WorldWideScience

Sample records for non-volatile memory cells

  1. Non-volatile memories

    CERN Document Server

    Lacaze, Pierre-Camille

    2014-01-01

    Written for scientists, researchers, and engineers, Non-volatile Memories describes the recent research and implementations in relation to the design of a new generation of non-volatile electronic memories. The objective is to replace existing memories (DRAM, SRAM, EEPROM, Flash, etc.) with a universal memory model likely to reach better performances than the current types of memory: extremely high commutation speeds, high implantation densities and retention time of information of about ten years.

  2. Emerging non-volatile memories

    CERN Document Server

    Hong, Seungbum; Wouters, Dirk

    2014-01-01

    This book is an introduction to the fundamentals of emerging non-volatile memories and provides an overview of future trends in the field. Readers will find coverage of seven important memory technologies, including Ferroelectric Random Access Memory (FeRAM), Ferromagnetic RAM (FMRAM), Multiferroic RAM (MFRAM), Phase-Change Memories (PCM), Oxide-based Resistive RAM (RRAM), Probe Storage, and Polymer Memories. Chapters are structured to reflect diffusions and clashes between different topics. Emerging Non-Volatile Memories is an ideal book for graduate students, faculty, and professionals working in the area of non-volatile memory. This book also: Covers key memory technologies, including Ferroelectric Random Access Memory (FeRAM), Ferromagnetic RAM (FMRAM), and Multiferroic RAM (MFRAM), among others. Provides an overview of non-volatile memory fundamentals. Broadens readers' understanding of future trends in non-volatile memories.

  3. A room-temperature non-volatile CNT-based molecular memory cell

    Science.gov (United States)

    Ye, Senbin; Jing, Qingshen; Han, Ray P. S.

    2013-04-01

    Recent experiments with a carbon nanotube (CNT) system confirmed that the innertube can oscillate back-and-forth even under a room-temperature excitation. This demonstration of relative motion suggests that it is now feasible to build a CNT-based molecular memory cell (MC), and the key to bring the concept to reality is the precision control of the moving tube for sustained and reliable read/write (RW) operations. Here, we show that by using a 2-section outertube design, we are able to suitably recalibrate the system energetics and obtain the designed performance characteristics of a MC. Further, the resulting energy modification enables the MC to operate as a non-volatile memory element at room temperatures. Our paper explores a fundamental understanding of a MC and its response at the molecular level to roadmap a novel approach in memory technologies that can be harnessed to overcome the miniaturization limit and memory volatility in memory technologies.

  4. Controlled data storage for non-volatile memory cells embedded in nano magnetic logic

    Science.gov (United States)

    Riente, Fabrizio; Ziemys, Grazvydas; Mattersdorfer, Clemens; Boche, Silke; Turvani, Giovanna; Raberg, Wolfgang; Luber, Sebastian; Breitkreutz-v. Gamm, Stephan

    2017-05-01

    Among the beyond-CMOS technologies, perpendicular Nano Magnetic Logic (pNML) is a promising candidate due to its low power consumption, its non-volatility and its monolithic 3D integrability, which makes it possible to integrate memory and logic into the same device by exploiting the interaction of bi-stable nanomagnets with perpendicular magnetic anisotropy. Logic computation and signal synchronization are achieved by focus ion beam irradiation and by pinning domain walls in magnetic notches. However, in realistic circuits, the information storage and their read-out are crucial issues, often ignored in the exploration of beyond-CMOS devices. In this paper we address these issues by experimentally demonstrating a pNML memory element, whose read and write operations can be controlled by two independent pulsed currents. Our results prove the correct behavior of the proposed structure that enables high density memory embedded in the logic plane of 3D-integrated pNML circuits.

  5. Carbon nanomaterials for non-volatile memories

    Science.gov (United States)

    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.

  6. Controlled data storage for non-volatile memory cells embedded in nano magnetic logic

    Directory of Open Access Journals (Sweden)

    Fabrizio Riente

    2017-05-01

    Full Text Available Among the beyond-CMOS technologies, perpendicular Nano Magnetic Logic (pNML is a promising candidate due to its low power consumption, its non-volatility and its monolithic 3D integrability, which makes it possible to integrate memory and logic into the same device by exploiting the interaction of bi-stable nanomagnets with perpendicular magnetic anisotropy. Logic computation and signal synchronization are achieved by focus ion beam irradiation and by pinning domain walls in magnetic notches. However, in realistic circuits, the information storage and their read-out are crucial issues, often ignored in the exploration of beyond-CMOS devices. In this paper we address these issues by experimentally demonstrating a pNML memory element, whose read and write operations can be controlled by two independent pulsed currents. Our results prove the correct behavior of the proposed structure that enables high density memory embedded in the logic plane of 3D-integrated pNML circuits.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Jovanović, B., E-mail: bojan.jovanovic@lirmm.fr, E-mail: lionel.torres@lirmm.fr; Brum, R. M.; Torres, L. [LIRMM—University of Montpellier 2/UMR CNRS 5506, 161 Rue Ada, 34095 Montpellier (France)

    2014-04-07

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

  9. Non-volatile memory based on the ferroelectric photovoltaic effect

    Science.gov (United States)

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

    2013-01-01

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

  10. Non Volatile Flash Memory Radiation Tests

    Science.gov (United States)

    Irom, Farokh; Nguyen, Duc N.; Allen, Greg

    2012-01-01

    Commercial flash memory industry has experienced a fast growth in the recent years, because of their wide spread usage in cell phones, mp3 players and digital cameras. On the other hand, there has been increased interest in the use of high density commercial nonvolatile flash memories in space because of ever increasing data requirements and strict power requirements. Because of flash memories complex structure; they cannot be treated as just simple memories in regards to testing and analysis. It becomes quite challenging to determine how they will respond in radiation environments.

  11. EDITORIAL: Non-volatile memory based on nanostructures Non-volatile memory based on nanostructures

    Science.gov (United States)

    Kalinin, Sergei; Yang, J. Joshua; Demming, Anna

    2011-06-01

    Non-volatile memory refers to the crucial ability of computers to store information once the power source has been removed. Traditionally this has been achieved through flash, magnetic computer storage and optical discs, and in the case of very early computers paper tape and punched cards. While computers have advanced considerably from paper and punched card memory devices, there are still limits to current non-volatile memory devices that restrict them to use as secondary storage from which data must be loaded and carefully saved when power is shut off. Denser, faster, low-energy non-volatile memory is highly desired and nanostructures are the critical enabler. This special issue on non-volatile memory based on nanostructures describes some of the new physics and technology that may revolutionise future computers. Phase change random access memory, which exploits the reversible phase change between crystalline and amorphous states, also holds potential for future memory devices. The chalcogenide Ge2Sb2Te5 (GST) is a promising material in this field because it combines a high activation energy for crystallization and a relatively low crystallization temperature, as well as a low melting temperature and low conductivity, which accommodates localized heating. Doping is often used to lower the current required to activate the phase change or 'reset' GST but this often aggravates other problems. Now researchers in Korea report in-depth studies of SiO2-doped GST and identify ways of optimising the material's properties for phase-change random access memory [1]. Resistance switching is an area that has attracted a particularly high level of interest for non-volatile memory technology, and a great deal of research has focused on the potential of TiO2 as a model system in this respect. Researchers at HP labs in the US have made notable progress in this field, and among the work reported in this special issue they describe means to control the switch resistance and show

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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 [Univ. Grenoble Alpes, INAC-SPINTEC, F-38000 Grenoble (France); CNRS, SPINTEC, F-38000 Grenoble (France); CEA, INAC-SPINTEC, F-38000 Grenoble (France); Beigne, E., E-mail: gregory.dipendina@cea.fr, E-mail: eldar.zianbetov@cea.fr, E-mail: edith.beigne@cea.fr [Univ. Grenoble Alpes, CEA, LETI, F-38000 Grenoble (France)

    2015-05-07

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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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

  15. Bioorganic nanodots for non-volatile memory devices

    International Nuclear Information System (INIS)

    Amdursky, Nadav; Shalev, Gil; Handelman, Amir; Natan, Amir; Rosenwaks, Yossi; Litsyn, Simon; Szwarcman, Daniel; Rosenman, Gil; Roizin, Yakov

    2013-01-01

    In recent years we are witnessing an intensive integration of bio-organic nanomaterials in electronic devices. Here we show that the diphenylalanine bio-molecule can self-assemble into tiny peptide nanodots (PNDs) of ∼2 nm size, and can be embedded into metal-oxide-semiconductor devices as charge storage nanounits in non-volatile memory. For that purpose, we first directly observe the crystallinity of a single PND by electron microscopy. We use these nanocrystalline PNDs units for the formation of a dense monolayer on SiO 2 surface, and study the electron/hole trapping mechanisms and charge retention ability of the monolayer, followed by fabrication of PND-based memory cell device

  16. Bioorganic nanodots for non-volatile memory devices

    Energy Technology Data Exchange (ETDEWEB)

    Amdursky, Nadav; Shalev, Gil; Handelman, Amir; Natan, Amir; Rosenwaks, Yossi [School of Electrical Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv 69978 (Israel); Litsyn, Simon; Szwarcman, Daniel; Rosenman, Gil, E-mail: rgil@post.tau.ac.il [School of Electrical Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv 69978 (Israel); StoreDot LTD, 16 Menahem Begin St., Ramat Gan (Israel); Roizin, Yakov [School of Electrical Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv 69978 (Israel); TowerJazz, P.O. Box 619, Migdal HaEmek 23105 (Israel)

    2013-12-01

    In recent years we are witnessing an intensive integration of bio-organic nanomaterials in electronic devices. Here we show that the diphenylalanine bio-molecule can self-assemble into tiny peptide nanodots (PNDs) of ∼2 nm size, and can be embedded into metal-oxide-semiconductor devices as charge storage nanounits in non-volatile memory. For that purpose, we first directly observe the crystallinity of a single PND by electron microscopy. We use these nanocrystalline PNDs units for the formation of a dense monolayer on SiO{sub 2} surface, and study the electron/hole trapping mechanisms and charge retention ability of the monolayer, followed by fabrication of PND-based memory cell device.

  17. Method for refreshing a non-volatile memory

    Science.gov (United States)

    Riekels, James E.; Schlesinger, Samuel

    2008-11-04

    A non-volatile memory and a method of refreshing a memory are described. The method includes allowing an external system to control refreshing operations within the memory. The memory may generate a refresh request signal and transmit the refresh request signal to the external system. When the external system finds an available time to process the refresh request, the external system acknowledges the refresh request and transmits a refresh acknowledge signal to the memory. The memory may also comprise a page register for reading and rewriting a data state back to the memory. The page register may comprise latches in lieu of supplemental non-volatile storage elements, thereby conserving real estate within the memory.

  18. Flexible and twistable non-volatile memory cell array with all-organic one diode-one resistor architecture.

    Science.gov (United States)

    Ji, Yongsung; Zeigler, David F; Lee, Dong Su; Choi, Hyejung; Jen, Alex K-Y; Ko, Heung Cho; Kim, Tae-Wook

    2013-01-01

    Flexible organic memory devices are one of the integral components for future flexible organic electronics. However, high-density all-organic memory cell arrays on malleable substrates without cross-talk have not been demonstrated because of difficulties in their fabrication and relatively poor performances to date. Here we demonstrate the first flexible all-organic 64-bit memory cell array possessing one diode-one resistor architectures. Our all-organic one diode-one resistor cell exhibits excellent rewritable switching characteristics, even during and after harsh physical stresses. The write-read-erase-read output sequence of the cells perfectly correspond to the external pulse signal regardless of substrate deformation. The one diode-one resistor cell array is clearly addressed at the specified cells and encoded letters based on the standard ASCII character code. Our study on integrated organic memory cell arrays suggests that the all-organic one diode-one resistor cell architecture is suitable for high-density flexible organic memory applications in the future.

  19. Active non-volatile memory post-processing

    Energy Technology Data Exchange (ETDEWEB)

    Kannan, Sudarsun; Milojicic, Dejan S.; Talwar, Vanish

    2017-04-11

    A computing node includes an active Non-Volatile Random Access Memory (NVRAM) component which includes memory and a sub-processor component. The memory is to store data chunks received from a processor core, the data chunks comprising metadata indicating a type of post-processing to be performed on data within the data chunks. The sub-processor component is to perform post-processing of said data chunks based on said metadata.

  20. Novel applications of non-volatile memories

    Energy Technology Data Exchange (ETDEWEB)

    Duthie, I

    1982-01-01

    The author reviews briefly the evolution of the programmable memory and the alternative technologies, before discussing the operation of a small EEPROM when used in conjunction with a microprocessor for typical applications. Some applications are reviewed and the opportunities which eeproms can offer for new applications are presented, together with the requirements for artificial intelligence to become a reality.

  1. Organic non-volatile memories from ferroelectric phase separated blends

    Science.gov (United States)

    Asadi, Kamal; de Leeuw, Dago; de Boer, Bert; Blom, Paul

    2009-03-01

    Ferroelectric polarisation is an attractive physical property for non-volatile binary switching. The functionality of the targeted memory should be based on resistive switching. Conductivity and ferroelectricity however cannot be tuned independently. The challenge is to develop a storage medium in which the favourable properties of ferroelectrics such as bistability and non-volatility can be combined with the beneficial properties provided by semiconductors such as conductivity and rectification. In this contribution we present an integrated solution by blending semiconducting and ferroelectric polymers into phase separated networks. The polarisation field of the ferroelectric modulates the injection barrier at the semiconductor--metal contact. This combination allows for solution-processed non-volatile memory arrays with a simple cross-bar architecture that can be read-out non-destructively. Based on this general concept a non-volatile, reversible switchable Schottky diode with relatively fast programming time of shorter than 100 microseconds, long information retention time of longer than 10^ days, and high programming cycle endurance with non-destructive read-out is demonstrated.

  2. Use of non-volatile memories for SSC detector readout

    International Nuclear Information System (INIS)

    Fennelly, A.J.; Woosley, J.K.; Johnson, M.B.

    1990-01-01

    Use of non-volatile memory units at the end of each fiber optic bunch/strand would substantially increase information available from experiments by providing a complete event history, in addition to easing real time processing requirements. This may be an alternative to enhancing technology to optical computing techniques. Available and low-risk projected technologies will be surveyed, with costing addressed. Some discussion will be given to covnersion of optical signals, to electronic information, concepts for providing timing pulses to the memory units, and to the magnetoresistive (MRAM) and ferroelectric (FERAM) random access memory technologies that may be utilized in the prototype system

  3. Low-temperature process steps for realization of non-volatile memory devices

    NARCIS (Netherlands)

    Brunets, I.; Boogaard, A.; Aarnink, Antonius A.I.; Kovalgin, Alexeij Y.; Wolters, Robertus A.M.; Holleman, J.; Schmitz, Jurriaan

    2007-01-01

    In this work, the low-temperature process steps required for the realization of nano-crystal non-volatile memory cells are discussed. An amorphous silicon film, crystallized using a diode pumped solid state green laser irradiating at 532 nm, is proposed as an active layer. The deposition of the

  4. Channel equalization techniques for non-volatile memristor memories

    KAUST Repository

    Naous, Rawan

    2016-03-16

    Channel coding and information theoretic approaches have been utilized in conventional non-volatile memories to overcome their inherent design limitations of leakage, coupling and refresh rates. However, the continuous scaling and integration constraints set on the current devices directed the attention towards emerging memory technologies as suitable alternatives. Memristive devices are prominent candidates to replace the conventional electronics due to its non-volatility and small feature size. Nonetheless, memristor-based memories still encounter an accuracy limitation throughout the read operation addressed as the sneak path phenomenon. The readout data is corrupted with added distortion that increases significantly the bit error rate and jeopardizes the reliability of the read operation. A novel technique is applied to alleviate this distorting effect where the communication channel model is proposed for the memory array. Noise cancellation principles are applied with the aid of preset pilots to extract channel information and adjust the readout values accordingly. The proposed technique has the virtue of high speed, energy efficiency, and low complexity design while achieving high reliability and error-free decoding.

  5. Channel equalization techniques for non-volatile memristor memories

    KAUST Repository

    Naous, Rawan; Zidan, Mohammed A.; Salem, Ahmed Sultan; Salama, Khaled N.

    2016-01-01

    Channel coding and information theoretic approaches have been utilized in conventional non-volatile memories to overcome their inherent design limitations of leakage, coupling and refresh rates. However, the continuous scaling and integration constraints set on the current devices directed the attention towards emerging memory technologies as suitable alternatives. Memristive devices are prominent candidates to replace the conventional electronics due to its non-volatility and small feature size. Nonetheless, memristor-based memories still encounter an accuracy limitation throughout the read operation addressed as the sneak path phenomenon. The readout data is corrupted with added distortion that increases significantly the bit error rate and jeopardizes the reliability of the read operation. A novel technique is applied to alleviate this distorting effect where the communication channel model is proposed for the memory array. Noise cancellation principles are applied with the aid of preset pilots to extract channel information and adjust the readout values accordingly. The proposed technique has the virtue of high speed, energy efficiency, and low complexity design while achieving high reliability and error-free decoding.

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

    Science.gov (United States)

    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

  7. Highly Stretchable Non-volatile Nylon Thread Memory

    Science.gov (United States)

    Kang, Ting-Kuo

    2016-04-01

    Integration of electronic elements into textiles, to afford e-textiles, can provide an ideal platform for the development of lightweight, thin, flexible, and stretchable e-textiles. This approach will enable us to meet the demands of the rapidly growing market of wearable-electronics on arbitrary non-conventional substrates. However the actual integration of the e-textiles that undergo mechanical deformations during both assembly and daily wear or satisfy the requirements of the low-end applications, remains a challenge. Resistive memory elements can also be fabricated onto a nylon thread (NT) for e-textile applications. In this study, a simple dip-and-dry process using graphene-PEDOT:PSS (poly(3,4-ethylenedioxythiophene) polystyrene sulfonate) ink is proposed for the fabrication of a highly stretchable non-volatile NT memory. The NT memory appears to have typical write-once-read-many-times characteristics. The results show that an ON/OFF ratio of approximately 103 is maintained for a retention time of 106 s. Furthermore, a highly stretchable strain and a long-term digital-storage capability of the ON-OFF-ON states are demonstrated in the NT memory. The actual integration of the knitted NT memories into textiles will enable new design possibilities for low-cost and large-area e-textile memory applications.

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

    Science.gov (United States)

    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.

  9. A graphene-based non-volatile memory

    Science.gov (United States)

    Loisel, Loïc.; Maurice, Ange; Lebental, Bérengère; Vezzoli, Stefano; Cojocaru, Costel-Sorin; Tay, Beng Kang

    2015-09-01

    We report on the development and characterization of a simple two-terminal non-volatile graphene switch. After an initial electroforming step during which Joule heating leads to the formation of a nano-gap impeding the current flow, the devices can be switched reversibly between two well-separated resistance states. To do so, either voltage sweeps or pulses can be used, with the condition that VSET achieve reversible switching on more than 100 cycles with resistance ratio values of 104. This approach of graphene memory is competitive as compared to other graphene approaches such as redox of graphene oxide, or electro-mechanical switches with suspended graphene. We suggest a switching model based on a planar electro-mechanical switch, whereby electrostatic, elastic and friction forces are competing to switch devices ON and OFF, and the stability in the ON state is achieved by the formation of covalent bonds between the two stretched sides of the graphene, hence bridging the nano-gap. Developing a planar electro-mechanical switch enables to obtain the advantages of electro-mechanical switches while avoiding most of their drawbacks.

  10. Microwave oven fabricated hybrid memristor devices for non-volatile memory storage

    International Nuclear Information System (INIS)

    Verrelli, E; Gray, R J; O’Neill, M; Kemp, N T; Kelly, S M

    2014-01-01

    Novel hybrid non-volatile memories made using an ultra-fast microwave heating method are reported for the first time. The devices, consisting of aligned ZnO nanorods embedded in poly (methyl methacrylate), require no forming step and exhibit reliable and reproducible bipolar resistive switching at low voltages and with low power usage. We attribute these properties to a combination of the high aspect ratio of the nanorods and the polymeric hybrid structure of the device. The extremely easy, fast and low-cost solution based method of fabrication makes possible the simple and quick production of cheap memory cells. (paper)

  11. Models for Total-Dose Radiation Effects in Non-Volatile Memory

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, Philip Montgomery; Wix, Steven D.

    2017-04-01

    The objective of this work is to develop models to predict radiation effects in non- volatile memory: flash memory and ferroelectric RAM. In flash memory experiments have found that the internal high-voltage generators (charge pumps) are the most sensitive to radiation damage. Models are presented for radiation effects in charge pumps that demonstrate the experimental results. Floating gate models are developed for the memory cell in two types of flash memory devices by Intel and Samsung. These models utilize Fowler-Nordheim tunneling and hot electron injection to charge and erase the floating gate. Erase times are calculated from the models and compared with experimental results for different radiation doses. FRAM is less sensitive to radiation than flash memory, but measurements show that above 100 Krad FRAM suffers from a large increase in leakage current. A model for this effect is developed which compares closely with the measurements.

  12. Design exploration of emerging nano-scale non-volatile memory

    CERN Document Server

    Yu, Hao

    2014-01-01

    This book presents the latest techniques for characterization, modeling and design for nano-scale non-volatile memory (NVM) devices.  Coverage focuses on fundamental NVM device fabrication and characterization, internal state identification of memristic dynamics with physics modeling, NVM circuit design, and hybrid NVM memory system design-space optimization. The authors discuss design methodologies for nano-scale NVM devices from a circuits/systems perspective, including the general foundations for the fundamental memristic dynamics in NVM devices.  Coverage includes physical modeling, as well as the development of a platform to explore novel hybrid CMOS and NVM circuit and system design.   • Offers readers a systematic and comprehensive treatment of emerging nano-scale non-volatile memory (NVM) devices; • Focuses on the internal state of NVM memristic dynamics, novel NVM readout and memory cell circuit design, and hybrid NVM memory system optimization; • Provides both theoretical analysis and pr...

  13. Rad Hard Non Volatile Memory for FPGA BootLoading, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Radiation-hardened non volatile memory (NVM) is needed to store the golden copy of the image(s) has not kept pace with the advances in FPGAs. Consider that a single...

  14. High-performance non-volatile organic ferroelectric memory on banknotes

    KAUST Repository

    Khan, Yasser; Bhansali, Unnat Sampatraj; Alshareef, Husam N.

    2012-01-01

    High-performance non-volatile polymer ferroelectric memory are fabricated on banknotes using poly(vinylidene fluoride trifluoroethylene). The devices show excellent performance with high remnant polarization, low operating voltages, low leakage

  15. Role of Non-Volatile Memories in Automotive and IoT Markets

    Science.gov (United States)

    2017-03-01

    Standard Manufacturing Supply Long Term Short to Medium Term Density Up to 16MB Up to 2MB IO Configuration Up to x128 Up to x32 Design for Test...Role of Non-Volatile Memories in Automotive and IoT Markets Vipin Tiwari Director, Business Development and Product Marketing SST – A Wholly Own...microcontrollers (MCU) and certainly one of the most challenging elements to master. This paper addresses the role of non-volatile memories for

  16. Quasi-unipolar pentacene films embedded with fullerene for non-volatile organic transistor memories

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Juhee; Lee, Sungpyo; Lee, Moo Hyung; Kang, Moon Sung, E-mail: mskang@ssu.ac.kr [Department of Chemical Engineering, Soongsil University, Seoul 156-743 (Korea, Republic of)

    2015-02-09

    Quasi-unipolar non-volatile organic transistor memory (NOTM) can combine the best characteristics of conventional unipolar and ambipolar NOTMs and, as a result, exhibit improved device performance. Unipolar NOTMs typically exhibit a large signal ratio between the programmed and erased current signals but also require a large voltage to program and erase the memory cells. Meanwhile, an ambipolar NOTM can be programmed and erased at lower voltages, but the resulting signal ratio is small. By embedding a discontinuous n-type fullerene layer within a p-type pentacene film, quasi-unipolar NOTMs are fabricated, of which the signal storage utilizes both electrons and holes while the electrical signal relies on only hole conduction. These devices exhibit superior memory performance relative to both pristine unipolar pentacene devices and ambipolar fullerene/pentacene bilayer devices. The quasi-unipolar NOTM exhibited a larger signal ratio between the programmed and erased states while also reducing the voltage required to program and erase a memory cell. This simple approach should be readily applicable for various combinations of advanced organic semiconductors that have been recently developed and thereby should make a significant impact on organic memory research.

  17. Origami-based tunable truss structures for non-volatile mechanical memory operation.

    Science.gov (United States)

    Yasuda, Hiromi; Tachi, Tomohiro; Lee, Mia; Yang, Jinkyu

    2017-10-17

    Origami has recently received significant interest from the scientific community as a method for designing building blocks to construct metamaterials. However, the primary focus has been placed on their kinematic applications by leveraging the compactness and auxeticity of planar origami platforms. Here, we present volumetric origami cells-specifically triangulated cylindrical origami (TCO)-with tunable stability and stiffness, and demonstrate their feasibility as non-volatile mechanical memory storage devices. We show that a pair of TCO cells can develop a double-well potential to store bit information. What makes this origami-based approach more appealing is the realization of two-bit mechanical memory, in which two pairs of TCO cells are interconnected and one pair acts as a control for the other pair. By assembling TCO-based truss structures, we experimentally verify the tunable nature of the TCO units and demonstrate the operation of purely mechanical one- and two-bit memory storage prototypes.Origami is a popular method to design building blocks for mechanical metamaterials. Here, the authors assemble a volumetric origami-based structure, predict its axial and rotational movements during folding, and demonstrate the operation of mechanical one- and two-bit memory storage.

  18. Non-volatile MOS RAM cell with capacitor-isolated nodes that are radiation accessible for rendering a non-permanent programmed information in the cell of a non-volatile one

    NARCIS (Netherlands)

    Widdershoven, Franciscus P.; Annema, Anne J.; Storms, Maurits M.N.; Pelgrom, Marcellinus J.M.; Pelgrom, Marcel J M

    2001-01-01

    A non-volatile, random access memory cell comprises first and second inverters each having an output node cross-coupled by cross-coupling means to an input node of the other inverter for forming a MOS RAM cell. The output node of each inverter is selectively connected via the conductor paths of

  19. Low-power non-volatile spintronic memory: STT-RAM and beyond

    International Nuclear Information System (INIS)

    Wang, K L; Alzate, J G; Khalili Amiri, P

    2013-01-01

    The quest for novel low-dissipation devices is one of the most critical for the future of semiconductor technology and nano-systems. The development of a low-power, universal memory will enable a new paradigm of non-volatile computation. Here we consider STT-RAM as one of the emerging candidates for low-power non-volatile memory. We show different configurations for STT memory and demonstrate strategies to optimize key performance parameters such as switching current and energy. The energy and scaling limits of STT-RAM are discussed, leading us to argue that alternative writing mechanisms may be required to achieve ultralow power dissipation, a necessary condition for direct integration with CMOS at the gate level for non-volatile logic purposes. As an example, we discuss the use of the giant spin Hall effect as a possible alternative to induce magnetization reversal in magnetic tunnel junctions using pure spin currents. Further, we concentrate on magnetoelectric effects, where electric fields are used instead of spin-polarized currents to manipulate the nanomagnets, as another candidate solution to address the challenges of energy efficiency and density. The possibility of an electric-field-controlled magnetoelectric RAM as a promising candidate for ultralow-power non-volatile memory is discussed in the light of experimental data demonstrating voltage-induced switching of the magnetization and reorientation of the magnetic easy axis by electric fields in nanomagnets. (paper)

  20. High-performance non-volatile organic ferroelectric memory on banknotes

    KAUST Repository

    Khan, Yasser

    2012-03-21

    High-performance non-volatile polymer ferroelectric memory are fabricated on banknotes using poly(vinylidene fluoride trifluoroethylene). The devices show excellent performance with high remnant polarization, low operating voltages, low leakage, high mobility, and long retention times. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. High-performance non-volatile organic ferroelectric memory on banknotes.

    Science.gov (United States)

    Khan, M A; Bhansali, Unnat S; Alshareef, H N

    2012-04-24

    High-performance non-volatile polymer ferroelectric memory are fabricated on banknotes using poly(vinylidene fluoride trifluoroethylene). The devices show excellent performance with high remnant polarization, low operating voltages, low leakage, high mobility, and long retention times. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Overview of radiation effects on emerging non-volatile memory technologies

    Directory of Open Access Journals (Sweden)

    Fetahović Irfan S.

    2017-01-01

    Full Text Available In this paper we give an overview of radiation effects in emergent, non-volatile memory technologies. Investigations into radiation hardness of resistive random access memory, ferroelectric random access memory, magneto-resistive random access memory, and phase change memory are presented in cases where these memory devices were subjected to different types of radiation. The obtained results proved high radiation tolerance of studied devices making them good candidates for application in radiation-intensive environments. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 171007

  3. Overview of one transistor type of hybrid organic ferroelectric non-volatile memory

    Institute of Scientific and Technical Information of China (English)

    Young; Tea; Chun; Daping; Chu

    2015-01-01

    Organic ferroelectric memory devices based on field effect transistors that can be configured between two stable states of on and off have been widely researched as the next generation data storage media in recent years.This emerging type of memory devices can lead to a new instrument system as a potential alternative to previous non-volatile memory building blocks in future processing units because of their numerous merits such as cost-effective process,simple structure and freedom in substrate choices.This bi-stable non-volatile memory device of information storage has been investigated using several organic or inorganic semiconductors with organic ferroelectric polymer materials.Recent progresses in this ferroelectric memory field,hybrid system have attracted a lot of attention due to their excellent device performance in comparison with that of all organic systems.In this paper,a general review of this type of ferroelectric non-volatile memory is provided,which include the device structure,organic ferroelectric materials,electrical characteristics and working principles.We also present some snapshots of our previous study on hybrid ferroelectric memories including our recent work based on zinc oxide nanowire channels.

  4. Silicon nano crystal-based non-volatile memory devices

    International Nuclear Information System (INIS)

    Ng, C.Y.; Chen, T.P.; Sreeduth, D.; Chen, Q.; Ding, L.; Du, A.

    2006-01-01

    In this work, we have investigated the performance and reliability of a Flash memory based on silicon nanocrystal synthesized with very-low energy ion beams. The devices are fabricated with a conventional CMOS process and the size of the nanocrystal is ∼ 4 nm as determined from TEM measurement. Electrical properties of the devices with a tunnel oxide of either 3 nm or 7 nm are evaluated. The devices exhibit good endurance up to 10 5 W/E cycles even at the high operation temperature of 85 deg. C for both the tunnel oxide thicknesses. For the thicker tunnel oxide (i.e., the 7-nm tunnel oxide), a good retention performance with an extrapolated 10-year memory window of ∼ 0.3 V (or ∼ 20% of charge lose after 10 years) is achieved. However, ∼ 70% of charge loss after 10 years is expected for the thinner tunnel oxide (i.e., the 3-nm tunnel oxide)

  5. Organic non-volatile memories from ferroelectric phase-separated blends

    Science.gov (United States)

    Asadi, Kamal; de Leeuw, Dago M.; de Boer, Bert; Blom, Paul W. M.

    2008-07-01

    New non-volatile memories are being investigated to keep up with the organic-electronics road map. Ferroelectric polarization is an attractive physical property as the mechanism for non-volatile switching, because the two polarizations can be used as two binary levels. However, in ferroelectric capacitors the read-out of the polarization charge is destructive. The functionality of the targeted memory should be based on resistive switching. In inorganic ferroelectrics conductivity and ferroelectricity cannot be tuned independently. The challenge is to develop a storage medium in which the favourable properties of ferroelectrics such as bistability and non-volatility can be combined with the beneficial properties provided by semiconductors such as conductivity and rectification. Here we present an integrated solution by blending semiconducting and ferroelectric polymers into phase-separated networks. The polarization field of the ferroelectric modulates the injection barrier at the semiconductor-metal contact. The combination of ferroelectric bistability with (semi)conductivity and rectification allows for solution-processed non-volatile memory arrays with a simple cross-bar architecture that can be read out non-destructively. The concept of an electrically tunable injection barrier as presented here is general and can be applied to other electronic devices such as light-emitting diodes with an integrated on/off switch.

  6. High-Speed Non-Volatile Optical Memory: Achievements and Challenges

    Directory of Open Access Journals (Sweden)

    Vadym Zayets

    2017-01-01

    Full Text Available We have proposed, fabricated, and studied a new design of a high-speed optical non-volatile memory. The recoding mechanism of the proposed memory utilizes a magnetization reversal of a nanomagnet by a spin-polarized photocurrent. It was shown experimentally that the operational speed of this memory may be extremely fast above 1 TBit/s. The challenges to realize both a high-speed recording and a high-speed reading are discussed. The memory is compact, integratable, and compatible with present semiconductor technology. If realized, it will advance data processing and computing technology towards a faster operation speed.

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

    Science.gov (United States)

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

    2016-01-01

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

  8. Scalable printed electronics: an organic decoder addressing ferroelectric non-volatile memory

    Science.gov (United States)

    Ng, Tse Nga; Schwartz, David E.; Lavery, Leah L.; Whiting, Gregory L.; Russo, Beverly; Krusor, Brent; Veres, Janos; Bröms, Per; Herlogsson, Lars; Alam, Naveed; Hagel, Olle; Nilsson, Jakob; Karlsson, Christer

    2012-01-01

    Scalable circuits of organic logic and memory are realized using all-additive printing processes. A 3-bit organic complementary decoder is fabricated and used to read and write non-volatile, rewritable ferroelectric memory. The decoder-memory array is patterned by inkjet and gravure printing on flexible plastics. Simulation models for the organic transistors are developed, enabling circuit designs tolerant of the variations in printed devices. We explain the key design rules in fabrication of complex printed circuits and elucidate the performance requirements of materials and devices for reliable organic digital logic. PMID:22900143

  9. Metal-organic molecular device for non-volatile memory storage

    International Nuclear Information System (INIS)

    Radha, B.; Sagade, Abhay A.; Kulkarni, G. U.

    2014-01-01

    Non-volatile memory devices have been of immense research interest for their use in active memory storage in powered off-state of electronic chips. In literature, various molecules and metal compounds have been investigated in this regard. Molecular memory devices are particularly attractive as they offer the ease of storing multiple memory states in a unique way and also represent ubiquitous choice for miniaturized devices. However, molecules are fragile and thus the device breakdown at nominal voltages during repeated cycles hinders their practical applicability. Here, in this report, a synergetic combination of an organic molecule and an inorganic metal, i.e., a metal-organic complex, namely, palladium hexadecylthiolate is investigated for memory device characteristics. Palladium hexadecylthiolate following partial thermolysis is converted to a molecular nanocomposite of Pd(II), Pd(0), and long chain hydrocarbons, which is shown to exhibit non-volatile memory characteristics with exceptional stability and retention. The devices are all solution-processed and the memory action stems from filament formation across the pre-formed cracks in the nanocomposite film.

  10. Non-volatile flash memory with discrete bionanodot floating gate assembled by protein template

    International Nuclear Information System (INIS)

    Miura, Atsushi; Yamashita, Ichiro; Uraoka, Yukiharu; Fuyuki, Takashi; Tsukamoto, Rikako; Yoshii, Shigeo

    2008-01-01

    We demonstrated non-volatile flash memory fabrication by utilizing uniformly sized cobalt oxide (Co 3 O 4 ) bionanodot (Co-BND) architecture assembled by a cage-shaped supramolecular protein template. A fabricated high-density Co-BND array was buried in a metal-oxide-semiconductor field-effect-transistor (MOSFET) structure to use as the charge storage node of a floating nanodot gate memory. We observed a clockwise hysteresis in the drain current-gate voltage characteristics of fabricated BND-embedded MOSFETs. Observed hysteresis obviously indicates a memory operation of Co-BND-embedded MOSFETs due to the charge confinement in the embedded BND and successful functioning of embedded BNDs as the charge storage nodes of the non-volatile flash memory. Fabricated Co-BND-embedded MOSFETs showed good memory properties such as wide memory windows, long charge retention and high tolerance to repeated write/erase operations. A new pathway for device fabrication by utilizing the versatile functionality of biomolecules is presented

  11. Future Trend of Non-Volatile Semiconductor Memory and Feasibility Study of BiCS Type Stacked Structure

    OpenAIRE

    渡辺, 重佳

    2009-01-01

    Future trend of non-volatile semiconductor memory—FeRAM, MRAM, PRAM, ReRAM—compared with NAND typeflash memory has been described based on its history, application and performance. In the realistic point of view,FeRAM and MRAM are suitable for embedded memory and main memory, and PRAM and ReRAM are promising candidatesfor main memory and mass-storage memory for multimedia. Furthermore, the feasibility study of aggressiveultra-low-cost high-speed universal non-volatile semiconductor memory has...

  12. ZnO as dielectric for optically transparent non-volatile memory

    International Nuclear Information System (INIS)

    Salim, N. Tjitra; Aw, K.C.; Gao, W.; Wright, Bryon E.

    2009-01-01

    This paper discusses the application of a DC sputtered ZnO thin film as a dielectric in an optically transparent non-volatile memory. The main motivation for using ZnO as a dielectric is due to its optical transparency and mechanical flexibility. We have established the relationship between the electrical resistivity (ρ) and the activation energy (E a ) of the electron transport in the conduction band of the ZnO film. The ρ of 2 x 10 4 -5 x 10 7 Ω-cm corresponds to E a of 0.36-0.76 eV, respectively. The k-value and optical band-gap for films sputtered with Ar:O 2 ratio of 4:1 are 53 ± 3.6 and 3.23 eV, respectively. In this paper, the basic charge storage element for a non-volatile memory is a triple layer dielectric structure in which a 50 nm thick ZnO film is sandwiched between two layers of methyl silsesquioxane sol-gel dielectric of varying thickness. A pronounced clockwise capacitance-voltage (C-V) hysteresis was observed with a memory window of 6 V. The integration with a solution-processable pentacene, 13,6-N-Sulfinylacetamodipentacene resulted in an optically transparent organic field effect transistor non-volatile memory (OFET-NVM). We have demonstrated that this OFET-NVM can be electrically programmed and erased at low voltage (± 10 V) with a threshold voltage shift of 4.0 V.

  13. Non-volatile main memory management methods based on a file system.

    Science.gov (United States)

    Oikawa, Shuichi

    2014-01-01

    There are upcoming non-volatile (NV) memory technologies that provide byte addressability and high performance. PCM, MRAM, and STT-RAM are such examples. Such NV memory can be used as storage because of its data persistency without power supply while it can be used as main memory because of its high performance that matches up with DRAM. There are a number of researches that investigated its uses for main memory and storage. They were, however, conducted independently. This paper presents the methods that enables the integration of the main memory and file system management for NV memory. Such integration makes NV memory simultaneously utilized as both main memory and storage. The presented methods use a file system as their basis for the NV memory management. We implemented the proposed methods in the Linux kernel, and performed the evaluation on the QEMU system emulator. The evaluation results show that 1) the proposed methods can perform comparably to the existing DRAM memory allocator and significantly better than the page swapping, 2) their performance is affected by the internal data structures of a file system, and 3) the data structures appropriate for traditional hard disk drives do not always work effectively for byte addressable NV memory. We also performed the evaluation of the effects caused by the longer access latency of NV memory by cycle-accurate full-system simulation. The results show that the effect on page allocation cost is limited if the increase of latency is moderate.

