified the Gurman's model by introducing the concept that the entropy is based on the bond arrangement rather than that on the structural units present. In the present work calculation based on this modification have been presented for optical properties, which find application in optical switching/memories, solar cells and other optical devices. It has been shown that the calculated optical parameters (for a typical case of GaxSe1-x) based on modified model are closer to the available experimental results. These parameters include refractive index, extinction coefficient, dielectric functions, optical band gap etc. GaxSe1-x has been found to be suitable for reversible optical memories also, where phase change (a yields c and vice versa) takes place at specified physical conditions. DTA/DSC studies also suggest the suitability of this material for optical switching/memory applications. We have also suggested possible use of GaxSe1-x (x = 0.4) in place of oxide layer in a Metal - Oxide - Semiconductor type solar cells. The new structure is Metal - Ga2Se3 - GaAs. The I-V characteristics and other parameters calculated for this structure are found to be much better than that for Si based solar cells. Maximum output power is obtained at the intermediate layer thickness approximately 40 angstroms for this typical solar cell.

Design of all-optical memory cell using EIT and lasing without inversion phenomena in optical micro ring resonators

NASA Astrophysics Data System (ADS)

Pasyar, N.; Yadipour, R.; Baghban, H.

2017-07-01

The proposed design of the optical memory unit cell contains dual micro ring resonators in which the effect of lasing without inversion (LWI) in three-level nano particles doped over the optical resonators or integrators as the gain segment is used for loss compensation. Also, an on/off phase shifter based on electromagnetically induced transparency (EIT) in three-level quantum dots (QDs) has been used for data reading at requested time. Device minimizing for integrated purposes and high speed data storage are the main advantages of the optical integrator based memory.

Oseltamivir Prophylaxis Reduces Inflammation and Facilitates Establishment of Cross-Strain Protective T Cell Memory to Influenza Viruses

PubMed Central

Hurt, Aeron C.; Oshansky, Christine M.; Oh, Ding Yuan; Reading, Patrick C.; Chua, Brendon Y.; Sun, Yilun; Tang, Li; Handel, Andreas; Jackson, David C.; Turner, Stephen J.; Thomas, Paul G.; Kedzierska, Katherine

2015-01-01

CD8+ T cells directed against conserved viral regions elicit broad immunity against distinct influenza viruses, promote rapid virus elimination and enhanced host recovery. The influenza neuraminidase inhibitor, oseltamivir, is prescribed for therapy and prophylaxis, although it remains unclear how the drug impacts disease severity and establishment of effector and memory CD8+ T cell immunity. We dissected the effects of oseltamivir on viral replication, inflammation, acute CD8+ T cell responses and the establishment of immunological CD8+ T cell memory. In mice, ferrets and humans, the effect of osteltamivir on viral titre was relatively modest. However, prophylactic oseltamivir treatment in mice markedly reduced morbidity, innate responses, inflammation and, ultimately, the magnitude of effector CD8+ T cell responses. Importantly, functional memory CD8+ T cells established during the drug-reduced effector phase were capable of mounting robust recall responses. Moreover, influenza-specific memory CD4+ T cells could be also recalled after the secondary challenge, while the antibody levels were unaffected. This provides evidence that long-term memory T cells can be generated during an oseltamivir-interrupted infection. The anti-inflammatory effect of oseltamivir was verified in H1N1-infected patients. Thus, in the case of an unpredicted influenza pandemic, while prophylactic oseltamivir treatment can reduce disease severity, the capacity to generate memory CD8+ T cells specific for the newly emerged virus is uncompromised. This could prove especially important for any new influenza pandemic which often occurs in separate waves. PMID:26086392

Visual long-term memory and change blindness: Different effects of pre- and post-change information on one-shot change detection using meaningless geometric objects.

PubMed

Nishiyama, Megumi; Kawaguchi, Jun

2014-11-01

To clarify the relationship between visual long-term memory (VLTM) and online visual processing, we investigated whether and how VLTM involuntarily affects the performance of a one-shot change detection task using images consisting of six meaningless geometric objects. In the study phase, participants observed pre-change (Experiment 1), post-change (Experiment 2), or both pre- and post-change (Experiment 3) images appearing in the subsequent change detection phase. In the change detection phase, one object always changed between pre- and post-change images and participants reported which object was changed. Results showed that VLTM of pre-change images enhanced the performance of change detection, while that of post-change images decreased accuracy. Prior exposure to both pre- and post-change images did not influence performance. These results indicate that pre-change information plays an important role in change detection, and that information in VLTM related to the current task does not always have a positive effect on performance. Copyright © 2014 Elsevier Inc. All rights reserved.

Two-bit multi-level phase change random access memory with a triple phase change material stack structure

NASA Astrophysics Data System (ADS)

Gyanathan, Ashvini; Yeo, Yee-Chia

2012-11-01

This work demonstrates a novel two-bit multi-level device structure comprising three phase change material (PCM) layers, separated by SiN thermal barrier layers. This triple PCM stack consisted of (from bottom to top), Ge2Sb2Te5 (GST), an ultrathin SiN barrier, nitrogen-doped GST, another ultrathin SiN barrier, and Ag0.5In0.5Sb3Te6. The PCM layers can selectively amorphize to form 4 different resistance levels ("00," "01," "10," and "11") using respective voltage pulses. Electrical characterization was extensively performed on these devices. Thermal analysis was also done to understand the physics behind the phase changing characteristics of the two-bit memory devices. The melting and crystallization temperatures of the PCMs play important roles in the power consumption of the multi-level devices. The electrical resistivities and thermal conductivities of the PCMs and the SiN thermal barrier are also crucial factors contributing to the phase changing behaviour of the PCMs in the two-bit multi-level PCRAM device.

Switched Memory B Cells Are Increased in Oligoarticular and Polyarticular Juvenile Idiopathic Arthritis and Their Change Over Time Is Related to Response to Tumor Necrosis Factor Inhibitors.

PubMed

Marasco, Emiliano; Aquilani, Angela; Cascioli, Simona; Moneta, Gian Marco; Caiello, Ivan; Farroni, Chiara; Giorda, Ezio; D'Oria, Valentina; Marafon, Denise Pires; Magni-Manzoni, Silvia; Carsetti, Rita; De Benedetti, Fabrizio

2018-04-01

To investigate whether abnormalities in B cell subsets in patients with juvenile idiopathic arthritis (JIA) correlate with clinical features and response to treatment. A total of 109 patients diagnosed as having oligoarticular JIA or polyarticular JIA were enrolled in the study. B cell subsets in peripheral blood and synovial fluid were analyzed by flow cytometry. Switched memory B cells were significantly increased in patients compared to age-matched healthy controls (P < 0.0001). When patients were divided according to age at onset of JIA, in patients with early-onset disease (presenting before age 6 years) the expansion in switched memory B cells was more pronounced than that in patients with late-onset disease and persisted throughout the disease course. In longitudinal studies, during methotrexate (MTX) treatment, regardless of the presence or absence of active disease, the number of switched memory B cells increased significantly (median change from baseline 36% [interquartile range {IQR} 15, 66]). During treatment with MTX plus tumor necrosis factor inhibitors (TNFi), in patients maintaining disease remission, the increase in switched memory B cells was significantly lower than that in patients who experienced active disease (median change from baseline 4% [IQR -6, 32] versus 41% [IQR 11, 73]; P = 0.004). The yearly rate of increases in switched memory B cells was 1.5% in healthy controls, 1.2% in patients who maintained remission during treatment with MTX plus TNFi, 4.7% in patients who experienced active disease during treatment with MTX plus TNFi, and ~4% in patients treated with MTX alone. Switched memory B cells expand during the disease course at a faster rate in JIA patients than in healthy children. This increase is more evident in patients with early-onset JIA. TNFi treatment inhibits this increase in patients who achieve and maintain remission, but not in those with active disease. © 2018, American College of Rheumatology.

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

PubMed

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

2011-10-15

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

Synaptic tagging, evaluation of memories, and the distal reward problem.

PubMed

Päpper, Marc; Kempter, Richard; Leibold, Christian

2011-01-01

Long-term synaptic plasticity exhibits distinct phases. The synaptic tagging hypothesis suggests an early phase in which synapses are prepared, or "tagged," for protein capture, and a late phase in which those proteins are integrated into the synapses to achieve memory consolidation. The synapse specificity of the tags is consistent with conventional neural network models of associative memory. Memory consolidation through protein synthesis, however, is neuron specific, and its functional role in those models has not been assessed. Here, using a theoretical network model, we test the tagging hypothesis on its potential to prolong memory lifetimes in an online-learning paradigm. We find that protein synthesis, though not synapse specific, prolongs memory lifetimes if it is used to evaluate memory items on a cellular level. In our model we assume that only "important" memory items evoke protein synthesis such that these become more stable than "unimportant" items, which do not evoke protein synthesis. The network model comprises an equilibrium distribution of synaptic states that is very susceptible to the storage of new items: Most synapses are in a state in which they are plastic and can be changed easily, whereas only those synapses that are essential for the retrieval of the important memory items are in the stable late phase. The model can solve the distal reward problem, where the initial exposure of a memory item and its evaluation are temporally separated. Synaptic tagging hence provides a viable mechanism to consolidate and evaluate memories on a synaptic basis.

Attrition of memory CD8 T cells during sepsis requires LFA-1.

PubMed

Serbanescu, Mara A; Ramonell, Kimberly M; Hadley, Annette; Margoles, Lindsay M; Mittal, Rohit; Lyons, John D; Liang, Zhe; Coopersmith, Craig M; Ford, Mandy L; McConnell, Kevin W

2016-11-01

CD8 T cell loss and dysfunction have been implicated in the increased susceptibility to opportunistic infections during the later immunosuppressive phase of sepsis, but CD8 T cell activation and attrition in early sepsis remain incompletely understood. With the use of a CLP model, we assessed CD8 T cell activation at 5 consecutive time points and found that activation after sepsis results in a distinct phenotype (CD69 + CD25 int CD62L HI ) independent of cognate antigen recognition and TCR engagement and likely through bystander-mediated cytokine effects. Additionally, we observed that sepsis concurrently results in the preferential depletion of a subset of memory-phenotype CD8 T cells that remain "unactivated" (i.e., fail to up-regulate activation markers) by apoptosis. Unactivated CD44 HI OT-I cells were spared from sepsis-induced attrition, as were memory-phenotype CD8 T cells of mice treated with anti-LFA-1 mAb, 1 h after CLP. Perhaps most importantly, we demonstrate that attrition of memory phenotype cells may have a pathologic significance, as elevated IL-6 levels were associated with decreased numbers of memory-phenotype CD8 T cells in septic mice, and preservation of this subset after administration of anti-LFA-1 mAb conferred improved survival at 7 d. Taken together, these data identify potentially modifiable responses of memory-phenotype CD8 T cells in early sepsis and may be particularly important in the application of immunomodulatory therapies in sepsis. © Society for Leukocyte Biology.

Attrition of memory CD8 T cells during sepsis requires LFA-1

PubMed Central

Serbanescu, Mara A.; Ramonell, Kimberly M.; Hadley, Annette; Margoles, Lindsay M.; Mittal, Rohit; Lyons, John D.; Liang, Zhe; Coopersmith, Craig M.; Ford, Mandy L.; McConnell, Kevin W.

2016-01-01

CD8 T cell loss and dysfunction have been implicated in the increased susceptibility to opportunistic infections during the later immunosuppressive phase of sepsis, but CD8 T cell activation and attrition in early sepsis remain incompletely understood. With the use of a CLP model, we assessed CD8 T cell activation at 5 consecutive time points and found that activation after sepsis results in a distinct phenotype (CD69+CD25intCD62LHI) independent of cognate antigen recognition and TCR engagement and likely through bystander-mediated cytokine effects. Additionally, we observed that sepsis concurrently results in the preferential depletion of a subset of memory-phenotype CD8 T cells that remain “unactivated” (i.e., fail to up-regulate activation markers) by apoptosis. Unactivated CD44HI OT-I cells were spared from sepsis-induced attrition, as were memory-phenotype CD8 T cells of mice treated with anti-LFA-1 mAb, 1 h after CLP. Perhaps most importantly, we demonstrate that attrition of memory phenotype cells may have a pathologic significance, as elevated IL-6 levels were associated with decreased numbers of memory-phenotype CD8 T cells in septic mice, and preservation of this subset after administration of anti-LFA-1 mAb conferred improved survival at 7 d. Taken together, these data identify potentially modifiable responses of memory-phenotype CD8 T cells in early sepsis and may be particularly important in the application of immunomodulatory therapies in sepsis. PMID:27286793

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

PubMed

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

2017-12-21

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

Rewriting magnetic phase change memory by laser heating

NASA Astrophysics Data System (ADS)

Timmerwilke, John; Liou, Sy-Hwang; Cheng, Shu Fan; Edelstein, Alan S.

2016-04-01

Magnetic phase change memory (MAG PCM) consists of bits with different magnetic permeability values. The bits are read by measuring their effect on a magnetic probe field. Previously low permeability crystalline bits had been written in high permeability amorphous films of Metglas via laser heating. Here data is presented showing that by applying short laser pulses with the appropriate power to previously crystallized regions they can first be vitrified and then again crystallized. Thus, MAG PCM is rewriteable. Technical issues in processing the bits are discussed and results on thermal modeling are presented.

The effects of velocity difference changes with memory on the dynamics characteristics and fuel economy of traffic flow

NASA Astrophysics Data System (ADS)

Yu, Shaowei; Zhao, Xiangmo; Xu, Zhigang; Zhang, Licheng

2016-11-01

To evaluate the effects of velocity difference changes with memory in the intelligent transportation environment on the dynamics and fuel consumptions of traffic flow, we first investigate the linkage between velocity difference changes with memory and car-following behaviors with the measured data in cities, and then propose an improved cooperative car-following model considering multiple velocity difference changes with memory in the cooperative adaptive cruise control strategy, finally carry out several numerical simulations under the periodic boundary condition and at signalized intersections to explore how velocity difference changes with memory affect car's velocity, velocity fluctuation, acceleration and fuel consumptions in the intelligent transportation environment. The results show that velocity difference changes with memory have obvious effects on car-following behaviors, that the improved cooperative car-following model can describe the phase transition of traffic flow and estimate the evolution of traffic congestion, that the stability and fuel economy of traffic flow simulated by the improved car-following model with velocity difference changes with memory is obviously superior to those without velocity difference changes, and that taking velocity difference changes with memory into account in designing the advanced adaptive cruise control strategy can significantly improve the stability and fuel economy of traffic flow.

Phonological awareness and the working memory of children with and without literacy difficulties.

PubMed

Cardoso, Andreia Martins de Souza; Silva, Mônica Marins da; Pereira, Mônica Medeiros de Britto

2013-01-01

To investigate phonological awareness and working memory skills as well as their influence on the literacy process in a group of intellectually normal children. Forty intellectually normal children (7.6-8.0 years) from the second and third grades of elementary school participated. Children were organized in two groups (20 children each): one with and another without literacy difficulties. These participants underwent RAVEN's intelligence quotient test, audiometric assessment, CONFIAS test of phonological awareness, written spelling task, and working memory test. Children in the alphabetic phase presented a good development of phonological awareness, and 85% of them showed a high-performance working memory. Children in the syllabic-alphabetic phase had changes in phonological awareness, and 91.6% of them showed an average working memory performance. The subjects at pre-syllabic and syllabic phases demonstrated more difficulties in phonological awareness than those at syllabic-alphabetic and had a poor working memory performance. Between-group differences were observed for CONFIAS and working memory tests (p<0.0001). There was also a significant correlation (r=0.78, p=0.01) between the skills of phonological awareness and working memory for the total sample of individuals. Based on these results, it was found that as phonological awareness and working memory levels increased, the literacy phase also advanced, therefore showing that these are directly proportional measures.

Pressure-induced reversible amorphization and an amorphous–amorphous transition in Ge2Sb2Te5 phase-change memory material

PubMed Central

Sun, Zhimei; Zhou, Jian; Pan, Yuanchun; Song, Zhitang; Mao, Ho-Kwang; Ahuja, Rajeev

2011-01-01

Ge2Sb2Te5 (GST) is a technologically very important phase-change material that is used in digital versatile disks-random access memory and is currently studied for the use in phase-change random access memory devices. This type of data storage is achieved by the fast reversible phase transition between amorphous and crystalline GST upon heat pulse. Here we report pressure-induced reversible crystalline-amorphous and polymorphic amorphous transitions in NaCl structured GST by ab initio molecular dynamics calculations. We have showed that the onset amorphization of GST starts at approximately 18 GPa and the system become completely random at approximately 22 GPa. This amorphous state has a cubic framework (c-amorphous) of sixfold coordinations. With further increasing pressure, the c-amorphous transforms to a high-density amorphous structure with trigonal framework (t-amorphous) and an average coordination number of eight. The pressure-induced amorphization is investigated to be due to large displacements of Te atoms for which weak Te–Te bonds exist or vacancies are nearby. Upon decompressing to ambient conditions, the original cubic crystalline structure is restored for c-amorphous, whereas t-amorphous transforms to another amorphous phase that is similar to the melt-quenched amorphous GST. PMID:21670255

Pressure-induced reversible amorphization and an amorphous-amorphous transition in Ge₂Sb₂Te₅ phase-change memory material.

PubMed

Sun, Zhimei; Zhou, Jian; Pan, Yuanchun; Song, Zhitang; Mao, Ho-Kwang; Ahuja, Rajeev

2011-06-28

Ge(2)Sb(2)Te(5) (GST) is a technologically very important phase-change material that is used in digital versatile disks-random access memory and is currently studied for the use in phase-change random access memory devices. This type of data storage is achieved by the fast reversible phase transition between amorphous and crystalline GST upon heat pulse. Here we report pressure-induced reversible crystalline-amorphous and polymorphic amorphous transitions in NaCl structured GST by ab initio molecular dynamics calculations. We have showed that the onset amorphization of GST starts at approximately 18 GPa and the system become completely random at approximately 22 GPa. This amorphous state has a cubic framework (c-amorphous) of sixfold coordinations. With further increasing pressure, the c-amorphous transforms to a high-density amorphous structure with trigonal framework (t-amorphous) and an average coordination number of eight. The pressure-induced amorphization is investigated to be due to large displacements of Te atoms for which weak Te-Te bonds exist or vacancies are nearby. Upon decompressing to ambient conditions, the original cubic crystalline structure is restored for c-amorphous, whereas t-amorphous transforms to another amorphous phase that is similar to the melt-quenched amorphous GST.

Phase-change memory function of correlated electrons in organic conductors

NASA Astrophysics Data System (ADS)

Oike, H.; Kagawa, F.; Ogawa, N.; Ueda, A.; Mori, H.; Kawasaki, M.; Tokura, Y.

2015-01-01

Phase-change memory (PCM), a promising candidate for next-generation nonvolatile memories, exploits quenched glassy and thermodynamically stable crystalline states as reversibly switchable state variables. We demonstrate PCM functions emerging from a charge-configuration degree of freedom in strongly correlated electron systems. Nonvolatile reversible switching between a high-resistivity charge-crystalline (or charge-ordered) state and a low-resistivity quenched state, charge glass, is achieved experimentally via heat pulses supplied by optical or electrical means in organic conductors θ -(BEDT-TTF)2X . Switching that is one order of magnitude faster is observed in another isostructural material that requires faster cooling to kinetically avoid charge crystallization, indicating that the material's critical cooling rate can be useful guidelines for pursuing a faster correlated-electron PCM function.

Increased memory T cell populations in Pb-exposed children from an e-waste-recycling area.

PubMed

Cao, Junjun; Xu, Xijin; Zhang, Yu; Zeng, Zhijun; Hylkema, Machteld N; Huo, Xia

2018-03-01

Chronic exposure to heavy metals could affect cell-mediated immunity. The aim of this study was to explore the status of memory T cell development in preschool children from an e-waste recycling area. Blood lead (Pb) levels, peripheral T cell subpopulations, and serum levels of cytokines (IL-2/IL-7/IL-15), relevant to generation and homeostasis of memory T cells were evaluated in preschool children from Guiyu (e-waste-exposed group) and Haojiang (reference group). The correlations between blood Pb levels and percentages of memory T cell subpopulations were also evaluated. Guiyu children had higher blood Pb levels and increased percentages of CD4 + central memory T cells and CD8 + central memory T cells than in the Haojiang group. Moreover, blood Pb levels were positively associated with the percentages of CD4 + central memory T cells. In contrast, Pb exposure contributed marginally in the change of percentages of CD8 + central memory T cells in children. There was no significant difference in the serum cytokine levels between the e-waste-exposed and reference children. Taken together, preschool children from an e-waste recycling area suffer from relatively higher levels of Pb exposure, which might facilitate the development of CD4 + central memory T cells in these children. Copyright © 2017. Published by Elsevier B.V.

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

PubMed

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

2010-09-01

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

Energy-Efficient Phase-Change Memory with Graphene as a Thermal Barrier.

PubMed

Ahn, Chiyui; Fong, Scott W; Kim, Yongsung; Lee, Seunghyun; Sood, Aditya; Neumann, Christopher M; Asheghi, Mehdi; Goodson, Kenneth E; Pop, Eric; Wong, H-S Philip

2015-10-14

Phase-change memory (PCM) is an important class of data storage, yet lowering the programming current of individual devices is known to be a significant challenge. Here we improve the energy-efficiency of PCM by placing a graphene layer at the interface between the phase-change material, Ge2Sb2Te5 (GST), and the bottom electrode (W) heater. Graphene-PCM (G-PCM) devices have ∼40% lower RESET current compared to control devices without the graphene. This is attributed to the graphene as an added interfacial thermal resistance which helps confine the generated heat inside the active PCM volume. The G-PCM achieves programming up to 10(5) cycles, and the graphene could further enhance the PCM endurance by limiting atomic migration or material segregation at the bottom electrode interface.

Design of an optimised readout architecture for phase-change probe memory using Ge2Sb2Te5 media

NASA Astrophysics Data System (ADS)

Wang, Lei; Wright, C. David; Aziz, Mustafa M.; Yang, Ci-Hui; Yang, Guo-Wei

2014-02-01

Phase-change probe memory has recently received considerable attention on its writing performance, while its readout performance is rarely evaluated. Therefore, a three-dimensional readout model has been developed for the first time to calculate the reading contrast by varying the electrical conductivities and the thickness of the capping and under layers as well as the thickness of the Ge2Sb2Te5 layer. It is found that a phase-change probe architecture, consisting of a 10 nm Ge2Sb2Te5 layer sandwiched by a 2 nm, 50 Ω-1 m-1 capping layer and a 40 nm, 5 × 106 Ω-1 m-1 under layer, has the capability of providing the optimal readout performance.

The electrophysiological correlates of recent and remote recollection.

PubMed

Roberts, J S; Tsivilis, D; Mayes, A R

2013-09-01

Research using event related potentials (ERPs) to explore recognition memory has linked late parietal old/new effects to the recollection of episodic information. In the vast majority of these studies, the retrieval phase immediately follows encoding and consequently, very little is known about the ERP correlates of long term recollection. This is despite the fact that in other areas of the memory literature there is considerable interest in consolidation theories and the way episodic memory changes over time. The present study explored the idea that consolidation and forgetting processes operating over a moderate retention interval can alter the ERP markers of recollection memory. A remember/know test probed memory for stimuli studied either 15 minutes (recent memory) or 1 week (remote memory) prior to the test phase. Results revealed an attenuated late parietal effect for remote compared to recent remember responses, a finding that remained significant even when these recognition judgments were matched for reaction time. Experiments 2a and 2b identified characteristic differences between recent and remote recognition at the behavioural level. The 1 week delay produced an overall decline in recognition confidence and a dramatic loss of episodic detail. These behavioural changes are thought to underlie the ERP effects reported in the first experiment. The results highlight that although the neural basis of memory may exhibit significant changes as the length of the retention interval increases, it is important to consider the extent to which this is a direct effect of time or an indirect effect due to changes in memory quality, such as the amount of detail that can be recollected. © 2013 Elsevier Ltd. All rights reserved.

Selective Resistance of CD44hi T Cells to p53 Dependent Cell Death Results in Persistence of Immunologic Memory after Total Body Irradiation1,2,3

PubMed Central

Yao, Zhenyu; Jones, Jennifer; Kohrt, Holbrook; Strober, Samuel

2011-01-01

Our previous studies showed that treatment of mice with total body irradiation (TBI) or total lymphoid tissue irradiation (TLI) markedly changes the balance of residual T cell subsets to favor CD4+CD44hi natural killer T (NKT) cells due to differential resistance of the latter subset to cell death. The object of the current study was to further elucidate the changed balance and mechanisms of differential radioresistance of T cell subsets after graded doses of TBI. The experimental results show that CD4+ T cells were markedly more resistant than CD8+ T cells, and CD44hi T cells including NKT cells and memory T cells were markedly more resistant than CD44lo (naïve) T cells. The memory T cells immunized to alloantigens persisted even after myeloabloative (1,000cGy) TBI, and were able to prevent engraftment of bone marrow transplants. Although T cell death after 1,000cGy was prevented in p53−/− mice, there was progressive T cell death in p53−/− mice at higher doses. Whereas, p53 dependent T cell death changed the balance of subsets, the p53 independent T cell death did not. In conclusion, resistance of CD44hi T cells to p53 dependent cell death results in the persistence of immunological memory after TBI, and can explain the immune mediated rejection of marrow transplants in sensitized recipients. PMID:21930972

Changes in Context-Specificity during Memory Reconsolidation: Selective Effects of Hippocampal Lesions

ERIC Educational Resources Information Center

Winocur, Gordon; Frankland, Paul W.; Sekeres, Melanie; Fogel, Stuart; Moscovitch, Morris

2009-01-01

After acquisition, memories associated with contextual fear conditioning pass through a labile phase, in which they are vulnerable to hippocampal lesions, to a more stable state, via consolidation, in which they engage extrahippocampal structures and are resistant to such disruption. The process is accompanied by changes in the form of the memory…

Sub-nanometre resolution of atomic motion during electronic excitation in phase-change materials.

PubMed

Mitrofanov, Kirill V; Fons, Paul; Makino, Kotaro; Terashima, Ryo; Shimada, Toru; Kolobov, Alexander V; Tominaga, Junji; Bragaglia, Valeria; Giussani, Alessandro; Calarco, Raffaella; Riechert, Henning; Sato, Takahiro; Katayama, Tetsuo; Ogawa, Kanade; Togashi, Tadashi; Yabashi, Makina; Wall, Simon; Brewe, Dale; Hase, Muneaki

2016-02-12

Phase-change materials based on Ge-Sb-Te alloys are widely used in industrial applications such as nonvolatile memories, but reaction pathways for crystalline-to-amorphous phase-change on picosecond timescales remain unknown. Femtosecond laser excitation and an ultrashort x-ray probe is used to show the temporal separation of electronic and thermal effects in a long-lived (>100 ps) transient metastable state of Ge2Sb2Te5 with muted interatomic interaction induced by a weakening of resonant bonding. Due to a specific electronic state, the lattice undergoes a reversible nondestructive modification over a nanoscale region, remaining cold for 4 ps. An independent time-resolved x-ray absorption fine structure experiment confirms the existence of an intermediate state with disordered bonds. This newly unveiled effect allows the utilization of non-thermal ultra-fast pathways enabling artificial manipulation of the switching process, ultimately leading to a redefined speed limit, and improved energy efficiency and reliability of phase-change memory technologies.

Sub-nanometre resolution of atomic motion during electronic excitation in phase-change materials

DOE PAGES

Mitrofanov, Kirill V.; Fons, Paul; Makino, Kotaro; ...

2016-02-12

Phase-change materials based on Ge-Sb-Te alloys are widely used in industrial applications such as nonvolatile memories, but reaction pathways for crystalline-to-amorphous phase-change on picosecond timescales remain unknown. Femtosecond laser excitation and an ultrashort x-ray probe is used to show the temporal separation of electronic and thermal effects in a long-lived (>100 ps) transient metastable state of Ge 2Sb 2Te 5 with muted interatomic interaction induced by a weakening of resonant bonding. Due to a specific electronic state, the lattice undergoes a reversible nondestructive modification over a nanoscale region, remaining cold for 4 ps. An independent time-resolved x-ray absorption fine structuremore » experiment confirms the existence of an intermediate state with disordered bonds. Furthermore, this newly unveiled effect allows the utilization of non-thermal ultra-fast pathways enabling artificial manipulation of the switching process, ultimately leading to a redefined speed limit, and improved energy efficiency and reliability of phase-change memory technologies.« less

A low jitter PLL clock used for phase change memory

NASA Astrophysics Data System (ADS)

Xiao, Hong; Houpeng, Chen; Zhitang, Song; Daolin, Cai; Xi, Li

2013-02-01

A fully integrated low-jitter, precise frequency CMOS phase-locked loop (PLL) clock for the phase change memory (PCM) drive circuit is presented. The design consists of a dynamic dual-reset phase frequency detector (PFD) with high frequency acquisition, a novel low jitter charge pump, a CMOS ring oscillator based voltage-controlled oscillator (VCO), a 2nd order passive loop filter, and a digital frequency divider. The design is fabricated in 0.35 μm CMOS technology and consumes 20 mW from a supply voltage of 5 V. In terms of the PCM's program operation requirement, the output frequency range is from 1 to 140 MHz. For the 140 MHz output frequency, the circuit features a cycle-to-cycle jitter of 28 ps RMS and 250 ps peak-to-peak.

Shape-Memory-Alloy Actuator For Flight Controls

NASA Technical Reports Server (NTRS)

Barret, Chris

1995-01-01

Report proposes use of shape-memory-alloy actuators, instead of hydraulic actuators, for aerodynamic flight-control surfaces. Actuator made of shape-memory alloy converts thermal energy into mechanical work by changing shape as it makes transitions between martensitic and austenitic crystalline phase states of alloy. Because both hot exhaust gases and cryogenic propellant liquids available aboard launch rockets, shape-memory-alloy actuators exceptionally suited for use aboard such rockets.

Phase change cellular automata modeling of GeTe, GaSb and SnSe stacked chalcogenide films

NASA Astrophysics Data System (ADS)

Mihai, C.; Velea, A.

2018-06-01

Data storage needs are increasing at a rapid pace across all economic sectors, so the need for new memory technologies with adequate capabilities is also high. Phase change memories (PCMs) are a leading contender in the emerging race for non-volatile memories due to their fast operation speed, high scalability, good reliability and low power consumption. However, in order to meet the present and future storage demands, PCM technologies must further increase the storage density. Here, we employ a probabilistic cellular automata approach to explore the multi-step threshold switching from the reset (off) to the set (on) state in chalcogenide stacked structures. Simulations have shown that in order to obtain multi-step switching with high contrast among different resistance states, the stacked structure needs to contain materials with a large difference among their crystallization temperatures and careful tuning of strata thicknesses. The crystallization dynamics can be controlled through the external energy pulses applied to the system, in such a way that a balance between nucleation and growth in phase change behavior can be achieved, optimized for PCMs.

IL-15 signaling promotes adoptive effector T-cell survival and memory formation in irradiation-induced lymphopenia.

PubMed

Xu, Aizhang; Bhanumathy, Kalpana Kalyanasundaram; Wu, Jie; Ye, Zhenmin; Freywald, Andrew; Leary, Scot C; Li, Rongxiu; Xiang, Jim

2016-01-01

Lymphopenia promotes naïve T-cell homeostatic proliferation and adoptive effector T-cell survival and memory formation. IL-7 plays a critical role in homeostatic proliferation, survival and memory formation of naïve T-cells in lymphopenia, and its underlying molecular mechanism has also been well studied. However, the mechanism for adoptively transferred effector T-cell survival and memory formation is not fully understood. Here, we transferred in vitro-activated transgenic OT-I CD8(+) effector T-cells into irradiation (600 rads)-induced lymphopenic C57BL/6, IL-7 knockout (KO) and IL-15 KO mice, and investigated the survival and memory formation of transferred T-cells in lymphopenia. We demonstrate that transferred T-cells prolong their survival and enhance their memory in lymphopenic mice, in a manner that depends on IL-15 signaling, but not IL-7. We determine that in vitro stimulation of naïve or effector T-cells with IL-7 and IL-15 reduces IL-7Rα, and increases and/or maintains IL-15Rβ expression, respectively. Consistent with these findings, the expression of IL-7Rα and IL-15Rβ is down- and up-regulated, respectively, in vivo on transferred T-cells in an early phase post T-cell transfer in lymphopenia. We further show that in vitro IL-15 restimulation-induced memory T-cells (compared to IL-2 restimulation-induced effector T-cells) and in vivo transferred T-cells in irradiated IL-15-sufficient C57BL/6 mice (compared to IL-15-deficient IL-15 KO mice) have increased mitochondrial content, but less NADH and lower mitochondrial potential (ΔΨm), and demonstrate greater phosphorylation of signal transducers and activators of transcription-5 (STAT5) and Unc-51-like kinase-1 (ULK1), and higher expression of B-cell leukemia/lymphoma-2 (Bcl2) and memory-, autophagy- and mitochondrial biogenesis-related molecules. Irradiation-induced lymphopenia promotes effector T-cell survival via IL-15 signaling the STAT5/Bcl2 pathway, enhances T-cell memory formation via IL-15 activation of the forkhead-box family of transcription factor (FOXO)/eomesodermin (Eomes) memory and ULK1/autophagy-related gene-7 (ATG7) autophagy pathways, and via IL-15 activation of the mitochondrial remodeling. Our data thus identify some important targets to consider when designing potent adoptive T-cell immunotherapies of cancer.

CogState computerized memory tests in patients with brain metastases: secondary endpoint results of NRG Oncology RTOG 0933.

PubMed

Caine, Chip; Deshmukh, Snehal; Gondi, Vinai; Mehta, Minesh; Tomé, Wolfgang; Corn, Benjamin W; Kanner, Andrew; Rowley, Howard; Kundapur, Vijayananda; DeNittis, Albert; Greenspoon, Jeffrey Noah; Konski, Andre A; Bauman, Glenn S; Raben, Adam; Shi, Wenyin; Wendland, Merideth; Kachnic, Lisa

2016-01-01

Whole brain radiotherapy (WBRT) is associated with memory dysfunction. As part of NRG Oncology RTOG 0933, a phase II study of WBRT for brain metastases that conformally avoided the hippocampal stem cell compartment (HA-WBRT), memory was assessed pre- and post-HA-WBRT using both traditional and computerized memory tests. We examined whether the computerized tests yielded similar findings and might serve as possible alternatives for assessment of memory in multi-institution clinical trials. Adult patients with brain metastases received HA-WBRT to 30 Gy in ten fractions and completed Hopkins Verbal Learning Test-Revised (HVLT-R), CogState International Shopping List Test (ISLT) and One Card Learning Test (OCLT), at baseline, 2 and 4 months. Tests' completion rates were 52-53 % at 2 months and 34-42 % at 4 months. All baseline correlations between HVLT-R and CogState tests were significant (p ≤ 0.003). At baseline, both CogState tests and one component of HVLT-R differentiated those who were alive at 6 months and those who had died (p ≤ 0.01). At 4 months, mean relative decline was 7.0 % for HVLT-R Delayed Recall and 18.0 % for ISLT Delayed Recall. OCLT showed an 8.0 % increase. A reliable change index found no significant changes from baseline to 2 and 4 months for ISLT Delayed Recall (z = -0.40, p = 0.34; z = -0.68, p = 0.25) or OCLT (z = 0.15, p = 0.56; z = 0.41, p = 0.66). Study findings support the possibility that hippocampal avoidance may be associated with preservation of memory test performance, and that these computerized tests also may be useful and valid memory assessments in multi-institution adult brain tumor trials.

Non-von Neumann computing using plasmon particles interacting with phase change materials (Conference Presentation)

NASA Astrophysics Data System (ADS)

Saiki, Toshiharu

2016-09-01

Control of localized surface plasmon resonance (LSPR) excited on metal nanostructures has drawn attention for applications in dynamic switching of plasmonic devices. As a reversible active media for LSPR control, chalcogenide phase-change materials (PCMs) such as GeSbTe (GST) are promising for high-contrast robust plasmonic switching. Owing to the plasticity and the threshold behavior during both amorphization and crystallization of PCMs, PCM-based LSPR switching elements possess a dual functionality of memory and processing. Integration of LSPR switching elements so that they interact with each other will allow us to build non-von-Neumann computing devices. As a specific demonstration, we discuss the implementation of a cellular automata (CA) algorithm into interacting LSPR switching elements. In the model we propose, PCM cells, which can be in one of two states (amorphous and crystalline), interact with each other by being linked by a AuNR, whose LSPR peak wavelength is determined by the phase of PCM cells on the both sides. The CA program proceeds by irradiating with a light pulse train. The local rule set is defined by the temperature rise in the PCM cells induced by the LSPR of the AuNR, which is subject to the intensity and wavelength of the irradiating pulse. We also investigate the possibility of solving a problem analogous to the spin-glass problem by using a coupled dipole system, in which the individual coupling strengths can be modified to optimize the system so that the exact solution can be easily reached. For this algorithm, we propose an implementation based on an idea that coupled plasmon particles can create long-range spatial correlations, and the interaction of this with a phase-change material allows the coupling strength to be modified.

Ratio of Circulating IFNγ (+) "Th17 Cells" in Memory Th Cells Is Inversely Correlated with the Titer of Anti-CCP Antibodies in Early-Onset Rheumatoid Arthritis Patients Based on Flow Cytometry Methods of the Human Immunology Project.

PubMed

Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

2016-01-01

Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic joint inflammation characterized by activated T cells. IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. However, it remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we validated the methods of the Human Immunology Project using only the cell-surface marker through measuring the actual expression of IL-17 and IFNγ. We also evaluated the expression of CD161 in human Th17 cells. We then tried to identify Th17 cells, IL-17(+)Th17 cells, and IFNγ (+)Th17 cells in the peripheral blood of early-onset RA patients using the standardized method of the Human Immunology Project. Our findings validated the method and the expression of CD161. The ratio of IFNγ (+)Th17 cells in memory T cells was inversely correlated to the titers of anti-CCP antibodies in the early-onset RA patients. These findings suggest that Th17 cells play important roles in the early phase of RA and that anti-IL-17 antibodies should be administered to patients with early phase RA, especially those with high titers of CCP antibodies.

Persistence of transgene expression influences CD8+ T-cell expansion and maintenance following immunization with recombinant adenovirus.

PubMed

Finn, Jonathan D; Bassett, Jennifer; Millar, James B; Grinshtein, Natalie; Yang, Teng Chih; Parsons, Robin; Evelegh, Carole; Wan, Yonghong; Parks, Robin J; Bramson, Jonathan L

2009-12-01

Previous studies determined that the CD8(+) T-cell response elicited by recombinant adenovirus exhibited a protracted contraction phase that was associated with long-term presentation of antigen. To gain further insight into this process, a doxycycline-regulated adenovirus was constructed to enable controlled extinction of transgene expression in vivo. We investigated the impact of premature termination of transgene expression at various time points (day 3 to day 60) following immunization. When transgene expression was terminated before the maximum response had been attained, overall expansion was attenuated, yielding a small memory population. When transgene expression was terminated between day 13 and day 30, the memory population was not sustained, demonstrating that the early memory population was antigen dependent. Extinction of transgene expression at day 60 had no obvious impact on memory maintenance, indicating that maintenance of the memory population may ultimately become independent of transgene expression. Premature termination of antigen expression had significant but modest effects on the phenotype and cytokine profile of the memory population. These results offer new insights into the mechanisms of memory CD8(+) T-cell maintenance following immunization with a recombinant adenovirus.

A rotating arm using shape-memory alloy

NASA Technical Reports Server (NTRS)

Jenkins, Phillip P.; Landis, Geoffrey A.

1995-01-01

NASA's Mars Pathfinder mission, to be launched in 1996, reflects a new philosophy of exploiting new technologies to reduce mission cost and accelerate the pace of space exploration. One of the experiments on board Pathfinder will demonstrate the first use in space of a multi-cycle, electrically-activated, shape-memory alloy (SMA) actuator. SMA's are metal alloys which, when heated, undergo a crystalline phase change. This change in phase alters the alloy lattice-constant, resulting in a change of dimension. Upon cooling, the alloy returns to its original lattice formation. Wire drawn from an SMA contracts in length when heated. The reversible change in length is 3 percent to 5 percent. The wire used in this actuator is a nickel-titanium alloy known as nitinol.

Atomistic to Continuum Multiscale and Multiphysics Simulation of NiTi Shape Memory Alloy

NASA Astrophysics Data System (ADS)

Gur, Sourav

Shape memory alloys (SMAs) are materials that show reversible, thermo-elastic, diffusionless, displacive (solid to solid) phase transformation, due to the application of temperature and/ or stress (/strain). Among different SMAs, NiTi is a popular one. NiTi shows reversible phase transformation, the shape memory effect (SME), where irreversible deformations are recovered upon heating, and superelasticity (SE), where large strains imposed at high enough temperatures are fully recovered. Phase transformation process in NiTi SMA is a very complex process that involves the competition between developed internal strain and phonon dispersion instability. In NiTi SMA, phase transformation occurs over a wide range of temperature and/ or stress (strain) which involves, evolution of different crystalline phases (cubic austenite i.e. B2, different monoclinic variant of martensite i.e. B19', and orthorhombic B19 or BCO structures). Further, it is observed from experimental and computational studies that the evolution kinetics and growth rate of different phases in NiTi SMA vary significantly over a wide spectrum of spatio-temporal scales, especially with length scales. At nano-meter length scale, phase transformation temperatures, critical transformation stress (or strain) and phase fraction evolution change significantly with sample or simulation cell size and grain size. Even, below a critical length scale, the phase transformation process stops. All these aspects make NiTi SMA very interesting to the science and engineering research community and in this context, the present focuses on the following aspects. At first this study address the stability, evolution and growth kinetics of different phases (B2 and variants of B19'), at different length scales, starting from the atomic level and ending at the continuum macroscopic level. The effects of simulation cell size, grain size, and presence of free surface and grain boundary on the phase transformation process (transformation temperature, phase fraction evolution kinetics due to temperature) are also demonstrated herein. Next, to couple and transfer the statistical information of length scale dependent phase transformation process, multiscale/ multiphysics methods are used. Here, the computational difficulty from the fact that the representative governing equations (i.e. different sub-methods such as molecular dynamics simulations, phase field simulations and continuum level constitutive/ material models) are only valid or can be implemented over a range of spatiotemporal scales. Therefore, in the present study, a wavelet based multiscale coupling method is used, where simulation results (phase fraction evolution kinetics) from different sub-methods are linked via concurrent multiscale coupling fashion. Finally, these multiscale/ multiphysics simulation results are used to develop/ modify the macro/ continuum scale thermo-mechanical constitutive relations for NiTi SMA. Finally, the improved material model is used to model new devices, such as thermal diodes and smart dampers.

Menstrual cycle phase effects on memory and Stroop task performance.

PubMed

Hatta, Takeshi; Nagaya, Keiko

2009-10-01

The present study examined differences in Stroop and memory task performances modulated by gonadal steroid hormones during the menstrual cycle in women. Thirty women with regular menstrual cycles performed a logical memory task (Wechsler Memory Scale) and the Stroop task. The results showed a significant difference in Stroop task performance between low and high levels of estradiol and progesterone during the menstrual cycle, but there was no significant difference in memory performance between the two phases, nor was there any significant mood change that might have influenced cognitive performance. These findings suggest that sex-related hormone modulation selectively affects cognitive functions depending on the type of task and low level secretion of estradiol appears to contribute to reducing the level of attention that relates to the prefrontal cortex.

Influence of silicon oxide on the performance of TiN bottom electrode in phase change memory

NASA Astrophysics Data System (ADS)

Gao, Dan; Liu, Bo; Xu, Zhen; Wang, Heng; Xia, Yangyang; Wang, Lei; Zhu, Nanfei; Li, Ying; Zhan, Yipeng; Song, Zhitang; Feng, Songlin

2016-10-01

The stability of TiN which is the preferred bottom electrode contact (BEC) of phase change memory (PCM) due to its low thermal conductivity and suitable electrical conductivity, is very essential to the reliability of PCM devices. In this work, in order to investigate the effect of high aspect ratio process (HARP) SiO2 on the performance of TiN, both TiN/SiO2, TiN/SiN thin films and TiN BEC device structures are analyzed. By combining transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDS), we found that the TiN would be oxidized after the deposition of HARP SiO2 and there exist a thin ( 4 nm) oxidation interfacial layer between TiN and SiO2. Electrical measurements were performed on the 1R PCM test-key die with 7 nm and 10 nm BEC-only cells. The statistical initial resistances of BEC have wide distribution and it is confirmed that the non-uniform oxidation of TiN BEC affects the astringency of the resistance of TiN BEC. The experimental results help to optimize the process of TiN BEC, and SiN is recommended as a better choice as the linear layer.

Naïve and memory CD8 T cell pool homeostasis in advanced aging: impact of age and of antigen-specific responses to cytomegalovirus.

PubMed

Vescovini, Rosanna; Fagnoni, Francesco Fausto; Telera, Anna Rita; Bucci, Laura; Pedrazzoni, Mario; Magalini, Francesca; Stella, Adriano; Pasin, Federico; Medici, Maria Cristina; Calderaro, Adriana; Volpi, Riccardo; Monti, Daniela; Franceschi, Claudio; Nikolich-Žugich, Janko; Sansoni, Paolo

2014-04-01

Alterations in the circulating CD8+ T cell pool, with a loss of naïve and accumulation of effector/effector memory cells, are pronounced in older adults. However, homeostatic forces that dictate such changes remain incompletely understood. This observational cross-sectional study explored the basis for variability of CD8+ T cell number and composition of its main subsets: naïve, central memory and effector memory T cells, in 131 cytomegalovirus (CMV) seropositive subjects aged over 60 years. We found great heterogeneity of CD8+ T cell numbers, which was mainly due to variability of the CD8 + CD28- T cell subset regardless of age. Analysis, by multiple regression, of distinct factors revealed that age was a predictor for the loss in absolute number of naïve T cells, but was not associated with changes in central or effector memory CD8+ T cell subsets. By contrast, the size of CD8+ T cells specific to pp65 and IE-1 antigens of CMV, predicted CD28 - CD8+ T cell, antigen-experienced CD8+ T cell, and even total CD8+ T cell numbers, but not naïve CD8+ T cell loss. These results indicate a clear dichotomy between the homeostasis of naïve and antigen-experienced subsets of CD8+ T cells which are independently affected, in human later life, by age and antigen-specific responses to CMV, respectively.

Towards Terabit Memories

NASA Astrophysics Data System (ADS)

Hoefflinger, Bernd

Memories have been the major yardstick for the continuing validity of Moore's law. In single-transistor-per-Bit dynamic random-access memories (DRAM), the number of bits per chip pretty much gives us the number of transistors. For decades, DRAM's have offered the largest storage capacity per chip. However, DRAM does not scale any longer, both in density and voltage, severely limiting its power efficiency to 10 fJ/b. A differential DRAM would gain four-times in density and eight-times in energy. Static CMOS RAM (SRAM) with its six transistors/cell is gaining in reputation because it scales well in cell size and operating voltage so that its fundamental advantage of speed, non-destructive read-out and low-power standby could lead to just 2.5 electrons/bit in standby and to a dynamic power efficiency of 2aJ/b. With a projected 2020 density of 16 Gb/cm², the SRAM would be as dense as normal DRAM and vastly better in power efficiency, which would mean a major change in the architecture and market scenario for DRAM versus SRAM. Non-volatile Flash memory have seen two quantum jumps in density well beyond the roadmap: Multi-Bit storage per transistor and high-density TSV (through-silicon via) technology. The number of electrons required per Bit on the storage gate has been reduced since their first realization in 1996 by more than an order of magnitude to 400 electrons/Bit in 2010 for a complexity of 32Gbit per chip at the 32 nm node. Chip stacking of eight chips with TSV has produced a 32GByte solid-state drive (SSD). A stack of 32 chips with 2 b/cell at the 16 nm node will reach a density of 2.5 Terabit/cm². Non-volatile memory with a density of 10 × 10 nm²/Bit is the target for widespread development. Phase-change memory (PCM) and resistive memory (RRAM) lead in cell density, and they will reach 20 Gb/cm² in 2D and higher with 3D chip stacking. This is still almost an order-of-magnitude less than Flash. However, their read-out speed is ~10-times faster, with as yet little data on their energy/b. As a read-out memory with unparalleled retention and lifetime, the ROM with electron-beam direct-write-lithography (Chap. 8) should be considered for its projected 2D density of 250 Gb/cm², a very small read energy of 0.1 μW/Gb/s. The lithography write-speed 10 ms/Terabit makes this ROM a serious contentender for the optimum in non-volatile, tamper-proof storage.

Ratio of Circulating IFNγ + “Th17 Cells” in Memory Th Cells Is Inversely Correlated with the Titer of Anti-CCP Antibodies in Early-Onset Rheumatoid Arthritis Patients Based on Flow Cytometry Methods of the Human Immunology Project

PubMed Central

Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

2016-01-01

Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic joint inflammation characterized by activated T cells. IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. However, it remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we validated the methods of the Human Immunology Project using only the cell-surface marker through measuring the actual expression of IL-17 and IFNγ. We also evaluated the expression of CD161 in human Th17 cells. We then tried to identify Th17 cells, IL-17+Th17 cells, and IFNγ +Th17 cells in the peripheral blood of early-onset RA patients using the standardized method of the Human Immunology Project. Our findings validated the method and the expression of CD161. The ratio of IFNγ +Th17 cells in memory T cells was inversely correlated to the titers of anti-CCP antibodies in the early-onset RA patients. These findings suggest that Th17 cells play important roles in the early phase of RA and that anti-IL-17 antibodies should be administered to patients with early phase RA, especially those with high titers of CCP antibodies. PMID:27294146

Early programming and late-acting checkpoints governing the development of CD4 T cell memory.