  14. A Survey of Soft-Error Mitigation Techniques for Non-Volatile Memories

    Directory of Open Access Journals (Sweden)

    Sparsh Mittal

    2017-02-01

    Full Text Available Non-volatile memories (NVMs offer superior density and energy characteristics compared to the conventional memories; however, NVMs suffer from severe reliability issues that can easily eclipse their energy efficiency advantages. In this paper, we survey architectural techniques for improving the soft-error reliability of NVMs, specifically PCM (phase change memory and STT-RAM (spin transfer torque RAM. We focus on soft-errors, such as resistance drift and write disturbance, in PCM and read disturbance and write failures in STT-RAM. By classifying the research works based on key parameters, we highlight their similarities and distinctions. We hope that this survey will underline the crucial importance of addressing NVM reliability for ensuring their system integration and will be useful for researchers, computer architects and processor designers.

  15. A direct metal transfer method for cross-bar type polymer non-volatile memory applications

    International Nuclear Information System (INIS)

    Kim, Tae-Wook; Lee, Kyeongmi; Oh, Seung-Hwan; Wang, Gunuk; Kim, Dong-Yu; Jung, Gun-Young; Lee, Takhee

    2008-01-01

    Polymer non-volatile memory devices in 8 x 8 array cross-bar architecture were fabricated by a non-aqueous direct metal transfer (DMT) method using a two-step thermal treatment. Top electrodes with a linewidth of 2 μm were transferred onto the polymer layer by the DMT method. The switching behaviour of memory devices fabricated by the DMT method was very similar to that of devices fabricated by the conventional shadow mask method. The devices fabricated using the DMT method showed three orders of magnitude of on/off ratio with stable resistance switching, demonstrating that the DMT method can be a simple process to fabricate organic memory array devices

  16. Non-volatile memory devices with redox-active diruthenium molecular compound

    International Nuclear Information System (INIS)

    Pookpanratana, S; Zhu, H; Bittle, E G; Richter, C A; Li, Q; Hacker, C A; Natoli, S N; Ren, T

    2016-01-01

    Reduction-oxidation (redox) active molecules hold potential for memory devices due to their many unique properties. We report the use of a novel diruthenium-based redox molecule incorporated into a non-volatile Flash-based memory device architecture. The memory capacitor device structure consists of a Pd/Al 2 O 3 /molecule/SiO 2 /Si structure. The bulky ruthenium redox molecule is attached to the surface by using a ‘click’ reaction and the monolayer structure is characterized by x-ray photoelectron spectroscopy to verify the Ru attachment and molecular density. The ‘click’ reaction is particularly advantageous for memory applications because of (1) ease of chemical design and synthesis, and (2) provides an additional spatial barrier between the oxide/silicon to the diruthenium molecule. Ultraviolet photoelectron spectroscopy data identified the energy of the electronic levels of the surface before and after surface modification. The molecular memory devices display an unsaturated charge storage window attributed to the intrinsic properties of the redox-active molecule. Our findings demonstrate the strengths and challenges with integrating molecular layers within solid-state devices, which will influence the future design of molecular memory devices. (paper)

  17. The floating-gate non-volatile semiconductor memory--from invention to the digital age.

    Science.gov (United States)

    Sze, S M

    2012-10-01

    In the past 45 years (from 1967 to 2012), the non-volatile semiconductor memory (NVSM) has emerged from a floating-gate concept to the prime technology driver of the largest industry in the world-the electronics industry. In this paper, we briefly review the historical development of NVSM and project its future trends to the year 2020. In addition, we consider NVSM's wide-range of applications from the digital cellular phone to tablet computer to digital television. As the device dimension is scaled down to the deca-nanometer regime, we expect that many innovations will be made to meet the scaling challenges, and NVSM-inspired technology will continue to enrich and improve our lives for decades to come.

  18. Investigation of High-k Dielectrics and Metal Gate Electrodes for Non-volatile Memory Applications

    Science.gov (United States)

    Jayanti, Srikant

    Due to the increasing demand of non-volatile flash memories in the portable electronics, the device structures need to be scaled down drastically. However, the scalability of traditional floating gate structures beyond 20 nm NAND flash technology node is uncertain. In this regard, the use of metal gates and high-k dielectrics as the gate and interpoly dielectrics respectively, seem to be promising substitutes in order to continue the flash scaling beyond 20nm. Furthermore, research of novel memory structures to overcome the scaling challenges need to be explored. Through this work, the use of high-k dielectrics as IPDs in a memory structure has been studied. For this purpose, IPD process optimization and barrier engineering were explored to determine and improve the memory performance. Specifically, the concept of high-k / low-k barrier engineering was studied in corroboration with simulations. In addition, a novel memory structure comprising a continuous metal floating gate was investigated in combination with high-k blocking oxides. Integration of thin metal FGs and high-k dielectrics into a dual floating gate memory structure to result in both volatile and non-volatile modes of operation has been demonstrated, for plausible application in future unified memory architectures. The electrical characterization was performed on simple MIS/MIM and memory capacitors, fabricated through CMOS compatible processes. Various analytical characterization techniques were done to gain more insight into the material behavior of the layers in the device structure. In the first part of this study, interfacial engineering was investigated by exploring La2O3 as SiO2 scavenging layer. Through the silicate formation, the consumption of low-k SiO2 was controlled and resulted in a significant improvement in dielectric leakage. The performance improvement was also gauged through memory capacitors. In the second part of the study, a novel memory structure consisting of continuous metal FG

  19. A Compute Capable SSD Architecture for Next-Generation Non-volatile Memories

    Energy Technology Data Exchange (ETDEWEB)

    De, Arup [Univ. of California, San Diego, CA (United States)

    2014-01-01

    Existing storage technologies (e.g., disks and ash) are failing to cope with the processor and main memory speed and are limiting the overall perfor- mance of many large scale I/O or data-intensive applications. Emerging fast byte-addressable non-volatile memory (NVM) technologies, such as phase-change memory (PCM), spin-transfer torque memory (STTM) and memristor are very promising and are approaching DRAM-like performance with lower power con- sumption and higher density as process technology scales. These new memories are narrowing down the performance gap between the storage and the main mem- ory and are putting forward challenging problems on existing SSD architecture, I/O interface (e.g, SATA, PCIe) and software. This dissertation addresses those challenges and presents a novel SSD architecture called XSSD. XSSD o oads com- putation in storage to exploit fast NVMs and reduce the redundant data tra c across the I/O bus. XSSD o ers a exible RPC-based programming framework that developers can use for application development on SSD without dealing with the complication of the underlying architecture and communication management. We have built a prototype of XSSD on the BEE3 FPGA prototyping system. We implement various data-intensive applications and achieve speedup and energy ef- ciency of 1.5-8.9 and 1.7-10.27 respectively. This dissertation also compares XSSD with previous work on intelligent storage and intelligent memory. The existing ecosystem and these new enabling technologies make this system more viable than earlier ones.

  20. Process Qualification Strategy for Advances Embedded Non Volatile Memory Technology : The Philips' 0.18um Embedded Flash Case

    NARCIS (Netherlands)

    Tao, Guoqiao; Scarpa, Andrea; van Dijk, Kitty; Kuper, Fred G.

    2003-01-01

    A qualification strategy for advanced embedded non-volatile memory technology has been revealed. This strategy consists of: a thorough understanding of the requirements, extensive use and frequent update of the FMEA (failure mode effect analysis), a qualification plan with excellent coverage of all

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

    Science.gov (United States)

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

    2018-04-09

    As conventional circuits based on field-effect transistors are approaching their physical limits due to quantum phenomena, semi-floating gate transistors have emerged as an alternative ultrafast and silicon-compatible technology. Here, we show a quasi-non-volatile memory featuring a semi-floating gate architecture with band-engineered van der Waals heterostructures. This two-dimensional semi-floating gate memory demonstrates 156 times longer refresh time with respect to that of dynamic random access memory and ultrahigh-speed writing operations on nanosecond timescales. The semi-floating gate architecture greatly enhances the writing operation performance and is approximately 10 6 times faster than other memories based on two-dimensional materials. The demonstrated characteristics suggest that the quasi-non-volatile memory has the potential to bridge the gap between volatile and non-volatile memory technologies and decrease the power consumption required for frequent refresh operations, enabling a high-speed and low-power random access memory.

  2. Four-state non-volatile memory in a multiferroic spin filter tunnel junction

    Science.gov (United States)

    Ruan, Jieji; Li, Chen; Yuan, Zhoushen; Wang, Peng; Li, Aidong; Wu, Di

    2016-12-01

    We report a spin filter type multiferroic tunnel junction with a ferromagnetic/ferroelectric bilayer barrier. Memory functions of a spin filter magnetic tunnel junction and a ferroelectric tunnel junction are combined in this single device, producing four non-volatile resistive states that can be read out in a non-destructive manner. This concept is demonstrated in a LaNiO3/Pr0.8Ca0.2MnO3/BaTiO3/La0.7Sr0.3MnO3 all-oxide tunnel junction. The ferromagnetic insulator Pr0.8Ca0.2MnO3 serves as the spin filter and the ferromagnetic metal La0.7Sr0.3MnO3 is the spin analyzer. The ferroelectric polarization reversal in the BaTiO3 barrier switches the tunneling barrier height to produce a tunneling electroresistance. The ferroelectric switching also modulates the spin polarization and the spin filtering efficiency in Pr0.8Ca0.2MnO3.

  3. Electric field mediated non-volatile tuning magnetism in CoPt/PMN-PT heterostructure for magnetoelectric memory devices

    Science.gov (United States)

    Yang, Y. T.; Li, J.; Peng, X. L.; Wang, X. Q.; Wang, D. H.; Cao, Q. Q.; Du, Y. W.

    2016-02-01

    We report a power efficient non-volatile magnetoelectric memory in the CoPt/(011)PMN-PT heterostructure. Two reversible and stable electric field induced coercivity states (i.e., high-HC or low-HC) are obtained due to the strain mediated converse magnetoelectric effect. The reading process of the different coercive field information written by electric fields is demonstrated by using a magnetoresistance read head. This result shows good prospects in the application of novel multiferroic devices.

  4. Novel ferroelectric capacitor for non-volatile memory storage and biomedical tactile sensor applications

    International Nuclear Information System (INIS)

    Liu, Shi Yang; Chua, Lynn; Tan, Kian Chuan; Valavan, S.E.

    2010-01-01

    We report on novel ferroelectric thin film compositions for use in non-volatile memory storage and biomedical tactile sensor applications. The lead zirconate titanate (PZT) composition was modified by lanthanum (La 3+ ) (PLZT) and vanadium (V 5+ ) (PZTV, PLZTV) doping. Hybrid films with PZTV and PLZTV as top layers are also made using seed layers of differing compositions using sol-gel and spin coating methods. La 3+ doping decreased the coercive field, polarization and leakage current, while increasing the relative permittivity. V 5+ doping, while having similar effects, results in an enhanced polarization, with comparable dielectric loss characteristics. Complex doping of both La 3+ and V 5+ in PLZTV, while reducing the polarization relative to PZTV, significantly decreases the coercive field. Hybrid films have a greater uniformity of grain formation than non-hybrid films, thus decreasing the coercive field, leakage current and polarization fatigue while increasing the relative permittivity. Analysis using X-ray diffraction (XRD) verified the retention of the PZT perovskite structure in the novel films. PLZT/PZTV has been identified as an optimal ferroelectric film composition due to its desirable ferroelectric, fatigue and dielectric properties, including the highest observed remnant polarization (P r ) of ∼ 25 μC/cm 2 , saturation polarization (P sat ) of ∼ 58 μC/cm 2 and low coercive field (E c ) of ∼ 60 kV/cm at an applied field of ∼ 1000 kV/cm, as well as a low leakage current density of ∼ 10 -5 A/cm 2 at 500 kV/cm and fatigue resistance of up to ∼ 10 10 switching cycles.

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

    Science.gov (United States)

    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

  6. Non-exponential resistive switching in Ag2S memristors: a key to nanometer-scale non-volatile memory devices.

    Science.gov (United States)

    Gubicza, Agnes; Csontos, Miklós; Halbritter, András; Mihály, György

    2015-03-14

    The dynamics of resistive switchings in nanometer-scale metallic junctions formed between an inert metallic tip and an Ag film covered by a thin Ag2S layer are investigated. Our thorough experimental analysis and numerical simulations revealed that the resistance change upon a switching bias voltage pulse exhibits a strongly non-exponential behaviour yielding markedly different response times at different bias levels. Our results demonstrate the merits of Ag2S nanojunctions as nanometer-scale non-volatile memory cells with stable switching ratios, high endurance as well as fast response to write/erase, and an outstanding stability against read operations at technologically optimal bias and current levels.

  7. Resistive switching characteristics of polymer non-volatile memory devices in a scalable via-hole structure

    International Nuclear Information System (INIS)

    Kim, Tae-Wook; Choi, Hyejung; Oh, Seung-Hwan; Jo, Minseok; Wang, Gunuk; Cho, Byungjin; Kim, Dong-Yu; Hwang, Hyunsang; Lee, Takhee

    2009-01-01

    The resistive switching characteristics of polyfluorene-derivative polymer material in a sub-micron scale via-hole device structure were investigated. The scalable via-hole sub-microstructure was fabricated using an e-beam lithographic technique. The polymer non-volatile memory devices varied in size from 40 x 40 μm 2 to 200 x 200 nm 2 . From the scaling of junction size, the memory mechanism can be attributed to the space-charge-limited current with filamentary conduction. Sub-micron scale polymer memory devices showed excellent resistive switching behaviours such as a large ON/OFF ratio (I ON /I OFF ∼10 4 ), excellent device-to-device switching uniformity, good sweep endurance, and good retention times (more than 10 000 s). The successful operation of sub-micron scale memory devices of our polyfluorene-derivative polymer shows promise to fabricate high-density polymer memory devices.

  8. Electrical and ferroelectric properties of RF sputtered PZT/SBN on silicon for non-volatile memory applications

    Science.gov (United States)

    Singh, Prashant; Jha, Rajesh Kumar; Singh, Rajat Kumar; Singh, B. R.

    2018-02-01

    We report the integration of multilayer ferroelectric film deposited by RF magnetron sputtering and explore the electrical characteristics for its application as the gate of ferroelectric field effect transistor for non-volatile memories. PZT (Pb[Zr0.35Ti0.65]O3) and SBN (SrBi2Nb2O9) ferroelectric materials were selected for the stack fabrication due to their large polarization and fatigue free properties respectively. Electrical characterization has been carried out to obtain memory window, leakage current density, PUND and endurance characteristics. Fabricated multilayer ferroelectric film capacitor structure shows large memory window of 17.73 V and leakage current density of the order 10-6 A cm-2 for the voltage sweep of -30 to +30 V. This multilayer gate stack of PZT/SBN shows promising endurance property with no degradation in the remnant polarization for the read/write iteration cycles upto 108.

  9. Unipolar resistive switching in metal oxide/organic semiconductor non-volatile memories as a critical phenomenon

    International Nuclear Information System (INIS)

    Bory, Benjamin F.; Meskers, Stefan C. J.; Rocha, Paulo R. F.; Gomes, Henrique L.; Leeuw, Dago M. de

    2015-01-01

    Diodes incorporating a bilayer of an organic semiconductor and a wide bandgap metal oxide can show unipolar, non-volatile memory behavior after electroforming. The prolonged bias voltage stress induces defects in the metal oxide with an areal density exceeding 10 17  m −2 . We explain the electrical bistability by the coexistence of two thermodynamically stable phases at the interface between an organic semiconductor and metal oxide. One phase contains mainly ionized defects and has a low work function, while the other phase has mainly neutral defects and a high work function. In the diodes, domains of the phase with a low work function constitute current filaments. The phase composition and critical temperature are derived from a 2D Ising model as a function of chemical potential. The model predicts filamentary conduction exhibiting a negative differential resistance and nonvolatile memory behavior. The model is expected to be generally applicable to any bilayer system that shows unipolar resistive switching

  10. Technology breakthroughs in high performance metal-oxide-semiconductor devices for ultra-high density, low power non-volatile memory applications

    Science.gov (United States)

    Hong, Augustin Jinwoo

    Non-volatile memory devices have attracted much attention because data can be retained without power consumption more than a decade. Therefore, non-volatile memory devices are essential to mobile electronic applications. Among state of the art non-volatile memory devices, NAND flash memory has earned the highest attention because of its ultra-high scalability and therefore its ultra-high storage capacity. However, human desire as well as market competition requires not only larger storage capacity but also lower power consumption for longer battery life time. One way to meet this human desire and extend the benefits of NAND flash memory is finding out new materials for storage layer inside the flash memory, which is called floating gate in the state of the art flash memory device. In this dissertation, we study new materials for the floating gate that can lower down the power consumption and increase the storage capacity at the same time. To this end, we employ various materials such as metal nanodot, metal thin film and graphene incorporating complementary-metal-oxide-semiconductor (CMOS) compatible processes. Experimental results show excellent memory effects at relatively low operating voltages. Detailed physics and analysis on experimental results are discussed. These new materials for data storage can be promising candidates for future non-volatile memory application beyond the state of the art flash technologies.

  11. Emerging Non-volatile Memory Technologies Exploration Flow for Processor Architecture

    OpenAIRE

    senni , sophiane; Torres , Lionel; Sassatelli , Gilles; Gamatié , Abdoulaye; Mussard , Bruno

    2015-01-01

    International audience; Most die area of today's systems-on-chips is occupied by memories. Hence, a significant proportion of total power is spent on memory systems. Moreover, since processing elements have to be fed with instructions and data from memories, memory plays a key role for system's performance. As a result, memories are a critical part of future embedded systems. Continuing CMOS scaling leads to manufacturing constraints and power consumption issues for the current three main mem...

  12. NVL-C: Static Analysis Techniques for Efficient, Correct Programming of Non-Volatile Main Memory Systems

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seyong [ORNL; Vetter, Jeffrey S [ORNL

    2016-01-01

    Computer architecture experts expect that non-volatile memory (NVM) hierarchies will play a more significant role in future systems including mobile, enterprise, and HPC architectures. With this expectation in mind, we present NVL-C: a novel programming system that facilitates the efficient and correct programming of NVM main memory systems. The NVL-C programming abstraction extends C with a small set of intuitive language features that target NVM main memory, and can be combined directly with traditional C memory model features for DRAM. We have designed these new features to enable compiler analyses and run-time checks that can improve performance and guard against a number of subtle programming errors, which, when left uncorrected, can corrupt NVM-stored data. Moreover, to enable recovery of data across application or system failures, these NVL-C features include a flexible directive for specifying NVM transactions. So that our implementation might be extended to other compiler front ends and languages, the majority of our compiler analyses are implemented in an extended version of LLVM's intermediate representation (LLVM IR). We evaluate NVL-C on a number of applications to show its flexibility, performance, and correctness.

  13. BLACKCOMB2: Hardware-software co-design for non-volatile memory in exascale systems

    Energy Technology Data Exchange (ETDEWEB)

    Mudge, Trevor [Univ. of Michigan, Ann Arbor, MI (United States)

    2017-12-15

    This work was part of a larger project, Blackcomb2, centered at Oak Ridge National Labs (Jeff Vetter PI) to investigate the opportunities for replacing or supplementing DRAM main memory with nonvolatile memory (NVmemory) in Exascale memory systems. The goal was to reduce the energy consumed by in future supercomputer memory systems and to improve their resiliency. Building on the accomplishments of the original Blackcomb Project, funded in 2010, the goal for Blackcomb2 was to identify, evaluate, and optimize the most promising emerging memory technologies, architecture hardware and software technologies, which are essential to provide the necessary memory capacity, performance, resilience, and energy efficiency in Exascale systems. Capacity and energy are the key drivers.

  14. Highly conducting leakage-free electrolyte for SrCoOx-based non-volatile memory device

    Science.gov (United States)

    Katase, Takayoshi; Suzuki, Yuki; Ohta, Hiromichi

    2017-10-01

    The electrochemical switching of SrCoOx-based non-volatile memory with a thin-film-transistor structure was examined by using liquid-leakage-free electrolytes with different conductivities (σ) as the gate insulator. We first examined leakage-free water, which is incorporated in the amorphous (a-) 12CaO.7Al2O3 film with a nanoporous structure (Calcium Aluminate with Nanopore), but the electrochemical oxidation/reduction of the SrCoOx layer required the application of a high gate voltage (Vg) up to 20 V for a very long current-flowing-time (t) ˜40 min, primarily due to the low σ [2.0 × 10-8 S cm-1 at room temperature (RT)] of leakage-free water. We then controlled the σ of the leakage-free electrolyte, infiltrated in the a-NaxTaO3 film with a nanopillar array structure, from 8.0 × 10-8 S cm-1 to 2.5 × 10-6 S cm-1 at RT by changing the x = 0.01-1.0. As the result, the t, required for the metallization of the SrCoOx layer under small Vg = -3 V, becomes two orders of magnitude shorter with increase of the σ of the a-NaxTaO3 leakage-free electrolyte. These results indicate that the ion migration in the leakage-free electrolyte is the rate-determining step for the electrochemical switching, compared to the other electrochemical process, and the high σ of the leakage-free electrolyte is the key factor for the development of the non-volatile SrCoOx-based electro-magnetic phase switching device.

  15. Silicon photonic integrated circuits with electrically programmable non-volatile memory functions.

    Science.gov (United States)

    Song, J-F; Lim, A E-J; Luo, X-S; Fang, Q; Li, C; Jia, L X; Tu, X-G; Huang, Y; Zhou, H-F; Liow, T-Y; Lo, G-Q

    2016-09-19

    Conventional silicon photonic integrated circuits do not normally possess memory functions, which require on-chip power in order to maintain circuit states in tuned or field-configured switching routes. In this context, we present an electrically programmable add/drop microring resonator with a wavelength shift of 426 pm between the ON/OFF states. Electrical pulses are used to control the choice of the state. Our experimental results show a wavelength shift of 2.8 pm/ms and a light intensity variation of ~0.12 dB/ms for a fixed wavelength in the OFF state. Theoretically, our device can accommodate up to 65 states of multi-level memory functions. Such memory functions can be integrated into wavelength division mutiplexing (WDM) filters and applied to optical routers and computing architectures fulfilling large data downloading demands.

  16. Fabrication of Pb (Zr, Ti) O3 Thin Film for Non-Volatile Memory Device Application

    International Nuclear Information System (INIS)

    Mar Lar Win

    2011-12-01

    Ferroelectric lead zirconate titanate powder was composed of mainly the oxides of titanium, zirconium and lead. PZT powder was firstly prepared by thermal synthesis at different Zr/Ti ratios with various sintering temperatures. PZT thin film was fabricated on SiO2/Si substrate by using thermal evaporation method. Physical and elemental analysis were carried out by using SEM, EDX and XRD The ferroelectric properties and the switching behaviour of the PZT thin films were investigated. The ferroelectric properties and switching properties of the PZT thin film (near morphotropic phase boundary sintered at 800 C) could function as a nonvolatile memory.

  17. The microstructure investigation of GeTi thin film used for non-volatile memory

    International Nuclear Information System (INIS)

    Shen Jie; Liu Bo; Song Zhitang; Xu Cheng; Liang Shuang; Feng Songlin; Chen Bomy

    2008-01-01

    GeTi thin film has been found to have the reversible resistance switching property in our previous work. In this paper, the microstructure of this material with a given composition was investigated. The film was synthesized by magnetron sputtering and treated by the rapid temperature process. The results indicate a coexist status of amorphous and polycrystalline states in the as-deposited GeTi film, and the grains in the film are extremely fine. Furthermore, not until the film annealed at 600 deg. C, can the polycrystalline state be detected by X-ray diffraction. Based on the morphological analysis, the sputtered GeTi has the column growth tendency, and the column structure vanishes with the temperature increasing. The microstructure and thermal property analysis indicate that GeTi does not undergo evident phase change process during the annealing process, which makes the switching mechanism of GeTi different from that of chalcogenide memory material, the most widely used phase change memory material

  18. In-chip optical CD measurements for non-volatile memory devices

    Science.gov (United States)

    Vasconi, Mauro; Kremer, Stephanie; Polli, M.; Severgnini, Ermes; Trovati, Silvia S.

    2006-03-01

    A potential limitation to a wider usage of the scatterometry technique for CD evaluation comes from its requirement of dedicated regular measurement gratings, located in wafer scribe lanes. In fact, the simplification of the original chip layout that is often requested to design these gratings may impact on their printed dimension and shape. Etched gratings might also suffer from micro-loading effects other than in the circuit. For all these reasons, measurements collected therein may not represent the real behavior of the device. On the other hand, memory devices come with large sectors that usually possess the characteristics required for a proper scatterometry evaluation. In particular, for a leading edge flash process this approach is in principle feasible for the most critical process steps. The impact of potential drawbacks, mainly lack of pattern regularity within the tool probe area, is investigated. More, a very large sampling plan on features with equal nominal CD and density spread over the same exposure shot becomes feasible, thus yielding a deeper insight of the overall lithographic process window and a quantitative method to evaluate process equipment performance along time by comparison to acceptance data and/or last preventive maintenance. All the results gathered in the device main array are compared to those collected in standard scatterometry targets, tailored to the characteristics of the considered layers in terms of designed CD, pitch, stack and orientation.

  19. Different importance of the volatile and non-volatile fractions of an olfactory signature for individual social recognition in rats versus mice and short-term versus long-term memory.

    Science.gov (United States)

    Noack, Julia; Richter, Karin; Laube, Gregor; Haghgoo, Hojjat Allah; Veh, Rüdiger W; Engelmann, Mario

    2010-11-01

    When tested in the olfactory cued social recognition/discrimination test, rats and mice differ in their retention of a recognition memory for a previously encountered conspecific juvenile: Rats are able to recognize a given juvenile for approximately 45 min only whereas mice show not only short-term, but also long-term recognition memory (≥ 24 h). Here we modified the social recognition/social discrimination procedure to investigate the neurobiological mechanism(s) underlying the species differences. We presented a conspecific juvenile repeatedly to the experimental subjects and monitored the investigation duration as a measure for recognition. Presentation of only the volatile fraction of the juvenile olfactory signature was sufficient for both short- and long-term recognition in mice but not rats. Applying additional volatile, mono-molecular odours to the "to be recognized" juveniles failed to affect short-term memory in both species, but interfered with long-term recognition in mice. Finally immunocytochemical analysis of c-Fos as a marker for cellular activation, revealed that juvenile exposure stimulated areas involved in the processing of olfactory signals in both the main and the accessory olfactory bulb in mice. In rats, we measured an increased c-Fos synthesis almost exclusively in cells of the accessory olfactory bulb. Our data suggest that the species difference in the retention of social recognition memory is based on differences in the processing of the volatile versus non-volatile fraction of the individuals' olfactory signature. The non-volatile fraction is sufficient for retaining a short-term social memory only. Long-term social memory - as observed in mice - requires a processing of both the volatile and non-volatile fractions of the olfactory signature. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. In search of the next memory inside the circuitry from the oldest to the emerging non-volatile memories

    CERN Document Server

    Campardo, Giovanni

    2017-01-01

    This book provides students and practicing chip designers with an easy-to-follow yet thorough, introductory treatment of the most promising emerging memories under development in the industry. Focusing on the chip designer rather than the end user, this book offers expanded, up-to-date coverage of emerging memories circuit design. After an introduction on the old solid-state memories and the fundamental limitations soon to be encountered, the working principle and main technology issues of each of the considered technologies (PCRAM, MRAM, FeRAM, ReRAM) are reviewed and a range of topics related to design is explored: the array organization, sensing and writing circuitry, programming algorithms and error correction techniques are reviewed comparing the approach followed and the constraints for each of the technologies considered. Finally the issue of radiation effects on memory devices has been briefly treated. Additionally some considerations are entertained about how emerging memories can find a place in the...

  1. The origin of traps and the effect of nitrogen plasma in oxide-nitride-oxide structures for non-volatile memories

    International Nuclear Information System (INIS)

    Kim, W. S.; Kwak, D. W.; Oh, J. S.; Lee, D. W.; Cho, H. Y.

    2010-01-01

    Ultrathin oxide-nitride-oxide (ONO) dielectric stacked layers are fundamental structures of silicon-oxide-nitride-oxide-silicon (SONOS) non-volatile memory devices in which information is known to be stored as charges trapped in silicon nitride. Deep-level transient spectroscopy (DLTS) and a capacitance-voltage (CV) analysis were introduced to observe the trap behavior related to the memory effect in memory devices. The DLTS results verified that the nitride-related traps were a dominant factor in the memory effect. The energy of hole traps was 0.307 eV above the balance band. To improve the memory effects of the non-volatile memory devices with ONO structures, we introduced a nitrogen plasma treatment. After the N-plasma treatment, the flat-band voltage shift (ΔV FB ) was increased by about 1.5 times. The program and the erase (P-E) characteristics were also shown to be better than those for the as-ONO structure. In addition, the retention characteristics were improved by over 2.4 times.

  2. Atomic layer-deposited Al–HfO{sub 2}/SiO{sub 2} bi-layers towards 3D charge trapping non-volatile memory

    Energy Technology Data Exchange (ETDEWEB)

    Congedo, Gabriele, E-mail: gabriele.congedo@mdm.imm.cnr.it; Wiemer, Claudia; Lamperti, Alessio; Cianci, Elena; Molle, Alessandro; Volpe, Flavio G.; Spiga, Sabina, E-mail: sabina.spiga@mdm.imm.cnr

    2013-04-30

    A metal/oxide/high-κ dielectric/oxide/silicon (MOHOS) planar charge trapping memory capacitor including SiO{sub 2} as tunnel oxide, Al–HfO{sub 2} as charge trapping layer, SiO{sub 2} as blocking oxide and TaN metal gate was fabricated and characterized as test vehicle in the view of integration into 3D cells. The thin charge trapping layer and blocking oxide were grown by atomic layer deposition, the technique of choice for the implementation of these stacks into 3D structures. The oxide stack shows a good thermal stability for annealing temperature of 900 °C in N{sub 2}, as required for standard complementary metal–oxide–semiconductor processes. MOHOS capacitors can be efficiently programmed and erased under the applied voltages of ± 20 V to ± 12 V. When compared to a benchmark structure including thin Si{sub 3}N{sub 4} as charge trapping layer, the MOHOS cell shows comparable program characteristics, with the further advantage of the equivalent oxide thickness scalability due to the high dielectric constant (κ) value of 32, and an excellent retention even for strong testing conditions. Our results proved that high-κ based oxide structures grown by atomic layer deposition can be of interest for the integration into three dimensionally stacked charge trapping devices. - Highlights: ► Charge trapping device with Al–HfO{sub 2} storage layer is fabricated and characterized. ► Al–HfO{sub 2} and SiO{sub 2} blocking oxides are deposited by atomic layer deposition. ► The oxide stack shows a good thermal stability after annealing at 900 °C. ► The device can be efficiently programmed/erased and retention is excellent. ► The oxide stack could be used for 3D-stacked Flash non-volatile memories.

  3. High performance non-volatile ferroelectric copolymer memory based on a ZnO nanowire transistor fabricated on a transparent substrate

    International Nuclear Information System (INIS)

    Nedic, Stanko; Welland, Mark; Tea Chun, Young; Chu, Daping; Hong, Woong-Ki

    2014-01-01

    A high performance ferroelectric non-volatile memory device based on a top-gate ZnO nanowire (NW) transistor fabricated on a glass substrate is demonstrated. The ZnO NW channel was spin-coated with a poly (vinylidenefluoride-co-trifluoroethylene) (P(VDF-TrFE)) layer acting as a top-gate dielectric without buffer layer. Electrical conductance modulation and memory hysteresis are achieved by a gate electric field induced reversible electrical polarization switching of the P(VDF-TrFE) thin film. Furthermore, the fabricated device exhibits a memory window of ∼16.5 V, a high drain current on/off ratio of ∼10 5 , a gate leakage current below ∼300 pA, and excellent retention characteristics for over 10 4 s

  4. Non-volatile nano-floating gate memory with Pt-Fe{sub 2}O{sub 3} composite nanoparticles and indium gallium zinc oxide channel

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Quanli [Myongji University, Department of Nano Science and Engineering (Korea, Republic of); Lee, Seung Chang; Baek, Yoon-Jae [Myongji University, Department of Materials Science and Engineering (Korea, Republic of); Lee, Hyun Ho [Myongji University, Department of Chemical Engineering (Korea, Republic of); Kang, Chi Jung [Myongji University, Department of Nano Science and Engineering (Korea, Republic of); Kim, Hyun-Mi; Kim, Ki-Bum [Seoul National University, Department of Materials Science and Engineering (Korea, Republic of); Yoon, Tae-Sik, E-mail: tsyoon@mju.ac.kr [Myongji University, Department of Nano Science and Engineering (Korea, Republic of)

    2013-02-15

    Non-volatile nano-floating gate memory characteristics with colloidal Pt-Fe{sub 2}O{sub 3} composite nanoparticles with a mostly core-shell structure and indium gallium zinc oxide channel layer were investigated. The Pt-Fe{sub 2}O{sub 3} nanoparticles were chemically synthesized through the preferential oxidation of Fe and subsequent pileup of Pt into the core in the colloidal solution. The uniformly assembled nanoparticles' layer could be formed with a density of {approx}3 Multiplication-Sign 10{sup 11} cm{sup -2} by a solution-based dip-coating process. The Pt core ({approx}3 nm in diameter) and Fe{sub 2}O{sub 3}-shell ({approx}6 nm in thickness) played the roles of the charge storage node and tunneling barrier, respectively. The device exhibited the hysteresis in current-voltage measurement with a threshold voltage shift of {approx}4.76 V by gate voltage sweeping to +30 V. It also showed the threshold shift of {approx}0.66 V after pulse programming at +20 V for 1 s with retention > {approx}65 % after 10{sup 4} s. These results demonstrate the feasibility of using colloidal nanoparticles with core-shell structure as gate stacks of the charge storage node and tunneling dielectric for low-temperature and solution-based processed non-volatile memory devices.

  5. Large scale integration of flexible non-volatile, re-addressable memories using P(VDF-TrFE) and amorphous oxide transistors

    International Nuclear Information System (INIS)

    Gelinck, Gerwin H; Cobb, Brian; Van Breemen, Albert J J M; Myny, Kris

    2015-01-01

    Ferroelectric polymers and amorphous metal oxide semiconductors have emerged as important materials for re-programmable non-volatile memories and high-performance, flexible thin-film transistors, respectively. However, realizing sophisticated transistor memory arrays has proven to be a challenge, and demonstrating reliable writing to and reading from such a large scale memory has thus far not been demonstrated. Here, we report an integration of ferroelectric, P(VDF-TrFE), transistor memory arrays with thin-film circuitry that can address each individual memory element in that array. n-type indium gallium zinc oxide is used as the active channel material in both the memory and logic thin-film transistors. The maximum process temperature is 200 °C, allowing plastic films to be used as substrate material. The technology was scaled up to 150 mm wafer size, and offers good reproducibility, high device yield and low device variation. This forms the basis for successful demonstration of memory arrays, read and write circuitry, and the integration of these. (paper)

  6. An ultra-low-power area-efficient non-volatile memory in a 0.18 μm single-poly CMOS process for passive RFID tags

    International Nuclear Information System (INIS)

    Jia Xiaoyun; Feng Peng; Zhang Shengguang; Wu Nanjian; Zhao Baiqin; Liu Su

    2013-01-01

    This paper presents an ultra-low-power area-efficient non-volatile memory (NVM) in a 0.18 μm single-poly standard CMOS process for passive radio frequency identification (RFID) tags. In the memory cell, a novel low-power operation method is proposed to realize bi-directional Fowler—Nordheim tunneling during write operation. Furthermore, the cell is designed with PMOS transistors and coupling capacitors to minimize its area. In order to improve its reliability, the cell consists of double floating gates to store the data, and the 1 kbit NVM was implemented in a 0.18 μm single-poly standard CMOS process. The area of the memory cell and 1 kbit memory array is 96 μm 2 and 0.12 mm 2 , respectively. The measured results indicate that the program/erase voltage ranges from 5 to 6 V The power consumption of the read/write operation is 0.19 μW/0.69 μW at a read/write rate of (268 kb/s)/(3.0 kb/s). (semiconductor integrated circuits)

  7. Laser Nanosoldering of Golden and Magnetite Particles and its Possible Application in 3D Printing Devices and Four-Valued Non-Volatile Memories

    Directory of Open Access Journals (Sweden)

    Jaworski Jacek

    2015-12-01

    Full Text Available In recent years the 3D printing methods have been developing rapidly. This article presents researches about a new composite consisted of golden and magnetite nanoparticles which could be used for this technique. Preparation of golden nanoparticles by laser ablation and their soldering by laser green light irradiation proceeded in water environment. Magnetite was obtained on chemical way. During experiments it was tested a change of a size of nanoparticles during laser irradiation, surface plasmon resonance, zeta potential. The obtained golden - magnetite composite material was magnetic after laser irradiation. On the end there was considered the application it for 3D printing devices, water filters and four-valued non-volatile memories.

  8. Monitoring of volatile and non-volatile urban air genotoxins using bacteria, human cells and plants.

    Science.gov (United States)

    Ceretti, E; Zani, C; Zerbini, I; Viola, G; Moretti, M; Villarini, M; Dominici, L; Monarca, S; Feretti, D

    2015-02-01

    Urban air contains many mutagenic pollutants. This research aimed to investigate the presence of mutagens in the air by short-term mutagenicity tests using bacteria, human cells and plants. Inflorescences of Tradescantia were exposed to air in situ for 6h, once a month from January to May, to monitor volatile compounds and micronuclei frequency was computed. On the same days PM10 was collected continuously for 24h. Half of each filter was extracted with organic solvents and studied by means of the Ames test, using Salmonella typhimurium TA98 and TA100 strains, and the comet assay on human leukocytes. A quarter of each filter was extracted with distilled water in which Tradescantia was exposed. PM10 concentration was particularly high in the winter season (> 50 μg/m(3)). In situ exposure of inflorescences to urban air induced a significant increase in micronuclei frequency at all the sites considered, but only in January (p bacteria, human cells and plants. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. GaAs metal-oxide-semiconductor based non-volatile flash memory devices with InAs quantum dots as charge storage nodes

    Energy Technology Data Exchange (ETDEWEB)

    Islam, Sk Masiul, E-mail: masiulelt@gmail.com; Chowdhury, Sisir; Sarkar, Krishnendu; Nagabhushan, B.; Banerji, P. [Materials Science Centre, Indian Institute of Technology, Kharagpur 721 302 (India); Chakraborty, S. [Applied Materials Science Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Sector-I, Kolkata 700 064 (India); Mukherjee, Rabibrata [Department of Chemical Engineering, Indian Institute of Technology, Kharagpur 721302 (India)

    2015-06-24

    Ultra-thin InP passivated GaAs metal-oxide-semiconductor based non-volatile flash memory devices were fabricated using InAs quantum dots (QDs) as charge storing elements by metal organic chemical vapor deposition technique to study the efficacy of the QDs as charge storage elements. The grown QDs were embedded between two high-k dielectric such as HfO{sub 2} and ZrO{sub 2}, which were used for tunneling and control oxide layers, respectively. The size and density of the QDs were found to be 5 nm and 1.8×10{sup 11} cm{sup −2}, respectively. The device with a structure Metal/ZrO{sub 2}/InAs QDs/HfO{sub 2}/GaAs/Metal shows maximum memory window equivalent to 6.87 V. The device also exhibits low leakage current density of the order of 10{sup −6} A/cm{sup 2} and reasonably good charge retention characteristics. The low value of leakage current in the fabricated memory device is attributed to the Coulomb blockade effect influenced by quantum confinement as well as reduction of interface trap states by ultra-thin InP passivation on GaAs prior to HfO{sub 2} deposition.