PubMed

Dhume, Kunal; McKinstry, K Kai

2018-04-27

CD4 T cells contribute to protection against pathogens through numerous mechanisms. Incorporating the goal of memory CD4 T cell generation into vaccine strategies thus offers a powerful approach to improve their efficacy, especially in situations where humoral responses alone cannot confer long-term immunity. These threats include viruses such as influenza that mutate coat proteins to avoid neutralizing antibodies, but that are targeted by T cells that recognize more conserved protein epitopes shared by different strains. A major barrier in the design of such vaccines is that the mechanisms controlling the efficiency with which memory cells form remain incompletely understood. Here, we discuss recent insights into fate decisions controlling memory generation. We focus on the importance of three general cues: interleukin-2, antigen, and costimulatory interactions. It is increasingly clear that these signals have a powerful influence on the capacity of CD4 T cells to form memory during two distinct phases of the immune response. First, through 'programming' that occurs during initial priming, and second, through 'checkpoints' that operate later during the effector stage. These findings indicate that novel vaccine strategies must seek to optimize cognate interactions, during which interleukin-2-, antigen, and costimulation-dependent signals are tightly linked, well beyond initial antigen encounter to induce robust memory CD4 T cells. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Running wheel training does not change neurogenesis levels or alter working memory tasks in adult rats

PubMed Central

Rojas, Manuel J.; Cardenas P., Fernando

2017-01-01

Background Exercise can change cellular structure and connectivity (neurogenesis or synaptogenesis), causing alterations in both behavior and working memory. The aim of this study was to evaluate the effect of exercise on working memory and hippocampal neurogenesis in adult male Wistar rats using a T-maze test. Methods An experimental design with two groups was developed: the experimental group (n = 12) was subject to a forced exercise program for five days, whereas the control group (n = 9) stayed in the home cage. Six to eight weeks after training, the rats’ working memory was evaluated in a T-maze test and four choice days were analyzed, taking into account alternation as a working memory indicator. Hippocampal neurogenesis was evaluated by means of immunohistochemistry of BrdU positive cells. Results No differences between groups were found in the behavioral variables (alternation, preference index, time of response, time of trial or feeding), or in the levels of BrdU positive cells. Discussion Results suggest that although exercise may have effects on brain structure, a construct such as working memory may require more complex changes in networks or connections to demonstrate a change at behavioral level. PMID:28503368

Reduced tonic inhibition in the dentate gyrus contributes to chronic stress-induced impairments in learning and memory.

PubMed

Lee, Vallent; MacKenzie, Georgina; Hooper, Andrew; Maguire, Jamie

2016-10-01

It is well established that stress impacts the underlying processes of learning and memory. The effects of stress on memory are thought to involve, at least in part, effects on the hippocampus, which is particularly vulnerable to stress. Chronic stress induces hippocampal alterations, including but not limited to dendritic atrophy and decreased neurogenesis, which are thought to contribute to chronic stress-induced hippocampal dysfunction and deficits in learning and memory. Changes in synaptic transmission, including changes in GABAergic inhibition, have been documented following chronic stress. Recently, our laboratory demonstrated shifts in EGABA in CA1 pyramidal neurons following chronic stress, compromising GABAergic transmission and increasing excitability of these neurons. Interestingly, here we demonstrate that these alterations are unique to CA1 pyramidal neurons, since we do not observe shifts in EGABA following chronic stress in dentate gyrus granule cells. Following chronic stress, there is a decrease in the expression of the GABAA receptor (GABAA R) δ subunit and tonic GABAergic inhibition in dentate gyrus granule cells, whereas there is an increase in the phasic component of GABAergic inhibition, evident by an increase in the peak amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs). Given the numerous changes observed in the hippocampus following stress, it is difficult to pinpoint the pertinent contributing pathophysiological factors. Here we directly assess the impact of a reduction in tonic GABAergic inhibition of dentate gyrus granule cells on learning and memory using a mouse model with a decrease in GABAA R δ subunit expression specifically in dentate gyrus granule cells (Gabrd/Pomc mice). Reduced GABAA R δ subunit expression and function in dentate gyrus granule cells is sufficient to induce deficits in learning and memory. Collectively, these findings suggest that the reduction in GABAA R δ subunit-mediated tonic inhibition in dentate gyrus granule cells contributes, at least in part, to deficits in learning and memory associated with chronic stress. These findings have significant implications regarding the pathophysiological mechanisms underlying impairments in learning and memory associated with stress and suggest a role for GABAA R δ subunit containing receptors in dentate gyrus granule cells. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Ultralow-power switching via defect engineering in germanium telluride phase-change memory devices.

PubMed

Nukala, Pavan; Lin, Chia-Chun; Composto, Russell; Agarwal, Ritesh

2016-01-25

Crystal-amorphous transformation achieved via the melt-quench pathway in phase-change memory involves fundamentally inefficient energy conversion events; and this translates to large switching current densities, responsible for chemical segregation and device degradation. Alternatively, introducing defects in the crystalline phase can engineer carrier localization effects enhancing carrier-lattice coupling; and this can efficiently extract work required to introduce bond distortions necessary for amorphization from input electrical energy. Here, by pre-inducing extended defects and thus carrier localization effects in crystalline GeTe via high-energy ion irradiation, we show tremendous improvement in amorphization current densities (0.13-0.6 MA cm(-2)) compared with the melt-quench strategy (∼50 MA cm(-2)). We show scaling behaviour and good reversibility on these devices, and explore several intermediate resistance states that are accessible during both amorphization and recrystallization pathways. Existence of multiple resistance states, along with ultralow-power switching and scaling capabilities, makes this approach promising in context of low-power memory and neuromorphic computation.

Ultralow-power switching via defect engineering in germanium telluride phase-change memory devices

PubMed Central

Nukala, Pavan; Lin, Chia-Chun; Composto, Russell; Agarwal, Ritesh

2016-01-01

Crystal–amorphous transformation achieved via the melt-quench pathway in phase-change memory involves fundamentally inefficient energy conversion events; and this translates to large switching current densities, responsible for chemical segregation and device degradation. Alternatively, introducing defects in the crystalline phase can engineer carrier localization effects enhancing carrier–lattice coupling; and this can efficiently extract work required to introduce bond distortions necessary for amorphization from input electrical energy. Here, by pre-inducing extended defects and thus carrier localization effects in crystalline GeTe via high-energy ion irradiation, we show tremendous improvement in amorphization current densities (0.13–0.6 MA cm−2) compared with the melt-quench strategy (∼50 MA cm−2). We show scaling behaviour and good reversibility on these devices, and explore several intermediate resistance states that are accessible during both amorphization and recrystallization pathways. Existence of multiple resistance states, along with ultralow-power switching and scaling capabilities, makes this approach promising in context of low-power memory and neuromorphic computation. PMID:26805748

Deformation and Phase Transformation Processes in Polycrystalline NiTi and NiTiHf High Temperature Shape Memory Alloys

NASA Technical Reports Server (NTRS)

Benafan, Othmane

2012-01-01

The deformation and transformation mechanisms of polycrystalline Ni49.9Ti50.1 and Ni50.3Ti29.7Hf20 (in at.%) shape memory alloys were investigated by combined experimental and modeling efforts aided by an in situ neutron diffraction technique at stress and temperature. The thermomechanical response of the low temperature martensite, the high temperature austenite phases, and changes between these two states during thermomechanical cycling were probed and reported. In the cubic austenite phase, stress-induced martensite, deformation twinning and slip processes were observed which helped in constructing a deformation map that contained the limits over which each of the identified mechanisms was dominant. Deformation of the monoclinic martensitic phase was also investigated where the microstructural changes (texture, lattice strains, and phase fractions) during room-temperature deformation and subsequent thermal cycling were compared to the bulk macroscopic response. When cycling between these two phases, the evolution of inelastic strains, along with the shape setting procedures were examined and used for the optimization of the transformation properties as a function of deformation levels and temperatures. Finally, this work was extended to the development of multiaxial capabilities at elevated temperatures for the in situ neutron diffraction measurements of shape memory alloys on the VULCAN Diffractometer at Oak Ridge National Laboratory.

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.

Intrahemispheric theta rhythm desynchronization impairs working memory.

PubMed

Alekseichuk, Ivan; Pabel, Stefanie Corinna; Antal, Andrea; Paulus, Walter

2017-01-01

There is a growing interest in large-scale connectivity as one of the crucial factors in working memory. Correlative evidence has revealed the anatomical and electrophysiological players in the working memory network, but understanding of the effective role of their connectivity remains elusive. In this double-blind, placebo-controlled study we aimed to identify the causal role of theta phase connectivity in visual-spatial working memory. The frontoparietal network was over- or de-synchronized in the anterior-posterior direction by multi-electrode, 6 Hz transcranial alternating current stimulation (tACS). A decrease in memory performance and increase in reaction time was caused by frontoparietal intrahemispheric desynchronization. According to the diffusion drift model, this originated in a lower signal-to-noise ratio, known as the drift rate index, in the memory system. The EEG analysis revealed a corresponding decrease in phase connectivity between prefrontal and parietal areas after tACS-driven desynchronization. The over-synchronization did not result in any changes in either the behavioral or electrophysiological levels in healthy participants. Taken together, we demonstrate the feasibility of manipulating multi-site large-scale networks in humans, and the disruptive effect of frontoparietal desynchronization on theta phase connectivity and visual-spatial working memory.

Changes in immunological profile as a function of urbanization and lifestyle

PubMed Central

Mbow, Moustapha; de Jong, Sanne E; Meurs, Lynn; Mboup, Souleymane; Dieye, Tandakha Ndiaye; Polman, Katja; Yazdanbakhsh, Maria

2014-01-01

Differences in lifestyle and break with natural environment appear to be associated with changes in the immune system resulting in various adverse health effects. Although genetics can have a major impact on the immune system and disease susceptibility, the contribution of environmental factors is thought to be substantial. Here, we investigated the immunological profile of healthy volunteers living in a rural and an urban area of a developing African country (Senegal), and in a European country (the Netherlands). Using flow cytometry, we investigated T helper type 1 (Th1), Th2, Th17, Th22 and regulatory T cells, as well as CD4+ T-cell and B-cell activation markers, and subsets of memory T and B cells in the peripheral blood. Rural Senegalese had significantly higher frequencies of Th1, Th2 and Th22 cells, memory CD4+ T and B cells, as well as activated CD4+ T and B cells compared with urban Senegalese and urban Dutch people. Within the Senegalese population, rural paritcipants displayed significantly higher frequencies of Th2 and Th22 cells, as well as higher pro-inflammatory and T-cell activation and memory profiles compared with the urban population. The greater magnitude of immune activation and the enlarged memory pool, together with Th2 polarization, seen in rural participants from Africa, followed by urban Africans and Europeans suggest that environmental changes may define immunological footprints, which could have consequences for disease patterns in general and vaccine responses in particular. PMID:24924958

[Effect of alcohol on electrical organisation in the brain during a visuospatial working memory task and its relationship with the menstrual cycle].

PubMed

Sanz-Martin, Araceli; Hernández-González, Marisela; Guevara, Miguel Ángel; Santana, Gloria; Gumá-Díaz, Emilio

2014-02-01

The metabolism of alcohol and cognitive functions can vary during the menstrual cycle. Also, both alcohol ingestion and hormonal variations during menstruation have been associated with characteristic changes in electroencephalographic (EEG) activity. AIM. To determine whether EEG activity during a working memory task is affected by acute alcohol consumption, and if these EEG patterns vary in relation to different phases of the menstrual cycle. 24 women who drank a moderate dose of alcohol or placebo during the follicular and early luteal phases of the menstrual cycle. The EEG activity was recorded during performance of viso-spatial working memory task. Although the alcohol did not deteriorate the performance of working memory task, it caused in the EEG a decrease of relative theta power and lower right fronto-parietal correlation in theta and alpha2 bands. Only women who drank alcohol in the follicular phase had a higher relative potency of alpha1, which could indicate a lower level of arousal and attention. These results contribute to a better understanding of the brain mechanisms underlying cognitive changes with alcohol and its relationship to the menstrual cycle.

Temperature-driven topological quantum phase transitions in a phase-change material Ge2Sb2Te5.

PubMed

Eremeev, S V; Rusinov, I P; Echenique, P M; Chulkov, E V

2016-12-13

The Ge 2 Sb 2 Te 5 is a phase-change material widely used in optical memory devices and is a leading candidate for next generation non-volatile random access memory devices which are key elements of various electronics and portable systems. Despite the compound is under intense investigation its electronic structure is currently not fully understood. The present work sheds new light on the electronic structure of the Ge 2 Sb 2 Te 5 crystalline phases. We demonstrate by predicting from first-principles calculations that stable crystal structures of Ge 2 Sb 2 Te 5 possess different topological quantum phases: a topological insulator phase is realized in low-temperature structure and Weyl semimetal phase is a characteristic of the high-temperature structure. Since the structural phase transitions are caused by the temperature the switching between different topologically non-trivial phases can be driven by variation of the temperature. The obtained results reveal the rich physics of the Ge 2 Sb 2 Te 5 compound and open previously unexplored possibility for spintronics applications of this material, substantially expanding its application potential.

Independent rate and temporal coding in hippocampal pyramidal cells.

PubMed

Huxter, John; Burgess, Neil; O'Keefe, John

2003-10-23

In the brain, hippocampal pyramidal cells use temporal as well as rate coding to signal spatial aspects of the animal's environment or behaviour. The temporal code takes the form of a phase relationship to the concurrent cycle of the hippocampal electroencephalogram theta rhythm. These two codes could each represent a different variable. However, this requires the rate and phase to vary independently, in contrast to recent suggestions that they are tightly coupled, both reflecting the amplitude of the cell's input. Here we show that the time of firing and firing rate are dissociable, and can represent two independent variables: respectively the animal's location within the place field, and its speed of movement through the field. Independent encoding of location together with actions and stimuli occurring there may help to explain the dual roles of the hippocampus in spatial and episodic memory, or may indicate a more general role of the hippocampus in relational/declarative memory.

Music training is associated with cortical synchronization reflected in EEG coherence during verbal memory encoding.

PubMed

Cheung, Mei-Chun; Chan, Agnes S; Liu, Ying; Law, Derry; Wong, Christina W Y

2017-01-01

Music training can improve cognitive functions. Previous studies have shown that children and adults with music training demonstrate better verbal learning and memory performance than those without such training. Although prior studies have shown an association between music training and changes in the structural and functional organization of the brain, there is no concrete evidence of the underlying neural correlates of the verbal memory encoding phase involved in such enhanced memory performance. Therefore, we carried out an electroencephalography (EEG) study to investigate how music training was associated with brain activity during the verbal memory encoding phase. Sixty participants were recruited, 30 of whom had received music training for at least one year (the MT group) and 30 of whom had never received music training (the NMT group). The participants in the two groups were matched for age, education, gender distribution, and cognitive capability. Their verbal and visual memory functions were assessed using standardized neuropsychological tests and EEG was used to record their brain activity during the verbal memory encoding phase. Consistent with previous studies, the MT group demonstrated better verbal memory than the NMT group during both the learning and the delayed recall trials in the paper-and-pencil tests. The MT group also exhibited greater learning capacity during the learning trials. Compared with the NMT group, the MT group showed an increase in long-range left and right intrahemispheric EEG coherence in the theta frequency band during the verbal memory encoding phase. In addition, their event-related left intrahemispheric theta coherence was positively associated with subsequent verbal memory performance as measured by discrimination scores. These results suggest that music training may modulate the cortical synchronization of the neural networks involved in verbal memory formation.

Music training is associated with cortical synchronization reflected in EEG coherence during verbal memory encoding

PubMed Central

Cheung, Mei-chun; Chan, Agnes S.; Liu, Ying; Law, Derry; Wong, Christina W. Y.

2017-01-01

Music training can improve cognitive functions. Previous studies have shown that children and adults with music training demonstrate better verbal learning and memory performance than those without such training. Although prior studies have shown an association between music training and changes in the structural and functional organization of the brain, there is no concrete evidence of the underlying neural correlates of the verbal memory encoding phase involved in such enhanced memory performance. Therefore, we carried out an electroencephalography (EEG) study to investigate how music training was associated with brain activity during the verbal memory encoding phase. Sixty participants were recruited, 30 of whom had received music training for at least one year (the MT group) and 30 of whom had never received music training (the NMT group). The participants in the two groups were matched for age, education, gender distribution, and cognitive capability. Their verbal and visual memory functions were assessed using standardized neuropsychological tests and EEG was used to record their brain activity during the verbal memory encoding phase. Consistent with previous studies, the MT group demonstrated better verbal memory than the NMT group during both the learning and the delayed recall trials in the paper-and-pencil tests. The MT group also exhibited greater learning capacity during the learning trials. Compared with the NMT group, the MT group showed an increase in long-range left and right intrahemispheric EEG coherence in the theta frequency band during the verbal memory encoding phase. In addition, their event-related left intrahemispheric theta coherence was positively associated with subsequent verbal memory performance as measured by discrimination scores. These results suggest that music training may modulate the cortical synchronization of the neural networks involved in verbal memory formation. PMID:28358852

Phase-image-based content-addressable holographic data storage

NASA Astrophysics Data System (ADS)

John, Renu; Joseph, Joby; Singh, Kehar

2004-03-01

We propose and demonstrate the use of phase images for content-addressable holographic data storage. Use of binary phase-based data pages with 0 and π phase changes, produces uniform spectral distribution at the Fourier plane. The absence of strong DC component at the Fourier plane and more intensity of higher order spatial frequencies facilitate better recording of higher spatial frequencies, and improves the discrimination capability of the content-addressable memory. This improves the results of the associative recall in a holographic memory system, and can give low number of false hits even for small search arguments. The phase-modulated pixels also provide an opportunity of subtraction among data pixels leading to better discrimination between similar data pages.

The Effect of SiC Polytypes on the Heat Distribution Efficiency of a Phase Change Memory.

NASA Astrophysics Data System (ADS)

Aziz, M. S.; Mohammed, Z.; Alip, R. I.

2018-03-01

The amorphous to crystalline transition of germanium-antimony-tellurium (GST) using three types of silicon carbide’s structure as a heating element was investigated. Simulation was done using COMSOL Multiphysic 5.0 software with separate heater structure. Silicon carbide (SiC) has three types of structure; 3C-SiC, 4H-SiC and 6H-SiC. These structures have a different thermal conductivity. The temperature of GST and phase transition of GST can be obtained from the simulation. The temperature of GST when using 3C-SiC, 4H-SiC and 6H-SiC are 467K, 466K and 460K, respectively. The phase transition of GST from amorphous to crystalline state for three type of SiC’s structure can be determined in this simulation. Based on the result, the thermal conductivity of SiC can affecting the temperature of GST and changed of phase change memory (PCM).

Fast Crystallization of the Phase Change Compound GeTe by Large-Scale Molecular Dynamics Simulations.

PubMed

Sosso, Gabriele C; Miceli, Giacomo; Caravati, Sebastiano; Giberti, Federico; Behler, Jörg; Bernasconi, Marco

2013-12-19

Phase change materials are of great interest as active layers in rewritable optical disks and novel electronic nonvolatile memories. These applications rest on a fast and reversible transformation between the amorphous and crystalline phases upon heating, taking place on the nanosecond time scale. In this work, we investigate the microscopic origin of the fast crystallization process by means of large-scale molecular dynamics simulations of the phase change compound GeTe. To this end, we use an interatomic potential generated from a Neural Network fitting of a large database of ab initio energies. We demonstrate that in the temperature range of the programming protocols of the electronic memories (500-700 K), nucleation of the crystal in the supercooled liquid is not rate-limiting. In this temperature range, the growth of supercritical nuclei is very fast because of a large atomic mobility, which is, in turn, the consequence of the high fragility of the supercooled liquid and the associated breakdown of the Stokes-Einstein relation between viscosity and diffusivity.

Anti-MAdCAM Antibody Increases ß7+ T Cells and CCR9 Gene Expression in the Peripheral Blood of Patients With Crohn’s Disease

PubMed Central

Hassan-Zahraee, Mina; Banerjee, Anindita; Cheng, John B; Zhang, Weidong; Ahmad, Alaa; Page, Karen; von Schack, David; Zhang, Baohong; Martin, Steven W; Nayak, Satyaprakash; Reddy, Padma; Xi, Li; Neubert, Hendrik; Fernandez Ocana, Mireia; Gorelick, Ken; Clare, Robert; Vincent, Michael; Cataldi, Fabio; Hung, Kenneth

2018-01-01

Abstract Objective To define pharmacodynamic biomarkers in the peripheral blood of patients with Crohn’s disease [CD] after treatment with PF-00547659, an anti-human mucosal addressin cell adhesion molecule-1 [MAdCAM-1] monoclonal antibody. Methods In this Phase 2, randomised, double-blind, controlled study [OPERA], blood samples were analysed from patients with moderate to severe active CD who received placebo or 22.5 mg, 75 mg, or 225 mg of PF-00547659 subcutaneously at baseline and at Weeks 4 and 8, with follow-up at Week 12. Soluble MAdCAM [sMAdCAM] was measured by mass spectrometry, β7-expressing T cells by flow cytometry, and gene transcriptome by RNA sequencing. Results A slight increase in sMAdCAM was measured in the placebo group from baseline to Week 12 [6%], compared with significant decreases in all PF-00547659 groups [–87% to –98%]. A slight increase from baseline to Week 12 was observed in frequency and molecules of equivalent soluble fluorochrome for β7+ central memory T cells in the placebo group [4%], versus statistically significant increases in the active treatment groups [48% to 81%]. Similar trends were seen for β7+ effector memory T cells [placebo, 8%; PF-00547659, 84–138%] and β7+ naïve T cells [8%; 13–50%]. CCR9 gene expression had statistically significant up-regulation [p = 1.09e-06; false discovery rate < 0.1] with PF-00547659 treatment, and was associated with an increase in β7+ T cells. Conclusions Results of the OPERA study demonstrate positive pharmacology and dose-dependent changes in pharmacodynamic biomarker measurements in blood, including changes in cellular composition of lymphocytes and corresponding CCR9 gene expression changes. PMID:28961803

Anti-MAdCAM Antibody Increases ß7+ T Cells and CCR9 Gene Expression in the Peripheral Blood of Patients With Crohn's Disease.

PubMed

Hassan-Zahraee, Mina; Banerjee, Anindita; Cheng, John B; Zhang, Weidong; Ahmad, Alaa; Page, Karen; von Schack, David; Zhang, Baohong; Martin, Steven W; Nayak, Satyaprakash; Reddy, Padma; Xi, Li; Neubert, Hendrik; Fernandez Ocana, Mireia; Gorelick, Ken; Clare, Robert; Vincent, Michael; Cataldi, Fabio; Hung, Kenneth

2018-01-05

To define pharmacodynamic biomarkers in the peripheral blood of patients with Crohn's disease [CD] after treatment with PF-00547659, an anti-human mucosal addressin cell adhesion molecule-1 [MAdCAM-1] monoclonal antibody. In this Phase 2, randomised, double-blind, controlled study [OPERA], blood samples were analysed from patients with moderate to severe active CD who received placebo or 22.5 mg, 75 mg, or 225 mg of PF-00547659 subcutaneously at baseline and at Weeks 4 and 8, with follow-up at Week 12. Soluble MAdCAM [sMAdCAM] was measured by mass spectrometry, β7-expressing T cells by flow cytometry, and gene transcriptome by RNA sequencing. A slight increase in sMAdCAM was measured in the placebo group from baseline to Week 12 [6%], compared with significant decreases in all PF-00547659 groups [-87% to -98%]. A slight increase from baseline to Week 12 was observed in frequency and molecules of equivalent soluble fluorochrome for β7+ central memory T cells in the placebo group [4%], versus statistically significant increases in the active treatment groups [48% to 81%]. Similar trends were seen for β7+ effector memory T cells [placebo, 8%; PF-00547659, 84-138%] and β7+ naïve T cells [8%; 13-50%]. CCR9 gene expression had statistically significant up-regulation [p = 1.09e-06; false discovery rate < 0.1] with PF-00547659 treatment, and was associated with an increase in β7+ T cells. Results of the OPERA study demonstrate positive pharmacology and dose-dependent changes in pharmacodynamic biomarker measurements in blood, including changes in cellular composition of lymphocytes and corresponding CCR9 gene expression changes. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

Increased numbers of pre-existing memory CD8 T cells and decreased T-bet expression can restrain terminal differentiation of secondary effector and memory CD8 T cells1

PubMed Central

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

2011-01-01

Memory CD8 T cells acquire TEM properties following reinfection, and may reach terminally differentiated, senescent states (“Hayflick limit”) after multiple infections. The signals controlling this process are not well understood, but we found that the degree of 2o effector and memory CD8 T cell differentiation was intimately linked to the amount of T-bet expressed upon reactivation and pre-existing memory CD8 T cell number (i.e., 1o memory CD8 T cell precursor frequency) present during secondary infection. Compared to naïve cells, memory CD8 T cells were predisposed towards terminal effector (TE) cell differentiation because they could immediately respond to IL-12 and induce T-bet, even in the absence of antigen. TE cell formation following 2o or 3o infections was dependent on increased T-bet expression because T-bet+/− cells were resistant to these phenotypic changes. Larger numbers of pre-existing memory CD8 T cells limited the duration of 2o infection and the amount of IL-12 produced, and consequently, this reduced T-bet expression and the proportion of 2o TE CD8 T cells that formed. Together, these data show that, over repeated infections, memory CD8 T cell quality and proliferative fitness is not strictly determined by the number of serial encounters with antigen or cell divisions, but is a function of the CD8 T cell differentiation state, which is genetically controlled in a T-bet-dependent manner. This differentiation state can be modulated by pre-existing memory CD8 T cell number and the intensity of inflammation during reinfection. These results have important implications for vaccinations involving prime-boost strategies. PMID:21930973

Kinetics of B cell responses to Plasmodium falciparum erythrocyte membrane protein 1 in Ghanaian women naturally exposed to malaria parasites.

PubMed

Ampomah, Paulina; Stevenson, Liz; Ofori, Michael F; Barfod, Lea; Hviid, Lars

2014-06-01

Naturally acquired protective immunity to Plasmodium falciparum malaria takes years to develop. It relies mainly on Abs, particularly IgG specific for Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) proteins on the infected erythrocyte surface. It is only partially understood why acquisition of clinical protection takes years to develop, but it probably involves a range of immune-evasive parasite features, not least of which are PfEMP1 polymorphism and clonal variation. Parasite-induced subversion of immunological memory and expansion of "atypical" memory B cells may also contribute. In this first, to our knowledge, longitudinal study of its kind, we measured B cell subset composition, as well as PfEMP1-specific Ab levels and memory B cell frequencies, in Ghanaian women followed from early pregnancy up to 1 y after delivery. Cell phenotypes and Ag-specific B cell function were assessed three times during and after pregnancy. Levels of IgG specific for pregnancy-restricted, VAR2CSA-type PfEMP1 increased markedly during pregnancy and declined after delivery, whereas IgG levels specific for two PfEMP1 proteins not restricted to pregnancy did not. Changes in VAR2CSA-specific memory B cell frequencies showed typical primary memory induction among primigravidae and recall expansion among multigravidae, followed by contraction postpartum in all. No systematic changes in the frequencies of memory B cells specific for the two other PfEMP1 proteins were identified. The B cell subset analysis confirmed earlier reports of high atypical memory B cell frequencies among residents of P. falciparum-endemic areas, and indicated an additional effect of pregnancy. Our study provides new knowledge regarding immunity to P. falciparum malaria and underpins efforts to develop PfEMP1-based vaccines against this disease. Copyright © 2014 by The American Association of Immunologists, Inc.

Facilitation of memory encoding in primate hippocampus by a neuroprosthesis that promotes task-specific neural firing

NASA Astrophysics Data System (ADS)

Hampson, Robert E.; Song, Dong; Opris, Ioan; Santos, Lucas M.; Shin, Dae C.; Gerhardt, Greg A.; Marmarelis, Vasilis Z.; Berger, Theodore W.; Deadwyler, Sam A.

2013-12-01

Objective. Memory accuracy is a major problem in human disease and is the primary factor that defines Alzheimer’s, ageing and dementia resulting from impaired hippocampal function in the medial temporal lobe. Development of a hippocampal memory neuroprosthesis that facilitates normal memory encoding in nonhuman primates (NHPs) could provide the basis for improving memory in human disease states. Approach. NHPs trained to perform a short-term delayed match-to-sample (DMS) memory task were examined with multi-neuron recordings from synaptically connected hippocampal cell fields, CA1 and CA3. Recordings were analyzed utilizing a previously developed nonlinear multi-input multi-output (MIMO) neuroprosthetic model, capable of extracting CA3-to-CA1 spatiotemporal firing patterns during DMS performance. Main results. The MIMO model verified that specific CA3-to-CA1 firing patterns were critical for the successful encoding of sample phase information on more difficult DMS trials. This was validated by the delivery of successful MIMO-derived encoding patterns via electrical stimulation to the same CA1 recording locations during the sample phase which facilitated task performance in the subsequent, delayed match phase, on difficult trials that required more precise encoding of sample information. Significance. These findings provide the first successful application of a neuroprosthesis designed to enhance and/or repair memory encoding in primate brain.

Facilitation of Memory Encoding in Primate Hippocampus by a Neuroprosthesis that Promotes Task Specific Neural Firing

PubMed Central

Hampson, Robert E.; Song, Dong; Opris, Ioan; Santos, Lucas M.; Shin, Dae C.; Gerhardt, Greg A.; Marmarelis, Vasilis Z.; Berger, Theodore W.; Deadwyler, Sam A.

2014-01-01

Objective Memory accuracy is a major problem in human disease and is the primary factor that defines Alzheimer’s’, aging and dementia resulting from impaired hippocampal function in medial temporal lobe. Development of a hippocampal memory neuroprosthesis that facilitates normal memory encoding in nonhuman primates (NHPs) could provide the basis for improving memory in human disease states. Approach NHPs trained to perform a short-term delayed match to sample (DMS) memory task were examined with multi-neuron recordings from synaptically connected hippocampal cell fields, CA1 and CA3. Recordings were analyzed utilizing a previously developed nonlinear multi-input multi-output (MIMO) neuroprosthetic model, capable of extracting CA3-to-CA1 spatiotemporal firing patterns during DMS performance. Main Results The MIMO model verified that specific CA3-to-CA1 firing patterns were critical for successful encoding of Sample phase information on more difficult DMS trials. This was validated by delivery of successful MIMO-derived encoding patterns via electrical stimulation to the same CA1 recording locations during the Sample phase which facilitated task performance in the subsequent delayed Match phase on difficult trials that required more precise encoding of Sample information. Significance These findings provide the first successful application of a neuroprosthesis designed to enhance and/or repair memory encoding in primate brain. PMID:24216292

B-cell activation with CD40L or CpG measures the function of B-cell subsets and identifies specific defects in immunodeficient patients.

PubMed

Marasco, Emiliano; Farroni, Chiara; Cascioli, Simona; Marcellini, Valentina; Scarsella, Marco; Giorda, Ezio; Piano Mortari, Eva; Leonardi, Lucia; Scarselli, Alessia; Valentini, Diletta; Cancrini, Caterina; Duse, Marzia; Grimsholm, Ola; Carsetti, Rita

2017-01-01

Around 65% of primary immunodeficiencies are antibody deficiencies. Functional tests are useful tools to study B-cell functions in vitro. However, no accepted guidelines for performing and evaluating functional tests have been issued yet. Here, we report our experience on the study of B-cell functions in infancy and throughout childhood. We show that T-independent stimulation with CpG measures proliferation and differentiation potential of memory B cells. Switched memory B cells respond better than IgM memory B cells. On the other hand, CD40L, a T-dependent stimulus, does not induce plasma cell differentiation, but causes proliferation of naïve and memory B cells. During childhood, the production of plasmablasts in response to CpG increases with age mirroring the development of memory B cells. The response to CD40L does not change with age. In patients with selective IgA deficiency (SIgAD), we observed that switched memory B cells are reduced due to the absence of IgA memory B cells. In agreement, IgA plasma cells are not generated in response to CpG. Unexpectedly, B cells from SIgAD patients show a reduced proliferative response to CD40L. Our results demonstrate that functional tests are an important tool to assess the functions of the humoral immune system. © 2016 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The transience and nature of cognitive impairments in transient global amnesia: a meta-analysis.

PubMed

Jäger, Theodor; Bäzner, Hansjörg; Kliegel, Matthias; Szabo, Kristina; Hennerici, Michael G

2009-01-01

Transient global amnesia (TGA) is a clinical syndrome characterized by the sudden onset of severe amnesia without concomitant focal neurological symptoms. This meta-analysis of the cognitive characteristics of TGA addressed two main issues. First, we examined the hypothesis that the acute phase of TGA is associated with changes of anterograde and retrograde episodic long-term memory sparing semantic and short-term memory, while we had no clear prediction for potential reductions of executive functions due to the relative lack of previous studies addressing this issue. Second, we analyzed the time-course of changes in cognitive functions throughout three time intervals--acute (0-24 hours after TGA onset), postacute (24 hours to 5 days), and long-term phase (5-30 days)--to reveal whether there is a fast versus a delayed recovery. The results of the meta-analysis on 152 effect sizes from 25 studies showed that TGA is characterized by an extraordinarily large reduction of anterograde (d* = 1.89) and a somewhat milder reduction of retrograde (d* = 1.28) episodic long-term memory. Moreover, our results indicate the existence of additional, nonamnestic cognitive changes during TGA, because executive functions were also diminished (d* = 0.79). Reductions in both anterograde episodic long-term memory and executive function recover slowly, as slightly poorer performance in these cognitive domains can be found in the postacute phase (d*s = 0.32 and 0.44). All cognitive diminutions resolved within the long-term phase, by this calling into question previous reports of poorer performance of TGA patients relative to comparison subjects weeks or months after the attack.

Proton Irradiation of the 16GB Intel Optane SSD

NASA Technical Reports Server (NTRS)

Wyrwas, E. J.

2017-01-01

The purpose of this test is to assess the single event effects (SEE) and radiation susceptibility of the Intel Optane Memory device (SSD) containing the 3D Xpoint phase change memory (PCM) technology. This test is supported by the NASA Electronics Parts and Packaging Program (NEPP).

Kinetics of Epstein-Barr virus load and virus-specific CD8+ T cells in acute infectious mononucleosis.

PubMed

Hoshino, Yo; Nishikawa, Kazuo; Ito, Yoshinori; Kuzushima, Kiyotaka; Kimura, Hiroshi

2011-03-01

During the convalescent phase of acute infectious mononucleosis (AIM), Epstein-Barr virus (EBV) load shrinks rapidly in association with a rapid decline in the number of EBV-specific CD8(+) T cells. The actual contribution of EBV-specific CD8(+) T cells in reducing EBV load, however, is not known. To clarify the impact of EBV-specific CD8(+) T cells on the contraction of EBV load in AIM, we estimated half-lives of both EBV load and EBV-specific CD8(+) T cells. Blood was serially taken from five pediatric patients with AIM during the convalescent period, including the very early phase, and both EBV load and EBV-specific CD8(+) T cell numbers were assayed. EBV load declined rapidly (half-life 1.5 d) during the first 2 weeks after onset of symptoms. This half-life was seven-fold shorter than that reported for CD27(+) memory B cells. Subsequently, the EBV load declined much more slowly, with a half-life of 38.7 d. EBV-specific CD8(+) T cell numbers also declined concomitantly with the decrease in EBV load. The half-life of EBV-specific CD8(+) T cells during first 2 weeks was 2.9 d. The number of EBV-specific CD8(+) T cells and the rate of change of viral load correlated significantly (R(2) ≥ 0.8; p ≤ 0.02). The short half-life of EBV load, together with the strong correlation between the number of EBV-specific CD8(+) T cells and the rate of change of viral load indicates an active role for EBV-specific CD8(+) T cells in elimination of EBV in AIM. Copyright © 2010 Elsevier B.V. All rights reserved.

Mcm3 replicative helicase mutation impairs neuroblast proliferation and memory in Drosophila.

PubMed

Blumröder, R; Glunz, A; Dunkelberger, B S; Serway, C N; Berger, C; Mentzel, B; de Belle, J S; Raabe, T

2016-09-01

In the developing Drosophila brain, a small number of neural progenitor cells (neuroblasts) generate in a co-ordinated manner a high variety of neuronal cells by integration of temporal, spatial and cell-intrinsic information. In this study, we performed the molecular and phenotypic characterization of a structural brain mutant called small mushroom bodies (smu), which was isolated in a screen for mutants with altered brain structure. Focusing on the mushroom body neuroblast lineages we show that failure of neuroblasts to generate the normal number of mushroom body neurons (Kenyon cells) is the major cause of the smu phenotype. In particular, the premature loss of mushroom body neuroblasts caused a pronounced effect on the number of late-born Kenyon cells. Neuroblasts showed no obvious defects in processes controlling asymmetric cell division, but generated less ganglion mother cells. Cloning of smu uncovered a single amino acid substitution in an evolutionarily conserved protein interaction domain of the Minichromosome maintenance 3 (Mcm3) protein. Mcm3 is part of the multimeric Cdc45/Mcm/GINS (CMG) complex, which functions as a helicase during DNA replication. We propose that at least in the case of mushroom body neuroblasts, timely replication is not only required for continuous proliferation but also for their survival. The absence of Kenyon cells in smu reduced learning and early phases of conditioned olfactory memory. Corresponding to the absence of late-born Kenyon cells projecting to α'/β' and α/β lobes, smu is profoundly defective in later phases of persistent memory. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Analysis of adenovirus-induced immunity to infection with Listeria monocytogenes: Fading protection coincides with declining CD8 T cell numbers and phenotypic changes.

PubMed

Jahn, Marie Louise; Steffensen, Maria Abildgaard; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup

2018-05-11

Defining correlates of T cell mediated protection is important in order to accelerate the development of efficient T cell based vaccines conferring long-term immunity. Extensive studies have provided important insight regarding the characteristics and functional properties of the effector and memory CD8 T cells induced by viral vector based vaccines. However, long-term protection has been difficult to achieve with T cell inducing vaccines, and the determinants underlying this loss in protection over time are still not fully defined. In this study we analyzed different parameters of the CD8 T cell response as a function of time after vaccination with a human serotype 5 adenovector expressing the glycoprotein (GP) of LCMV tethered to the MHC class II-associated invariant chain. Using this vector we have previously found that CD8 T cells mediate protection from challenge with GP-expressing Listeria monocytogenes at 60 days post vaccination, but only little protection after further 60 days, and we now confirm this observation. A comparison of vaccine-primed CD8 T cells early and late after vaccination revealed a minor decline in the overall numbers of antigen specific memory CD8 T cells during this interval. More importantly, we also observed phenotypic changes over time with a distinct decline in the frequency and number of KLRG1 + CD8 T cells, and, notably, adoptive transfer studies confirmed that memory CD8 T cells expressing KLRG1 are central to protection from systemic L. monocytogenes infection. Together these findings imply that multiple factors including changes in memory T cell numbers and phenotypic composition over time influence the longevity of CD8 T-cell mediated protection. Copyright © 2018 Elsevier Ltd. All rights reserved.

Active cells for redundant and configurable articulated structures

NASA Astrophysics Data System (ADS)

Swensen, John P.; Nawroj, Ahsan I.; Pounds, Paul E. I.; Dollar, Aaron M.

2014-10-01

The proposed research effort explores the development of active cells—simple contractile electro-mechanical units that can be used as the material basis for larger articulable structures. Each cell, which might be considered a ‘muscle unit,’ consists of a contractile Nitinol Shape Memory Alloy (SMA) core with conductive terminals. Large numbers of these cells might be combined and externally powered to change phase, contracting to either articulate with a large strain or increase the stiffness of the ensemble, depending on the cell design. Unlike traditional work in modular robotics, the approach presented here focuses on cells that have a simplistic design and function, are inexpensive to fabricate, and are eventually scalable to sub-millimeter sizes, working toward our vision of articulated and robotic structures that can be custom-fabricated from large numbers of general cell units, similar to biological structures. In this paper, we present the design of the active cells and demonstrate their usage with three articulated structures built with them.

Genetic and epigenetic profiling of CLL disease progression reveals limited somatic evolution and suggests a relationship to memory-cell development.

PubMed

Smith, E N; Ghia, E M; DeBoever, C M; Rassenti, L Z; Jepsen, K; Yoon, K-A; Matsui, H; Rozenzhak, S; Alakus, H; Shepard, P J; Dai, Y; Khosroheidari, M; Bina, M; Gunderson, K L; Messer, K; Muthuswamy, L; Hudson, T J; Harismendy, O; Barrett, C L; Jamieson, C H M; Carson, D A; Kipps, T J; Frazer, K A

2015-04-10

We examined genetic and epigenetic changes that occur during disease progression from indolent to aggressive forms of chronic lymphocytic leukemia (CLL) using serial samples from 27 patients. Analysis of DNA mutations grouped the leukemia cases into three categories: evolving (26%), expanding (26%) and static (47%). Thus, approximately three-quarters of the CLL cases had little to no genetic subclonal evolution. However, we identified significant recurrent DNA methylation changes during progression at 4752 CpGs enriched for regions near Polycomb 2 repressive complex (PRC2) targets. Progression-associated CpGs near the PRC2 targets undergo methylation changes in the same direction during disease progression as during normal development from naive to memory B cells. Our study shows that CLL progression does not typically occur via subclonal evolution, but that certain CpG sites undergo recurrent methylation changes. Our results suggest CLL progression may involve developmental processes shared in common with the generation of normal memory B cells.

FPGA-based prototype storage system with phase change memory

NASA Astrophysics Data System (ADS)

Li, Gezi; Chen, Xiaogang; Chen, Bomy; Li, Shunfen; Zhou, Mi; Han, Wenbing; Song, Zhitang

2016-10-01

With the ever-increasing amount of data being stored via social media, mobile telephony base stations, and network devices etc. the database systems face severe bandwidth bottlenecks when moving vast amounts of data from storage to the processing nodes. At the same time, Storage Class Memory (SCM) technologies such as Phase Change Memory (PCM) with unique features like fast read access, high density, non-volatility, byte-addressability, positive response to increasing temperature, superior scalability, and zero standby leakage have changed the landscape of modern computing and storage systems. In such a scenario, we present a storage system called FLEET which can off-load partial or whole SQL queries to the storage engine from CPU. FLEET uses an FPGA rather than conventional CPUs to implement the off-load engine due to its highly parallel nature. We have implemented an initial prototype of FLEET with PCM-based storage. The results demonstrate that significant performance and CPU utilization gains can be achieved by pushing selected query processing components inside in PCM-based storage.

Observation of polyamorphism in the phase change alloy Ge1Sb2Te4

NASA Astrophysics Data System (ADS)

Kalkan, B.; Sen, S.; Cho, J.-Y.; Joo, Y.-C.; Clark, S. M.

2012-10-01

A high-pressure synchrotron x-ray diffraction study of the phase change alloy Ge1Sb2Te4 demonstrates the existence of a polyamorphic phase transition between the "as deposited" low density amorphous (LDA) phase and a high density amorphous (HDA) phase at ˜10 GPa. The entropy of the HDA phase is expected to be higher than that of the LDA phase resulting in a negative Clapeyron slope for this transition. These phase relations may enable the polyamorphic transition to play a role in the memory and data storage applications.

YOCAS©® Yoga Reduces Self-reported Memory Difficulty in Cancer Survivors in a Nationwide Randomized Clinical Trial: Investigating Relationships Between Memory and Sleep.

PubMed

Janelsins, Michelle C; Peppone, Luke J; Heckler, Charles E; Kesler, Shelli R; Sprod, Lisa K; Atkins, James; Melnik, Marianne; Kamen, Charles; Giguere, Jeffrey; Messino, Michael J; Mohile, Supriya G; Mustian, Karen M

2016-09-01

Background Interventions are needed to alleviate memory difficulty in cancer survivors. We previously showed in a phase III randomized clinical trial that YOCAS©® yoga-a program that consists of breathing exercises, postures, and meditation-significantly improved sleep quality in cancer survivors. This study assessed the effects of YOCAS©® on memory and identified relationships between memory and sleep. Survivors were randomized to standard care (SC) or SC with YOCAS©® . 328 participants who provided data on the memory difficulty item of the MD Anderson Symptom Inventory are included. Sleep quality was measured using the Pittsburgh Sleep Quality Index. General linear modeling (GLM) determined the group effect of YOCAS©® on memory difficulty compared with SC. GLM also determined moderation of baseline memory difficulty on postintervention sleep and vice versa. Path modeling assessed the mediating effects of changes in memory difficulty on YOCAS©® changes in sleep and vice versa. YOCAS©® significantly reduced memory difficulty at postintervention compared with SC (mean change: yoga=-0.60; SC=-0.16; P<.05). Baseline memory difficulty did not moderate the effects of postintervention sleep quality in YOCAS©® compared with SC. Baseline sleep quality did moderate the effects of postintervention memory difficulty in YOCAS©® compared with SC (P<.05). Changes in sleep quality was a significant mediator of reduced memory difficulty in YOCAS©® compared with SC (P<.05); however, changes in memory difficulty did not significantly mediate improved sleep quality in YOCAS©® compared with SC. In this large nationwide trial, YOCAS©® yoga significantly reduced patient-reported memory difficulty in cancer survivors. © The Author(s) 2015.

Phase-Change Thermoplastic Elastomer Blends for Tunable Shape Memory by Physical Design

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

Mineart, Kenneth P.; Tallury, Syamal S.; Li, Tao

Shape-memory polymers (SMPs) change shape upon exposure to an environmental stimulus.1-3 They are of considerable importance in the ongoing development of stimuli-responsive biomedical4,5 and deployable6 devices, and their function depends on the presence of two components.7 The first provides mechanical rigidity to ensure retention of one or more temporary strain states and also serves as a switch capable of releasing a temporary strain state. The second, a network-forming component, is required to restore the polymer to a prior strain state upon stimulation. In thermally-activated SMPs, the switching element typically relies on a melting or glass transition temperature,1-3,7 and broad ormore » multiple switches permit several temporary strain states.8-10 Chemical integration of network-forming and switching species endows SMPs with specific properties.8,10,11 Here, we demonstrate that phase-change materials incorporated into network-forming macromolecules yield shape-memory polymer blends (SMPBs) with physically tunable switching temperatures and recovery kinetics for use in multi-responsive laminates and shape-change electronics.« less

White matter microstructure alterations correlate with terminally differentiated CD8+ effector T cell depletion in the peripheral blood in mania: Combined DTI and immunological investigation in the different phases of bipolar disorder.

PubMed

Magioncalda, Paola; Martino, Matteo; Tardito, Samuele; Sterlini, Bruno; Conio, Benedetta; Marozzi, Valentina; Adavastro, Giulia; Capobianco, Laura; Russo, Daniel; Parodi, Alessia; Kalli, Francesca; Nasi, Giorgia; Altosole, Tiziana; Piaggio, Niccolò; Northoff, Georg; Fenoglio, Daniela; Inglese, Matilde; Filaci, Gilberto; Amore, Mario

2018-05-01

White matter (WM) microstructural abnormalities and, independently, signs of immunological activation were consistently demonstrated in bipolar disorder (BD). However, the relationship between WM and immunological alterations as well as their occurrence in the various phases of BD remain unclear. In 60 type I BD patients - 20 in manic, 20 in depressive, 20 in euthymic phases - and 20 controls we investigated: (i) diffusion tensor imaging (DTI)-derived fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) using a tract-based spatial statistics (TBSS) approach; (ii) circulating T cell subpopulations frequencies, as well as plasma levels of different cytokines; (iii) potential relationships between WM and immunological data. We found: (i) a significant widespread combined FA-RD alteration mainly in mania, with involvement of the body of corpus callosum (BCC) and superior corona radiata (SCR); (ii) significant increase in CD4+ T cells as well as significant decrease in CD8+ T cells and their subpopulations effector memory (CD8+ CD28-CD45RA-), terminal effector memory (CD8+ CD28-CD45RA+) and CD8+ IFNγ+ in mania; (iii) a significant relationship between WM and immunological alterations in the whole cohort, and a significant correlation of FA-RD abnormalities in the BCC and SCR with reduced frequencies of CD8+ terminal effector memory and CD8+ IFNγ+ T cells in mania only. Our data show a combined occurrence of WM and immunological alterations in mania. WM abnormalities highly correlated with reduction in circulating CD8+ T cell subpopulations that are terminally differentiated effector cells prone to tissue migration, suggesting that these T cells could play a role in WM alteration in BD. Copyright © 2018 Elsevier Inc. All rights reserved.

Declarative and Non-declarative Memory Consolidation in Children with Sleep Disorder.

PubMed

Csábi, Eszter; Benedek, Pálma; Janacsek, Karolina; Zavecz, Zsófia; Katona, Gábor; Nemeth, Dezso

2015-01-01

Healthy sleep is essential in children's cognitive, behavioral, and emotional development. However, remarkably little is known about the influence of sleep disorders on different memory processes in childhood. Such data could give us a deeper insight into the effect of sleep on the developing brain and memory functions and how the relationship between sleep and memory changes from childhood to adulthood. In the present study we examined the effect of sleep disorder on declarative and non-declarative memory consolidation by testing children with sleep-disordered breathing (SDB) which is characterized by disrupted sleep structure. We used a story recall task to measure declarative memory and Alternating Serial Reaction time (ASRT) task to assess non-declarative memory. This task enables us to measure two aspects of non-declarative memory, namely general motor skill learning and sequence-specific learning. There were two sessions: a learning phase and a testing phase, separated by a 12 h offline period with sleep. Our data showed that children with SDB exhibited a generally lower declarative memory performance both in the learning and testing phase; however, both the SDB and control groups exhibited retention of the previously recalled items after the offline period. Here we showed intact non-declarative consolidation in SDB group in both sequence-specific and general motor skill. These findings suggest that sleep disorders in childhood have a differential effect on different memory processes (online vs. offline) and give us insight into how sleep disturbances affects developing brain.

Declarative and Non-declarative Memory Consolidation in Children with Sleep Disorder

PubMed Central

Csábi, Eszter; Benedek, Pálma; Janacsek, Karolina; Zavecz, Zsófia; Katona, Gábor; Nemeth, Dezso

2016-01-01

Healthy sleep is essential in children’s cognitive, behavioral, and emotional development. However, remarkably little is known about the influence of sleep disorders on different memory processes in childhood. Such data could give us a deeper insight into the effect of sleep on the developing brain and memory functions and how the relationship between sleep and memory changes from childhood to adulthood. In the present study we examined the effect of sleep disorder on declarative and non-declarative memory consolidation by testing children with sleep-disordered breathing (SDB) which is characterized by disrupted sleep structure. We used a story recall task to measure declarative memory and Alternating Serial Reaction time (ASRT) task to assess non-declarative memory. This task enables us to measure two aspects of non-declarative memory, namely general motor skill learning and sequence-specific learning. There were two sessions: a learning phase and a testing phase, separated by a 12 h offline period with sleep. Our data showed that children with SDB exhibited a generally lower declarative memory performance both in the learning and testing phase; however, both the SDB and control groups exhibited retention of the previously recalled items after the offline period. Here we showed intact non-declarative consolidation in SDB group in both sequence-specific and general motor skill. These findings suggest that sleep disorders in childhood have a differential effect on different memory processes (online vs. offline) and give us insight into how sleep disturbances affects developing brain. PMID:26793090

Fucosyltransferase Induction during Influenza Virus Infection Is Required for the Generation of Functional Memory CD4+ T Cells

PubMed Central

Carrette, Florent; Henriquez, Monique L.; Fujita, Yu

2018-01-01

T cells mediating influenza viral control are instructed in lymphoid and nonlymphoid tissues to differentiate into memory T cells that confer protective immunity. The mechanisms by which influenza virus–specific memory CD4+ T cells arise have been attributed to changes in transcription factors, cytokines and cytokine receptors, and metabolic programming. The molecules involved in these biosynthetic pathways, including proteins and lipids, are modified to varying degrees of glycosylation, fucosylation, sialation, and sulfation, which can alter their function. It is currently unknown how the glycome enzymatic machinery regulates CD4+ T cell effector and memory differentiation. In a murine model of influenza virus infection, we found that fucosyltransferase enzymatic activity was induced in effector and memory CD4+ T cells. Using CD4+ T cells deficient in the Fut4/7 enzymes that are expressed only in hematopoietic cells, we found decreased frequencies of effector cells with reduced expression of T-bet and NKG2A/C/E in the lungs during primary infection. Furthermore, Fut4/7−/− effector CD4+ T cells had reduced survival with no difference in proliferation or capacity for effector function. Although Fut4/7−/− CD4+ T cells seeded the memory pool after primary infection, they failed to form tissue-resident cells, were dysfunctional, and were unable to re-expand after secondary infection. Our findings highlight an important regulatory axis mediated by cell-intrinsic fucosyltransferase activity in CD4+ T cell effectors that ensure the development of functional memory CD4+ T cells. PMID:29491007

Kinetic memory based on the enzyme-limited competition.

PubMed

Hatakeyama, Tetsuhiro S; Kaneko, Kunihiko

2014-08-01

Cellular memory, which allows cells to retain information from their environment, is important for a variety of cellular functions, such as adaptation to external stimuli, cell differentiation, and synaptic plasticity. Although posttranslational modifications have received much attention as a source of cellular memory, the mechanisms directing such alterations have not been fully uncovered. It may be possible to embed memory in multiple stable states in dynamical systems governing modifications. However, several experiments on modifications of proteins suggest long-term relaxation depending on experienced external conditions, without explicit switches over multi-stable states. As an alternative to a multistability memory scheme, we propose "kinetic memory" for epigenetic cellular memory, in which memory is stored as a slow-relaxation process far from a stable fixed state. Information from previous environmental exposure is retained as the long-term maintenance of a cellular state, rather than switches over fixed states. To demonstrate this kinetic memory, we study several models in which multimeric proteins undergo catalytic modifications (e.g., phosphorylation and methylation), and find that a slow relaxation process of the modification state, logarithmic in time, appears when the concentration of a catalyst (enzyme) involved in the modification reactions is lower than that of the substrates. Sharp transitions from a normal fast-relaxation phase into this slow-relaxation phase are revealed, and explained by enzyme-limited competition among modification reactions. The slow-relaxation process is confirmed by simulations of several models of catalytic reactions of protein modifications, and it enables the memorization of external stimuli, as its time course depends crucially on the history of the stimuli. This kinetic memory provides novel insight into a broad class of cellular memory and functions. In particular, applications for long-term potentiation are discussed, including dynamic modifications of calcium-calmodulin kinase II and cAMP-response element-binding protein essential for synaptic plasticity.

Memory on time

PubMed Central

Eichenbaum, Howard

2013-01-01

Considerable recent work has shown that the hippocampus is critical for remembering the order of events in distinct experiences, a defining feature of episodic memory. Correspondingly, hippocampal neuronal activity can ‘replay’ sequential events in memories and hippocampal neuronal ensembles represent a gradually changing temporal context signal. Most strikingly, single hippocampal neurons – called time cells – encode moments in temporally structured experiences much as the well-known place cells encode locations in spatially structured experiences. These observations bridge largely disconnected literatures on the role of the hippocampus in episodic memory and spatial mapping, and suggest that the fundamental function of the hippocampus is to establish spatio-temporal frameworks for organizing memories. PMID:23318095

Switching kinetics of SiC resistive memory for harsh environments

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

Morgan, K. A., E-mail: kam2g11@soton.ac.uk; Huang, R.; Groot, C. H. de

2015-07-15

Cu/a-SiC/Au resistive memory cells are measured using voltage pulses and exhibit the highest R{sub OFF}/R{sub ON} ratio recorded for any resistive memory. The switching kinetics are investigated and fitted to a numerical model, using thermal conductivity and resistivity properties of the dielectric. The SET mechanism of the Cu/a-SiC/Au memory cells is found to be due to ionic motion without joule heating contributions, whereas the RESET mechanism is found to be due to thermally assisted ionic motion. The conductive filament diameter is extracted to be around 4nm. The high thermal conductivity and resistivity for the Cu/a-SiC/Au memory cells result in slowmore » switching but with high thermal reliability and stability, showing potential for use in harsh environments. Radiation properties of SiC memory cells are investigated. No change was seen in DC sweep or pulsed switching nor in conductive mechanisms, up to 2Mrad(Si) using {sup 60}Co gamma irradiation.« less

Realization of memory effect in smectic X* phase

NASA Astrophysics Data System (ADS)

Kishor, Murthynedi Hari; Madhu Mohan, M. L. N.

2018-09-01

Homologous series of DTA + nBA (where n varies from 2 to 8) comprises of seven homologues, out of which DTA+4BA alone exhibits a new smectic ordering labelled as smectic X*. Hence DTA+4BA is chosen to investigate various chemical, thermal optical and electrical studies. DSC thermograms reveal the transition temperature and enthalpy values of smectic X* phase. FTIR spectroscopy confirms the formation of hydrogen bonding. Variation of tilt angle with temperature is studied and fitted to a power law confirming the Mean field theory predicted value. An interesting feature of this work is the observation of memory effect in smectic X* phase. When an external field is applied to the mesogen in smectic X* phase, the texture undergoes a change and remains invariant even after the field is removed, further the texture of the phase can be erased only by taking it to isotropic temperature. Another proof for memory effect is the dielectric hysteresis in smectic X* recorded with field. Helix in smectic X* is reported. Yet another interesting observation is the identification of parachromatism in smectic X* phase namely the textures remain the same while the colour of the textures changes completely with decrement in the temperature of the mesogen. Dielectric relaxations in Goldstone mode are studied and analyzed with Cole-Cole plots. The relaxation is suppressed on application of field indicative of Arrhenius in nature.

Altered hippocampal replay is associated with memory impairment in mice heterozygous for the Scn2a gene.

PubMed

Middleton, Steven J; Kneller, Emily M; Chen, Shuo; Ogiwara, Ikuo; Montal, Mauricio; Yamakawa, Kazuhiro; McHugh, Thomas J

2018-06-04

An accumulating body of experimental evidence has implicated hippocampal replay occurring within sharp wave ripples (SPW-Rs) as crucial for learning and memory in healthy subjects. This raises speculation that neurological disorders impairing memory disrupt either SPW-Rs or their underlying neuronal activity. We report that mice heterozygous for the gene Scn2a, a site of frequent de novo mutations in humans with intellectual disability, displayed impaired spatial memory. While we observed no changes during encoding, to either single place cells or cell assemblies, we identified abnormalities restricted to SPW-R episodes that manifest as decreased cell assembly reactivation strengths and truncated hippocampal replay sequences. Our results suggest that alterations to hippocampal replay content may underlie disease-associated memory deficits.

Comprehensive Approach for Identifying the T Cell Subset Origin of CD3 and CD28 Antibody-Activated Chimeric Antigen Receptor-Modified T Cells.

PubMed

Schmueck-Henneresse, Michael; Omer, Bilal; Shum, Thomas; Tashiro, Haruko; Mamonkin, Maksim; Lapteva, Natalia; Sharma, Sandhya; Rollins, Lisa; Dotti, Gianpietro; Reinke, Petra; Volk, Hans-Dieter; Rooney, Cliona M

2017-07-01

The outcome of therapy with chimeric Ag receptor (CAR)-modified T cells is strongly influenced by the subset origin of the infused T cells. However, because polyclonally activated T cells acquire a largely CD45RO + CCR7 - effector memory phenotype after expansion, regardless of subset origin, it is impossible to know which subsets contribute to the final T cell product. To determine the contribution of naive T cell, memory stem T cell, central memory T cell, effector memory T cell, and terminally differentiated effector T cell populations to the CD3 and CD28-activated CAR-modified T cells that we use for therapy, we followed the fate and function of individually sorted CAR-modified T cell subsets after activation with CD3 and CD28 Abs (CD3/28), transduction and culture alone, or after reconstitution into the relevant subset-depleted population. We show that all subsets are sensitive to CAR transduction, and each developed a distinct T cell functional profile during culture. Naive-derived T cells showed the greatest rate of proliferation but had more limited effector functions and reduced killing compared with memory-derived populations. When cultured in the presence of memory T cells, naive-derived T cells show increased differentiation, reduced effector cytokine production, and a reduced reproliferative response to CAR stimulation. CD3/28-activated T cells expanded in IL-7 and IL-15 produced greater expansion of memory stem T cells and central memory T cell-derived T cells compared with IL-2. Our strategy provides a powerful tool to elucidate the characteristics of CAR-modified T cells, regardless of the protocol used for expansion, reveals the functional properties of each expanded T cell subset, and paves the way for a more detailed evaluation of the effects of manufacturing changes on the subset contribution to in vitro-expanded T cells. Copyright © 2017 by The American Association of Immunologists, Inc.

Interaction between Neurogenesis and Hippocampal Memory System: New Vistas

PubMed Central

Abrous, Djoher Nora; Wojtowicz, Jan Martin

2015-01-01

During the last decade, the questions on the functionality of adult neurogenesis have changed their emphasis from if to how the adult-born neurons participate in a variety of memory processes. The emerging answers are complex because we are overwhelmed by a variety of behavioral tasks that apparently require new neurons to be performed optimally. With few exceptions, the hippocampal memory system seems to use the newly generated neurons for multiple roles. Adult neurogenesis has given the dentate gyrus new capabilities not previously thought possible within the scope of traditional synaptic plasticity. Looking at these new developments from the perspective of past discoveries, the science of adult neurogenesis has emerged from its initial phase of being, first, a surprising oddity and, later, exciting possibility, to the present state of being an integral part of mainstream neuroscience. The answers to many remaining questions regarding adult neurogenesis will come along only with our growing understanding of the functionality of the brain as a whole. This, in turn, will require integration of multiple levels of organization from molecules and cells to circuits and systems, ultimately resulting in comprehension of behavioral outcomes. PMID:26032718

Magnetically Controlled Shape Memory Behaviour—Materials and Applications

NASA Astrophysics Data System (ADS)

Gandy, A. P.; Sheikh, A.; Neumann, K.; Neumann, K.-U.; Pooley, D.; Ziebeck, K. R. A.

2008-06-01

For most metals a microscopic change in shape occurs above the elastic limit by the irreversible creation and movement of dislocations. However a large number of metallic systems undergo structural, martensitic, phase transformations which are diffusionless, displacive first order transitions from a high-temperature phase to one of lower symmetry below a certain temperature TM. These transitions which have been studied for more than a century are of vital importance because of their key role in producing shape memory phenomena enabling the system to reverse large deformations in the martensitic phase by heating into the austenite phase. In addition to a change in shape (displacement) the effect can also produce a force or a combination of both. Materials having this unique property are increasing being used in medical applications—scoliosis correction, arterial clips, stents, orthodontic wire, orthopaedic implants etc. The structural phase transition essential for shape memory behaviour is usually activated by a change in temperature or applied stress. However for many applications such as for actuators the transformation is not sufficiently rapid. Poor energy conversion also limits the applicability of many shape memory alloys. In medicine a change of temperature or pressure is often inappropriate and new ferromagnetic materials are being considered in which the phenomena can be controlled by an applied magnetic field at constant temperature. In order to achieve this, it is important to optimise three fundamental parameters. These are the saturation magnetisation σs, the Curie temperature Tc and the martensitic temperature TM. Here, σs is important because the magnetic pressure driving the twin boundary motion is 2σsH. Furthermore the material must be in the martensitic state at the operating temperature which should be at or above room temperature. This may be achieved by alloying or controlling the stoichiometry. Recently new intermetallic compounds based on the ferromagnetic prototype Ni2MnGa have been discovered which offer the possibility of controlling the structural phase transition by a magnetic field, hence opening up new possible applications particularly in the field of medicine. The properties of these new materials will be presented and their suitability for applications discussed.

An x-ray absorption spectroscopy study of Ni-Mn-Ga shape memory alloys.

PubMed

Sathe, V G; Dubey, Aditi; Banik, Soma; Barman, S R; Olivi, L

2013-01-30

The austenite to martensite phase transition in Ni-Mn-Ga ferromagnetic shape memory alloys was studied by extended x-ray absorption fine structure (EXAFS) and x-ray absorption near-edge structure (XANES) spectroscopy. The spectra at all the three elements', namely, Mn, Ga and Ni, K-edges in several Ni-Mn-Ga samples (with both Ni and Mn excess) were analyzed at room temperature and low temperatures. The EXAFS analysis suggested a displacement of Mn and Ga atoms in opposite direction with respect to the Ni atoms when the compound transforms from the austenite phase to the martensite phase. The first coordination distances around the Mn and Ga atoms remained undisturbed on transition, while the second and subsequent shells showed dramatic changes indicating the presence of a modulated structure. The Mn rich compounds showed the presence of antisite disorder of Mn and Ga. The XANES results showed remarkable changes in the unoccupied partial density of states corresponding to Mn and Ni, while the electronic structure of Ga remained unperturbed across the martensite transition. The post-edge features in the Mn K-edge XANES spectra changed from a double peak like structure to a flat peak like structure upon phase transition. The study establishes strong correlation between the crystal structure and the unoccupied electronic structure in these shape memory alloys.

First principles investigation of the unipolar resistive switching mechanism in an interfacial phase change memory based on a GeTe/Sb2Te3 superlattice

NASA Astrophysics Data System (ADS)

Shirakawa, Hiroki; Araidai, Masaaki; Shiraishi, Kenji

2018-04-01

The interfacial phase change memory (iPCM) based on a GeTe/Sb2Te3 superlattice is one of the candidates for future storage class memories. However, the atomic structures of the high and low resistance states (HRS/LRS) remain unclear and the resistive switching mechanism is still under debate. Clarifying the switching mechanism is essential for developing further high-reliability and low-power-consumption iPCM. We propose, on the basis of the results of first-principles molecular dynamics simulations, a mechanism for resistive switching, and describe the atomic structures of the high and low resistance states of iPCM for unipolar switching. Our simulations indicated that switching from HRS to LRS occurs with Joule heating only, while that from LRS to HRS occurs with both hole injection and Joule heating.

Design rules for phase-change materials in data storage applications.

PubMed

Lencer, Dominic; Salinga, Martin; Wuttig, Matthias

2011-05-10

Phase-change materials can rapidly and reversibly be switched between an amorphous and a crystalline phase. Since both phases are characterized by very different optical and electrical properties, these materials can be employed for rewritable optical and electrical data storage. Hence, there are considerable efforts to identify suitable materials, and to optimize them with respect to specific applications. Design rules that can explain why the materials identified so far enable phase-change based devices would hence be very beneficial. This article describes materials that have been successfully employed and dicusses common features regarding both typical structures and bonding mechanisms. It is shown that typical structural motifs and electronic properties can be found in the crystalline state that are indicative for resonant bonding, from which the employed contrast originates. The occurence of resonance is linked to the composition, thus providing a design rule for phase-change materials. This understanding helps to unravel characteristic properties such as electrical and thermal conductivity which are discussed in the subsequent section. Then, turning to the transition kinetics between the phases, the current understanding and modeling of the processes of amorphization and crystallization are discussed. Finally, present approaches for improved high-capacity optical discs and fast non-volatile electrical memories, that hold the potential to succeed present-day's Flash memory, are presented. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical and structural arrangement of the trigonal phase in GeSbTe thin films.

PubMed

Mio, Antonio M; Privitera, Stefania M S; Bragaglia, Valeria; Arciprete, Fabrizio; Bongiorno, Corrado; Calarco, Raffaella; Rimini, Emanuele

2017-02-10

The thermal and electrical properties of phase change materials, mainly GeSbTe alloys, in the crystalline state strongly depend on their phase and on the associated degree of order. The switching of Ge atoms in superlattice structures with trigonal phase has been recently proposed to develop memories with reduced switching energy, in which two differently ordered crystalline phases are the logic states. A detailed knowledge of the stacking plane sequence, of the local composition and of the vacancy distribution is therefore crucial in order to understand the underlying mechanism of phase transformations in the crystalline state and to evaluate the retention properties. This information is provided, as reported in this paper, by scanning transmission electron microscopy analysis of polycrystalline and epitaxial Ge 2 Sb 2 Te 5 thin samples, using the Z-contrast high-angle annular dark field method. Electron diffraction clearly confirms the presence of compositional mixing with stacking blocks of 11, 9 or 7 planes corresponding to Ge 3 Sb 2 Te 6 , Ge 2 Sb 2 Te 5 , and GeSb 2 Te 4 , alloys respectively in the same trigonal phase. By increasing the degree of order (according to the annealing temperature, the growth condition, etc) the spread in the statistical distribution of the blocks reduces and the distribution of the atoms in the cation planes also changes from a homogenous Ge/Sb mixing towards a Sb-enrichment in the planes closest to the van der Waals gaps. Therefore we show that the trigonal phase of Ge 2 Sb 2 Te 5 , the most studied chalcogenide for phase-change memories, is actually obtained in different configurations depending on the distribution of the stacking blocks (7-9-11 planes) and on the atomic occupation (Ge/Sb) at the cation planes. These results give an insight in the factors determining the stability of the trigonal phase and suggest a dynamic path evolution that could have a key role in the switching mechanism of interfacial phase change memories and in their data retention.

Refractive index modulation of Sb70Te30 phase-change thin films by multiple femtosecond laser pulses

NASA Astrophysics Data System (ADS)

Lei, Kai; Wang, Yang; Jiang, Minghui; Wu, Yiqun

2016-05-01

In this study, the controllable effective refractive index modulation of Sb70Te30 phase-change thin films between amorphous and crystalline states was achieved experimentally by multiple femtosecond laser pulses. The modulation mechanism was analyzed comprehensively by a spectral ellipsometer measurement, surface morphology observation, and two-temperature model calculations. We numerically demonstrate the application of the optically modulated refractive index of the phase-change thin films in a precisely adjustable color display. These results may provide further insights into ultrafast phase-transition mechanics and are useful in the design of programmable photonic and opto-electrical devices based on phase-change memory materials.

Refractive index modulation of Sb{sub 70}Te{sub 30} phase-change thin films by multiple femtosecond laser pulses

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

Lei, Kai; Wang, Yang, E-mail: ywang@siom.ac.cn; Jiang, Minghui

2016-05-07

In this study, the controllable effective refractive index modulation of Sb{sub 70}Te{sub 30} phase-change thin films between amorphous and crystalline states was achieved experimentally by multiple femtosecond laser pulses. The modulation mechanism was analyzed comprehensively by a spectral ellipsometer measurement, surface morphology observation, and two-temperature model calculations. We numerically demonstrate the application of the optically modulated refractive index of the phase-change thin films in a precisely adjustable color display. These results may provide further insights into ultrafast phase-transition mechanics and are useful in the design of programmable photonic and opto-electrical devices based on phase-change memory materials.

Understanding the fast phase-change mechanism of tetrahedrally bonded Cu2GeTe3 : Comprehensive analyses of electronic structure and transport phenomena

NASA Astrophysics Data System (ADS)

Kobayashi, Keisuke; Skelton, Jonathan M.; Saito, Yuta; Shindo, Satoshi; Kobata, Masaaki; Fons, Paul; Kolobov, Alexander V.; Elliott, Stephen; Ando, Daisuke; Sutou, Yuji

2018-05-01

Cu2GeTe3 (CGT) phase-change material, a promising candidate for advanced fast nonvolatile random-access-memory devices, has a chalcopyritelike structure with s p3 bonding in the crystalline phase; thus, the phase-change (PC) mechanism is considered to be essentially different from that of the standard PC materials (e.g., Ge-Sb-Te) with threefold to sixfold p -like bonding. In order to reveal the PC mechanism of CGT, the electronic structure change due to PC has been investigated by laboratory hard x-ray photoelectron spectroscopy and combined first-principles density-functional theory molecular-dynamics simulations. The valence-band spectra, in both crystalline and amorphous phases, are well simulated by the calculations. An inherent tendency of Te 5 s lone-pair formation and an enhanced participation of Cu 3 d orbitals in the bonding are found to play dominant roles in the PC mechanism. The electrical conductivity of as-deposited films and its change during the PC process is investigated in connection with valence-band spectral changes near the Fermi level. The results are successfully analyzed, based on a model proposed by Davis and Mott for chalcogenide amorphous semiconductors. The results suggest that robustness of the defect-band states against thermal stress is a key to the practical application of this material for memory devices.

Identification and optogenetic manipulation of memory engrams in the hippocampus

PubMed Central

Ramirez, Steve; Tonegawa, Susumu; Liu, Xu

2014-01-01

With the accumulation of our knowledge about how memories are formed, consolidated, retrieved, and updated, neuroscience is now reaching a point where discrete memories can be identified and manipulated at rapid timescales. Here, we start with historical studies that lead to the modern memory engram theory. Then, we will review recent advances in memory engram research that combine transgenic and optogenetic approaches to reveal the underlying neuronal substrates sufficient for activating mnemonic processes. We will focus on three concepts: (1) isolating memory engrams at the level of single cells to tag them for subsequent manipulation; (2) testing the sufficiency of these engrams for memory recall by artificially activating them; and (3) presenting new stimuli during the artificial activation of these engrams to induce an association between the two to form a false memory. We propose that hippocampal cells that show activity-dependent changes during learning construct a cellular basis for contextual memory engrams. PMID:24478647

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

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

Di Pendina, G., E-mail: gregory.dipendina@cea.fr, E-mail: eldar.zianbetov@cea.fr, E-mail: edith.beigne@cea.fr; Zianbetov, E., E-mail: gregory.dipendina@cea.fr, E-mail: eldar.zianbetov@cea.fr, E-mail: edith.beigne@cea.fr; CNRS, SPINTEC, F-38000 Grenoble

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 remainingmore » 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.« less

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

NASA Astrophysics Data System (ADS)

Huffman, James Douglas

2001-11-01

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

IL-7 differentially regulates cell cycle progression and HIV-1-based vector infection in neonatal and adult CD4+ T cells.

PubMed

Dardalhon, V; Jaleco, S; Kinet, S; Herpers, B; Steinberg, M; Ferrand, C; Froger, D; Leveau, C; Tiberghien, P; Charneau, P; Noraz, N; Taylor, N

2001-07-31

Differences in the immunological reactivity of umbilical cord (UC) and adult peripheral blood (APB) T cells are poorly understood. Here, we show that IL-7, a cytokine involved in lymphoid homeostasis, has distinct regulatory effects on APB and UC lymphocytes. Neither naive nor memory APB CD4(+) cells proliferated in response to IL-7, whereas naive UC CD4(+) lymphocytes underwent multiple divisions. Nevertheless, both naive and memory IL-7-treated APB T cells progressed into the G(1b) phase of the cell cycle, albeit at higher levels in the latter subset. The IL-7-treated memory CD4(+) lymphocyte population was significantly more susceptible to infection with an HIV-1-derived vector than dividing CD4(+) UC lymphocytes. However, activation through the T cell receptor rendered UC lymphocytes fully susceptible to HIV-1-based vector infection. These data unveil differences between UC and APB CD4(+) T cells with regard to IL-7-mediated cell cycle progression and HIV-1-based vector infectivity. This evidence indicates that IL-7 differentially regulates lymphoid homeostasis in adults and neonates.

IL-7 differentially regulates cell cycle progression and HIV-1-based vector infection in neonatal and adult CD4+ T cells

PubMed Central

Dardalhon, Valérie; Jaleco, Sara; Kinet, Sandrina; Herpers, Bjorn; Steinberg, Marcos; Ferrand, Christophe; Froger, Delphine; Leveau, Christelle; Tiberghien, Pierre; Charneau, Pierre; Noraz, Nelly; Taylor, Naomi

2001-01-01

Differences in the immunological reactivity of umbilical cord (UC) and adult peripheral blood (APB) T cells are poorly understood. Here, we show that IL-7, a cytokine involved in lymphoid homeostasis, has distinct regulatory effects on APB and UC lymphocytes. Neither naive nor memory APB CD4+ cells proliferated in response to IL-7, whereas naive UC CD4+ lymphocytes underwent multiple divisions. Nevertheless, both naive and memory IL-7-treated APB T cells progressed into the G1b phase of the cell cycle, albeit at higher levels in the latter subset. The IL-7-treated memory CD4+ lymphocyte population was significantly more susceptible to infection with an HIV-1-derived vector than dividing CD4+ UC lymphocytes. However, activation through the T cell receptor rendered UC lymphocytes fully susceptible to HIV-1-based vector infection. These data unveil differences between UC and APB CD4+ T cells with regard to IL-7-mediated cell cycle progression and HIV-1-based vector infectivity. This evidence indicates that IL-7 differentially regulates lymphoid homeostasis in adults and neonates. PMID:11470908

Constant volume gas cell optical phase-shifter

DOEpatents

Phillion, Donald W.

2002-01-01

A constant volume gas cell optical phase-shifter, particularly applicable for phase-shifting interferometry, contains a sealed volume of atmospheric gas at a pressure somewhat different than atmospheric. An optical window is present at each end of the cell, and as the length of the cell is changed, the optical path length of a laser beam traversing the cell changes. The cell comprises movable coaxial tubes with seals and a volume equalizing opening. Because the cell is constant volume, the pressure, temperature, and density of the contained gas do not change as the cell changes length. This produces an exactly linear relationship between the change in the length of the gas cell and the change in optical phase of the laser beam traversing it. Because the refractive index difference between the gas inside and the atmosphere outside is very much the same, a large motion must be made to change the optical phase by the small fraction of a wavelength that is required by phase-shifting interferometry for its phase step. This motion can be made to great fractional accuracy.

Binaural interaction in low-frequency neurons in inferior colliculus of the cat. II. Effects of changing rate and direction of interaural phase.

PubMed

Yin, T C; Kuwada, S

1983-10-01

We used the binaural beat stimulus to study the interaural phase sensitivity of inferior colliculus (IC) neurons in the cat. The binaural beat, produced by delivering tones of slightly different frequencies to the two ears, generates continuous and graded changes in interaural phase. Over 90% of the cells that exhibit a sensitivity to changes in the interaural delay also show a sensitivity to interaural phase disparities with the binaural beat. Cells respond with a burst of impulses with each complete cycle of the beat frequency. The period histogram obtained by binning the poststimulus time histogram on the beat frequency gives a measure of the interaural phase sensitivity of the cell. In general, there is good correspondence in the shapes of the period histograms generated from binaural beats and the interaural phase curves derived from interaural delays and in the mean interaural phase angle calculated from them. The magnitude of the beat frequency determines the rate of change of interaural phase and the sign determines the direction of phase change. While most cells respond in a phase-locked manner up to beat frequencies of 10 Hz, there are some cells tht will phase lock up to 80 Hz. Beat frequency and mean interaural phase angle are linearly related for most cells. Most cells respond equally in the two directions of phase change and with different rates of change, at least up to 10 Hz. However, some IC cells exhibit marked sensitivity to the speed of phase change, either responding more vigorously at low beat frequencies or at high beat frequencies. In addition, other cells demonstrate a clear directional sensitivity. The cells that show sensitivity to the direction and speed of phase changes would be expected to demonstrate a sensitivity to moving sound sources in the free field. Changes in the mean interaural phase of the binaural beat period histograms are used to determine the effects of changes in average and interaural intensity on the phase sensitivity of the cells. The effects of both forms of intensity variation are continuously distributed. The binaural beat offers a number of advantages for studying the interaural phase sensitivity of binaural cells. The dynamic characteristics of the interaural phase can be varied so that the speed and direction of phase change are under direct control. The data can be obtained in a much more efficient manner, as the binaural beat is about 10 times faster in terms of data collection than the interaural delay.

The spectro-contextual encoding and retrieval theory of episodic memory.

PubMed

Watrous, Andrew J; Ekstrom, Arne D

2014-01-01

The spectral fingerprint hypothesis, which posits that different frequencies of oscillations underlie different cognitive operations, provides one account for how interactions between brain regions support perceptual and attentive processes (Siegel etal., 2012). Here, we explore and extend this idea to the domain of human episodic memory encoding and retrieval. Incorporating findings from the synaptic to cognitive levels of organization, we argue that spectrally precise cross-frequency coupling and phase-synchronization promote the formation of hippocampal-neocortical cell assemblies that form the basis for episodic memory. We suggest that both cell assembly firing patterns as well as the global pattern of brain oscillatory activity within hippocampal-neocortical networks represents the contents of a particular memory. Drawing upon the ideas of context reinstatement and multiple trace theory, we argue that memory retrieval is driven by internal and/or external factors which recreate these frequency-specific oscillatory patterns which occur during episodic encoding. These ideas are synthesized into a novel model of episodic memory (the spectro-contextual encoding and retrieval theory, or "SCERT") that provides several testable predictions for future research.

Environmental enrichment alters dentate granule cell morphology in oldest-old rat.

PubMed

Darmopil, Sanja; Petanjek, Zdravko; Mohammed, Abdul H; Bogdanović, Nenad

2009-08-01

The hippocampus of aged rats shows marked age-related morphological changes that could cause memory deficits. Experimental evidence has established that environmental enrichment attenuates memory deficits in aged rats. We therefore studied whether environmental enrichment produces morphological changes on the dentate granule cells of aged rats. Fifteen male Sprague-Dawley rats, 24 months of age, were randomly distributed in two groups that were housed under standard (n = 7) or enriched (n = 8) environmental conditions for 26 days. Quantitative data of dendritic morphology from dentate gyrus granule cells were obtained on Golgi-Cox stained sections. Environmental enrichment significantly increased the complexity and size of dendritic tree (total number of segments increased by 61% and length by 116%), and spine density (88% increase). There were large interindividual differences within the enriched group, indicating differential individual responses to environmental stimulation. Previous studies in young animals have shown changes produced by environmental enrichment in the morphology of dentate gyrus granule cells. The results of the present study show that environmental enrichment can also produce changes in dentate granule cell morphology in the senescent brain. In conclusion, the hippocampus retains its neuroplastic capacity during aging, and enriched environmental housing conditions can attenuate age-related dendritic regression and synaptic loss, thus preserving memory functions.

Cell-assembly coding in several memory processes.

PubMed

Sakurai, Y

1998-01-01

The present paper discusses why the cell assembly, i.e., an ensemble population of neurons with flexible functional connections, is a tenable view of the basic code for information processes in the brain. The main properties indicating the reality of cell-assembly coding are neurons overlaps among different assemblies and connection dynamics within and among the assemblies. The former can be detected as multiple functions of individual neurons in processing different kinds of information. Individual neurons appear to be involved in multiple information processes. The latter can be detected as changes of functional synaptic connections in processing different kinds of information. Correlations of activity among some of the recorded neurons appear to change in multiple information processes. Recent experiments have compared several different memory processes (tasks) and detected these two main properties, indicating cell-assembly coding of memory in the working brain. The first experiment compared different types of processing of identical stimuli, i.e., working memory and reference memory of auditory stimuli. The second experiment compared identical processes of different types of stimuli, i.e., discriminations of simple auditory, simple visual, and configural auditory-visual stimuli. The third experiment compared identical processes of different types of stimuli with or without temporal processing of stimuli, i.e., discriminations of elemental auditory, configural auditory-visual, and sequential auditory-visual stimuli. Some possible features of the cell-assembly coding, especially "dual coding" by individual neurons and cell assemblies, are discussed for future experimental approaches. Copyright 1998 Academic Press.

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.

Micromechanics of composites with shape memory alloy fibers in uniform thermal fields

NASA Technical Reports Server (NTRS)

Birman, Victor; Saravanos, Dimitris A.; Hopkins, Dale A.

1995-01-01

Analytical procedures are developed for a composite system consisting of shape memory alloy fibers within an elastic matrix subject to uniform temperature fluctuations. Micromechanics for the calculation of the equivalent properties of the composite are presented by extending the multi-cell model to incorporate shape memory alloy fibers. A three phase concentric cylinder model is developed for the analysis of local stresses which includes the fiber, the matrix, and the surrounding homogenized composite. The solution addresses the complexities induced by the nonlinear dependence of the in-situ martensite fraction of the fibers to the local stresses and temperature, and the local stresses developed from interactions between the fibers and matrix during the martensitic and reverse phase transformations. Results are presented for a nitinol/epoxy composite. The applications illustrate the response of the composite in isothermal longitudinal loading and unloading, and in temperature induced actuation. The local stresses developed in the composite under various stages of the martensitic and reverse phase transformation are also shown.

Nonvolatile Memory Technology for Space Applications

NASA Technical Reports Server (NTRS)

Oldham, Timothy R.; Irom, Farokh; Friendlich, Mark; Nguyen, Duc; Kim, Hak; Berg, Melanie; LaBel, Kenneth A.

2010-01-01

This slide presentation reviews several forms of nonvolatile memory for use in space applications. The intent is to: (1) Determine inherent radiation tolerance and sensitivities, (2) Identify challenges for future radiation hardening efforts, (3) Investigate new failure modes and effects, and technology modeling programs. Testing includes total dose, single event (proton, laser, heavy ion), and proton damage (where appropriate). Test vehicles are expected to be a variety of non-volatile memory devices as available including Flash (NAND and NOR), Charge Trap, Nanocrystal Flash, Magnetic Memory (MRAM), Phase Change--Chalcogenide, (CRAM), Ferroelectric (FRAM), CNT, and Resistive RAM.

Static and Dynamic Properties of Ferroelectric Thin Film Memories.

NASA Astrophysics Data System (ADS)

Duiker, Hendrik Matthew

Several properties of ferroelectric thin-film memories have been modeled. First, it has been observed experimentally that the bulk phase KNO_3 has a first-order phase transition, and that the transition temperature of KNO_3 thin-films increases as the thickness of the film is decreased. A Landau theory of first-order phase transitions in bulk systems has been generalized by adding surface terms to the free energy expansion to account for these transition properties. The model successfully describes the observed transition properties and predicts the existence of films in which the surfaces are ordered at temperatures higher than the bulk transition temperature. Second, the Avrami model of polarization-reversal kinetics has been modified to describe the following cases: ferroelectrics composed of a large number of small grains; ferroelectric thin-films in which nucleation occurs at the surfaces, not in the bulk; ferroelectrics in which long-range dipolar interactions significantly affect the nucleation rate; and non-square wave switching pulses. The models were verified by applying them to the results of two-dimensional Ising model simulations. It was shown that the models allow the possibility of directly obtaining microscopic parameters, such as the nucleation rate and domain wall velocity, from bulk measurements. Finally, a model describing the fatigue of ferroelectric memories has been developed. As a ferroelectric memory fatigues the spontaneous polarization per unit volume decreases, the switching time decreases, and eventually the memory "shorts out" and becomes conducting. The model assumes the following: during each polarization reversal the film undergoes, every unit cell in the film has a chance of "degrading" and thus losing an ion. Degraded cells no longer contribute to the polarization. The ions are allowed to diffuse to the surfaces of the film and form, with other ions, conducting dendrites which grow into the bulk of the film. Computer simulations performed on a two dimensional lattice with the above model successfully described the phenomena observed during the fatigue of PZT and other types of ferroelectric thin-film memories films.

The Regulation of Transcription in Memory Consolidation

PubMed Central

Alberini, Cristina M.; Kandel, Eric R.

2015-01-01

De novo transcription of DNA is a fundamental requirement for the formation of long-term memory. It is required during both consolidation and reconsolidation, the posttraining and postreactivation phases that change the state of the memory from a fragile into a stable and long-lasting form. Transcription generates both mRNAs that are translated into proteins, which are necessary for the growth of new synaptic connections, as well as noncoding RNA transcripts that have regulatory or effector roles in gene expression. The result is a cascade of events that ultimately leads to structural changes in the neurons that mediate long-term memory storage. The de novo transcription, critical for synaptic plasticity and memory formation, is orchestrated by chromatin and epigenetic modifications. The complexity of transcription regulation, its temporal progression, and the effectors produced all contribute to the flexibility and persistence of long-term memory formation. In this article, we provide an overview of the mechanisms contributing to this transcriptional regulation underlying long-term memory formation. PMID:25475090

Generation and application of human induced-stem cell memory T (iTSCM ) cells for adoptive immunotherapy.

PubMed

Kondo, Taisuke; Imura, Yuuki; Chikuma, Shunsuke; Hibino, Sana; Omata-Mise, Setsuko; Ando, Makoto; Akanuma, Takashi; Iizuka, Mana; Sakai, Ryota; Morita, Rimpei; Yoshimura, Akihiko

2018-05-23

Adoptive T cell therapy is an effective strategy for cancer immunotherapy. However, infused T cells frequently become functionally exhausted, and consequently offer a poor prognosis after transplantation into patients. Adoptive transfer of tumor antigen-specific stem cell memory T (T SCM ) cells is expected to overcome this shortcoming since T SCM cells are close to naïve T cells, but are also highly proliferative, long-lived, and produce a large number of effector T cells in response to antigen stimulation. We previously reported that activated effector T cells can be converted into T SCM -like cells (iT SCM ) by co-culturing with OP9 cells expressing Notch ligand, Delta-like 1 (OP9-hDLL1). Here we show the methodological parameters of human CD8 + iT SCM cell generation and their application to adoptive cancer immunotherapy. Regardless of the stimulation by anti-CD3/CD28 antibodies or by antigen-presenting cells, human iT SCM cells were more efficiently induced from central memory type T cells than from effector memory T cells. During the induction phase by co-culture with OP9-hDLL1 cells, IL-7 and IL-15 (but not IL-2 or IL-21) could efficiently generate iT SCM cells. Epstein Barr (EB) virus-specific iT SCM cells showed much stronger antitumor potentials than conventionally activated T cells did in humanized EB virus transformed-tumor model mice. Thus, adoptive T cell therapy with iT SCM offers a promising therapeutic strategy for cancer immunotherapy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Changes of EEG Spectra and Functional Connectivity during an Object-Location Memory Task in Alzheimer's Disease.

PubMed

Han, Yuliang; Wang, Kai; Jia, Jianjun; Wu, Weiping

2017-01-01

Object-location memory is particularly fragile and specifically impaired in Alzheimer's disease (AD) patients. Electroencephalogram (EEG) was utilized to objectively measure memory impairment for memory formation correlates of EEG oscillatory activities. We aimed to construct an object-location memory paradigm and explore EEG signs of it. Two groups of 20 probable mild AD patients and 19 healthy older adults were included in a cross-sectional analysis. All subjects took an object-location memory task. EEG recordings performed during object-location memory tasks were compared between the two groups in the two EEG parameters (spectral parameters and phase synchronization). The memory performance of AD patients was worse than that of healthy elderly adults The power of object-location memory of the AD group was significantly higher than the NC group (healthy elderly adults) in the alpha band in the encoding session, and alpha and theta bands in the retrieval session. The channels-pairs the phase lag index value of object-location memory in the AD group was clearly higher than the NC group in the delta, theta, and alpha bands in encoding sessions and delta and theta bands in retrieval sessions. The results provide support for the hypothesis that the AD patients may use compensation mechanisms to remember the items and episode.

Monozygotic twins discordant for common variable immunodeficiency reveal impaired DNA demethylation during naïve-to-memory B-cell transition

PubMed Central

Rodríguez-Cortez, Virginia C.; del Pino-Molina, Lucia; Rodríguez-Ubreva, Javier; Ciudad, Laura; Gómez-Cabrero, David; Company, Carlos; Urquiza, José M.; Tegnér, Jesper; Rodríguez-Gallego, Carlos; López-Granados, Eduardo; Ballestar, Esteban

2015-01-01

Common variable immunodeficiency (CVID), the most frequent primary immunodeficiency characterized by loss of B-cell function, depends partly on genetic defects, and epigenetic changes are thought to contribute to its aetiology. Here we perform a high-throughput DNA methylation analysis of this disorder using a pair of CVID-discordant MZ twins and show predominant gain of DNA methylation in CVID B cells with respect to those from the healthy sibling in critical B lymphocyte genes, such as PIK3CD, BCL2L1, RPS6KB2, TCF3 and KCNN4. Individual analysis confirms hypermethylation of these genes. Analysis in naive, unswitched and switched memory B cells in a CVID patient cohort shows impaired ability to demethylate and upregulate these genes in transitioning from naive to memory cells in CVID. Our results not only indicate a role for epigenetic alterations in CVID but also identify relevant DNA methylation changes in B cells that could explain the clinical manifestations of CVID individuals. PMID:26081581

Controlling the volatility of the written optical state in electrochromic DNA liquid crystals

NASA Astrophysics Data System (ADS)

Liu, Kai; Varghese, Justin; Gerasimov, Jennifer Y.; Polyakov, Alexey O.; Shuai, Min; Su, Juanjuan; Chen, Dong; Zajaczkowski, Wojciech; Marcozzi, Alessio; Pisula, Wojciech; Noheda, Beatriz; Palstra, Thomas T. M.; Clark, Noel A.; Herrmann, Andreas

2016-05-01

Liquid crystals are widely used in displays for portable electronic information display. To broaden their scope for other applications like smart windows and tags, new material properties such as polarizer-free operation and tunable memory of a written state become important. Here, we describe an anhydrous nanoDNA-surfactant thermotropic liquid crystal system, which exhibits distinctive electrically controlled optical absorption, and temperature-dependent memory. In the liquid crystal isotropic phase, electric field-induced colouration and bleaching have a switching time of seconds. Upon transition to the smectic liquid crystal phase, optical memory of the written state is observed for many hours without applied voltage. The reorientation of the DNA-surfactant lamellar layers plays an important role in preventing colour decay. Thereby, the volatility of optoelectronic state can be controlled simply by changing the phase of the material. This research may pave the way for developing a new generation of DNA-based, phase-modulated, photoelectronic devices.

Working memory activation of neural networks in the elderly as a function of information processing phase and task complexity.

PubMed

Charroud, Céline; Steffener, Jason; Le Bars, Emmanuelle; Deverdun, Jérémy; Bonafe, Alain; Abdennour, Meriem; Portet, Florence; Molino, François; Stern, Yaakov; Ritchie, Karen; Menjot de Champfleur, Nicolas; Akbaraly, Tasnime N

2015-11-01

Changes in working memory are sensitive indicators of both normal and pathological brain aging and associated disability. The present study aims to further understanding of working memory in normal aging using a large cohort of healthy elderly in order to examine three separate phases of information processing in relation to changes in task load activation. Using covariance analysis, increasing and decreasing neural activation was observed on fMRI in response to a delayed item recognition task in 337 cognitively healthy elderly persons as part of the CRESCENDO (Cognitive REServe and Clinical ENDOphenotypes) study. During three phases of the task (stimulation, retention, probe), increased activation was observed with increasing task load in bilateral regions of the prefrontal cortex, parietal lobule, cingulate gyrus, insula and in deep gray matter nuclei, suggesting an involvement of central executive and salience networks. Decreased activation associated with increasing task load was observed during the stimulation phase, in bilateral temporal cortex, parietal lobule, cingulate gyrus and prefrontal cortex. This spatial distribution of decreased activation is suggestive of the default mode network. These findings support the hypothesis of an increased activation in salience and central executive networks and a decreased activation in default mode network concomitant to increasing task load. Copyright © 2015 Elsevier Inc. All rights reserved.

Size-dependent and tunable crystallization of GeSbTe phase-change nanoparticles

NASA Astrophysics Data System (ADS)

Chen, Bin; Ten Brink, Gert H.; Palasantzas, George; Kooi, Bart J.

2016-12-01

Chalcogenide-based nanostructured phase-change materials (PCMs) are considered promising building blocks for non-volatile memory due to their high write and read speeds, high data-storage density, and low power consumption. Top-down fabrication of PCM nanoparticles (NPs), however, often results in damage and deterioration of their useful properties. Gas-phase condensation based on magnetron sputtering offers an attractive and straightforward solution to continuously down-scale the PCMs into sub-lithographic sizes. Here we unprecedentedly present the size dependence of crystallization for Ge2Sb2Te5 (GST) NPs, whose production is currently highly challenging for chemical synthesis or top-down fabrication. Both amorphous and crystalline NPs have been produced with excellent size and composition control with average diameters varying between 8 and 17 nm. The size-dependent crystallization of these NPs was carefully analyzed through in-situ heating in a transmission electron microscope, where the crystallization temperatures (Tc) decrease when the NPs become smaller. Moreover, methane incorporation has been observed as an effective method to enhance the amorphous phase stability of the NPs. This work therefore elucidates that GST NPs synthesized by gas-phase condensation with tailored properties are promising alternatives in designing phase-change memories constrained by optical lithography limitations.

Can Oxytocin Enhance the Placebo Effect?

ClinicalTrials.gov

2018-02-06

Oxytocin Effect on Memory Performance During Phase 1; Oxytocin Effect on Memory Performance During Phase 2; Oxytocin Effect on Memory Performance During Phase 3; Oxytocin Effect on Memory Performance During Phase 4

The effect of magnetic field on shape memory behavior in Heusler-type nickel(,2)manganese-gallium-based compounds

NASA Astrophysics Data System (ADS)

Jeong, Soon-Jong

2000-08-01

Shape memory alloys (SMAs) have excellent mechanical properties showing large stroke and high power density when used as actuators. In terms of response speed, however, conventional SMAs have a drawback due to the isothermal nature of the associated phase transformation. A new type of SMA, called ferromagnetic SMA, is considered to replace conventional SMAs and is hoped to overcome such a slow response drawback by changing driving mode of shape memory behaviors from thermal to magnetic. The new type of ferromagnetic SMAs is expected to exhibit not only a large displacement but also rapid response when magnetic field is applied and removed. There are three kinds of ferromagnetic SMAs and among them, Ni2MnGa-based compounds exhibit prominent shape memory effects and superelasticity. In this study, Ni2MnGa-based alloys were chosen and studied to characterize shape memory behavior upon the application and removal of magnetic field. The relevance of the magnetic field-induced shape memory behavior to the magnetization process was investigated by using transformation and/or the movement of martensite variant interfaces. Two mechanisms have been proposed for controlling magnetic field-induced shape memory behaviors. One mechanism is related to shape memory behavior associated with magnetic field-induced martensitic transformation. The other is related to the rearrangement of martensite variants by magnetic field application. Magnetic field-induced martensitic transformation and shape memory effects for single- and poly-crystalline Ni2MnGa alloys were investigated under various conditions. In single crystalline specimens, it was observed that considerable strain changes are a function of magnetic field at temperatures below Mf (martensite finish temperature). Such strain changes, by application and subsequent removal of magnetic field, may be attributed to the martensite variant motion at lower temperatures than Mf. Magnetic field application made a significant contribution to the martensite transformation and related strain changes (0.3%--0.82%) at temperatures above Af (austenite finish temperature) in some polycrystalline Ni2MnGa alloys, where austenite and martensite phases possess paramagnetic and ferromagnetic properties, respectively.

Olfactory short-term memory encoding and maintenance - an event-related potential study.

PubMed

Lenk, Steffen; Bluschke, Annet; Beste, Christian; Iannilli, Emilia; Rößner, Veit; Hummel, Thomas; Bender, Stephan

2014-09-01

This study examined whether the memory encoding and short term maintenance of olfactory stimuli is associated with neurophysiological activation patterns which parallel those described for sensory modalities such as vision and auditory. We examined olfactory event-related potentials in an olfactory change detection task in twenty-four healthy adults and compared the measured activation to that found during passive olfactory stimulation. During the early olfactory post-processing phase, we found a sustained negativity over bilateral frontotemporal areas in the passive perception condition which was enhanced in the active memory task. There was no significant lateralization in either experimental condition. During the maintenance interval at the end of the delay period, we still found sustained activation over bilateral frontotemporal areas which was more negative in trials with correct - as compared to incorrect - behavioural responses. This was complemented by a general significantly stronger frontocentral activation. Summarizing, we were able to show that olfactory short term memory involves a parallel sequence of activation as found in other sensory modalities. In addition to olfactory-specific frontotemporal activations in the memory encoding phase, we found slow cortical potentials over frontocentral areas during the memory maintenance phase indicating the activation of a supramodal memory maintenance system. These findings could represent the neurophysiological underpinning of the 'olfactory flacon', the olfactory counter-part to the visual sketchpad and phonological loop embedded in Baddeley's working memory model. Copyright © 2014 Elsevier Inc. All rights reserved.

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

NASA Astrophysics Data System (ADS)

Ogasawara, Ryosuke; Endoh, Tetsuo

2018-04-01

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

Mirror-symmetric magneto-optical Kerr rotation using visible light in [(GeTe)2(Sb2Te3)1]n topological superlattices.

PubMed

Bang, Do; Awano, Hiroyuki; Tominaga, Junji; Kolobov, Alexander V; Fons, Paul; Saito, Yuta; Makino, Kotaro; Nakano, Takashi; Hase, Muneaki; Takagaki, Yukihiko; Giussani, Alessandro; Calarco, Raffaella; Murakami, Shuichi

2014-07-17

Interfacial phase change memory (iPCM), that has a structure of a superlattice made of alternating atomically thin GeTe and Sb2Te3 layers, has recently attracted attention not only due to its superior performance compared to the alloy of the same average composition in terms of energy consumption but also due to its strong response to an external magnetic field (giant magnetoresistance) that has been speculated to arise from switching between topological insulator (RESET) and normal insulator (SET) phases. Here we report magneto-optical Kerr rotation loops in the visible range, that have mirror symmetric resonances with respect to the magnetic field polarity at temperatures above 380 K when the material is in the SET phase that has Kramers-pairs in spin-split bands. We further found that this threshold temperature may be controlled if the sample was cooled in a magnetic field. The observed results open new possibilities for use of iPCM beyond phase-change memory applications.