  10. A radiation-tolerant, low-power non-volatile memory based on silicon nanocrystal quantum dots

    OpenAIRE

    Bell, L. D.; Boer, E.; Ostraat, M.; Brongersma, M. L.; Flagan, R. C.; Atwater, H. A.; De Blauwe, J.; Green, M. L.

    2001-01-01

    Nanocrystal nonvolatile floating-gate memories are a good candidate for space applications - initial results suggest they are fast, more reliable and consume less power than conventional floating gate memories. In the nanocrystal based NVM device, charge is not stored on a continuous polysilicon layer (so-called floating gate), but instead on a layer of discrete nanocrystals. Charge injection and storage in dense arrays of silicon nanocrystals in SiO_2 is a critical aspect of the performance ...

  11. Nanocrystals manufacturing by ultra-low-energy ion-beam-synthesis for non-volatile memory applications

    Energy Technology Data Exchange (ETDEWEB)

    Normand, P. E-mail: p.normand@imel.demokritos.gr; Kapetanakis, E.; Dimitrakis, P.; Skarlatos, D.; Beltsios, K.; Tsoukalas, D.; Bonafos, C.; Ben Assayag, G.; Cherkashin, N.; Claverie, A.; Berg, J.A. van den; Soncini, V.; Agarwal, A.; Ameen, M.; Perego, M.; Fanciulli, M

    2004-02-01

    An overview of recent developments regarding the fabrication and structure of thin silicon dioxide films with embedded nanocrystals through ultra-low-energy ion-beam-synthesis (ULE-IBS) is presented. Advances in fabrication, increased understanding of structure formation processes and ways to control them allow for the fabrication of reproducible and attractive silicon-nanocrystal memory devices for a wide-range of memory applications as herein demonstrated in the case of low-voltage EEPROM-like applications.

  12. Nanocrystals manufacturing by ultra-low-energy ion-beam-synthesis for non-volatile memory applications

    International Nuclear Information System (INIS)

    Normand, P.; Kapetanakis, E.; Dimitrakis, P.; Skarlatos, D.; Beltsios, K.; Tsoukalas, D.; Bonafos, C.; Ben Assayag, G.; Cherkashin, N.; Claverie, A.; Berg, J.A. van den; Soncini, V.; Agarwal, A.; Ameen, M.; Perego, M.; Fanciulli, M.

    2004-01-01

    An overview of recent developments regarding the fabrication and structure of thin silicon dioxide films with embedded nanocrystals through ultra-low-energy ion-beam-synthesis (ULE-IBS) is presented. Advances in fabrication, increased understanding of structure formation processes and ways to control them allow for the fabrication of reproducible and attractive silicon-nanocrystal memory devices for a wide-range of memory applications as herein demonstrated in the case of low-voltage EEPROM-like applications

  13. Surface directed phase separation of semiconductor ferroelectric polymer blends and their use in non-volatile memories

    NARCIS (Netherlands)

    Breemen, A.J.J.M. van; Zaba, T.; Khikhlovskyi, V.; Michels, J.; Janssen, R.; Kemerink, M.; Gelinck, G.

    2015-01-01

    The polymer phase separation of P(VDF-TrFE):F8BT blends is studied in detail. Its morphology is key to the operation and performance of memory diodes. In this study, it is demonstrated that it is possible to direct the semiconducting domains of a phase-separating mixture of P(VDF-TrFE) and F8BT in a

  14. An overview of Experimental Condensed Matter Physics in Argentina by 2014, and Oxides for Non Volatile Memory Devices: The MeMOSat Project

    Science.gov (United States)

    Levy, Pablo

    2015-03-01

    In the first part of my talk, I will describe the status of the experimental research in Condensed Matter Physics in Argentina, biased towards developments related to micro and nanotechnology. In the second part, I will describe the MeMOSat Project, a consortium aimed at producing non-volatile memory devices to work in aggressive environments, like those found in the aerospace and nuclear industries. Our devices rely on the Resistive Switching mechanism, which produces a permanent but reversible change in the electrical resistance across a metal-insulator-metal structure by means of a pulsed protocol of electrical stimuli. Our project is devoted to the study of Memory Mechanisms in Oxides (MeMO) in order to establish a technological platform that tests the Resistive RAM (ReRAM) technology for aerospace applications. A review of MeMOSat's activities is presented, covering the initial Proof of Concept in ceramic millimeter sized samples; the study of different oxide-metal couples including (LaPr)2/3Ca1/3MnO, La2/3Ca1/3MnO3, YBa2Cu3O7, TiO2, HfO2, MgO and CuO; and recent miniaturized arrays of micrometer sized devices controlled by in-house designed electronics, which were launched with the BugSat01 satellite in June2014 by the argentinian company Satellogic.

  15. Impact of process parameters on the structural and electrical properties of metal/PZT/Al2O3/silicon gate stack for non-volatile memory applications

    Science.gov (United States)

    Singh, Prashant; Jha, Rajesh Kumar; Singh, Rajat Kumar; Singh, B. R.

    2018-02-01

    In this paper, we present the structural and electrical properties of the Al2O3 buffer layer on non-volatile memory behavior using Metal/PZT/Al2O3/Silicon structures. Metal/PZT/Silicon and Metal/Al2O3/Silicon structures were also fabricated and characterized to obtain capacitance and leakage current parameters. Lead zirconate titanate (PZT::35:65) and Al2O3 films were deposited by sputtering on the silicon substrate. Memory window, PUND, endurance, breakdown voltage, effective charges, flat-band voltage and leakage current density parameters were measured and the effects of process parameters on the structural and electrical characteristics were investigated. X-ray data show dominant (110) tetragonal phase of the PZT film, which crystallizes at 500 °C. The sputtered Al2O3 film annealed at different temperatures show dominant (312) orientation and amorphous nature at 425 °C. Multiple angle laser ellipsometric analysis reveals the temperature dependence of PZT film refractive index and extinction coefficient. Electrical characterization shows the maximum memory window of 3.9 V and breakdown voltage of 25 V for the Metal/Ferroelectric/Silicon (MFeS) structures annealed at 500 °C. With 10 nm Al2O3 layer in the Metal/Ferroelectric/Insulator/Silicon (MFeIS) structure, the memory window and breakdown voltage was improved to 7.21 and 35 V, respectively. Such structures show high endurance with no significant reduction polarization charge for upto 2.2 × 109 iteration cycles.

  16. Effect of Ag nanoparticles on resistive switching of polyfluorene-based organic non-volatile memory devices

    International Nuclear Information System (INIS)

    Kim, Tae-Wook; Oh, Seung-Hwan; Choi, Hye-Jung; Wang, Gun-Uk; Kim, Dong-Yu; Hwang, Hyun-Sang; Lee, Tak-Hee

    2010-01-01

    The effects of Ag nanoparticles on the switching behavior of polyfluorene-based organic nonvolatile memory devices were investigated. Polyfluorene-derivatives (WPF-oxy-F) with and without Ag nanoparticles were synthesized, and the presence of Ag nanoparticles in Ag-WPF-oxy-F was identified by transmission electron microscopy and X-ray photoelectron spectroscopy analyses. The Ag-nanoparticles did not significantly affect the basic switching performances, such as the current-voltage characteristics, the distribution of on/off resistance, and the retention. The pulse switching time of Ag-WPF-oxy-F was faster than that of WPF-oxy-F. Ag-WPF-oxy-F memory devices showed an area dependence in the high resistance state, implying that formation of a Ag metallic channel for current conduction.

  17. Pulsed ion-beam assisted deposition of Ge nanocrystals on SiO2 for non-volatile memory device

    International Nuclear Information System (INIS)

    Stepina, N.P.; Dvurechenskii, A.V.; Armbrister, V.A.; Kirienko, V.V.; Novikov, P.L.; Kesler, V.G.; Gutakovskii, A.K.; Smagina, Z.V.; Spesivtzev, E.V.

    2008-01-01

    A floating gate memory structure, utilizing Ge nanocrystals (NCs) deposited on tunnel SiO 2 , have been fabricated using pulsed low energy ion-beam induced molecular-beam deposition (MBD) in ultra-high vacuum. The ion-beam action is shown to stimulate the nucleation of Ge NCs when being applied after thin Ge layer deposition. Growth conditions for independent change of NCs size and array density were established allowing to optimize the structure parameters required for memory device. Activation energy E = 0.25 eV was determined from the temperature dependence of NCs array density. Monte Carlo simulation has shown that the process, determining NCs array density, is the surface diffusion. Embedding of the crystalline Ge dots into silicon oxide was carried out by selective oxidation of Si(100)/SiO 2 /Ge(NCs)/poly-Si structure. MOS-capacitor obtained after oxidation showed a hysteresis in its C-V curves attributed to charge retention in the Ge dots

  18. Piezoelectric control of magnetoelectric coupling driven non-volatile memory switching and self cooling effects in FE/FSMA multiferroic heterostructures

    Science.gov (United States)

    Singh, Kirandeep; Kaur, Davinder

    2017-02-01

    The manipulation of magnetic states and materials' spin degree-of-freedom via a control of an electric (E-) field has been recently pursued to develop magnetoelectric (ME) coupling-driven electronic data storage devices with high read/write endurance, fast dynamic response, and low energy dissipation. One major hurdle for this approach is to develop reliable materials which should be compatible with prevailing silicon (Si)-based complementary metal-oxide-semiconductor (CMOS) technology, simultaneously allowing small voltage for the tuning of magnetization switching. In this regard, multiferroic heterostructures where ferromagnetic (FM) and ferroelectric (FE) layers are alternatively grown on conventional Si substrates are promising as the piezoelectric control of magnetization switching is anticipated to be possible by an E-field. In this work, we study the ferromagnetic shape memory alloys based PbZr0.52Ti0.48O3/Ni50Mn35In15 (PZT/Ni-Mn-In) multiferroic heterostructures, and investigate their potential for CMOS compatible non-volatile magnetic data storage applications. We demonstrate the voltage-impulse controlled nonvolatile, reversible, and bistable magnetization switching at room temperature in Si-integrated PZT/Ni-Mn-In thin film multiferroic heterostructures. We also thoroughly unveil the various intriguing features in these materials, such as E-field tuned ME coupling and magnetocaloric effect, shape memory induced ferroelectric modulation, improved fatigue endurance as well as Refrigeration Capacity (RC). This comprehensive study suggests that these novel materials have a great potential for the development of unconventional nanoscale memory and refrigeration devices with self-cooling effect and enhanced refrigeration efficiency, thus providing a new venue for their applications.

  19. Bipolar resistive switching in graphene oxide based metal insulator metal structure for non-volatile memory applications

    Science.gov (United States)

    Singh, Rakesh; Kumar, Ravi; Kumar, Anil; Kashyap, Rajesh; Kumar, Mukesh; Kumar, Dinesh

    2018-05-01

    Graphene oxide based devices have attracted much attention recently because of their possible application in next generation electronic devices. In this study, bipolar resistive switching characteristics of graphene oxide based metal insulator metal structure were investigated for nonvolatile memories. The graphene oxide was prepared by the conventional Hummer's method and deposited on ITO coated glass by spin-coating technique. The dominant mechanism of resistive switching is the formation and rupture of the conductive filament inside the graphene oxide. The conduction mechanism for low and high resistance states are dominated by two mechanism the ohmic conduction and space charge limited current (SCLC) mechanism, respectively. Atomic Force Microscopy, X-ray diffraction, Cyclic-Voltammetry were conducted to observe the morphology, structure and behavior of the material. The fabricated device with Al/GO/ITO structure exhibited reliable bipolar resistive switching with set & reset voltage of -2.3 V and 3V respectively.

  20. Improvement of multi-level resistive switching characteristics in solution-processed AlO x -based non-volatile resistive memory using microwave irradiation

    Science.gov (United States)

    Kim, Seung-Tae; Cho, Won-Ju

    2018-01-01

    We fabricated a resistive random access memory (ReRAM) device on a Ti/AlO x /Pt structure with solution-processed AlO x switching layer using microwave irradiation (MWI), and demonstrated multi-level cell (MLC) operation. To investigate the effect of MWI power on the MLC characteristics, post-deposition annealing was performed at 600-3000 W after AlO x switching layer deposition, and the MLC operation was compared with as-deposited (as-dep) and conventional thermally annealing (CTA) treated devices. All solution-processed AlO x -based ReRAM devices exhibited bipolar resistive switching (BRS) behavior. We found that these devices have four-resistance states (2 bits) of MLC operation according to the modulation of the high-resistance state (HRSs) through reset voltage control. Particularly, compared to the as-dep and CTA ReRAM devices, the MWI-treated ReRAM devices showed a significant increase in the memory window and stable endurance for multi-level operation. Moreover, as the MWI power increased, excellent MLC characteristics were exhibited because the resistance ratio between each resistance state was increased. In addition, it exhibited reliable retention characteristics without deterioration at 25 °C and 85 °C for 10 000 s. Finally, the relationship between the chemical characteristics of the solution-processed AlO x switching layer and BRS-based multi-level operation according to the annealing method and MWI power was investigated using x-ray photoelectron spectroscopy.

  1. Observing the amorphous-to-crystalline phase transition in Ge{sub 2}Sb{sub 2}Te{sub 5} non-volatile memory materials from ab initio molecular-dynamics simulations

    Energy Technology Data Exchange (ETDEWEB)

    Lee, T.H.; Elliott, S.R. [Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW Cambridge (United Kingdom)

    2012-10-15

    Phase-change memory is a promising candidate for the next generation of non-volatile memory devices. This technology utilizes reversible phase transitions between amorphous and crystalline phases of a recording material, and has been successfully used in rewritable optical data storage, revealing its feasibility. In spite of the importance of understanding the nucleation and growth processes that play a critical role in the phase transition, this understanding is still incomplete. Here, we present observations of the early stages of crystallization in Ge{sub 2}Sb{sub 2}Te{sub 5} materials through ab initio molecular-dynamics simulations. Planar structures, including fourfold rings and planes, play an important role in the formation and growth of crystalline clusters in the amorphous matrix. At the same time, vacancies facilitate crystallization by providing space at the glass-crystalline interface for atomic diffusion, which results in fast crystal growth, as observed in simulations and experiments. The microscopic mechanism of crystallization presented here may deepen our understanding of the phase transition occurring in real devices, providing an opportunity to optimize the memory performance of phase-change materials. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  2. A New Concept for Non-Volatile Memory: The Electric-Pulse Induced Resistive Change Effect in Colossal Magnetoresistive Thin Films

    Science.gov (United States)

    Liu, S. Q.; Wu, N. J.; Ignatiev, A.

    2001-01-01

    A novel electric pulse-induced resistive change (EPIR) effect has been found in thin film colossal magnetoresistive (CMR) materials, and has shown promise for the development of resistive, nonvolatile memory. The EPIR effect is induced by the application of low voltage (resistance of the thin film sample depending on pulse polarity. The sample resistance change has been shown to be over two orders of magnitude, and is nonvolatile after pulsing. The sample resistance can also be changed through multiple levels - as many as 50 have been shown. Such a device can provide a way for the development of a new kind of nonvolatile multiple-valued memory with high density, fast write/read speed, low power-consumption, and potential high radiation-hardness.

  3. A fast, high-endurance and scalable non-volatile memory device made from asymmetric Ta2O5-x/TaO2-x bilayer structures

    Science.gov (United States)

    Lee, Myoung-Jae; Lee, Chang Bum; Lee, Dongsoo; Lee, Seung Ryul; Chang, Man; Hur, Ji Hyun; Kim, Young-Bae; Kim, Chang-Jung; Seo, David H.; Seo, Sunae; Chung, U.-In; Yoo, In-Kyeong; Kim, Kinam

    2011-08-01

    Numerous candidates attempting to replace Si-based flash memory have failed for a variety of reasons over the years. Oxide-based resistance memory and the related memristor have succeeded in surpassing the specifications for a number of device requirements. However, a material or device structure that satisfies high-density, switching-speed, endurance, retention and most importantly power-consumption criteria has yet to be announced. In this work we demonstrate a TaOx-based asymmetric passive switching device with which we were able to localize resistance switching and satisfy all aforementioned requirements. In particular, the reduction of switching current drastically reduces power consumption and results in extreme cycling endurances of over 1012. Along with the 10 ns switching times, this allows for possible applications to the working-memory space as well. Furthermore, by combining two such devices each with an intrinsic Schottky barrier we eliminate any need for a discrete transistor or diode in solving issues of stray leakage current paths in high-density crossbar arrays.

  4. Acoustically assisted spin-transfer-torque switching of nanomagnets: An energy-efficient hybrid writing scheme for non-volatile memory

    International Nuclear Information System (INIS)

    Biswas, Ayan K.; Bandyopadhyay, Supriyo; Atulasimha, Jayasimha

    2013-01-01

    We show that the energy dissipated to write bits in spin-transfer-torque random access memory can be reduced by an order of magnitude if a surface acoustic wave (SAW) is launched underneath the magneto-tunneling junctions (MTJs) storing the bits. The SAW-generated strain rotates the magnetization of every MTJs' soft magnet from the easy towards the hard axis, whereupon passage of a small spin-polarized current through a target MTJ selectively switches it to the desired state with > 99.99% probability at room temperature, thereby writing the bit. The other MTJs return to their original states at the completion of the SAW cycle

  5. Pulsed ion-beam assisted deposition of Ge nanocrystals on SiO{sub 2} for non-volatile memory device

    Energy Technology Data Exchange (ETDEWEB)

    Stepina, N.P. [Institute of Semiconductor Physics, Lavrenteva 13, 630090 Novosibirsk (Russian Federation)], E-mail: nstepina@mail.ru; Dvurechenskii, A.V.; Armbrister, V.A.; Kirienko, V.V.; Novikov, P.L.; Kesler, V.G.; Gutakovskii, A.K.; Smagina, Z.V.; Spesivtzev, E.V. [Institute of Semiconductor Physics, Lavrenteva 13, 630090 Novosibirsk (Russian Federation)

    2008-11-03

    A floating gate memory structure, utilizing Ge nanocrystals (NCs) deposited on tunnel SiO{sub 2}, have been fabricated using pulsed low energy ion-beam induced molecular-beam deposition (MBD) in ultra-high vacuum. The ion-beam action is shown to stimulate the nucleation of Ge NCs when being applied after thin Ge layer deposition. Growth conditions for independent change of NCs size and array density were established allowing to optimize the structure parameters required for memory device. Activation energy E = 0.25 eV was determined from the temperature dependence of NCs array density. Monte Carlo simulation has shown that the process, determining NCs array density, is the surface diffusion. Embedding of the crystalline Ge dots into silicon oxide was carried out by selective oxidation of Si(100)/SiO{sub 2} /Ge(NCs)/poly-Si structure. MOS-capacitor obtained after oxidation showed a hysteresis in its C-V curves attributed to charge retention in the Ge dots.

  6. Phase change materials in non-volatile storage

    OpenAIRE

    Ielmini, Daniele; Lacaita, Andrea L.

    2011-01-01

    After revolutionizing the technology of optical data storage, phase change materials are being adopted in non-volatile semiconductor memories. Their success in electronic storage is mostly due to the unique properties of the amorphous state where carrier transport phenomena and thermally-induced phase change cooperate to enable high-speed, low-voltage operation and stable data retention possible within the same material. This paper reviews the key physical properties that make this phase so s...

  7. Effect of AlN layer on the bipolar resistive switching behavior in TiN thin film based ReRAM device for non-volatile memory application

    Science.gov (United States)

    Prakash, Ravi; Kaur, Davinder

    2018-05-01

    The effect of an additional AlN layer in the Cu/TiN/AlN/Pt stack configuration deposited using sputtering has been investigated. The Cu/TiN/AlN/Pt device shows a tristate resistive switching. Multilevel switching is facilitated by ionic and metallic filament formation, and the nature of the filaments formed is confirmed by performing a resistance vs. temperature measurement. Ohmic behaviour and trap controlled space charge limited current (SCLC) conduction mechanisms are confirmed as dominant conduction mechanism at low resistance state (LRS) and high resistance state (HRS). High resistance ratio (102) corresponding to HRS and LRS, good write/erase endurance (105) and non-volatile long retention (105s) are also observed. Higher thermal conductivity of the AlN layer is the main reasons for the enhancement of resistive switching performance in Cu/TiN/AlN/Pt cell. The above result suggests the feasibility of Cu/TiN/AlN/Pt devices for multilevel nonvolatile ReRAM application.

  8. Feasibility and limitations of anti-fuses based on bistable non-volatile switches for power electronic applications

    Science.gov (United States)

    Erlbacher, T.; Huerner, A.; Bauer, A. J.; Frey, L.

    2012-09-01

    Anti-fuse devices based on non-volatile memory cells and suitable for power electronic applications are demonstrated for the first time using silicon technology. These devices may be applied as stand alone devices or integrated using standard junction-isolation into application-specific and smart-power integrated circuits. The on-resistance of such devices can be permanently switched by nine orders of magnitude by triggering the anti-fuse with a positive voltage pulse. Extrapolation of measurement data and 2D TCAD process and device simulations indicate that 20 A anti-fuses with 10 mΩ can be reliably fabricated in 0.35 μm technology with a footprint of 2.5 mm2. Moreover, this concept offers distinguished added-values compared to existing mechanical relays, e.g. pre-test, temporary and permanent reset functions, gradual turn-on mode, non-volatility, and extendibility to high voltage capability.

  9. Memory T Cell Migration

    OpenAIRE

    Qianqian eZhang; Qianqian eZhang; Fadi G. Lakkis

    2015-01-01

    Immunological memory is a key feature of adaptive immunity. It provides the organism with long-lived and robust protection against infection. In organ transplantation, memory T cells pose a significant threat by causing allograft rejection that is generally resistant to immunosuppressive therapy. Therefore, a more thorough understanding of memory T cell biology is needed to improve the survival of transplanted organs without compromising the host’s ability to fight infections. This review...

  10. Resistive Memory Devices for Radiation Resistant Non-Volatile Memory

    Data.gov (United States)

    National Aeronautics and Space Administration — Ionizing radiation in space can damage electronic equipment, corrupting data and even disabling computers. Radiation resistant (rad hard) strategies must be employed...

  11. DESTINY: A Comprehensive Tool with 3D and Multi-Level Cell Memory Modeling Capability

    Directory of Open Access Journals (Sweden)

    Sparsh Mittal

    2017-09-01

    Full Text Available To enable the design of large capacity memory structures, novel memory technologies such as non-volatile memory (NVM and novel fabrication approaches, e.g., 3D stacking and multi-level cell (MLC design have been explored. The existing modeling tools, however, cover only a few memory technologies, technology nodes and fabrication approaches. We present DESTINY, a tool for modeling 2D/3D memories designed using SRAM, resistive RAM (ReRAM, spin transfer torque RAM (STT-RAM, phase change RAM (PCM and embedded DRAM (eDRAM and 2D memories designed using spin orbit torque RAM (SOT-RAM, domain wall memory (DWM and Flash memory. In addition to single-level cell (SLC designs for all of these memories, DESTINY also supports modeling MLC designs for NVMs. We have extensively validated DESTINY against commercial and research prototypes of these memories. DESTINY is very useful for performing design-space exploration across several dimensions, such as optimizing for a target (e.g., latency, area or energy-delay product for a given memory technology, choosing the suitable memory technology or fabrication method (i.e., 2D v/s 3D for a given optimization target, etc. We believe that DESTINY will boost studies of next-generation memory architectures used in systems ranging from mobile devices to extreme-scale supercomputers. The latest source-code of DESTINY is available from the following git repository: https://bitbucket.org/sparshmittal/destinyv2.

  12. Reconfigurable Electronics and Non-Volatile Memory Research

    Science.gov (United States)

    2011-10-14

    October 2009. The films were etched off wafer pieces using a blend of sulfuric, nitric and hydrofluoric acids and diluted for analysis. Table 5...interactions. A weak peak is also seen around g = 1.98 which intensifies under light illumination. This peak can be assigned to the charge defects of base...evidence of amorphous/crystalline GST. It is not clear why significantly oxidized devices were capable of switching. Dr. Miotti theorized that

  13. Reconfigurable Electronics and Non-Volatile Memory Research

    Science.gov (United States)

    2015-11-10

    spectrophotometer tool uses film reflectance to calculate film thickness via a set of proprietary algorithms and a developed recipe for material type. The...tool can also be used to collect transmission spectra. Recipes must be developed for each film type (and stack) that is measured. Once the recipe has...Regner, J.K.; Balasubramanian, M; Cook , B.; Li, Y.; Kassayebetre, H. Sharma, A.; Baker, R.J.; Campbell, K.A., “Integration of IC Industry Feature

  14. Magnetization Dynamics in Two Novel Current-Driven Spintronic Memory Cell Structures

    KAUST Repository

    Velazquez-Rizo, Martin

    2017-07-01

    In this work, two new spintronic memory cell structures are proposed. The first cell uses the diffusion of polarized spins into ferromagnets with perpendicular anisotropy to tilt their magnetization followed by their dipolar coupling to a fixed magnet (Bhowmik et al., 2014). The possibility of setting the magnetization to both stable magnetization states in a controlled manner using a similar concept remains unknown, but the proposed structure poses to be a solution to this difficulty. The second cell proposed takes advantage of the multiple stable magnetic states that exist in ferromagnets with configurational anisotropy and also uses spin torques to manipulate its magnetization. It utilizes a square-shaped ferromagnet whose stable magnetization has preferred directions along the diagonals of the square, giving four stable magnetic states allowing to use the structure as a multi-bit memory cell. Both devices use spin currents generated in heavy metals by the Spin Hall effect present in these materials. Among the advantages of the structures proposed are their inherent non-volatility and the fact that there is no need for applying external magnetic fields during their operation, which drastically improves the energy efficiency of the devices. Computational simulations using the Object Oriented Micromagnetic Framework (OOMMF) software package were performed to study the dynamics of the magnetization process in both structures and predict their behavior. Besides, we fabricated a 4-terminal memory cell with configurational anisotropy similar to the device proposed, and found four stable resistive states on the structure, proving the feasibility of this technology for implementation of high-density, non-volatile memory cells.

  15. Non-volatile resistive switching in the Mott insulator (V1-xCrx)2O3

    Science.gov (United States)

    Querré, M.; Tranchant, J.; Corraze, B.; Cordier, S.; Bouquet, V.; Députier, S.; Guilloux-Viry, M.; Besland, M.-P.; Janod, E.; Cario, L.

    2018-05-01

    The discovery of non-volatile resistive switching in Mott insulators related to an electric-field-induced insulator to metal transition (IMT) has paved the way for their use in a new type of non-volatile memories, the Mott memories. While most of the previous studies were dedicated to uncover the resistive switching mechanism and explore the memory potential of chalcogenide Mott insulators, we present here a comprehensive study of resistive switching in the canonical oxide Mott insulator (V1-xCrx)2O3. Our work demonstrates that this compound undergoes a non-volatile resistive switching under electric field. This resistive switching is induced by a Mott transition at the local scale which creates metallic domains closely related to existing phases of the temperature-pressure phase diagram of (V1-xCrx)2O3. Our work demonstrates also reversible resistive switching in (V1-xCrx)2O3 crystals and thin film devices. Preliminary performances obtained on 880 nm thick layers with 500 nm electrodes show the strong potential of Mott memories based on the Mott insulator (V1-xCrx)2O3.

  16. Radiation hard memory cell and array thereof

    International Nuclear Information System (INIS)

    Gunckel, T.L. II; Rovell, A.; Nielsen, R.L.

    1978-01-01

    A memory cell configuration that is implemented to be relatively hard to the adverse effects of a nuclear event is discussed. The presently disclosed memory cell can be interconnected with other like memory cells to form a high speed radiation hard register file. Information is selectively written into and read out of a memory cell comprising the register file, which memory cell preserves previously stored data without alteration in the event of exposure to high levels of nuclear radiation

  17. Two-dimensional non-volatile programmable p-n junctions

    Science.gov (United States)

    Li, Dong; Chen, Mingyuan; Sun, Zhengzong; Yu, Peng; Liu, Zheng; Ajayan, Pulickel M.; Zhang, Zengxing

    2017-09-01

    Semiconductor p-n junctions are the elementary building blocks of most electronic and optoelectronic devices. The need for their miniaturization has fuelled the rapid growth of interest in two-dimensional (2D) materials. However, the performance of a p-n junction considerably degrades as its thickness approaches a few nanometres and traditional technologies, such as doping and implantation, become invalid at the nanoscale. Here we report stable non-volatile programmable p-n junctions fabricated from the vertically stacked all-2D semiconductor/insulator/metal layers (WSe2/hexagonal boron nitride/graphene) in a semifloating gate field-effect transistor configuration. The junction exhibits a good rectifying behaviour with a rectification ratio of 104 and photovoltaic properties with a power conversion efficiency up to 4.1% under a 6.8 nW light. Based on the non-volatile programmable properties controlled by gate voltages, the 2D p-n junctions have been exploited for various electronic and optoelectronic applications, such as memories, photovoltaics, logic rectifiers and logic optoelectronic circuits.

  18. Ferroelectric polymer gates for non-volatile field effect control of ferromagnetism in (Ga, Mn)As layers

    International Nuclear Information System (INIS)

    Stolichnov, I; Riester, S W E; Mikheev, E; Setter, N; Rushforth, A W; Edmonds, K W; Campion, R P; Foxon, C T; Gallagher, B L; Jungwirth, T; Trodahl, H J

    2011-01-01

    (Ga, Mn)As and other diluted magnetic semiconductors (DMS) attract a great deal of attention for potential spintronic applications because of the possibility of controlling the magnetic properties via electrical gating. Integration of a ferroelectric gate on the DMS channel adds to the system a non-volatile memory functionality and permits nanopatterning via the polarization domain engineering. This topical review is focused on the multiferroic system, where the ferromagnetism in the (Ga, Mn)As DMS channel is controlled by the non-volatile field effect of the spontaneous polarization. Use of ferroelectric polymer gates in such heterostructures offers a viable alternative to the traditional oxide ferroelectrics generally incompatible with DMS. Here we review the proof-of-concept experiments demonstrating the ferroelectric control of ferromagnetism, analyze the performance issues of the ferroelectric gates and discuss prospects for further development of the ferroelectric/DMS heterostructures toward the multiferroic field effect transistor. (topical review)

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

    Science.gov (United States)

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

    2018-05-01

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

  20. Carbon nanotube network-silicon oxide non-volatile switches.

    Science.gov (United States)

    Liao, Albert D; Araujo, Paulo T; Xu, Runjie; Dresselhaus, Mildred S

    2014-12-08

    The integration of carbon nanotubes with silicon is important for their incorporation into next-generation nano-electronics. Here we demonstrate a non-volatile switch that utilizes carbon nanotube networks to electrically contact a conductive nanocrystal silicon filament in silicon dioxide. We form this device by biasing a nanotube network until it physically breaks in vacuum, creating the conductive silicon filament connected across a small nano-gap. From Raman spectroscopy, we observe coalescence of nanotubes during breakdown, which stabilizes the system to form very small gaps in the network~15 nm. We report that carbon nanotubes themselves are involved in switching the device to a high resistive state. Calculations reveal that this switching event occurs at ~600 °C, the temperature associated with the oxidation of nanotubes. Therefore, we propose that, in switching to a resistive state, the nanotube oxidizes by extracting oxygen from the substrate.

  1. Non-volatile polarization switch of magnetic domain wall velocity

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Z.; Stolichnov, I.; Setter, N. [Ceramics Laboratory, EPFL-Swiss Federal Institute of Technology, Lausanne 1015 (Switzerland); Bernand-Mantel, A.; Schott, Marine; Pizzini, S.; Ranno, L. [University of Grenoble Alpes, Institut Néel, F-38042 Grenoble (France); CNRS, Institut Néel, F-38042 Grenoble (France); Auffret, S.; Gaudin, G. [SPINTEC, UMR-8191, CEA/CNRS/UJF/GINP, INAC, F-38054 Grenoble (France)

    2015-12-21

    Controlled propagation speed of individual magnetic domains in metal channels at the room temperature is obtained via the non-volatile field effect associated with the switchable polarization of P(VDF-TrFE) (polyvinylidene fluoride-trifluoroethylene) ferroelectric polymer. Polarization domains directly written using conducting atomic force microscope probe locally accelerate/decelerate the magnetic domains in the 0.6 nm thick Co film. The change of the magnetic domain wall velocity is consistent with the magnetic anisotropy energy modulation through the polarization upward/downward orientation. Excellent retention is observed. The demonstrated local non-destructive and reversible change of magnetic properties via rewritable patterning of ferroelectric domains could be attractive for exploring the ultimate limit of miniaturization in devices based on ferromagnetic/ferroelectric bilayers.

  2. Atmospheric fate of non volatile and ionizable compounds

    DEFF Research Database (Denmark)

    Franco, Antonio; Hauschild, Michael Zwicky; Jolliet, Olivier

    2011-01-01

    , and the parameters describing air–water partitioning (KAW and temperature) and ionization (pKa and pH) are the key parameters determining the potential for long range transport. Wet deposition is an important removal process, but its efficiency is limited, primarily by the duration of the dry period between...... simulations describing the uncertainty of substance and environmental input properties were run to evaluate the impact of atmospheric parameters, ionization and air–water (or air–ice) interface enrichment. The rate of degradation and the concentration of OH radicals, the duration of dry and wet periods...... precipitation events. Given the underlying model assumptions, the presence of clouds contributes to the higher persistence in the troposphere because of the capacity of cloud water to accumulate and transport non-volatile (e.g.2,4-D) and surface-active chemicals (e.g. PFOA). This limits the efficiency of wet...

  3. Volatile and non-volatile/semi-volatile compounds and in vitro bioactive properties of Chilean Ulmo (Eucryphia cordifolia Cav.) honey.

    Science.gov (United States)

    Acevedo, Francisca; Torres, Paulina; Oomah, B Dave; de Alencar, Severino Matias; Massarioli, Adna Prado; Martín-Venegas, Raquel; Albarral-Ávila, Vicenta; Burgos-Díaz, César; Ferrer, Ruth; Rubilar, Mónica

    2017-04-01

    Ulmo honey originating from Eucryphia cordifolia tree, known locally in the Araucania region as the Ulmo tree is a natural product with valuable nutritional and medicinal qualities. It has been used in the Mapuche culture to treat infections. This study aimed to identify the volatile and non-volatile/semi-volatile compounds of Ulmo honey and elucidate its in vitro biological properties by evaluating its antioxidant, antibacterial, antiproliferative and hemolytic properties and cytotoxicity in Caco-2 cells. Headspace volatiles of Ulmo honey were isolated by solid-phase microextraction (SPME); non-volatiles/semi-volatiles were obtained by removing all saccharides with acidified water and the compounds were identified by GC/MS analysis. Ulmo honey volatiles consisted of 50 compounds predominated by 20 flavor components. Two of the volatile compounds, lyrame and anethol have never been reported before as honey compounds. The non-volatile/semi-volatile components of Ulmo honey comprised 27 compounds including 13 benzene derivatives accounting 75% of the total peak area. Ulmo honey exhibited weak antioxidant activity but strong antibacterial activity particularly against gram-negative bacteria and methicillin-resistant Staphylococcus aureus (MRSA), the main strain involved in wounds and skin infections. At concentrations >0.5%, Ulmo honey reduced Caco-2 cell viability, released lactate dehydrogenase (LDH) and increased reactive oxygen species (ROS) production in a dose dependent manner in the presence of foetal bovine serum (FBS). The wide array of volatile and non-volatile/semi-volatile constituents of Ulmo honey rich in benzene derivatives may partly account for its strong antibacterial and antiproliferative properties important for its therapeutic use. Our results indicate that Ulmo honey can potentially inhibit cancer growth at least partly by modulating oxidative stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. The cellular memory disc of reprogrammed cells.

    Science.gov (United States)

    Anjamrooz, Seyed Hadi

    2013-04-01

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

  5. A Josephson ternary associative memory cell

    International Nuclear Information System (INIS)

    Morisue, M.; Suzuki, K.

    1989-01-01

    This paper describes a three-valued content addressable memory cell using a Josephson complementary ternary logic circuit named as JCTL. The memory cell proposed here can perform three operations of searching, writing and reading in ternary logic system. The principle of the memory circuit is illustrated in detail by using the threshold-characteristics of the JCTL. In order to investigate how a high performance operation can be achieved, computer simulations have been made. Simulation results show that the cycle time of memory operation is 120psec, power consumption is about 0.5 μW/cell and tolerances of writing and reading operation are +-15% and +-24%, respectively

  6. Multi-bits memory cell using degenerated magnetic states in a synthetic antiferromagnetic reference layer

    International Nuclear Information System (INIS)

    Fukushima, Akio; Yakushiji, Kay; Konoto, Makoto; Kubota, Hitoshi; Imamura, Hiroshi; Yuasa, Shinji

    2016-01-01

    We newly developed a magnetic memory cell having multi-bit function. The memory cell composed of a perpendicularly magnetized magnetic tunnel junction (MB-pMTJ) and a synthetic antiferromagnetic reference layer. The multi-bit function is realized by combining the freedom of states of the magnetic free layer and that in the antiferromagnetically coupled reference layer. The structure of the reference layer is (FeB/Ta/[Co/Pt]_3)/Ru/([Co/Pt]_6); the top and the bottom layers are coupled through Ru layer where the reference layer has two degrees of freedom of a head-to-head and a bottom-to-bottom magnetic configuration. A four-state memory cell is realized by combination of both degrees of freedom. The states in the reference layer however is hardly detected by the total resistance of MB-pMTJ, because the magnetoresistance effect in the reference layer is negligibly small. That implies that the resistance values for the different states in the reference layer are degenerated. On the other hand, the two different states in the reference layer bring different stray fields to the free layer, which generate two different minor loop with different switching fields. Therefore, the magnetic states in the reference layer can be differentiated by the two-step reading, before and after applying the appropriately pulsed magnetic field which can identify the initial state in the reference layer. This method is similar to distinguishing different magnetic states in an in-plane magnetized spin-valve element. We demonstrated that four different states in the MB-pMTJ can be distinguished by the two-step read-out. The important feature of the two-step reading is a practically large operation margins (large resistance change in reading) which is equal to that of a single MTJ. Even though the two-step reading is a destructive method by which 50% of the magnetic state is changed, this MB-pMTJ is promising for high density non-volatile memory cell with a minor cost of operation speed

  7. Atomic crystals resistive switching memory

    International Nuclear Information System (INIS)

    Liu Chunsen; Zhang David Wei; Zhou Peng

    2017-01-01

    Facing the growing data storage and computing demands, a high accessing speed memory with low power and non-volatile character is urgently needed. Resistive access random memory with 4F 2 cell size, switching in sub-nanosecond, cycling endurances of over 10 12 cycles, and information retention exceeding 10 years, is considered as promising next-generation non-volatile memory. However, the energy per bit is still too high to compete against static random access memory and dynamic random access memory. The sneak leakage path and metal film sheet resistance issues hinder the further scaling down. The variation of resistance between different devices and even various cycles in the same device, hold resistive access random memory back from commercialization. The emerging of atomic crystals, possessing fine interface without dangling bonds in low dimension, can provide atomic level solutions for the obsessional issues. Moreover, the unique properties of atomic crystals also enable new type resistive switching memories, which provide a brand-new direction for the resistive access random memory. (topical reviews)

  8. Asymptomatic memory CD8+ T cells

    Science.gov (United States)

    Khan, Arif Azam; Srivastava, Ruchi; Lopes, Patricia Prado; Wang, Christine; Pham, Thanh T; Cochrane, Justin; Thai, Nhi Thi Uyen; Gutierrez, Lucas; BenMohamed, Lbachir

    2014-01-01

    Generation and maintenance of high quantity and quality memory CD8+ T cells determine the level of protection from viral, bacterial, and parasitic re-infections, and hence constitutes a primary goal for T cell epitope-based human vaccines and immunotherapeutics. Phenotypically and functionally characterizing memory CD8+ T cells that provide protection against herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) infections, which cause blinding ocular herpes, genital herpes, and oro-facial herpes, is critical for better vaccine design. We have recently categorized 2 new major sub-populations of memory symptomatic and asymptomatic CD8+ T cells based on their phenotype, protective vs. pathogenic function, and anatomical locations. In this report we are discussing a new direction in developing T cell-based human herpes vaccines and immunotherapeutics based on the emerging new concept of “symptomatic and asymptomatic memory CD8+ T cells.” PMID:24499824

  9. Transparent Memory For Harsh Electronics

    KAUST Repository

    Ho, C. H.; Duran Retamal, Jose Ramon; Yang, P. K.; Lee, C. P.; Tsai, M. L.; Kang, C. F.; He, Jr-Hau

    2017-01-01

    As a new class of non-volatile memory, resistive random access memory (RRAM) offers not only superior electronic characteristics, but also advanced functionalities, such as transparency and radiation hardness. However, the environmental tolerance

  10. Shape Memory of Human Red Blood Cells

    OpenAIRE

    Fischer, Thomas M.