Multilevel radiative thermal memory realized by the hysteretic metal-insulator transition of vanadium dioxide

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

Ito, Kota, E-mail: kotaito@mosk.tytlabs.co.jp; Nishikawa, Kazutaka; Iizuka, Hideo

Thermal information processing is attracting much interest as an analog of electronic computing. We experimentally demonstrated a radiative thermal memory utilizing a phase change material. The hysteretic metal-insulator transition of vanadium dioxide (VO{sub 2}) allows us to obtain a multilevel memory. We developed a Preisach model to explain the hysteretic radiative heat transfer between a VO{sub 2} film and a fused quartz substrate. The transient response of our memory predicted by the Preisach model agrees well with the measured response. Our multilevel thermal memory paves the way for thermal information processing as well as contactless thermal management.

Donor CD8+ T Cells Prevent Toxoplasma gondii De-Encystation but Fail To Rescue the Exhausted Endogenous CD8+ T Cell Population

PubMed Central

Bhadra, Rajarshi; Cobb, Dustin A.

2013-01-01

Functional exhaustion of CD8+ T cells due to increased expression of inhibitory molecule PD-1 (Programmed Death-1) causes reactivation of latent disease during later phases of chronic toxoplasmosis. Onset of disease recrudescence results in decreased parasite cyst burden concomitant with parasites undergoing stage conversion from a primarily encysted, quiescent bradyzoite to a fast-replicating, highly motile tachyzoite. Thus, reduced cyst burden is one of the early hallmarks of disease recrudescence. This was further validated by depleting gamma interferon (IFN-γ), a cytokine known to control latent toxoplasmosis, in chronically infected prerecrudescent mice. Since CD8+ T cells (an important source of IFN-γ) lose their functionality during the later phases of chronic toxoplasmosis, we next examined if adoptive transfer of functional CD8+ T cells from acutely infected donors to the chronically infected prerecrudescent hosts could impede parasite de-encystation and rescue exhausted CD8+ T cells. While the transfer of immune CD8+ T cells temporarily restricted the breakdown of cysts, the exhausted endogenous CD8+ T cell population was not rescued. Over time, the donor population got deleted, resulting in parasite de-encystation and host mortality. Considering that donor CD8+ T cells fail to become long-lived, one of the cardinal features of memory CD8+ T cells, it bears the implication that memory CD8 differentiation is impaired during chronic toxoplasmosis. Moreover, our data strongly suggest that while adoptive immunotherapy can prevent parasite de-encystation transiently, reduced antigen burden in the chronic phase by itself is insufficient for rescue of exhausted CD8+ T cells. The conclusions of this study have profound ramifications in designing immunotherapeutics against chronic toxoplasmosis. PMID:23817617

Synthesis and Screening of Phase Change Chalcogenide Thin Film Materials for Data Storage.

PubMed

Guerin, Samuel; Hayden, Brian; Hewak, Daniel W; Vian, Chris

2017-07-10

A combinatorial synthetic methodology based on evaporation sources under an ultrahigh vacuum has been used to directly synthesize compositional gradient thin film libraries of the amorphous phases of GeSbTe alloys at room temperature over a wide compositional range. An optical screen is described that allows rapid parallel mapping of the amorphous-to-crystalline phase transition temperature and optical contrast associated with the phase change on such libraries. The results are shown to be consistent with the literature for compositions where published data are available along the Sb 2 Te 3 -GeTe tie line. The results reveal a minimum in the crystallization temperature along the Sb 2 Te 3 -Ge 2 Te 3 tie line, and the method is able to resolve subsequent cubic-to-hexagonal phase transitions in the GST crystalline phase. HT-XRD has been used to map the phases at sequentially higher temperatures, and the results are reconciled with the literature and trends in crystallization temperatures. The results clearly delineate compositions that crystallize to pure GST phases and those that cocrystallize Te. High-throughput measurement of the resistivity of the amorphous and crystalline phases has allowed the compositional and structural correlation of the resistivity contrast associated with the amorphous-to-crystalline transition, which range from 5-to-8 orders of magnitude for the compositions investigated. The results are discussed in terms of the compromises in the selection of these materials for phase change memory applications and the potential for further exploration through more detailed secondary screening of doped GST or similar classes of phase change materials designed for the demands of future memory devices.

Developmental differences in the neural correlates of relational encoding and recall in children: An event-related fMRI study

PubMed Central

Güler, O. Evren; Thomas, Kathleen M.

2012-01-01

Despite vast knowledge on the behavioral processes mediating the development of episodic memory, little is known about the neural mechanisms underlying these changes. We used event-related fMRI to examine the neural correlates of both encoding and recall processes during an episodic memory task in two different groups of school age children (8–9 & 12–13 years). The memory task was composed of an encoding phase in which children were presented with a series of unrelated pictorial pairs, and a retrieval phase during which one of these items acted as a cue to prompt recall of the paired item. Age-related differences in activations were observed for both encoding and recall. Younger children recruited additional regions in the right dorsolateral prefrontal and right temporal cortex compared to older children during successful encoding of the pairs. During successful recall, older children recruited additional regions in the left ventrolateral prefrontal and left inferior parietal cortex compared to younger children. The results suggest that the prefrontal cortex contributes to not only the formation of memories but also access to them, and this contribution changes with development. The protracted development of the prefrontal cortex has implications for our understanding of the development of episodic memory. PMID:22884992

Materials and other needs for advanced phase change memory (Presentation Recording)

NASA Astrophysics Data System (ADS)

Sosa, Norma E.

2015-09-01

Phase change memory (PCM), with its long history, may now hold its brightest promise to date. This bright future is being fueled by the "push" from big data. PCM is a non-volatile memory technology used to create solid-state random access memory devices that operate based the resistance properties of materials. Employing the electrical resistance differences-as opposed to differences in charge stored-between the amorphous and crystalline phases of the material, PCM can store bits, namely one's and zero's. Indeed, owing to the method of storage, PCM can in fact be designed to hold multiple bits thus leading to a high-density technology twice the storage density and less than half the cost of DRAM, the main kind found in typical personal computers. It has been long known that PCM can fill a need gap that spans 3 decades in performance from DRAM to solid state drive (NAND Flash). Furthermore, PCM devices can lead to performance and reliability improvements essential to enabling significant steps forward to supporting big data centric computing. This talk will focus on the science and challenges of aggressive scaling to realize the density needed, how this scaling challenge is intertwined with materials needs for endurance into the giga-cycles, and the associated forefront research aiming to realizing multi-level functionality into these nanoscale programmable resistor devices.

a Thermal Conduction Switch Based on Low Hysteresis Nitife Shape Memory Alloy Helical Springs

NASA Astrophysics Data System (ADS)

Krishnan, V. B.; Bewerse, C.; Notardonato, W. U.; Vaidyanathan, R.

2008-03-01

Shape memory alloy (SMA) actuators possess an inherent property of sensing a change in temperature and delivering significant force against external loads through a shape change resulting from a temperature-induced phase transformation. The utilization of a reversible trigonal (R-phase) to cubic phase transformation in NiTiFe SMAs allows for this strain recovery to occur with reduced hysteresis between the forward and reverse transformations. However, the magnitude of the strain recovery associated with the R-phase transformation is lower than that of the monoclinic to cubic phase transformation. The use of helical springs can compensate for this design constraint as they produce significant stroke when compared to straight elements such as thin strips and wires. This work reports on the development and implementation of NiTiFe helical springs in a low-hysteresis thermal conduction switch for advanced spaceport applications associated with NASA's requirements for future lunar and Mars missions. Such a low-hysteresis thermal conduction switch can provide on-demand heat transfer between two reservoirs at different temperatures.

Carbon nanomaterials for non-volatile memories

NASA Astrophysics Data System (ADS)

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

2018-03-01

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

Origin of the OFF state variability in ReRAM cells

NASA Astrophysics Data System (ADS)

Salaoru, Iulia; Khiat, Ali; Li, Qingjiang; Berdan, Radu; Papavassiliou, Christos; Prodromakis, Themistoklis

2014-04-01

This work exploits the switching dynamics of nanoscale resistive random access memory (ReRAM) cells with particular emphasis on the origin of the observed variability when cells are consecutively cycled/programmed at distinct memory states. It is demonstrated that this variance is a common feature of all ReRAM elements and is ascribed to the formation and rupture of conductive filaments that expand across the active core, independently of the material employed as the active switching core, the causal physical switching mechanism, the switching mode (bipolar/unipolar) or even the unit cells' dimensions. Our hypothesis is supported through both experimental and theoretical studies on TiO2 and In2O3 : SnO2 (ITO) based ReRAM cells programmed at three distinct resistive states. Our prototypes employed TiO2 or ITO active cores over 5 × 5 µm2 and 100 × 100 µm2 cell areas, with all tested devices demonstrating both unipolar and bipolar switching modalities. In the case of TiO2-based cells, the underlying switching mechanism is based on the non-uniform displacement of ionic species that foster the formation of conductive filaments. On the other hand, the resistive switching observed in the ITO-based devices is considered to be due to a phase change mechanism. The selected experimental parameters allowed us to demonstrate that the observed programming variance is a common feature of all ReRAM devices, proving that its origin is dependent upon randomly oriented local disorders within the active core that have a substantial impact on the overall state variance, particularly for high-resistive states.

Treating verbal working memory in a boy with intellectual disability

PubMed Central

Orsolini, Margherita; Melogno, Sergio; Latini, Nausica; Penge, Roberta; Conforti, Sara

2015-01-01

The present case study investigates the effects of a cognitive training of verbal working memory that was proposed for Davide, a 14-year-old boy diagnosed with mild intellectual disability. The program stimulated attention, inhibition, switching, and the ability to engage either in verbal dual tasks or in producing inferences after the content of a short passage had been encoded in episodic memory. Key elements in our program included (1) core training of target cognitive mechanisms; (2) guided practice emphasizing concrete strategies to engage in exercises; and (3) a variable amount of adult support. The study explored whether such a complex program produced “near transfer” effects on an untrained dual task assessing verbal working memory and whether effects on this and other target cognitive mechanisms (i.e., attention, inhibition, and switching) were long-lasting and produced “far transfer” effects on cognitive flexibility. The effects of the intervention program were investigated with a research design consisting of four subsequent phases lasting 8 or 10 weeks, each preceded and followed by testing. There was a control condition (phase 1) in which the boy received, at home, a stimulation focused on the visuospatial domain. Subsequently, there were three experimental training phases, in which stimulation in the verbal domain was first focused on attention and inhibition (phase 2a), then on switching and simple working memory tasks (phase 2b), then on complex working memory tasks (phase 3). A battery of neuropsychological tests was administered before and after each training phase and 7 months after the conclusion of the intervention. The main finding was that Davide changed from being incapable of addressing the dual task request of the listening span test in the initial assessment to performing close to the normal limits of a 13-year-old boy in the follow-up assessment with this test, when he was 15 years old. PMID:26284014

Atomic Migration Induced Crystal Structure Transformation and Core-Centered Phase Transition in Single Crystal Ge2Sb2Te5 Nanowires.

PubMed

Lee, Jun-Young; Kim, Jeong-Hyeon; Jeon, Deok-Jin; Han, Jaehyun; Yeo, Jong-Souk

2016-10-12

A phase change nanowire holds a promise for nonvolatile memory applications, but its transition mechanism has remained unclear due to the analytical difficulties at atomic resolution. Here we obtain a deeper understanding on the phase transition of a single crystalline Ge 2 Sb 2 Te 5 nanowire (GST NW) using atomic scale imaging, diffraction, and chemical analysis. Our cross-sectional analysis has shown that the as-grown hexagonal close-packed structure of the single crystal GST NW transforms to a metastable face-centered cubic structure due to the atomic migration to the pre-existing vacancy layers in the hcp structure going through iterative electrical switching. We call this crystal structure transformation "metastabilization", which is also confirmed by the increase of set-resistance during the switching operation. For the set to reset transition between crystalline and amorphous phases, high-resolution imaging indicates that the longitudinal center of the nanowire mainly undergoes phase transition. According to the atomic scale analysis of the GST NW after repeated electrical switching, partial crystallites are distributed around the core-centered amorphous region of the nanowire where atomic migration is mainly induced, thus potentially leading to low power electrical switching. These results provide a novel understanding of phase change nanowires, and can be applied to enhance the design of nanowire phase change memory devices for improved electrical performance.

Improved Functional Properties and Efficiencies of Nitinol Wires Under High-Performance Shape Memory Effect (HP-SME)

NASA Astrophysics Data System (ADS)

Casati, R.; Saghafi, F.; Biffi, C. A.; Vedani, M.; Tuissi, A.

2017-10-01

Martensitic Ti-rich NiTi intermetallics are broadly used in various cyclic applications as actuators, which exploit the shape memory effect (SME). Recently, a new approach for exploiting austenitic Ni-rich NiTi shape memory alloys as actuators was proposed and named high-performance shape memory effect (HP-SME). HP-SME is based on thermal recovery of de-twinned martensite produced by mechanical loading of the parent phase. The aim of the manuscript consists in evaluating and comparing the fatigue and actuation properties of austenitic HP-SME wires and conventional martensitic SME wires. The effect of the thermomechanical cycling on the actuation response and the changes in the electrical resistivity of both shape memory materials were studied by performing the actuation tests at different stages of the fatigue life. Finally, the changes in the transition temperatures before and after cycling were also investigated by differential calorimetric tests.

Effect of Thermal Treatments on Ni-Mn-Ga and Ni-Rich Ni-Ti-Hf/Zr High-Temperature Shape Memory Alloys

NASA Astrophysics Data System (ADS)

Santamarta, Ruben; Evirgen, Alper; Perez-Sierra, Aquilina M.; Pons, Jaume; Cesari, Eduard; Karaman, Ibrahim; Noebe, Ron D.

2015-11-01

Among all the promising high-temperature shape memory alloys (HTSMAs), the Ni-Mn-Ga and the Ni-Ti-Hf/Zr systems exhibit interesting shape memory and superelastic properties that may place them in a good position for potential applications. The present work shows that thermal treatments play a crucial role in controlling the martensitic phase transformation characteristics of both systems, but in different ways. On one hand, the equilibrium phase diagram of the Ni-Mn-Ga family allows selecting compositions with high transformation temperatures and outstanding thermal stability at relatively high temperatures in air, showing no significant changes in the transformation behavior for continuous aging up to ˜5 years at 500 °C. Moreover, the excellent thermal stability correlates with a good thermal cyclic stability and an exceptional oxidation resistance of the parent phase. On the other hand, precipitation processes controlled by thermal treatments are needed to manipulate the transformation temperatures, mechanical properties, and thermal stability of Ni-rich Ni-Ti-Hf/Zr alloys to become HTSMAs. These changes in the functional properties are a consequence of the competition between the mechanical and compositional effects of the precipitates on the martensitic transformation.

Phase Measurement of Cognitive Impairment Specific to Radiotherapy

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

Armstrong, Carol L., E-mail: armstrongc@email.chop.edu; Department of Pediatrics, Division of Neuro-Oncology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania; Shera, David M.

Purpose: Memory impairment is an early-delayed effect of radiotherapy (RT). The prospective longitudinal measurement of the cognitive phase effects from RT was conducted on treated and untreated brain tumor patients. The study design investigated semantic vs. perceptual and visual vs. verbal memory to determine the most disease-specific measure of RT-related changes and understanding of the neurotoxicity from RT to the brain. Methods and Materials: Tests of memory that had previously shown RT-related phasic changes were compared with experimental tests of memory to test hypotheses about cognition targeted to the neural toxicity of RT. The results from 41 irradiated and 29more » nonirradiated patients with low-grade, supratentorial tumors were analyzed. The methods controlled for comorbid white matter risk, recurrence, interval after treatment, and age (18-69 years). The effects were examined before RT and at three points after RT to 1 year using a mixed effects model that included interval, group, surgical status, medication use, practice, and individual random effects. Four new tests of memory and other candidate cognitive tests were investigated, and a post hoc analysis of a comprehensive battery of tests was performed to identify the cognitive processes most specific to RT. Results: The RT effects on memory were identified in the treated group only; among the new tests of memory and the complete neurocognitive battery, the RT effects were significant only for delayed recall (p < 0.009) and interval to recognize (p < 0.002). Tumor location was not related to the treatment effect. Memory decline was specific to retrieval of semantic memories; a double dissociation of semantic from perceptual visual memory was demonstrated in the RT group. Conclusions: These results implicate memory dependent on the semantic cortex and the hippocampal memory system. A cognitive measurement that is brief but specific to neural mechanisms is effective and feasible for studies of RT damage.« less

Cellular basis for neonatally induced T-suppressor activity. Primary B cell maturation is blocked by suppressor-helper interactions restricted by loci on chromosome 12

PubMed Central

1985-01-01

The cellular mechanism and genetic restriction of neonatally induced HA- specific suppressor T (Ts) cells have been examined. The in vivo effect of these Ts cells on antibody production, primary B cell proliferation, B cell surface marker changes, and helper T (Th) cell priming during primary responses to HA have been determined. The results indicate that, although antigen-induced B cell proliferative responses and surface marker changes occur in the presence of Ts cells, differentiation to Ig secretion, and long-lived memory B cell production are prevented. Further, antigen-specific Th cell priming is completely ablated by Ts cells, suggesting that Ts act by preventing the delivery of Th signals required for both the later stages of primary B cell maturation, and the formation of memory B cell populations. Finally, in vivo cell mixing experiments using congenic mice indicate that this Ts-Th interaction is restricted by loci on mouse chromosome 12. PMID:2580040

Temporal dynamics of the primary human T cell response to yellow fever virus 17D as it matures from an effector- to a memory-type response.

PubMed

Blom, Kim; Braun, Monika; Ivarsson, Martin A; Gonzalez, Veronica D; Falconer, Karolin; Moll, Markus; Ljunggren, Hans-Gustaf; Michaëlsson, Jakob; Sandberg, Johan K

2013-03-01

The live attenuated yellow fever virus (YFV) 17D vaccine provides a good model to study immune responses to an acute viral infection in humans. We studied the temporal dynamics, composition, and character of the primary human T cell response to YFV. The acute YFV-specific effector CD8 T cell response was broad and complex; it was composed of dominant responses that persisted into the memory population, as well as of transient subdominant responses that were not detected at the memory stage. Furthermore, HLA-A2- and HLA-B7-restricted YFV epitope-specific effector cells predominantly displayed a CD45RA(-)CCR7(-)PD-1(+)CD27(high) phenotype, which transitioned into a CD45RA(+)CCR7(-)PD-1(-)CD27(low) memory population phenotype. The functional profile of the YFV-specific CD8 T cell response changed in composition as it matured from an effector- to a memory-type response, and it tended to become less polyfunctional during the course of this transition. Interestingly, activation of CD4 T cells, as well as FOXP3(+) T regulatory cells, in response to YFV vaccination preceded the kinetics of the CD8 T cell response. The present results contribute to our understanding of how immunodominance patterns develop, as well as the phenotypic and functional characteristics of the primary human T cell response to a viral infection as it evolves and matures into memory.

Young T Cells Age During a Redirected Anti-Tumor Attack: Chimeric Antigen Receptor-Provided Dual Costimulation is Half the Battle

PubMed Central

Hombach, Andreas A.; Abken, Hinrich

2013-01-01

Adoptive therapy with chimeric antigen receptor (CAR)-redirected T cells showed spectacular efficacy in the treatment of leukemia in recent early phase trials. Patient’s T cells were ex vivo genetically engineered with a CAR, amplified and re-administered to the patient. While T cells mediating the primary response were predominantly of young effector and central memory phenotype, repetitive antigen engagement irreversible triggers T cell maturation leaving late memory cells with the KLRG1+ CD57+ CD7− CCR7− phenotype in the long-term. These cells preferentially accumulate in the periphery, are hypo-responsive upon TCR engagement and prone to activation-induced cell death. A recent report indicates that those T cells can be rescued by CAR provided CD28 and OX40 (CD134) stimulation. We discuss the strategy with respect to prolong the anti-tumor response and to improve the over-all efficacy of adoptive cell therapy. PMID:23761793

Young T Cells Age During a Redirected Anti-Tumor Attack: Chimeric Antigen Receptor-Provided Dual Costimulation is Half the Battle.

PubMed

Hombach, Andreas A; Abken, Hinrich

2013-01-01

Adoptive therapy with chimeric antigen receptor (CAR)-redirected T cells showed spectacular efficacy in the treatment of leukemia in recent early phase trials. Patient's T cells were ex vivo genetically engineered with a CAR, amplified and re-administered to the patient. While T cells mediating the primary response were predominantly of young effector and central memory phenotype, repetitive antigen engagement irreversible triggers T cell maturation leaving late memory cells with the KLRG1(+) CD57(+) CD7(-) CCR7(-) phenotype in the long-term. These cells preferentially accumulate in the periphery, are hypo-responsive upon TCR engagement and prone to activation-induced cell death. A recent report indicates that those T cells can be rescued by CAR provided CD28 and OX40 (CD134) stimulation. We discuss the strategy with respect to prolong the anti-tumor response and to improve the over-all efficacy of adoptive cell therapy.

Alpha tumor necrosis factor contributes to CD8{sup +} T cell survival in the transition phase

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

Shi, Meiqing; Ye, Zhenmin; Umeshappa, Keshav Sokke

Cytokine and costimulation signals determine CD8{sup +} T cell responses in proliferation phase. In this study, we assessed the potential effect of cytokines and costimulations to CD8{sup +} T cell survival in transition phase by transferring in vitro ovalbumin (OVA)-pulsed dendritic cell-activated CD8{sup +} T cells derived from OVA-specific T cell receptor transgenic OT I mice into wild-type C57BL/6 mice or mice with designated gene knockout. We found that deficiency of IL-10, IL-12, IFN-{gamma}, CD28, CD40, CD80, CD40L, and 41BBL in recipients did not affect CD8{sup +} T cell survival after adoptive transfer. In contrast, TNF-{alpha} deficiency in both recipientsmore » and donor CD8{sup +} effector T cells significantly reduced CD8{sup +} T cell survival. Therefore, our data demonstrate that the host- and T cell-derived TNF-{alpha} signaling contributes to CD8{sup +} effector T cell survival and their transition to memory T cells in the transition phase, and may be useful information when designing vaccination.« less

Age-Related Reversals in Neural Recruitment across Memory Retrieval Phases

PubMed Central

Kensinger, Elizabeth A.

2017-01-01

Over the last several decades, neuroimaging research has identified age-related neural changes that occur during cognitive tasks. These changes are used to help researchers identify functional changes that contribute to age-related impairments in cognitive performance. One commonly reported example of such a change is an age-related decrease in the recruitment of posterior sensory regions coupled with an increased recruitment of prefrontal regions across multiple cognitive tasks. This shift is often described as a compensatory recruitment of prefrontal regions due to age-related sensory-processing deficits in posterior regions. However, age is not only associated with spatial shifts in recruitment, but also with temporal shifts, in which younger and older adults recruit the same neural region at different points in a task trial. The current study examines the possible contribution of temporal modifications in the often-reported posterior–anterior shift. Participants, ages 19–85, took part in a memory retrieval task with a protracted retrieval trial consisting of an initial memory search phase and a subsequent detail elaboration phase. Age-related neural patterns during search replicated prior reports of age-related decreases in posterior recruitment and increases in prefrontal recruitment. However, during the later elaboration phase, the same posterior regions were associated with age-related increases in activation. Further, ROI and functional connectivity results suggest that these posterior regions function similarly during search and elaboration. These results suggest that the often-reported posterior–anterior shift may not reflect the inability of older adults to engage in sensory processing, but rather a change in when they recruit this processing. SIGNIFICANCE STATEMENT The current study provides evidence that the often-reported posterior–anterior shift in aging may not reflect a global sensory-processing deficit, as has often been reported, but rather a temporal modification in this processing in which older adults engage the same neural regions during a detail elaboration phase that younger adults engage during memory search. In other words, older adults may ultimately be able to engage the same processes as younger adults during some cognitive tasks when given the time to do so. Future research should examine the generalizability of this effect and the importance of encouraging older adults to engage in these processes through task instruction or questions. PMID:28442537

Sign reversal of transformation entropy change in Co{sub 2}Cr(Ga,Si) shape memory alloys

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

Xu, Xiao, E-mail: xu@material.tohoku.ac.jp; Omori, Toshihiro; Kainuma, Ryosuke

2015-11-02

In situ X-ray diffraction (XRD) measurements and compression tests were performed on Co{sub 2}Cr(Ga,Si) shape memory alloys. The reentrant martensitic transformation behavior was directly observed during the in situ XRD measurements. The high-temperature parent phase and low-temperature reentrant parent phase were found to have a continuous temperature dependence of lattice parameter, therefore suggesting that they are the same phase in nature. Moreover, compression tests were performed on a parent-phase single crystal sample; an evolution from normal to inverse temperature dependence of critical stress for martensitic transformation was directly observed. Based on the Clausius-Clapeyron analysis, a sign reversal of entropy changemore » can be expected on the same alloy.« less

Storage and retrieval of vector beams of light in a multiple-degree-of-freedom quantum memory.

PubMed

Parigi, Valentina; D'Ambrosio, Vincenzo; Arnold, Christophe; Marrucci, Lorenzo; Sciarrino, Fabio; Laurat, Julien

2015-07-13

The full structuration of light in the transverse plane, including intensity, phase and polarization, holds the promise of unprecedented capabilities for applications in classical optics as well as in quantum optics and information sciences. Harnessing special topologies can lead to enhanced focusing, data multiplexing or advanced sensing and metrology. Here we experimentally demonstrate the storage of such spatio-polarization-patterned beams into an optical memory. A set of vectorial vortex modes is generated via liquid crystal cell with topological charge in the optic axis distribution, and preservation of the phase and polarization singularities is demonstrated after retrieval, at the single-photon level. The realized multiple-degree-of-freedom memory can find applications in classical data processing but also in quantum network scenarios where structured states have been shown to provide promising attributes, such as rotational invariance.

Storage and retrieval of vector beams of light in a multiple-degree-of-freedom quantum memory

PubMed Central

Parigi, Valentina; D'Ambrosio, Vincenzo; Arnold, Christophe; Marrucci, Lorenzo; Sciarrino, Fabio; Laurat, Julien

2015-01-01

The full structuration of light in the transverse plane, including intensity, phase and polarization, holds the promise of unprecedented capabilities for applications in classical optics as well as in quantum optics and information sciences. Harnessing special topologies can lead to enhanced focusing, data multiplexing or advanced sensing and metrology. Here we experimentally demonstrate the storage of such spatio-polarization-patterned beams into an optical memory. A set of vectorial vortex modes is generated via liquid crystal cell with topological charge in the optic axis distribution, and preservation of the phase and polarization singularities is demonstrated after retrieval, at the single-photon level. The realized multiple-degree-of-freedom memory can find applications in classical data processing but also in quantum network scenarios where structured states have been shown to provide promising attributes, such as rotational invariance. PMID:26166257

Shape memory behavior of single and polycrystalline nickel rich nickel titanium alloys

NASA Astrophysics Data System (ADS)

Kaya, Irfan

NiTi is the most commonly used shape memory alloy (SMA) and has been widely used for bio-medical, electrical and mechanical applications. Nickel rich NiTi shape memory alloys are coming into prominence due to their distinct superelasticity and shape memory properties as compared to near equi-atomic NiTi shape memory alloys. Besides, their lower density and higher work output than steels makes these alloys an excellent candidate for aerospace and automotive industry. Shape memory properties and phase transformation behavior of high Ni-rich Ni54Ti46 (at.%) polycrystals and Ni-rich Ni 51Ti49 (at.%) single-crystals are determined. Their properties are sensitive to heat treatments that affect the phase transformation behavior of these alloys. Phase transformation properties and microstructure were investigated in aged Ni54Ti46 alloys with differential scanning calorimetry (DSC) and transmission electron microscopy (TEM) to reveal the precipitation characteristics and R-phase formation. It was found that Ni54Ti46 has the ability to exhibit perfect superelasticity under high stress levels (~2 GPa) with 4% total strain after 550°C-3h aging. Stress independent R-phase transformation was found to be responsible for the change in shape memory behavior with stress. The shape memory responses of [001], [011] and [111] oriented Ni 51Ti49 single-crystals alloy were reported under compression to reveal the orientation dependence of their shape memory behavior. It has been found that transformation strain, temperatures and hysteresis, Classius-Clapeyron slopes, critical stress for plastic deformation are highly orientation dependent. The effects of precipitation formation and compressive loading at selected temperatures on the two-way shape memory effect (TWSME) properties of a [111]- oriented Ni51Ti49 shape memory alloy were revealed. Additionally, aligned Ni4Ti3 precipitates were formed in a single crystal of Ni51Ti49 alloy by aging under applied compression stress along the [111] direction. Formation of a single family of Ni4Ti3 precipitates were exhibited significant TWSME without any training or deformation. When the homogenized and aged specimens were loaded in martensite, positive TWSME was observed. After loading at high temperature in austenite, the homogenized specimen did not show TWSME while the aged specimen revealed negative TWSME.

Impact of Aging, Cytomegalovirus Infection, and Long-Term Treatment for Human Immunodeficiency Virus on CD8+ T-Cell Subsets

PubMed Central

Veel, Ellen; Westera, Liset; van Gent, Rogier; Bont, Louis; Otto, Sigrid; Ruijsink, Bram; Rabouw, Huib H.; Mudrikova, Tania; Wensing, Annemarie; Hoepelman, Andy I. M.; Borghans, José A. M.; Tesselaar, Kiki

2018-01-01

Both healthy aging and human immunodeficiency virus (HIV) infection lead to a progressive decline in naive CD8+ T-cell numbers and expansion of the CD8+ T-cell memory and effector compartments. HIV infection is therefore often considered a condition of premature aging. Total CD8+ T-cell numbers of HIV-infected individuals typically stay increased even after long-term (LT) combination antiretroviral treatment (cART), which is associated with an increased risk of non-AIDS morbidity and mortality. The causes of these persistent changes in the CD8+ T-cell pool remain debated. Here, we studied the impact of age, CMV infection, and LT successful cART on absolute cell numbers in different CD8+ T-cell subsets. While naïve CD8+ T-cell numbers in cART-treated individuals (N = 38) increased to healthy levels, central memory (CM), effector memory (EM), and effector CD8+ T-cell numbers remained higher than in (unselected) age-matched healthy controls (N = 107). Longitudinal analysis in a subset of patients showed that cART did result in a loss of memory CD8+ T-cells, mainly during the first year of cART, after which memory cell numbers remained relatively stable. As CMV infection is known to increase CD8+ T-cell numbers in healthy individuals, we studied whether any of the persistent changes in the CD8+ T-cell pools of cART-treated patients could be a direct reflection of the high CMV prevalence among HIV-infected individuals. We found that EM and effector CD8+ T-cell numbers in CMV+ healthy individuals (N = 87) were significantly higher than in CMV− (N = 170) healthy individuals. As a result, EM and effector CD8+ T-cell numbers in successfully cART-treated HIV-infected individuals did not deviate significantly from those of age-matched CMV+ healthy controls (N = 39). By contrast, CM T-cell numbers were quite similar in CMV+ and CMV− healthy individuals across all ages. The LT expansion of the CM CD8+ T-cell pool in cART-treated individuals could thus not be attributed directly to CMV and was also not related to residual HIV RNA or to the presence of HIV-specific CM T-cells. It remains to be investigated why the CM CD8+ T-cell subset shows seemingly irreversible changes despite years of effective treatment. PMID:29619031

Age-related differences in associative memory: Empirical evidence and theoretical perspectives.

PubMed

Naveh-Benjamin, Moshe; Mayr, Ulrich

2018-02-01

Systematic research and anecdotal evidence both indicate declines in episodic memory in older adults in good health without dementia-related disorders. Several hypotheses have been proposed to explain these age-related changes in episodic memory, some of which attribute such declines to a deterioration in associative memory. The current special issue of Psychology and Aging on Age-Related Differences in Associative Memory includes 16 articles by top researchers in the area of memory and aging. Their contributions provide a wealth of empirical work that addresses different aspects of aging and associative memory, including different mediators and predictors of age-related declines in binding and associative memory, cognitive, noncognitive, genetic, and neuro-related ones. The contributions also address the processing phases where these declines manifest themselves and look at ways to ameliorate these age-related declines. Furthermore, the contributions in this issue draw on different theoretical perspectives to explain age-related changes in associative memory and provide a wealth of varying methodologies to assess older and younger adults' performance. Finally, although most of the studies focus on normative/healthy aging, some of them contain insights that are potentially applicable to disorders and pathologies. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

The theta/gamma discrete phase code occuring during the hippocampal phase precession may be a more general brain coding scheme.

PubMed

Lisman, John

2005-01-01

In the hippocampus, oscillations in the theta and gamma frequency range occur together and interact in several ways, indicating that they are part of a common functional system. It is argued that these oscillations form a coding scheme that is used in the hippocampus to organize the readout from long-term memory of the discrete sequence of upcoming places, as cued by current position. This readout of place cells has been analyzed in several ways. First, plots of the theta phase of spikes vs. position on a track show a systematic progression of phase as rats run through a place field. This is termed the phase precession. Second, two cells with nearby place fields have a systematic difference in phase, as indicated by a cross-correlation having a peak with a temporal offset that is a significant fraction of a theta cycle. Third, several different decoding algorithms demonstrate the information content of theta phase in predicting the animal's position. It appears that small phase differences corresponding to jitter within a gamma cycle do not carry information. This evidence, together with the finding that principle cells fire preferentially at a given gamma phase, supports the concept of theta/gamma coding: a given place is encoded by the spatial pattern of neurons that fire in a given gamma cycle (the exact timing within a gamma cycle being unimportant); sequential places are encoded in sequential gamma subcycles of the theta cycle (i.e., with different discrete theta phase). It appears that this general form of coding is not restricted to readout of information from long-term memory in the hippocampus because similar patterns of theta/gamma oscillations have been observed in multiple brain regions, including regions involved in working memory and sensory integration. It is suggested that dual oscillations serve a general function: the encoding of multiple units of information (items) in a way that preserves their serial order. The relationship of such coding to that proposed by Singer and von der Malsburg is discussed; in their scheme, theta is not considered. It is argued that what theta provides is the absolute phase reference needed for encoding order. Theta/gamma coding therefore bears some relationship to the concept of "word" in digital computers, with word length corresponding to the number of gamma cycles within a theta cycle, and discrete phase corresponding to the ordered "place" within a word. Copyright 2005 Wiley-Liss, Inc.

The Effect of 4-Octyldecyloxybenzoic Acid on Liquid-Crystalline Polyurethane Composites with Triple-Shape Memory and Self-Healing Properties

PubMed Central

Ban, Jianfeng; Zhu, Linjiang; Chen, Shaojun; Wang, Yiping

2016-01-01

To better understand shape memory materials and self-healing materials, a new series of liquid-crystalline shape memory polyurethane (LC-SMPU) composites, named SMPU-OOBAm, were successfully prepared by incorporating 4-octyldecyloxybenzoic acid (OOBA) into the PEG-based SMPU. The effect of OOBA on the structure, morphology, and properties of the material has been carefully investigated. The results demonstrate that SMPU-OOBAm has liquid crystalline properties, triple-shape memory properties, and self-healing properties. The incorporated OOBA promotes the crystallizability of both soft and hard segments of SMPU, and the crystallization rate of the hard segment of SMPU decreases when the OOBA-content increases. Additionally, the SMPU-OOBAm forms a two-phase separated structure (SMPU phase and OOBA phase), and it shows two-step modulus changes upon heating. Therefore, the SMPU-OOBAm exhibits triple-shape memory behavior, and the shape recovery ratio decreases with an increase in the OOBA content. Finally, SMPU-OOBAm exhibits self-healing properties. The new mechanism can be ascribed to the heating-induced “bleeding” of OOBA in the liquid crystalline state and the subsequent re-crystallization upon cooling. This successful combination of liquid crystalline properties, triple-shape memory properties, and self-healing properties make the SMPU-OOBAm composites ideal for many promising applications in smart optical devices, smart electronic devices, and smart sensors. PMID:28773914

Design of single phase inverter using microcontroller assisted by data processing applications software

NASA Astrophysics Data System (ADS)

Ismail, K.; Muharam, A.; Amin; Widodo Budi, S.

2015-12-01

Inverter is widely used for industrial, office, and residential purposes. Inverter supports the development of alternative energy such as solar cells, wind turbines and fuel cells by converting dc voltage to ac voltage. Inverter has been made with a variety of hardware and software combinations, such as the use of pure analog circuit and various types of microcontroller as controller. When using pure analog circuit, modification would be difficult because it will change the entire hardware components. In inverter with microcontroller based design (with software), calculations to generate AC modulation is done in the microcontroller. This increases programming complexity and amount of coding downloaded to the microcontroller chip (capacity flash memory in the microcontroller is limited). This paper discusses the design of a single phase inverter using unipolar modulation of sine wave and triangular wave, which is done outside the microcontroller using data processing software application (Microsoft Excel), result shows that complexity programming was reduce and resolution sampling data is very influence to THD. Resolution sampling must taking ½ A degree to get best THD (15.8%).

Nanoscale cross-point diode array accessing embedded high density PCM

NASA Astrophysics Data System (ADS)

Wang, Heng; Liu, Yan; Liu, Bo; Gao, Dan; Xu, Zhen; Zhan, Yipeng; Song, Zhitang; Feng, Songlin

2017-08-01

The main bottlenecks in the development of current embedded phase change memory (PCM) technology are the current density and data storage density. In this paper, we present a PCM with 4F2 cross-point diode selector and blade-type bottom electrode contact (BEC). A blade TiN BEC with a cross-sectional area of 630 nm2 (10 nm × 63 nm) reduces the reset current down to about 750 μA. The optimized diode array could supply this 750 μA reset current at about 1.7 V and low off-current 1 × 10-4 μA at about -5.05 V. The on-off ratio of this device is 7.5 × 106. The proposed nanoscale PCM device simultaneously exhibits an operation voltage as low as 3 V and a high density drive current with an ultra small cell size of 4F2 (108 nm × 108 nm). Over 106 cycling endurance properties guarantee that it can work effectively on the embedded memory.

Cortical dendritic activity correlates with spindle-rich oscillations during sleep in rodents.

PubMed

Seibt, Julie; Richard, Clément J; Sigl-Glöckner, Johanna; Takahashi, Naoya; Kaplan, David I; Doron, Guy; de Limoges, Denis; Bocklisch, Christina; Larkum, Matthew E

2017-09-25

How sleep influences brain plasticity is not known. In particular, why certain electroencephalographic (EEG) rhythms are linked to memory consolidation is poorly understood. Calcium activity in dendrites is known to be necessary for structural plasticity changes, but this has never been carefully examined during sleep. Here, we report that calcium activity in populations of neocortical dendrites is increased and synchronised during oscillations in the spindle range in naturally sleeping rodents. Remarkably, the same relationship is not found in cell bodies of the same neurons and throughout the cortical column. Spindles during sleep have been suggested to be important for brain development and plasticity. Our results provide evidence for a physiological link of spindles in the cortex specific to dendrites, the main site of synaptic plasticity.Different stages of sleep, marked by particular electroencephalographic (EEG) signatures, have been linked to memory consolidation, but underlying mechanisms are poorly understood. Here, the authors show that dendritic calcium synchronisation correlates with spindle-rich sleep phases.

Shape memory thermal conduction switch

NASA Technical Reports Server (NTRS)

Krishnan, Vinu (Inventor); Vaidyanathan, Rajan (Inventor); Notardonato, William U. (Inventor)

2010-01-01

A thermal conduction switch includes a thermally-conductive first member having a first thermal contacting structure for securing the first member as a stationary member to a thermally regulated body or a body requiring thermal regulation. A movable thermally-conductive second member has a second thermal contacting surface. A thermally conductive coupler is interposed between the first member and the second member for thermally coupling the first member to the second member. At least one control spring is coupled between the first member and the second member. The control spring includes a NiTiFe comprising shape memory (SM) material that provides a phase change temperature <273 K, a transformation range <40 K, and a hysteresis of <10 K. A bias spring is between the first member and the second member. At the phase change the switch provides a distance change (displacement) between first and second member by at least 1 mm, such as 2 to 4 mm.

A simple method used to evaluate phase-change materials based on focused-ion beam technique

NASA Astrophysics Data System (ADS)

Peng, Cheng; Wu, Liangcai; Rao, Feng; Song, Zhitang; Lv, Shilong; Zhou, Xilin; Du, Xiaofeng; Cheng, Yan; Yang, Pingxiong; Chu, Junhao

2013-05-01

A nanoscale phase-change line cell based on focused-ion beam (FIB) technique has been proposed to evaluate the electrical property of the phase-change material. Thanks to the FIB-deposited SiO2 hardmask, only one etching step has been used during the fabrication process of the cell. Reversible phase-change behaviors are observed in the line cells based on Al-Sb-Te and Ge-Sb-Te films. The low power consumption of the Al-Sb-Te based cell has been explained by theoretical calculation accompanying with thermal simulation. This line cell is considered to be a simple and reliable method in evaluating the application prospect of a certain phase-change material.

Large Deflection of Ideal Pseudo-Elastic Shape Memory Alloy Cantilever Beam

NASA Astrophysics Data System (ADS)

Cui, Shitang; Hu, Liming; Yan, Jun

This paper deals with the large deflections of pseudo-elastic shape memory alloy cantilever beams subjected to a concentrated load at the free end. Because of the large deflections, geometry nonlinearity arises and this analysis employs the nonlinear bending theory. The exact expression of curvature is used in the moment-curvature relationship. As a vertical force at the tip of cantilever, curvature and bending moment distribution expressions are deduced. The curvature changed distinctly when the surface material undergoes phase transformation. The length of phase transformation region was affected greatly with the force at the free end.

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

NASA Astrophysics Data System (ADS)

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

2006-09-01

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

RTS,S/AS01E Malaria Vaccine Induces Memory and Polyfunctional T Cell Responses in a Pediatric African Phase III Trial.

PubMed

Moncunill, Gemma; De Rosa, Stephen C; Ayestaran, Aintzane; Nhabomba, Augusto J; Mpina, Maximillian; Cohen, Kristen W; Jairoce, Chenjerai; Rutishauser, Tobias; Campo, Joseph J; Harezlak, Jaroslaw; Sanz, Héctor; Díez-Padrisa, Núria; Williams, Nana Aba; Morris, Daryl; Aponte, John J; Valim, Clarissa; Daubenberger, Claudia; Dobaño, Carlota; McElrath, M Juliana

2017-01-01

Comprehensive assessment of cellular responses to the RTS,S/AS01E vaccine is needed to understand potential correlates and ultimately mechanisms of protection against malaria disease. Cellular responses recognizing the RTS,S/AS01E-containing circumsporozoite protein (CSP) and Hepatitis B surface antigen (HBsAg) were assessed before and 1 month after primary vaccination by intracellular cytokine staining and 16-color flow cytometry in 105 RTS,S/AS01-vaccinated and 74 rabies-vaccinated participants (controls) in a pediatric phase III trial in Africa. RTS,S/AS01E-vaccinated children had significantly higher frequencies of CSP- and HBsAg-specific CD4 + T cells producing IL-2, TNF-α, and CD40L and HBsAg-specific CD4 + T producing IFN-γ and IL-17 than baseline and the control group. Vaccine-induced responses were identified in both central and effector memory (EM) compartments. EM CD4 + T cells expressing IL-4 and IL-21 were detected recognizing both vaccine antigens. Consistently higher response rates to both antigens in RTS,S/AS01E-vaccinated than comparator-vaccinated children were observed. RTS,S/AS01E induced polyfunctional CSP- and HBsAg-specific CD4 + T cells, with a greater degree of polyfunctionality in HBsAg responses. In conclusion, RTS,S/AS01E vaccine induces T cells of higher functional heterogeneity and polyfunctionality than previously characterized. Responses detected in memory CD4 + T cell compartments may provide correlates of RTS,S/AS01-induced immunity and duration of protection in future correlates of immunity studies.

The relation between lattice parameters and very low twinning stress in Ni50Mn25+x Ga25-x magnetic shape memory alloys

NASA Astrophysics Data System (ADS)

Straka, L.; Drahokoupil, J.; Pacherová, O.; Fabiánová, K.; Kopecký, V.; Seiner, H.; Hänninen, H.; Heczko, O.

2016-02-01

In search of the origins of the extraordinary low twinning stress of Ni-Mn-Ga 10M martensite, we studied the temperature induced changes in lattice parameters of Ni50Mn25+x Ga25-x (x = 2.7-3.9) single crystal samples and compared them with twinning stress dependences. The alloys exhibited transformation to five-layered (10M) martensite structure (cubic to monoclinic) between 297 to 328 K and exhibited the magnetic shape memory effect in martensite. The structural changes were monitored using x-ray diffraction in the temperature range 200-343 K. The 10M structure was approximated by monoclinic lattice, a = b > c, γ > 90° with the coordinates derived from the cubic unit cell of the parent L21 phase. The lattice parameters γ and c/a correlate well with the universal linear increase of twinning stress of type 1 twins with decreasing temperature. On the contrary, the twinning stress is not affected by differences between a and b and thus a/b twins seem to play no role in a - c twin boundary motion resulting in magnetically induced reorientation.

Declarative memory performance is associated with the number of sleep spindles in elderly women.

PubMed

Seeck-Hirschner, Mareen; Baier, Paul Christian; Weinhold, Sara Lena; Dittmar, Manuela; Heiermann, Steffanie; Aldenhoff, Josef B; Göder, Robert

2012-09-01

Recent evidence suggests that the sleep-dependent consolidation of declarative memory relies on the nonrapid eye movement rather than the rapid eye movement phase of sleep. In addition, it is known that aging is accompanied by changes in sleep and memory processes. Hence, the purpose of this study was to investigate the overnight consolidation of declarative memory in healthy elderly women. Sleep laboratory of University. Nineteen healthy elderly women (age range: 61-74 years). We used laboratory-based measures of sleep. To test declarative memory, the Rey-Osterrieth Complex Figure Test was performed. Declarative memory performance in elderly women was associated with Stage 2 sleep spindle density. Women characterized by high memory performance exhibited significantly higher numbers of sleep spindles and higher spindle density compared with women with generally low memory performance. The data strongly support theories suggesting a link between sleep spindle activity and declarative memory consolidation.

CD4(+) T-cell help amplifies innate signals for primary CD8(+) T-cell immunity.

PubMed

Bedoui, Sammy; Heath, William R; Mueller, Scott N

2016-07-01

CD8(+) T cells provide an important component of protection against intracellular infections and cancer. Immune responses by these T cells involve a primary phase of effector expansion and differentiation, followed by a contraction phase leading to memory formation and, if antigen is re-encountered, a secondary expansion phase with more rapid differentiation. Both primary and secondary phases of CD8(+) T-cell immunity have been shown to depend on CD4(+) T-cell help, although during certain infections the primary phase is variable in this requirement. One explanation for such variability relates to the strength of associated inflammatory signals, with weak signals requiring help. Here, we focus on our studies that have dissected the requirements for help in the primary phase of the CTL response to herpes simplex virus, elucidating intricate interactions and communications between CD4(+) T cells, various dendritic cell subsets, and CD8(+) T cells. We place our studies in the context of others and describe a simple model of help where CD40 signaling amplifies innate signals to enable efficient CD8(+) T-cell expansion and differentiation. This model facilitates CTL induction to various different agents, without altering the qualitative innate signals that direct other important arms of immunity. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Position, scale, and rotation invariant holographic associative memory

NASA Astrophysics Data System (ADS)

Fielding, Kenneth H.; Rogers, Steven K.; Kabrisky, Matthew; Mills, James P.

1989-08-01

This paper describes the development and characterization of a holographic associative memory (HAM) system that is able to recall stored objects whose inputs were changed in position, scale, and rotation. The HAM is based on the single iteration model described by Owechko et al. (1987); however, the system described uses a self-pumped BaTiO3 phase conjugate mirror, rather than a degenerate four-wave mixing proposed by Owechko and his coworkers. The HAM system can store objects in a position, scale, and rotation invariant feature space. The angularly multiplexed diffuse Fourier transform holograms of the HAM feature space are characterized as the memory unit; distorted input objects are correlated with the hologram, and the nonlinear phase conjugate mirror reduces cross-correlation noise and provides object discrimination. Applications of the HAM system are presented.

Implementation of nitrogen-doped titanium-tungsten tunable heater in phase change random access memory and its effects on device performance

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

Tan, Chun Chia; Zhao, Rong, E-mail: zhao-rong@sutd.edu.sg; Chong, Tow Chong

2014-10-13

Nitrogen-doped titanium-tungsten (N-TiW) was proposed as a tunable heater in Phase Change Random Access Memory (PCRAM). By tuning N-TiW's material properties through doping, the heater can be tailored to optimize the access speed and programming current of PCRAM. Experiments reveal that N-TiW's resistivity increases and thermal conductivity decreases with increasing nitrogen-doping ratio, and N-TiW devices displayed (∼33% to ∼55%) reduced programming currents. However, there is a tradeoff between the current and speed for heater-based PCRAM. Analysis of devices with different N-TiW heaters shows that N-TiW doping levels could be optimized to enable low RESET currents and fast access speeds.

Performance analysis of three-dimensional-triple-level cell and two-dimensional-multi-level cell NAND flash hybrid solid-state drives

NASA Astrophysics Data System (ADS)

Sakaki, Yukiya; Yamada, Tomoaki; Matsui, Chihiro; Yamaga, Yusuke; Takeuchi, Ken

2018-04-01

In order to improve performance of solid-state drives (SSDs), hybrid SSDs have been proposed. Hybrid SSDs consist of more than two types of NAND flash memories or NAND flash memories and storage-class memories (SCMs). However, the cost of hybrid SSDs adopting SCMs is more expensive than that of NAND flash only SSDs because of the high bit cost of SCMs. This paper proposes unique hybrid SSDs with two-dimensional (2D) horizontal multi-level cell (MLC)/three-dimensional (3D) vertical triple-level cell (TLC) NAND flash memories to achieve higher cost-performance. The 2D-MLC/3D-TLC hybrid SSD achieves up to 31% higher performance than the conventional 2D-MLC/2D-TLC hybrid SSD. The factors of different performance between the proposed hybrid SSD and the conventional hybrid SSD are analyzed by changing its block size, read/write/erase latencies, and write unit of 3D-TLC NAND flash memory, by means of a transaction-level modeling simulator.

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

PubMed

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

2018-05-01

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

The epigenetic basis of memory formation and storage.

PubMed

Jarome, Timothy J; Thomas, Jasmyne S; Lubin, Farah D

2014-01-01

The formation of long-term memory requires a series of cellular and molecular changes that involve transcriptional regulation of gene expression. While these changes in gene transcription were initially thought to be largely regulated by the activation of transcription factors by intracellular signaling molecules, epigenetic mechanisms have emerged as an important regulator of transcriptional processes across multiple brain regions to form a memory circuit for a learned event or experience. Due to their self-perpetuating nature and ability to bidirectionally control gene expression, these epigenetic mechanisms have the potential to not only regulate initial memory formation but also modify and update memory over time. This chapter focuses on the established, but poorly understood, role for epigenetic mechanisms such as posttranslational modifications of histone proteins and DNA methylation at the different stages of memory storage. Additionally, this chapter emphasizes how these mechanisms interact to control the ideal epigenetic environment for memory formation and modification in neurons. The reader will gain insights into the limitations in our current understanding of epigenetic regulation of memory storage, especially in terms of their cell-type specificity and the lack of understanding in the interactions of various epigenetic modifiers to one another to impact gene expression changes during memory formation.

[Advances in Acupuncture Mechanism Research on the Changes of Synaptic Plasticity: "Pain Memory" for Chronic Pain].

PubMed

Yang, Yi-Ling; Huang, Jian-Peng; Jiang, Li; Liu, Jian-Hua

2017-12-25

Previous studies have shown that there are many common structures between the neural network of pain and memory, and the main structure in the pain network is also part of the memory network. Chronic pain is characterized by recurrent attacks and is associated with persistent ectopic impulse, which causes changes in synaptic structure and function based on nerve activity. These changes may induce long-term potentiation of synaptic transmission, and ultimately lead to changes in the central nervous system to produce "pain memory". Acupuncture is an effective method in treating chronic pain. It has been proven that acupuncture can affect the spinal cord dorsal horn, hippocampus, cingulate gyrus and other related areas. The possible mechanisms of action include opioid-induced analgesia, activation of glial cells, and the expression of brain derived neurotrophic factor (BDNF). In this study, we systematically review the brain structures, stage of "pain memory" and the mechanisms of acupuncture on synaptic plasticity in chronic pain.

Origin and fate of lymphocytic choriomeningitis virus-specific CD8+ T cells coexpressing the inhibitory NK cell receptor Ly49G2.

PubMed

Peacock, Craig D; Welsh, Raymond M

2004-07-01

CD8+ T cells that coexpress the inhibitory NK cell receptor, Ly49G2 (G2), are present in immunologically naive C57BL/6 mice but display Ags found on memory T cells. To assess how G2+CD8+ cells relate to bona fide memory cells, we examined the origin and fate of lymphocytic choriomeningitis virus (LCMV)-induced G2+CD8+ cells. During early (day 4) acute LCMV infection, both G2+ and G2-CD8+ T cell subsets underwent an attrition in number and displayed an activation (CD69(high)1B11(high)CD62L(low)) phenotype. By day 8, both subsets synthesized IFN-gamma in response to immunodominant LCMV peptides, though the expansion of G2+ cells was less than that of G2- cells. Adoptive transfer experiments with purified G2- or G2+CD8+ cells from naive mice indicated that the LCMV-specific G2+ subset was derived from a pre-existing G2+ population and not generated from G2- cells responding to LCMV infection. Their participation in the LCMV-specific T cell response increased with age, reflecting an increase in the size of the pre-existing G2+ pool. Following establishment of stable LCMV memory, the proportion of CD8+ cells coexpressing G2 was reduced in comparison to naive controls, presumably due to displacement by G2- LCMV-specific memory cells. LCMV-specific G2+ cells were present in the memory pool, but at low frequencies, and they did not exhibit the typical phenotypic changes of reactivation during secondary challenge. We suggest that G2+CD8+ cells represent a cell lineage distinct from bona fide memory T cells, but that they can participate in an acute virus-specific T cell response.

Longevity of T-cell memory following acute viral infection.

PubMed

Walker, Joshua M; Slifka, Mark K

2010-01-01

Investigation of T-cell-mediated immunity following acute viral infection represents an area of research with broad implications for both fundamental immunology research as well as vaccine development. Here, we review techniques that are used to assess T-cell memory including limiting dilution analysis, enzyme-linked immunospot (ELISPOT) assays, intracellular cytokine staining (ICCS) and peptide-MHC Class I tetramer staining. The durability of T-cell memory is explored in the context of several acute viral infections including vaccinia virus (VV), measles virus (MV) and yellow fever virus (YFV). Following acute infection, different virus-specific T-cell subpopulations exhibit distinct cytokine profiles and these profiles change over the course of infection. Differential regulation of the cytotoxic proteins, granzyme A, granzyme B and perforin are also observed in virus-specific T cells following infection. As a result of this work, we have gained a broader understanding of the kinetics and magnitude of antiviral T-cell immunity as well as new insight into the patterns of immunodominance and differential regulation of cytokines and cytotoxicity-associated molecules. This information may eventually lead to the generation of more effective vaccines that elicit T-cell memory with the optimal combination of functional characteristics required for providing protective immunity against infectious disease.

Progress of the Phase-Change Optical Disk Memory

DTIC Science & Technology

2001-04-01

layer DVD for a DVD 8.5 GB ROM disk for a cinema title. Rewritable 8.5 GB phase-change dual-layer experimental results were announced in 1998". Figure...multi level recording. 1000 70 0 u p..".5 NA0.6 b uper-1l’ENS .... 60 -10 ,.00 nm _o-2o . ’-40 -30 -"a Dual C Supu]RE•S Ouat I) VR -Blue U30 -40 10 20

Energy-Efficient Phase-Change Memory with Graphene as a Thermal Barrier

DTIC Science & Technology

2015-09-02

Joule heating should be restricted inside a small volume of the phase-change material and heat loss by thermal conduction to the surroundings needs to...technique (see Figure 1a). TDTR is a well-established pump− probe technique, capable of measuring the cross-plane thermal conductivity of nanometer-thin...films and thermal conductance per unit area across interfaces of particular interest27 (see Supporting Information, Section 1 and Figure S1

Tumour cell lysate-loaded dendritic cell vaccine induces biochemical and memory immune response in castration-resistant prostate cancer patients

PubMed Central

Reyes, D; Salazar, L; Espinoza, E; Pereda, C; Castellón, E; Valdevenito, R; Huidobro, C; Inés Becker, M; Lladser, A; López, M N; Salazar-Onfray, F

2013-01-01

Background: Recently, we produced a tumour antigen-presenting cells (TAPCells) vaccine using a melanoma cell lysate, called TRIMEL, as an antigen source and an activation factor. Tumour antigen-presenting cells induced immunological responses and increased melanoma patient survival. Herein, we investigated the effect of TAPCells loaded with prostate cancer cell lysates (PCCL) as an antigen source, and TRIMEL as a dendritic cell (DC) activation factor; which were co-injected with the Concholepas concholepas haemocyanin (CCH) as an adjuvant on castration-resistant prostate cancer (CRPC) patients. Methods: The lysate mix capacity, for inducing T-cell activation, was analysed by flow cytometry and Elispot. Delayed-type hypersensitivity (DTH) reaction against PCCL, frequency of CD8+ memory T cells (Tm) in blood and prostate-specific antigen (PSA) levels in serum were measured in treated patients. Results: The lysate mix induced functional mature DCs that were capable of activating PCCL-specific T cells. No relevant adverse reactions were observed. Six out of 14 patients showed a significant decrease in levels of PSA. DTH+ patients showed a prolonged PSA doubling-time after treatment. Expansion of functional central and effector CD8+ Tm were detected. Conclusion: Treatment of CRPC patients with lysate-loaded TAPCells and CCH as an adjuvant is safe: generating biochemical and memory immune responses. However, the limited number of cases requires confirmation in a phase II clinical trial. PMID:23989944

Tumour cell lysate-loaded dendritic cell vaccine induces biochemical and memory immune response in castration-resistant prostate cancer patients.

PubMed

Reyes, D; Salazar, L; Espinoza, E; Pereda, C; Castellón, E; Valdevenito, R; Huidobro, C; Inés Becker, M; Lladser, A; López, M N; Salazar-Onfray, F

2013-09-17

Recently, we produced a tumour antigen-presenting cells (TAPCells) vaccine using a melanoma cell lysate, called TRIMEL, as an antigen source and an activation factor. Tumour antigen-presenting cells induced immunological responses and increased melanoma patient survival. Herein, we investigated the effect of TAPCells loaded with prostate cancer cell lysates (PCCL) as an antigen source, and TRIMEL as a dendritic cell (DC) activation factor; which were co-injected with the Concholepas concholepas haemocyanin (CCH) as an adjuvant on castration-resistant prostate cancer (CRPC) patients. The lysate mix capacity, for inducing T-cell activation, was analysed by flow cytometry and Elispot. Delayed-type hypersensitivity (DTH) reaction against PCCL, frequency of CD8(+) memory T cells (Tm) in blood and prostate-specific antigen (PSA) levels in serum were measured in treated patients. The lysate mix induced functional mature DCs that were capable of activating PCCL-specific T cells. No relevant adverse reactions were observed. Six out of 14 patients showed a significant decrease in levels of PSA. DTH(+) patients showed a prolonged PSA doubling-time after treatment. Expansion of functional central and effector CD8(+) Tm were detected. Treatment of CRPC patients with lysate-loaded TAPCells and CCH as an adjuvant is safe: generating biochemical and memory immune responses. However, the limited number of cases requires confirmation in a phase II clinical trial.

Simultaneous thermal stability and phase change speed improvement of Sn15Sb85 thin film through erbium doping

NASA Astrophysics Data System (ADS)

Zou, Hua; Zhu, Xiaoqin; Hu, Yifeng; Sui, Yongxing; Sun, Yuemei; Zhang, Jianhao; Zheng, Long; Song, Zhitang

2016-12-01

In general, there is a trade off between the phase change speed and thermal stability in chalcogenide phase change materials, which leads to sacrifice the one in order to ensure the other. For improving the performance, doping is a widely applied technological process. Here, we fabricated Er doped Sn15Sb85 thin films by magnetron sputtering. Compared with the pure Sn15Sb85, we show that Er doped Sn15Sb85 thin films exhibit simultaneous improvement over the thermal stability and the phase change speed. Thus, our results suggest that Er doping provides the opportunity to solve the contradiction. The main reason for improvement of both thermal stability and crystallization speed is due to the existence of Er-Sb and Er-Sn bonds in Er doped Sn15Sb85 films. Hence, Er doped Sn15Sb85 thin films are promising candidates for the phase change memory application, and this method could be extended to other lanthanide-doped phase change materials.

Constitutive modeling of glassy shape memory polymers

NASA Astrophysics Data System (ADS)

Khanolkar, Mahesh

The aim of this research is to develop constitutive models for non-linear materials. Here, issues related for developing constitutive model for glassy shape memory polymers are addressed in detail. Shape memory polymers are novel material that can be easily formed into complex shapes, retaining memory of their original shape even after undergoing large deformations. The temporary shape is stable and return to the original shape is triggered by a suitable mechanism such heating the polymer above a transition temperature. Glassy shape memory polymers are called glassy because the temporary shape is fixed by the formation of a glassy solid, while return to the original shape is due to the melting of this glassy phase. The constitutive model has been developed to capture the thermo-mechanical behavior of glassy shape memory polymers using elements of nonlinear mechanics and polymer physics. The key feature of this framework is that a body can exist stress free in numerous natural configurations, the underlying natural configuration of the body changing during the process, with the response of the body being elastic from these evolving natural configurations. The aim of this research is to formulate a constitutive model for glassy shape memory polymers (GSMP) which takes in to account the fact that the stress-strain response depends on thermal expansion of polymers. The model developed is for the original amorphous phase, the temporary glassy phase and transition between these phases. The glass transition process has been modeled using a framework that was developed recently for studying crystallization in polymers and is based on the theory of multiple natural configurations. Using the same frame work, the melting of the glassy phase to capture the return of the polymer to its original shape is also modeled. The effect of nanoreinforcement on the response of shape memory polymers (GSMP) is studied and a model is developed. In addition to modeling and solving boundary value problems for GSMP's, problems of importance for CSMP, specifically a shape memory cycle (Torsion of a Cylinder) is solved using the developed crystallizable shape memory polymer model. To solve complex boundary value problems in realistic geometries a user material subroutine (UMAT) for GSMP model has been developed for use in conjunction with the commercial finite element software ABAQUS. The accuracy of the UMAT has been verified by testing it against problems for which the results are known.

Combination of chronic stress and ovariectomy causes conditioned fear memory deficits and hippocampal cholinergic neuronal loss in mice.

PubMed

Takuma, K; Mizoguchi, H; Funatsu, Y; Hoshina, Y; Himeno, Y; Fukuzaki, E; Kitahara, Y; Arai, S; Ibi, D; Kamei, H; Matsuda, T; Koike, K; Inoue, M; Nagai, T; Yamada, K

2012-04-05

We have recently found that the combination of ovariectomy (OVX) and chronic restraint stress (CS) causes hippocampal pyramidal cell loss and cognitive dysfunction in female rats and that estrogen replacement prevents the OVX/CS-induced morphological and behavioral changes. In this study, to clarify the mechanisms underlying the OVX/CS-mediated memory impairment further, we examined the roles of cholinergic systems in the OVX/CS-induced memory impairment in mice. Female Slc:ICR strain mice were randomly divided into two groups: OVX and sham-operated groups. Two weeks after the operation, the mice of each group were further assigned to CS (6 h/day) or non-stress group. Following the 3-week-stress period, all mice were subjected to contextual fear conditioning, and context- and tone-dependent memory tests were conducted 1 or 24 h after the conditioning. Overburden with 3 weeks of CS from 2 weeks after OVX impaired context- and tone-dependent freezing and the OVX/CS caused significant Nissl-stained neuron-like cell loss in the hippocampal CA3 region, although OVX and CS alone did not cause such behavioral and histological changes. Replacement of 17β-estradiol for 5 weeks after OVX suppressed OVX/CS-induced memory impairment and hippocampal Nissl-positive cell loss. Furthermore, the OVX/CS mice exhibited a significant decrease in choline acetyltransferase in the hippocampus compared with other groups. The cholinesterase inhibitors donepezil and galantamine ameliorated OVX/CS-induced memory impairment. These data suggest that cholinergic dysfunction may be involved in the OVX/CS-induced conditioned fear memory impairment. Overall, our findings suggest that the OVX/CS mouse model is useful to study the mechanisms underlying estrogen loss-induced memory deficits. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Mirror-symmetric Magneto-optical Kerr Rotation using Visible Light in [(GeTe)2(Sb2Te3)1]n Topological Superlattices

PubMed Central

Bang, Do; Awano, Hiroyuki; Tominaga, Junji; Kolobov, Alexander V.; Fons, Paul; Saito, Yuta; Makino, Kotaro; Nakano, Takashi; Hase, Muneaki; Takagaki, Yukihiko; Giussani, Alessandro; Calarco, Raffaella; Murakami, Shuichi

2014-01-01

Interfacial phase change memory (iPCM), that has a structure of a superlattice made of alternating atomically thin GeTe and Sb2Te3 layers, has recently attracted attention not only due to its superior performance compared to the alloy of the same average composition in terms of energy consumption but also due to its strong response to an external magnetic field (giant magnetoresistance) that has been speculated to arise from switching between topological insulator (RESET) and normal insulator (SET) phases. Here we report magneto-optical Kerr rotation loops in the visible range, that have mirror symmetric resonances with respect to the magnetic field polarity at temperatures above 380 K when the material is in the SET phase that has Kramers-pairs in spin-split bands. We further found that this threshold temperature may be controlled if the sample was cooled in a magnetic field. The observed results open new possibilities for use of iPCM beyond phase-change memory applications. PMID:25030304

Neural Protein Synthesis during Aging: Effects on Plasticity and Memory

PubMed Central

Schimanski, Lesley A.; Barnes, Carol A.

2010-01-01

During aging, many experience a decline in cognitive function that includes memory loss. The encoding of long-term memories depends on new protein synthesis, and this is also reduced during aging. Thus, it is possible that changes in the regulation of protein synthesis contribute to the memory impairments observed in older animals. Several lines of evidence support this hypothesis. For instance, protein synthesis is required for a longer period following learning to establish long-term memory in aged rodents. Also, under some conditions, synaptic activity or pharmacological activation can induce de novo protein synthesis and lasting changes in synaptic transmission in aged, but not young, rodents; the opposite results can be observed in other conditions. These changes in plasticity likely play a role in manifesting the altered place field properties observed in awake and behaving aged rats. The collective evidence suggests a link between memory loss and the regulation of protein synthesis in senescence. In fact, pharmaceuticals that target the signaling pathways required for induction of protein synthesis have improved memory, synaptic plasticity, and place cell properties in aged animals. We suggest that a better understanding of the mechanisms that lead to different protein expression patterns in the neural circuits that change as a function of age will enable the development of more effective therapeutic treatments for memory loss. PMID:20802800

Ab Initio Molecular-Dynamics Simulation of Neuromorphic Computing in Phase-Change Memory Materials.

PubMed

Skelton, Jonathan M; Loke, Desmond; Lee, Taehoon; Elliott, Stephen R

2015-07-08

We present an in silico study of the neuromorphic-computing behavior of the prototypical phase-change material, Ge2Sb2Te5, using ab initio molecular-dynamics simulations. Stepwise changes in structural order in response to temperature pulses of varying length and duration are observed, and a good reproduction of the spike-timing-dependent plasticity observed in nanoelectronic synapses is demonstrated. Short above-melting pulses lead to instantaneous loss of structural and chemical order, followed by delayed partial recovery upon structural relaxation. We also investigate the link between structural order and electrical and optical properties. These results pave the way toward a first-principles understanding of phase-change physics beyond binary switching.

Fast Magnetoresistive Random-Access Memory

NASA Technical Reports Server (NTRS)

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

1991-01-01

Magnetoresistive binary digital memories of proposed new type expected to feature high speed, nonvolatility, ability to withstand ionizing radiation, high density, and low power. In memory cell, magnetoresistive effect exploited more efficiently by use of ferromagnetic material to store datum and adjacent magnetoresistive material to sense datum for readout. Because relative change in sensed resistance between "zero" and "one" states greater, shorter sampling and readout access times achievable.

Parietal EEG alpha suppression time of memory retrieval reflects memory load while the alpha power of memory maintenance is a composite of the visual process according to simultaneous and successive Sternberg memory tasks.

PubMed

Okuhata, Shiho; Kusanagi, Takuya; Kobayashi, Tetsuo

2013-10-25

The present study investigated EEG alpha activity during visual Sternberg memory tasks using two different stimulus presentation modes to elucidate how the presentation mode affected parietal alpha activity. EEGs were recorded from 10 healthy adults during the Sternberg tasks in which memory items were presented simultaneously and successively. EEG power and suppression time (ST) in the alpha band (8-13Hz) were computed for the memory maintenance and retrieval phases. The alpha activity differed according to the presentation mode during the maintenance phase but not during the retrieval phase. Results indicated that parietal alpha power recorded during the maintenance phase did not reflect the memory load alone. In contrast, ST during the retrieval phase increased with the memory load for both presentation modes, indicating a serial memory scanning process, regardless of the presentation mode. These results indicate that there was a dynamic transition in the memory process from the maintenance phase, which was sensitive to external factors, toward the retrieval phase, during which the process converged on the sequential scanning process, the Sternberg task essentially required. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Mechanisms for Selective Single-Cell Reactivation during Offline Sharp-Wave Ripples and Their Distortion by Fast Ripples.

PubMed

Valero, Manuel; Averkin, Robert G; Fernandez-Lamo, Ivan; Aguilar, Juan; Lopez-Pigozzi, Diego; Brotons-Mas, Jorge R; Cid, Elena; Tamas, Gabor; Menendez de la Prida, Liset

2017-06-21

Memory traces are reactivated selectively during sharp-wave ripples. The mechanisms of selective reactivation, and how degraded reactivation affects memory, are poorly understood. We evaluated hippocampal single-cell activity during physiological and pathological sharp-wave ripples using juxtacellular and intracellular recordings in normal and epileptic rats with different memory abilities. CA1 pyramidal cells participate selectively during physiological events but fired together during epileptic fast ripples. We found that firing selectivity was dominated by an event- and cell-specific synaptic drive, modulated in single cells by changes in the excitatory/inhibitory ratio measured intracellularly. This mechanism collapses during pathological fast ripples to exacerbate and randomize neuronal firing. Acute administration of a use- and cell-type-dependent sodium channel blocker reduced neuronal collapse and randomness and improved recall in epileptic rats. We propose that cell-specific synaptic inputs govern firing selectivity of CA1 pyramidal cells during sharp-wave ripples. Copyright © 2017 Elsevier Inc. All rights reserved.

Charge collection microscopy of in-situ switchable PRAM line cells in a scanning electron microscope: Technique development and unique observations

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

Oosthoek, J. L. M.; Schuitema, R. W.; Brink, G. H. ten

2015-03-15

An imaging method has been developed based on charge collection in a scanning electron microscope (SEM) that allows discrimination between the amorphous and crystalline states of Phase-change Random Access Memory (PRAM) line cells. During imaging, the cells are electrically connected and can be switched between the states and the resistance can be measured. This allows for electrical characterization of the line cells in-situ in the SEM. Details on sample and measurement system requirements are provided which turned out to be crucial for the successful development of this method. Results show that the amorphous or crystalline state of the line cellsmore » can be readily discerned, but the spatial resolution is relatively poor. Nevertheless, it is still possible to estimate the length of the amorphous mark, and also for the first time, we could directly observe the shift of the amorphous mark from one side of the line cell to the other side when the polarity of the applied (50 ns) RESET pulse was reversed.« less

Abnormal neural activation patterns underlying working memory impairment in chronic phencyclidine-treated mice.

PubMed

Arime, Yosefu; Akiyama, Kazufumi

2017-01-01

Working memory impairment is a hallmark feature of schizophrenia and is thought be caused by dysfunctions in the prefrontal cortex (PFC) and associated brain regions. However, the neural circuit anomalies underlying this impairment are poorly understood. The aim of this study is to assess working memory performance in the chronic phencyclidine (PCP) mouse model of schizophrenia, and to identify the neural substrates of working memory. To address this issue, we conducted the following experiments for mice after withdrawal from chronic administration (14 days) of either saline or PCP (10 mg/kg): (1) a discrete paired-trial variable-delay task in T-maze to assess working memory, and (2) brain-wide c-Fos mapping to identify activated brain regions relevant to this task performance either 90 min or 0 min after the completion of the task, with each time point examined under working memory effort and basal conditions. Correct responses in the test phase of the task were significantly reduced across delays (5, 15, and 30 s) in chronic PCP-treated mice compared with chronic saline-treated controls, suggesting delay-independent impairments in working memory in the PCP group. In layer 2-3 of the prelimbic cortex, the number of working memory effort-elicited c-Fos+ cells was significantly higher in the chronic PCP group than in the chronic saline group. The main effect of working memory effort relative to basal conditions was to induce significantly increased c-Fos+ cells in the other layers of prelimbic cortex and the anterior cingulate and infralimbic cortex regardless of the different chronic regimens. Conversely, this working memory effort had a negative effect (fewer c-Fos+ cells) in the ventral hippocampus. These results shed light on some putative neural networks relevant to working memory impairments in mice chronically treated with PCP, and emphasize the importance of the layer 2-3 of the prelimbic cortex of the PFC.

Abnormal neural activation patterns underlying working memory impairment in chronic phencyclidine-treated mice

PubMed Central

Akiyama, Kazufumi

2017-01-01

Working memory impairment is a hallmark feature of schizophrenia and is thought be caused by dysfunctions in the prefrontal cortex (PFC) and associated brain regions. However, the neural circuit anomalies underlying this impairment are poorly understood. The aim of this study is to assess working memory performance in the chronic phencyclidine (PCP) mouse model of schizophrenia, and to identify the neural substrates of working memory. To address this issue, we conducted the following experiments for mice after withdrawal from chronic administration (14 days) of either saline or PCP (10 mg/kg): (1) a discrete paired-trial variable-delay task in T-maze to assess working memory, and (2) brain-wide c-Fos mapping to identify activated brain regions relevant to this task performance either 90 min or 0 min after the completion of the task, with each time point examined under working memory effort and basal conditions. Correct responses in the test phase of the task were significantly reduced across delays (5, 15, and 30 s) in chronic PCP-treated mice compared with chronic saline-treated controls, suggesting delay-independent impairments in working memory in the PCP group. In layer 2–3 of the prelimbic cortex, the number of working memory effort-elicited c-Fos+ cells was significantly higher in the chronic PCP group than in the chronic saline group. The main effect of working memory effort relative to basal conditions was to induce significantly increased c-Fos+ cells in the other layers of prelimbic cortex and the anterior cingulate and infralimbic cortex regardless of the different chronic regimens. Conversely, this working memory effort had a negative effect (fewer c-Fos+ cells) in the ventral hippocampus. These results shed light on some putative neural networks relevant to working memory impairments in mice chronically treated with PCP, and emphasize the importance of the layer 2–3 of the prelimbic cortex of the PFC. PMID:29253020

Gold fillings unravel the vacancy role in the phase transition of GeTe

NASA Astrophysics Data System (ADS)

Feng, Jinlong; Xu, Meng; Wang, Xiaojie; Lin, Qi; Cheng, Xiaomin; Xu, Ming; Tong, Hao; Miao, Xiangshui

2018-02-01

Phase change memory (PCM) is an important candidate for future memory devices. The crystalline phase of PCM materials contains abundant intrinsic vacancies, which plays an important role in the rapid phase transition upon memory switching. However, few experimental efforts have been invested to study these invisible entities. In this work, Au dopants are alloyed into the crystalline GeTe to fill the intrinsic Ge vacancies so that the role of these vacancies in the amorphization of GeTe can be indirectly studied. As a result, the reduction of Ge vacancies induced by Au dopants hampers the amorphization of GeTe as the activation energy of this process becomes higher. This is because the vacancy-interrupted lattice can be "repaired" by Au dopants with the recovery of bond connectivity. Our results demonstrate the importance of vacancies in the phase transition of chalcogenides, and we employ the percolation theory to explain the impact of these intrinsic defects on this vacancy-ridden crystal quantitatively. Specifically, the threshold of amorphization increases with the decrease in vacancies. The understanding of the vacancy effect sheds light on the long-standing puzzle of the mechanism of ultra-fast phase transition in PCMs. It also paves the way for designing low-power-consumption electronic devices by reducing the threshold of amorphization in chalcogenides.

PD-1 is a marker for abnormal distribution of naïve/memory T cell subsets in HIV-1 infection

PubMed Central

Breton, Gaëlle; Chomont, Nicolas; Takata, Hiroshi; Fromentin, Rémi; Ahlers, Jeffrey; Filali-Mouhim, Abdelali; Riou, Catherine; Boulassel, Mohamed-Rachid; Routy, Jean-Pierre; Yassine-Diab, Bader; Sékaly, Rafick-Pierre

2013-01-01

Chronic activation of T cells is a hallmark of HIV-1 infection and plays an important role in disease progression. We previously showed that the engagement of the inhibitory receptor PD-1 on HIV-1 specific CD4+ and CD8+ T cells leads to their functional exhaustion in vitro. However, little is known about the impact of PD-1 expression on the turnover and maturation status of T cells during the course of the disease. Here, we show that PD-1 is up regulated on all T cell subsets including naïve, central memory and transitional memory T cells in HIV-1 infected subjects. PD-1 is expressed at similar levels on most CD4+ T cells during the acute and the chronic phase of disease and identifies cells that have recently entered the cell cycle. In contrast, PD-1 expression dramatically increased in CD8+ T cells during the transition from acute to chronic infection and this was associated with reduced levels of cell proliferation. The failure to down regulate expression of PD-1 in most T cells during chronic HIV-1 infection was associated to persistent alterations in the distribution of T cell subsets and was associated with impaired responses to IL-7. Our findings identify PD-1 as a marker for aberrant distribution of T cell subsets in HIV-1 infection. PMID:23918986

Nanoelectronic programmable synapses based on phase change materials for brain-inspired computing.

PubMed

Kuzum, Duygu; Jeyasingh, Rakesh G D; Lee, Byoungil; Wong, H-S Philip

2012-05-09

Brain-inspired computing is an emerging field, which aims to extend the capabilities of information technology beyond digital logic. A compact nanoscale device, emulating biological synapses, is needed as the building block for brain-like computational systems. Here, we report a new nanoscale electronic synapse based on technologically mature phase change materials employed in optical data storage and nonvolatile memory applications. We utilize continuous resistance transitions in phase change materials to mimic the analog nature of biological synapses, enabling the implementation of a synaptic learning rule. We demonstrate different forms of spike-timing-dependent plasticity using the same nanoscale synapse with picojoule level energy consumption.

The HIV-1 reservoir in eight patients on long-term suppressive antiretroviral therapy is stable with few genetic changes over time

PubMed Central

Josefsson, Lina; von Stockenstrom, Susanne; Faria, Nuno R.; Sinclair, Elizabeth; Bacchetti, Peter; Killian, Maudi; Epling, Lorrie; Tan, Alice; Ho, Terence; Lemey, Philippe; Shao, Wei; Hunt, Peter W.; Somsouk, Ma; Wylie, Will; Douek, Daniel C.; Loeb, Lisa; Custer, Jeff; Hoh, Rebecca; Poole, Lauren; Deeks, Steven G.; Hecht, Frederick; Palmer, Sarah

2013-01-01

The source and dynamics of persistent HIV-1 during long-term combinational antiretroviral therapy (cART) are critical to understanding the barriers to curing HIV-1 infection. To address this issue, we isolated and genetically characterized HIV-1 DNA from naïve and memory T cells from peripheral blood and gut-associated lymphoid tissue (GALT) from eight patients after 4–12 y of suppressive cART. Our detailed analysis of these eight patients indicates that persistent HIV-1 in peripheral blood and GALT is found primarily in memory CD4+ T cells [CD45RO+/CD27(+/−)]. The HIV-1 infection frequency of CD4+ T cells from peripheral blood and GALT was higher in patients who initiated treatment during chronic compared with acute/early infection, indicating that early initiation of therapy results in lower HIV-1 reservoir size in blood and gut. Phylogenetic analysis revealed an HIV-1 genetic change between RNA sequences isolated before initiation of cART and intracellular HIV-1 sequences from the T-cell subsets after 4–12 y of suppressive cART in four of the eight patients. However, evolutionary rate analyses estimated no greater than three nucleotide substitutions per gene region analyzed during all of the 4–12 y of suppressive therapy. We also identified a clearly replication-incompetent viral sequence in multiple memory T cells in one patient, strongly supporting asynchronous cell replication of a cell containing integrated HIV-1 DNA as the source. This study indicates that persistence of a remarkably stable population of infected memory cells will be the primary barrier to a cure, and, with little evidence of viral replication, this population could be maintained by homeostatic cell proliferation or other processes. PMID:24277811

Effect of Nano CeO2 Addition on the Microstructure and Properties of a Cu-Al-Ni Shape Memory Alloy

NASA Astrophysics Data System (ADS)

Pandey, Abhishek; Jain, Ashish Kumar; Hussain, Shahadat; Sampath, V.; Dasgupta, Rupa

2016-08-01

This article deals with the effect of adding nano CeO2 to act as a grain pinner/refiner to a known Cu-Al-Ni shape memory alloy. Elements were taken in a predefined ratio to prepare 300 g alloy per batch and melted in an induction furnace. Casting was followed by homogenization at 1173 K (900 °C) and rolling to make sheets of 0.5-mm thickness. Further, samples were characterized for microstructure using optical and electron microscope, hardness, and different phase studies by X-ray and transformation temperatures by differential scanning calorimetry. X-ray peak broadenings and changes were investigated to estimate the crystallite size, lattice strain, and phase changes due to different processing steps. A nearly uniform distribution of CeO2 and better martensitic structure were observed with increasing CeO2. The addition of CeO2 also shows a visible effect on the transformation temperature and phase formation.

Optical and magneto-optical studies of martensitic transformation in Ni-Mn-Ga magnetic shape memory alloys

NASA Astrophysics Data System (ADS)

Beran, L.; Cejpek, P.; Kulda, M.; Antos, R.; Holy, V.; Veis, M.; Straka, L.; Heczko, O.

2015-05-01

Optical and magneto-optical properties of single crystal of Ni50.1Mn28.4Ga21.5 magnetic shape memory alloy during its transformation from martensite to austenite phase were systematically studied. Crystal orientation was approximately along {100} planes of parent cubic austenite. X-ray reciprocal mapping confirmed modulated 10 M martensite phase. Temperature depended measurements of saturation magnetization revealed the martensitic transformation at 335 K during heating. Magneto-optical spectroscopy and spectroscopic ellipsometry were measured in the sample temperature range from 297 to 373 K and photon energy range from 1.2 to 6.5 eV. Magneto-optical spectra of polar Kerr rotation as well as the spectra of ellipsometric parameter Ψ exhibited significant changes when crossing the transformation temperature. These changes were assigned to different optical properties of Ni-Mn-Ga in martensite and austenite phases due to modification of electronic structure near the Fermi energy during martensitic transformation.

MoSbTe for high-speed and high-thermal-stability phase-change memory applications

NASA Astrophysics Data System (ADS)

Liu, Wanliang; Wu, Liangcai; Li, Tao; Song, Zhitang; Shi, Jianjun; Zhang, Jing; Feng, Songlin

2018-04-01

Mo-doped Sb1.8Te materials and electrical devices were investigated for high-thermal-stability and high-speed phase-change memory applications. The crystallization temperature (t c = 185 °C) and 10-year data retention (t 10-year = 112 °C) were greatly enhanced compared with those of Ge2Sb2Te5 (t c = 150 °C, t 10-year = 85 °C) and pure Sb1.8Te (t c = 166 °C, t 10-year = 74 °C). X-ray diffraction and transmission electron microscopy results show that the Mo dopant suppresses crystallization, reducing the crystalline grain size. Mo2.0(Sb1.8Te)98.0-based devices were fabricated to evaluate the reversible phase transition properties. SET/RESET with a large operation window can be realized using a 10 ns pulse, which is considerably better than that required for Ge2Sb2Te5 (∼50 ns). Furthermore, ∼1 × 106 switching cycles were achieved.

Selective visual processing across competition episodes: a theory of task-driven visual attention and working memory

PubMed Central

Schneider, Werner X.

2013-01-01

The goal of this review is to introduce a theory of task-driven visual attention and working memory (TRAM). Based on a specific biased competition model, the ‘theory of visual attention’ (TVA) and its neural interpretation (NTVA), TRAM introduces the following assumption. First, selective visual processing over time is structured in competition episodes. Within an episode, that is, during its first two phases, a limited number of proto-objects are competitively encoded—modulated by the current task—in activation-based visual working memory (VWM). In processing phase 3, relevant VWM objects are transferred via a short-term consolidation into passive VWM. Second, each time attentional priorities change (e.g. after an eye movement), a new competition episode is initiated. Third, if a phase 3 VWM process (e.g. short-term consolidation) is not finished, whereas a new episode is called, a protective maintenance process allows its completion. After a VWM object change, its protective maintenance process is followed by an encapsulation of the VWM object causing attentional resource costs in trailing competition episodes. Viewed from this perspective, a new explanation of key findings of the attentional blink will be offered. Finally, a new suggestion will be made as to how VWM items might interact with visual search processes. PMID:24018722

How do plants achieve immunity? Defence without specialized immune cells.

PubMed

Spoel, Steven H; Dong, Xinnian

2012-01-25

Vertebrates have evolved a sophisticated adaptive immune system that relies on an almost infinite diversity of antigen receptors that are clonally expressed by specialized immune cells that roam the circulatory system. These immune cells provide vertebrates with extraordinary antigen-specific immune capacity and memory, while minimizing self-reactivity. Plants, however, lack specialized mobile immune cells. Instead, every plant cell is thought to be capable of launching an effective immune response. So how do plants achieve specific, self-tolerant immunity and establish immune memory? Recent developments point towards a multilayered plant innate immune system comprised of self-surveillance, systemic signalling and chromosomal changes that together establish effective immunity.

The dynamics of neuronal redundancy in decision making

NASA Astrophysics Data System (ADS)

Daniels, Bryan; Flack, Jessica; Krakauer, David

We propose two temporal phases of collective computation in a visual motion direction discrimination task by analyzing recordings from 169 neural channels in the prefrontal cortex of macaque monkeys. Phase I is a distributed phase in which uncertainty is substantially reduced by pooling information from many cells. Phase II is a redundant phase in which numerous single cells contain all the information present at the population level in Phase I. A dynamic distributed model connects low redundancy to a slow timescale of information aggregation, and provides a common explanation for both behaviors that differs only in the degree of recurrent excitation. We attribute the slow timescale of information accumulation to critical slowing down near the transition to a memory-carrying collective state. We suggest that this dynamic of slow distributed accumulation followed by fast collective propagation is a generic feature of robust collective computing systems related to consensus formation.

The costs of changing an intended action: movement planning, but not execution, interferes with verbal working memory.

PubMed

Spiegel, M A; Koester, D; Weigelt, M; Schack, T

2012-02-16

How much cognitive effort does it take to change a movement plan? In previous studies, it has been shown that humans plan and represent actions in advance, but it remains unclear whether or not action planning and verbal working memory share cognitive resources. Using a novel experimental paradigm, we combined in two experiments a grasp-to-place task with a verbal working memory task. Participants planned a placing movement toward one of two target positions and subsequently encoded and maintained visually presented letters. Both experiments revealed that re-planning the intended action reduced letter recall performance; execution time, however, was not influenced by action modifications. The results of Experiment 2 suggest that the action's interference with verbal working memory arose during the planning rather than the execution phase of the movement. Together, our results strongly suggest that movement planning and verbal working memory share common cognitive resources. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Characterization of NiTi Shape Memory Damping Elements designed for Automotive Safety Systems

NASA Astrophysics Data System (ADS)

Strittmatter, Joachim; Clipa, Victor; Gheorghita, Viorel; Gümpel, Paul

2014-07-01

Actuator elements made of NiTi shape memory material are more and more known in industry because of their unique properties. Due to the martensitic phase change, they can revert to their original shape by heating when subjected to an appropriate treatment. This thermal shape memory effect (SME) can show a significant shape change combined with a considerable force. Therefore such elements can be used to solve many technical tasks in the field of actuating elements and mechatronics and will play an increasing role in the next years, especially within the automotive technology, energy management, power, and mechanical engineering as well as medical technology. Beside this thermal SME, these materials also show a mechanical SME, characterized by a superelastic plateau with reversible elongations in the range of 8%. This behavior is based on the building of stress-induced martensite of loaded austenite material at constant temperature and facilitates a lot of applications especially in the medical field. Both SMEs are attended by energy dissipation during the martensitic phase change. This paper describes the first results obtained on different actuator and superelastic NiTi wires concerning their use as damping elements in automotive safety systems. In a first step, the damping behavior of small NiTi wires up to 0.5 mm diameter was examined at testing speeds varying between 0.1 and 50 mm/s upon an adapted tensile testing machine. In order to realize higher testing speeds, a drop impact testing machine was designed, which allows testing speeds up to 4000 mm/s. After introducing this new type of testing machine, the first results of vertical-shock tests of superelastic and electrically activated actuator wires are presented. The characterization of these high dynamic phase change parameters represents the basis for new applications for shape memory damping elements, especially in automotive safety systems.

Low temperature nickel titanium iron shape memory alloys: Actuator engineering and investigation of deformation mechanisms using in situ neutron diffraction at Los Alamos National Laboratory

NASA Astrophysics Data System (ADS)

Krishnan, Vinu B.

Shape memory alloys are incorporated as actuator elements due to their inherent ability to sense a change in temperature and actuate against external loads by undergoing a shape change as a result of a temperature-induced phase transformation. The cubic so-called austenite to the trigonal so-called R-phase transformation in NiTiFe shape memory alloys offers a practical temperature range for actuator operation at low temperatures, as it exhibits a narrow temperature-hysteresis with a desirable fatigue response. Overall, this work is an investigation of selected science and engineering aspects of low temperature NiTiFe shape memory alloys. The scientific study was performed using in situ neutron diffraction measurements at the newly developed low temperature loading capability on the Spectrometer for Materials Research at Temperature and Stress (SMARTS) at Los Alamos National Laboratory and encompasses three aspects of the behavior of Ni46.8Ti50Fe3.2 at 92 K (the lowest steady state temperature attainable with the capability). First, in order to study deformation mechanisms in the R-phase in NiTiFe, measurements were performed at a constant temperature of 92 K under external loading. Second, with the objective of examining NiTiFe in one-time, high-stroke, actuator applications (such as in safety valves), a NiTiFe sample was strained to approximately 5% (the R-phase was transformed to B19' phase in the process) at 92 K and subsequently heated to full strain recovery under a load. Third, with the objective of examining NiTiFe in cyclic, low-stroke, actuator applications (such as in cryogenic thermal switches), a NiTiFe sample was strained to 1% at 92 K and subsequently heated to full strain recovery under load. Neutron diffraction spectra were recorded at selected time and stress intervals during these experiments. The spectra were subsequently used to obtain quantitative information related to the phase-specific strain, texture and phase fraction evolution using the Rietveld technique. The mechanical characterization of NiTiFe alloys using the cryogenic capability at SMARTS provided considerable insight into the mechanisms of phase transformation and twinning at cryogenic temperatures. Both mechanisms contribute to shape memory and pseudoelasticity phenomena. Three phases (R, B19' and B33 phases) were found to coexist at 92 K in the unloaded condition (nominal holding stress of 8 MPa). For the first time the elastic modulus of R-phase was reported from neutron diffraction experiments. Furthermore, for the first time a base-centered orthorhombic (B33) martensitic phase was identified experimentally in a NiTi-based shape memory alloy. The orthorhombic B33 phase has been theoretically predicted in NiTi from density function theory (DFT) calculations but hitherto has never been observed experimentally. The orthorhombic B33 phase was observed while observing shifting of a peak (identified to be {021}B33) between the {111}R and {100}B19' peaks in the diffraction spectra collected during loading. Given the existing ambiguity in the published literature as to whether the trigonal R-phase belongs to the P3 or P3¯ space groups, Rietveld analyses were separately carried out incorporating the symmetries associated with both space groups and the impact of this choice evaluated. The constrained recovery of the B19' phase to the R-phase recorded approximately 4% strain recovery between 150 K and 170 K, with half of that recovery occurring between 160 K and 162 K. Additionally, the aforementioned research methodology developed for Ni46.8Ti50Fe3.2 shape memory alloys was applied to experiments performed on a new high temperature Ni 29.5Ti50.5Pd20 shape memory alloys. The engineering aspect focused on the development of (i) a NiTiFe based thermal conduction switch that minimized the heat gradient across the shape memory actuator element, (ii) a NiTiFe based thermal conduction switch that incorporated the actuator element in the form of helical springs, and (iii) a NiTi based release mechanism. Patents are being filed for all the three shape memory actuators developed as a part of this work. This work was supported by grants from SRI, NASA (NAG3-2751) and NSF (CAREER DMR-0239512) to UCF. Additionally, this work benefited from the use of the Lujan Center at the Los Alamos Neutron Science Center, funded by the United States Department of Energy, Office of Basic Energy Sciences, under Contract No. W-7405-ENG-36.

A Shape Memory Alloy Based Cryogenic Thermal Conduction Switch

NASA Technical Reports Server (NTRS)

Notardonato, W. U.; Krishnan, V. B.; Singh, J. D.; Woodruff, T. R.; Vaidyanathan, R.

2005-01-01

Shape memory alloys (SMAs) can produce large strains when deformed (e.g., up to 8%). Heating results in a phase transformation and associated recovery of all the accumulated strain. This strain recovery can occur against large forces, resulting in their use as actuators. Thus an SMA element can integrate both sensory and actuation functions, by inherently sensing a change in temperature and actuating by undergoing a shape change as a result of a temperature-induced phase transformation. Two aspects of our work on cryogenic SMAs are addressed here. First - a shape memory alloy based cryogenic thermal conduction switch for operation between dewars of liquid methane and liquid oxygen in a common bulkhead arrangement is discussed. Such a switch integrates the sensor element and the actuator element and can be used to create a variable thermal sink to other cryogenic tanks for liquefaction, densification, and zero boil-off systems for advanced spaceport applications. Second - fabrication via arc-melting and subsequent materials testing of SMAs with cryogenic transformation temperatures for use in the aforementioned switch is discussed.

Microscopic Mechanism of Doping-Induced Kinetically Constrained Crystallization in Phase-Change Materials.

PubMed

Lee, Tae Hoon; Loke, Desmond; Elliott, Stephen R

2015-10-07

A comprehensive microscopic mechanism of doping-induced kinetically constrained crystallization in phase-change materials is provided by investigating structural and dynamical dopant characteristics via ab initio molecular dynamics simulations. The information gained from this study may provide a basis for a fast screening of dopant species for electronic memory devices, or for understanding the general physics involved in the crystallization of doped glasses. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In-situ crystallization of GeTe\\GaSb phase change memory stacked films

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

Velea, A., E-mail: alin.velea@psi.ch; National Institute of Materials Physics, RO-077125 Magurele, Ilfov; Borca, C. N.

2014-12-21

Single and double layer phase change memory structures based on GeTe and GaSb thin films were deposited by pulsed laser deposition (PLD). Their crystallization behavior was studied using in-situ synchrotron techniques. Electrical resistance vs. temperature investigations, using the four points probe method, showed transition temperatures of 138 °C and 198 °C for GeTe and GaSb single films, respectively. It was found that after GeTe crystallization in the stacked films, Ga atoms from the GaSb layer diffused in the vacancies of the GeTe crystalline structure. Therefore, the crystallization temperature of the Sb-rich GaSb layer is decreased by more than 30 °C. Furthermore, at 210 °C,more » the antimony excess from GaSb films crystallizes as a secondary phase. At higher annealing temperatures, the crystalline Sb phase increased on the expense of GaSb crystalline phase which was reduced. Extended X-ray absorption fine structure (EXAFS) measurements at the Ga and Ge K-edges revealed changes in their local atomic environments as a function of the annealing temperature. Simulations unveil a tetrahedral configuration in the amorphous state and octahedral configuration in the crystalline state for Ge atoms, while Ga is four-fold coordinated in both as-deposited and annealed samples.« less

Magneto-optical spectroscopy of ferromagnetic shape-memory Ni-Mn-Ga alloy

NASA Astrophysics Data System (ADS)

Veis, M.; Beran, L.; Zahradnik, M.; Antos, R.; Straka, L.; Kopecek, J.; Fekete, L.; Heczko, O.

2014-05-01

Magneto-optical properties of single crystal of Ni50.1Mn28.4Ga21.5 magnetic shape memory alloy in martensite and austenite phase were systematically studied. Crystal orientation was approximately along {100} planes of parent cubic austenite. At room temperature, the sample was in modulated 10M martensite phase and transformed to cubic austenite at 323 K. Spectral dependence of polar magneto-optical Kerr effect was obtained by generalized magneto-optical ellipsometry with rotating analyzer in the photon energy range from 1.2 to 4 eV, and from room temperature to temperature above the Curie point. The Kerr rotation spectra exhibit prominent features typical for complexes containing Mn atoms. Significant spectral changes during transformation to austenite can be explained by different optical properties caused by changes in density of states near the Fermi energy.

Evaluation of profile and functionality of memory T cells in pulmonary tuberculosis.

PubMed

Tonaco, Marcela M; Moreira, Jôsimar D; Nunes, Fernanda F C; Loures, Cristina M G; Souza, Larissa R; Martins, Janaina M; Silva, Henrique R; Porto, Arthur Henrique R; Toledo, Vicente Paulo C P; Miranda, Silvana S; Guimarães, Tânia Mara P D

2017-12-01

The cells T CD4+ T and CD8+ can be subdivided into phenotypes naïve, T of central memory, T of effector memory and effector, according to the expression of surface molecules CD45RO and CD27. The T lymphocytes are cells of long life with capacity of rapid expansion and function, after a new antigenic exposure. In tuberculosis, it was found that specific memory T cells are present, however, gaps remain about the role of such cells in the disease immunology. In this study, the phenotypic profile was analyzed and characterized the functionality of CD4+ T lymphocytes and CD8+ T cells of memory and effector, in response to specific stimuli in vitro, in patients with active pulmonary TB, compared to individuals with latent infection with Mycobacterium tuberculosis the ones treated with pulmonary TB. It was observed that the group of patients with active pulmonary tuberculosis was the one which presented the highest proportion of cells T CD4+ of central memory IFN-ɣ+ e TNF-α+, suggesting that in TB, these T of central memory cells would have a profile of protective response, being an important target of study for the development of more effective vaccines; this group also developed lower proportion of CD8+ T effector lymphocytes than the others, a probable cause of specific and less effective response against the bacillus in these individuals; the ones treated for pulmonary tuberculosis were those who developed higher proportion of T CD4+ of memory central IL-17+ cells, indicating that the stimulation of long duration, with high antigenic load, followed by elimination of the pathogen, contribute to more significant generation of such cells; individuals with latent infection by M. tuberculosis and treated for pulmonary tuberculosis, showed greater response of CD8+ T effector lymphocytes IFN-ɣ+ than the controls, suggesting that these cells, as well as CD4+ T lymphocytes, have crucial role of protection against M. tuberculosis. These findings have contributed to a better understanding of the immunologic changes in M. tuberculosis infection and the development of new strategies for diagnosis and prevention of tuberculosis. Copyright © 2017. Published by Elsevier B.V.