    2004-01-01

    The human red cell can be deformed by external forces but returns to the biconcave resting shape after removal of the forces. If after such shape excursions the rim is always formed by the same part of the membrane, the cell is said to have a memory of its biconcave shape. If the rim can form anywhere on the membrane, the cell would have no shape memory. The shape memory was probed by an experiment called go-and-stop. Locations on the membrane were marked by spontaneously adhering latex spher...

  11. Inkjet-printing of non-volatile organic resistive devices and crossbar array structures

    Science.gov (United States)

    Sax, Stefan; Nau, Sebastian; Popovic, Karl; Bluemel, Alexander; Klug, Andreas; List-Kratochvil, Emil J. W.

    2015-09-01

    Due to the increasing demand for storage capacity in various electronic gadgets like mobile phones or tablets, new types of non-volatile memory devices have gained a lot of attention over the last few years. Especially multilevel conductance switching elements based on organic semiconductors are of great interest due to their relatively simple device architecture and their small feature size. Since organic semiconductors combine the electronic properties of inorganic materials with the mechanical characteristics of polymers, this class of materials is suitable for solution based large area device preparation techniques. Consequently, inkjet based deposition techniques are highly capable of facing preparation related challenges. By gradually replacing the evaporated electrodes with inkjet printed silver, the preparation related influence onto device performance parameters such as the ON/OFF ratio was investigated with IV measurements and high resolution transmission electron microscopy. Due to the electrode surface roughness the solvent load during the printing of the top electrode as well as organic layer inhomogeneity's the utilization in array applications is hampered. As a prototypical example a 1diode-1resistor element and a 2×2 subarray from 5×5 array matrix were fully characterized demonstrating the versatility of inkjet printing for device preparation.

  12. Human T Cell Memory: A Dynamic View

    Directory of Open Access Journals (Sweden)

    Derek C. Macallan

    2017-02-01

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

  13. Modeling of SONOS Memory Cell Erase Cycle

    Science.gov (United States)

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

    2011-01-01

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

  14. Shape memory of human red blood cells.

    Science.gov (United States)

    Fischer, Thomas M

    2004-05-01

    The human red cell can be deformed by external forces but returns to the biconcave resting shape after removal of the forces. If after such shape excursions the rim is always formed by the same part of the membrane, the cell is said to have a memory of its biconcave shape. If the rim can form anywhere on the membrane, the cell would have no shape memory. The shape memory was probed by an experiment called go-and-stop. Locations on the membrane were marked by spontaneously adhering latex spheres. Shape excursions were induced by shear flow. In virtually all red cells, a shape memory was found. After stop of flow and during the return of the latex spheres to the original location, the red cell shape was biconcave. The return occurred by a tank-tread motion of the membrane. The memory could not be eliminated by deforming the red cells in shear flow up to 4 h at room temperature as well as at 37 degrees C. It is suggested that 1). the characteristic time of stress relaxation is >80 min and 2). red cells in vivo also have a shape memory.

  15. A vertically integrated capacitorless memory cell

    International Nuclear Information System (INIS)

    Tong Xiaodong; Wu Hao; Zhao Lichuan; Wang Ming; Zhong Huicai

    2013-01-01

    A two-port capacitorless PNPN device with high density, high speed and low power memory fabricated using standard CMOS technology is presented. Experiments and calibrated simulations were conducted which prove that this new memory cell has a high operation speed (ns level), large read current margin (read current ratio of 10 4 ×), low process variation, good thermal reliability and available retention time (190 ms). Furthermore, the new memory cell is free of the cyclic endurance/reliability problems induced by hot-carrier injection due to the gateless structure. (semiconductor devices)

  16. Electric Field Tuning Non-volatile Magnetism in Half-Metallic Alloys Co2FeAl/Pb(Mg1/3Nb2/3)O3-PbTiO3 Heterostructure

    Science.gov (United States)

    Dunzhu, Gesang; Wang, Fenglong; Zhou, Cai; Jiang, Changjun

    2018-03-01

    We reported the non-volatile electric field-mediated magnetic properties in the half-metallic Heusler alloy Co2FeAl/Pb(Mg1/3Nb2/3)O3-PbTiO3 heterostructure at room temperature. The remanent magnetization with different applied electric field along [100] and [01-1] directions was achieved, which showed the non-volatile remanent magnetization driven by an electric field. The two giant reversible and stable remanent magnetization states were obtained by applying pulsed electric field. This can be attributed to the piezostrain effect originating from the piezoelectric substrate, which can be used for magnetoelectric-based memory devices.

  17. Memory NK cells: why do they reside in the liver?

    OpenAIRE

    Jiang, Xiaojun; Chen, Yonglin; Peng, Hui; Tian, Zhigang

    2013-01-01

    Immune memory is the hallmark of adaptive immunity. However, recent studies have shown that natural killer (NK) cells, key components of the innate immune system, also mediate memory responses in mice and humans. Strikingly, memory NK cells were liver-resident in some models, raising the question as to whether the liver is a special organ for the acquisition of NK cell memory. Here, we review the characteristics of NK cell memory by summarizing recent progress and discuss how the liver may ge...

  18. Enhanced non-volatile and updatable holography using a polymer composite system.

    Science.gov (United States)

    Wu, Pengfei; Sun, Sam Q; Baig, Sarfaraz; Wang, Michael R

    2012-03-12

    Updatable holography is considered as the ultimate technique for true 3D information recording and display. However, there is no practical solution to preserve the required features of both non-volatility and reversibility which conflict with each other when the reading has the same wavelength as the recording. We demonstrate a non-volatile and updatable holographic approach by exploiting new features of molecular transformations in a polymer recording system. In addition, by using a new composite recording film containing photo-reconfigurable liquid-crystal (LC) polymer, the holographic recording is enhanced due to the collective reorientation of LC molecules around the reconfigured polymer chains.

  19. Pregnancy persistently affects memory T cell populations

    NARCIS (Netherlands)

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

    Pregnancy is an immune challenge to the maternal immune system. The effects of pregnancy on maternal immunity and particularly on memory T cells during and after pregnancy are not fully known. This observational study aims to show the short term and the long term effects of pregnancy on the

  20. Cell characteristics of FePt nano-dot memories with a high-k Al2O3 blocking oxide

    International Nuclear Information System (INIS)

    Lee, Gae Hun; Lee, Jung Min; Yang, Hyung Jun; Song, Yun Heub; Bea, Ji Cheol; Tanaka, Testsu

    2012-01-01

    The cell characteristics of an alloy FePt nano-dot (ND) charge trapping memory with a high-k dielectric as a blocking oxide was investigated. Adoption of a high-k Al 2 O 3 material as a blocking oxide for the metal nano-dot memory provided a superior scaling of the operation voltage compared to silicon oxide under a similar gate leakage level. For the 40-nm-thick high-k (Al 2 O 3 ) blocking oxide, we confirmed an operation voltage reduction of ∼7 V under the same memory window on for silicon dioxide. Also, this device showed a large memory window of 7.8 V and a low leakage current under 10 -10 A in an area of Φ 0.25 mm. From these results, the use of a dielectric (Al 2 O 3 ) as a blocking oxide for a metal nano-dot device is essential, and a metal nano-dot memory with a high-k dielectric will be one of the candidates for a high-density non-volatile memory device.

  1. Overcoming thermal noise in non-volatile spin wave logic

    Science.gov (United States)

    Dutta, Sourav; Nikonov, Dmitri; Manipatruni, Sasikanth; Young, Ian; Naeemi, Azad

    Spin waves are propagating disturbances in magnetically ordered materials. To compete as a promising candidate for beyond-CMOS application, the all-magnon based computing system must undergo the essential steps of careful selection of materials and demonstrate robustness with respect to thermal noise/variability. Here, we identify suitable materials and investigate two viable options for translating the theoretical idea of phase-dependent switching of the spin wave detector to a practical realization of a thermally reliable magnonic device by - (a) using the built-in strain in the ME cell, arising from the lattice mismatch and/or thermal expansion coefficient mismatch between the film and the substrate, for compensation of the demagnetization, and (b) using an exchange-spring structure that exhibits a strong exchange-coupling between the ME cell and PMA SWB and provides a modification of the energy landscape of the ME cell magnet. A high switching success and error-free logic functionality can be ensured if the amplitude of the detected spin wave () remains higher than a threshold value of around 6°C and the detected phase falls within the window from 280°C through 0 to 20°C or from 100°C to 200°C with a maximum allowable ϕ range of around 100°C.

  2. A hybrid ferroelectric-flash memory cells

    Science.gov (United States)

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

    2014-09-01

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

  3. WORKSHOP REPORT - CONSIDERATIONS FOR DEVELOPING LEACHING TEST METHODS FOR SEMI- AND NON-VOLATILE ORGANIC COMPOUNDS

    Science.gov (United States)

    The report provides a summary of the information exchange at a workshop on the potential for release of semi- or non-volatile organic constituents at contaminated sites where sub-surface treatment has been used to control migration, and from waste that is disposed or re-used. The...

  4. Doped SbTe phase change material in memory cells

    NARCIS (Netherlands)

    in ‘t Zandt, M.A.A.; Jedema, F.J.; Gravesteijn, Dirk J; Gravesteijn, D.J.; Attenborough, K.; Wolters, Robertus A.M.

    2009-01-01

    Phase Change Random Access Memory (PCRAM) is investigated as replacement for Flash. The memory concept is based on switching a chalcogenide from the crystalline (low ohmic) to the amorphous (high ohmic) state and vice versa. Basically two memory cell concepts exist: the Ovonic Unified Memory (OUM)

  5. Studying the fate of non-volatile organic compounds in a commercial plasma air purifier

    Energy Technology Data Exchange (ETDEWEB)

    Schmid, Stefan [ETH Zürich, Department of Chemistry and Applied Biosciences, CH-8093 Zürich (Switzerland); Seiler, Cornelia; Gerecke, Andreas C. [Swiss Federal Laboratories for Material Science and Technology (EMPA), CH-8600 Dübendorf (Switzerland); Hächler, Herbert [University of Zürich, Institute for Food Safety and Hygiene, National Centre for Enteropathogenic Bacteria and Listeria (NENT), CH-8057 Zürich (Switzerland); Hilbi, Hubert [Ludwig-Maximilians-Universität München Max von Pettenkofer-Institut, D-80336 München (Germany); Frey, Joachim [University of Bern, Institute for Veterinary Bacteriology, CH-3001 Bern (Switzerland); Weidmann, Simon; Meier, Lukas; Berchtold, Christian [ETH Zürich, Department of Chemistry and Applied Biosciences, CH-8093 Zürich (Switzerland); Zenobi, Renato, E-mail: zenobi@org.chem.ethz.ch [ETH Zürich, Department of Chemistry and Applied Biosciences, CH-8093 Zürich (Switzerland)

    2013-07-15

    Highlights: • Degradation of environmental toxins, a protein, and bioparticles were studied. • A commercial air purifier based on a cold plasma was used. • Passage through the device reduced the concentration of the compounds/particles. • Deposition inside the plasma air purifier was the main removal process. -- Abstract: Degradation of non-volatile organic compounds–environmental toxins (methyltriclosane and phenanthrene), bovine serum albumin, as well as bioparticles (Legionella pneumophila, Bacillus subtilis, and Bacillus anthracis)–in a commercially available plasma air purifier based on a cold plasma was studied in detail, focusing on its efficiency and on the resulting degradation products. This system is capable of handling air flow velocities of up to 3.0 m s{sup −1} (3200 L min{sup −1}), much higher than other plasma-based reactors described in the literature, which generally are limited to air flow rates below 10 L min{sup −1}. Mass balance studies consistently indicated a reduction in concentration of the compounds/particles after passage through the plasma air purifier, 31% for phenanthrene, 17% for methyltriclosane, and 80% for bovine serum albumin. L. pneumophila did not survive passage through the plasma air purifier, and cell counts of aerosolized spores of B. subtilis and B. anthracis were reduced by 26- and 15-fold, depending on whether it was run at 10 Hz or 50 Hz, respectively. However rather than chemical degradation, deposition on the inner surfaces of the plasma air purifier occured. Our interpretation is that putative “degradation” efficiencies were largely due to electrostatic precipitation rather than to decomposition into smaller molecules.

  6. Measurements of a vortex transitional ndro Josephson memory cell

    International Nuclear Information System (INIS)

    Tahara, S.; Ishida, I.; Hidaka, M.; Nagasawa, S.; Ajisawa, Y.; Wada, Y.

    1988-01-01

    A novel vortex transitional NDRO Jospehson memory cell has been successfully fabricated and tested. The memory cell consists of two superconducting loops and a two-junction interferometer gate as a sense gate. The superconducting loop contains one Josephson junction and inductances, and stores single flux quantum. The memory cell employs vortex transitions in the superconducting loops for writing and reading data. The memory cell chips have been fabricated using niobium planarization process. The +-21 percent address signal current margin and the +-33 percent sense gate current margin have been obtained experimentally. The memory operation of the cell driven by the two-junction interferometer gates has been accurately demonstrated

  7. Measurements of non-volatile aerosols with a VTDMA and their correlations with carbonaceous aerosols in Guangzhou, China

    Science.gov (United States)

    Cheung, Heidi H. Y.; Tan, Haobo; Xu, Hanbing; Li, Fei; Wu, Cheng; Yu, Jian Z.; Chan, Chak K.

    2016-07-01

    Simultaneous measurements of aerosol volatility and carbonaceous matters were conducted at a suburban site in Guangzhou, China, in February and March 2014 using a volatility tandem differential mobility analyzer (VTDMA) and an organic carbon/elemental carbon (OC / EC) analyzer. Low volatility (LV) particles, with a volatility shrink factor (VSF) at 300 °C exceeding 0.9, contributed 5 % of number concentrations of the 40 nm particles and 11-15 % of the 80-300 nm particles. They were composed of non-volatile material externally mixed with volatile material, and therefore did not evaporate significantly at 300 °C. Non-volatile material mixed internally with the volatile material was referred to as medium volatility (MV, 0.4 transported at low altitudes (below 1500 m) for over 40 h before arrival. Further comparison with the diurnal variations in the mass fractions of EC and the non-volatile OC in PM2.5 suggests that the non-volatile residuals may be related to both EC and non-volatile OC in the afternoon, during which the concentration of aged organics increased. A closure analysis of the total mass of LV and MV residuals and the mass of EC or the sum of EC and non-volatile OC was conducted. It suggests that non-volatile OC, in addition to EC, was one of the components of the non-volatile residuals measured by the VTDMA in this study.

  8. Flash memories economic principles of performance, cost and reliability optimization

    CERN Document Server

    Richter, Detlev

    2014-01-01

    The subject of this book is to introduce a model-based quantitative performance indicator methodology applicable for performance, cost and reliability optimization of non-volatile memories. The complex example of flash memories is used to introduce and apply the methodology. It has been developed by the author based on an industrial 2-bit to 4-bit per cell flash development project. For the first time, design and cost aspects of 3D integration of flash memory are treated in this book. Cell, array, performance and reliability effects of flash memories are introduced and analyzed. Key performance parameters are derived to handle the flash complexity. A performance and array memory model is developed and a set of performance indicators characterizing architecture, cost and durability is defined.   Flash memories are selected to apply the Performance Indicator Methodology to quantify design and technology innovation. A graphical representation based on trend lines is introduced to support a requirement based pr...

  9. Memory NK cells: why do they reside in the liver?

    Science.gov (United States)

    Jiang, Xiaojun; Chen, Yonglin; Peng, Hui; Tian, Zhigang

    2013-05-01

    Immune memory is the hallmark of adaptive immunity. However, recent studies have shown that natural killer (NK) cells, key components of the innate immune system, also mediate memory responses in mice and humans. Strikingly, memory NK cells were liver-resident in some models, raising the question as to whether the liver is a special organ for the acquisition of NK cell memory. Here, we review the characteristics of NK cell memory by summarizing recent progress and discuss how the liver may generate both the initiation and the recall phase of memory. We propose that the liver may have unique precursors for memory NK cells, which are developmentally distinct from NK cells derived from bone marrow.

  10. Engrampigenetics: Epigenetics of engram memory cells.

    Science.gov (United States)

    Ripoli, Cristian

    2017-05-15

    For long time, the epidemiology of late-onset sporadic Alzheimer's disease (AD) risk factors has centered on adult life-style. Recent studies have, instead, focused on the role of early life experiences in progression of such disease especially in the context of prenatal and postnatal life. Although no single unfavorable environmental event has been shown to be neither necessary nor sufficient for AD development, it is possible that the sum of several environmentally induced effects, over time, contribute to its pathophysiology through epigenetic mechanisms. Indeed, epigenetic changes are influenced by environmental factors and have been proposed to play a role in multifactorial pathologies such as AD. At the same time, recent findings suggest that epigenetic mechanisms are one method that neurons use to translate transient stimuli into stable memories. Thus, the characteristics of epigenetics being a critical link between the environment and genes and playing a crucial role in memory formation make candidate epigenetic mechanisms a natural substrate for AD research. Indeed, independent groups have reported several epigenetically dysregulated genes in AD models; however, the role of epigenetic mechanisms in AD has remained elusive owing to contradictory results. Here, I propose that restricting the analysis of epigenetic changes specifically to subpopulations of neurons (namely, engram memory cells) might be helpful in understanding the role of the epigenetic process in the memory-related specific epigenetic code and might constitute a new template for therapeutic interventions against AD. Copyright © 2016. Published by Elsevier B.V.

  11. Identifying Non-Volatile Data Storage Areas: Unique Notebook Identification Information as Digital Evidence

    Directory of Open Access Journals (Sweden)

    Nikica Budimir

    2007-03-01

    Full Text Available The research reported in this paper introduces new techniques to aid in the identification of recovered notebook computers so they may be returned to the rightful owner. We identify non-volatile data storage areas as a means of facilitating the safe storing of computer identification information. A forensic proof of concept tool has been designed to test the feasibility of several storage locations identified within this work to hold the data needed to uniquely identify a computer. The tool was used to perform the creation and extraction of created information in order to allow the analysis of the non-volatile storage locations as valid storage areas capable of holding and preserving the data created within them.  While the format of the information used to identify the machine itself is important, this research only discusses the insertion, storage and ability to retain such information.

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

    Science.gov (United States)

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

    2018-05-01

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

  13. The Effect of Shape Memory on Red Blood Cell Motions

    Science.gov (United States)

    Niu, Xiting; Shi, Lingling; Pan, Tsorng-Whay; Glowinski, Roland

    2013-11-01

    An elastic spring model is applied to study the effect of the shape memory on the motion of red blood cell in flows. In shear flow, shape memory also plays an important role to obtain all three motions: tumbling, swinging, and tank-treading. In Poiseuille flow, cell has an equilibrium shape as a slipper or parachute depending on capillary number. To ensure the tank-treading motion while in slippery shape, a modified model is proposed by introducing a shape memory coefficient which describes the degree of shape memory in cells. The effect of the coefficient on the cell motion of red blood cell will be presented.

  14. Supercritical fluid extraction of volatile and non-volatile compounds from Schinus molle L.

    Directory of Open Access Journals (Sweden)

    M. S. T. Barroso

    2011-06-01

    Full Text Available Schinus molle L., also known as pepper tree, has been reported to have antimicrobial, antifungal, anti-inflammatory, antispasmodic, antipyretic, antitumoural and cicatrizing properties. This work studies supercritical fluid extraction (SFE to obtain volatile and non-volatile compounds from the aerial parts of Schinus molle L. and the influence of the process on the composition of the extracts. Experiments were performed in a pilot-scale extractor with a capacity of 1 L at pressures of 9, 10, 12, 15 and 20 MPa at 323.15 K. The volatile compounds were obtained by CO2 supercritical extraction with moderate pressure (9 MPa, whereas the non-volatile compounds were extracted at higher pressure (12 to 20 MPa. The analysis of the essential oil was carried out by GC-MS and the main compounds identified were sabinene, limonene, D-germacrene, bicyclogermacrene, and spathulenol. For the non-volatile extracts, the total phenolic content was determined by the Folin-Ciocalteau method. Moreover, one of the goals of this study was to compare the experimental data with the simulated yields predicted by a mathematical model based on mass transfer. The model used requires three adjustable parameters to predict the experimental extraction yield curves.

  15. CD4 T-Cell Memory Generation and Maintenance

    Science.gov (United States)

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

    2014-01-01

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

  16. Low power and reliable SRAM memory cell and array design

    CERN Document Server

    Ishibashi, Koichiro

    2011-01-01

    Success in the development of recent advanced semiconductor device technologies is due to the success of SRAM memory cells. This book addresses various issues for designing SRAM memory cells for advanced CMOS technology. To study LSI design, SRAM cell design is the best materials subject because issues about variability, leakage and reliability have to be taken into account for the design.

  17. EqualChance: Addressing Intra-set Write Variation to Increase Lifetime of Non-volatile Caches

    Energy Technology Data Exchange (ETDEWEB)

    Mittal, Sparsh [ORNL; Vetter, Jeffrey S [ORNL

    2014-01-01

    To address the limitations of SRAM such as high-leakage and low-density, researchers have explored use of non-volatile memory (NVM) devices, such as ReRAM (resistive RAM) and STT-RAM (spin transfer torque RAM) for designing on-chip caches. A crucial limitation of NVMs, however, is that their write endurance is low and the large intra-set write variation introduced by existing cache management policies may further exacerbate this problem, thereby reducing the cache lifetime significantly. We present EqualChance, a technique to increase cache lifetime by reducing intra-set write variation. EqualChance works by periodically changing the physical cache-block location of a write-intensive data item within a set to achieve wear-leveling. Simulations using workloads from SPEC CPU2006 suite and HPC (high-performance computing) field show that EqualChance improves the cache lifetime by 4.29X. Also, its implementation overhead is small, and it incurs very small performance and energy loss.

  18. Integrating Two-Dimensional Nanomaterials and Molecular Dielectrics for Radiation-Hard Non-Volatile Memory

    Data.gov (United States)

    National Aeronautics and Space Administration — The space radiation environment presents a significant hazard to the critical electronic components used in a variety of space applications. Many such applications...

  19. Integration of organic based Schottky junctions for crossbar non-volatile memory applications

    DEFF Research Database (Denmark)

    Katsia, E.; Tallarida, G.; Ferrari, S.

    2008-01-01

    Small size Schottky junctions using two different synthesized organic semiconductors (oligophenylene-vinylenes) were integrated by standard UV lithography into crossbar arrays. The proposed integration scheme can be applied to a wide class of organics without affecting material properties. Current...

  20. Interregional synaptic maps among engram cells underlie memory formation.

    Science.gov (United States)

    Choi, Jun-Hyeok; Sim, Su-Eon; Kim, Ji-Il; Choi, Dong Il; Oh, Jihae; Ye, Sanghyun; Lee, Jaehyun; Kim, TaeHyun; Ko, Hyoung-Gon; Lim, Chae-Seok; Kaang, Bong-Kiun

    2018-04-27

    Memory resides in engram cells distributed across the brain. However, the site-specific substrate within these engram cells remains theoretical, even though it is generally accepted that synaptic plasticity encodes memories. We developed the dual-eGRASP (green fluorescent protein reconstitution across synaptic partners) technique to examine synapses between engram cells to identify the specific neuronal site for memory storage. We found an increased number and size of spines on CA1 engram cells receiving input from CA3 engram cells. In contextual fear conditioning, this enhanced connectivity between engram cells encoded memory strength. CA3 engram to CA1 engram projections strongly occluded long-term potentiation. These results indicate that enhanced structural and functional connectivity between engram cells across two directly connected brain regions forms the synaptic correlate for memory formation. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  1. Radiation damage in flash memory cells

    International Nuclear Information System (INIS)

    Claeys, C.; Ohyama, H.; Simoen, E.; Nakabayashi, M.; Kobayashi, K.

    2002-01-01

    Results are presented of a study on the effects of total ionization dose and displacement damage, induced by high-energy electrons, protons and alphas, on the performance degradation of flash memory cells integrated in a microcomputer. A conventional stacked-gate n-channel flash memory cell using a 0.8 μm n-polysilicon gate technology is employed. Irradiations by 1-MeV electrons and 20-MeV protons and alpha particles were done at room temperature. The impact of the fluence on the input characteristics, threshold voltage shift and drain and gate leakage was investigated. The threshold voltage change for proton and alpha irradiations is about three orders of magnitude larger than that for electrons. The performance degradation is mainly caused by the total ionization dose (TID) damage in the tunnel oxide and in the interpoly dielectric layer and by the creation of interface traps at the Si-SiO 2 interface. The impact of the irradiation temperature on the device degradation was studied for electrons and gammas, pointing out that irradiation at room temperature is mostly the worst case. Finally, attention is given to the impact of isochronal and isothermal annealing on the recovery of the degradation introduced after room temperature proton and electron irradiation

  2. Demonstration of Novel Sampling Techniques for Measurement of Turbine Engine Volatile and Non-Volatile Particulate Matter (PM) Emissions

    Science.gov (United States)

    2017-03-06

    WP-201317) Demonstration of Novel Sampling Techniques for Measurement of Turbine Engine Volatile and Non-volatile Particulate Matter (PM... Engine Volatile and Non-Volatile Particulate Matter (PM) Emissions 6. AUTHOR(S) E. Corporan, M. DeWitt, C. Klingshirn, M.D. Cheng, R. Miake-Lye, J. Peck...the performance and viability of two devices to condition aircraft turbine engine exhaust to allow the accurate measurement of total (volatile and non

  3. Cathode and ion-luminescence of Eu:ZnO thin films prepared by reactive magnetron sputtering and plasma decomposition of non-volatile precursors

    Energy Technology Data Exchange (ETDEWEB)

    Gil-Rostra, Jorge [Instituto de Ciencia de Materiales de Sevilla, CSIC, Univ. Sevilla, C/Américo Vespucio 49, E-41092 Sevilla (Spain); Ferrer, Francisco J. [Centro Nacional de Aceleradores, CSIC, Univ. Sevilla, Av. Thomas A. Edison 7, E-41092 Sevilla (Spain); Martín, Inocencio R. [Departamento de Física Fundamental y Experimental, Electrónica y Sistemas, U. La Laguna, C/Astrofísico Francisco Sánchez s/n, E-38206 La Laguna, Santa Cruz de Tenerife (Spain); González-Elipe, Agustín R.; Yubero, Francisco [Instituto de Ciencia de Materiales de Sevilla, CSIC, Univ. Sevilla, C/Américo Vespucio 49, E-41092 Sevilla (Spain)

    2016-10-15

    This paper reports the luminescent behavior of Eu:ZnO thin films prepared by an one-step procedure that combines reactive magnetron sputtering deposition of ZnO with the plasma activated decomposition of a non-volatile acetylacetonate precursor of Eu sublimated in an effusion cell. Chemical composition and microstructure of the Eu:ZnO thin films have been characterized by several methods and their photo-, cathode- and ion-luminescent properties studied as a function of Eu concentration. The high transparency and well controlled optical properties of the films have demonstrated to be ideal for the development of cathode- and ion- luminescence sensors.

  4. Large non-volatile tuning of magnetism mediated by electric field in Fe–Al/Pb(Mg1/3Nb2/3)O3–PbTiO3 heterostructure

    International Nuclear Information System (INIS)

    Chen, Zhendong; Gao, Cunxu; Wei, Yanping; Zhang, Peng; Wang, Yutian; Zhang, Chao; Ma, Zhikun

    2017-01-01

    Electric-field control of magnetism is now an attractive trend to approach a new kind of fast, low-power-cost memory device. In this work, we report a strong non-volatile electric control of magnetism in an Fe–Al/Pb(Mg 1/3 Nb 2/3 )O 3 –PbTiO 3 heterostructure. In this system, a 90° rotation of the in-plane uniaxial magnetic anisotropy is exhibited during the increase of the external electric field, which means the easy axis turns into a hard axis and the hard axis turns into an easy one. Additionally, a non-volatile switch of the remanence is observed after a sweeping of the electric field from 0 kV cm −1 to  ±  10 kV cm −1 , then back to 0 kV cm −1 . More interestingly, a 20% non-volatile magnetic state tuning driven by individual pulse electric fields is shown in contrast to large tuning up to 120% caused by pulse electric fields with small assistant pulse magnetic fields, which means a 180° reverse of the magnetization. These remarkable behaviors demonstrated in this heterostructure reveal a promising potential application in magnetic memory devices mediated by electric fields. (paper)

  5. Memory CD8 T cell inflation vs tissue-resident memory T cells: Same patrollers, same controllers?

    Science.gov (United States)

    Welten, Suzanne P M; Sandu, Ioana; Baumann, Nicolas S; Oxenius, Annette

    2018-05-01

    The induction of long-lived populations of memory T cells residing in peripheral tissues is of considerable interest for T cell-based vaccines, as they can execute immediate effector functions and thus provide protection in case of pathogen encounter at mucosal and barrier sites. Cytomegalovirus (CMV)-based vaccines support the induction and accumulation of a large population of effector memory CD8 T cells in peripheral tissues, in a process called memory inflation. Tissue-resident memory (T RM ) T cells, induced by various infections and vaccination regimens, constitute another subset of memory cells that take long-term residence in peripheral tissues. Both memory T cell subsets have evoked substantial interest in exploitation for vaccine purposes. However, a direct comparison between these two peripheral tissue-localizing memory T cell subsets with respect to their short- and long-term ability to provide protection against heterologous challenge is pending. Here, we discuss communalities and differences between T RM and inflationary CD8 T cells with respect to their development, maintenance, function, and protective capacity. In addition, we discuss differences and similarities between the transcriptional profiles of T RM and inflationary T cells, supporting the notion that they are distinct memory T cell populations. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Determination of non-volatile radiolytic compounds in ethylene co-vinyl alcohol

    International Nuclear Information System (INIS)

    Kothapalli, A.; Sadler, G.

    2003-01-01

    The use of ionizing radiation on food contact polymers is increasing due to the critical role of the package in holding or containing the irradiated foods [Food Add. Contam. 18(6) (2001) 475]. Irradiation benefits the food if properly applied and the food is pre-packaged prior to irradiation to protect it from subsequent recontamination. The United States Food and Drug Administration (USFDA) has approved the use of ionizing radiation within the dosage range of 0-60 kGy on limited films since the 1960s [USFDA 21CFR 179.45]. The obstacle in the way of approval of additional polymers is that FDA fears that these materials may undergo changes during irradiation producing toxic radiolytic fragments. Ethylene co-vinyl alcohol (EVOH), which is often used in food applications, is not approved by the FDA for pre-packaged irradiated foods. The present work examines the non-volatile radiolytic compounds, which may be formed due to exposure to gamma irradiation at the dosage levels of 3 and 10 kGy versus a non-radiated control. Irradiated EVOH is subjected to extraction with 95:5 ethanol and water (by volume) as the food simulating solvent (FSS) for a period of 10 days at 40 deg. C, which models the amount of radiolytic compound a food would extract in 1 year [USFDA Chemistry Requirement for Food Contact Notification]. The FSS is then analyzed for the presence of non-volatile compounds using advanced liquid chromatographic techniques. The chromatograms obtained from different dosages show that non-volatile radiolytic compounds are not formed in EVOH and it would, therefore be in compliance with safety demands of USFDA [Available at: http://www.cfsan.fda.gov/~dms/opa-guid.htmlref and http://www.access.gpo.gov/nara/cfr/cfr-table-search.htmlpage1

  7. Characteristics of a non-volatile liquid propellant in liquid-fed ablative pulsed plasma thrusters

    Science.gov (United States)

    Ling, William Yeong Liang; Schönherr, Tony; Koizumi, Hiroyuki

    2017-02-01

    In the past several decades, the use of electric propulsion in spacecraft has experienced tremendous growth. With the increasing adoption of small satellites in the kilogram range, suitable propulsion systems will be necessary in the near future. Pulsed plasma thrusters (PPTs) were the first form of electric propulsion to be deployed in orbit, and are highly suitable for small satellites due to their inherent simplicity. However, their lifetime is limited by disadvantages such as carbon deposition leading to thruster failure, and complicated feeding systems required due to the conventional use of solid propellants (usually polytetrafluoroethylene (PTFE)). A promising alternative to solid propellants has recently emerged in the form of non-volatile liquids that are stable in vacuum. This study presents a broad comparison of the non-volatile liquid perfluoropolyether (PFPE) and solid PTFE as propellants on a PPT with a common design base. We show that liquid PFPE can be successfully used as a propellant, and exhibits similar plasma discharge properties to conventional solid PTFE, but with a mass bit that is an order of magnitude higher for an identical ablation area. We also demonstrate that the liquid PFPE propellant has exceptional resistance to carbon deposition, completely negating one of the major causes of thruster failure, while solid PTFE exhibited considerable carbon build-up. Energy dispersive X-ray spectroscopy was used to examine the elemental compositions of the surface deposition on the electrodes and the ablation area of the propellant (or PFPE encapsulator). The results show that based on its physical characteristics and behavior, non-volatile liquid PFPE is an extremely promising propellant for use in PPTs, with an extensive scope available for future research and development.

  8. Determination of non-volatile radiolytic compounds in ethylene co-vinyl alcohol

    Science.gov (United States)

    Kothapalli, A.; Sadler, G.

    2003-08-01

    The use of ionizing radiation on food contact polymers is increasing due to the critical role of the package in holding or containing the irradiated foods [Food Add. Contam. 18(6) (2001) 475]. Irradiation benefits the food if properly applied and the food is pre-packaged prior to irradiation to protect it from subsequent recontamination. The United States Food and Drug Administration (USFDA) has approved the use of ionizing radiation within the dosage range of 0-60 kGy on limited films since the 1960s [USFDA 21CFR 179.45]. The obstacle in the way of approval of additional polymers is that FDA fears that these materials may undergo changes during irradiation producing toxic radiolytic fragments. Ethylene co-vinyl alcohol (EVOH), which is often used in food applications, is not approved by the FDA for pre-packaged irradiated foods. The present work examines the non-volatile radiolytic compounds, which may be formed due to exposure to gamma irradiation at the dosage levels of 3 and 10 kGy versus a non-radiated control. Irradiated EVOH is subjected to extraction with 95:5 ethanol and water (by volume) as the food simulating solvent (FSS) for a period of 10 days at 40 °C, which models the amount of radiolytic compound a food would extract in 1 year [USFDA Chemistry Requirement for Food Contact Notification]. The FSS is then analyzed for the presence of non-volatile compounds using advanced liquid chromatographic techniques. The chromatograms obtained from different dosages show that non-volatile radiolytic compounds are not formed in EVOH and it would, therefore be in compliance with safety demands of USFDA [Available at: http://www.cfsan.fda.gov/~dms/opa-guid.html#ref and http://www.access.gpo.gov/nara/cfr/cfr-table-search.html#page1].

  9. Distributed Shared Memory for the Cell Broadband Engine (DSMCBE)

    DEFF Research Database (Denmark)

    Larsen, Morten Nørgaard; Skovhede, Kenneth; Vinter, Brian

    2009-01-01

    in and out of non-coherent local storage blocks for each special processor element. In this paper we present a software library, namely the Distributed Shared Memory for the Cell Broadband Engine (DSMCBE). By using techniques known from distributed shared memory DSMCBE allows programmers to program the CELL...

  10. Low-field Switching Four-state Nonvolatile Memory Based on Multiferroic Tunnel Junctions

    Science.gov (United States)

    Yau, H. M.; Yan, Z. B.; Chan, N. Y.; Au, K.; Wong, C. M.; Leung, C. W.; Zhang, F. Y.; Gao, X. S.; Dai, J. Y.

    2015-08-01

    Multiferroic tunneling junction based four-state non-volatile memories are very promising for future memory industry since this kind of memories hold the advantages of not only the higher density by scaling down memory cell but also the function of magnetically written and electrically reading. In this work, we demonstrate a success of this four-state memory in a material system of NiFe/BaTiO3/La0.7Sr0.3MnO3 with improved memory characteristics such as lower switching field and larger tunneling magnetoresistance (TMR). Ferroelectric switching induced resistive change memory with OFF/ON ratio of 16 and 0.3% TMR effect have been achieved in this multiferroic tunneling structure.

  11. CD4 T cell autophagy is integral to memory maintenance.

    Science.gov (United States)

    Murera, Diane; Arbogast, Florent; Arnold, Johan; Bouis, Delphine; Muller, Sylviane; Gros, Frédéric

    2018-04-13

    Studies of mice deficient for autophagy in T cells since thymic development, concluded that autophagy is integral to mature T cell homeostasis. Basal survival and functional impairments in vivo, limited the use of these models to delineate the role of autophagy during the immune response. We generated Atg5 f/f distal Lck (dLck)-cre mice, with deletion of autophagy only at a mature stage. In this model, autophagy deficiency impacts CD8 + T cell survival but has no influence on CD4 + T cell number and short-term activation. Moreover, autophagy in T cells is dispensable during early humoral response but critical for long-term antibody production. Autophagy in CD4 + T cells is required to transfer humoral memory as shown by injection of antigen-experienced cells in naive mice. We also observed a selection of autophagy-competent cells in the CD4 + T cell memory compartment. We performed in vitro differentiation of memory CD4 + T cells, to better characterize autophagy-deficient memory cells. We identified mitochondrial and lipid load defects in differentiated memory CD4 + T cells, together with a compromised survival, without any collapse of energy production. We then propose that memory CD4 + T cells rely on autophagy for their survival to regulate toxic effects of mitochondrial activity and lipid overload.

  12. Emerging memory technologies design, architecture, and applications

    CERN Document Server

    2014-01-01

    This book explores the design implications of emerging, non-volatile memory (NVM) technologies on future computer memory hierarchy architecture designs. Since NVM technologies combine the speed of SRAM, the density of DRAM, and the non-volatility of Flash memory, they are very attractive as the basis for future universal memories. This book provides a holistic perspective on the topic, covering modeling, design, architecture and applications. The practical information included in this book will enable designers to exploit emerging memory technologies to improve significantly the performance/power/reliability of future, mainstream integrated circuits. • Provides a comprehensive reference on designing modern circuits with emerging, non-volatile memory technologies, such as MRAM and PCRAM; • Explores new design opportunities offered by emerging memory technologies, from a holistic perspective; • Describes topics in technology, modeling, architecture and applications; • Enables circuit designers to ex...