HIV dynamics linked to memory CD4+ T cell homeostasis.

PubMed

Murray, John M; Zaunders, John; Emery, Sean; Cooper, David A; Hey-Nguyen, William J; Koelsch, Kersten K; Kelleher, Anthony D

2017-01-01

The dynamics of latent HIV is linked to infection and clearance of resting memory CD4+ T cells. Infection also resides within activated, non-dividing memory cells and can be impacted by antigen-driven and homeostatic proliferation despite suppressive antiretroviral therapy (ART). We investigated whether plasma viral level (pVL) and HIV DNA dynamics could be explained by HIV's impact on memory CD4+ T cell homeostasis. Median total, 2-LTR and integrated HIV DNA levels per μL of peripheral blood, for 8 primary (PHI) and 8 chronic HIV infected (CHI) individuals enrolled on a raltegravir (RAL) based regimen, exhibited greatest changes over the 1st year of ART. Dynamics slowed over the following 2 years so that total HIV DNA levels were equivalent to reported values for individuals after 10 years of ART. The mathematical model reproduced the multiphasic dynamics of pVL, and levels of total, 2-LTR and integrated HIV DNA in both PHI and CHI over 3 years of ART. Under these simulations, residual viremia originated from reactivated latently infected cells where most of these cells arose from clonal expansion within the resting phenotype. Since virion production from clonally expanded cells will not be affected by antiretroviral drugs, simulations of ART intensification had little impact on pVL. HIV DNA decay over the first year of ART followed the loss of activated memory cells (120 day half-life) while the 5.9 year half-life of total HIV DNA after this point mirrored the slower decay of resting memory cells. Simulations had difficulty reproducing the fast early HIV DNA dynamics, including 2-LTR levels peaking at week 12, and the later slow loss of total and 2-LTR HIV DNA, suggesting some ongoing infection. In summary, our modelling indicates that much of the dynamical behavior of HIV can be explained by its impact on memory CD4+ T cell homeostasis.

Leptin attenuates the detrimental effects of β-amyloid on spatial memory and hippocampal later-phase long term potentiation in rats.

PubMed

Tong, Jia-Qing; Zhang, Jun; Hao, Ming; Yang, Ju; Han, Yu-Fei; Liu, Xiao-Jie; Shi, Hui; Wu, Mei-Na; Liu, Qing-Song; Qi, Jin-Shun

2015-07-01

β-Amyloid (Aβ) is the main component of amyloid plaques developed in the brain of patients with Alzheimer's disease (AD). The increasing burden of Aβ in the cortex and hippocampus is closely correlated with memory loss and cognition deficits in AD. Recently, leptin, a 16kD peptide derived mainly from white adipocyte tissue, has been appreciated for its neuroprotective function, although less is known about the effects of leptin on spatial memory and synaptic plasticity. The present study investigated the neuroprotective effects of leptin against Aβ-induced deficits in spatial memory and in vivo hippocampal late-phase long-term potentiation (L-LTP) in rats. Y maze spontaneous alternation was used to assess short term working memory, and the Morris water maze task was used to assess long term reference memory. Hippocampal field potential recordings were performed to observe changes in L-LTP. We found that chronically intracerebroventricular injection of leptin (1μg) effectively alleviated Aβ1-42 (20μg)-induced spatial memory impairments of Y maze spontaneous alternation and Morris water maze. In addition, chronic administration of leptin also reversed Aβ1-42-induced suppression of in vivo hippocampal L-LTP in rats. Together, these results suggest that chronic leptin treatments reversed Aβ-induced deficits in learning and memory and the maintenance of L-LTP. Copyright © 2015 Elsevier Inc. All rights reserved.

Initiation of Antiretroviral Therapy Restores CD4+ T Memory Stem Cell Homeostasis in Simian Immunodeficiency Virus-Infected Macaques.

PubMed

Cartwright, Emily K; Palesch, David; Mavigner, Maud; Paiardini, Mirko; Chahroudi, Ann; Silvestri, Guido

2016-08-01

Treatment of human immunodeficiency virus (HIV) infection with antiretroviral therapy (ART) has significantly improved prognosis. Unfortunately, interruption of ART almost invariably results in viral rebound, attributed to a pool of long-lived, latently infected cells. Based on their longevity and proliferative potential, CD4(+) T memory stem cells (TSCM) have been proposed as an important site of HIV persistence. In a previous study, we found that in simian immunodeficiency virus (SIV)-infected rhesus macaques (RM), CD4(+) TSCM are preserved in number but show (i) a decrease in the frequency of CCR5(+) cells, (ii) an expansion of the fraction of proliferating Ki-67(+) cells, and (iii) high levels of SIV DNA. To understand the impact of ART on both CD4(+) TSCM homeostasis and virus persistence, we conducted a longitudinal analysis of these cells in the blood and lymph nodes of 25 SIV-infected RM. We found that ART induced a significant restoration of CD4(+) CCR5(+) TSCM both in blood and in lymph nodes and a reduction in the fraction of proliferating CD4(+) Ki-67(+) TSCM in blood (but not lymph nodes). Importantly, we found that the level of SIV DNA in CD4(+) transitional memory (TTM) and effector memory (TEM) T cells declined ∼100-fold after ART in both blood and lymph nodes, while the level of SIV DNA in CD4(+) TSCM and central memory T cells (TCM-) did not significantly change. These data suggest that ART is effective at partially restoring CD4(+) TSCM homeostasis, and the observed stable level of virus in TSCM supports the hypothesis that these cells are a critical contributor to SIV persistence. Understanding the roles of various CD4(+) T cell memory subsets in immune homeostasis and HIV/SIV persistence during antiretroviral therapy (ART) is critical to effectively treat and cure HIV infection. T memory stem cells (TSCM) are a unique memory T cell subset with enhanced self-renewal capacity and the ability to differentiate into other memory T cell subsets, such as central and transitional memory T cells (TCM and TTM, respectively). CD4(+) TSCM are disrupted but not depleted during pathogenic SIV infection. We find that ART is partially effective at restoring CD4(+) TSCM homeostasis and that SIV DNA harbored within this subset contracts more slowly than virus harbored in shorter-lived subsets, such as TTM and effector memory (TEM). Because of their ability to persist long-term in an individual, understanding the dynamics of virally infected CD4(+) TSCM during suppressive ART is important for future therapeutic interventions aimed at modulating immune activation and purging the HIV reservoir. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Initiation of Antiretroviral Therapy Restores CD4+ T Memory Stem Cell Homeostasis in Simian Immunodeficiency Virus-Infected Macaques

PubMed Central

Cartwright, Emily K.; Palesch, David; Mavigner, Maud; Paiardini, Mirko; Chahroudi, Ann

2016-01-01

ABSTRACT Treatment of human immunodeficiency virus (HIV) infection with antiretroviral therapy (ART) has significantly improved prognosis. Unfortunately, interruption of ART almost invariably results in viral rebound, attributed to a pool of long-lived, latently infected cells. Based on their longevity and proliferative potential, CD4+ T memory stem cells (TSCM) have been proposed as an important site of HIV persistence. In a previous study, we found that in simian immunodeficiency virus (SIV)-infected rhesus macaques (RM), CD4+ TSCM are preserved in number but show (i) a decrease in the frequency of CCR5+ cells, (ii) an expansion of the fraction of proliferating Ki-67+ cells, and (iii) high levels of SIV DNA. To understand the impact of ART on both CD4+ TSCM homeostasis and virus persistence, we conducted a longitudinal analysis of these cells in the blood and lymph nodes of 25 SIV-infected RM. We found that ART induced a significant restoration of CD4+ CCR5+ TSCM both in blood and in lymph nodes and a reduction in the fraction of proliferating CD4+ Ki-67+ TSCM in blood (but not lymph nodes). Importantly, we found that the level of SIV DNA in CD4+ transitional memory (TTM) and effector memory (TEM) T cells declined ∼100-fold after ART in both blood and lymph nodes, while the level of SIV DNA in CD4+ TSCM and central memory T cells (TCM-) did not significantly change. These data suggest that ART is effective at partially restoring CD4+ TSCM homeostasis, and the observed stable level of virus in TSCM supports the hypothesis that these cells are a critical contributor to SIV persistence. IMPORTANCE Understanding the roles of various CD4+ T cell memory subsets in immune homeostasis and HIV/SIV persistence during antiretroviral therapy (ART) is critical to effectively treat and cure HIV infection. T memory stem cells (TSCM) are a unique memory T cell subset with enhanced self-renewal capacity and the ability to differentiate into other memory T cell subsets, such as central and transitional memory T cells (TCM and TTM, respectively). CD4+ TSCM are disrupted but not depleted during pathogenic SIV infection. We find that ART is partially effective at restoring CD4+ TSCM homeostasis and that SIV DNA harbored within this subset contracts more slowly than virus harbored in shorter-lived subsets, such as TTM and effector memory (TEM). Because of their ability to persist long-term in an individual, understanding the dynamics of virally infected CD4+ TSCM during suppressive ART is important for future therapeutic interventions aimed at modulating immune activation and purging the HIV reservoir. PMID:27170752

In vitro investigation of NiTiW shape memory alloy as potential biomaterial with enhanced radiopacity.

PubMed

Li, Huafang; Cong, Ying; Zheng, Yufeng; Cui, Lishan

2016-03-01

In the present study, a novel kind of NiTiW shape memory alloy with chemical composition of Ni43.5Ti45.5W11 (at.%) has been successfully developed with excellent X-ray radiopacity by the introduction of pure W precipitates into the NiTi matrix phase. Its microstructure, X-ray radiopacity, mechanical properties, corrosion resistance in simulated body fluid, hemocompatibility and in vitro cytocompatibility were systematically investigated. The typical microstructural feature of NiTiW alloy at room temperature was tiny pure W particles randomly distributing in the NiTi matrix phase. The presence of W precipitates was found to result in enhanced radiopacity and microhardness of NiTiW alloy in comparison to that of NiTi binary alloy. NiTiW alloy exhibits excellent shape memory effect, and a maximum shape recovery ratio of about 30% was obtained with a total prestrain of 8% for the NiTiW alloy sample. In the electrochemical test, NiTiW alloy presented an excellent corrosion resistance in simulated body fluid, comparable to that of NiTi alloy. Hemocompatibility tests indicated that the NiTiW alloy has quite low hemolysis (lower than 0.5%) and the adherent platelet showed round shape without pseudopod. Besides, in vitro cell viability tests demonstrated that the cell viability is all above 90%, and the cells spread well on the NiTiW alloy, having polygon or spindle healthy morphology. The hemocompatibility tests, in vitro cell viability tests and morphology observation indicated that the NiTiW shape memory alloys have excellent biocompatibility. The excellent X-ray radiopacity makes the NiTiW alloys show obvious advantages in orthopedic, stomatological, neurological and cardiovascular domains where radiopacity is quite important factor in order to guarantee successful implantation. Copyright © 2015 Elsevier B.V. All rights reserved.

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

High-Throughput Sequencing of Islet-Infiltrating Memory CD4+ T Cells Reveals a Similar Pattern of TCR Vβ Usage in Prediabetic and Diabetic NOD Mice

PubMed Central

Marrero, Idania; Hamm, David E.; Davies, Joanna D.

2013-01-01

Autoreactive memory CD4+ T cells play a critical role in the development of type 1 diabetes, but it is not yet known how the clonotypic composition and TCRβ repertoire of the memory CD4+ T cell compartment changes during the transition from prediabetes to diabetes. In this study, we used high-throughput sequencing to analyze the TCRβ repertoire of sorted islet-infiltrating memory CD4+CD44high T cells in 10-week-old prediabetic and recently diabetic NOD mice. We show that most clonotypes of islet-infiltrating CD4+CD44high T cells were rare, but high-frequency clonotypes were significantly more common in diabetic than in prediabetic mice. Moreover, although the CD4+CD44high TCRβ repertoires were highly diverse at both stages of disease development, dominant use of TRBV1 (Vβ2), TRBV13-3 (Vβ8.1), and TRBV19 (Vβ6) was evident in both prediabetic and diabetic mice. Our findings strongly suggest that therapeutic targeting of cells specifically expressing the dominant TCRβ might reduce pancreatic infiltration in prediabetic mice and attenuate the progression to diabetes. PMID:24146886

Place Cell Networks in Pre-weanling Rats Show Associative Memory Properties from the Onset of Exploratory Behavior.

PubMed

Muessig, L; Hauser, J; Wills, T J; Cacucci, F

2016-08-01

Place cells are hippocampal pyramidal cells that are active when an animal visits a restricted area of the environment, and collectively their activity constitutes a neural representation of space. Place cell populations in the adult rat hippocampus display fundamental properties consistent with an associative memory network: the ability to 1) generate new and distinct spatial firing patterns when encountering novel spatial contexts or changes in sensory input ("remapping") and 2) reinstate previously stored firing patterns when encountering a familiar context, including on the basis of an incomplete/degraded set of sensory cues ("pattern completion"). To date, it is unknown when these spatial memory responses emerge during brain development. Here, we show that, from the age of first exploration (postnatal day 16) onwards, place cell populations already exhibit these key features: they generate new representations upon exposure to a novel context and can reactivate familiar representations on the basis of an incomplete set of sensory cues. These results demonstrate that, as early as exploratory behaviors emerge, and despite the absence of an adult-like grid cell network, the developing hippocampus processes incoming sensory information as an associative memory network. © The Author 2016. Published by Oxford University Press.

Effects of Immersion Solvent on Photovoltaic and Photophysical Properties of Porphyrin-Sensitized Solar Cells.

PubMed

Hayashi, Hironobu; Higashino, Tomohiro; Kinjo, Yuriko; Fujimori, Yamato; Kurotobi, Kei; Chabera, Pavel; Sundström, Villy; Isoda, Seiji; Imahori, Hiroshi

2015-08-26

Memory effects in self-assembled monolayers (SAMs) of zinc porphyrin carboxylic acid on TiO2 electrodes have been demonstrated for the first time by evaluating the photovoltaic and electron transfer properties of porphyrin-sensitized solar cells prepared by using different immersion solvents sequentially. The structure of the SAM of the porphyrin on the TiO2 was maintained even after treating the porphyrin monolayer with different neat immersion solvents (memory effect), whereas it was altered by treatment with solutions containing different porphyrins (inverse memory effect). Infrared spectroscopy shows that the porphyrins in the SAM on the TiO2 could be exchanged with the same or analogous porphyrin, leading to a change in the structure of the porphyrin SAM. The memory and inverse memory effects are well correlated with a change in porphyrin geometry, mainly the tilt angle of the porphyrin along the long molecular axis from the surface normal on the TiO2, as well as with kinetics of electron transfer between the porphyrin and TiO2. Such a new structure-function relationship for DSSCs will be very useful for the rational design and optimization of photoelectrochemical and photovoltaic properties of molecular assemblies on semiconductor surfaces.

The PD-1: PD-L1 pathway promotes development of brain-resident memory T cells following acute viral encephalitis.

PubMed

Prasad, Sujata; Hu, Shuxian; Sheng, Wen S; Chauhan, Priyanka; Singh, Amar; Lokensgard, James R

2017-04-13

Previous work from our laboratory has demonstrated that during acute viral brain infection, glial cells modulate antiviral T cell effector responses through the PD-1: PD-L1 pathway, thereby limiting the deleterious consequences of unrestrained neuroinflammation. Here, we evaluated the PD-1: PD-L1 pathway in development of brain-resident memory T cells (bT RM ) following murine cytomegalovirus (MCMV) infection. Flow cytometric analysis of immune cells was performed at 7, 14, and 30 days post-infection (dpi) to assess the shift of brain-infiltrating CD8 + T cell populations from short-lived effector cells (SLEC) to memory precursor effector cells (MPEC), as well as generation of bT RMs . In wild-type (WT) animals, we observed a switch in the phenotype of brain-infiltrating CD8 + T cell populations from KLRG1 + CD127 - (SLEC) to KLRG1 - CD127 + (MPEC) during transition from acute through chronic phases of infection. At 14 and 30 dpi, the majority of CD8 + T cells expressed CD127, a marker of memory cells. In contrast, fewer CD8 + T cells expressed CD127 within brains of infected, PD-L1 knockout (KO) animals. Notably, in WT mice, a large population of CD8 + T cells was phenotyped as CD103 + CD69 + , markers of bT RM , and differences were observed in the numbers of these cells when compared to PD-L1 KOs. Immunohistochemical studies revealed that brain-resident CD103 + bT RM cells were localized to the parenchyma. Higher frequencies of CXCR3 were also observed among WT animals in contrast to PD-L1 KOs. Taken together, our results indicate that bT RMs are present within the CNS following viral infection and the PD-1: PD-L1 pathway plays a role in the generation of this brain-resident population.

Annealing effects on the structural and magnetic properties of off-stoichiometric Fe-Mn-Ga ferromagnetic shape memory alloys

DOE PAGES

Chen, Yan; Bei, Hongbin; Dela Cruz, Clarina R; ...

2016-05-07

Annealing plays an important role in modifying structures and properties of ferromagnetic shape memory alloys (FSMAs). The annealing effect on the structures and magnetic properties of off-stoichiometric Fe 45Mn 26Ga 29 FSMA has been investigated at different elevated temperatures. Rietveld refinements of neutron diffraction patterns display that the formation of the γ phase in Fe 45Mn 26Ga 29 annealed at 1073 K increases the martensitic transformation temperature and reduces the thermal hysteresis in comparison to the homogenized sample. The phase segregation of a Fe-rich cubic phase and a Ga-rich cubic phase occurs at the annealing temperature of 773 K. Themore » atomic occupancies of the alloys are determined thanks to the neutron's capability of differentiating transition metals. The annealing effects at different temperatures introduce a different magnetic characteristic that is associated with distinctive structural changes in the crystal.« less

Nanoscale phase transition behavior of shape memory alloys — closed form solution of 1D effective modelling

NASA Astrophysics Data System (ADS)

Li, M. P.; Sun, Q. P.

2018-01-01

We investigate the roles of grain size (lg) and grain boundary thickness (lb) on the stress-induced phase transition (PT) behaviors of nanocrystalline shape memory alloys (SMAs) by using a Core-shell type "crystallite-amorphous composite" model. A non-dimensionalized length scale lbarg(=lg /lb) is identified as the governing parameter which is indicative of the energy competition between the crystallite and the grain boundary. Closed form analytical solutions of a reduced effective 1D model with embedded microstructure length scales of lg and lb are presented in this paper. It is shown that, with lbarg reduction, the energy of the elastic non-transformable grain boundary will gradually become dominant in the phase transition process, and eventually bring fundamental changes of the deformation behaviors: breakdown of two-phase coexistence and vanishing of superelastic hysteresis. The predictions are supported by experimental data of nanocrystalline NiTi SMAs.

Aging and cytomegalovirus (CMV) infection differentially and jointly affect distinct circulating T cell subsets in humans1

PubMed Central

Wertheimer, Anne M.; Bennett, Michael S.; Park, Byung; Uhrlaub, Jennifer L.; Martinez, Carmine; Pulko, Vesna; Currier, Noreen L.; Nikolich-Zugich, Dragana; Kaye, Jeffrey; Nikolich-Zugich, Janko

2014-01-01

The impact of intrinsic aging upon human peripheral blood T-cell subsets remains incompletely quantified and understood. This impact must be distinguished from the influence of latent persistent microorganisms, particularly cytomegalovirus (CMV), which has been associated with age-related changes in the T cell pool. In a cross-sectional cohort of 152 CMV-negative individuals, aged 21–101 years, we found that aging correlated strictly to an absolute loss of naïve CD8, but not CD4, T cells, but, contrary to many reports, did not lead to an increase in memory T cell numbers. The loss of naïve CD8 T cells was not altered by CMV in 239 subjects (range 21–96 years) but the decline in CD4+ naïve cells showed significance in CMV+ individuals. These individuals also exhibited an absolute increase in the effector/effector memory CD4+ and CD8+ cells with age. That increase was seen mainly, if not exclusively, in older subjects with elevated anti-CMV Ab titers, suggesting that efficacy of viral control over time may determine the magnitude of CMV impact upon T cell memory, and perhaps upon immune defense. These findings provide important new insights into the age-related changes in the peripheral blood pool of older adults, demonstrating that aging and CMV exert both distinct and joint influence upon blood T cell homeostasis in humans. PMID:24501199

Reverse Shape Memory Effect Related to α → γ Transformation in a Fe-Mn-Al-Ni Shape Memory Alloy

NASA Astrophysics Data System (ADS)

Peng, Huabei; Huang, Pan; Zhou, Tiannan; Wang, Shanling; Wen, Yuhua

2017-05-01

In this study, we investigated the shape memory behavior and phase transformations of solution-treated Fe43.61Mn34.74Al13.38Ni8.27 alloy between room temperature and 1173 K (900 °C). This alloy exhibits the reverse shape memory effect resulting from the phase transformation of α (bcc) → γ (fcc) between 673 K and 1073 K (400 °C and 800 °C) in addition to the shape memory effect resulting from the martensitic reverse transformation of γ' (fcc) → α (bcc) below 673 K (400 °C). There is a high density of hairpin-shaped dislocations in the α phase undergoing the martensitic reverse transformation of γ' → α. The lath γ phase, which preferentially nucleates and grows in the reversed α phase, has the same crystal orientation with the reverse-transformed γ' martensite. However, the vermiculate γ phase, which is precipitated in the α phase between lath γ phase, has different crystal orientations. The lath γ phase is beneficial to attaining better reverse shape memory effect than the vermiculate γ phase.

The evolving roles of memory immune cells in transplantation

PubMed Central

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

2015-01-01

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

Method of preparing a two-way shape memory alloy

DOEpatents

Johnson, Alfred D.

1984-01-01

A two-way shape memory alloy, a method of training a shape memory alloy, and a heat engine employing the two-way shape memory alloy to do external work during both heating and cooling phases. The alloy is heated under a first training stress to a temperature which is above the upper operating temperature of the alloy, then cooled to a cold temperature below the zero-force transition temperature of the alloy, then deformed while applying a second training stress which is greater in magnitude than the stress at which the alloy is to be operated, then heated back to the hot temperature, changing from the second training stress back to the first training stress.

Treatment for moderate to severe atopic dermatitis in alpine and moderate maritime climates differentially affects helper T cells and memory B cells in children.

PubMed

Heeringa, J J; Fieten, K B; Bruins, F M; van Hoffen, E; Knol, E F; Pasmans, S G M A; van Zelm, M C

2018-06-01

Treatment of atopic dermatitis (AD) is focused on topical anti-inflammatory therapy, epidermal barrier repair and trigger avoidance. Multidisciplinary treatment in both moderate maritime and alpine climates can successfully reduce disease activity in children with AD. However, it remains unclear whether abnormalities in B cell and T cell memory normalize and whether this differs between treatment strategies. To determine whether successful treatment in maritime and alpine climates normalizes B- and T lymphocytes in children with moderate to severe AD. The study was performed in the context of a trial (DAVOS trial, registered at Current Controlled Trials ISCRTN88136485) in which eighty-eight children with moderate to severe AD were randomized to 6 weeks of treatment in moderate maritime climate (outpatient setting) or in the alpine climate (inpatient setting). Before and directly after treatment, disease activity was determined with SA-EASI and serum TARC, and T cell and B cell subsets were quantified in blood. Both treatment protocols achieved a significant decrease in disease activity, which was accompanied by a reduction in circulating memory Treg, transitional B cell and plasmablast numbers. Alpine climate treatment had a significantly greater effect on disease activity and was accompanied by a reduction in blood eosinophils and increases in memory B cells, CD8+ TemRO, CD4+ Tcm and CCR7+ Th2 subsets. Clinically successful treatment of AD induces changes in blood B- and T cell subsets reflecting reduced chronic inflammation. In addition, multidisciplinary inpatient treatment in the alpine climate specifically affects memory B cells, CD8+ T cells and Th2 cells. These cell types could represent good markers for treatment efficacy. © 2018 John Wiley & Sons Ltd.

Protein Energy Malnutrition during Vaccination Has Limited Influence on Vaccine Efficacy but Abolishes Immunity if Administered during Mycobacterium tuberculosis Infection

PubMed Central

Hoang, Truc; Agger, Else Marie; Cassidy, Joseph P.; Christensen, Jan P.

2015-01-01

Protein energy malnutrition (PEM) increases susceptibility to infectious diseases, including tuberculosis (TB), but it is not clear how PEM influences vaccine-promoted immunity to TB. We demonstrate that PEM during low-level steady-state TB infection in a mouse model results in rapid relapse of Mycobacterium tuberculosis, as well as increased pathology, in both Mycobacterium bovis BCG-vaccinated and unvaccinated animals. PEM did not change the overall numbers of CD4 T cells in BCG-vaccinated animals but resulted in an almost complete loss of antigen-specific cytokine production. Furthermore, there was a change in cytokine expression characterized by a gradual loss of multifunctional antigen-specific CD4 T cells and an increased proportion of effector cells expressing gamma interferon and tumor necrosis factor alpha (IFN-γ+ TNF-α+ and IFN-γ+ cells). PEM during M. tuberculosis infection completely blocked the protection afforded by the H56-CAF01 subunit vaccine, and this was associated with a very substantial loss of the interleukin-2-positive memory CD4 T cells promoted by this vaccine. Similarly, PEM during the vaccination phase markedly reduced the H56-CAF01 vaccine response, influencing all cytokine-producing CD4 T cell subsets, with the exception of CD4 T cells positive for TNF-α only. Importantly, this impairment was reversible and resupplementation of protein during infection rescued both the vaccine-promoted T cell response and the protective effect of the vaccine against M. tuberculosis infection. PMID:25754202

Disorder-induced localization in crystalline phase-change materials.

PubMed

Siegrist, T; Jost, P; Volker, H; Woda, M; Merkelbach, P; Schlockermann, C; Wuttig, M

2011-03-01

Localization of charge carriers in crystalline solids has been the subject of numerous investigations over more than half a century. Materials that show a metal-insulator transition without a structural change are therefore of interest. Mechanisms leading to metal-insulator transition include electron correlation (Mott transition) or disorder (Anderson localization), but a clear distinction is difficult. Here we report on a metal-insulator transition on increasing annealing temperature for a group of crystalline phase-change materials, where the metal-insulator transition is due to strong disorder usually associated only with amorphous solids. With pronounced disorder but weak electron correlation, these phase-change materials form an unparalleled quantum state of matter. Their universal electronic behaviour seems to be at the origin of the remarkable reproducibility of the resistance switching that is crucial to their applications in non-volatile-memory devices. Controlling the degree of disorder in crystalline phase-change materials might enable multilevel resistance states in upcoming storage devices.

Evaluation of phase transformation in ferromagnetic shape memory Fe-Pd alloy by magnetic Barkhausen noise

NASA Astrophysics Data System (ADS)

Furuya, Yasubumi; Tamoto, Shizuka; Kubota, Takeshi; Okazaki, Teiko; Hagood, Nesbitt W.; Spearing, S. Mark

2002-07-01

The possibility to detect the phase transformation with martensites by heating or cooling as well as stress-loading in ferromagnetic shape memory Fe-30at percent Pd alloy thin foil by using magnetic Markhausen noise sensor was studied. MBHN is caused by the irregular interactions between magnetic domain and thermally activated martensite twins during magnetization. In general, the envelope of the MBHN voltage versus time signals in Fe-29at percent Pd ribbon showed two peaks during magnetization, where secondary peak at intermediate state of magnetization process decreased with increasing temperature, while the MBHN envelopes in pure iron did not change with increasing temperature. The variety of MBHN due to the phase transformation was apt to arise at higher frequency part of spectrum during intermediate state of magnetization process and it decreased with disappearance of martensite twins. Besides, MBHN increased monotonically with increasing loading stress and then, it decreased with unloading, however MBHN showed large hysteresis between loading and unloading passes. Based on the experimental results from MBHN measurements for both thermoelastic and stress-induced martensite phase transformations in Fe-30at percent Pd ribbon samples, MBHN method seems a useful technique to non-destructive evaluation of martensite phase transformation of ferromagnetic shape memory alloy.

Subtle persistent working memory and selective attention deficits in women with premenstrual syndrome.

PubMed

Slyepchenko, Anastasiya; Lokuge, Sonali; Nicholls, Brianne; Steiner, Meir; Hall, Geoffrey B C; Soares, Claudio N; Frey, Benicio N

2017-03-01

As a recurrent, cyclical phenomenon, premenstrual syndrome (PMS) affects a significant proportion of women of the reproductive age, and leads to regular monthly days of functional impairment. Symptoms of PMS include somatic and psychological symptoms, such as headaches, sleep disturbances, social withdrawal and mood changes, during the late luteal phase of the menstrual cycle, which alleviate during the follicular phase. This study investigated neurocognitive functioning in women with moderate to severe PMS symptoms (n=13) compared to women with mild/no PMS (n=27) through administration of a battery of neuropsychological tests during the asymptomatic follicular phase of the menstrual cycle. Relative to women with mild/no PMS symptoms, women with moderate to severe PMS showed significantly poorer accuracy and more errors of omission on the N-0-back, as well as more errors of omission on the N-2-back task, indicating the presence of impairment in selective attention and working memory. This study provides evidence of persistent, subtle working memory and selective attention difficulties in those with moderate to severe PMS during the follicular phase of the menstrual cycle. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

The anti-caspase inhibitor Q-VD-OPH prevents AIDS disease progression in SIV-infected rhesus macaques.

PubMed

Laforge, Mireille; Silvestre, Ricardo; Rodrigues, Vasco; Garibal, Julie; Campillo-Gimenez, Laure; Mouhamad, Shahul; Monceaux, Valérie; Cumont, Marie-Christine; Rabezanahary, Henintsoa; Pruvost, Alain; Cordeiro-da-Silva, Anabela; Hurtrel, Bruno; Silvestri, Guido; Senik, Anna; Estaquier, Jérôme

2018-04-02

Apoptosis has been proposed as a key mechanism responsible for CD4+ T cell depletion and immune dysfunction during HIV infection. We demonstrated that Q-VD-OPH, a caspase inhibitor, inhibits spontaneous and activation-induced death of T cells from SIV-infected rhesus macaques (RMs). When administered during the acute phase of infection, Q-VD-OPH was associated with (a) reduced levels of T cell death, (b) preservation of CD4+/CD8+ T cell ratio in lymphoid organs and in the gut, (c) maintenance of memory CD4+ T cells, and (d) increased specific CD4+ T cell response associated with the expression of cytotoxic molecules. Although therapy was limited to the acute phase of infection, Q-VD-OPH-treated RMs showed lower levels of both viral load and cell-associated SIV DNA as compared with control SIV-infected RMs throughout the chronic phase of infection, and prevented the development of AIDS. Overall, our data demonstrate that Q-VD-OPH injection in SIV-infected RMs may represent an adjunctive therapeutic agent to control HIV infection and delaying disease progression to AIDS.

Probing Phase Transformations and Microstructural Evolutions at the Small Scales: Synchrotron X-ray Microdiffraction for Advanced Applications in [Phase 3 Memory,] 3D IC (Integrated Circuits) and Solar PV (Photovoltaic) Devices

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

Radchenko, I.; Tippabhotla, S. K.; Tamura, N.

2016-10-21

Synchrotron x-ray microdiffraction (μXRD) allows characterization of a crystalline material in small, localized volumes. Phase composition, crystal orientation and strain can all be probed in few-second time scales. Crystalline changes over a large areas can be also probed in a reasonable amount of time with submicron spatial resolution. However, despite all the listed capabilities, μXRD is mostly used to study pure materials but its application in actual device characterization is rather limited. This article will explore the recent developments of the μXRD technique illustrated with its advanced applications in microelectronic devices and solar photovoltaic systems. Application of μXRD in microelectronicsmore » will be illustrated by studying stress and microstructure evolution in Cu TSV (through silicon via) during and after annealing. Here, the approach allowing study of the microstructural evolution in the solder joint of crystalline Si solar cells due to thermal cycling will be also demonstrated.« less

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

PubMed Central

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

2012-01-01

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

Deciphering the role of CA1 inhibitory circuits in sharp wave-ripple complexes.

PubMed

Cutsuridis, Vassilis; Taxidis, Jiannis

2013-01-01

Sharp wave-ripples (SWRs) are population oscillatory patterns in hippocampal LFPs during deep sleep and immobility, involved in the replay of memories acquired during wakefulness. SWRs have been extensively studied, but their exact generation mechanism is still unknown. A computational model has suggested that fast perisomatic inhibition may generate the high frequency ripples (~200 Hz). Another model showed how replay of memories can be controlled by various classes of inhibitory interneurons targeting specific parts of pyramidal cells (PC) and firing at particular SWR phases. Optogenetic studies revealed new roles for interneuronal classes and rich dynamic interplays between them, shedding new light in their potential role in SWRs. Here, we integrate these findings in a conceptual model of how dendritic and somatic inhibition may collectively contribute to the SWR generation. We suggest that sharp wave excitation and basket cell (BC) recurrent inhibition synchronises BC spiking in ripple frequencies. This rhythm is imposed on bistratified cells which prevent pyramidal bursting. Axo-axonic and stratum lacunosum/moleculare interneurons are silenced by inhibitory inputs originating in the medial septum. PCs receiving rippling inhibition in both dendritic and perisomatic areas and excitation in their apical dendrites, exhibit sparse ripple phase-locked spiking.

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

PubMed Central

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

2016-01-01

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

Genome-wide chromatin and gene expression profiling during memory formation and maintenance in adult mice.

PubMed

Centeno, Tonatiuh Pena; Shomroni, Orr; Hennion, Magali; Halder, Rashi; Vidal, Ramon; Rahman, Raza-Ur; Bonn, Stefan

2016-10-11

Recent evidence suggests that the formation and maintenance of memory requires epigenetic changes. In an effort to understand the spatio-temporal extent of learning and memory-related epigenetic changes we have charted genome-wide histone and DNA methylation profiles, in two different brain regions, two cell types, and three time-points, before and after learning. In this data descriptor we provide detailed information on data generation, give insights into the rationale of experiments, highlight necessary steps to assess data quality, offer guidelines for future use of the data and supply ready-to-use code to replicate the analysis results. The data provides a blueprint of the gene regulatory network underlying short- and long-term memory formation and maintenance. This 'healthy' gene regulatory network of learning can now be compared to changes in neurological or psychiatric diseases, providing mechanistic insights into brain disorders and highlighting potential therapeutic avenues.

The unified mechanism of aging effects in both martensite and parent phase for shape-memory alloys: atomic-level simulations

NASA Astrophysics Data System (ADS)

Deng, J.; Ding, X.; Suzuki, T.; Otsuka, K.; Lookman, T.; Saxena, A.; Sun, J.; Ren, X.

2011-03-01

Most shape-memory alloys (SMAs) subject to the aging effects not only in the martensite phase but also in the parent phase. These aging effects have been attracted much attention as they strongly affect the practical applications of SMAs. So far, the intrinsic mechanism of them has remained controversial due to the difficulty in visualization of what happens in atomic scale. In the present study, by using a combination of molecular dynamics method and Monte-Carlo method [1], we investigate the aging effects in both martensite and parent phase. We successfully reproduced the thermal behaviors of aging effects for SMAs, i.e., the Af temperature increase with aging time in martensite and the Ms temperature decrease with aging time in parent phase, which keep good agreement with the experimental observations [2]. In addition, quantitative analysis of the atomic configurations during aging reveals that the aging effects are not associated with a change in the average structure.

W-Sb-Te phase-change material: A candidate for the trade-off between programming speed and data retention

NASA Astrophysics Data System (ADS)

Peng, Cheng; Wu, Liangcai; Rao, Feng; Song, Zhitang; Yang, Pingxiong; Song, Hongjia; Ren, Kun; Zhou, Xilin; Zhu, Min; Liu, Bo; Chu, Junhao

2012-09-01

W-Sb-Te phase-change material has been proposed to improve the performance of phase-change memory (PCM). Crystallization temperature, crystalline resistance, and 10-year data retention of Sb2Te increase markedly by W doping. The Wx(Sb2Te)1-x films crystallize quickly into a stable hexagonal phase with W uniformly distributing in the crystal lattice, which ensures faster SET speed and better operation stability for the application in practical device. PCM device based on W0.07(Sb2Te)0.93 shows ultrafast SET operation (6 ns) and good endurance (1.8 × 105 cycles). W-Sb-Te material is a promising candidate for the trade-off between programming speed and data retention.

Nicotinic modulation of hippocampal cell signaling and associated effects on learning and memory.

PubMed

Kutlu, Munir Gunes; Gould, Thomas J

2016-03-01

The hippocampus is a key brain structure involved in synaptic plasticity associated with long-term declarative memory formation. Importantly, nicotine and activation of nicotinic acetylcholine receptors (nAChRs) can alter hippocampal plasticity and these changes may occur through modulation of hippocampal kinases and transcription factors. Hippocampal kinases such as cAMP-dependent protein kinase (PKA), calcium/calmodulin-dependent protein kinases (CAMKs), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and c-jun N-terminal kinase 1 (JNK1), and the transcription factor cAMP-response element-binding protein (CREB) that are activated either directly or indirectly by nicotine may modulate hippocampal plasticity and in parallel hippocampus-dependent learning and memory. Evidence suggests that nicotine may alter hippocampus-dependent learning by changing the time and magnitude of activation of kinases and transcription factors normally involved in learning and by recruiting additional cell signaling molecules. Understanding how nicotine alters learning and memory will advance basic understanding of the neural substrates of learning and aid in understanding mental disorders that involve cognitive and learning deficits. Copyright © 2015 Elsevier Inc. All rights reserved.

Memory Dynamics in Cross-linked Actin Networks

NASA Astrophysics Data System (ADS)

Scheff, Danielle; Majumdar, Sayantan; Gardel, Margaret

Cells demonstrate the remarkable ability to adapt to mechanical stimuli through rearrangement of the actin cytoskeleton, a cross-linked network of actin filaments. In addition to its importance in cell biology, understanding this mechanical response provides strategies for creation of novel materials. A recent study has demonstrated that applied stress can encode mechanical memory in these networks through changes in network geometry, which gives rise to anisotropic shear response. Under later shear, the network is stiffer in the direction of the previously applied stress. However, the dynamics behind the encoding of this memory are unknown. To address this question, we explore the effect of varying either the rigidity of the cross-linkers or the length of actin filament on the time scales required for both memory encoding and over which it later decays. While previous experiments saw only a long-lived memory, initial results suggest another mechanism where memories relax relatively quickly. Overall, our study is crucial for understanding the process by which an external stress can impact network arrangement and thus the dynamics of memory formation.

Decreased Load on General Motor Preparation and Visual-Working Memory while Preparing Familiar as Compared to Unfamiliar Movement Sequences

ERIC Educational Resources Information Center

De Kleine, Elian; Van der Lubbe, Rob H. J.

2011-01-01

Learning movement sequences is thought to develop from an initial controlled attentive phase to a more automatic inattentive phase. Furthermore, execution of sequences becomes faster with practice, which may result from changes at a general motor processing level rather than at an effector specific motor processing level. In the current study, we…

Mechanical and Infrared Thermography Analysis of Shape Memory Polyurethane

NASA Astrophysics Data System (ADS)

Pieczyska, Elzbieta Alicja; Maj, Michal; Kowalczyk-Gajewska, Katarzyna; Staszczak, Maria; Urbanski, Leszek; Tobushi, Hisaaki; Hayashi, Shunichi; Cristea, Mariana

2014-07-01

Multifunctional new material—polyurethane shape memory polymer (PU-SMP)—was subjected to tension carried out at room temperature at various strain rates. The influence of effects of thermomechanical couplings on the SMP mechanical properties was studied, based on the sample temperature changes, measured by a fast and sensitive infrared camera. It was found that the polymer deformation process strongly depends on the strain rate applied. The initial reversible strain is accompanied by a small drop in temperature, called thermoelastic effect. Its maximal value is related to the SMP yield point and increases upon increase of the strain rate. At higher strains, the stress and temperature significantly increase, caused by reorientation of the polymer molecular chains, followed by the stress drop and its subsequent increase accompanying the sample rupture. The higher strain rate, the higher stress, and temperature changes were obtained, since the deformation process was more dynamic and has occurred in almost adiabatic conditions. The constitutive model of SMP valid in finite strain regime was developed. In the proposed approach, SMP is described as a two-phase material composed of hyperelastic rubbery phase and elastic-viscoplastic glassy phase, while the volume content of phases is specified by the current temperature.

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

PubMed

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

2017-10-10

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

Magneto-optical spectroscopy of ferromagnetic shape-memory Ni-Mn-Ga alloy

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

Veis, M., E-mail: veis@karlov.mff.cuni.cz; Beran, L.; Zahradnik, M.

2014-05-07

Magneto-optical properties of single crystal of Ni{sub 50.1}Mn{sub 28.4}Ga{sub 21.5} magnetic shape memory alloy in martensite and austenite phase were systematically studied. Crystal orientation was approximately along (100) planes of parent cubic austenite. At room temperature, the sample was in modulated 10M martensite phase and transformed to cubic austenite at 323 K. Spectral dependence of polar magneto-optical Kerr effect was obtained by generalized magneto-optical ellipsometry with rotating analyzer in the photon energy range from 1.2 to 4 eV, and from room temperature to temperature above the Curie point. The Kerr rotation spectra exhibit prominent features typical for complexes containing Mn atoms. Significantmore » spectral changes during transformation to austenite can be explained by different optical properties caused by changes in density of states near the Fermi energy.« less

Beneficial Effects of cART Initiated during Primary and Chronic HIV-1 Infection on Immunoglobulin-Expression of Memory B-Cell Subsets

PubMed Central

Pensieroso, Simone; Tolazzi, Monica; Chiappetta, Stefania; Nozza, Silvia; Lazzarin, Adriano; Tambussi, Giuseppe; Scarlatti, Gabriella

2015-01-01

Introduction During HIV-1 infection the B-cell compartment undergoes profound changes towards terminal differentiation, which are only partially restored by antiretroviral therapy (cART). Materials and Methods To investigate the impact of infection as early as during primary HIV-1 infection (PHI) we assessed distribution of B-cell subsets in 19 PHI and 25 chronic HIV-1-infected (CHI) individuals before and during 48 weeks of cART as compared to healthy controls (n = 23). We also analysed Immunoglobulin-expression of memory B-cell subsets to identify alterations in Immunoglobulin-maturation. Results Determination of B-cell subsets at baseline showed that total and Naive B-cells were decreased whereas Activated Memory (AM), Tissue-like Memory (TLM) B-cells and Plasma cells were increased in both PHI and CHI patients. After 4 weeks of cART total B-cells increased, while AM, TLM B-cells and Plasma cells decreased, although without reaching normal levels in either group of individuals. This trend was maintained until week 48, though only total B-cells normalized in both PHI and CHI. Resting Memory (RM) B-cells were preserved since baseline. This subset remained stable in CHI, while was expanded by an early initiation of cART during PHI. Untreated CHI patients showed IgM-overexpression at the expenses of switched (IgM-IgD-) phenotypes of the memory subsets. Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets. After 48 weeks of therapy, Immunoglobulin-expression of AM and RM almost normalized, but remained perturbed in TLM cells in both groups. Conclusions In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART. After 48 weeks of cART B-cell subsets distribution improved although without full normalization, while Immunoglobulin-expression normalized among AM and RM, remaining perturbed in TLM B-cells of PHI and CHI. PMID:26474181

Beneficial Effects of cART Initiated during Primary and Chronic HIV-1 Infection on Immunoglobulin-Expression of Memory B-Cell Subsets.

PubMed

Pogliaghi, Manuela; Ripa, Marco; Pensieroso, Simone; Tolazzi, Monica; Chiappetta, Stefania; Nozza, Silvia; Lazzarin, Adriano; Tambussi, Giuseppe; Scarlatti, Gabriella

2015-01-01

During HIV-1 infection the B-cell compartment undergoes profound changes towards terminal differentiation, which are only partially restored by antiretroviral therapy (cART). To investigate the impact of infection as early as during primary HIV-1 infection (PHI) we assessed distribution of B-cell subsets in 19 PHI and 25 chronic HIV-1-infected (CHI) individuals before and during 48 weeks of cART as compared to healthy controls (n = 23). We also analysed Immunoglobulin-expression of memory B-cell subsets to identify alterations in Immunoglobulin-maturation. Determination of B-cell subsets at baseline showed that total and Naive B-cells were decreased whereas Activated Memory (AM), Tissue-like Memory (TLM) B-cells and Plasma cells were increased in both PHI and CHI patients. After 4 weeks of cART total B-cells increased, while AM, TLM B-cells and Plasma cells decreased, although without reaching normal levels in either group of individuals. This trend was maintained until week 48, though only total B-cells normalized in both PHI and CHI. Resting Memory (RM) B-cells were preserved since baseline. This subset remained stable in CHI, while was expanded by an early initiation of cART during PHI. Untreated CHI patients showed IgM-overexpression at the expenses of switched (IgM-IgD-) phenotypes of the memory subsets. Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets. After 48 weeks of therapy, Immunoglobulin-expression of AM and RM almost normalized, but remained perturbed in TLM cells in both groups. In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART. After 48 weeks of cART B-cell subsets distribution improved although without full normalization, while Immunoglobulin-expression normalized among AM and RM, remaining perturbed in TLM B-cells of PHI and CHI.

Dichroic Liquid Crystal Displays

NASA Astrophysics Data System (ADS)

Bahadur, Birendra

The following sections are included: * INTRODUCTION * DICHROIC DYES * Chemical Structure * Chemical and Photochemical Stability * THEORETICAL MODELLING * DEFECTS CAUSED BY PROLONGED LIGHT IRRADIATION * CHEMICAL STRUCTURE AND PHOTOSTABILITY * OTHER PARAMETERS AFFECTING PHOTOSTABILITY * CELL PREPARATION * DICHROIC PARAMETERS AND THEIR MEASUREMENTS * Order Parameter and Dichroic Ratio Of Dyes * Absorbance, Order Parameter and Dichroic Ratio Measurements * IMPACT OF DYE STRUCTURE AND LIQUID CRYSTAL HOST ON PHYSICAL PROPERTIES OF A DICHROIC MIXTURE * Order Parameter and Dichroic Ratio * EFFECT OF LENGTH OF DICHROIC DYES ON THE ORDER PARAMETER * EFFECT OF THE BREADTH OF DYE ON THE ORDER PARAMETER * EFFECT OF THE HOST ON THE ORDER PARAMETER * TEMPERATURE VARIATION OF THE ORDER PARAMETER OF DYES IN A LIQUID CRYSTAL HOST * IMPACT OF DYE CONCENTRATION ON THE ORDER PARAMETER * Temperature Range * Viscosity * Dielectric Constant and Anisotropy * Refractive Indices and Birefringence * solubility43,153-156 * Absorption Wavelength and Auxochromic Groups * Molecular Engineering of Dichroic Dyes * OPTICAL, ELECTRO-OPTICAL AND LIFE PARAMETERS * Colour And CIE Colour space120,160-166 * CIE 1931 COLOUR SPACE * CIE 1976 CHROMATICITY DIAGRAM * CIE UNIFORM COLOUR SPACES & COLOUR DIFFERENCE FORMULAE120,160-166 * Electro-Optical Parameters120 * LUMINANCE * CONTRAST AND CONTRAST RATIO * SWITCHING SPEED * Life Parameters and Failure Modes * DICHROIC MIXTURE FORMULATION * Monochrome Mixture * Black Mixture * ACHROMATIC BLACK MIXTURE FOR HEILMEIER DISPLAYS * Effect of Illuminant on Display Colour * Colour of the Field-On State * Effect of Dye Linewidth * Optimum Centroid Wavelengths * Effect of Dye Concentration * Mixture Formulation Using More Than Three Dyes * ACHROMATIC MIXTURE FOR WHITE-TAYLOR TYPE DISPLAYS * HEILMEIER DISPLAYS * Theoretical Modelling * Threshold Characteristic * Effects of Dye Concentration on Electro-optical Parameters * Effect of Cholesteric Doping * Effect of Alignment * Effect of Thickness * Impact of Order Parameter * Impact of the Host * Impact of Polarizer * Colour Applications * Multiplexing * QUARTER WAVE PLATE DICHROIC DISPLAYS * Operational Principle and Display Configuration11-13 * Electro-Optical Performance * DYE-DOPED TN DISPLAYS * Threshold Characteristic, Contrast Ratio and Switching Speed * PHASE CHANGE EFFECT DICHROIC LCDs * Theoretical Background * Threshold Characteristic and Molecular Orientation * MOLECULAR ORIENTATION DURING FIELD-INDUCED PHASE TRANSITION WITH HOMOGENEOUS WALL ALIGNMENT * MOLECULAR ORIENTATION DURING FIELD-INDUCED PHASE TRANSITION WITH HOMEOTROPIC WALL ALIGNMENT * Contrast Ratio, Transmission, Brightness and Switching Speed3,7,10,198-214 * Memory or Reminiscent Contrast * Electro-optical Performance vs. Temperature * Multiplexing Phase Change Dichroic LCDs * DOUBLE CELL DICHROIC LCDs3,9,14-17,232-234 * Double Cell Nematic Dichroic LCD3,8,9,14,15,233 * Double Cell One Pitch Cholesteric LCD16,17 * Double Cell Phase Change Dichroic LCD214,232 * POSITIVE MODE DICHROIC LCDS3,8,9 * Positive Mode Heilmeier Cells3,8,9,43,77,78,235-238 * USING PLEOCHROIC DYES3,8,9,43,235-238 * USING NEGATIVE DICHROIC DYES3,8,9,63,77,78156 * DUAL FREQUENCY ADDRESSED DICHROIC DISPLAYS75,238 * Positive Mode Dichroic LCDs Using λ/4 Plate * Positive Mode Double Cell Dichroic LCD * Positive Mode Dichroic LCDs Using Special Electrode patterns7,8,239-241 * Positive Mode Phase Change Dichroic LCDs3,8,9,230,243-248 * Dichroic LCDs Using an Admixture of Pleochroic and Negative Dichroic Dyes78,118 * SUPERTWIST DICHROIC EFFECT (SDE) DISPLAYS21-23 * FERROELECTRIC DICHROIC LCDs24-27 * Devices Using A Single Polarizer * Devices Using No Polarizer24-27 * POLYMER DISPERSED DICHROIC LCDs28-30,252-259 * DICHROIC POLYMER LIQUID CRYSTAL DISPLAYS * Heilmeier Type Displays * Guest-Host Cell Using an Admixture Of L.C. Polymer and Low Molecular Weight Liquid Crysta As Host * Polymeric Ferroelectric Dichroic LCDs * SMECTIC A DICHROIC LCDs * Laser Addressed Dichroic SA Displays * Thermally and Electrically Addressed Dichroic SA Displays * FLUORESCENT DICHROIC LCDs * ACKNOWLEDGEMENTS * REFERENCES

An ultra-fast optical shutter exploiting total light absorption in a phase change material

NASA Astrophysics Data System (ADS)

Jafari, Mohsen; Guo, L. Jay; Rais-Zadeh, Mina

2017-02-01

In this paper, we present an ultra-fast and high-contrast optical shutter with applications in atomic clock assemblies, integrated photonic systems, communication hardware, etc. The shutter design exploits the total light absorption phenomenon in a thin phase change (PC) material placed over a metal layer. The shutter switches between ON and OFF states by changing PC material phase and thus its refractive index. The PC material used in this work is Germanium Telluride (GeTe), a group IV-VI chalcogenide compound, which exhibits good optical contrast when switching from amorphous to crystalline state and vice versa. The stable phase changing behavior and reliability of GeTe and GeSbTe (GST) have been verified in optical memories and RF switches. Here, GeTe is used as it has a lower extinction coefficient in near-IR regions compared to GST. GeTe can be thermally transitioned between two phases by applying electrical pulses to an integrated heater. The memory behavior of GeTe results in zero static power consumption which is useful in applications requiring long time periods between switching activities. We previously demonstrated a meta-surface employing GeTe in sub-wavelength slits with >14 dB isolation at 1.5 μm by exciting the surface plasmon polariton and localized slit resonances. In this work, strong interference effects in a thin layer of GeTe over a gold mirror result in near total light absorption of up to 40 dB (21 dB measured) in the amorphous phase of the shutter at 780 nm with much less fabrication complexity. The optical loss at the shutter ON state is less than 1.5 dB. A nickel chrome (NiCr) heater provides the Joule heating energy required to achieve the crystallographic phase change. The measured switching speed is 2 μs.

Properties of TiNi intermetallic compound industrially produced by combustion synthesis

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

Kaieda, Yoshinari

Most TiNi shape memory intermetallic compounds are conventionally produced by the process including high frequency induction vacuum melting and casting. A gravity segregation occurs in a cast TiNi ingot because of the big difference in the specific gravity between Ti and Ni. It is difficult to control accurately the phase transformation temperature of TiNi shape memory intermetallic compound produced by the conventional process, because the martensitic transformation temperature shifts by 10K due to the change in 0.1 % of Ni content. Homogeneous TiNi intermetallic compound is produced by the industrial process including combustion synthesis method, which is a newly developedmore » manufacturing process. In the new process, phase transformation temperatures of TiNi can be controlled accurately by controlling the ratio of Ti and Ni elemental starting powders. The chemical component, the impurities and the phase transformation temperatures of the TiNi products industrially produced by the process are revealed. These properties are vitally important when combustion synthesis method is applied to an industrial mass production process for producing TiNi shape memory intermetallic compounds. TiNi shape memory products are industrially and commercially produced today the industrial process including combustion synthesis. The total production weight in a year is 30 tins in 1994.« less

Ki-67 expression reveals strong, transient influenza specific CD4 T cell responses after adult vaccination.

PubMed

Li, Xi; Miao, Hongyu; Henn, Alicia; Topham, David J; Wu, Hulin; Zand, Martin S; Mosmann, Tim R

2012-06-29

Although previous studies have found minimal changes in CD4 T cell responses after vaccination of adults with trivalent inactivated influenza vaccine, daily sampling and monitoring of the proliferation marker Ki-67 have now been used to reveal that a substantial fraction of influenza-specific CD4 T cells respond to vaccination. At 4-6 days after vaccination, there is a sharp rise in the numbers of Ki-67-expressing PBMC that produce IFNγ, IL-2 and/or TNFα in vitro in response to influenza vaccine or peptide. Ki-67(+) cell numbers then decline rapidly, and 10 days after vaccination, both Ki-67(+) and overall influenza-specific cell numbers are similar to pre-vaccination levels. These results provide a tool for assessing the quality and quantity of CD4 T cell responses to different influenza vaccines, and raise the possibility that the anti-influenza T cell memory response may be qualitatively altered by vaccination, even if the overall memory cell numbers do not change significantly. Copyright © 2012. Published by Elsevier Ltd.

A brain-computer interface based cognitive training system for healthy elderly: a randomized control pilot study for usability and preliminary efficacy.

PubMed

Lee, Tih-Shih; Goh, Siau Juinn Alexa; Quek, Shin Yi; Phillips, Rachel; Guan, Cuntai; Cheung, Yin Bun; Feng, Lei; Teng, Stephanie Sze Wei; Wang, Chuan Chu; Chin, Zheng Yang; Zhang, Haihong; Ng, Tze Pin; Lee, Jimmy; Keefe, Richard; Krishnan, K Ranga Rama

2013-01-01

Cognitive decline in aging is a pressing issue associated with significant healthcare costs and deterioration in quality of life. Previously, we reported the successful use of a novel brain-computer interface (BCI) training system in improving symptoms of attention deficit hyperactivity disorder. Here, we examine the feasibility of the BCI system with a new game that incorporates memory training in improving memory and attention in a pilot sample of healthy elderly. This study investigates the safety, usability and acceptability of our BCI system to elderly, and obtains an efficacy estimate to warrant a phase III trial. Thirty-one healthy elderly were randomized into intervention (n = 15) and waitlist control arms (n = 16). Intervention consisted of an 8-week training comprising 24 half-hour sessions. A usability and acceptability questionnaire was administered at the end of training. Safety was investigated by querying users about adverse events after every session. Efficacy of the system was measured by the change of total score from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) before and after training. Feedback on the usability and acceptability questionnaire was positive. No adverse events were reported for all participants across all sessions. Though the median difference in the RBANS change scores between arms was not statistically significant, an effect size of 0.6SD was obtained, which reflects potential clinical utility according to Simon's randomized phase II trial design. Pooled data from both arms also showed that the median change in total scores pre and post-training was statistically significant (Mdn = 4.0; p<0.001). Specifically, there were significant improvements in immediate memory (p = 0.038), visuospatial/constructional (p = 0.014), attention (p = 0.039), and delayed memory (p<0.001) scores. Our BCI-based system shows promise in improving memory and attention in healthy elderly, and appears to be safe, user-friendly and acceptable to senior users. Given the efficacy signal, a phase III trial is warranted. ClinicalTrials.gov NCT01661894.

Protection by and maintenance of CD4 effector memory and effector T cell subsets in persistent malaria infection.

PubMed

Opata, Michael M; Ibitokou, Samad A; Carpio, Victor H; Marshall, Karis M; Dillon, Brian E; Carl, Jordan C; Wilson, Kyle D; Arcari, Christine M; Stephens, Robin

2018-04-01

Protection at the peak of Plasmodium chabaudi blood-stage malaria infection is provided by CD4 T cells. We have shown that an increase in Th1 cells also correlates with protection during the persistent phase of malaria; however, it is unclear how these T cells are maintained. Persistent malaria infection promotes protection and generates both effector T cells (Teff), and effector memory T cells (Tem). We have previously defined new CD4 Teff (IL-7Rα-) subsets from Early (TeffEarly, CD62LhiCD27+) to Late (TeffLate, CD62LloCD27-) activation states. Here, we tested these effector and memory T cell subsets for their ability to survive and protect in vivo. We found that both polyclonal and P. chabaudi Merozoite Surface Protein-1 (MSP-1)-specific B5 TCR transgenic Tem survive better than Teff. Surprisingly, as Tem are associated with antigen persistence, Tem survive well even after clearance of infection. As previously shown during T cell contraction, TeffEarly, which can generate Tem, also survive better than other Teff subsets in uninfected recipients. Two other Tem survival mechanisms identified here are that low-level chronic infection promotes Tem both by driving their proliferation, and by programming production of Tem from Tcm. Protective CD4 T cell phenotypes have not been precisely determined in malaria, or other persistent infections. Therefore, we tested purified memory (Tmem) and Teff subsets in protection from peak pathology and parasitemia in immunocompromised recipient mice. Strikingly, among Tmem (IL-7Rαhi) subsets, only TemLate (CD62LloCD27-) reduced peak parasitemia (19%), though the dominant memory subset is TemEarly, which is not protective. In contrast, all Teff subsets reduced peak parasitemia by more than half, and mature Teff can generate Tem, though less. In summary, we have elucidated four mechanisms of Tem maintenance, and identified two long-lived T cell subsets (TemLate, TeffEarly) that may represent correlates of protection or a target for longer-lived vaccine-induced protection against malaria blood-stages.

Astrocyte glycogen and lactate: New insights into learning and memory mechanisms.

PubMed

Alberini, Cristina M; Cruz, Emmanuel; Descalzi, Giannina; Bessières, Benjamin; Gao, Virginia

2018-06-01

Memory, the ability to retain learned information, is necessary for survival. Thus far, molecular and cellular investigations of memory formation and storage have mainly focused on neuronal mechanisms. In addition to neurons, however, the brain comprises other types of cells and systems, including glia and vasculature. Accordingly, recent experimental work has begun to ask questions about the roles of non-neuronal cells in memory formation. These studies provide evidence that all types of glial cells (astrocytes, oligodendrocytes, and microglia) make important contributions to the processing of encoded information and storing memories. In this review, we summarize and discuss recent findings on the critical role of astrocytes as providers of energy for the long-lasting neuronal changes that are necessary for long-term memory formation. We focus on three main findings: first, the role of glucose metabolism and the learning- and activity-dependent metabolic coupling between astrocytes and neurons in the service of long-term memory formation; second, the role of astrocytic glucose metabolism in arousal, a state that contributes to the formation of very long-lasting and detailed memories; and finally, in light of the high energy demands of the brain during early development, we will discuss the possible role of astrocytic and neuronal glucose metabolisms in the formation of early-life memories. We conclude by proposing future directions and discussing the implications of these findings for brain health and disease. Astrocyte glycogenolysis and lactate play a critical role in memory formation. Emotionally salient experiences form strong memories by recruiting astrocytic β2 adrenergic receptors and astrocyte-generated lactate. Glycogenolysis and astrocyte-neuron metabolic coupling may also play critical roles in memory formation during development, when the energy requirements of brain metabolism are at their peak. © 2017 Wiley Periodicals, Inc.

Impairment of working memory maintenance and response in schizophrenia: functional magnetic resonance imaging evidence.

PubMed

Driesen, Naomi R; Leung, Hoi-Chung; Calhoun, Vincent D; Constable, R Todd; Gueorguieva, Ralitza; Hoffman, Ralph; Skudlarski, Pawel; Goldman-Rakic, Patricia S; Krystal, John H

2008-12-15

Comparing prefrontal cortical activity during particular phases of working memory in healthy subjects and individuals diagnosed with schizophrenia might help to define the phase-specific deficits in cortical function that contribute to cognitive impairments associated with schizophrenia. This study featured a spatial working memory task, similar to that used in nonhuman primates, that was designed to facilitate separating brain activation into encoding, maintenance, and response phases. Fourteen patients with schizophrenia (4 medication-free) and 12 healthy comparison participants completed functional magnetic resonance imaging while performing a spatial working memory task with two levels of memory load. Task accuracy was similar in patients and healthy participants. However, patients showed reductions in brain activation during maintenance and response phases but not during the encoding phase. The reduced prefrontal activity during the maintenance phase of working memory was attributed to a greater rate of decay of prefrontal activity over time in patients. Cortical deficits in patients did not appear to be related to antipsychotic treatment. In patients and in healthy subjects, the time-dependent reduction in prefrontal activity during working memory maintenance correlated with poorer performance on the memory task. Overall, these data highlight that basic research insights into the distinct neurobiologies of the maintenance and response phases of working memory are of potential importance for understanding the neurobiology of cognitive impairment in schizophrenia and advancing its treatment.

Porous NiTi shape memory alloys produced by SHS: microstructure and biocompatibility in comparison with Ti2Ni and TiNi3.

PubMed

Bassani, Paola; Panseri, Silvia; Ruffini, Andrea; Montesi, Monica; Ghetti, Martina; Zanotti, Claudio; Tampieri, Anna; Tuissi, Ausonio

2014-10-01

Shape memory alloys based on NiTi have found their main applications in manufacturing of new biomedical devices mainly in surgery tools, stents and orthopedics. Porous NiTi can exhibit an engineering elastic modulus comparable to that of cortical bone (12-17 GPa). This condition, combined with proper pore size, allows good osteointegration. Open cells porous NiTi was produced by self propagating high temperature synthesis (SHS), starting from Ni and Ti mixed powders. The main NiTi phase is formed during SHS together with other Ni-Ti compounds. The biocompatibility of such material was investigated by single culture experiment and ionic release on small specimen. In particular, NiTi and porous NiTi were evaluated together with elemental Ti and Ni reference metals and the two intermetallic TiNi3, Ti2Ni phases. This approach permitted to clearly identify the influence of secondary phases in porous NiTi materials and relation with Ni-ion release. The results indicated, apart the well-known high toxicity of Ni, also toxicity of TiNi3, whilst phases with higher Ti content showed high biocompatibility. A slightly reduced biocompatibility of porous NiTi was ascribed to combined effect of TiNi3 presence and topography that requires higher effort for the cells to adapt to the surface.

Inter-individual Differences in Exercise-Induced Spatial Working Memory Improvement: A Near-Infrared Spectroscopy Study.

PubMed

Yamazaki, Yudai; Sato, Daisuke; Yamashiro, Koya; Tsubaki, Atsuhiro; Yamaguchi, Yui; Takehara, Nana; Maruyama, Atsuo

2017-01-01

Acute aerobic exercise at a mild intensity improves cognitive function. However, the response to exercise exhibits inter-individual differences, and the mechanisms underlying these differences remain unclear. The objective of this study was to determine potential factors in the brain that underlie differential responses to exercise in terms of cognitive improvement using functional near-infrared spectroscopy. Fourteen healthy subjects participated in these experiments. Participants performed a low intensity cycling exercise at 30% maximal oxygen uptake (VO 2peak ) for 10 min and performed a spatial memory task before and after exercising (5 and 30 min). The spatial memory task comprised two levels of difficulty (low: 1-dot EXERCISE, high: 3-dot EXERCISE). Cortical oxy-hemoglobin (O 2 Hb) levels were recorded using near-infrared spectroscopy during both the exercise and the spatial memory task phases. Regions of interests included the dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), and frontopolar area (FPA). The participants were divided into two groups depending on whether they were responders (improved task reaction time) or non-responders (no improvement). Subsequently, we analyzed the group characteristics and differences in the change in O 2 Hb levels during exercise and spatial working memory tasks. Acute mild exercise significantly improved mean reaction times in the 1-dot memory task but not in the 3-dot task across the participants. In the 1-dot EXERCISE, 10 subjects were responders and four subjects were non-responders, whereas in the 3-dot EXERCISE, seven subjects were non-responders. In responders, during exercise, we found higher O 2 Hb levels in the right VLPFC response for the 1-dot memory task. Acute mild exercise caused inter-individual differences in spatial memory improvement, which were associated with changes in O 2 Hb activity in the prefrontal area during the exercise phase but not during the actual spatial memory task. Therefore, individuals who respond with higher reactivity to mild intensity exercise in the VLPFC might obtain larger spatial working memory improvements following exercise than non-responders.

Prior Dengue Virus Exposure Shapes T Cell Immunity to Zika Virus in Humans

PubMed Central

Grifoni, Alba; Pham, John; Sidney, John; O'Rourke, Patrick H.; Paul, Sinu; Peters, Bjoern; Martini, Sheridan R.; de Silva, Aruna D.; Ricciardi, Michael J.; Silveira, Cassia G. T.; Maestri, Alvino; Costa, Priscilla R.; de-Oliveira-Pinto, Luzia Maria; de Azeredo, Elzinandes Leal; Damasco, Paulo Vieira; Phillips, Elizabeth; Mallal, Simon; de Silva, Aravinda M.; Collins, Matthew; Durbin, Anna; Diehl, Sean A.; Cerpas, Cristhiam; Balmaseda, Angel; Kuan, Guillermina; Coloma, Josefina; Harris, Eva; Crowe, James E.; Stone, Mars; Busch, Michael; Vivanco-Cid, Hector; Cox, Josephine; Graham, Barney S.; Ledgerwood, Julie E.; Turtle, Lance; Solomon, Tom; Kallas, Esper G.; Watkins, David I.; Weiskopf, Daniela

2017-01-01

ABSTRACT While progress has been made in characterizing humoral immunity to Zika virus (ZIKV) in humans, little is known regarding the corresponding T cell responses to ZIKV. Here, we investigate the kinetics and viral epitopes targeted by T cells responding to ZIKV and address the critical question of whether preexisting dengue virus (DENV) T cell immunity modulates these responses. We find that memory T cell responses elicited by prior infection with DENV or vaccination with tetravalent dengue attenuated vaccines (TDLAV) recognize ZIKV-derived peptides. This cross-reactivity is explained by the sequence similarity of the two viruses, as the ZIKV peptides recognized by DENV-elicited memory T cells are identical or highly conserved in DENV and ZIKV. DENV exposure prior to ZIKV infection also influences the timing and magnitude of the T cell response. ZIKV-reactive T cells in the acute phase of infection are detected earlier and in greater magnitude in DENV-immune patients. Conversely, the frequency of ZIKV-reactive T cells continues to rise in the convalescent phase in DENV-naive donors but declines in DENV-preexposed donors, compatible with more efficient control of ZIKV replication and/or clearance of ZIKV antigen. The quality of responses is also influenced by previous DENV exposure, and ZIKV-specific CD8 T cells from DENV-preexposed donors selectively upregulated granzyme B and PD1, unlike DENV-naive donors. Finally, we discovered that ZIKV structural proteins (E, prM, and C) are major targets of both the CD4 and CD8 T cell responses, whereas DENV T cell epitopes are found primarily in nonstructural proteins. IMPORTANCE The issue of potential ZIKV and DENV cross-reactivity and how preexisting DENV T cell immunity modulates Zika T cell responses is of great relevance, as the two viruses often cocirculate and Zika virus has been spreading in geographical regions where DENV is endemic or hyperendemic. Our data show that memory T cell responses elicited by prior infection with DENV recognize ZIKV-derived peptides and that DENV exposure prior to ZIKV infection influences the timing, magnitude, and quality of the T cell response. Additionally, we show that ZIKV-specific responses target different proteins than DENV-specific responses, pointing toward important implications for vaccine design against this global threat. PMID:28978707

Prior Dengue virus exposure shapes T cell immunity to Zika virus in humans.

PubMed

Grifoni, Alba; Pham, John; Sidney, John; O'Rourke, Patrick H; Paul, Sinu; Peters, Bjoern; Martini, Sheridan R; de Silva, Aruna D; Ricciardi, Michael J; Magnani, Diogo M; Silveira, Cassia G T; Maestri, Alvino; Costa, Priscilla R; de-Oliveira-Pinto, Luzia Maria; de Azeredo, Elzinandes Leal; Damasco, Paulo Vieira; Phillips, Elizabeth; Mallal, Simon; de Silva, Aravinda M; Collins, Matthew; Durbin, Anna; Diehl, Sean A; Cerpas, Cristhiam; Balmaseda, Angel; Kuan, Guillermina; Coloma, Josefina; Harris, Eva; Crowe, James E; Stone, Mars; Norris, Phillip J; Busch, Michael; Vivanco-Cid, Hector; Cox, Josephine; Graham, Barney S; Ledgerwood, Julie E; Turtle, Lance; Solomon, Tom; Kallas, Esper G; Watkins, David I; Weiskopf, Daniela; Sette, Alessandro

2017-10-04

While progress has been made in characterizing humoral immunity to Zika virus (ZIKV) in humans, little is known regarding the corresponding T cell responses to ZIKV. Here we investigate the kinetics and viral epitopes targeted by T cells responding to ZIKV and address the critical question of whether pre-existing dengue virus (DENV) T cell immunity modulates these responses. We find that memory T cell responses elicited by prior infection with DENV or vaccination with Tetravalent Dengue Attenuated Vaccines (TDLAV) recognize ZIKV-derived peptides. This cross-reactivity is explained by the sequence similarity of the two viruses, as the ZIKV peptides recognized by DENV-elicited memory T cells are identical or highly conserved in DENV and ZIKV. DENV exposure prior to ZIKV infection also influences the timing and magnitude of the T cell response. ZIKV-reactive T cells in the acute phase of infection are detected earlier and in greater magnitude in DENV-immune patients. Conversely, the frequency of ZIKV-reactive T cells continues to rise in the convalescent phase in DENV-naive donors, but declines in DENV pre-exposed donors, compatible with more efficient control of ZIKV replication and/or clearance of ZIKV antigen. The quality of responses is also influenced by previous DENV exposure, and ZIKV-specific CD8 T cells form DENV pre-exposed donors selectively up-regulated granzyme B and PD1, as compared to DENV-naïve donors. Finally, we discovered that ZIKV structural proteins (E, prM and C) are major targets of both the CD4 and CD8 T cell responses, whereas DENV T cell epitopes are found primarily in nonstructural proteins. IMPORTANCE The issue of potential ZIKV and DENV cross-reactivity and how pre-existing DENV T cell immunity modulates ZIKA T cell responses is of great relevance as the two viruses often co-circulate and ZIKA virus has been spreading in geographical regions where DENV is endemic or hyper-endemic. Our data show that memory T cell responses elicited by prior infection with DENV recognize ZIKV-derived peptides and that DENV exposure prior to ZIKV infection influences the timing, magnitude and quality of the T cell response. Additionally we show that ZIKV-specific responses target different proteins than DENV-specific responses, pointing towards important implications for vaccine design against this global threat. Copyright © 2017 American Society for Microbiology.

Changes in endometrial natural killer cell expression of CD94, CD158a and CD158b are associated with infertility.

PubMed

McGrath, Emma; Ryan, Elizabeth J; Lynch, Lydia; Golden-Mason, Lucy; Mooney, Eoghan; Eogan, Maeve; O'Herlihy, Colm; O'Farrelly, Cliona

2009-04-01

Cycle-dependent fluctuations in natural killer (NK) cell populations in endometrium and circulation may differ, contributing to unexplained infertility. NK cell phenotypes were determined by flow cytometry in endometrial biopsies and matched blood samples. While circulating and endometrial T cell populations remained constant throughout the menstrual cycle in fertile and infertile women, circulating NK cells in infertile women increased during the secretory phase. However, increased expression of CD94, CD158b (secretory phase), and CD158a (proliferative phase) by endometrial NK cells from infertile women was observed. These changes were not reflected in the circulation. In infertile women, changes in circulating NK cell percentages are found exclusively during the secretory phase and not in endometrium; cycle-related changes in NK receptor expression are observed only in infertile endometrium. While having exciting implications for understanding NK cell function in fertility, our data emphasize the difficulty in attaching diagnostic or prognostic significance to NK cell analyses in individual patients.

In silico optimization of phase-change materials for digital memories: a survey of first-row transition-metal dopants for Ge₂Sb₂Te₅.

PubMed

Skelton, J M; Elliott, S R

2013-05-22

Phase-change materials are the alloys at the heart of an emerging class of next-generation, non-volatile digital memory technologies. However, the widely studied Ge-Sb-Te system possesses several undesirable properties, and enhancing its properties, e.g. by doping, is an area of active research. Various first-row transition-metal dopants have been shown to impart useful property enhancements, but a systematic study of the entire period has yet to be undertaken, and little has been done to investigate their interaction with the host material at the atomic level. We have carried out first-principles computer simulations of the complete phase-change cycle in Ge2Sb2Te5 doped with each of the ten first-row transition metals. In this article, we present a comprehensive survey of the electronic, magnetic and optical properties of these doped materials. We discuss in detail their atomic-level structure, and relate the microscopic behaviours of the dopant atoms to their influence on the Ge2Sb2Te5 host. By considering an entire family of similar materials, we identify trends and patterns which might be used to predict suitable dopants for optimizing materials for specific phase-change applications. The computational method employed here is general, and this materials-discovery approach could be applied in the future to study other families of potential dopants for such materials.

Prefrontal electroencephalographic activity during the working memory processes involved in a sexually motivated task in male rats.

PubMed

Hernández-González, Marisela; Almanza-Sepúlveda, Mayra Linné; Olvera-Cortés, María Esther; Gutiérrez-Guzmán, Blanca Erika; Guevara, Miguel Angel

2012-08-01

The prefrontal cortex is involved in working memory functions, and several studies using food or drink as rewards have demonstrated that the rat is capable of performing tasks that involve working memory. Sexual activity is another highly-rewarding, motivated behaviour that has proven to be an efficient incentive in classical operant tasks. The objective of this study was to determine whether the functional activity of the medial prefrontal cortex (mPFC) changes in relation to the working memory processes involved in a sexually motivated task performed in male rats. Thus, male Wistar rats implanted in the mPFC were subjected to a nonmatching-to-sample task in a T-maze using sexual interaction as a reinforcer during a 4-day training period. On the basis of their performance during training, the rats were classified as 'good-learners' or 'bad-learners'. Only the good-learner rats showed an increase in the absolute power of the 8-13 Hz band during both the sample and test runs; a finding that could be related to learning of the working memory elements entailed in the task. During the maintenance phase only (i.e., once the rule had been learned well), the good-learner rats also showed an increased correlation of the 8-13 Hz band during the sample run, indicating that a high degree of coupling between the prefrontal cortices is necessary for the processing required to allow the rats to make correct decisions in the maintenance phase. Taken together, these data show that mPFC activity changes in relation to the working memory processes involved in a sexually motivated task in male rats.

Experimental evidence of stress-field-induced selection of variants in Ni-Mn-Ga ferromagnetic shape-memory alloys

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

Wang, Y. D.; Key Laboratory for Anisotropy and Texture of Materials; Brown, D. W.

2007-05-01

The in situ time-of-flight neutron-diffraction measurements captured well the martensitic transformation behavior of the Ni-Mn-Ga ferromagnetic shape-memory alloys under uniaxial stress fields. We found that a small uniaxial stress applied during phase transformation dramatically disturbed the distribution of variants in the product phase. The observed changes in the distributions of variants may be explained by considering the role of the minimum distortion energy of the Bain transformation in the effective partition among the variants belonging to the same orientation of parent phase. It was also found that transformation kinetics under various stress fields follows the scale law. The present investigationsmore » provide the fundamental approach for scaling the evolution of microstructures in martensitic transitions, which is of general interest to the condensed matter community.« less

Resistance switching behavior of atomic layer deposited SrTiO3 film through possible formation of Sr2Ti6O13 or Sr1Ti11O20 phases

PubMed Central

Lee, Woongkyu; Yoo, Sijung; Yoon, Kyung Jean; Yeu, In Won; Chang, Hye Jung; Choi, Jung-Hae; Hoffmann-Eifert, Susanne; Waser, Rainer; Hwang, Cheol Seong

2016-01-01

Identification of microstructural evolution of nanoscale conducting phase, such as conducting filament (CF), in many resistance switching (RS) devices is a crucial factor to unambiguously understand the electrical behaviours of the RS-based electronic devices. Among the diverse RS material systems, oxide-based redox system comprises the major category of these intriguing electronic devices, where the local, along both lateral and vertical directions of thin films, changes in oxygen chemistry has been suggested to be the main RS mechanism. However, there are systems which involve distinctive crystallographic phases as CF; the Magnéli phase in TiO2 is one of the very well-known examples. The current research reports the possible presence of distinctive local conducting phase in atomic layer deposited SrTiO3 RS thin film. The conducting phase was identified through extensive transmission electron microscopy studies, which indicated that oxygen-deficient Sr2Ti6O13 or Sr1Ti11O20 phase was presumably present mainly along the grain boundaries of SrTiO3 after the unipolar set switching in Pt/TiN/SrTiO3/Pt structure. A detailed electrical characterization revealed that the samples showed typical bipolar and complementary RS after the memory cell was unipolar reset. PMID:26830978

Sleep supports cued fear extinction memory consolidation independent of circadian phase.

PubMed

Melo, Irene; Ehrlich, Ingrid

2016-07-01

Sleep promotes memory, particularly for declarative learning. However, its role in non-declarative, emotional memories is less well understood. Some studies suggest that sleep may influence fear-related memories, and thus may be an important factor determining the outcome of treatments for emotional disorders such as post-traumatic stress disorder. Here, we investigated the effect of sleep deprivation and time of day on fear extinction memory consolidation. Mice were subjected to a cued Pavlovian fear and extinction paradigm at the beginning of their resting or active phase. Immediate post-extinction learning sleep deprivation for 5h compromised extinction memory when tested 24h after learning. Context-dependent extinction memory recall was completely prevented by sleep-manipulation during the resting phase, while impairment was milder during the active phase and extinction memory retained its context-specificity. Importantly, control experiments excluded confounding factors such as differences in baseline locomotion, fear generalization and stress hormone levels. Together, our findings indicate that post-learning sleep supports cued fear extinction memory consolidation in both circadian phases. The lack of correlation between memory efficacy and sleep time suggests that extinction memory may be influenced by specific sleep events in the early consolidation period. Copyright © 2016 Elsevier Inc. All rights reserved.

An Attempt at Blocking of Position Learning by Training with Reward-Memory Associations

ERIC Educational Resources Information Center

Burns, Richard A.; Johnson, Kendra S.

2006-01-01

Rats were runway trained with sequences of rewards that changed in 3 phases. In Phase 1 (24 days), the sequences were NP', SNP', and P'SNP' (n = 3), or NS', PNS', and S'PNS', where P and P' refer to 4 and 8 plain Noyes pellets, and S and S' are 4 and 8 sucrose pellets. N was a 30-s confinement in the goal without reward. In Phase 2 (14 days) the…

Intensification of Antiretroviral Therapy with a CCR5 Antagonist in Patients with Chronic HIV-1 Infection: Effect on T Cells Latently Infected

PubMed Central

Vallejo, Alejandro; Hernández-Novoa, Beatriz; Abad, María; Madrid, Nadia; Dahl, Viktor; Rubio, Rafael; Moreno, Ana M.; Dronda, Fernando; Casado, José Luis; Navas, Enrique; Pérez-Elías, María Jesús; Zamora, Javier; Palmer, Sarah; Muñoz, Eduardo; Muñoz-Fernández, María Ángeles; Moreno, Santiago

2011-01-01

Objective The primary objective was to assess the effect of MVC intensification on latently infected CD4+ T cells in chronically HIV-1-infected patients receiving antiretroviral therapy. Methods We performed an open-label pilot phase II clinical trial involving chronically HIV-1-infected patients receiving stable antiretroviral therapy whose regimen was intensified with 48 weeks of maraviroc therapy. We analyzed the latent reservoir, the residual viremia and episomal 2LTR DNA to examine the relationship between these measures and the HIV-1 latent reservoir, immune activation, lymphocyte subsets (including effector and central memory T cells), and markers associated with bacterial translocation. Results Overall a non significant reduction in the size of the latent reservoir was found (p = 0.068). A mean reduction of 1.82 IUPM was observed in 4 patients with detectable latent reservoir at baseline after 48 weeks of intensification. No effect on plasma residual viremia was observed. Unexpectedly, all the patients had detectable 2LTR DNA circles at week 24, while none of them showed those circles at the end of the study. No changes were detected in CD4+ or CD8+ counts, although a significant decrease was found in the proportion of HLA-DR+/CD38+ CD4+ and CD8+ T-cells. LPS and sCD14 levels increased. Conclusions Intensification with MVC was associated with a trend to a decrease in the size of the latent HIV-1 reservoir in memory T cells. No impact on residual viremia was detected. Additional studies with larger samples are needed to confirm the results. Trial Registration ClinicalTrials.gov NCT00795444 PMID:22174752

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

PubMed

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

2012-06-01

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

Functional and evolutionary trade-offs co-occur between two consolidated memory phases in Drosophila melanogaster

PubMed Central

Lagasse, Fabrice; Moreno, Celine; Preat, Thomas; Mery, Frederic

2012-01-01

Memory is a complex and dynamic process that is composed of different phases. Its evolution under natural selection probably depends on a balance between fitness benefits and costs. In Drosophila, two separate forms of consolidated memory phases can be generated experimentally: anaesthesia-resistant memory (ARM) and long-term memory (LTM). In recent years, several studies have focused on the differences between these long-lasting memory types and have found that, at the functional level, ARM and LTM are antagonistic. How this functional relationship will affect their evolutionary dynamics remains unknown. We selected for flies with either improved ARM or improved LTM over several generations, and found that flies selected specifically for improvement of one consolidated memory phase show reduced performance in the other memory phase. We also found that improved LTM was linked to decreased longevity in male flies but not in females. Conversely, males with improved ARM had increased longevity. We found no correlation between either improved ARM or LTM and other phenotypic traits. This is, to our knowledge, the first evidence of a symmetrical evolutionary trade-off between two memory phases for the same learning task. Such trade-offs may have an important impact on the evolution of cognitive capacities. On a neural level, these results support the hypothesis that mechanisms underlying these forms of consolidated memory are, to some degree, antagonistic. PMID:22859595

Picosecond electric-field-induced threshold switching in phase-change materials [THz-induced threshold switching and crystallization of phase-change materials

DOE PAGES

Zalden, Peter; Shu, Michael J.; Chen, Frank; ...

2016-08-05

Many chalcogenide glasses undergo a breakdown in electronic resistance above a critical field strength. Known as threshold switching, this mechanism enables field-induced crystallization in emerging phase-change memory. Purely electronic as well as crystal nucleation assisted models have been employed to explain the electronic breakdown. Here, picosecond electric pulses are used to excite amorphous Ag 4In 3Sb 67Te 26. Field-dependent reversible changes in conductivity and pulse-driven crystallization are observed. The present results show that threshold switching can take place within the electric pulse on subpicosecond time scales—faster than crystals can nucleate. As a result, this supports purely electronic models of thresholdmore » switching and reveals potential applications as an ultrafast electronic switch.« less

The Effect of Consistency on Short-Term Memory for Scenes.

PubMed

Gong, Mingliang; Xuan, Yuming; Xu, Xinwen; Fu, Xiaolan

2017-01-01

Which is more detectable, the change of a consistent or an inconsistent object in a scene? This question has been debated for decades. We noted that the change of objects in scenes might simultaneously be accompanied with gist changes. In the present study we aimed to examine how the alteration of gist, as well as the consistency of the changed objects, modulated change detection. In Experiment 1, we manipulated the semantic content by either keeping or changing the consistency of the scene. Results showed that the changes of consistent and inconsistent scenes were equally detected. More importantly, the changes were more accurately detected when scene consistency changed than when the consistency remained unchanged, regardless of the consistency of the memory scenes. A phase-scrambled version of stimuli was adopted in Experiment 2 to decouple the possible confounding effect of low-level factors. The results of Experiment 2 demonstrated that the effect found in Experiment 1 was indeed due to the change of high-level semantic consistency rather than the change of low-level physical features. Together, the study suggests that the change of consistency plays an important role in scene short-term memory, which might be attributed to the sensitivity to the change of semantic content.

The Effect of Consistency on Short-Term Memory for Scenes

PubMed Central

Gong, Mingliang; Xuan, Yuming; Xu, Xinwen; Fu, Xiaolan

2017-01-01

Which is more detectable, the change of a consistent or an inconsistent object in a scene? This question has been debated for decades. We noted that the change of objects in scenes might simultaneously be accompanied with gist changes. In the present study we aimed to examine how the alteration of gist, as well as the consistency of the changed objects, modulated change detection. In Experiment 1, we manipulated the semantic content by either keeping or changing the consistency of the scene. Results showed that the changes of consistent and inconsistent scenes were equally detected. More importantly, the changes were more accurately detected when scene consistency changed than when the consistency remained unchanged, regardless of the consistency of the memory scenes. A phase-scrambled version of stimuli was adopted in Experiment 2 to decouple the possible confounding effect of low-level factors. The results of Experiment 2 demonstrated that the effect found in Experiment 1 was indeed due to the change of high-level semantic consistency rather than the change of low-level physical features. Together, the study suggests that the change of consistency plays an important role in scene short-term memory, which might be attributed to the sensitivity to the change of semantic content. PMID:29046654

Experimental 'jet lag' inhibits adult neurogenesis and produces long-term cognitive deficits in female hamsters.

PubMed

Gibson, Erin M; Wang, Connie; Tjho, Stephanie; Khattar, Neera; Kriegsfeld, Lance J

2010-12-01

Circadian disruptions through frequent transmeridian travel, rotating shift work, and poor sleep hygiene are associated with an array of physical and mental health maladies, including marked deficits in human cognitive function. Despite anecdotal and correlational reports suggesting a negative impact of circadian disruptions on brain function, this possibility has not been experimentally examined. In the present study, we investigated whether experimental 'jet lag' (i.e., phase advances of the light:dark cycle) negatively impacts learning and memory and whether any deficits observed are associated with reductions in hippocampal cell proliferation and neurogenesis. Because insults to circadian timing alter circulating glucocorticoid and sex steroid concentrations, both of which influence neurogenesis and learning/memory, we assessed the contribution of these endocrine factors to any observed alterations. Circadian disruption resulted in pronounced deficits in learning and memory paralleled by marked reductions in hippocampal cell proliferation and neurogenesis. Significantly, deficits in hippocampal-dependent learning and memory were not only seen during the period of the circadian disruption, but also persisted well after the cessation of jet lag, suggesting long-lasting negative consequences on brain function. Together, these findings support the view that circadian disruptions suppress hippocampal neurogenesis via a glucocorticoid-independent mechanism, imposing pronounced and persistent impairments on learning and memory.

Mild traumatic brain injury: graph-model characterization of brain networks for episodic memory.

PubMed

Tsirka, Vasso; Simos, Panagiotis G; Vakis, Antonios; Kanatsouli, Kassiani; Vourkas, Michael; Erimaki, Sofia; Pachou, Ellie; Stam, Cornelis Jan; Micheloyannis, Sifis

2011-02-01

Episodic memory is among the cognitive functions that can be affected in the acute phase following mild traumatic brain injury (MTBI). The present study used EEG recordings to evaluate global synchronization and network organization of rhythmic activity during the encoding and recognition phases of an episodic memory task varying in stimulus type (kaleidoscope images, pictures, words, and pseudowords). Synchronization of oscillatory activity was assessed using a linear and nonlinear connectivity estimator and network analyses were performed using algorithms derived from graph theory. Twenty five MTBI patients (tested within days post-injury) and healthy volunteers were closely matched on demographic variables, verbal ability, psychological status variables, as well as on overall task performance. Patients demonstrated sub-optimal network organization, as reflected by changes in graph parameters in the theta and alpha bands during both encoding and recognition. There were no group differences in spectral energy during task performance or on network parameters during a control condition (rest). Evidence of less optimally organized functional networks during memory tasks was more prominent for pictorial than for verbal stimuli. Copyright © 2010 Elsevier B.V. All rights reserved.

Ultralow-fatigue shape memory alloy films

NASA Astrophysics Data System (ADS)

Chluba, Christoph; Ge, Wenwei; Lima de Miranda, Rodrigo; Strobel, Julian; Kienle, Lorenz; Quandt, Eckhard; Wuttig, Manfred

2015-05-01

Functional shape memory alloys need to operate reversibly and repeatedly. Quantitative measures of reversibility include the relative volume change of the participating phases and compatibility matrices for twinning. But no similar argument is known for repeatability. This is especially crucial for many future applications, such as artificial heart valves or elastocaloric cooling, in which more than 10 million transformation cycles will be required. We report on the discovery of an ultralow-fatigue shape memory alloy film system based on TiNiCu that allows at least 10 million transformation cycles. We found that these films contain Ti2Cu precipitates embedded in the base alloy that serve as sentinels to ensure complete and reproducible transformation in the course of each memory cycle.

Method of preparing a two-way shape memory alloy

DOEpatents

Johnson, A.D.

1984-03-06

A two-way shape memory alloy, a method of training a shape memory alloy, and a heat engine employing the two-way shape memory alloy to do external work during both heating and cooling phases are disclosed. The alloy is heated under a first training stress to a temperature which is above the upper operating temperature of the alloy, then cooled to a cold temperature below the zero-force transition temperature of the alloy, then deformed while applying a second training stress which is greater in magnitude than the stress at which the alloy is to be operated, then heated back to the hot temperature, changing from the second training stress back to the first training stress. 8 figs.

Enhanced Memory Consolidation Via Automatic Sound Stimulation During Non-REM Sleep.

PubMed

Leminen, Miika M; Virkkala, Jussi; Saure, Emma; Paajanen, Teemu; Zee, Phyllis C; Santostasi, Giovanni; Hublin, Christer; Müller, Kiti; Porkka-Heiskanen, Tarja; Huotilainen, Minna; Paunio, Tiina

2017-03-01

Slow-wave sleep (SWS) slow waves and sleep spindle activity have been shown to be crucial for memory consolidation. Recently, memory consolidation has been causally facilitated in human participants via auditory stimuli phase-locked to SWS slow waves. Here, we aimed to develop a new acoustic stimulus protocol to facilitate learning and to validate it using different memory tasks. Most importantly, the stimulation setup was automated to be applicable for ambulatory home use. Fifteen healthy participants slept 3 nights in the laboratory. Learning was tested with 4 memory tasks (word pairs, serial finger tapping, picture recognition, and face-name association). Additional questionnaires addressed subjective sleep quality and overnight changes in mood. During the stimulus night, auditory stimuli were adjusted and targeted by an unsupervised algorithm to be phase-locked to the negative peak of slow waves in SWS. During the control night no sounds were presented. Results showed that the sound stimulation increased both slow wave (p = .002) and sleep spindle activity (p < .001). When overnight improvement of memory performance was compared between stimulus and control nights, we found a significant effect in word pair task but not in other memory tasks. The stimulation did not affect sleep structure or subjective sleep quality. We showed that the memory effect of the SWS-targeted individually triggered single-sound stimulation is specific to verbal associative memory. Moreover, the ambulatory and automated sound stimulus setup was promising and allows for a broad range of potential follow-up studies in the future. © Sleep Research Society 2017. Published by Oxford University Press [on behalf of the Sleep Research Society].

Memory. Engram cells retain memory under retrograde amnesia.

PubMed

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

2015-05-29

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

Structural health monitoring for DOT using magnetic shape memory alloy cables in concrete

NASA Astrophysics Data System (ADS)

Davis, Allen; Mirsayar, Mirmilad; Sheahan, Emery; Hartl, Darren

2018-03-01

Embedding shape memory alloy (SMA) wires in concrete components offers the potential to monitor their structural health via external magnetic field sensing. Currently, structural health monitoring (SHM) is dominated by acoustic emission and vibration-based methods. Thus, it is attractive to pursue alternative damage sensing techniques that may lower the cost or increase the accuracy of SHM. In this work, SHM via magnetic field detection applied to embedded magnetic shape memory alloy (MSMA) is demonstrated both experimentally and using computational models. A concrete beam containing iron-based MSMA wire is subjected to a 3-point bend test where structural damage is induced, thereby resulting in a localized phase change of the MSMA wire. Magnetic field lines passing through the embedded MSMA domain are altered by this phase change and can thus be used to detect damage within the structure. A good correlation is observed between the computational and experimental results. Additionally, the implementation of stranded MSMA cables in place of the MSMA wire is assessed through similar computational models. The combination of these computational models and their subsequent experimental validation provide sufficient support for the feasibility of SHM using magnetic field sensing via MSMA embedded components.

Sleep-Dependent Oscillatory Synchronization: A Role in Fear Memory Consolidation.

PubMed

Totty, Michael S; Chesney, Logan A; Geist, Phillip A; Datta, Subimal

2017-01-01

Sleep plays an important role in memory consolidation through the facilitation of neuronal plasticity; however, how sleep accomplishes this remains to be completely understood. It has previously been demonstrated that neural oscillations are an intrinsic mechanism by which the brain precisely controls neural ensembles. Inter-regional synchronization of these oscillations is also known to facilitate long-range communication and long-term potentiation (LTP). In the present study, we investigated how the characteristic rhythms found in local field potentials (LFPs) during non-REM and REM sleep play a role in emotional memory consolidation. Chronically implanted bipolar electrodes in the lateral amygdala (LA), dorsal and ventral hippocampus (DH, VH), and the infra-limbic (IL), and pre-limbic (PL) prefrontal cortex were used to record LFPs across sleep-wake activity following each day of a Pavlovian cued fear conditioning paradigm. This resulted in three principle findings: (1) theta rhythms during REM sleep are highly synchronized between regions; (2) the extent of inter-regional synchronization during REM and non-REM sleep is altered by FC and EX; (3) the mean phase difference of synchronization between the LA and VH during REM sleep predicts changes in freezing after cued fear extinction. These results both oppose a currently proposed model of sleep-dependent memory consolidation and provide a novel finding which suggests that the role of REM sleep theta rhythms in memory consolidation may rely more on the relative phase-shift between neural oscillations, rather than the extent of phase synchronization.

Dynamic reconfiguration of human brain functional networks through neurofeedback.

PubMed

Haller, Sven; Kopel, Rotem; Jhooti, Permi; Haas, Tanja; Scharnowski, Frank; Lovblad, Karl-Olof; Scheffler, Klaus; Van De Ville, Dimitri

2013-11-01

Recent fMRI studies demonstrated that functional connectivity is altered following cognitive tasks (e.g., learning) or due to various neurological disorders. We tested whether real-time fMRI-based neurofeedback can be a tool to voluntarily reconfigure brain network interactions. To disentangle learning-related from regulation-related effects, we first trained participants to voluntarily regulate activity in the auditory cortex (training phase) and subsequently asked participants to exert learned voluntary self-regulation in the absence of feedback (transfer phase without learning). Using independent component analysis (ICA), we found network reconfigurations (increases in functional network connectivity) during the neurofeedback training phase between the auditory target region and (1) the auditory pathway; (2) visual regions related to visual feedback processing; (3) insula related to introspection and self-regulation and (4) working memory and high-level visual attention areas related to cognitive effort. Interestingly, the auditory target region was identified as the hub of the reconfigured functional networks without a-priori assumptions. During the transfer phase, we again found specific functional connectivity reconfiguration between auditory and attention network confirming the specific effect of self-regulation on functional connectivity. Functional connectivity to working memory related networks was no longer altered consistent with the absent demand on working memory. We demonstrate that neurofeedback learning is mediated by widespread changes in functional connectivity. In contrast, applying learned self-regulation involves more limited and specific network changes in an auditory setup intended as a model for tinnitus. Hence, neurofeedback training might be used to promote recovery from neurological disorders that are linked to abnormal patterns of brain connectivity. Copyright © 2013 Elsevier Inc. All rights reserved.

Modulation of recognition memory performance by light requires both melanopsin and classical photoreceptors

PubMed Central

Tam, Shu K. E.; Hasan, Sibah; Hughes, Steven; Hankins, Mark W.; Foster, Russell G.; Bannerman, David M.

2016-01-01

Acute light exposure exerts various effects on physiology and behaviour. Although the effects of light on brain network activity in humans are well demonstrated, the effects of light on cognitive performance are inconclusive, with the size, as well as direction, of the effect depending on the nature of the task. Similarly, in nocturnal rodents, bright light can either facilitate or disrupt performance depending on the type of task employed. Crucially, it is unclear whether the effects of light on behavioural performance are mediated via the classical image-forming rods and cones or the melanopsin-expressing photosensitive retinal ganglion cells. Here, we investigate the modulatory effects of light on memory performance in mice using the spontaneous object recognition task. Importantly, we examine which photoreceptors are required to mediate the effects of light on memory performance. By using a cross-over design, we show that object recognition memory is disrupted when the test phase is conducted under a bright light (350 lux), regardless of the light level in the sample phase (10 or 350 lux), demonstrating that exposure to a bright light at the time of test, rather than at the time of encoding, impairs performance. Strikingly, the modulatory effect of light on memory performance is completely abolished in both melanopsin-deficient and rodless–coneless mice. Our findings provide direct evidence that melanopsin-driven and rod/cone-driven photoresponses are integrated in order to mediate the effect of light on memory performance. PMID:28003454

Modulation of recognition memory performance by light requires both melanopsin and classical photoreceptors.

PubMed

Tam, Shu K E; Hasan, Sibah; Hughes, Steven; Hankins, Mark W; Foster, Russell G; Bannerman, David M; Peirson, Stuart N

2016-12-28

Acute light exposure exerts various effects on physiology and behaviour. Although the effects of light on brain network activity in humans are well demonstrated, the effects of light on cognitive performance are inconclusive, with the size, as well as direction, of the effect depending on the nature of the task. Similarly, in nocturnal rodents, bright light can either facilitate or disrupt performance depending on the type of task employed. Crucially, it is unclear whether the effects of light on behavioural performance are mediated via the classical image-forming rods and cones or the melanopsin-expressing photosensitive retinal ganglion cells. Here, we investigate the modulatory effects of light on memory performance in mice using the spontaneous object recognition task. Importantly, we examine which photoreceptors are required to mediate the effects of light on memory performance. By using a cross-over design, we show that object recognition memory is disrupted when the test phase is conducted under a bright light (350 lux), regardless of the light level in the sample phase (10 or 350 lux), demonstrating that exposure to a bright light at the time of test, rather than at the time of encoding, impairs performance. Strikingly, the modulatory effect of light on memory performance is completely abolished in both melanopsin-deficient and rodless-coneless mice. Our findings provide direct evidence that melanopsin-driven and rod/cone-driven photoresponses are integrated in order to mediate the effect of light on memory performance. © 2016 The Authors.

On-command on/off switching of progenitor cell and cancer cell polarized motility and aligned morphology via a cytocompatible shape memory polymer scaffold.