  13. Memory T follicular helper CD4 T cells

    Directory of Open Access Journals (Sweden)

    J. Scott eHale

    2015-02-01

    Full Text Available T follicular helper (Tfh cells are the subset of CD4 T helper cells that are required for generation and maintenance of germinal center reactions and the generation of long-lived humoral immunity. This specialized T helper subset provides help to cognate B cells via their expression of CD40 ligand, IL-21, IL-4, and other molecules. Tfh cells are characterized by their expression of the chemokine receptor CXCR5, expression of the transcriptional repressor Bcl6, and their capacity to migrate to the follicle and promote germinal center B cell responses. Until recently, it remained unclear whether Tfh cells differentiated into memory cells and whether they maintain their Tfh commitment at the memory phase. This review will highlight several recent studies that support the idea of Tfh-committed CD4 T cells at the memory stage of the immune response. The implication of these findings is that memory Tfh cells retain their capacity to recall their Tfh-specific effector functions upon reactivation to provide help for B cell responses and play an important role in prime and boost vaccination or during recall responses to infection. The markers that are useful for distinguishing Tfh effector and memory cells, as well as the limitations of using these markers will be discussed. Tfh effector and memory generation, lineage maintenance, and plasticity relative to other T helper lineages (Th1, Th2, Th17, etc will also be discussed. Ongoing discoveries regarding the maintenance and lineage stability versus plasticity of memory Tfh cells will improve strategies that utilize CD4 T cell memory to modulate antibody responses during prime and boost vaccination.

  14. Impact of time and space evolution of ion tracks in nonvolatile memory cells approaching nanoscale

    International Nuclear Information System (INIS)

    Cellere, G.; Paccagnella, A.; Murat, M.; Barak, J.; Akkerman, A.; Harboe-Sorensen, R.; Virtanen, A.; Visconti, A.; Bonanomi, M.

    2010-01-01

    Swift heavy ions impacting on matter lose energy through the creation of dense tracks of charges. The study of the space and time evolution of energy exchange allows understanding the single event effects behavior in advanced microelectronic devices. In particular, the shrinking of minimum feature size of most advanced memory devices makes them very interesting test vehicles to study these effects since the device and the track dimensions are comparable; hence, measured effects are directly correlated with the time and space evolution of the energy release. In this work we are studying the time and space evolution of ion tracks by using advanced non volatile memories and Monte Carlo simulations. Experimental results are very well explained by the theoretical calculations.

  15. Generation of memory B cells and their reactivation.

    Science.gov (United States)

    Inoue, Takeshi; Moran, Imogen; Shinnakasu, Ryo; Phan, Tri Giang; Kurosaki, Tomohiro

    2018-05-01

    The successful establishment of humoral memory response depends on at least two layers of defense. Pre-existing protective antibodies secreted by long-lived plasma cells act as a first line of defense against reinfection ("constitutive humoral memory"). Previously, a second line of defense in which pathogen-experienced memory B cells are rapidly reactivated to produce antibodies ("reactive humoral memory"), was considered as simply a back-up system for the first line (particularly for re-infection with homologous viruses). However, in the case of re-infection with similar but different strains of viruses, or in response to viral escape mutants, the reactive humoral memory plays a crucial role. Here, we review recent progress in our understanding of how memory B cells are generated in the pre-GC stage and during the GC reaction, and how these memory B cells are robustly reactivated with the help of memory Tfh cells to generate the secondary antibody response. In addition, we discuss how these advances may be relevant to the quest for a vaccine that can induce broadly reactive antibodies against influenza and HIV. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Measurements of non-volatile aerosols with a VTDMA and their correlations with carbonaceous aerosols in Guangzhou, China

    Directory of Open Access Journals (Sweden)

    H. H. Y. Cheung

    2016-07-01

    Full Text Available Simultaneous measurements of aerosol volatility and carbonaceous matters were conducted at a suburban site in Guangzhou, China, in February and March 2014 using a volatility tandem differential mobility analyzer (VTDMA and an organic carbon/elemental carbon (OC ∕ EC analyzer. Low volatility (LV particles, with a volatility shrink factor (VSF at 300 °C exceeding 0.9, contributed 5 % of number concentrations of the 40 nm particles and 11–15 % of the 80–300 nm particles. They were composed of non-volatile material externally mixed with volatile material, and therefore did not evaporate significantly at 300 °C. Non-volatile material mixed internally with the volatile material was referred to as medium volatility (MV, 0.4  <  VSF  <  0.9 and high volatility (HV, VSF  <  0.4 particles. The MV and HV particles contributed 57–71 % of number concentration for the particles between 40 and 300 nm in size. The average EC and OC concentrations measured by the OC ∕ EC analyzer were 3.4 ± 3.0 and 9.0 ± 6.0 µg m−3, respectively. Non-volatile OC evaporating at 475 °C or above, together with EC, contributed 67 % of the total carbon mass. In spite of the daily maximum and minimum, the diurnal variations in the volume fractions of the volatile material, HV, MV and LV residuals were less than 15 % for the 80–300 nm particles. Back trajectory analysis also suggests that over 90 % of the air masses influencing the sampling site were well aged as they were transported at low altitudes (below 1500 m for over 40 h before arrival. Further comparison with the diurnal variations in the mass fractions of EC and the non-volatile OC in PM2.5 suggests that the non-volatile residuals may be related to both EC and non-volatile OC in the afternoon, during which the concentration of aged organics increased. A closure analysis of the total mass of LV and MV residuals and the mass of EC or the

  17. Associative memory cells and their working principle in the brain

    Science.gov (United States)

    Wang, Jin-Hui; Cui, Shan

    2018-01-01

    The acquisition, integration and storage of exogenous associated signals are termed as associative learning and memory. The consequences and processes of associative thinking and logical reasoning based on these stored exogenous signals can be memorized as endogenous signals, which are essential for decision making, intention, and planning. Associative memory cells recruited in these primary and secondary associative memories are presumably the foundation for the brain to fulfill cognition events and emotional reactions in life, though the plasticity of synaptic connectivity and neuronal activity has been believed to be involved in learning and memory. Current reports indicate that associative memory cells are recruited by their mutual synapse innervations among co-activated brain regions to fulfill the integration, storage and retrieval of associated signals. The activation of these associative memory cells initiates information recall in the mind, and the successful activation of their downstream neurons endorses memory presentations through behaviors and emotion reactions. In this review, we aim to draw a comprehensive diagram for associative memory cells, working principle and modulation, as well as propose their roles in cognition, emotion and behaviors. PMID:29487741

  18. Tumor cells and memory T cells converge at glycolysis

    Science.gov (United States)

    Karthikeyan, Swathi; Geschwind, Jean-Francois; Ganapathy-Kanniappan, Shanmugasundaram

    2014-01-01

    In the immune system, activation of naïve T (Tn) cells into effector T cells (Teff) involves a metabolic switch to glycolysis to promote rapid proliferation and differentiation. In the October issue of The Journal of Clinical Investigation, Sukumar et al. have demonstrated that in CD8+ memory T (Tems) cells glycolytic phenotype contributes to the shortened lifespan of Tems. Conversely, inhibition of glycolysis in Tems not only extended their viability but also augmented desirable properties. Notably, they also demonstrate that glycolytic inhibition during the ex vivo clonal expansion of tumor-specific Tems enhanced their antitumor function. Overall, the data suggest that an antiglycolytic strategy targeting the Tems could enhance antitumor immune response. On the other hand, cancer cells have long been known to exhibit metabolic reprogramming which involves a shift toward glycolysis (the conversion of glucose into lactate) to facilitate uninterrupted growth. Interestingly, antiglycolytic treatment of cancer cells has been known to trigger antitumor immune response as well. Taken together, it is probable that a strategy involving concurrent inhibition of glycolysis in tumor cells and Tems could promote a dual attack on cancer by inducing an effective antitumor immune response and an immunogenic chemotherapy. PMID:24556820

  19. Flavor Compounds in Pixian Broad-Bean Paste: Non-Volatile Organic Acids and Amino Acids

    Directory of Open Access Journals (Sweden)

    Hongbin Lin

    2018-05-01

    Full Text Available Non-volatile organic acids and amino acids are important flavor compounds in Pixian broad-bean paste, which is a traditional Chinese seasoning product. In this study, non-volatile organic acids, formed in the broad-bean paste due to the metabolism of large molecular compounds, are qualitatively and quantitatively determined by high-performance liquid chromatography (HPLC. Amino acids, mainly produced by hydrolysis of soybean proteins, were determined by the amino acid automatic analyzer. Results indicated that seven common organic acids and eighteen common amino acids were found in six Pixian broad-bean paste samples. The content of citric acid was found to be the highest in each sample, between 4.1 mg/g to 6.3 mg/g, and malic acid were between 2.1 mg/g to 3.6 mg/g ranked as the second. Moreover, fumaric acid was first detected in fermented bean pastes albeit with a low content. For amino acids, savory with lower sour taste including glutamine (Gln, glutamic acid (Glu, aspartic acid (Asp and asparagines (Asn were the most abundant, noted to be 6.5 mg/g, 4.0 mg/g, 6.4 mg/g, 4.9 mg/g, 6.2 mg/g and 10.2 mg/g, and bitter taste amino acids followed. More importantly, as important flavor materials in Pixian broad-bean paste, these two groups of substances are expected to be used to evaluate and represent the flavor quality of Pixian broad-bean paste. Moreover, the results revealed that citric acid, glutamic acid, methionine and proline were the most important flavor compounds. These findings are agreat contribution for evaluating the quality and further assessment of Pixian broad-bean paste.

  20. Flavor Compounds in Pixian Broad-Bean Paste: Non-Volatile Organic Acids and Amino Acids.

    Science.gov (United States)

    Lin, Hongbin; Yu, Xiaoyu; Fang, Jiaxing; Lu, Yunhao; Liu, Ping; Xing, Yage; Wang, Qin; Che, Zhenming; He, Qiang

    2018-05-29

    Non-volatile organic acids and amino acids are important flavor compounds in Pixian broad-bean paste, which is a traditional Chinese seasoning product. In this study, non-volatile organic acids, formed in the broad-bean paste due to the metabolism of large molecular compounds, are qualitatively and quantitatively determined by high-performance liquid chromatography (HPLC). Amino acids, mainly produced by hydrolysis of soybean proteins, were determined by the amino acid automatic analyzer. Results indicated that seven common organic acids and eighteen common amino acids were found in six Pixian broad-bean paste samples. The content of citric acid was found to be the highest in each sample, between 4.1 mg/g to 6.3 mg/g, and malic acid were between 2.1 mg/g to 3.6 mg/g ranked as the second. Moreover, fumaric acid was first detected in fermented bean pastes albeit with a low content. For amino acids, savory with lower sour taste including glutamine (Gln), glutamic acid (Glu), aspartic acid (Asp) and asparagines (Asn) were the most abundant, noted to be 6.5 mg/g, 4.0 mg/g, 6.4 mg/g, 4.9 mg/g, 6.2 mg/g and 10.2 mg/g, and bitter taste amino acids followed. More importantly, as important flavor materials in Pixian broad-bean paste, these two groups of substances are expected to be used to evaluate and represent the flavor quality of Pixian broad-bean paste. Moreover, the results revealed that citric acid, glutamic acid, methionine and proline were the most important flavor compounds. These findings are agreat contribution for evaluating the quality and further assessment of Pixian broad-bean paste.

  1. PD-1 Blockade Expands Intratumoral Memory T Cells

    DEFF Research Database (Denmark)

    Ribas, Antoni; Shin, Daniel Sanghoon; Zaretsky, Jesse

    2016-01-01

    by multicolor flow cytometry using two computational approaches to resolve the leukocyte phenotypes at the single-cell level. There was a statistically significant increase in the frequency of T cells in patients who responded to therapy. The frequency of intratumoral B cells and monocytic myeloid......-derived suppressor cells significantly increased in patients' biopsies taken on treatment. The percentage of cells with a regulatory T-cell phenotype, monocytes, and natural killer cells did not change while on PD-1 blockade therapy. CD8+ memory T cells were the most prominent phenotype that expanded intratumorally...... on therapy. However, the frequency of CD4+ effector memory T cells significantly decreased on treatment, whereas CD4+ effector T cells significantly increased in nonresponding tumors on therapy. In peripheral blood, an unusual population of blood cells expressing CD56 was detected in two patients...

  2. Organic ferroelectric opto-electronic memories

    NARCIS (Netherlands)

    Asadi, K.; Li, M.; Blom, P.W.M.; Kemerink, M.; Leeuw, D.M. de

    2011-01-01

    Memory is a prerequisite for many electronic devices. Organic non-volatile memory devices based on ferroelectricity are a promising approach towards the development of a low-cost memory technology based on a simple cross-bar array. In this review article we discuss the latest developments in this

  3. Brain-like associative learning using a nanoscale non-volatile phase change synaptic device array

    Directory of Open Access Journals (Sweden)

    Sukru Burc Eryilmaz

    2014-07-01

    Full Text Available Recent advances in neuroscience together with nanoscale electronic device technology have resulted in huge interests in realizing brain-like computing hardwares using emerging nanoscale memory devices as synaptic elements. Although there has been experimental work that demonstrated the operation of nanoscale synaptic element at the single device level, network level studies have been limited to simulations. In this work, we demonstrate, using experiments, array level associative learning using phase change synaptic devices connected in a grid like configuration similar to the organization of the biological brain. Implementing Hebbian learning with phase change memory cells, the synaptic grid was able to store presented patterns and recall missing patterns in an associative brain-like fashion. We found that the system is robust to device variations, and large variations in cell resistance states can be accommodated by increasing the number of training epochs. We illustrated the tradeoff between variation tolerance of the network and the overall energy consumption, and found that energy consumption is decreased significantly for lower variation tolerance.

  4. Towards Terabit Memories

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  7. Non-Volatile Ferroelectric Switching of Ferromagnetic Resonance in NiFe/PLZT Multiferroic Thin Film Heterostructures (Postprint)

    Science.gov (United States)

    2016-09-01

    deformation potentially leads to fatigue and fracture over time. Moreover, we show that by simply applying voltage pulses, a robust, non-volatile...polarization such as PZT , BiFeO3, or doped HfO2. Our results thus provide a pathway towards ferroelectric switching of magnetism that could be useful for

  8. Dietary exposure to volatile and non-volatile N-nitrosamines from processed meat products in Denmark

    DEFF Research Database (Denmark)

    Herrmann, Susan Strange; Duedahl-Olesen, Lene; Christensen, Tue

    2015-01-01

    the carcinogenicity for the majority of the non-volatile NA (NVNA) remains to be elucidated. Danish adults (15–75 years) and children (4–6 years) consume 20 g and 16 g of processed meat per day (95th percentile), respectively. The consumption is primarily accounted for by sausages, salami, pork flank (spiced...

  9. Decreased memory B cells and increased CD8 memory T cells in blood of breastfed children: the generation R study.

    Science.gov (United States)

    Jansen, Michelle A E; van den Heuvel, Diana; van Zelm, Menno C; Jaddoe, Vincent W V; Hofman, Albert; de Jongste, Johan C; Hooijkaas, Herbert; Moll, Henriette A

    2015-01-01

    Breastfeeding provides a protective effect against infectious diseases in infancy. Still, immunological evidence for enhanced adaptive immunity in breastfed children remains inconclusive. To determine whether breastfeeding affects B- and T-cell memory in the first years of life. We performed immunophenotypic analysis on blood samples within a population-based prospective cohort study. Participants included children at 6 months (n=258), 14 months (n=166), 25 months (n=112) and 6 years of age (n=332) with both data on breastfeeding and blood lymphocytes. Total B- and T-cell numbers and their memory subsets were determined with 6-color flow cytometry. Mothers completed questionnaires on breastfeeding when their children were aged 2, 6, and 12 months. Multiple linear regression models with adjustments for potential confounders were performed. Per month continuation of breastfeeding, a 3% (95% CI -6, -1) decrease in CD27+IgM+, a 2% (95 CI % -5, -1) decrease in CD27+IgA+ and a 2% (95% CI -4, -1) decrease in CD27-IgG+ memory B cell numbers were observed at 6 months of age. CD8 T-cell numbers at 6 months of age were 20% (95% CI 3, 37) higher in breastfed than in non-breastfed infants. This was mainly found for central memory CD8 T cells and associated with exposure to breast milk, rather than duration. The same trend was observed at 14 months, but associations disappeared at older ages. Longer breastfeeding is associated with increased CD8 T-cell memory, but not B-cell memory numbers in the first 6 months of life. This transient skewing towards T cell memory might contribute to the protective effect against infectious diseases in infancy.

  10. Decreased memory B cells and increased CD8 memory T cells in blood of breastfed children: the generation R study.

    Directory of Open Access Journals (Sweden)

    Michelle A E Jansen

    Full Text Available Breastfeeding provides a protective effect against infectious diseases in infancy. Still, immunological evidence for enhanced adaptive immunity in breastfed children remains inconclusive.To determine whether breastfeeding affects B- and T-cell memory in the first years of life.We performed immunophenotypic analysis on blood samples within a population-based prospective cohort study. Participants included children at 6 months (n=258, 14 months (n=166, 25 months (n=112 and 6 years of age (n=332 with both data on breastfeeding and blood lymphocytes. Total B- and T-cell numbers and their memory subsets were determined with 6-color flow cytometry. Mothers completed questionnaires on breastfeeding when their children were aged 2, 6, and 12 months. Multiple linear regression models with adjustments for potential confounders were performed.Per month continuation of breastfeeding, a 3% (95% CI -6, -1 decrease in CD27+IgM+, a 2% (95 CI % -5, -1 decrease in CD27+IgA+ and a 2% (95% CI -4, -1 decrease in CD27-IgG+ memory B cell numbers were observed at 6 months of age. CD8 T-cell numbers at 6 months of age were 20% (95% CI 3, 37 higher in breastfed than in non-breastfed infants. This was mainly found for central memory CD8 T cells and associated with exposure to breast milk, rather than duration. The same trend was observed at 14 months, but associations disappeared at older ages.Longer breastfeeding is associated with increased CD8 T-cell memory, but not B-cell memory numbers in the first 6 months of life. This transient skewing towards T cell memory might contribute to the protective effect against infectious diseases in infancy.

  11. High frequency electromechanical memory cells based on telescoping carbon nanotubes.

    Science.gov (United States)

    Popov, A M; Lozovik, Y E; Kulish, A S; Bichoutskaia, E

    2010-07-01

    A new method to increase the operational frequency of electromechanical memory cells based on the telescoping motion of multi-walled carbon nanotubes through the selection of the form of the switching voltage pulse is proposed. The relative motion of the walls of carbon nanotubes can be controlled through the shape of the interwall interaction energy surface. This allows the use of the memory cells in nonvolatile or volatile regime, depending on the structure of carbon nanotube. Simulations based on ab initio and semi-empirical calculations of the interwall interaction energies are used to estimate the switching voltage and the operational frequency of volatile cells with the electrodes made of carbon nanotubes. The lifetime of nonvolatile memory cells is also predicted.

  12. Single-cell atomic quantum memory for light

    International Nuclear Information System (INIS)

    Opatrny, Tomas

    2006-01-01

    Recent experiments demonstrating atomic quantum memory for light [B. Julsgaard et al., Nature 432, 482 (2004)] involve two macroscopic samples of atoms, each with opposite spin polarization. It is shown here that a single atomic cell is enough for the memory function if the atoms are optically pumped with suitable linearly polarized light, and quadratic Zeeman shift and/or ac Stark shift are used to manipulate rotations of the quadratures. This should enhance the performance of our quantum memory devices since less resources are needed and losses of light in crossing different media boundaries are avoided

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

    Science.gov (United States)

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

    2017-01-01

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

  14. Chemical composition and non-volatile components of three wild edible mushrooms collected from northwest Tunisia

    Directory of Open Access Journals (Sweden)

    ibtissem Kacem Jedidi

    2016-04-01

    Full Text Available In Tunisia, many people collect wild edible mushrooms as pickers for their own consumption. The present work aims at contributing to the determination of the chemical composition, non volatile components content (soluble sugars, free amino acids and minerals and trace elements of three popular Tunisian wild edible mushrooms species collected from the northwest of Tunisia (Agaricus campestris, Boletus edulis and Cantharellus cibarius.All investigated mushrooms revealed that these species are rich sources of proteins (123.70 – 374.10 g kg-1 dry weight (DW and carbohydrates (403.3 – 722.40 g kg-1 DW, and low content of fat (28.2 – 39.9 g kg-1 DW; the highest energetic contribution was guaranteed by C. cibarius (1542.71 kJ / 100 g. A. compestris (33.14 mg/g DW showed the highest concentration of essential amino acids. The composition in individual sugars was also determined, mannitol and trehalose being the most abundant sugars. C. cibarius revealed the highest concentrations of carbohydrates (722.4 g kg-1 DW and A. compestris the lowest concentration (403.3 g kg-1 DW. Potassium (K and sodium (Na are the most abundant minerals in analyzed samples (A. compestris showed the highest concentrations of K and Na, 49141.44 and 9263.886 µg/g DW respectively.

  15. Comparison of non-volatile umami components in chicken soup and chicken enzymatic hydrolysate.

    Science.gov (United States)

    Kong, Yan; Yang, Xiao; Ding, Qi; Zhang, Yu-Yu; Sun, Bao-Guo; Chen, Hai-Tao; Sun, Ying

    2017-12-01

    Umami taste is an important part to the taste of chicken. To isolate and identify non-volatile umami compounds, fractions from chicken soup and hydrolysate were prepared and analyzed. Amino acids were analyzed by amino acid analyzer. Organic acids and nucleotides were determined by ultra-performance liquid chromatography. Separation procedures utilizing ultrafiltration, Sephadex G-15 and reversed-phase high-performance liquid chromatography were used to isolate umami taste peptides. Combined with sensory evaluation and LC-Q-TOF-MS, the amino acid sequences of 12 oligopeptides were determined. The amount of taste compounds was higher in chicken enzymatic hydrolysate than that of chicken soup. Eight oligopeptides from chicken enzymatic hydrolysate were identified, including Ala-Asp, Ala-Met, His-Ser, Val-Glu, Ala-Glu, Asp-Ala-Gly, Glu-Asp and Ala-Glu-Ala. Four oligopeptides from chicken soup were identified, including Val-Thr, Ala-His, Ala-Phe and Thr-Glu. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Discharge characteristics of an ablative pulsed plasma thruster with non-volatile liquid propellant

    Science.gov (United States)

    Ling, William Yeong Liang; Schönherr, Tony; Koizumi, Hiroyuki

    2017-07-01

    Pulsed plasma thrusters (PPTs) are a form of electric spacecraft propulsion. They have an extremely simple structure and are highly suitable for nano/micro-spacecraft with weights in the kilogram range. Such small spacecraft have recently experienced increased growth but still lack suitable efficient propulsion systems. PPTs operate in a pulsed mode (one discharge = one shot) and typically use solid polytetrafluoroethylene (PTFE) as a propellant. However, new non-volatile liquids in the perfluoropolyether (PFPE) family have recently been found to be promising alternatives. A recent study presented results on the physical characteristics of PFPE vs. PTFE, showing that PFPE is superior in terms of physical characteristics such as its resistance to carbon deposition. This letter will examine the electrical discharge characteristics of PFPE vs. PTFE. The results demonstrate that PFPE has excellent shot-to-shot repeatability and a lower discharge resistance when compared with PTFE. Taken together with its physical characteristics, PFPE appears to be a strong contender to PTFE as a PPT propellant.

  17. Investigations concerning the exchange of iodine from non-volatile organic iodine compounds

    International Nuclear Information System (INIS)

    Psarros, N.; Duschner, H.; Molzahn, D.; Schmidt, L.; Heise, S.; Jungclas, H.; Brandt, R.; Patzelt, P.

    1990-10-01

    The iodine produced by nuclear fission is removed during the reprocessing of exhausted nuclear fuel elements by desorption achieving good decontamination factors. Nevertheless the further optimization of the process requires detailed information about the iodine speciation during fuel reprocessing, and about possible reactions. For the study of decomposition reactions of iodo-alcanes, which are built up during the fuel recycling process, we developed a method for the synthesis of labelled iodo-dodecane, which was used as tracer. In order to identify the iodo species in the organic phase of the reprocessing cycle we applied plasma desorption time-of-flight mass spectroscopy. The problem of the volatility of the iodo-compounds in the ultra vacuum of the mass spectrometer was overcome by derivatization of the iodo-alcanes with dithizon, which yielded non-volatile ionic alcyltetrazolium iodides. Beta-spectrometric analysis of the exhaust condensates collected from the organic phase of the WAK reprocessing cycle revealed beside iodine-129 the existence of a low-energetic beta emitter, which has yet to be identified. A literature survey on the topic was also performed. (orig.) With 42 refs., 9 figs [de

  18. Analysis of the build-up of semi and non volatile organic compounds on urban roads.

    Science.gov (United States)

    Mahbub, Parvez; Ayoko, Godwin A; Goonetilleke, Ashantha; Egodawatta, Prasanna

    2011-04-01

    Vehicular traffic in urban areas may adversely affect urban water quality through the build-up of traffic generated semi and non volatile organic compounds (SVOCs and NVOCs) on road surfaces. The characterisation of the build-up processes is the key to developing mitigation measures for the removal of such pollutants from urban stormwater. An in-depth analysis of the build-up of SVOCs and NVOCs was undertaken in the Gold Coast region in Australia. Principal Component Analysis (PCA) and Multicriteria Decision tools such as PROMETHEE and GAIA were employed to understand the SVOC and NVOC build-up under combined traffic scenarios of low, moderate, and high traffic in different land uses. It was found that congestion in the commercial areas and use of lubricants and motor oils in the industrial areas were the main sources of SVOCs and NVOCs on urban roads, respectively. The contribution from residential areas to the build-up of such pollutants was hardly noticeable. It was also revealed through this investigation that the target SVOCs and NVOCs were mainly attached to particulate fractions of 75-300 μm whilst the redistribution of coarse fractions due to vehicle activity mainly occurred in the >300 μm size range. Lastly, under combined traffic scenario, moderate traffic with average daily traffic ranging from 2300 to 5900 and average congestion of 0.47 were found to dominate SVOC and NVOC build-up on roads. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Selected microRNAs define cell fate determination of murine central memory CD8 T cells.

    Directory of Open Access Journals (Sweden)

    Gonzalo Almanza

    2010-06-01

    Full Text Available During an immune response T cells enter memory fate determination, a program that divides them into two main populations: effector memory and central memory T cells. Since in many systems protection appears to be preferentially mediated by T cells of the central memory it is important to understand when and how fate determination takes place. To date, cell intrinsic molecular events that determine their differentiation remains unclear. MicroRNAs are a class of small, evolutionarily conserved RNA molecules that negatively regulate gene expression, causing translational repression and/or messenger RNA degradation. Here, using an in vitro system where activated CD8 T cells driven by IL-2 or IL-15 become either effector memory or central memory cells, we assessed the role of microRNAs in memory T cell fate determination. We found that fate determination to central memory T cells is under the balancing effects of a discrete number of microRNAs including miR-150, miR-155 and the let-7 family. Based on miR-150 a new target, KChIP.1 (K (+ channel interacting protein 1, was uncovered, which is specifically upregulated in developing central memory CD8 T cells. Our studies indicate that cell fate determination such as surface phenotype and self-renewal may be decided at the pre-effector stage on the basis of the balancing effects of a discrete number of microRNAs. These results may have implications for the development of T cell vaccines and T cell-based adoptive therapies.

  20. Ultra-Low Voltage Class AB Switched Current Memory Cell

    DEFF Research Database (Denmark)

    Igor, Mucha

    1996-01-01

    This paper presents the theoretical basis for the design of class AB switched current memory cells employing floating-gate MOS transistors, suitable for ultra-low-voltage applications. To support the theoretical assumptions circuits based on these cells were designed using a CMOS process with thr......This paper presents the theoretical basis for the design of class AB switched current memory cells employing floating-gate MOS transistors, suitable for ultra-low-voltage applications. To support the theoretical assumptions circuits based on these cells were designed using a CMOS process...... with threshold voltages of 0.9V. Both hand calculations and PSPICE simulations showed that the cells designed allowed a maximum signal range better than +/-13 micoamp, with a supply voltage down to 1V and a quiescent bias current of 1 microamp, resulting in a very high current efficiency and effective power...

  1. Cell-assembly coding in several memory processes.

    Science.gov (United States)

    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.

  2. Early events governing memory CD8+ T-cell differentiation.

    Science.gov (United States)

    Obar, Joshua J; Lefrançois, Leo

    2010-08-01

    Understanding the regulation of the CD8(+) T-cell response and how protective memory cells are generated has been intensely studied. It is now appreciated that a naive CD8(+) T cell requires at least three signals to mount an effective immune response: (i) TCR triggering, (ii) co-stimulation and (iii) inflammatory cytokines. Only recently have we begun to understand the molecular integration of those signals and how early events regulate the fate decisions of the responding CD8(+) T cells. This review will discuss the recent findings about both the extracellular and intracellular factors that regulate the destiny of responding CD8(+) T cells.

  3. Influence of mineral salts upon activity of Trichoderma harzianum non-volatile metabolites on Armillaria spp. rhizomorphs

    Directory of Open Access Journals (Sweden)

    Krystyna Przybył

    2011-01-01

    Full Text Available Effect of non-volatile metabolites of Trichoderma harzianum together with certain salts containing Mg++, Fe+++, Mn++, Cu++, Al+++, Ca++, K++, Na+, PO4--- and SO3--- on the production and length of rhizomorphs of Armillaria borealis, A. gallica and A. ostoyae was studied. In pure medium, T. harzianum exhibited stimulating effect on rhizomorphs of A. borealis (both number and length and A. ostoyae (only initiation. Cu++ salt totaly inhibited the initiation of rhizomorphs of Armillaria borealis, A. gallica and A. ostoyae. Effect of other compounds on the activity of T. harzianum depended on Armillaria species. The majority of chemical compounds tested supressed the activity of non-volatile metabolites of T. harzianum. Evident stimulating effect was observed under influence of sulphate salts consisting Al++ and Fe+++ on the rhizomorph number of A. borealis and A. gallica, respectively.

  4. Volatile and non-volatile compounds in green tea affected in harvesting time and their correlation to consumer preference.

    Science.gov (United States)

    Kim, Youngmok; Lee, Kwang-Geun; Kim, Mina K

    2016-10-01

    Current study was designed to find out how tea harvesting time affects the volatile and non-volatile compounds profiles of green tea. In addition, correlation of instrumental volatile and non-volatile compounds analyses to consumer perception were analyzed. Overall, earlier harvested green tea had stronger antioxidant capacity (~61.0%) due to the polyphenolic compounds from catechin (23,164 mg/L), in comparison to later harvested green teas (11,961 mg/L). However, high catechin content in green tea influenced negatively the consumer likings of green tea, due to high bitterness (27.6%) and astringency (13.4%). Volatile compounds drive consumer liking of green tea products were also identified, that included linalool, 2,3-methyl butanal, 2-heptanone, (E,E)-3,5-Octadien-2-one. Finding from current study are useful for green tea industry as it provide the difference in physiochemical properties of green tea harvested at different intervals.

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

    Science.gov (United States)

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

    2016-08-01

    The presence of inflammatory infiltrates with B cells, specifically plasma cells, is the hallmark of periodontitis lesions. The composition of these infiltrates in various stages of homeostasis and disease development is not well documented. Human tissue biopsies from sites with gingival health (n = 29), gingivitis (n = 8), and periodontitis (n = 21) as well as gingival tissue after treated periodontitis (n = 6) were obtained and analyzed for their composition of B cell subsets. Ag specificity, Ig secretion, and expression of receptor activator of NF-κB ligand and granzyme B were performed. Although most of the B cell subsets in healthy gingiva and gingivitis tissues were CD19(+)CD27(+)CD38(-) memory B cells, the major B cell component in periodontitis was CD19(+)CD27(+)CD38(+)CD138(+)HLA-DR(low) plasma cells, not plasmablasts. Plasma cell aggregates were observed at the base of the periodontal pocket and scattered throughout the gingiva, especially apically toward the advancing front of the lesion. High expression of CXCL12, a proliferation-inducing ligand, B cell-activating factor, IL-10, IL-6, and IL-21 molecules involved in local B cell responses was detected in both gingivitis and periodontitis tissues. Periodontitis tissue plasma cells mainly secreted IgG specific to periodontal pathogens and also expressed receptor activator of NF-κB ligand, a bone resorption cytokine. Memory B cells resided in the connective tissue subjacent to the junctional epithelium in healthy gingiva. This suggested a role of memory B cells in maintaining periodontal homeostasis. Copyright © 2016 by The American Association of Immunologists, Inc.

  6. Memory control by the B cell antigen receptor.

    Science.gov (United States)

    Engels, Niklas; Wienands, Jürgen

    2018-05-01

    The generation of memory B cells (MBCs) that have undergone immunoglobulin class switching from IgM, which dominates primary antibody responses, to other immunoglobulin isoforms is a hallmark of immune memory. Hence, humoral immunological memory is characterized by the presence of serum immunoglobulins of IgG subtypes known as the γ-globulin fraction of blood plasma proteins. These antibodies reflect the antigen experience of B lymphocytes and their repeated triggering. In fact, efficient protection against a previously encountered pathogen is critically linked to the production of pathogen-specific IgG molecules even in those cases where the primary immune response required cellular immunity, for example, T cell-mediated clearance of intracellular pathogens such as viruses. Besides IgG, also IgA and IgE can provide humoral immunity depending on the microbe's nature and infection route. The molecular mechanisms underlying the preponderance of switched immunoglobulin isotypes during memory antibody responses are a matter of active and controversial debate. Here, we summarize the phenotypic characteristics of distinct MBC subpopulations and discuss the decisive roles of different B cell antigen receptor isotypes for the functional traits of class-switched B cell populations. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. FOXO3 regulates CD8 T cell memory by T cell-intrinsic mechanisms.

    Directory of Open Access Journals (Sweden)

    Jeremy A Sullivan

    2012-02-01

    Full Text Available CD8 T cell responses have three phases: expansion, contraction, and memory. Dynamic alterations in proliferation and apoptotic rates control CD8 T cell numbers at each phase, which in turn dictate the magnitude of CD8 T cell memory. Identification of signaling pathways that control CD8 T cell memory is incomplete. The PI3K/Akt signaling pathway controls cell growth in many cell types by modulating the activity of FOXO transcription factors. But the role of FOXOs in regulating CD8 T cell memory remains unknown. We show that phosphorylation of Akt, FOXO and mTOR in CD8 T cells occurs in a dynamic fashion in vivo during an acute viral infection. To elucidate the potentially dynamic role for FOXO3 in regulating homeostasis of activated CD8 T cells in lymphoid and non-lymphoid organs, we infected global and T cell-specific FOXO3-deficient mice with Lymphocytic Choriomeningitis Virus (LCMV. We found that FOXO3 deficiency induced a marked increase in the expansion of effector CD8 T cells, preferentially in the spleen, by T cell-intrinsic mechanisms. Mechanistically, the enhanced accumulation of proliferating CD8 T cells in FOXO3-deficient mice was not attributed to an augmented rate of cell division, but instead was linked to a reduction in cellular apoptosis. These data suggested that FOXO3 might inhibit accumulation of growth factor-deprived proliferating CD8 T cells by reducing their viability. By virtue of greater accumulation of memory precursor effector cells during expansion, the numbers of memory CD8 T cells were strikingly increased in the spleens of both global and T cell-specific FOXO3-deficient mice. The augmented CD8 T cell memory was durable, and FOXO3 deficiency did not perturb any of the qualitative attributes of memory T cells. In summary, we have identified FOXO3 as a critical regulator of CD8 T cell memory, and therapeutic modulation of FOXO3 might enhance vaccine-induced protective immunity against intracellular pathogens.

  8. Out-of-Sequence Preventative Cell Dispatching for Multicast Input-Queued Space-Memory-Memory Clos-Network

    DEFF Research Database (Denmark)

    Yu, Hao; Ruepp, Sarah Renée; Berger, Michael Stübert

    2011-01-01

    This paper proposes two out-of-sequence (OOS) preventative cell dispatching algorithms for the multicast input-queued space-memory-memory (IQ-SMM) Clos-network switch architecture, i.e. the multicast flow-based DSRR (MF-DSRR) and the multicast flow-based round-robin (MFRR). Treating each cell...

  9. Embedded Memory Hierarchy Exploration Based on Magnetic Random Access Memory

    Directory of Open Access Journals (Sweden)

    Luís Vitório Cargnini

    2014-08-01

    Full Text Available Static random access memory (SRAM is the most commonly employed semiconductor in the design of on-chip processor memory. However, it is unlikely that the SRAM technology will have a cell size that will continue to scale below 45 nm, due to the leakage current that is caused by the quantum tunneling effect. Magnetic random access memory (MRAM is a candidate technology to replace SRAM, assuming appropriate dimensioning given an operating threshold voltage. The write current of spin transfer torque (STT-MRAM is a known limitation; however, this has been recently mitigated by leveraging perpendicular magnetic tunneling junctions. In this article, we present a comprehensive comparison of spin transfer torque-MRAM (STT-MRAM and SRAM cache set banks. The non-volatility of STT-MRAM allows the definition of new instant on/off policies and leakage current optimizations. Through our experiments, we demonstrate that STT-MRAM is a candidate for the memory hierarchy of embedded systems, due to the higher densities and reduced leakage of MRAM.We demonstrate that adopting STT-MRAM in L1 and L2 caches mitigates the impact of higher write latencies and increased current draw due to the use of MRAM. With the correct system-on-chip (SoC design, we believe that STT-MRAM is a viable alternative to SRAM, which minimizes leakage current and the total power consumed by the SoC.

  10. Phase change memory

    CERN Document Server

    Qureshi, Moinuddin K

    2011-01-01

    As conventional memory technologies such as DRAM and Flash run into scaling challenges, architects and system designers are forced to look at alternative technologies for building future computer systems. This synthesis lecture begins by listing the requirements for a next generation memory technology and briefly surveys the landscape of novel non-volatile memories. Among these, Phase Change Memory (PCM) is emerging as a leading contender, and the authors discuss the material, device, and circuit advances underlying this exciting technology. The lecture then describes architectural solutions t

  11. CellSs: Scheduling Techniques to Better Exploit Memory Hierarchy

    Directory of Open Access Journals (Sweden)

    Pieter Bellens

    2009-01-01

    Full Text Available Cell Superscalar's (CellSs main goal is to provide a simple, flexible and easy programming approach for the Cell Broadband Engine (Cell/B.E. that automatically exploits the inherent concurrency of the applications at a task level. The CellSs environment is based on a source-to-source compiler that translates annotated C or Fortran code and a runtime library tailored for the Cell/B.E. that takes care of the concurrent execution of the application. The first efforts for task scheduling in CellSs derived from very simple heuristics. This paper presents new scheduling techniques that have been developed for CellSs for the purpose of improving an application's performance. Additionally, the design of a new scheduling algorithm is detailed and the algorithm evaluated. The CellSs scheduler takes an extension of the memory hierarchy for Cell/B.E. into account, with a cache memory shared between the SPEs. All new scheduling practices have been evaluated showing better behavior of our system.

  12. Radiation-hardened MRAM-based LUT for non-volatile FPGA soft error mitigation with multi-node upset tolerance

    Science.gov (United States)

    Zand, Ramtin; DeMara, Ronald F.

    2017-12-01

    In this paper, we have developed a radiation-hardened non-volatile lookup table (LUT) circuit utilizing spin Hall effect (SHE)-magnetic random access memory (MRAM) devices. The design is motivated by modeling the effect of radiation particles striking hybrid complementary metal oxide semiconductor/spin based circuits, and the resistive behavior of SHE-MRAM devices via established and precise physics equations. The models developed are leveraged in the SPICE circuit simulator to verify the functionality of the proposed design. The proposed hardening technique is based on using feedback transistors, as well as increasing the radiation capacity of the sensitive nodes. Simulation results show that our proposed LUT circuit can achieve multiple node upset (MNU) tolerance with more than 38% and 60% power-delay product improvement as well as 26% and 50% reduction in device count compared to the previous energy-efficient radiation-hardened LUT designs. Finally, we have performed a process variation analysis showing that the MNU immunity of our proposed circuit is realized at the cost of increased susceptibility to transistor and MRAM variations compared to an unprotected LUT design.

  13. B Cell Intrinsic Mechanisms Constraining IgE Memory

    Directory of Open Access Journals (Sweden)

    Brice Laffleur

    2017-11-01

    Full Text Available Memory B cells and long-lived plasma cells are key elements of adaptive humoral immunity. Regardless of the immunoglobulin class produced, these cells can ensure long-lasting protection but also long-lasting immunopathology, thus requiring tight regulation of their generation and survival. Among all antibody classes, this is especially true for IgE, which stands as the most potent, and can trigger dramatic inflammatory reactions even when present in minute amounts. IgE responses and memory crucially protect against parasites and toxic components of venoms, conferring selective advantages and explaining their conservation in all mammalian species despite a parallel broad spectrum of IgE-mediated immunopathology. Long-term memory of sensitization and anaphylactic responses to allergens constitute the dark side of IgE responses, which can trigger multiple acute or chronic pathologic manifestations, some punctuated with life-threatening events. This Janus face of the IgE response and memory, both necessary and potentially dangerous, thus obviously deserves the most elaborated self-control schemes.

  14. Vaccination Expands Antigen-Specific CD4+ Memory T Cells and Mobilizes Bystander Central Memory T Cells

    Science.gov (United States)

    Li Causi, Eleonora; Parikh, Suraj C.; Chudley, Lindsey; Layfield, David M.; Ottensmeier, Christian H.; Stevenson, Freda K.; Di Genova, Gianfranco

    2015-01-01

    CD4+ T helper memory (Thmem) cells influence both natural and vaccine-boosted immunity, but mechanisms for their maintenance remain unclear. Pro-survival signals from the common gamma-chain cytokines, in particular IL-7, appear important. Previously we showed in healthy volunteers that a booster vaccination with tetanus toxoid (TT) expanded peripheral blood TT-specific Thmem cells as expected, but was accompanied by parallel increase of Thmem cells specific for two unrelated and non cross-reactive common recall antigens. Here, in a new cohort of healthy human subjects, we compare blood vaccine-specific and bystander Thmem cells in terms of differentiation stage, function, activation and proliferative status. Both responses peaked 1 week post-vaccination. Vaccine-specific cytokine-producing Thmem cells were predominantly effector memory, whereas bystander cells were mainly of central memory phenotype. Importantly, TT-specific Thmem cells were activated (CD38High HLA-DR+), cycling or recently divided (Ki-67+), and apparently vulnerable to death (IL-7RαLow and Bcl-2 Low). In contrast, bystander Thmem cells were resting (CD38Low HLA-DR- Ki-67-) with high expression of IL-7Rα and Bcl-2. These findings allow a clear distinction between vaccine-specific and bystander Thmem cells, suggesting the latter do not derive from recent proliferation but from cells mobilized from as yet undefined reservoirs. Furthermore, they reveal the interdependent dynamics of specific and bystander T-cell responses which will inform assessments of responses to vaccines. PMID:26332995

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

    Science.gov (United States)

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

    2018-05-11

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

  16. Cellular memory and, hematopoietic stem cell aging

    NARCIS (Netherlands)

    Kamminga, Leonie M.; de Haan, Gerald

    Hematopoietic stem cells (HSCs) balance self-renewal and differentiation in order to sustain lifelong blood production and simultaneously maintain the HSC pool. However, there is clear evidence that HSCs are subject to quantitative and qualitative exhaustion. In this review, we briefly discuss

  17. Memory CD8+ T cells protect dendritic cells from CTL killing

    NARCIS (Netherlands)

    Watchmaker, Payal B.; Urban, Julie A.; Berk, Erik; Nakamura, Yutaro; Mailliard, Robbie B.; Watkins, Simon C.; van Ham, S. Marieke; Kalinski, Pawel

    2008-01-01

    CD8(+) T cells have been shown to be capable of either suppressing or promoting immune responses. To reconcile these contrasting regulatory functions, we compared the ability of human effector and memory CD8(+) T cells to regulate survival and functions of dendritic cells (DC). We report that, in

  18. Memory

    Science.gov (United States)

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

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

    KAUST Repository

    Wu, Xing; Li, Kun; Raghavan, Nagarajan; Bosman, Michel; Wang, Qing-Xiao; Cha, Dong Kyu; Zhang, Xixiang; Pey, Kin-Leong

    2011-01-01

    Resistive switching in transition metal oxides could form the basis for next-generation non-volatile memory (NVM). It has been reported that the current in the high-conductivity state of several technologically relevant oxide materials flows through

  20. 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.

    Science.gov (United States)

    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.

  1. Occurence and dietary exposure of volatile and non-volatile N-Nitrosamines in processed meat products

    DEFF Research Database (Denmark)

    Herrmann, Susan Strange; Duedahl-Olesen, Lene; Granby, Kit

    Nitrite and nitrate have for many decades been used for preservation of meat. However, nitrite can react with secondary amines in meat to form N-Nitrosamines (NAs), many of which have been shown to be genotoxic1 . The use of nitrite therefore ought to be limited as much as possible. To maintain...... a high level of consumer protection Denmark obtains National low limits of the nitrite use in meat products. An estimation of the dietary exposure to volatile NAs (VNA) and non-volatile NAs (NVNA) is necessary when performing a risk assessment of the use of nitrite and nitrate for meat preservation....

  2. A novel 2 T P-channel nano-crystal memory for low power/high speed embedded NVM applications

    International Nuclear Information System (INIS)

    Zhang Junyu; Wang Yong; Liu Jing; Zhang Manhong; Xu Zhongguang; Huo Zongliang; Liu Ming

    2012-01-01

    We introduce a novel 2 T P-channel nano-crystal memory structure for low power and high speed embedded non-volatile memory (NVM) applications. By using the band-to-band tunneling-induced hot-electron (BTBTIHE) injection scheme, both high-speed and low power programming can be achieved at the same time. Due to the use of a select transistor, the 'erased states' can be set to below 0 V, so that the periphery HV circuit (high-voltage generating and management) and read-out circuit can be simplified. Good memory cell performance has also been achieved, including a fast program/erase (P/E) speed (a 1.15 V memory window under 10 μs program pulse), an excellent data retention (only 20% charge loss for 10 years). The data shows that the device has strong potential for future embedded NVM applications. (semiconductor devices)

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

    Science.gov (United States)

    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.

  4. Methyltransferases mediate cell memory of a genotoxic insult.

    Science.gov (United States)

    Rugo, R E; Mutamba, J T; Mohan, K N; Yee, T; Chaillet, J R; Greenberger, J S; Engelward, B P

    2011-02-10

    Characterization of the direct effects of DNA-damaging agents shows how DNA lesions lead to specific mutations. Yet, serum from Hiroshima survivors, Chernobyl liquidators and radiotherapy patients can induce a clastogenic effect on naive cells, showing indirect induction of genomic instability that persists years after exposure. Such indirect effects are not restricted to ionizing radiation, as chemical genotoxins also induce heritable and transmissible genomic instability phenotypes. Although such indirect induction of genomic instability is well described, the underlying mechanism has remained enigmatic. Here, we show that mouse embryonic stem cells exposed to γ-radiation bear the effects of the insult for weeks. Specifically, conditioned media from the progeny of exposed cells can induce DNA damage and homologous recombination in naive cells. Notably, cells exposed to conditioned media also elicit a genome-destabilizing effect on their neighbouring cells, thus demonstrating transmission of genomic instability. Moreover, we show that the underlying basis for the memory of an insult is completely dependent on two of the major DNA cytosine methyltransferases, Dnmt1 and Dnmt3a. Targeted disruption of these genes in exposed cells completely eliminates transmission of genomic instability. Furthermore, transient inactivation of Dnmt1, using a tet-suppressible allele, clears the memory of the insult, thus protecting neighbouring cells from indirect induction of genomic instability. We have thus demonstrated that a single exposure can lead to long-term, genome-destabilizing effects that spread from cell to cell, and we provide a specific molecular mechanism for these persistent bystander effects. Collectively, our results impact the current understanding of risks from toxin exposures and suggest modes of intervention for suppressing genomic instability in people exposed to carcinogenic genotoxins.

  5. Efficient Management for Hybrid Memory in Managed Language Runtime

    OpenAIRE

    Wang , Chenxi; Cao , Ting; Zigman , John; Lv , Fang; Zhang , Yunquan; Feng , Xiaobing

    2016-01-01

    Part 1: Memory: Non-Volatile, Solid State Drives, Hybrid Systems; International audience; Hybrid memory, which leverages the benefits of traditional DRAM and emerging memory technologies, is a promising alternative for future main memory design. However popular management policies through memory-access recording and page migration may invoke non-trivial overhead in execution time and hardware space. Nowadays, managed language applications are increasingly dominant in every kind of platform. M...

  6. New memory devices based on the proton transfer process

    International Nuclear Information System (INIS)

    Wierzbowska, Małgorzata

    2016-01-01

    Memory devices operating due to the fast proton transfer (PT) process are proposed by the means of first-principles calculations. Writing  information is performed using the electrostatic potential of scanning tunneling microscopy (STM). Reading information is based on the effect of the local magnetization induced at the zigzag graphene nanoribbon (Z-GNR) edge—saturated with oxygen or the hydroxy group—and can be realized with the use of giant magnetoresistance (GMR), a magnetic tunnel junction or spin-transfer torque devices. The energetic barriers for the hop forward and backward processes can be tuned by the distance and potential of the STM tip; this thus enables us to tailor the non-volatile logic states. The proposed system enables very dense packing of the logic cells and could be used in random access and flash memory devices. (paper)

  7. New memory devices based on the proton transfer process

    Science.gov (United States)

    Wierzbowska, Małgorzata

    2016-01-01

    Memory devices operating due to the fast proton transfer (PT) process are proposed by the means of first-principles calculations. Writing information is performed using the electrostatic potential of scanning tunneling microscopy (STM). Reading information is based on the effect of the local magnetization induced at the zigzag graphene nanoribbon (Z-GNR) edge—saturated with oxygen or the hydroxy group—and can be realized with the use of giant magnetoresistance (GMR), a magnetic tunnel junction or spin-transfer torque devices. The energetic barriers for the hop forward and backward processes can be tuned by the distance and potential of the STM tip; this thus enables us to tailor the non-volatile logic states. The proposed system enables very dense packing of the logic cells and could be used in random access and flash memory devices.

  8. On the shape memory of red blood cells

    Science.gov (United States)

    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

  9. Optimization of poly(vinylidene fluoride-trifluoroethylene) films as non-volatile memory for flexible electronics

    KAUST Repository

    Mao, Duo

    2010-05-01

    The impact of thermal treatment and thickness on the polarization and leakage current of poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)] copolymer thin film capacitors has been studied. The evolution of the film morphology, crystallinity and bonding orientation as a function of annealing temperature and thickness were characterized using multiple techniques. Electrical performance of the devices was correlated with the material properties. It was found that annealing at or slightly above the Curie temperature (Tc) is the optimal temperature for high polarization, smooth surface morphology and low leakage current. Higher annealing temperature (but below the melting temperature Tm) favors larger size β crystallites through molecular chain self-organization, resulting in increased film roughness, and the vertical polarization tends to saturate. Metal-Ferroelectric-Metal (MFM) capacitors consistently achieved Ps, Pr and Vc of 8.5 μC/cm2, 7.4 μC/cm2 and 10.2 V, respectively.

  10. Polarity-Free Resistive Switching Characteristics of CuxO Films for Non-volatile Memory Applications

    International Nuclear Information System (INIS)

    Hang-Bing, Lv; Peng, Zhou; Xiu-Feng, Fu; Ming, Yin; Ya-Li, Song; Li, Tang; Ting-Ao, Tang; Yin-Yin, Lin

    2008-01-01

    Resistive switching characteristics of Cu x O films grown by plasma oxidation process at room temperature are investigated. Both bipolar and unipolar stable resistive switching behaviours are observed and confirmed by repeated current–voltage measurements. It is found that the RESET current is dependent on SET compliance current. The mechanism behind this new phenomenon can be understood in terms of conductive filaments formation/rupture with the contribution of Joule heating

  11. Optimization of poly(vinylidene fluoride-trifluoroethylene) films as non-volatile memory for flexible electronics

    KAUST Repository

    Mao, Duo; Quevedo-Ló pez, Manuel Angel Quevedo; Stiegler, Harvey J.; Gnade, Bruce E.; Alshareef, Husam N.

    2010-01-01

    The impact of thermal treatment and thickness on the polarization and leakage current of poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)] copolymer thin film capacitors has been studied. The evolution of the film morphology, crystallinity and bonding orientation as a function of annealing temperature and thickness were characterized using multiple techniques. Electrical performance of the devices was correlated with the material properties. It was found that annealing at or slightly above the Curie temperature (Tc) is the optimal temperature for high polarization, smooth surface morphology and low leakage current. Higher annealing temperature (but below the melting temperature Tm) favors larger size β crystallites through molecular chain self-organization, resulting in increased film roughness, and the vertical polarization tends to saturate. Metal-Ferroelectric-Metal (MFM) capacitors consistently achieved Ps, Pr and Vc of 8.5 μC/cm2, 7.4 μC/cm2 and 10.2 V, respectively.

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

    Science.gov (United States)

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

    2009-01-01

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

  13. Reducing the influence of STI on SONOS memory through optimizing added boron implantation technology

    International Nuclear Information System (INIS)

    Xu Yue; Yan Feng; Li Zhiguo; Yang Fan; Wang Yonggang; Chang Jianguang

    2010-01-01

    The influence of shallow trench isolation (STI) on a 90 nm polysilicon-oxide-nitride-oxide-silicon structure non-volatile memory has been studied based on experiments. It has been found that the performance of edge memory cells adjacent to STI deteriorates remarkably. The compressive stress and boron segregation induced by STI are thought to be the main causes of this problem. In order to mitigate the STI impact, an added boron implantation in the STI region is developed as a new solution. Four kinds of boron implantation experiments have been implemented to evaluate the impact of STI on edge cells, respectively. The experimental results show that the performance of edge cells can be greatly improved through optimizing added boron implantation technology. (semiconductor devices)

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

    OpenAIRE

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

    2009-01-01

    The ability of the adaptive immune system to respond rapidly and robustly upon repeated antigen exposure is known as immunologic memory, and it is thought that acquisition of memory T-cell function is an irreversible differentiation event. In this study, we report that many phenotypic and functional characteristics of antigen-specific CD8 memory T cells are lost when they are deprived of contact with dendritic cells. Under these circumstances, memory T cells reverted from G1 to the G0 cell-cy...

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

    Science.gov (United States)

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

    2004-01-01

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

  16. Notch controls the survival of memory CD4+ T cells by regulating glucose uptake.

    Science.gov (United States)

    Maekawa, Yoichi; Ishifune, Chieko; Tsukumo, Shin-ichi; Hozumi, Katsuto; Yagita, Hideo; Yasutomo, Koji

    2015-01-01

    CD4+ T cells differentiate into memory T cells that protect the host from subsequent infection. In contrast, autoreactive memory CD4+ T cells harm the body by persisting in the tissues. The underlying pathways controlling the maintenance of memory CD4+ T cells remain undefined. We show here that memory CD4+ T cell survival is impaired in the absence of the Notch signaling protein known as recombination signal binding protein for immunoglobulin κ J region (Rbpj). Treatment of mice with a Notch inhibitor reduced memory CD4+ T cell numbers and prevented the recurrent induction of experimental autoimmune encephalomyelitis. Rbpj-deficient CD4+ memory T cells exhibit reduced glucose uptake due to impaired AKT phosphorylation, resulting in low Glut1 expression. Treating mice with pyruvic acid, which bypasses glucose uptake and supplies the metabolite downstream of glucose uptake, inhibited the decrease of autoimmune memory CD4+ T cells in the absence of Notch signaling, suggesting memory CD4+ T cell survival relies on glucose metabolism. Together, these data define a central role for Notch signaling in maintaining memory CD4+ T cells through the regulation of glucose uptake.

  17. Tumor cells and memory T cells converge at glycolysis: Therapeutic implications

    OpenAIRE

    Karthikeyan, Swathi; Geschwind, Jean-Francois; Ganapathy-Kanniappan, Shanmugasundaram

    2014-01-01

    In the immune system, activation of naïve T (Tn) cells into effector T cells (Teff) involves a metabolic switch to glycolysis to promote rapid proliferation and differentiation. In the October issue of The Journal of Clinical Investigation, Sukumar et al. have demonstrated that in CD8+ memory T (Tems) cells glycolytic phenotype contributes to the shortened lifespan of Tems. Conversely, inhibition of glycolysis in Tems not only extended their viability but also augmented desirable properties. ...

  18. Pro-apoptotic protein Noxa regulates memory T cell population size and protects against lethal immunopathology

    NARCIS (Netherlands)

    Wensveen, Felix M.; Klarenbeek, Paul L.; van Gisbergen, Klaas P. J. M.; Pascutti, Maria F.; Derks, Ingrid A. M.; van Schaik, Barbera D. C.; ten Brinke, Anja; de Vries, Niek; Cekinovic, Durdica; Jonjic, Stipan; van Lier, René A. W.; Eldering, Eric

    2013-01-01

    Memory T cells form a highly specific defense layer against reinfection with previously encountered pathogens. In addition, memory T cells provide protection against pathogens that are similar, but not identical to the original infectious agent. This is because each T cell response harbors multiple

  19. Untargeted metabolomic analysis using liquid chromatography quadrupole time-of-flight mass spectrometry for non-volatile profiling of wines

    International Nuclear Information System (INIS)

    Arbulu, M.; Sampedro, M.C.; Gómez-Caballero, A.; Goicolea, M.A.; Barrio, R.J.

    2015-01-01

    Highlights: • An untargeted metabolomic method for the non-volatile profile of the Graciano wine was developed. • 411 different metabolites in Graciano Vitis vinifera red wine were identified. • 15 compounds could serve to differentiate Graciano and Tempranillo wines. • An enological database (WinMet) with 2080 compounds was constructed. - Abstract: The current study presents a method for comprehensive untargeted metabolomic fingerprinting of the non-volatile profile of the Graciano Vitis vinifera wine variety, using liquid chromatography/electrospray ionization time of flight mass spectrometry (LC–ESI-QTOF). Pre-treatment of samples, chromatographic columns, mobile phases, elution gradients and ionization sources, were evaluated for the extraction of the maximum number of metabolites in red wine. Putative compounds were extracted from the raw data using the extraction algorithm, molecular feature extractor (MFE). For the metabolite identification the WinMet database was designed based on electronic databases and literature research and includes only the putative metabolites reported to be present in oenological matrices. The results from WinMet were compared with those in the METLIN database to evaluate how much the databases overlap for performing identifications. The reproducibility of the analysis was assessed using manual processing following replicate injections of Vitis vinifera cv. Graciano wine spiked with external standards. In the present work, 411 different metabolites in Graciano Vitis vinifera red wine were identified, including primary wine metabolites such as sugars (4%), amino acids (23%), biogenic amines (4%), fatty acids (2%), and organic acids (32%) and secondary metabolites such as phenols (27%) and esters (8%). Significant differences between varieties Tempranillo and Graciano were related to the presence of fifteen specific compounds

  20. Untargeted metabolomic analysis using liquid chromatography quadrupole time-of-flight mass spectrometry for non-volatile profiling of wines

    Energy Technology Data Exchange (ETDEWEB)

    Arbulu, M. [Department of Analytical Chemistry, Faculty of Pharmacy, University of the Basque Country, 01006 Vitoria-Gasteiz (Spain); Sampedro, M.C. [Central Service of Analysis, SGIker, University of the Basque Country, 01006 Vitoria-Gasteiz (Spain); Gómez-Caballero, A.; Goicolea, M.A. [Department of Analytical Chemistry, Faculty of Pharmacy, University of the Basque Country, 01006 Vitoria-Gasteiz (Spain); Barrio, R.J., E-mail: r.barrio@ehu.es [Department of Analytical Chemistry, Faculty of Pharmacy, University of the Basque Country, 01006 Vitoria-Gasteiz (Spain)

    2015-02-09

    Highlights: • An untargeted metabolomic method for the non-volatile profile of the Graciano wine was developed. • 411 different metabolites in Graciano Vitis vinifera red wine were identified. • 15 compounds could serve to differentiate Graciano and Tempranillo wines. • An enological database (WinMet) with 2080 compounds was constructed. - Abstract: The current study presents a method for comprehensive untargeted metabolomic fingerprinting of the non-volatile profile of the Graciano Vitis vinifera wine variety, using liquid chromatography/electrospray ionization time of flight mass spectrometry (LC–ESI-QTOF). Pre-treatment of samples, chromatographic columns, mobile phases, elution gradients and ionization sources, were evaluated for the extraction of the maximum number of metabolites in red wine. Putative compounds were extracted from the raw data using the extraction algorithm, molecular feature extractor (MFE). For the metabolite identification the WinMet database was designed based on electronic databases and literature research and includes only the putative metabolites reported to be present in oenological matrices. The results from WinMet were compared with those in the METLIN database to evaluate how much the databases overlap for performing identifications. The reproducibility of the analysis was assessed using manual processing following replicate injections of Vitis vinifera cv. Graciano wine spiked with external standards. In the present work, 411 different metabolites in Graciano Vitis vinifera red wine were identified, including primary wine metabolites such as sugars (4%), amino acids (23%), biogenic amines (4%), fatty acids (2%), and organic acids (32%) and secondary metabolites such as phenols (27%) and esters (8%). Significant differences between varieties Tempranillo and Graciano were related to the presence of fifteen specific compounds.

  1. Specifically activated memory T cell subsets from cancer patients recognize and reject xenotransplanted autologous tumors

    Science.gov (United States)

    Beckhove, Philipp; Feuerer, Markus; Dolenc, Mathias; Schuetz, Florian; Choi, Carmen; Sommerfeldt, Nora; Schwendemann, Jochen; Ehlert, Katrin; Altevogt, Peter; Bastert, Gunther; Schirrmacher, Volker; Umansky, Viktor

    2004-01-01

    Bone marrow of breast cancer patients was found to contain CD8+ T cells specific for peptides derived from breast cancer–associated proteins MUC1 and Her-2/neu. Most of these cells had a central or effector memory phenotype (CD45RA–CD62L+ or CD45RA–CD62L–, respectively). To test their in vivo function, we separated bone marrow–derived CD45RA+ naive or CD45RA–CD45RO+ memory T cells, stimulated them with autologous dendritic cells pulsed with tumor lysate, and transferred them into NOD/SCID mice bearing autologous breast tumors and normal skin transplants. CD45RA– memory but not CD45RA+ naive T cells infiltrated autologous tumor but not skin tissues after the transfer. These tumor-infiltrating cells had a central or effector memory phenotype and produced perforin. Many of them expressed the P-selectin glycoprotein ligand 1 and were found around P-selectin+ tumor endothelium. Tumor infiltration included cluster formation in tumor tissue by memory T cells with cotransferred dendritic cells. It was associated with the induction of tumor cell apoptosis and significant tumor reduction. We thus demonstrate selective homing of memory T cells to human tumors and suggest that tumor rejection is based on the recognition of tumor-associated antigens on tumor cells and dendritic cells by autologous specifically activated central and effector memory T cells. PMID:15232613

  2. CD4+CD62L+ Central Memory T Cells Can Be Converted to Foxp3+ T Cells

    Science.gov (United States)

    Zhang, Xiaolong; Chang Li, Xian; Xiao, Xiang; Sun, Rui; Tian, Zhigang; Wei, Haiming

    2013-01-01

    The peripheral Foxp3+ Treg pool consists of naturally arising Treg (nTreg) and adaptive Treg cells (iTreg). It is well known that naive CD4+ T cells can be readily converted to Foxp3+ iTreg in vitro, and memory CD4+ T cells are resistant to conversion. In this study, we investigated the induction of Foxp3+ T cells from various CD4+ T-cell subsets in human peripheral blood. Though naive CD4+ T cells were readily converted to Foxp3+ T cells with TGF-β and IL-2 treatment in vitro, such Foxp3+ T cells did not express the memory marker CD45RO as do Foxp3+ T cells induced in the peripheral blood of Hepatitis B Virus (HBV) patients. Interestingly, a subset of human memory CD4+ T cells, defined as CD62L+ central memory T cells, could be induced by TGF-β to differentiate into Foxp3+ T cells. It is well known that Foxp3+ T cells derived from human CD4+CD25- T cells in vitro are lack suppressive functions. Our data about the suppressive functions of CD4+CD62L+ central memory T cell-derived Foxp3+ T cells support this conception, and an epigenetic analysis of these cells showed a similar methylation pattern in the FOXP3 Treg-specific demethylated region as the naive CD4+ T cell-derived Foxp3+ T cells. But further research showed that mouse CD4+ central memory T cells also could be induced to differentiate into Foxp3+ T cells, such Foxp3+ T cells could suppress the proliferation of effector T cells. Thus, our study identified CD4+CD62L+ central memory T cells as a novel potential source of iTreg. PMID:24155942

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

    Science.gov (United States)

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

    2017-06-05

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

  4. CD49b-dependent establishment of T helper cell memory.

    Science.gov (United States)

    Hanazawa, Asami; Hayashizaki, Koji; Shinoda, Kenta; Yagita, Hideo; Okumura, Ko; Löhning, Max; Hara, Takahiro; Tani-ichi, Shizue; Ikuta, Koichi; Eckes, Beate; Radbruch, Andreas; Tokoyoda, Koji; Nakayama, Toshinori

    2013-09-01

    CD4 T cells play a key role in immunological memory. We have demonstrated that professional memory CD4 T cells reside and rest in the bone marrow (BM). However, the molecular mechanisms of their establishment in the BM and their maintenance remain unclear. We here show that memory CD4 T cells express high levels of CD49b and that CD49b-deficient or -blocked memory CD4 T-cell precursors fail to migrate from blood into the marrow of the bone, and they especially fail to transmigrate through sinusoidal endothelial cells of the BM. In the marrow, memory CD4 T cells and the precursors contact stromal cells expressing collagen II that are specific ligands for CD49b. Interestingly, memory CD4 T cells on day 117 of an immune response also dock on IL-7(+)/collagen XI(+) stromal cells, whereas memory precursors on day 12 do not. These results indicate that the collagen receptor CD49b is required for the migration of memory CD4 T-cell precursors into their survival niches of the bone marrow.

  5. Splenectomy associated changes in IgM memory B cells in an adult spleen registry cohort.

    Directory of Open Access Journals (Sweden)

    Paul U Cameron

    Full Text Available Asplenic patients have a lifelong risk of overwhelming post-splenectomy infection and have been reported to have low numbers of peripheral blood IgM memory B cells. The clinical value of quantitation of memory B cells as an indicator of splenic abnormality or risk of infection has been unclear. To assess changes in B cell sub-populations after splenectomy we studied patients recruited to a spleen registry (n = 591. A subset of 209 adult asplenic or hyposplenic subjects, and normal controls (n = 140 were tested for IgM memory B cells. We also determined a changes in IgM memory B cells with time after splenectomy using the cross-sectional data from patients on the registry and b the kinetics of changes in haematological markers associated with splenectomy(n = 45. Total B cells in splenectomy patients did not differ from controls, but memory B cells, IgM memory B cells and switched B cells were significantly (p<0.001 reduced. The reduction was similar for different indications for splenectomy. Changes of asplenia in routine blood films including presence of Howell-Jolly bodies (HJB, occurred early (median 25 days and splenectomy associated thrombocytosis and lymphocytosis peaked by 50 days. There was a more gradual decrease in IgM memory B cells reaching a stable level within 6 months after splenectomy. IgM memory B cells as proportion of B cells was the best discriminator between splenectomized patients and normal controls and at the optimal cut-off of 4.53, showed a true positive rate of 95% and false positive rate of 20%. In a survey of 152 registry patients stratified by IgM memory B cells around this cut-off there was no association with minor infections and no registry patients experienced OPSI during the study. Despite significant changes after splenectomy, conventional measures of IgM memory cells have limited clinical utility in this population.

  6. Splenectomy Associated Changes in IgM Memory B Cells in an Adult Spleen Registry Cohort

    Science.gov (United States)

    Cameron, Paul U.; Jones, Penelope; Gorniak, Malgorzata; Dunster, Kate; Paul, Eldho; Lewin, Sharon; Woolley, Ian; Spelman, Denis

    2011-01-01

    Asplenic patients have a lifelong risk of overwhelming post-splenectomy infection and have been reported to have low numbers of peripheral blood IgM memory B cells. The clinical value of quantitation of memory B cells as an indicator of splenic abnormality or risk of infection has been unclear. To assess changes in B cell sub-populations after splenectomy we studied patients recruited to a spleen registry (n = 591). A subset of 209 adult asplenic or hyposplenic subjects, and normal controls (n = 140) were tested for IgM memory B cells. We also determined a) changes in IgM memory B cells with time after splenectomy using the cross-sectional data from patients on the registry and b) the kinetics of changes in haematological markers associated with splenectomy(n = 45). Total B cells in splenectomy patients did not differ from controls, but memory B cells, IgM memory B cells and switched B cells were significantly (psplenectomy. Changes of asplenia in routine blood films including presence of Howell-Jolly bodies (HJB), occurred early (median 25 days) and splenectomy associated thrombocytosis and lymphocytosis peaked by 50 days. There was a more gradual decrease in IgM memory B cells reaching a stable level within 6 months after splenectomy. IgM memory B cells as proportion of B cells was the best discriminator between splenectomized patients and normal controls and at the optimal cut-off of 4.53, showed a true positive rate of 95% and false positive rate of 20%. In a survey of 152 registry patients stratified by IgM memory B cells around this cut-off there was no association with minor infections and no registry patients experienced OPSI during the study. Despite significant changes after splenectomy, conventional measures of IgM memory cells have limited clinical utility in this population. PMID:21829713

  7. Size distributions of non-volatile particle residuals (Dp<800 nm at a rural site in Germany and relation to air mass origin

    Directory of Open Access Journals (Sweden)

    T. Tuch

    2007-11-01

    Full Text Available Atmospheric aerosol particle size distributions at a continental background site in Eastern Germany were examined for a one-year period. Particles were classified using a twin differential mobility particle sizer in a size range between 3 and 800 nm. As a novelty, every second measurement of this experiment involved the removal of volatile chemical compounds in a thermodenuder at 300°C. This concept allowed to quantify the number size distribution of non-volatile particle cores – primarily associated with elemental carbon, and to compare this to the original non-conditioned size distribution. As a byproduct of the volatility analysis, new particles originating from nucleation inside the thermodenuder can be observed, however, overwhelmingly at diameters below 6 nm. Within the measurement uncertainty, every particle down to particle sizes of 15 nm is concluded to contain a non-volatile core. The volume fraction of non-volatile particulate matter (non-conditioned diameter < 800 nm varied between 10 and 30% and was largely consistent with the experimentally determined mass fraction of elemental carbon. The average size of the non-volatile particle cores was estimated as a function of original non-conditioned size using a summation method, which showed that larger particles (>200 nm contained more non-volatile compounds than smaller particles (<50 nm, thus indicating a significantly different chemical composition. Two alternative air mass classification schemes based on either, synoptic chart analysis (Berliner Wetterkarte or back trajectories showed that the volume and number fraction of non-volatile cores depended less on air mass than the total particle number concentration. In all air masses, the non-volatile size distributions showed a more and a less volatile ("soot" mode, the latter being located at about 50 nm. During unstable conditions and in maritime air masses, smaller values were observed compared to stable or continental conditions

  8. LOCAL IMMUNITY BY TISSUE-RESIDENT CD8+ MEMORY T CELLS

    Directory of Open Access Journals (Sweden)

    Thomas eGebhardt

    2012-11-01

    Full Text Available Microbial infection primes a CD8+ cytotoxic T cell response that gives rise to a long-lived population of circulating memory cells able to provide protection against systemic reinfection. Despite this, effective CD8+ T cell surveillance of barrier tissues such as skin and mucosa typically wanes with time, resulting in limited T cell-mediated protection in these peripheral tissues. However, recent evidence suggests that a specialized subset of CD103+ memory T cells can permanently lodge and persist in peripheral tissues, and that these cells can compensate for the loss of peripheral immune surveillance by circulating memory T cells. Here, we review evolving concepts regarding the generation and long-term persistence of these tissue-resident memory T cells (TRM in epithelial and neuronal tissues. We further discuss the role of TRM cells in local infection control and their contribution to localized immune phenomena, in both mice and humans.

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

    Directory of Open Access Journals (Sweden)

    Matthew D Martin

    2015-10-01

    Full Text Available 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

  10. A nanowire magnetic memory cell based on a periodic magnetic superlattice

    International Nuclear Information System (INIS)

    Song, J-F; Bird, J P; Ochiai, Y

    2005-01-01

    We analyse the operation of a semiconductor nanowire-based memory cell. Large changes in the nanowire conductance result when the magnetization of a periodic array of nanoscale magnetic gates, which comprise the other key component of the memory cell, is switched between distinct configurations by an external magnetic field. The resulting conductance change provides the basis for a robust memory effect, which can be implemented in a semiconductor structure compatible with conventional semiconductor integrated circuits

  11. Design and Simulation of a Quaternary Memory Cell based on a Physical Memristor

    DEFF Research Database (Denmark)

    Nannarelli, Alberto; Taylor, Jonathan

    2016-01-01

    Memristors were theorized more than fifty years ago, but only recently physical devices with memristor’s behavior have been fabricated and shipped. In this work, we experiment on one of these physical memristors by designing a memristorbased memory cell, implementing the cell, and testing it. Our...... experiments demonstrate that the memristor technology is not yet mature for practical applications, but, nevertheless, when production will provide reliable and dependable devices, memristorbased memory systems may replace CMOS memories with some advantages....

  12. Activated iNKT cells promote memory CD8+ T cell differentiation during viral infection.

    Directory of Open Access Journals (Sweden)

    Emma C Reilly

    Full Text Available α-Galactosylceramide (α-GalCer is the prototypical lipid ligand for invariant NKT cells. Recent studies have proposed that α-GalCer is an effective adjuvant in vaccination against a range of immune challenges, however its mechanism of action has not been completely elucidated. A variety of delivery methods have been examined including pulsing dendritic cells with α-GalCer to optimize the potential of α-GalCer. These methods are currently being used in a variety of clinical trials in patients with advanced cancer but cannot be used in the context of vaccine development against pathogens due to their complexity. Using a simple delivery method, we evaluated α-GalCer adjuvant properties, using the mouse model for cytomegalovirus (MCMV. We measured several key parameters of the immune response to MCMV, including inflammation, effector, and central memory CD8(+ T cell responses. We found that α-GalCer injection at the time of the infection decreases viral titers, alters the kinetics of the inflammatory response, and promotes both increased frequencies and numbers of virus-specific memory CD8(+ T cells. Overall, our data suggest that iNKT cell activation by α-GalCer promotes the development of long-term protective immunity through increased fitness of central memory CD8(+ T cells, as a consequence of reduced inflammation.

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

    Science.gov (United States)

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

    2017-11-01

    The concept of a "topographical memory" in lymphocytes implies a stable expression of homing receptors mediating trafficking of lymphocytes back to the tissue of initial activation. However, a significant plasticity of the gut-homing receptor α 4 β 7 was found in CD8 + T cells, questioning the concept. We now demonstrate that α 4 β 7 expression in murine CD4 + memory T cells is, in contrast, imprinted and remains stable in the absence of the inducing factor retinoic acid (RA) or other stimuli from mucosal environments. Repetitive rounds of RA treatment enhanced the stability of de novo induced α 4 β 7 . A novel enhancer element in the murine Itga4 locus was identified that showed, correlating to stability, selective DNA demethylation in mucosa-seeking memory cells and methylation-dependent transcriptional activity in a reporter gene assay. This implies that epigenetic mechanisms contribute to the stabilization of α 4 β 7 expression. Analogous DNA methylation patterns could be observed in the human ITGA4 locus, suggesting that its epigenetic regulation is conserved between mice and men. These data prove that mucosa-specific homing mediated by α 4 β 7 is imprinted in CD4 + memory T cells, reinstating the validity of the concept of "topographical memory" for mucosal tissues, and imply a critical role of epigenetic mechanisms.

  14. Effects of annealing temperature in a metal alloy nano-dot memory

    International Nuclear Information System (INIS)

    Lee, Jung Min; Lee, Gae Hun; Song, Yun Heub; Bea, Ji Cheol; Tanaka, Tetsu

    2011-01-01

    The annealing temperature dependence of the capacitance-voltage (C-V) characteristic has been studied in a metal-oxide semiconductor structure containing FePt nano-dots. Several in-situ annealing temperatures from 400 to ∼700 .deg. C in a high vacuum ambience (under 1 x 10 -5 Pa) were evaluated in view of the cell's characteristics and its reliability. Here, we demonstrate that the annealing temperature is significant for memory performance in an alloy metal nano-dot structure. A higher in-situ temperature provides better retention and a more reliable memory window. In the sample with an in-situ annealing condition of 700 .deg. C for 30 min, a memory window of 9.2 V at the initial stage was obtained, and a memory window of 6.2 V after 10 years was estimated, which is reliable for a non-volatile memory. From these results, the annealing condition for an alloy metal nano-dot memory is one of the critical parameters for the memory characteristics, and should be optimized for better memory performance.

  15. Magnetization Dynamics in Two Novel Current-Driven Spintronic Memory Cell Structures

    KAUST Repository

    Velazquez-Rizo, Martin

    2017-01-01

    In this work, two new spintronic memory cell structures are proposed. The first cell uses the diffusion of polarized spins into ferromagnets with perpendicular anisotropy to tilt their magnetization followed by their dipolar coupling to a fixed

  16. Altered T cell memory and effector cell development in chronic lymphatic filarial infection that is independent of persistent parasite antigen.

    Directory of Open Access Journals (Sweden)

    Cathy Steel

    2011-04-01

    Full Text Available Chronic lymphatic filarial (LF infection is associated with suppression of parasite-specific T cell responses that persist even following elimination of infection. While several mechanisms have been implicated in mediating this T cell specific downregulation, a role for alterations in the homeostasis of T effector and memory cell populations has not been explored. Using multiparameter flow cytometry, we investigated the role of persistent filarial infection on the maintenance of T cell memory in patients from the filarial-endemic Cook Islands. Compared to filarial-uninfected endemic normals (EN, microfilaria (mf positive infected patients (Inf had a reduced CD4 central memory (T(CM compartment. In addition, Inf patients tended to have more effector memory cells (T(EM and fewer effector cells (T(EFF than did ENs giving significantly smaller T(EFF:T(EM ratios. These contracted T(CM and T(EFF populations were still evident in patients previously mf+ who had cleared their infection (CLInf. Moreover, the density of IL-7Rα, necessary for T memory cell maintenance (but decreased in T effector cells, was significantly higher on memory cells of Inf and CLInf patients, although there was no evidence for decreased IL-7 or increased soluble IL7-Rα, both possible mechanisms for signaling defects in memory cells. However, effector cells that were present in Inf and CLInf patients had lower percentages of HLA-DR suggesting impaired function. These changes in T cell populations appear to reflect chronicity of infection, as filarial-infected children, despite the presence of active infection, did not show alterations in the frequencies of these T cell phenotypes. These data indicate that filarial-infected patients have contracted T(CM compartments and a defect in effector cell development, defects that persist even following clearance of infection. The fact that these global changes in memory and effector cell compartments do not yet occur in infected children

  17. CD4+ virtual memory: Antigen-inexperienced T cells reside in the naïve, regulatory, and memory T cell compartments at similar frequencies, implications for autoimmunity.