PubMed

Wang, Jing; Quach, Andy; Brasch, Megan E; Turner, Christopher E; Henderson, James H

2017-09-01

In vitro biomaterial models have enabled advances in understanding the role of extracellular matrix (ECM) architecture in the control of cell motility and polarity. Most models are, however, static and cannot mimic dynamic aspects of in vivo ECM remodeling and function. To address this limitation, we present an electrospun shape memory polymer scaffold that can change fiber alignment on command under cytocompatible conditions. Cellular response was studied using the human fibrosarcoma cell line HT-1080 and the murine mesenchymal stem cell line C3H/10T1/2. The results demonstrate successful on-command on/off switching of cell polarized motility and alignment. Decrease in fiber alignment causes a change from polarized motility along the direction of fiber alignment to non-polarized motility and from aligned to unaligned morphology, while increase in fiber alignment causes a change from non-polarized to polarized motility along the direction of fiber alignment and from unaligned to aligned morphology. In addition, the findings are consistent with the hypothesis that increased fiber alignment causes increased cell velocity, while decreased fiber alignment causes decreased cell velocity. On-command on/off switching of cell polarized motility and alignment is anticipated to enable new study of directed cell motility in tumor metastasis, in cell homing, and in tissue engineering. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mechanical memory

DOEpatents

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

2006-08-15

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

Mechanical memory

DOEpatents

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

2006-05-16

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

What is the function of hippocampal theta rhythm?--Linking behavioral data to phasic properties of field potential and unit recording data.

PubMed

Hasselmo, Michael E

2005-01-01

The extensive physiological data on hippocampal theta rhythm provide an opportunity to evaluate hypotheses about the role of theta rhythm for hippocampal network function. Computational models based on these hypotheses help to link behavioral data with physiological measurements of different variables during theta rhythm. This paper reviews work on network models in which theta rhythm contributes to the following functions: (1) separating the dynamics of encoding and retrieval, (2) enhancing the context-dependent retrieval of sequences, (3) buffering of novel information in entorhinal cortex (EC) for episodic encoding, and (4) timing interactions between prefrontal cortex and hippocampus for memory-guided action selection. Modeling shows how these functional mechanisms are related to physiological data from the hippocampal formation, including (1) the phase relationships of synaptic currents during theta rhythm measured by current source density analysis of electroencephalographic data from region CA1 and dentate gyrus, (2) the timing of action potentials, including the theta phase precession of single place cells during running on a linear track, the context-dependent changes in theta phase precession across trials on each day, and the context-dependent firing properties of hippocampal neurons in spatial alternation (e.g., "splitter cells"), (3) the cholinergic regulation of sustained activity in entorhinal cortical neurons, and (4) the phasic timing of prefrontal cortical neurons relative to hippocampal theta rhythm. Copyright 2005 Wiley-Liss, Inc.

A Recollection of mTOR Signaling in Learning and Memory

ERIC Educational Resources Information Center

Graber, Tyson E.; McCamphill, Patrick K.; Sossin, Wayne S.

2013-01-01

Mechanistic target of rapamcyin (mTOR) is a central player in cell growth throughout the organism. However, mTOR takes on an additional, more specialized role in the developed neuron, where it regulates the protein synthesis-dependent, plastic changes underlying learning and memory. mTOR is sequestered in two multiprotein complexes (mTORC1 and…

Chalcogenide phase-change thin films used as grayscale photolithography materials.

PubMed

Wang, Rui; Wei, Jingsong; Fan, Yongtao

2014-03-10

Chalcogenide phase-change thin films are used in many fields, such as optical information storage and solid-state memory. In this work, we present another application of chalcogenide phase-change thin films, i.e., as grayscale photolithgraphy materials. The grayscale patterns can be directly inscribed on the chalcogenide phase-change thin films by a single process through direct laser writing method. In grayscale photolithography, the laser pulse can induce the formation of bump structure, and the bump height and size can be precisely controlled by changing laser energy. Bumps with different height and size present different optical reflection and transmission spectra, leading to the different gray levels. For example, the continuous-tone grayscale images of lifelike bird and cat are successfully inscribed onto Sb(2)Te(3) chalcogenide phase-change thin films using a home-built laser direct writer, where the expression and appearance of the lifelike bird and cat are fully presented. This work provides a way to fabricate complicated grayscale patterns using laser-induced bump structures onto chalcogenide phase-change thin films, different from current techniques such as photolithography, electron beam lithography, and focused ion beam lithography. The ability to form grayscale patterns of chalcogenide phase-change thin films reveals many potential applications in high-resolution optical images for micro/nano image storage, microartworks, and grayscale photomasks.

Solid-solid phase change thermal storage application to space-suit battery pack

NASA Astrophysics Data System (ADS)

Son, Chang H.; Morehouse, Jeffrey H.

1989-01-01

High cell temperatures are seen as the primary safety problem in the Li-BCX space battery. The exothermic heat from the chemical reactions could raise the temperature of the lithium electrode above the melting temperature. Also, high temperature causes the cell efficiency to decrease. Solid-solid phase-change materials were used as a thermal storage medium to lower this battery cell temperature by utilizing their phase-change (latent heat storage) characteristics. Solid-solid phase-change materials focused on in this study are neopentyl glycol and pentaglycerine. Because of their favorable phase-change characteristics, these materials appear appropriate for space-suit battery pack use. The results of testing various materials are reported as thermophysical property values, and the space-suit battery operating temperature is discussed in terms of these property results.

B cell expression of the inhibitory Fc gamma receptor is unchanged in early MS.

PubMed

Comabella, Manuel; Montalban, Xavier; Kakalacheva, Kristina; Osman, Deeqa; Nimmerjahn, Falk; Tintoré, Mar; Lünemann, Jan D

2010-06-01

Expression of the inhibitory Fcgamma receptor IIB (FcgammaRIIB) has emerged as a late checkpoint during peripheral B cell development which prevents autoreactive memory B lymphocytes from becoming long-lived plasma cells. Decreased expression of FcgammaRIIB or non-functional FcgammaRIIB variants are associated with the development of autoimmune tissue inflammation. We determined the expression profile of FcgammaRIIB in peripheral blood cells in treatment-naïve patients with early MS. Twenty-five patients with clinically isolated syndrome (CIS) who converted to clinically definite MS (CDMS) and 25 demographically matched healthy donors were included in the study. Frequencies of peripheral blood monocytes and B cell subsets as well as FcgammaRIIB expression profile was determined by flow cytometry. FcgammaRIIB expression levels were higher in B cells compared to monocytes (p<0.0001) and higher in memory B cells compared to their naïve counterparts (p<0.0001). However, FcgammaRIIB expression in naïve and memory B cells as well as monocytes was unchanged in patients with early MS at onset of symptoms as well as after conversion to CDMS compared to controls. No significant correlations were found between FcgammaRIIB expression levels and brain MRI-derived metrics or EDSS progression during follow-up. These data indicate that FcgammaRIIB expression, a critical late B cell differentiation checkpoint preventing the occurrence of autoreactive long-lived plasma cells, is not impaired in treatment-naïve patients with MS, at least in the early phases of the disease. Copyright 2010 Elsevier B.V. All rights reserved.

Dynamic phase differences based on quantitative phase imaging for the objective evaluation of cell behavior.

PubMed

Krizova, Aneta; Collakova, Jana; Dostal, Zbynek; Kvasnica, Lukas; Uhlirova, Hana; Zikmund, Tomas; Vesely, Pavel; Chmelik, Radim

2015-01-01

Quantitative phase imaging (QPI) brought innovation to noninvasive observation of live cell dynamics seen as cell behavior. Unlike the Zernike phase contrast or differential interference contrast, QPI provides quantitative information about cell dry mass distribution. We used such data for objective evaluation of live cell behavioral dynamics by the advanced method of dynamic phase differences (DPDs). The DPDs method is considered a rational instrument offered by QPI. By subtracting the antecedent from the subsequent image in a time-lapse series, only the changes in mass distribution in the cell are detected. The result is either visualized as a two dimensional color-coded projection of these two states of the cell or as a time dependence of changes quantified in picograms. Then in a series of time-lapse recordings, the chain of cell mass distribution changes that would otherwise escape attention is revealed. Consequently, new salient features of live cell behavior should emerge. Construction of the DPDs method and results exhibiting the approach are presented. Advantage of the DPDs application is demonstrated on cells exposed to an osmotic challenge. For time-lapse acquisition of quantitative phase images, the recently developed coherence-controlled holographic microscope was employed.

Dynamic phase differences based on quantitative phase imaging for the objective evaluation of cell behavior

NASA Astrophysics Data System (ADS)

Krizova, Aneta; Collakova, Jana; Dostal, Zbynek; Kvasnica, Lukas; Uhlirova, Hana; Zikmund, Tomas; Vesely, Pavel; Chmelik, Radim

2015-11-01

Quantitative phase imaging (QPI) brought innovation to noninvasive observation of live cell dynamics seen as cell behavior. Unlike the Zernike phase contrast or differential interference contrast, QPI provides quantitative information about cell dry mass distribution. We used such data for objective evaluation of live cell behavioral dynamics by the advanced method of dynamic phase differences (DPDs). The DPDs method is considered a rational instrument offered by QPI. By subtracting the antecedent from the subsequent image in a time-lapse series, only the changes in mass distribution in the cell are detected. The result is either visualized as a two-dimensional color-coded projection of these two states of the cell or as a time dependence of changes quantified in picograms. Then in a series of time-lapse recordings, the chain of cell mass distribution changes that would otherwise escape attention is revealed. Consequently, new salient features of live cell behavior should emerge. Construction of the DPDs method and results exhibiting the approach are presented. Advantage of the DPDs application is demonstrated on cells exposed to an osmotic challenge. For time-lapse acquisition of quantitative phase images, the recently developed coherence-controlled holographic microscope was employed.

Novelty-Sensitive Dopaminergic Neurons in the Human Substantia Nigra Predict Success of Declarative Memory Formation.

PubMed

Kamiński, Jan; Mamelak, Adam N; Birch, Kurtis; Mosher, Clayton P; Tagliati, Michele; Rutishauser, Ueli

2018-05-07

The encoding of information into long-term declarative memory is facilitated by dopamine. This process depends on hippocampal novelty signals, but it remains unknown how midbrain dopaminergic neurons are modulated by declarative-memory-based information. We recorded individual substantia nigra (SN) neurons and cortical field potentials in human patients performing a recognition memory task. We found that 25% of SN neurons were modulated by stimulus novelty. Extracellular waveform shape and anatomical location indicated that these memory-selective neurons were putatively dopaminergic. The responses of memory-selective neurons appeared 527 ms after stimulus onset, changed after a single trial, and were indicative of recognition accuracy. SN neurons phase locked to frontal cortical theta-frequency oscillations, and the extent of this coordination predicted successful memory formation. These data reveal that dopaminergic neurons in the human SN are modulated by memory signals and demonstrate a progression of information flow in the hippocampal-basal ganglia-frontal cortex loop for memory encoding. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Femtosecond laser pulse induced phase transition of Cr-doped Sb2Te1 films studied with a pump-probe system

NASA Astrophysics Data System (ADS)

Jiang, Minghui; Wang, Qing; Lei, Kai; Wang, Yang; Liu, Bo; Song, Zhitang

2016-10-01

The Femtosecond laser pulse induced phase transition dynamics of Cr-doped Sb2Te1 films was studied by real-time reflectivity measurements with a pump-probe system. It was found that crystallization of the as-deposited CrxSb2Te1 phase-change thin films exhibits a multi-stage process lasting for about 40ns.The time required for the multi-stage process seems to be not related to the contents of Cr element. The durations of the crystallization and amorphization processes are approximately the same. Doping Cr into Sb2Te1 thin film can improve its photo-thermal stability without obvious change in the crystallization rate. Optical images and image intensity cross sections are used to visualize the transformed regions. This work may provide further insight into the phase-change mechanism of CrxSb2Te1 under extra-non-equilibrium conditions and aid to develop new ultrafast phase-change memory materials.

Immune responses induced by T-cell vaccination in patients with rheumatoid arthritis

PubMed Central

Ivanova, Irina; Seledtsova, Galina; Mamaev, Sergey; Shishkov, Alexey; Seledtsov, Viktor

2014-01-01

Patients with rheumatoid arthritis (RA) were treated with a cellular vaccine, which consisted of autologous collagen-reactive T-cells. This study showed that antigen-specific proliferative activity of the peripheral blood mononuclear cells was significantly downregulated after T-cell vaccination in RA patients. T-cell vaccination resulted in a statistically significant decrease in plasma IFNγ levels and a concomitant increase in IL-4 levels in treated patients. Accordingly, following T-cell vaccination the number of IFNγ-producing CD4+ and CD8+ T-cells was decreased by 1.6–1.8-fold, which was paralleled by 1.7-fold increases in IL-4-producing CD4+ T-cells. In addition, the present study showed 5–7-fold increase in the CD8+CD45RO+CD62L– effector memory T-cells and central memory T-cells (both CD4+ CD45RO+CD62L+ T-cells and CD8+CD45RO+CD62L+ T-cells) in RA patients, as compared with healthy individuals. We observed significant reduction in CD4+ and CD8+ central memory T-cells, as well as reduction in CD8+ effector memory T-cells in vaccinated patients in the course of the treatment. We also demonstrated that CD4+CD25+FoxP3+ regulatory T-cell levels were significantly up-regulated in the peripheral blood of RA patients following T-cell vaccination. However, CD4+CD25-FoxP3+ Т-cell levels did not significantly change during the entire T-cell vaccination course. In conclusion, the T-cell immunotherapy regimen used resulted in the clinical improvement, which was achieved in 87% patients. PMID:24633313

Dual-modality wide-field photothermal quantitative phase microscopy and depletion of cell populations

NASA Astrophysics Data System (ADS)

Turko, Nir A.; Barnea, Itay; Blum, Omry; Korenstein, Rafi; Shaked, Natan T.

2015-03-01

We review our dual-modality technique for quantitative imaging and selective depletion of populations of cells based on wide-field photothermal (PT) quantitative phase imaging and simultaneous PT cell extermination. The cells are first labeled by plasmonic gold nanoparticles, which evoke local plasmonic resonance when illuminated by light in a wavelength corresponding to their specific plasmonic resonance peak. This reaction creates changes of temperature, resulting in changes of phase. This phase changes are recorded by a quantitative phase microscope (QPM), producing specific imaging contrast, and enabling bio-labeling in phase microscopy. Using this technique, we have shown discrimination of EGFR over-expressing (EGFR+) cancer cells from EGFR under-expressing (EGFR-) cancer cells. Then, we have increased the excitation power in order to evoke greater temperatures, which caused specific cell death, all under real-time phase acquisition using QPM. Close to 100% of all EGFR+ cells were immediately exterminated when illuminated with the strong excitation beam, while all EGFR- cells survived. For the second experiment, in order to simulate a condition where circulating tumor cells (CTCs) are present in blood, we have mixed the EGFR+ cancer cells with white blood cells (WBCs) from a healthy donor. Here too, we have used QPM to observe and record the phase of the cells as they were excited for selective visualization and then exterminated. The WBCs survival rate was over 95%, while the EGFR+ survival rate was under 5%. The technique may be the basis for real-time detection and controlled treatment of CTCs.

Time-dependent Mechanisms in Beta-cell Glucose Sensing

PubMed Central

Vagn Korsgaard, Thomas

2006-01-01

The relation between plasma glucose and insulin release from pancreatic beta-cells is not stationary in the sense that a given glucose concentration leads to a specific rate of insulin secretion. A number of time-dependent mechanisms appear to exist that modify insulin release both on a short and a longer time scale. Typically, two phases are described. The first phase, lasting up to 10 min, is a pulse of insulin release in response to fast changes in glucose concentration. The second phase is a more steady increase of insulin release over minutes to hours, if the elevated glucose concentration is sustained. The paper describes the glucose sensing mechanism via the complex dynamics of the key enzyme glucokinase, which controls the first step in glucose metabolism: phosphorylation of glucose to glucose-6-phosphate. Three time-dependent phenomena (mechanisms) are described. The fastest, corresponding to the first phase, is a delayed negative feedback regulating the glucokinase activity. Due to the delay, a rapid glucose increase will cause a burst of activity in the glucose sensing system, before the glucokinase is down-regulated. The second mechanism corresponds to the translocation of glucokinase from an inactive to an active form. As the translocation is controlled by the product(s) of the glucokinase reaction rather than by the substrate glucose, this mechanism gives a positive, but saturable, feedback. Finally, the release of the insulin granules is assumed to be enhanced by previous glucose exposure, giving a so-called glucose memory to the beta-cells. The effect depends on the insulin release of the cells, and this mechanism constitutes a second positive, saturable feedback system. Taken together, the three phenomena describe most of the glucose sensing behaviour of the beta-cells. The results indicate that the insulin release is not a precise function of the plasma glucose concentration. It rather looks as if the beta-cells just increase the insulin production, until the plasma glucose has returned to normal. This type of integral control has the advantage that the precise glucose sensitivity of the beta-cells is not important for normal glucose homeostasis. PMID:19669468

Entorhinal-CA3 Dual-Input Control of Spike Timing in the Hippocampus by Theta-Gamma Coupling.

PubMed

Fernández-Ruiz, Antonio; Oliva, Azahara; Nagy, Gergő A; Maurer, Andrew P; Berényi, Antal; Buzsáki, György

2017-03-08

Theta-gamma phase coupling and spike timing within theta oscillations are prominent features of the hippocampus and are often related to navigation and memory. However, the mechanisms that give rise to these relationships are not well understood. Using high spatial resolution electrophysiology, we investigated the influence of CA3 and entorhinal inputs on the timing of CA1 neurons. The theta-phase preference and excitatory strength of the afferent CA3 and entorhinal inputs effectively timed the principal neuron activity, as well as regulated distinct CA1 interneuron populations in multiple tasks and behavioral states. Feedback potentiation of distal dendritic inhibition by CA1 place cells attenuated the excitatory entorhinal input at place field entry, coupled with feedback depression of proximal dendritic and perisomatic inhibition, allowing the CA3 input to gain control toward the exit. Thus, upstream inputs interact with local mechanisms to determine theta-phase timing of hippocampal neurons to support memory and spatial navigation. Copyright © 2017 Elsevier Inc. All rights reserved.

Engram Cells Retain Memory Under Retrograde Amnesia

PubMed Central

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

2017-01-01

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

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

Gargarella, P., E-mail: piter@ufscar.br; Departamento de Engenharia de Materiais, Universidade Federal de São Carlos, Rodovia Washington Luiz, Km 235, 13565-905 São Carlos, São Paulo; Pauly, S.

The structural evolution of Ti{sub 50}Cu{sub 43}Ni{sub 7} and Ti{sub 55}Cu{sub 35}Ni{sub 10} metallic glasses during heating was investigated by in-situ synchrotron X-ray diffraction. The width of the most intense diffraction maximum of the glassy phase decreases slightly during relaxation below the glass transition temperature. Significant structural changes only occur above the glass transition manifesting in a change in the respective peak positions. At even higher temperatures, nanocrystals of the shape memory B2-Ti(Cu,Ni) phase precipitate, and their small size hampers the occurrence of a martensitic transformation.

Coadministration of the Human Umbilical Cord Matrix-Derived Mesenchymal Cells and Aspirin Alters Postischemic Brain Injury in Rats.

PubMed

Shams ara, Ali; Sheibani, Vahid; Esmaeilpour, Khadije; Eslaminejad, Touba; Nematollahi-Mahani, Seyed N

2015-09-01

Ischemic stroke is an acute brain insult that induces dramatic changes in the neurons. Treatment of brain stroke is one of the main therapeutic targets of neuroprotective therapies. The aim of this study was to evaluate the protective potential of implanted human umbilical cord mesenchymal stem (hUCMs) cells with/without aspirin (ASA) against focal cerebral ischemia. We assessed the migration and distribution of PKH26-labeled cells after transplantation. After day 10 of transient occlusion, we evaluated the effect of ASA and hUCMs on the recovery of learning and memory in rats by Morris water maze. Afterward, animals were sacrificed, and the infarct area in the brain was evaluated using 2, 3, 5-triphenyltetrazolium chloride staining and also by hematoxylin and eosin. The recovery of learning and memory in ischemic animals that received ASA and hUCM cells improved significantly compared with the untreated ischemic animals. Coadministration of ASA and hUCM cells did not improve the outcome at a comparable rate with ASA and hUCM cells alone. PKH26-labeled cells were detectable in the ischemic area of the brain tissue sections. 2,3,5-Triphenyltetrazolium chloride staining and histologic examinations showed that treatment with ASA and hUCM cells could significantly alter the ischemic area. The results of the present study suggest that ASA and hUCM cells can withstand degenerative changes induced by artificial stroke in the rat. Also the learning and memory disturbance in the ASA and cell-treated animals is less pronounced than ischemic animals. Coadministration of ASA and hUCM cells did not raise the outcome higher than administration of ASA and hUCM cells alone. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Extinction of Learned Fear Induces Hippocampal Place Cell Remapping

PubMed Central

Wang, Melissa E.; Yuan, Robin K.; Keinath, Alexander T.; Ramos Álvarez, Manuel M.

2015-01-01

The extinction of learned fear is a hippocampus-dependent process thought to embody new learning rather than erasure of the original fear memory, although it is unknown how these competing contextual memories are represented in the hippocampus. We previously demonstrated that contextual fear conditioning results in hippocampal place cell remapping and long-term stabilization of novel representations. Here we report that extinction learning also induces place cell remapping in C57BL/6 mice. Specifically, we observed cells that preferentially remapped during different stages of learning. While some cells remapped in both fear conditioning and extinction, others responded predominantly during extinction, which may serve to modify previous representations as well as encode new safe associations. Additionally, we found cells that remapped primarily during fear conditioning, which could facilitate reacquisition of the original fear association. Moreover, we also observed cells that were stable throughout learning, which may serve to encode the static aspects of the environment. The short-term remapping observed during extinction was not found in animals that did not undergo fear conditioning, or when extinction was conducted outside of the conditioning context. Finally, conditioning and extinction produced an increase in spike phase locking to the theta and gamma frequencies. However, the degree of remapping seen during conditioning and extinction only correlated with gamma synchronization. Our results suggest that the extinction learning is a complex process that involves both modification of pre-existing memories and formation of new ones, and these traces coexist within the same hippocampal representation. PMID:26085635

Oscillatory dynamics and place field maps reflect hippocampal ensemble processing of sequence and place memory under NMDA receptor control.

PubMed

Cabral, Henrique O; Vinck, Martin; Fouquet, Celine; Pennartz, Cyriel M A; Rondi-Reig, Laure; Battaglia, Francesco P

2014-01-22

Place coding in the hippocampus requires flexible combination of sensory inputs (e.g., environmental and self-motion information) with memory of past events. We show that mouse CA1 hippocampal spatial representations may either be anchored to external landmarks (place memory) or reflect memorized sequences of cell assemblies depending on the behavioral strategy spontaneously selected. These computational modalities correspond to different CA1 dynamical states, as expressed by theta and low- and high-frequency gamma oscillations, when switching from place to sequence memory-based processing. These changes are consistent with a shift from entorhinal to CA3 input dominance on CA1. In mice with a deletion of forebrain NMDA receptors, the ability of place cells to maintain a map based on sequence memory is selectively impaired and oscillatory dynamics are correspondingly altered, suggesting that oscillations contribute to selecting behaviorally appropriate computations in the hippocampus and that NMDA receptors are crucial for this function. Copyright © 2014 Elsevier Inc. All rights reserved.

Memory-updating abrogates extinction of learned immunosuppression.

PubMed

Hadamitzky, Martin; Bösche, Katharina; Wirth, Timo; Buck, Benjamin; Beetz, Oliver; Christians, Uwe; Schniedewind, Björn; Lückemann, Laura; Güntürkün, Onur; Engler, Harald; Schedlowski, Manfred

2016-02-01

When memories are recalled, they enter a transient labile phase in which they can be impaired or enhanced followed by a new stabilization process termed reconsolidation. It is unknown, however, whether reconsolidation is restricted to neurocognitive processes such as fear memories or can be extended to peripheral physiological functions as well. Here, we show in a paradigm of behaviorally conditioned taste aversion in rats memory-updating in learned immunosuppression. The administration of sub-therapeutic doses of the immunosuppressant cyclosporin A together with the conditioned stimulus (CS/saccharin) during retrieval blocked extinction of conditioned taste aversion and learned suppression of T cell cytokine (interleukin-2; interferon-γ) production. This conditioned immunosuppression is of clinical relevance since it significantly prolonged the survival time of heterotopically transplanted heart allografts in rats. Collectively, these findings demonstrate that memories can be updated on both neural and behavioral levels as well as on the level of peripheral physiological systems such as immune functioning. Copyright © 2015 Elsevier Inc. All rights reserved.

Cell-adhesion molecules in memory formation.

PubMed

Schmidt, R

1995-01-23

After learning events the CNS of higher organisms selects, which acquired informations are permanently stored as a memory trace. This period of memory consolidation is susceptible to interference by biochemical inhibitors of transcription and translation. Ependymin is a specific CNS glycoprotein functionally involved in memory consolidation in goldfish: after active shock-avoidance conditioning ependymin mRNA is rapidly induced in meningeal fibroblasts followed by enhanced synthesis and secretion of several closely related forms of the protein. Intracranial injections of anti-ependymin antisera or antisense oligodeoxynucleotides interfere specifically with memory consolidation, indicating that only de novo synthesized ependymin molecules are involved. Ependymin is capable of directing the growth of central axons in vitro and participates in neuronal regeneration in situ, presumably by its HNK-1 cell-adhesion epitope. Experiments reviewed in this article suggest a model that involves two regulation mechanisms for the function of ependymin in behavioural plasticity: while hormones appear to determine, how much of this cell adhesion molecule is synthesized after learning, local changes of metal cation concentrations in the micro-environment of activated neurons may polymerize ependymin at those synapses, that have to be consolidated to improve their efficacy for future use.

Age Is Associated with Reduced Sharp-Wave Ripple Frequency and Altered Patterns of Neuronal Variability

PubMed Central

Wiegand, Jean-Paul L.; Gray, Daniel T.; Schimanski, Lesley A.; Lipa, Peter; Barnes, C. A.

2016-01-01

Spatial and episodic memory performance declines with age, and the neural basis for this decline is not well understood. Sharp-wave ripples are brief (∼70 ms) high-frequency oscillatory events generated in the hippocampus and are associated with the consolidation of spatial memories. Given the connection between ripple oscillations and memory consolidation, we investigated whether the structure of ripple oscillations and ripple-triggered patterns of single-unit activity are altered in aged rats. Local field and single-unit activity surrounding sharp-wave ripple events were examined in the CA1 region of the hippocampus of old (n = 5) and young (n = 6) F344 rats during periods of rest preceding and following performance on a place-dependent eyeblink-conditioning task. Neural responses in aged rats differed from responses in young rats in several ways. First, compared with young rats, the rate of ripple occurrence (ripple density) is reduced in aged rats during postbehavior rest. Second, mean ripple frequency during prebehavior and postbehavior rest is lower in aged animals (aged: 132 Hz; young: 146 Hz). Third, single neurons in aged animals responded more consistently from ripple to ripple. Fourth, variability in interspike intervals was greater in aged rats. Finally, neurons were tuned to a narrower range of phases of the ripple oscillation relative to young animals. Together, these results suggest that the CA1 network in aged animals has a reduced “vocabulary” of available representational states. SIGNIFICANCE STATEMENT The hippocampus is a structure that is critical for the formation of episodic memories. Sharp-wave ripple events generated in the hippocampus have been implicated in memory consolidation processes critical to memory stabilization. We examine here whether these ripple oscillations are altered over the course of the life span, which could contribute to hippocampus-dependent memory deficits that occur during aging. This experiment used young and aged memory-impaired rats to examine age-related changes in ripple architecture, ripple-triggered spike variance, and spike-phase coherence. We found that there are, indeed, significant changes in characteristics of ripples in older animals that could impact consolidation processes and memory stabilization in the aged brain. PMID:27194342

Trained immunity: a program of innate immune memory in health and disease

PubMed Central

Netea, Mihai G.; Joosten, Leo A.B.; Latz, Eicke; Mills, Kingston H.G.; Natoli, Gioacchino; Stunnenberg, Hendrik G.; O’Neill, Luke A.J.; Xavier, Ramnik J.

2016-01-01

The general view that only adaptive immunity can build immunological memory has recently been challenged. In organisms lacking adaptive immunity as well as in mammals, the innate immune system can mount resistance to reinfection, a phenomenon termed trained immunity or innate immune memory. Trained immunity is orchestrated by epigenetic reprogramming, broadly defined as sustained changes in gene expression and cell physiology that do not involve permanent genetic changes such as mutations and recombination, which are essential for adaptive immunity. The discovery of trained immunity may open the door for novel vaccine approaches, for new therapeutic strategies for the treatment of immune deficiency states, and for modulation of exaggerated inflammation in autoinflammatory diseases. PMID:27102489

Bidirectional switch of the valence associated with a hippocampal contextual memory engram.

PubMed

Redondo, Roger L; Kim, Joshua; Arons, Autumn L; Ramirez, Steve; Liu, Xu; Tonegawa, Susumu

2014-09-18

The valence of memories is malleable because of their intrinsic reconstructive property. This property of memory has been used clinically to treat maladaptive behaviours. However, the neuronal mechanisms and brain circuits that enable the switching of the valence of memories remain largely unknown. Here we investigated these mechanisms by applying the recently developed memory engram cell- manipulation technique. We labelled with channelrhodopsin-2 (ChR2) a population of cells in either the dorsal dentate gyrus (DG) of the hippocampus or the basolateral complex of the amygdala (BLA) that were specifically activated during contextual fear or reward conditioning. Both groups of fear-conditioned mice displayed aversive light-dependent responses in an optogenetic place avoidance test, whereas both DG- and BLA-labelled mice that underwent reward conditioning exhibited an appetitive response in an optogenetic place preference test. Next, in an attempt to reverse the valence of memory within a subject, mice whose DG or BLA engram had initially been labelled by contextual fear or reward conditioning were subjected to a second conditioning of the opposite valence while their original DG or BLA engram was reactivated by blue light. Subsequent optogenetic place avoidance and preference tests revealed that although the DG-engram group displayed a response indicating a switch of the memory valence, the BLA-engram group did not. This switch was also evident at the cellular level by a change in functional connectivity between DG engram-bearing cells and BLA engram-bearing cells. Thus, we found that in the DG, the neurons carrying the memory engram of a given neutral context have plasticity such that the valence of a conditioned response evoked by their reactivation can be reversed by re-associating this contextual memory engram with a new unconditioned stimulus of an opposite valence. Our present work provides new insight into the functional neural circuits underlying the malleability of emotional memory.

Bidirectional switch of the valence associated with a hippocampal contextual memory engram

PubMed Central

Redondo, Roger L; Kim, Joshua; Arons, Autumn L; Ramirez, Steve; Liu, Xu; Tonegawa, Susumu

2014-01-01

The valence of memories is malleable because of their intrinsic reconstructive property1. This property of memory has been used clinically to treat maladaptive behaviours2. However, the neuronal mechanisms and brain circuits that enable the switching of the valence of memories remain largely unknown. Here, we investigated these mechanisms by applying the recently developed memory engram cell-labelling and -manipulation technique 3,4. We labelled, with Channelrhodopsin-2 (ChR2), a population of cells in either the dorsal dentate gyrus (DG) of the hippocampus or the basolateral complex of the amygdala (BLA) that were specifically activated during contextual fear or reward conditioning. Both groups of fear-conditioned mice displayed aversive light-dependent responses in an optogenetic place avoidance test, whereas both DG- and BLA-labelled mice that underwent reward conditioning exhibited an appetitive response in an optogenetic place preference test. Next, in an attempt to reverse the valence of memory within a subject, mice whose DG or BLA engram had initially been labelled by contextual fear or reward conditioning were subjected to a second conditioning of the opposite valence while their original DG or BLA engram was reactivated by blue light. Subsequent optogenetic place avoidance and preference tests revealed that while the DG-engram group displayed a response indicating a switch of the memory valence, the BLA-engram group did not. This switch was also evident at the cellular level by a change in functional connectivity between DG engram-bearing cells and BLA engram-bearing cells. Thus, we found that in the DG, the neurons carrying the memory engram of a given neutral context have plasticity such that the valence of a conditioned response evoked by their reactivation can be reversed by re-associating this contextual memory engram with a new US of an opposite valence. Our present work provides new insight into the functional neural circuit underlying the malleability of emotional memory. PMID:25162525

On the dynamic nature of the engram: evidence for circuit-level reorganization of object memory traces following reactivation.

PubMed

Winters, Boyer D; Tucci, Mark C; Jacklin, Derek L; Reid, James M; Newsome, James

2011-11-30

Research has implicated the perirhinal cortex (PRh) in several aspects of object recognition memory. The specific role of the hippocampus (HPC) remains controversial, but its involvement in object recognition may pertain to processing contextual information in relation to objects rather than object representation per se. Here we investigated the roles of the PRh and HPC in object memory reconsolidation using the spontaneous object recognition task for rats. Intra-PRh infusions of the protein synthesis inhibitor anisomycin immediately following memory reactivation prevented object memory reconsolidation. Similar deficits were observed when a novel object or a salient contextual change was introduced during the reactivation phase. Intra-HPC infusions of anisomycin, however, blocked object memory reconsolidation only when a contextual change was introduced during reactivation. Moreover, disrupting functional interaction between the HPC and PRh by infusing anisomycin unilaterally into each structure in opposite hemispheres also impaired reconsolidation when reactivation was done in an altered context. These results show for the first time that the PRh is critical for reconsolidation of object memory traces and provide insight into the dynamic process of object memory storage; the selective requirement for hippocampal involvement following reactivation in an altered context suggests a substantial circuit level object trace reorganization whereby an initially PRh-dependent object memory becomes reliant on both the HPC and PRh and their interaction. Such trace reorganization may play a central role in reconsolidation-mediated memory updating and could represent an important aspect of lingering consolidation processes proposed to underlie long-term memory modulation and stabilization.

Visual Working Memory Load-Related Changes in Neural Activity and Functional Connectivity

PubMed Central

Li, Ling; Zhang, Jin-Xiang; Jiang, Tao

2011-01-01

Background Visual working memory (VWM) helps us store visual information to prepare for subsequent behavior. The neuronal mechanisms for sustaining coherent visual information and the mechanisms for limited VWM capacity have remained uncharacterized. Although numerous studies have utilized behavioral accuracy, neural activity, and connectivity to explore the mechanism of VWM retention, little is known about the load-related changes in functional connectivity for hemi-field VWM retention. Methodology/Principal Findings In this study, we recorded electroencephalography (EEG) from 14 normal young adults while they performed a bilateral visual field memory task. Subjects had more rapid and accurate responses to the left visual field (LVF) memory condition. The difference in mean amplitude between the ipsilateral and contralateral event-related potential (ERP) at parietal-occipital electrodes in retention interval period was obtained with six different memory loads. Functional connectivity between 128 scalp regions was measured by EEG phase synchronization in the theta- (4–8 Hz), alpha- (8–12 Hz), beta- (12–32 Hz), and gamma- (32–40 Hz) frequency bands. The resulting matrices were converted to graphs, and mean degree, clustering coefficient and shortest path length was computed as a function of memory load. The results showed that brain networks of theta-, alpha-, beta-, and gamma- frequency bands were load-dependent and visual-field dependent. The networks of theta- and alpha- bands phase synchrony were most predominant in retention period for right visual field (RVF) WM than for LVF WM. Furthermore, only for RVF memory condition, brain network density of theta-band during the retention interval were linked to the delay of behavior reaction time, and the topological property of alpha-band network was negative correlation with behavior accuracy. Conclusions/Significance We suggest that the differences in theta- and alpha- bands between LVF and RVF conditions in functional connectivity and topological properties during retention period may result in the decline of behavioral performance in RVF task. PMID:21789253

Motor skill learning and offline-changes in TGA patients with acute hippocampal CA1 lesions.

PubMed

Döhring, Juliane; Stoldt, Anne; Witt, Karsten; Schönfeld, Robby; Deuschl, Günther; Born, Jan; Bartsch, Thorsten

2017-04-01

Learning and the formation of memory are reflected in various memory systems in the human brain such as the hippocampus based declarative memory system and the striatum-cortex based system involved in motor sequence learning. It is a matter of debate how both memory systems interact in humans during learning and consolidation and how this interaction is influenced by sleep. We studied the effect of an acute dysfunction of hippocampal CA1 neurons on the acquisition (on-line condition) and off-line changes of a motor skill in patients with a transient global amnesia (TGA). Sixteen patients (68 ± 4.4 yrs) were studied in the acute phase and during follow-up using a declarative and procedural test, and were compared to controls. Acute TGA patients displayed profound deficits in all declarative memory functions. During the acute amnestic phase, patients were able to acquire the motor skill task reflected by increasing finger tapping speed across the on-line condition, albeit to a lesser degree than during follow-up or compared to controls. Retrieval two days later indicated a greater off-line gain in motor speed in patients than controls. Moreover, this gain in motor skill performance was negatively correlated to the declarative learning deficit. Our results suggest a differential interaction between procedural and declarative memory systems during acquisition and consolidation of motor sequences in older humans. During acquisition, hippocampal dysfunction attenuates fast learning and thus unmasks the slow and rigid learning curve of striatum-based procedural learning. The stronger gains in the post-consolidation condition in motor skill in CA1 lesioned patients indicate a facilitated consolidation process probably occurring during sleep, and suggest a competitive interaction between the memory systems. These findings might be a reflection of network reorganization and plasticity in older humans and in the presence of CA1 hippocampal pathology. Copyright © 2016 Elsevier Ltd. All rights reserved.

Transient impairment of hippocampus-dependent learning and memory in relatively low-dose of acute radiation syndrome is associated with inhibition of hippocampal neurogenesis.

PubMed

Kim, Joong-Sun; Lee, Hae-June; Kim, Jong Choon; Kang, Seong Soo; Bae, Chun-Sik; Shin, Taekyun; Jin, Jae-Kwang; Kim, Sung Ho; Wang, Hongbing; Moon, Changjong

2008-09-01

Neurogenesis in the adult hippocampus, which occurs constitutively, is vulnerable to ionizing radiation. In the relatively low-dose exposure of acute radiation syndrome (ARS), the change in the adult hippocampal function is poorly understood. This study analyzed the changes in apoptotic cell death and neurogenesis in the DGs of hippocampi from adult ICR mice with single whole-body gamma-irradiation using the TUNEL method and immunohistochemical markers of neurogenesis, Ki-67 and doublecortin (DCX). In addition, the hippocampus-dependent learning and memory tasks after single whole-body gamma-irradiation were examined in order to evaluate the hippocampus-related behavioral dysfunction in the relatively low-dose exposure of ARS. The number of TUNEL-positive apoptotic nuclei in the dentate gyrus (DG) was increased 6-12 h after acute gamma-irradiation (a single dose of 0.5 to 4 Gy). In contrast, the number of Ki-67- and DCX-positive cells began to decrease significantly 6 h postirradiation, reaching its lowest level 24 h after irradiation. The level of Ki-67 and DCX immunoreactivity decreased in a dose-dependent manner within the range of irradiation applied (0-4 Gy). In passive avoidance and object recognition memory test, the mice trained 1 day after acute irradiation (2 Gy) showed significant memory deficits, compared with the sham controls. In conclusion, the pattern of the hippocampus-dependent memory dysfunction is consistent with the change in neurogenesis after acute irradiation. It is suggested that a relatively low dose of ARS in adult ICR mice is sufficiently detrimental to interrupt the functioning of the hippocampus, including learning and memory, possibly through the inhibition of neurogenesis.

Mechanisms of mechanical strain memory in airway smooth muscle.

PubMed

Kim, Hak Rim; Hai, Chi-Ming

2005-10-01

We evaluated the hypothesis that mechanical deformation of airway smooth muscle induces structural remodeling of airway smooth muscle cells, thereby modulating mechanical performance in subsequent contractions. This hypothesis implied that past experience of mechanical deformation was retained (or "memorized") as structural changes in airway smooth muscle cells, which modulated the cell's subsequent contractile responses. We termed this phenomenon mechanical strain memory. Preshortening has been found to induce attenuation of both force and isotonic shortening velocity in cholinergic receptor-activated airway smooth muscle. Rapid stretching of cholinergic receptor-activated airway smooth muscle from an initial length to a final length resulted in post-stretch force and myosin light chain phosphorylation that correlated significantly with initial length. Thus post-stretch muscle strips appeared to retain memory of the initial length prior to rapid stretch (mechanical strain memory). Cytoskeletal recruitment of actin- and integrin-binding proteins and Erk 1/2 MAPK appeared to be important mechanisms of mechanical strain memory. Sinusoidal length oscillation led to force attenuation during oscillation and in subsequent contractions in intact airway smooth muscle, and p38 MAPK appeared to be an important mechanism. In contrast, application of local mechanical strain to cultured airway smooth muscle cells induced local actin polymerization and cytoskeletal stiffening. It is conceivable that deep inspiration-induced bronchoprotection may be a manifestation of mechanical strain memory such that mechanical deformation from past breathing cycles modulated the mechanical performance of airway smooth muscle in subsequent cycles in a continuous and dynamic manner.

Encoding mechano-memories in filamentous-actin networks

NASA Astrophysics Data System (ADS)

Majumdar, Sayantan; Foucard, Louis; Levine, Alex; Gardel, Margaret L.

History-dependent adaptation is a central feature of learning and memory. Incorporating such features into `adaptable materials' that can modify their mechanical properties in response to external cues, remains an outstanding challenge in materials science. Here, we study a novel mechanism of mechano-memory in cross-linked F-actin networks, the essential determinants of the mechanical behavior of eukaryotic cells. We find that the non-linear mechanical response of such networks can be reversibly programmed through induction of mechano-memories. In particular, the direction, magnitude, and duration of previously applied shear stresses can be encoded into the network architecture. The `memory' of the forcing history is long-lived, but it can be erased by force applied in the opposite direction. These results demonstrate that F-actin networks can encode analog read-write mechano-memories which can be used for adaptation to mechanical stimuli. We further show that the mechano-memory arises from changes in the nematic order of the constituent filaments. Our results suggest a new mechanism of mechanical sensing in eukaryotic cells and provide a strategy for designing a novel class of materials. S.M. acknowledges U. Chicago MRSEC for support through a Kadanoff-Rice fellowship.

Complex multicellular functions at a unicellular eukaryote level: Learning, memory, and immunity.

PubMed

Csaba, György

2017-06-01

According to experimental data, eukaryote unicellulars are able to learn, have immunity and memory. Learning is carried out in a very primitive form, and the memory is not neural but an epigenetic one. However, this epigenetic memory, which is well justified by the presence and manifestation of hormonal imprinting, is strong and permanent in the life of cell and also in its progenies. This memory is epigenetically executed by the alteration and fixation of methylation pattern of genes without changes in base sequences. The immunity of unicellulars is based on self/non-self discrimination, which leads to the destruction of non-self invaders and utilization of them as nourishment (by phagocytosis). The tools of learning, memory, and immunity of unicellulars are uniformly found in plasma membrane receptors, which formed under the effect of dynamic receptor pattern generation, suggested by Koch et al., and this is the basis of hormonal imprinting, by which the encounter between a chemical substance and the cell is specifically memorized. The receptors and imprinting are also used in the later steps of evolution up to mammals (including man) in each mentioned functions. This means that learning, memory, and immunity can be deduced to a unicellular eukaryote level.

Oscillatory mechanisms of process binding in memory.

PubMed

Klimesch, Wolfgang; Freunberger, Roman; Sauseng, Paul

2010-06-01

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

Enhanced stability of Bi-doped Ge2Sb2Te5 amorphous films

NASA Astrophysics Data System (ADS)

Dyussembayev, S.; Prikhodko, O.; Tsendin, K.; Timoshenkov, S.; Korobova, N.

2014-09-01

Although, several reviews have appeared on various physical properties and applications of chalcogenide glasses, there is no thorough study of local atomic structure and its modification for eutectic Ge-Sb-Te alloys doped with Bi. Ge2Sb2Te5 pure and Bi-doped films were deposited by ion-plasma sputtering method of synthesized GTS material on Si (100) and glass substrates coated with a conductive Al layer which was used as a bottom electrode. Current-voltage characteristics of different points of the same samples have been measured. Random distribution of inclusions within the sample made it possible to investigate the dependence of switching and memory effects on the phase composition at a constant value of other parameters. Measurements in the current controlled mode clearly showed that the memory state formation voltage does not depend on current in a wide range. Results indicate that the development of imaging technologies phase memory cells need to pay special attention to the conditions of Ge-Sb-Te film preparation. To increase the number of cycles "write - erase" should be additional prolonged annealing of the synthesized films.

Projection specificity in heterogeneous locus coeruleus cell populations: implications for learning and memory

PubMed Central

Uematsu, Akira; Tan, Bao Zhen

2015-01-01

Noradrenergic neurons in the locus coeruleus (LC) play a critical role in many functions including learning and memory. This relatively small population of cells sends widespread projections throughout the brain including to a number of regions such as the amygdala which is involved in emotional associative learning and the medial prefrontal cortex which is important for facilitating flexibility when learning rules change. LC noradrenergic cells participate in both of these functions, but it is not clear how this small population of neurons modulates these partially distinct processes. Here we review anatomical, behavioral, and electrophysiological studies to assess how LC noradrenergic neurons regulate these different aspects of learning and memory. Previous work has demonstrated that subpopulations of LC noradrenergic cells innervate specific brain regions suggesting heterogeneity of function in LC neurons. Furthermore, noradrenaline in mPFC and amygdala has distinct effects on emotional learning and cognitive flexibility. Finally, neural recording data show that LC neurons respond during associative learning and when previously learned task contingencies change. Together, these studies suggest a working model in which distinct and potentially opposing subsets of LC neurons modulate particular learning functions through restricted efferent connectivity with amygdala or mPFC. This type of model may provide a general framework for understanding other neuromodulatory systems, which also exhibit cell type heterogeneity and projection specificity. PMID:26330494

The default mode network and the working memory network are not anti-correlated during all phases of a working memory task.

PubMed

Piccoli, Tommaso; Valente, Giancarlo; Linden, David E J; Re, Marta; Esposito, Fabrizio; Sack, Alexander T; Di Salle, Francesco

2015-01-01

The default mode network and the working memory network are known to be anti-correlated during sustained cognitive processing, in a load-dependent manner. We hypothesized that functional connectivity among nodes of the two networks could be dynamically modulated by task phases across time. To address the dynamic links between default mode network and the working memory network, we used a delayed visuo-spatial working memory paradigm, which allowed us to separate three different phases of working memory (encoding, maintenance, and retrieval), and analyzed the functional connectivity during each phase within and between the default mode network and the working memory network networks. We found that the two networks are anti-correlated only during the maintenance phase of working memory, i.e. when attention is focused on a memorized stimulus in the absence of external input. Conversely, during the encoding and retrieval phases, when the external stimulation is present, the default mode network is positively coupled with the working memory network, suggesting the existence of a dynamically switching of functional connectivity between "task-positive" and "task-negative" brain networks. Our results demonstrate that the well-established dichotomy of the human brain (anti-correlated networks during rest and balanced activation-deactivation during cognition) has a more nuanced organization than previously thought and engages in different patterns of correlation and anti-correlation during specific sub-phases of a cognitive task. This nuanced organization reinforces the hypothesis of a direct involvement of the default mode network in cognitive functions, as represented by a dynamic rather than static interaction with specific task-positive networks, such as the working memory network.

The Default Mode Network and the Working Memory Network Are Not Anti-Correlated during All Phases of a Working Memory Task

PubMed Central

Piccoli, Tommaso; Valente, Giancarlo; Linden, David E. J.; Re, Marta; Esposito, Fabrizio; Sack, Alexander T.; Salle, Francesco Di

2015-01-01

Introduction The default mode network and the working memory network are known to be anti-correlated during sustained cognitive processing, in a load-dependent manner. We hypothesized that functional connectivity among nodes of the two networks could be dynamically modulated by task phases across time. Methods To address the dynamic links between default mode network and the working memory network, we used a delayed visuo-spatial working memory paradigm, which allowed us to separate three different phases of working memory (encoding, maintenance, and retrieval), and analyzed the functional connectivity during each phase within and between the default mode network and the working memory network networks. Results We found that the two networks are anti-correlated only during the maintenance phase of working memory, i.e. when attention is focused on a memorized stimulus in the absence of external input. Conversely, during the encoding and retrieval phases, when the external stimulation is present, the default mode network is positively coupled with the working memory network, suggesting the existence of a dynamically switching of functional connectivity between “task-positive” and “task-negative” brain networks. Conclusions Our results demonstrate that the well-established dichotomy of the human brain (anti-correlated networks during rest and balanced activation-deactivation during cognition) has a more nuanced organization than previously thought and engages in different patterns of correlation and anti-correlation during specific sub-phases of a cognitive task. This nuanced organization reinforces the hypothesis of a direct involvement of the default mode network in cognitive functions, as represented by a dynamic rather than static interaction with specific task-positive networks, such as the working memory network. PMID:25848951

Changes of ploidy during the Azotobacter vinelandii growth cycle.

PubMed Central

Maldonado, R; Jiménez, J; Casadesús, J

1994-01-01

The size of the Azotobacter vinelandii chromosome is approximately 4,700 kb, as calculated by pulsed-field electrophoretic separation of fragments digested with the rarely cutting endonucleases SpeI and SwaI. Surveys of DNA content per cell by flow cytometry indicated the existence of ploidy changes during the A. vinelandii growth cycle in rich medium. Early-exponential-phase cells have a ploidy level similar to that of Escherichia coli or Salmonella typhimurium (probably ca. four chromosomes per cell), but a continuous increase of DNA content per cell is observed during growth. Late-exponential-phase cells may contain > 40 chromosomes per cell, while cells in the early stationary stage may contain > 80 chromosomes per cell. In late-stationary-phase cultures, the DNA content per cell is even higher, probably over 100 chromosome equivalents per cell. A dramatic change is observed in old stationary-phase cultures, when the population of highly polyploid bacteria segregates cells with low ploidy. The DNA content of the latter cells resembles that of cysts, suggesting that the process may reflect the onset of cyst differentiation. Cells with low ploidy are also formed when old stationary-phase cultures are diluted into fresh medium. Addition of rifampin to exponential-phase cultures causes a rapid increase in DNA content, indicating that A. vinelandii initiates multiple rounds of chromosome replication per cell division. Growth in minimal medium does not result in the spectacular changes of ploidy observed during rapid growth; this observation suggests that the polyploidy of A. vinelandii may not exist outside the laboratory. Images PMID:8021173