    Science.gov (United States)

    Marusina, Alina I; Ono, Yoko; Merleev, Alexander A; Shimoda, Michiko; Ogawa, Hiromi; Wang, Elizabeth A; Kondo, Kayo; Olney, Laura; Luxardi, Guillaume; Miyamura, Yoshinori; Yilma, Tilahun D; Villalobos, Itzel Bustos; Bergstrom, Jennifer W; Kronenberg, Daniel G; Soulika, Athena M; Adamopoulos, Iannis E; Maverakis, Emanual

    2017-02-01

    It is widely accepted that central and effector memory CD4 + T cells originate from naïve T cells after they have encountered their cognate antigen in the setting of appropriate co-stimulation. However, if this were true the diversity of T cell receptor (TCR) sequences within the naïve T cell compartment should be far greater than that of the memory T cell compartment, which is not supported by TCR sequencing data. Here we demonstrate that aged mice with far fewer naïve T cells, respond to the model antigen, hen eggwhite lysozyme (HEL), by utilizing the same TCR sequence as their younger counterparts. CD4 + T cell repertoire analysis of highly purified T cell populations from naive animals revealed that the HEL-specific clones displayed effector and central "memory" cell surface phenotypes even prior to having encountered their cognate antigen. Furthermore, HEL-inexperienced CD4 + T cells were found to reside within the naïve, regulatory, central memory, and effector memory T cell populations at similar frequencies and the majority of the CD4 + T cells within the regulatory and memory populations were unexpanded. These findings support a new paradigm for CD4 + T cell maturation in which a specific clone can undergo a differentiation process to exhibit a "memory" or regulatory phenotype without having undergone a clonal expansion event. It also demonstrates that a foreign-specific T cell is just as likely to reside within the regulatory T cell compartment as it would the naïve compartment, arguing against the specificity of the regulatory T cell compartment being skewed towards self-reactive T cell clones. Finally, we demonstrate that the same set of foreign and autoreactive CD4 + T cell clones are repetitively generated throughout adulthood. The latter observation argues against T cell-depleting strategies or autologous stem cell transplantation as therapies for autoimmunity-as the immune system has the ability to regenerate pathogenic clones. Published by

  18. Crystal growth within a phase change memory cell.

    Science.gov (United States)

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

    2014-07-07

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

  19. Eight-logic memory cell based on multiferroic junctions

    International Nuclear Information System (INIS)

    Yang Feng; Zhou, Y C; Tang, M H; Liu Fen; Ma Ying; Zheng, X J; Zhao, W F; Xu, H Y; Sun, Z H

    2009-01-01

    A model is proposed for a device combining a multiferroic tunnel junction with a magnetoelectric (ME) film in which the magnetic configuration is controlled by the electric field. Calculations embodying the Green's function approach show that the magnetic polarization can be switched on and off by an electric field in the ME film due to the effect of elastic coupling interaction. Using a model including the spin-filter effect and screening of polarization charges, we have produced eight logic states of tunnelling resistance in the tunnel junction and have obtained corresponding laws that control them. The results provide some insights into the realization of an eight-logic memory cell. (fast track communication)

  20. Expression of MEP Pathway Genes and Non-volatile Sequestration Are Associated with Circadian Rhythm of Dominant Terpenoids Emission in Osmanthus fragrans Lour. Flowers

    Directory of Open Access Journals (Sweden)

    Riru Zheng

    2017-10-01

    Full Text Available Osmanthus fragrans Lour. is one of the top 10 traditional ornamental flowers in China famous for its unique fragrance. Preliminary study proved that the terpenoids including ionone, linalool, and ocimene and their derivatives are the dominant aroma-active compounds that contribute greatly to the scent bouquet. Pollination observation implies the emission of aromatic terpenoids may follow a circadian rhythm. In this study, we investigated the variation of volatile terpenoids and its potential regulators. The results showed that both volatile and non-volatile terpenoids presented circadian oscillation with high emission or accumulation during the day and low emission or accumulation during the night. The volatile terpenoids always increased to reach their maximum values at 12:00 h, while free and glycosylated compounds continued increasing throughout the day. The depletion of non-volatile pool might provide the substrates for volatile emission at 0:00–6:00, suggesting the sequestration of non-volatile compounds acted like a buffer regulating emission of terpenoids. Further detection of MEP pathway genes demonstrated that their expressions increased significantly in parallel with the evident increase of both volatile and non-volatile terpenoids during the day, indicating that the gene expressions were also closely associated with terpenoid formation. Thus, the expression of MEP pathway genes and internal sequestration both played crucial roles in modulating circadian rhythm of terpenoid emission in O. fragrans.

  1. Analysis of drugs of forensic interest with capillary zone electrophoresis/time-of-flight mass spectrometry based on the use of non-volatile buffers

    Czech Academy of Sciences Publication Activity Database

    Gottardo, R.; Mikšík, Ivan; Aturki, Z.; Sorio, D.; Seri, C.; Fanali, S.; Tagliaro, F.

    2012-01-01

    Roč. 33, č. 4 (2012), s. 599-606 ISSN 0173-0835 R&D Projects: GA ČR(CZ) GA203/08/1428 Institutional research plan: CEZ:AV0Z50110509 Keywords : capillary electrophoresis * drugs of abuse * non-volatile buffer * CE-MS Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 3.261, year: 2012

  2. Memory phenotype CD4 T cells undergoing rapid, nonburst-like, cytokine-driven proliferation can be distinguished from antigen-experienced memory cells.

    Directory of Open Access Journals (Sweden)

    Souheil-Antoine Younes

    2011-10-01

    Full Text Available Memory phenotype (CD44(bright, CD25(negative CD4 spleen and lymph node T cells (MP cells proliferate rapidly in normal or germ-free donors, with BrdU uptake rates of 6% to 10% per day and Ki-67 positivity of 18% to 35%. The rapid proliferation of MP cells stands in contrast to the much slower proliferation of lymphocytic choriomeningitis virus (LCMV-specific memory cells that divide at rates ranging from <1% to 2% per day over the period from 15 to 60 days after LCMV infection. Anti-MHC class II antibodies fail to inhibit the in situ proliferation of MP cells, implying a non-T-cell receptor (TCR-driven proliferation. Such proliferation is partially inhibited by anti-IL-7Rα antibody. The sequence diversity of TCRβ CDR3 gene segments is comparable among the proliferating and quiescent MP cells from conventional and germ-free mice, implying that the majority of proliferating MP cells have not recently derived from a small cohort of cells that expand through multiple continuous rounds of cell division. We propose that MP cells constitute a diverse cell population, containing a subpopulation of slowly dividing authentic antigen-primed memory cells and a majority population of rapidly proliferating cells that did not arise from naïve cells through conventional antigen-driven clonal expansion.

  3. Incomplete Memories: The Natural Suppression of Tissue-Resident Memory CD8 T Cells in the Lung

    Directory of Open Access Journals (Sweden)

    Katie L. Reagin

    2018-01-01

    Full Text Available The yearly, cyclic impact of viruses like influenza on human health and the economy is due to the high rates of mutation of traditional antibody targets, which negate any preexisting humoral immunity. However, the seasonality of influenza infections can equally be attributed to an absent or defective memory CD8 T cell response since the epitopes recognized by these cells are derived from essential virus proteins that mutate infrequently. Experiments in mouse models show that protection from heterologous influenza infection is temporally limited and conferred by a population of tissue-resident memory (TRM cells residing in the lung and lung airways. TRM are elicited by a diverse set of pathogens penetrating mucosal barriers and broadly identified by extravascular staining and expression of the activation and adhesion molecules CD69 and CD103. Interestingly, lung TRM fail to express these molecules, which could limit tissue retention, resulting in airway expulsion or death with concomitant loss of heterologous protection. Here, we make the case that respiratory infections uniquely evoke a form of natural immunosuppression whereby specific cytokines and cell–cell interactions negatively impact memory cell programming and differentiation. Respiratory memory is not only short-lived but most of the memory cells in the lung parenchyma may not be bona fide TRM. Given the quantity of microbes humans inhale over a lifetime, limiting cellular residence could be a mechanism employed by the respiratory tract to preserve organismal vitality. Therefore, successful efforts to improve respiratory immunity must carefully and selectively breach these inherent tissue barriers.

  4. Dissociating markers of senescence and protective ability in memory T cells.

    Directory of Open Access Journals (Sweden)

    Martin Prlic

    Full Text Available No unique transcription factor or biomarker has been identified to reliably distinguish effector from memory T cells. Instead a set of surface markers including IL-7Rα and KLRG1 is commonly used to predict the potential of CD8 effector T cells to differentiate into memory cells. Similarly, these surface markers together with the tumor necrosis factor family member CD27 are frequently used to predict a memory T cell's ability to mount a recall response. Expression of these markers changes every time a memory cell is stimulated and repeated stimulation can lead to T cell senescence and loss of memory T cell responsiveness. This is a concern for prime-boost vaccine strategies which repeatedly stimulate T cells with the aim of increasing memory T cell frequency. The molecular cues that cause senescence are still unknown, but cell division history is likely to play a major role. We sought to dissect the roles of inflammation and cell division history in developing T cell senescence and their impact on the expression pattern of commonly used markers of senescence. We developed a system that allows priming of CD8 T cells with minimal inflammation and without acquisition of maximal effector function, such as granzyme expression, but a cell division history similar to priming with systemic inflammation. Memory cells derived from minimal effector T cells are fully functional upon rechallenge, have full access to non-lymphoid tissue and appear to be less senescent by phenotype upon rechallenge. However, we report here that these currently used biomarkers to measure senescence do not predict proliferative potential or protective ability, but merely reflect initial priming conditions.

  5. Localization of functional memory B cells at sites of antigen localization and its relationship to local aspects of immunological memory

    International Nuclear Information System (INIS)

    Ponzio, N.M.; Baine, Y.; Thorbecke, G.J.

    1980-01-01

    Experiments are described which have been designed to test whether antigen in a draining lymph node can mediate local accumulation of passively transferred antigen-specific memory B cells, using recipients whose own immune response is inhibited via γ-irradiation or by injection of cyclophosphamide. (Auth.)

  6. Liver-primed memory T cells generated under noninflammatory conditions provide anti-infectious immunity.

    Science.gov (United States)

    Böttcher, Jan P; Schanz, Oliver; Wohlleber, Dirk; Abdullah, Zeinab; Debey-Pascher, Svenja; Staratschek-Jox, Andrea; Höchst, Bastian; Hegenbarth, Silke; Grell, Jessica; Limmer, Andreas; Atreya, Imke; Neurath, Markus F; Busch, Dirk H; Schmitt, Edgar; van Endert, Peter; Kolanus, Waldemar; Kurts, Christian; Schultze, Joachim L; Diehl, Linda; Knolle, Percy A

    2013-03-28

    Development of CD8(+) T cell (CTL) immunity or tolerance is linked to the conditions during T cell priming. Dendritic cells (DCs) matured during inflammation generate effector/memory T cells, whereas immature DCs cause T cell deletion/anergy. We identify a third outcome of T cell priming in absence of inflammation enabled by cross-presenting liver sinusoidal endothelial cells. Such priming generated memory T cells that were spared from deletion by immature DCs. Similar to central memory T cells, liver-primed T cells differentiated into effector CTLs upon antigen re-encounter on matured DCs even after prolonged absence of antigen. Their reactivation required combinatorial signaling through the TCR, CD28, and IL-12R and controlled bacterial and viral infections. Gene expression profiling identified liver-primed T cells as a distinct Neuropilin-1(+) memory population. Generation of liver-primed memory T cells may prevent pathogens that avoid DC maturation by innate immune escape from also escaping adaptive immunity through attrition of the T cell repertoire. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Liver-Primed Memory T Cells Generated under Noninflammatory Conditions Provide Anti-infectious Immunity

    Directory of Open Access Journals (Sweden)

    Jan P. Böttcher

    2013-03-01

    Full Text Available Development of CD8+ T cell (CTL immunity or tolerance is linked to the conditions during T cell priming. Dendritic cells (DCs matured during inflammation generate effector/memorycells, whereas immature DCs cause T cell deletion/anergy. We identify a third outcome of T cell priming in absence of inflammation enabled by cross-presenting liver sinusoidal endothelial cells. Such priming generated memorycells that were spared from deletion by immature DCs. Similar to central memorycells, liver-primed T cells differentiated into effector CTLs upon antigen re-encounter on matured DCs even after prolonged absence of antigen. Their reactivation required combinatorial signaling through the TCR, CD28, and IL-12R and controlled bacterial and viral infections. Gene expression profiling identified liver-primed T cells as a distinct Neuropilin-1+ memory population. Generation of liver-primed memorycells may prevent pathogens that avoid DC maturation by innate immune escape from also escaping adaptive immunity through attrition of the T cell repertoire.

  8. 1Protein Energy Malnutrition Impairs Homeostatic Proliferation of Memory CD8 T cells

    Science.gov (United States)

    Iyer, Smita S.; Chatraw, Janel Hart; Tan, Wendy G.; Wherry, E. John; Becker, Todd C.; Ahmed, Rafi; Kapasi, Zoher F.

    2011-01-01

    Nutrition is a critical but poorly understood determinant of immunity. There is abundant epidemiological evidence linking protein malnutrition to impaired vaccine efficacy and increased susceptibility to infections; yet, the role of dietary protein in immune memory homeostasis remains poorly understood. Here we show that protein energy malnutrition (PEM) induced in mice by low-protein (LP) feeding has a detrimental impact on CD8 memory. Relative to adequate-protein (AP) fed controls, LP feeding in lymphocytic choriomeningitis virus (LCMV) immune mice resulted in a 2-fold decrease in LCMV-specific CD8 memory T cells. Adoptive transfer of memory cells, labeled with a division tracking dye, from AP mice into naive LP or AP mice demonstrated that PEM caused profound defects in homeostatic proliferation. Remarkably, this defect occurred despite the lymphopenic environment in LP hosts. While antigen-specific memory cells in LP and AP hosts were phenotypically similar, memory cells in LP hosts were markedly less-responsive to poly(I:C)-induced acute proliferative signals. Furthermore, upon recall, memory cells in LP hosts displayed reduced proliferation and protection from challenge with LCMV-clone 13 resulting in impaired viral clearance in the liver. The findings show a metabolic requirement of dietary protein in sustaining functional CD8 memory and suggest that interventions to optimize dietary protein intake may improve vaccine efficacy in malnourished individuals. PMID:22116826

  9. Protein energy malnutrition impairs homeostatic proliferation of memory CD8 T cells.

    Science.gov (United States)

    Iyer, Smita S; Chatraw, Janel Hart; Tan, Wendy G; Wherry, E John; Becker, Todd C; Ahmed, Rafi; Kapasi, Zoher F

    2012-01-01

    Nutrition is a critical but poorly understood determinant of immunity. There is abundant epidemiological evidence linking protein malnutrition to impaired vaccine efficacy and increased susceptibility to infections; yet, the role of dietary protein in immune memory homeostasis remains poorly understood. In this study, we show that protein-energy malnutrition induced in mice by low-protein (LP) feeding has a detrimental impact on CD8 memory. Relative to adequate protein (AP)-fed controls, LP feeding in lymphocytic choriomeningitis virus (LCMV)-immune mice resulted in a 2-fold decrease in LCMV-specific CD8 memory T cells. Adoptive transfer of memory cells, labeled with a division tracking dye, from AP mice into naive LP or AP mice demonstrated that protein-energy malnutrition caused profound defects in homeostatic proliferation. Remarkably, this defect occurred despite the lymphopenic environment in LP hosts. Whereas Ag-specific memory cells in LP and AP hosts were phenotypically similar, memory cells in LP hosts were markedly less responsive to polyinosinic-polycytidylic acid-induced acute proliferative signals. Furthermore, upon recall, memory cells in LP hosts displayed reduced proliferation and protection from challenge with LCMV-clone 13, resulting in impaired viral clearance in the liver. The findings show a metabolic requirement of dietary protein in sustaining functional CD8 memory and suggest that interventions to optimize dietary protein intake may improve vaccine efficacy in malnourished individuals.

  10. The effects of centrally administered fluorocitrate via inhibiting glial cells on working memory in rats

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Although prefrontal and hippocampal neurons are critical for spatial working memory,the function of glial cells in spatial working memory remains uncertain.In this study we investigated the function of glial cells in rats’ working memory.The glial cells of rat brain were inhibited by intracerebroventricular(icv) injection of fluorocitrate(FC).The effects of FC on the glial cells were examined by using electroencephalogram(EEG) recordings and delayed spatial alternation tasks.After icv injection of 10 μL of 0.5 nmol/L or 5 nmol/L FC,the EEG power spectrum recorded from the hippocampus increased,but the power spectrum for the prefrontal cortex did not change,and working memory was unaffected.Following an icv injection of 10 μL of 20 nmol/L FC,the EEG power spectra in both the prefrontal cortex and the hippocampus increased,and working memory improved.The icv injection of 10 μL of 50 nmol/L FC,the EEG power spectra in both the prefrontal cortex and in the hippocampus decreased,and working memory was impaired.These results suggest that spatial working memory is affected by centrally administered FC,but only if there are changes in the EEG power spectrum in the prefrontal cortex.Presumably,the prefrontal glial cells relate to the working memory.

  11. High-throughput gene expression profiling of memory differentiation in primary human T cells

    Directory of Open Access Journals (Sweden)

    Russell Kate

    2008-08-01

    Full Text Available Abstract Background The differentiation of naive T and B cells into memory lymphocytes is essential for immunity to pathogens. Therapeutic manipulation of this cellular differentiation program could improve vaccine efficacy and the in vitro expansion of memory cells. However, chemical screens to identify compounds that induce memory differentiation have been limited by 1 the lack of reporter-gene or functional assays that can distinguish naive and memory-phenotype T cells at high throughput and 2 a suitable cell-line representative of naive T cells. Results Here, we describe a method for gene-expression based screening that allows primary naive and memory-phenotype lymphocytes to be discriminated based on complex genes signatures corresponding to these differentiation states. We used ligation-mediated amplification and a fluorescent, bead-based detection system to quantify simultaneously 55 transcripts representing naive and memory-phenotype signatures in purified populations of human T cells. The use of a multi-gene panel allowed better resolution than any constituent single gene. The method was precise, correlated well with Affymetrix microarray data, and could be easily scaled up for high-throughput. Conclusion This method provides a generic solution for high-throughput differentiation screens in primary human T cells where no single-gene or functional assay is available. This screening platform will allow the identification of small molecules, genes or soluble factors that direct memory differentiation in naive human lymphocytes.

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

    Science.gov (United States)

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

    2015-04-01

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

  13. VHDL-based programming environment for Floating-Gate analog memory cell

    Directory of Open Access Journals (Sweden)

    Carlos Alberto dos Reis Filho

    2005-02-01

    Full Text Available An implementation in CMOS technology of a Floating-Gate Analog Memory Cell and Programming Environment is presented. A digital closed-loop control compares a reference value set by user and the memory output and after cycling, the memory output is updated and the new value stored. The circuit can be used as analog trimming for VLSI applications where mechanical trimming associated with postprocessing chip is prohibitive due to high costs.

  14. Memory

    OpenAIRE

    Wager, Nadia

    2017-01-01

    This chapter will explore a response to traumatic victimisation which has divided the opinions of psychologists at an exponential rate. We will be examining amnesia for memories of childhood sexual abuse and the potential to recover these memories in adulthood. Whilst this phenomenon is generally accepted in clinical circles, it is seen as highly contentious amongst research psychologists, particularly experimental cognitive psychologists. The chapter will begin with a real case study of a wo...

  15. Partial reconstitution of virus-specific memory CD8+ T cells following whole body γ-irradiation

    International Nuclear Information System (INIS)

    Grayson, Jason M.; Laniewski, Nathan G.; Holbrook, Beth C.

    2006-01-01

    CD8 + memory T cells are critical in providing immunity to viral infection. Previous studies documented that antigen-specific CD8 + memory T cells are more resistant to radiation-induced apoptosis than naive T cells. Here, we determined the number and in vivo function of memory CD8 + T cells as immune reconstitution progressed following irradiation. Immediately following irradiation, the number of memory CD8 + T cells declined 80%. As reconstitution progressed, the number of memory cells reached a zenith at 33% of pre-irradiation levels, and was maintained for 120 days post-irradiation. In vitro, memory CD8 + T cells were able to produce cytokines at all times post-irradiation, but when adoptively transferred, they were not able to expand upon rechallenge immediately following irradiation, but regained this ability as reconstitution progressed. When proliferation was examined in vitro, irradiated memory CD8 + T cells were able to respond to mitogenic growth but were unable to divide

  16. Memory CD8+ T Cells: Orchestrators and Key Players of Innate Immunity?

    Directory of Open Access Journals (Sweden)

    Grégoire Lauvau

    2016-09-01

    Full Text Available Over the past decades, the dichotomy between innate and adaptive immune responses has largely dominated our understanding of immunology. Upon primary encounter with microbial pathogens, differentiation of adaptive immune cells into functional effectors usually takes several days or even longer, making them contribute to host protection only late during primary infection. However, once generated, antigen-experienced T lymphocytes can persist in the organism and constitute a pool of memory cells that mediate fast and effective protection to a recall infection with the same microbial pathogen. Herein, we challenge this classical paradigm by highlighting the "innate nature" of memory CD8+ T cells. First, within the thymus or in the periphery, naïve CD8+ T cells may acquire phenotypic and functional characteristics of memory CD8+ T cells independently of challenge with foreign antigens. Second, both the "unconventional" and the "conventional" memory cells can rapidly express protective effector functions in response to sets of inflammatory cytokines and chemokines signals, independent of cognate antigen triggering. Third, memory CD8+ T cells can act by orchestrating the recruitment, activation, and licensing of innate cells, leading to broad antimicrobial states. Thus, collectively, memory CD8+ T cells may represent important actors of innate immune defenses.

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

    Science.gov (United States)

    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.

  18. Bystander chronic infection negatively impacts development of CD8+ T cell memory

    Science.gov (United States)

    Stelekati, Erietta; Shin, Haina; Doering, Travis A.; Dolfi, Douglas V.; Ziegler, Carly G.; Beiting, Daniel P.; Dawson, Lucas; Liboon, Jennifer; Wolski, David; Ali, Mohammed-Alkhatim A.; Katsikis, Peter D.; Shen, Hao; Roos, David S.; Haining, W. Nicholas; Lauer, Georg M.; Wherry, E. John

    2014-01-01

    Summary Epidemiological evidence suggests that chronic infections impair immune responses to unrelated pathogens and vaccines. The underlying mechanisms, however, are unclear and distinguishing effects on priming versus development of immunological memory has been challenging. We investigated whether bystander chronic infections impact differentiation of memory CD8+ T cells, the hallmark of protective immunity against intracellular pathogens. Chronic bystander infections impaired development of memory CD8+ T cells in several mouse models and humans. These effects were independent of initial priming and were associated with chronic inflammatory signatures. Chronic inflammation negatively impacted the number of bystander CD8+ T cells and their memory development. Distinct underlying mechanisms of altered survival and differentiation were revealed with the latter regulated by the transcription factors T-bet and Blimp-1. Thus, exposure to prolonged bystander inflammation impairs the effector to memory transition. These data have relevance for immunity and vaccination during persisting infections and chronic inflammation. PMID:24837104

  19. Ultra Low Voltage Class AB Switched Current Memory Cells Based on Floating Gate Transistors

    DEFF Research Database (Denmark)

    Mucha, Igor

    1999-01-01

    current memory cells were designed using a CMOS process with threshold voltages V-T0n = \\V-T0p\\ = 0.9 V for the n- and p-channel devices. Both hand calculations and PSPICE simulations showed that the designed example switched current memory cell allowed a maximum signal range better than +/-18 mu......A proposal for a class AB switched current memory cell, suitable for ultra-low-voltage applications is presented. The proposal employs transistors with floating gates, allowing to build analog building blocks for ultralow supply voltage operation also in CMOS processes with high threshold voltages....... This paper presents the theoretical basis for the design of "floating-gate'' switched current memory cells by giving a detailed description and analysis of the most important impacts degrading the performance of the cells. To support the theoretical assumptions circuits based on "floating-gate'' switched...

  20. Persistent expansion of CD4(+) effector memory T cells in Wegener's granulomatosis

    NARCIS (Netherlands)

    Abdulahad, W. H.; van der Geld, Y. M.; Stegeman, C. A.; Kallenberg, C. G. M.

    In order to test the hypothesis that Wegener's granulomatosis (WG) is associated with an ongoing immune effector response, even in remission, we examined the distribution of peripheral naive and memory T-lymphocytes in this disease, and analyzed the function-related phenotypes of the memory T-cell

  1. Associative memory cells and their working principle in the brain [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Jin-Hui Wang

    2018-01-01

    Full Text Available The acquisition, integration and storage of exogenous associated signals are termed as associative learning and memory. The consequences and processes of associative thinking and logical reasoning based on these stored exogenous signals can be memorized as endogenous signals, which are essential for decision making, intention, and planning. Associative memory cells recruited in these primary and secondary associative memories are presumably the foundation for the brain to fulfill cognition events and emotional reactions in life, though the plasticity of synaptic connectivity and neuronal activity has been believed to be involved in learning and memory. Current reports indicate that associative memory cells are recruited by their mutual synapse innervations among co-activated brain regions to fulfill the integration, storage and retrieval of associated signals. The activation of these associative memory cells initiates information recall in the mind, and the successful activation of their downstream neurons endorses memory presentations through behaviors and emotion reactions. In this review, we aim to draw a comprehensive diagram for associative memory cells, working principle and modulation, as well as propose their roles in cognition, emotion and behaviors.

  2. Scaling Techniques for Massive Scale-Free Graphs in Distributed (External) Memory

    KAUST Repository

    Pearce, Roger; Gokhale, Maya; Amato, Nancy M.

    2013-01-01

    We present techniques to process large scale-free graphs in distributed memory. Our aim is to scale to trillions of edges, and our research is targeted at leadership class supercomputers and clusters with local non-volatile memory, e.g., NAND Flash

  3. Telomere length dynamics in human memory T cells specific for viruses causing acute or latent infections.

    Science.gov (United States)

    O'Bryan, Joel M; Woda, Marcia; Co, Mary; Mathew, Anuja; Rothman, Alan L

    2013-08-26

    Declining telomere length (TL) is associated with T cell senescence. While TL in naïve and memory T cells declines with increasing age, there is limited data on TL dynamics in virus-specific memory CD4+ T cells in healthy adults. We combined BrdU-labeling of virus-stimulated T cells followed with flow cytometry-fluorescent in situ hybridization for TL determination. We analyzed TL in T cells specific for several virus infections: non-recurring acute (vaccinia virus, VACV), recurring-acute (influenza A virus, IAV), and reactivating viruses (varicella-zoster virus, VZV, and cytomegalovirus, CMV) in 10 healthy subjects. Additionally, five subjects provided multiple blood samples separated by up to 10 years. VACV- and CMV-specific T cells had longer average TL than IAV-specific CD4+ T cells. Although most virus-specific cells were CD45RA-, we observed a minor population of BrdU+ CD45RA+ T cells characterized by long telomeres. Longitudinal analysis demonstrated a slow decline in average TL in virus-specific T cells. However, in one subject, VZV reactivation led to an increase in average TL in VZV-specific memory T cells, suggesting a conversion of longer TL cells from the naïve T cell repertoire. TLs in memory CD4+ T cells in otherwise healthy adults are heterogeneous and follow distinct virus-specific kinetics. These findings suggests that the distribution of TL and the creation and maintenance of long TL memory T cells could be important for the persistence of long-lived T cell memory.

  4. Magnetic vortex racetrack memory

    Science.gov (United States)

    Geng, Liwei D.; Jin, Yongmei M.

    2017-02-01

    We report a new type of racetrack memory based on current-controlled movement of magnetic vortices in magnetic nanowires with rectangular cross-section and weak perpendicular anisotropy. Data are stored through the core polarity of vortices and each vortex carries a data bit. Besides high density, non-volatility, fast data access, and low power as offered by domain wall racetrack memory, magnetic vortex racetrack memory has additional advantages of no need for constrictions to define data bits, changeable information density, adjustable current magnitude for data propagation, and versatile means of ultrafast vortex core switching. By using micromagnetic simulations, current-controlled motion of magnetic vortices in cobalt nanowire is demonstrated for racetrack memory applications.

  5. Memristive behavior in a junctionless flash memory cell

    Energy Technology Data Exchange (ETDEWEB)

    Orak, Ikram [Vocational School of Health Services, Bingöl University, 12000 Bingöl (Turkey); Department of Physics, Faculty of Science and Art, Bingöl University, 12000 Bingöl (Turkey); Ürel, Mustafa; Dana, Aykutlu, E-mail: aykutlu@unam.bilkent.edu.tr [UNAM Institute of Materials Science and Nanotechnology, Bilkent University, 06800 Ankara (Turkey); Bakan, Gokhan [Faculty of Engineering, Antalya International University, 07190 Antalya (Turkey)

    2015-06-08

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

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  7. Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection.

    Directory of Open Access Journals (Sweden)

    Megan E Schmidt

    2018-01-01

    Full Text Available Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-γ in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.

  8. Changes in non-volatile taste components of button mushroom (Agaricus bisporus) during different stages of freeze drying and freeze drying combined with microwave vacuum drying.

    Science.gov (United States)

    Pei, Fei; Shi, Ying; Gao, Xingyang; Wu, Fangning; Mariga, Alfred Mugambi; Yang, Wenjian; Zhao, Liyan; An, Xinxin; Xin, Zhihong; Yang, Fangmei; Hu, Qiuhui

    2014-12-15

    Button mushroom slices were dehydrated using freeze drying (FD) or FD combined with microwave vacuum drying (FMVD), and the non-volatile component profiles were studied. The results showed that the level of non-volatile components in button mushroom firstly increased during sublimation of FD/FMVD process and then fell during desorption in FD process and MVD in FMVD process. Compared to FD products, the contents of soluble sugars and polyols in FMVD products were relatively low, whereas the contents of total free amino acids were significantly higher, close to the level of fresh mushroom. However, there was no significant difference in the contents of 5'-nucleotides and organic acids between FD and FMVD products. The equivalent umami concentration (EUC) values for FD and FMVD products did not differ from fresh, indicating that both drying methods could effectively preserve MSG (monosodium glutamate)-like components in button mushroom. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Organic ferroelectric/semiconducting nanowire hybrid layer for memory storage

    NARCIS (Netherlands)

    Cai, R.; Kassa, H.G.; Haouari, R.; Marrani, A.; Geerts, Y.H.; Ruzié, C.; Breemen, A.J.J.M. van; Gelinck, G.H.; Nysten, B.; Hu, Z.; Jonas, A.M.

    2016-01-01

    Ferroelectric materials are important components of sensors, actuators and non-volatile memories. However, possible device configurations are limited due to the need to provide screening charges to ferroelectric interfaces to avoid depolarization. Here we show that, by alternating ferroelectric and

  10. Antigen modulation of the immune response. III. Evaluation of the hypothetical short-lived memory cell

    International Nuclear Information System (INIS)

    Feldbush, T.L.; Lande, I.; Bryan, B.; O'Neill, E.

    1974-01-01

    The putative short-lived memory cells, whose existence has been suggested by the results of secondary adoptive transfer experiments, were investigated. On the basis of the following evidences we have concluded that the short-lived memory cell is probably an artifact of the adoptive transfer technique: when immune thoracic duct lymphocytes, known to consist predominantly of long-lived memory cells, were transferred to irradiated recipients and challenged at various times after transfer, approximately 80 to 90 percent of the initial response was absent by Day 14 challenge; preirradiating adoptive recipients with increasing dose of x-irradiation tended to lengthen the observed half life of memory cells; single or multiple treatments of immune donors with 0.3 mg Vinblastin before transfer resulted in neither a depression of the initial secondary response nor an alteration in the rate of decline of the memory potential; reconstitution of irradiated hosts with normal spleen cells one day before transfer of memory cells and challenge resulted in inhibition of the adoptive secondary response; and the transfer of memory cells to antigen free intermediate hosts, in which they were allowed to reside for one day or fourteen days before transfer to irradiated recipients, resulted in only a slight decline in their capacity to respond. We propose that the rapid decline of memory potential in adoptive recipients challenged at various times after transfer is due to modulating effects by the hosts as it recovers from irradiation. These effects may be the result of cell crowding or the loss of irradiation-produced stimulatory factors. The relevance of these findings to adoptive transfer systems in general and the secondary response of intact animals is discussed

  11. Memories.

    Science.gov (United States)

    Brand, Judith, Ed.

    1998-01-01

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

  12. Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells.

    Science.gov (United States)

    Hurton, Lenka V; Singh, Harjeet; Najjar, Amer M; Switzer, Kirsten C; Mi, Tiejuan; Maiti, Sourindra; Olivares, Simon; Rabinovich, Brian; Huls, Helen; Forget, Marie-Andrée; Datar, Vrushali; Kebriaei, Partow; Lee, Dean A; Champlin, Richard E; Cooper, Laurence J N

    2016-11-29

    Adoptive immunotherapy retargeting T cells to CD19 via a chimeric antigen receptor (CAR) is an investigational treatment capable of inducing complete tumor regression of B-cell malignancies when there is sustained survival of infused cells. T-memory stem cells (T SCM ) retain superior potential for long-lived persistence, but challenges exist in manufacturing this T-cell subset because they are rare among circulating lymphocytes. We report a clinically relevant approach to generating CAR + T cells with preserved T SCM potential using the Sleeping Beauty platform. Because IL-15 is fundamental to T-cell memory, we incorporated its costimulatory properties by coexpressing CAR with a membrane-bound chimeric IL-15 (mbIL15). The mbIL15-CAR T cells signaled through signal transducer and activator of transcription 5 to yield improved T-cell persistence independent of CAR signaling, without apparent autonomous growth or transformation, and achieved potent rejection of CD19 + leukemia. Long-lived T cells were CD45RO neg CCR7 + CD95 + , phenotypically most similar to T SCM , and possessed a memory-like transcriptional profile. Overall, these results demonstrate that CAR + T cells can develop long-term persistence with a memory stem-cell phenotype sustained by signaling through mbIL15. This observation warrants evaluation in clinical trials.

  13. Niches for the Long-Term Maintenance of Tissue-Resident Memory T Cells

    Science.gov (United States)

    Takamura, Shiki

    2018-01-01

    Tissue-resident memory T cells (TRM cells) are a population of immune cells that reside in the lymphoid and non-lymphoid organs without recirculation through the blood. These important cells occupy and utilize unique anatomical and physiological niches that are distinct from those for other memory T cell populations, such as central memory T cells in the secondary lymphoid organs and effector memory T cells that circulate through the tissues. CD8+ TRM cells typically localize in the epithelial layers of barrier tissues where they are optimally positioned to act as sentinels to trigger antigen-specific protection against reinfection. CD4+ TRM cells typically localize below the epithelial layers, such as below the basement membrane, and cluster in lymphoid structures designed to optimize interactions with antigen-presenting cells upon reinfection. A key feature of TRM populations is their ability to be maintained in barrier tissues for prolonged periods of time. For example, skin CD8+ TRM cells displace epidermal niches originally occupied by γδ T cells, thereby enabling their stable persistence for years. It is also clear that the long-term maintenance of TRM cells in different microenvironments is dependent on multiple tissue-specific survival cues, although the specific details are poorly understood. However, not all TRM persist over the long term. Recently, we identified a new spatial niche for the maintenance of CD8+ TRM cells in the lung, which is created at the site of tissue regeneration after injury [termed repair-associated memory depots (RAMD)]. The short-lived nature of RAMD potentially explains the short lifespans of CD8+ TRM cells in this particular tissue. Clearly, a better understanding of the niche-dependent maintenance of TRM cells will be important for the development of vaccines designed to promote barrier immunity. In this review, we discuss recent advances in our understanding of the properties and nature of tissue-specific niches that

  14. Ability of spleen cells from tumor bearing mice to transfer immunologic memory

    Energy Technology Data Exchange (ETDEWEB)

    Plavsic, B.; Jurin, M. (Zagreb Univ. (Yugoslavia)); Ugarkovic, B. (Institut Rudjer Boskovic, Zagreb (Yugoslavia))

    1983-01-01

    The ability of splenocytes from tumorous mice to transfer immunologic memory was tested. Three syngeneic experimental tumors from highly inbred strains were used; fibrosarcoma, lymphoma and Lewis lung carcinoma. Splenocytes from tumorous mice were collected after rejection of allogeneic skin which had been grafted at different stages of the tumor disease, and injected into lethally irradiated syngeneic recipients. These secondary hosts were grafted with the same allogeneic skin graft as their donors and the ability of cells transplanted from tumorous donors to transfer memory to allograft was tested. Tumorous mice seemed to have more memory cells (T lymphocytes) in their spleens than the controls.

  15. Ti–Al–O nanocrystal charge trapping memory cells fabricated by atomic layer deposition

    International Nuclear Information System (INIS)

    Cao, Zheng-Yi; Li, Ai-Dong; Li, Xin; Cao, Yan-Qiang; Wu, Di

    2014-01-01

    Charge trapping memory cells using Ti–Al–O (TAO) film as charge trapping layer and amorphous Al 2 O 3 as the tunneling and blocking layers were fabricated on Si substrates by atomic layer deposition method. As-deposited TAO films were annealed at 700 °C, 800 °C and 900 °C for 3 min in N 2 with a rapid thermal annealing process to form nanocrystals. High-resolution transmission electron microscopy and X-ray photoelectron spectroscopy were used to characterize the microstructure and band diagram of the heterostructures. The electrical characteristics and charge storage properties of the Al 2 O 3 /TAO/Al 2 O 3 /Si stack structures were also evaluated. Compared to 700 °C and 900 °C samples, the memory cells annealed at 800 °C exhibit better memory performance with larger memory window of 4.8 V at ± 6 V sweeping, higher program/erase speed and excellent endurance. - Highlights: • The charge trapping memory cells were fabricated by atomic layer deposition method. • The anneal temperature plays a key role in forming nanocrystals. • The memory cells annealed at 800 °C exhibit better memory performance. • The band alignment is beneficial to enhance the retention characteristics

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

    Directory of Open Access Journals (Sweden)

    Claire Louse Gordon

    2018-04-01

    Full Text Available Summary: The induction and maintenance of T cell memory is critical to the success of vaccines. A recently described subset of memory CD8+ T cells defined by intermediate expression of the chemokine receptor CX3CR1 was shown to have self-renewal, proliferative, and tissue-surveillance properties relevant to vaccine-induced memory. We tracked these cells when memory is sustained at high levels: memory inflation induced by cytomegalovirus (CMV and adenovirus-vectored vaccines. In mice, both CMV and vaccine-induced inflationary T cells showed sustained high levels of CX3R1int cells exhibiting an effector-memory phenotype, characteristic of inflationary pools, in early memory. In humans, CX3CR1int CD8+ T cells were strongly induced following adenovirus-vectored vaccination for hepatitis C virus (HCV (ChAd3-NSmut and during natural CMV infection and were associated with a memory phenotype similar to that in mice. These data indicate that CX3CR1int cells form an important component of the memory pool in response to persistent viruses and vaccines in both mice and humans. : Gordon et al. demonstrate that CX3CR1int peripheral memorycells are a substantial component of memory inflation induced by persistent CMVs and adenoviral vaccination. They are characterized by sustained proliferation and an effector-memory phenotype linked to these expanded CD8+ T cell memory responses. Core phenotypic features are shared by humans and mice. Keywords: cytomegalovirus, T cells, memory, adenovirus, vaccination, CX3CR1, memory inflation, mouse, human

  17. How Polycomb-Mediated Cell Memory Deals With a Changing Environment

    KAUST Repository

    Marasca, Federica; Bodega, Beatrice; Orlando, Valerio

    2018-01-01

    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.

  18. How Polycomb-Mediated Cell Memory Deals With a Changing Environment

    KAUST Repository

    Marasca, Federica

    2018-03-09

    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.

  19. Differential gene expression by integrin β7+ and β7- memory T helper cells

    Directory of Open Access Journals (Sweden)

    Yang Yee

    2004-07-01

    Full Text Available Abstract Background The cell adhesion molecule integrin α4β7 helps direct the migration of blood lymphocytes to the intestine and associated lymphoid tissues. We hypothesized that β7+ and β7- blood memory T helper cells differ in their expression of genes that play a role in the adhesion or migration of T cells. Results RNA was prepared from β7+ and β7- CD4+ CD45RA- blood T cells from nine normal human subjects and analyzed using oligonucleotide microarrays. Of 21357 genes represented on the arrays, 16 were more highly expressed in β7+ cells and 18 were more highly expressed in β7- cells (≥1.5 fold difference and adjusted P + memory/effector T cells than on β7- cells. Conclusions Memory/effector T cells that express integrin β7 have a distinct pattern of expression of a set of gene transcripts. Several of these molecules can affect cell adhesion or chemotaxis and are therefore likely to modulate the complex multistep process that regulates trafficking of CD4+ memory T cell subsets with different homing behaviors.

  20. Homeostatic proliferation fails to efficiently reactivate HIV-1 latently infected central memory CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Alberto Bosque

    2011-10-01

    Full Text Available Homeostatic proliferation ensures the longevity of central memory T-cells by inducing cell proliferation in the absence of cellular differentiation or activation. This process is governed mainly by IL-7. Central memory T-cells can also be stimulated via engagement of the T-cell receptor, leading to cell proliferation but also activation and differentiation. Using an in vitro model of HIV-1 latency, we have examined in detail the effects of homeostatic proliferation on latently infected central memory T cells. We have also used antigenic stimulation via anti-CD3/anti-CD28 antibodies and established a comparison with a homeostatic proliferation stimulus, to evaluate potential differences in how either treatment affects the dynamics of latent virus populations. First, we show that homeostatic proliferation, as induced by a combination of IL-2 plus IL-7, leads to partial reactivation of latent HIV-1 but is unable to reduce the size of the reservoir in vitro. Second, latently infected cells are able to homeostatically proliferate in the absence of viral reactivation or cell differentiation. These results indicate that IL-2 plus IL-7 may induce a detrimental effect by favoring the maintenance of the latent HIV-1 reservoir. On the other hand, antigenic stimulation efficiently reactivated latent HIV-1 in cultured central memory cells and led to depletion of the latently infected cells via virus-induced cell death.

  1. Distribution of Peripheral Memory T Follicular Helper Cells in Patients with Schistosomiasis Japonica.

    Directory of Open Access Journals (Sweden)

    Xiaojun Chen

    Full Text Available Schistosomiasis is a helminthic disease that affects more than 200 million people. An effective vaccine would be a major step towards eliminating the disease. Studies suggest that T follicular helper (Tfh cells provide help to B cells to generate the long-term humoral immunity, which would be a crucial component of successful vaccines. Thus, understanding the biological characteristics of Tfh cells in patients with schistosomiasis, which has never been explored, is essential for vaccine design.In this study, we investigated the biological characteristics of peripheral memory Tfh cells in schistosomiasis patients by flow cytometry. Our data showed that the frequencies of total and activated peripheral memory Tfh cells in patients were significantly increased during Schistosoma japonicum infection. Moreover, Tfh2 cells, which were reported to be a specific subpopulation to facilitate the generation of protective antibodies, were increased more greatly than other subpopulations of total peripheral memory Tfh cells in patients with schistosomiasis japonica. More importantly, our result showed significant correlations of the percentage of Tfh2 cells with both the frequency of plasma cells and the level of IgG antibody. In addition, our results showed that the percentage of T follicular regulatory (Tfr cells was also increased in patients with schistosomiasis.Our report is the first characterization of peripheral memory Tfh cells in schistosomasis patients, which not only provides potential targets to improve immune response to vaccination, but also is important for the development of vaccination strategies to control schistosomiasis.

  2. Atypical and classical memory B cells produce Plasmodium falciparum neutralizing antibodies

    DEFF Research Database (Denmark)

    Muellenbeck, Matthias F; Ueberheide, Beatrix; Amulic, Borko

    2013-01-01

    signs of active antibody secretion. AtM and CM were also different in their IgG gene repertoire, suggesting that they develop from different precursors. The findings provide direct evidence that natural Pf infection leads to the development of protective memory B cell antibody responses and suggest......Antibodies can protect from Plasmodium falciparum (Pf) infection and clinical malaria disease. However, in the absence of constant reexposure, serum immunoglobulin (Ig) levels rapidly decline and full protection from clinical symptoms is lost, suggesting that B cell memory is functionally impaired...... that constant immune activation rather than impaired memory function leads to the accumulation of AtM in malaria. Understanding the memory B cell response to natural Pf infection may be key to the development of a malaria vaccine that induces long-lived protection....

  3. Next generation spin torque memories

    CERN Document Server

    Kaushik, Brajesh Kumar; Kulkarni, Anant Aravind; Prajapati, Sanjay

    2017-01-01

    This book offers detailed insights into spin transfer torque (STT) based devices, circuits and memories. Starting with the basic concepts and device physics, it then addresses advanced STT applications and discusses the outlook for this cutting-edge technology. It also describes the architectures, performance parameters, fabrication, and the prospects of STT based devices. Further, moving from the device to the system perspective it presents a non-volatile computing architecture composed of STT based magneto-resistive and all-spin logic devices and demonstrates that efficient STT based magneto-resistive and all-spin logic devices can turn the dream of instant on/off non-volatile computing into reality.

  4. Qualitative and quantitative analysis of adenovirus type 5 vector-induced memory CD8 T cells

    DEFF Research Database (Denmark)

    Steffensen, Maria Abildgaard; Holst, Peter Johannes; Steengaard, Sanne Skovvang

    2013-01-01

    infection with lymphocytic choriomeningitis virus. We found that localized immunization with intermediate doses of Ad vector induce a moderate number of functional CD8 T cells, which qualitatively match those found in LCMV-infected mice. Numbers of these cells may be efficiently increased by additional...... adenoviral boosting and, importantly, the generated secondary memory cells cannot be qualitatively differentiated from those induced by primary infection with replicating virus. Quantitatively, DNA priming prior to Ad-vaccination will lead to even higher numbers of memory cells. In this case, the vaccination...

  5. The Cholinergic System Modulates Memory and Hippocampal Plasticity via Its Interactions with Non-Neuronal Cells

    Directory of Open Access Journals (Sweden)

    Sara V. Maurer

    2017-11-01

    Full Text Available Degeneration of central cholinergic neurons impairs memory, and enhancement of cholinergic synapses improves cognitive processes. Cholinergic signaling is also anti-inflammatory, and neuroinflammation is increasingly linked to adverse memory, especially in Alzheimer’s disease. Much of the evidence surrounding cholinergic impacts on the neuroimmune system focuses on the α7 nicotinic acetylcholine (ACh receptor, as stimulation of this receptor prevents many of the effects of immune activation. Microglia and astrocytes both express this receptor, so it is possible that some cholinergic effects may be via these non-neuronal cells. Though the presence of microglia is required for memory, overactivated microglia due to an immune challenge overproduce inflammatory cytokines, which is adverse for memory. Blocking these exaggerated effects, specifically by decreasing the release of tumor necrosis factor α (TNF-α, interleukin 1β (IL-1β, and interleukin 6 (IL-6, has been shown to prevent inflammation-induced memory impairment. While there is considerable evidence that cholinergic signaling improves memory, fewer studies have linked the “cholinergic anti-inflammatory pathway” to memory processes. This review will summarize the current understanding of the cholinergic anti-inflammatory pathway as it relates to memory and will argue that one mechanism by which the cholinergic system modulates hippocampal memory processes is its influence on neuroimmune function via the α7 nicotinic ACh receptor.

  6. Real-time tracking of cell cycle progression during CD8+ effector and memory T-cell differentiation.

    Science.gov (United States)

    Kinjyo, Ichiko; Qin, Jim; Tan, Sioh-Yang; Wellard, Cameron J; Mrass, Paulus; Ritchie, William; Doi, Atsushi; Cavanagh, Lois L; Tomura, Michio; Sakaue-Sawano, Asako; Kanagawa, Osami; Miyawaki, Atsushi; Hodgkin, Philip D; Weninger, Wolfgang

    2015-02-24

    The precise pathways of memory T-cell differentiation are incompletely understood. Here we exploit transgenic mice expressing fluorescent cell cycle indicators to longitudinally track the division dynamics of individual CD8(+) T cells. During influenza virus infection in vivo, naive T cells enter a CD62L(intermediate) state of fast proliferation, which continues for at least nine generations. At the peak of the anti-viral immune response, a subpopulation of these cells markedly reduces their cycling speed and acquires a CD62L(hi) central memory cell phenotype. Construction of T-cell family division trees in vitro reveals two patterns of proliferation dynamics. While cells initially divide rapidly with moderate stochastic variations of cycling times after each generation, a slow-cycling subpopulation displaying a CD62L(hi) memory phenotype appears after eight divisions. Phenotype and cell cycle duration are inherited by the progeny of slow cyclers. We propose that memory precursors cell-intrinsically modulate their proliferative activity to diversify differentiation pathways.

  7. Posttraining ablation of adult-generated olfactory granule cells degrades odor-reward memories.

    Science.gov (United States)

    Arruda-Carvalho, Maithe; Akers, Katherine G; Guskjolen, Axel; Sakaguchi, Masanori; Josselyn, Sheena A; Frankland, Paul W

    2014-11-19

    Proliferation of neural progenitor cells in the subventricular zone leads to the continuous generation of new olfactory granule cells (OGCs) throughout life. These cells synaptically integrate into olfactory bulb circuits after ∼2 weeks and transiently exhibit heightened plasticity and responses to novel odors. Although these observations suggest that adult-generated OGCs play important roles in olfactory-related memories, global suppression of olfactory neurogenesis does not typically prevent the formation of odor-reward memories, perhaps because residual OGCs can compensate. Here, we used a transgenic strategy to selectively ablate large numbers of adult-generated OGCs either before or after learning in mice. Consistent with previous studies, pretraining ablation of adult-generated OGCs did not prevent the formation of an odor-reward memory, presumably because existing OGCs can support memory formation in their absence. However, ablation of a similar cohort of adult-generated OGCs after training impaired subsequent memory expression, indicating that if these cells are available at the time of training, they play an essential role in subsequent expression of odor-reward memories. Memory impairment was associated with the loss of adult-generated OGCs that were >10 d in age and did not depend on the developmental stage in which they were generated, suggesting that, once sufficiently mature, OGCs generated during juvenility and adulthood play similar roles in the expression of odor-reward memories. Finally, ablation of adult-generated OGCs 1 month after training did not produce amnesia, indicating that adult-generated OGCs play a time-limited role in the expression of odor-reward memories. Copyright © 2014 the authors 0270-6474/14/3415793-11$15.00/0.

  8. Freeze-thaw lysates of Plasmodium falciparum-infected red blood cells induce differentiation of functionally competent regulatory T cells from memory T cells.

    Science.gov (United States)

    Finney, Olivia C; Lawrence, Emma; Gray, Alice P; Njie, Madi; Riley, Eleanor M; Walther, Michael

    2012-07-01

    In addition to naturally occurring regulatory T (nTreg) cells derived from the thymus, functionally competent Treg cells can be induced in vitro from peripheral blood lymphocytes in response to TCR stimulation with cytokine costimulation. Using these artificial stimulation conditions, both naïve as well as memory CD4(+) T cells can be converted into induced Treg (iTreg) cells, but the cellular origin of such iTreg cells in vivo or in response to more physiologic stimulation with pathogen-derived antigens is less clear. Here, we demonstrate that a freeze/thaw lysate of Plasmodium falciparum schizont extract (PfSE) can induce functionally competent Treg cells from peripheral lymphocytes in a time- and dose-dependent manner without the addition of exogenous costimulatory factors. The PfSE-mediated induction of Treg cells required the presence of nTreg cells in the starting culture. Further experiments mixing either memory or naïve T cells with antigen presenting cells and CFSE-labeled Treg cells identified CD4(+) CD45RO(+) CD25(-) memory T cells rather than Treg cells as the primary source of PfSE-induced Treg cells. Taken together, these data suggest that in the presence of nTreg cells, PfSE induces memory T cells to convert into iTreg cells that subsequently expand alongside PfSE-induced effector T cells. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Tumor cells and memory T cells converge at glycolysis: therapeutic implications.

    Science.gov (United States)

    Karthikeyan, Swathi; Geschwind, Jean-Francois; Ganapathy-Kanniappan, Shanmugasundaram

    2014-05-01

    In the immune system, activation of naïve T (Tn) cells into effector T cells (Teff) involves a metabolic switch to glycolysis to promote rapid proliferation and differentiation. In the October issue of The Journal of Clinical Investigation, Sukumar et al. have demonstrated that in CD8(+) memory T (Tems) cells glycolytic phenotype contributes to the shortened lifespan of Tems. Conversely, inhibition of glycolysis in Tems not only extended their viability but also augmented desirable properties. Notably, they also demonstrate that glycolytic inhibition during the ex vivo clonal expansion of tumor-specific Tems enhanced their antitumor function. Overall, the data suggest that an antiglycolytic strategy targeting the Tems could enhance antitumor immune response. On the other hand, cancer cells have long been known to exhibit metabolic reprogramming which involves a shift toward glycolysis (the conversion of glucose into lactate) to facilitate uninterrupted growth. Interestingly, antiglycolytic treatment of cancer cells has been known to trigger antitumor immune response as well. Taken together, it is probable that a strategy involving concurrent inhibition of glycolysis in tumor cells and Tems could promote a dual attack on cancer by inducing an effective antitumor immune response and an immunogenic chemotherapy.

  10. B-cell activating factor detected on both naïve and memory B cells in bullous pemphigoid.

    Science.gov (United States)

    Qian, Hua; Kusuhara, Masahiro; Li, Xiaoguang; Tsuruta, Daisuke; Tsuchisaka, Atsunari; Ishii, Norito; Koga, Hiroshi; Hayakawa, Taihei; Ohara, Koji; Karashima, Tadashi; Ohyama, Bungo; Ohata, Chika; Furumura, Minao; Hashimoto, Takashi

    2014-08-01

    B-cell activating factor (BAFF), an important immune regulatory cytokine, is involved in development of autoimmune diseases. Although BAFF is expressed in various cells, including dendritic cells (DCs) and monocytes, BAFF expression on B cells has not been well documented. In the present study, BAFF molecules on DCs and naïve and memory B cells in autoimmune bullous diseases, including pemphigus vulgaris, pemphigus foliaceus and bullous pemphigoid (BP), were analysed by flow cytometry. Compared with healthy controls (HC), BAFF expression on naïve and memory B cells increased significantly in BP. No difference in BAFF receptor expression in naïve and memory B cells was shown among all study groups. Furthermore, BAFF expression in both naïve and memory B cells of BP, but not HC, was detected by confocal microscopic analysis. These results implied that BAFF expressed by B cells may play a pathogenic role in autoimmune bullous diseases, particularly BP. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Early appearance of germinal center–derived memory B cells and plasma cells in blood after primary immunization

    Science.gov (United States)

    Blink, Elizabeth J.; Light, Amanda; Kallies, Axel; Nutt, Stephen L.; Hodgkin, Philip D.; Tarlinton, David M.

    2005-01-01

    Immunization with a T cell–dependent antigen elicits production of specific memory B cells and antibody-secreting cells (ASCs). The kinetic and developmental relationships between these populations and the phenotypic forms they and their precursors may take remain unclear. Therefore, we examined the early stages of a primary immune response, focusing on the appearance of antigen-specific B cells in blood. Within 1 wk, antigen-specific B cells appear in the blood with either a memory phenotype or as immunoglobulin (Ig)G1 ASCs expressing blimp-1. The memory cells have mutated VH genes; respond to the chemokine CXCL13 but not CXCL12, suggesting recirculation to secondary lymphoid organs; uniformly express B220; show limited differentiation potential unless stimulated by antigen; and develop independently of blimp-1 expression. The antigen-specific IgG1 ASCs in blood show affinity maturation paralleling that of bone marrow ASCs, raising the possibility that this compartment is established directly by blood-borne ASCs. We find no evidence for a blimp-1–expressing preplasma memory compartment, suggesting germinal center output is restricted to ASCs and B220+ memory B cells, and this is sufficient to account for the process of affinity maturation. PMID:15710653

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

    Science.gov (United States)

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

    2017-05-01

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

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

    Science.gov (United States)

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

    2015-09-08

    A simple dissolvable microneedle array (MA) platform has emerged as a promising technology for vaccine delivery, due to needle-free injection with a formulation that preserves the immunogenicity of live viral vectored vaccines dried in the MA matrix. While recent studies have focused largely on design parameters optimized to induce primary CD8(+) T cell responses, the hallmark of a vaccine is synonymous with engendering long-lasting memory. Here, we address the capacity of dried MA vaccination to programme phenotypic markers indicative of effector/memory CD8(+) T cell subsets and also responsiveness to recall antigen benchmarked against conventional intradermal (ID) injection. We show that despite a slightly lower frequency of dividing T cell receptor transgenic CD8(+) T cells in secondary lymphoid tissue at an early time point, the absolute number of CD8(+) T cells expressing an effector memory (CD62L(-)CD127(+)) and central memory (CD62L(+)CD127(+)) phenotype during peak expansion were comparable after MA and ID vaccination with a recombinant human adenovirus type 5 vector (AdHu5) encoding HIV-1 gag. Similarly, both vaccination routes generated CD8(+) memory T cell subsets detected in draining LNs for at least two years post-vaccination capable of responding to secondary antigen. These data suggest that CD8(+) T cell effector/memory generation and long-term memory is largely unaffected by physical differences in vaccine delivery to the skin via dried MA or ID suspension. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Single-Cell Memory Regulates a Neural Circuit for Sensory Behavior.

    Science.gov (United States)

    Kobayashi, Kyogo; Nakano, Shunji; Amano, Mutsuki; Tsuboi, Daisuke; Nishioka, Tomoki; Ikeda, Shingo; Yokoyama, Genta; Kaibuchi, Kozo; Mori, Ikue

    2016-01-05

    Unveiling the molecular and cellular mechanisms underlying memory has been a challenge for the past few decades. Although synaptic plasticity is proven to be essential for memory formation, the significance of "single-cell memory" still remains elusive. Here, we exploited a primary culture system for the analysis of C. elegans neurons and show that a single thermosensory neuron has an ability to form, retain, and reset a temperature memory. Genetic and proteomic analyses found that the expression of the single-cell memory exhibits inter-individual variability, which is controlled by the evolutionarily conserved CaMKI/IV and Raf pathway. The variable responses of a sensory neuron influenced the neural activity of downstream interneurons, suggesting that modulation of the sensory neurons ultimately determines the behavioral output in C. elegans. Our results provide proof of single-cell memory and suggest that the individual differences in neural responses at the single-cell level can confer individuality. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

  16. Autoimmune Memory T Helper 17 Cell Function and Expansion Are Dependent on Interleukin-23

    Directory of Open Access Journals (Sweden)

    Christopher J. Haines

    2013-05-01

    Full Text Available Interleukin-23 (IL-23 is essential for the differentiation of pathogenic effector T helper 17 (Th17 cells, but its role in memory Th17 cell responses is unclear. Using the experimental autoimmune encephalomyelitis (EAE model, we report that memory Th17 cells rapidly expanded in response to rechallenge and migrated to the CNS in high numbers, resulting in earlier onset and increased severity of clinical disease. Memory Th17 cells were generated from IL-17+ and RORγt+ precursors, and the stability of the Th17 cell phenotype depended on the amount of time allowed for the primary response. IL-23 was required for this enhanced recall response. IL-23 receptor blockade did not directly impact IL-17 production, but did impair the subsequent proliferation and generation of effectors coexpressing the Th1 cell-specific transcription factor T-bet. In addition, many genes required for cell-cycle progression were downregulated in Th17 cells that lacked IL-23 signaling, showing that a major mechanism for IL-23 in primary and memory Th17 cell responses operates via regulation of proliferation-associated pathways.

  17. Functional memory B cells and long-lived plasma cells are generated after a single Plasmodium chabaudi infection in mice.

    Directory of Open Access Journals (Sweden)

    Francis Maina Ndungu

    2009-12-01

    Full Text Available Antibodies have long been shown to play a critical role in naturally acquired immunity to malaria, but it has been suggested that Plasmodium-specific antibodies in humans may not be long lived. The cellular mechanisms underlying B cell and antibody responses are difficult to study in human infections; therefore, we have investigated the kinetics, duration and characteristics of the Plasmodium-specific memory B cell response in an infection of P. chabaudi in mice. Memory B cells and plasma cells specific for the C-terminal region of Merozoite Surface Protein 1 were detectable for more than eight months following primary infection. Furthermore, a classical memory response comprised predominantly of the T-cell dependent isotypes IgG2c, IgG2b and IgG1 was elicited upon rechallenge with the homologous parasite, confirming the generation of functional memory B cells. Using cyclophosphamide treatment to discriminate between long-lived and short-lived plasma cells, we demonstrated long-lived cells secreting Plasmodium-specific IgG in both bone marrow and in spleens of infected mice. The presence of these long-lived cells was independent of the presence of chronic infection, as removal of parasites with anti-malarial drugs had no impact on their numbers. Thus, in this model of malaria, both functional Plasmodium-specific memory B cells and long-lived plasma cells can be generated, suggesting that defects in generating these cell populations may not be the reason for generating short-lived antibody responses.

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

    Science.gov (United States)

    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.

  19. Working memory cells' behavior may be explained by cross-regional networks with synaptic facilitation.

    Directory of Open Access Journals (Sweden)

    Sergio Verduzco-Flores

    2009-08-01

    Full Text Available Neurons in the cortex exhibit a number of patterns that correlate with working memory. Specifically, averaged across trials of working memory tasks, neurons exhibit different firing rate patterns during the delay of those tasks. These patterns include: 1 persistent fixed-frequency elevated rates above baseline, 2 elevated rates that decay throughout the tasks memory period, 3 rates that accelerate throughout the delay, and 4 patterns of inhibited firing (below baseline analogous to each of the preceding excitatory patterns. Persistent elevated rate patterns are believed to be the neural correlate of working memory retention and preparation for execution of behavioral/motor responses as required in working memory tasks. Models have proposed that such activity corresponds to stable attractors in cortical neural networks with fixed synaptic weights. However, the variability in patterned behavior and the firing statistics of real neurons across the entire range of those behaviors across and within trials of working memory tasks are typical not reproduced. Here we examine the effect of dynamic synapses and network architectures with multiple cortical areas on the states and dynamics of working memory networks. The analysis indicates that the multiple pattern types exhibited by cells in working memory networks are inherent in networks with dynamic synapses, and that the variability and firing statistics in such networks with distributed architectures agree with that observed in the cortex.

  20. Programming voltage reduction in phase change memory cells with tungsten trioxide bottom heating layer/electrode

    International Nuclear Information System (INIS)

    Rao Feng; Song Zhitang; Gong Yuefeng; Wu Liangcai; Feng Songlin; Chen, Bomy

    2008-01-01

    A phase change memory cell with tungsten trioxide bottom heating layer/electrode is investigated. The crystalline tungsten trioxide heating layer promotes the temperature rise in the Ge 2 Sb 2 Te 5 layer which causes the reduction in the reset voltage compared to a conventional phase change memory cell. Theoretical thermal simulation and calculation for the reset process are applied to understand the thermal effect of the tungsten trioxide heating layer/electrode. The improvement in thermal efficiency of the PCM cell mainly originates from the low thermal conductivity of the crystalline tungsten trioxide material.

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

    Directory of Open Access Journals (Sweden)

    Sema eKurtulus

    2013-01-01

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

  2. Multilevel SOT-MRAM Cell with a Novel Sensing Scheme for High-Density Memory Applications

    DEFF Research Database (Denmark)

    Zeinali, Behzad; Esmaeili, Mahsa; Madsen, Jens Kargaard

    2017-01-01

    This paper presents a multilevel spin-orbit torque magnetic random access memory (SOT-MRAM). The conventional SOT-MRAMs enables a reliable and energy efficient write operation. However, these cells require two access transistors per cell, hence the efficiency of the SOTMRAMs can be questioned in ...

  3. Working Memory in Children With Neurocognitive Effects From Sickle Cell Disease: Contributions of the Central Executive and Processing Speed

    Science.gov (United States)

    Smith, Kelsey E.; Schatz, Jeffrey

    2017-01-01

    Children with sickle cell disease (SCD) are at risk for working memory deficits due to multiple disease processes. We assessed working memory abilities and related functions in 32 school-age children with SCD and 85 matched comparison children using Baddeley’s working memory model as a framework. Children with SCD performed worse than controls for working memory, central executive function, and processing/rehearsal speed. Central executive function was found to mediate the relationship between SCD status and working memory, but processing speed did not. Cognitive remediation strategies that focus on central executive processes may be important for remediating working memory deficits in SCD. PMID:27759435

  4. Different Subsets of T Cells, Memory, Effector Functions, and CAR-T Immunotherapy.

    Science.gov (United States)

    Golubovskaya, Vita; Wu, Lijun

    2016-03-15

    This review is focused on different subsets of T cells: CD4 and CD8, memory and effector functions, and their role in CAR-T therapy--a cellular adoptive immunotherapy with T cells expressing chimeric antigen receptor. The CAR-T cells recognize tumor antigens and induce cytotoxic activities against tumor cells. Recently, differences in T cell functions and the role of memory and effector T cells were shown to be important in CAR-T cell immunotherapy. The CD4⁺ subsets (Th1, Th2, Th9, Th17, Th22, Treg, and Tfh) and CD8⁺ memory and effector subsets differ in extra-cellular (CD25, CD45RO, CD45RA, CCR-7, L-Selectin [CD62L], etc.); intracellular markers (FOXP3); epigenetic and genetic programs; and metabolic pathways (catabolic or anabolic); and these differences can be modulated to improve CAR-T therapy. In addition, CD4⁺ Treg cells suppress the efficacy of CAR-T cell therapy, and different approaches to overcome this suppression are discussed in this review. Thus, next-generation CAR-T immunotherapy can be improved, based on our knowledge of T cell subsets functions, differentiation, proliferation, and signaling pathways to generate more active CAR-T cells against tumors.

  5. Different Subsets of T Cells, Memory, Effector Functions, and CAR-T Immunotherapy

    Directory of Open Access Journals (Sweden)

    Vita Golubovskaya

    2016-03-01

    Full Text Available This review is focused on different subsets of T cells: CD4 and CD8, memory and effector functions, and their role in CAR-T therapy––a cellular adoptive immunotherapy with T cells expressing chimeric antigen receptor. The CAR-T cells recognize tumor antigens and induce cytotoxic activities against tumor cells. Recently, differences in T cell functions and the role of memory and effector T cells were shown to be important in CAR-T cell immunotherapy. The CD4+ subsets (Th1, Th2, Th9, Th17, Th22, Treg, and Tfh and CD8+ memory and effector subsets differ in extra-cellular (CD25, CD45RO, CD45RA, CCR-7, L-Selectin [CD62L], etc.; intracellular markers (FOXP3; epigenetic and genetic programs; and metabolic pathways (catabolic or anabolic; and these differences can be modulated to improve CAR-T therapy. In addition, CD4+ Treg cells suppress the efficacy of CAR-T cell therapy, and different approaches to overcome this suppression are discussed in this review. Thus, next-generation CAR-T immunotherapy can be improved, based on our knowledge of T cell subsets functions, differentiation, proliferation, and signaling pathways to generate more active CAR-T cells against tumors.

  6. Nonvolatile Memory Technology for Space Applications

    Science.gov (United States)

    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.

  7. Working Memory in Children With Neurocognitive Effects From Sickle Cell Disease: Contributions of the Central Executive and Processing Speed

    OpenAIRE

    Smith, Kelsey E.; Schatz, Jeffrey

    2016-01-01

    Children with sickle cell disease (SCD) are at risk for working memory deficits due to multiple disease processes. We assessed working memory abilities and related functions in 32 school-age children with SCD and 85 matched comparison children using Baddeley’s working memory model as a framework. Children with SCD performed worse than controls for working memory, central executive function, and processing/rehearsal speed. Central executive function was found to mediate the relationship betwee...

  8. Rapid allergen-induced interleukin-17 and interferon-γ secretion by skin-resident memory CD8(+) T cells

    DEFF Research Database (Denmark)

    Schmidt, Jonas D; Ahlström, Malin G; Johansen, Jeanne D

    2017-01-01

    , the mechanisms whereby TRM cells induce rapid recall responses need further investigation. OBJECTIVES: To study whether contact allergens induce local and/or global memory, and to determine the mechanisms involved in memory responses in the skin. METHODS: To address these questions, we analysed responses......BACKGROUND: Skin-resident memory T (TRM ) cells are associated with immunological memory in the skin. Whether immunological memory responses to allergens in the skin are solely localized to previously allergen-exposed sites or are present globally in the skin is not clear. Furthermore......, long-lasting local memory and a weaker, temporary global immunological memory response to the allergen that is mediated by IL-17A-producing and IFN-γ-producing CD8(+) TRM cells....

  9. Inducible colitis-associated glycome capable of stimulating the proliferation of memory CD4+ T cells.

    Science.gov (United States)

    Nishida, Atsushi; Nagahama, Kiyotaka; Imaeda, Hirotsugu; Ogawa, Atsuhiro; Lau, Cindy W; Kobayashi, Taku; Hisamatsu, Tadakazu; Preffer, Frederic I; Mizoguchi, Emiko; Ikeuchi, Hiroki; Hibi, Toshifumi; Fukuda, Minoru; Andoh, Akira; Blumberg, Richard S; Mizoguchi, Atsushi

    2012-12-17

    Immune responses are modified by a diverse and abundant repertoire of carbohydrate structures on the cell surface, which is known as the glycome. In this study, we propose that a unique glycome that can be identified through the binding of galectin-4 is created on local, but not systemic, memory CD4+ T cells under diverse intestinal inflammatory conditions, but not in the healthy state. The colitis-associated glycome (CAG) represents an immature core 1-expressing O-glycan. Development of CAG may be mediated by down-regulation of the expression of core-2 β1,6-N-acetylglucosaminyltransferase (C2GnT) 1, a key enzyme responsible for the production of core-2 O-glycan branch through addition of N-acetylglucosamine (GlcNAc) to a core-1 O-glycan structure. Mechanistically, the CAG seems to contribute to super raft formation associated with the immunological synapse on colonic memory CD4+ T cells and to the consequent stabilization of protein kinase C θ activation, resulting in the stimulation of memory CD4+ T cell expansion in the inflamed intestine. Functionally, CAG-mediated CD4+ T cell expansion contributes to the exacerbation of T cell-mediated experimental intestinal inflammations. Therefore, the CAG may be an attractive therapeutic target to specifically suppress the expansion of effector memory CD4+ T cells in intestinal inflammation such as that seen in inflammatory bowel disease.

  10. Contribution of non-volatile and aroma fractions to in-mouth sensory properties of red wines: wine reconstitution strategies and sensory sorting task.

    Science.gov (United States)

    Sáenz-Navajas, María-Pilar; Campo, Eva; Avizcuri, José Miguel; Valentin, Dominique; Fernández-Zurbano, Purificación; Ferreira, Vicente

    2012-06-30

    This work explores to what extent the aroma or the non-volatile fractions of red wines are responsible for the overall flavor differences perceived in-mouth. For this purpose, 14 samples (4 commercial and 10 reconstituted wines), were sorted by a panel of 30 trained assessors according to their sensory in-mouth similarities. Reconstituted wines were prepared by adding the same volatile fraction (coming from a red wine) to the non-volatile fraction of 10 different red wines showing large differences in perceived astringency. Sorting was performed under three different conditions: (a) no aroma perception: nose-close condition (NA), (b) retronasal aroma perception only (RA), and (c) allowing retro- and involuntary orthonasal aroma perception (ROA). Similarity estimates were derived from the sorting and submitted to multidimensional scaling (MDS) followed by hierarchical cluster analysis (HCA). Results have clearly shown that, globally, aroma perception is not the major driver of the in-mouth sensory perception of red wine, which is undoubtedly primarily driven by the perception of astringency and by the chemical compounds causing it, particularly protein precipitable proanthocyanidins (PAs). However, aroma perception plays a significant role on the perception of sweetness and bitterness. The impact of aroma seems to be more important whenever astringency, total polyphenols and protein precipitable PAs levels are smaller. Results also indicate that when a red-black fruit odor nuance is clearly perceived in conditions in which orthonasal odor perception is allowed, a strong reduction in astringency takes place. Such red-black fruit odor nuance seems to be the result of a specific aroma release pattern as a consequence of the interaction between aroma compounds and the non-volatile matrix. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Analysis of Non-Volatile Chemical Constituents of Menthae Haplocalycis Herba by Ultra-High Performance Liquid Chromatography-High Resolution Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Lu-Lu Xu

    2017-10-01

    Full Text Available Menthae Haplocalycis herba, one kind of Chinese edible herbs, has been widely utilized for the clinical use in China for thousands of years. Over the last decades, studies on chemical constituents of Menthae Haplocalycis herba have been widely performed. However, less attention has been paid to non-volatile components which are also responsible for its medical efficacy than the volatile constituents. Therefore, a rapid and sensitive method was developed for the comprehensive identification of the non-volatile constituents in Menthae Haplocalycis herba using ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap. Separation was performed with Acquity UPLC® BEH C18 column (2.1 mm × 100 mm, 1.7 μm with 0.2% formic acid aqueous solution and acetonitrile as the mobile phase under gradient conditions. Based on the accurate mass measurement (<5 ppm, MS/MS fragmentation patterns and different chromatographic behaviors, a total of 64 compounds were unambiguously or tentatively characterized, including 30 flavonoids, 20 phenolic acids, 12 terpenoids and two phenylpropanoids. Finally, target isolation of three compounds named Acacetin, Rosmarinic acid and Clemastanin A (first isolated from Menthae Haplocalycis herba were performed based on the obtained results, which further confirmed the deduction of fragmentation patterns and identified the compounds profile in Menthae Haplocalycis herba. Our research firstly systematically elucidated the non-volatile components of Menthae Haplocalycis herba, which laid the foundation for further pharmacological and metabolic studies. Meanwhile, our established method was useful and efficient to screen and identify targeted constituents from traditional Chinese medicine extracts.

  12. Low-cost fabrication of ternary CuInSe{sub 2} nanocrystals by colloidal route using a novel combination of volatile and non-volatile capping agents

    Energy Technology Data Exchange (ETDEWEB)

    Chawla, Parul; Narain Sharma, Shailesh, E-mail: shailesh@nplindia.org; Singh, Son

    2014-11-15

    Wet-route synthesis of CuInSe{sub 2} (CISe) nanocrystals has been envisaged with the utilization of the unique combination of coordinating ligand and non coordinating solvent. Our work demonstrates the formation of a single-phase, nearly stoichiometric and monodispersive, stable and well-passivated colloidal ternary CISe nanocrystals (band gap (E{sub g})∼1.16 eV) using a novel combination of ligands; viz. volatile arylamine aniline and non-volatile solvent 1-octadecene. The synthesis and growth conditions have been manoeuvred using the colligative properties of the mixture and thus higher growth temperature (∼250 °C) could be attained that promoted larger grain growth. The beneficial influence of the capping agents (aniline and 1-octadecene) on the properties of chalcopyrite nanocrystals has enabled us to pictorally model the structural, morphological and optoelectronic aspects of CISe nanoparticles. - Graphical abstract: Without resorting to any post-selenization process and using the colligative properties of the mixture comprising of volatile aniline and non-volatile 1-octadecene to manoeuvre the growth conditions to promote Ostwald ripening, a single phase, monodispersive and nearly stoichiometric ternary CISe nanocrystals are formed by wet-synthesis route. - Highlights: • Wet-route synthesis of CISe nanocrystals reported without post-selenization process. • Single-phase, stable and well-passivated colloidal ternary CISe nanocrystals formed. • Novel combination of capping agents: volatile aniline and non-volatile 1-octadecene. • Higher growth temperature attained using the colligative properties of the mixture. • Metallic salts presence explains exp. and theoretical boiling point difference.

  13. Medial Entorhinal Cortex Lesions Only Partially Disrupt Hippocampal Place Cells and Hippocampus-Dependent Place Memory

    Directory of Open Access Journals (Sweden)

    Jena B. Hales

    2014-11-01

    Full Text Available The entorhinal cortex provides the primary cortical projections to the hippocampus, a brain structure critical for memory. However, it remains unclear how the precise firing patterns of medial entorhinal cortex (MEC cells influence hippocampal physiology and hippocampus-dependent behavior. We found that complete bilateral lesions of the MEC resulted in a lower proportion of active hippocampal cells. The remaining active cells had place fields, but with decreased spatial precision and decreased long-term spatial stability. In addition, MEC rats were as impaired in the water maze as hippocampus rats, while rats with combined MEC and hippocampal lesions had an even greater deficit. However, MEC rats were not impaired on other hippocampus-dependent tasks, including those in which an object location or context was remembered. Thus, the MEC is not necessary for all types of spatial coding or for all types of hippocampus-dependent memory, but it is necessary for the normal acquisition of place memory.

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

    Science.gov (United States)

    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.

  15. Conventional CD4+ T cells present bacterial antigens to induce cytotoxic and memory CD8+ T cell responses.

    Science.gov (United States)

    Cruz-Adalia, Aránzazu; Ramirez-Santiago, Guillermo; Osuna-Pérez, Jesús; Torres-Torresano, Mónica; Zorita, Virgina; Martínez-Riaño, Ana; Boccasavia, Viola; Borroto, Aldo; Martínez Del Hoyo, Gloria; González-Granado, José María; Alarcón, Balbino; Sánchez-Madrid, Francisco; Veiga, Esteban

    2017-11-17

    Bacterial phagocytosis and antigen cross-presentation to activate CD8 + T cells are principal functions of professional antigen presenting cells. However, conventional CD4 + T cells also capture and kill bacteria from infected dendritic cells in a process termed transphagocytosis (also known as transinfection). Here, we show that transphagocytic T cells present bacterial antigens to naive CD8 + T cells, which proliferate and become cytotoxic in response. CD4 + T-cell-mediated antigen presentation also occurs in vivo in the course of infection, and induces the generation of central memory CD8 + T cells with low PD-1 expression. Moreover, transphagocytic CD4 + T cells induce protective anti-tumour immune responses by priming CD8 + T cells, highlighting the potential of CD4 + T cells as a tool for cancer immunotherapy.

  16. Therapeutic effect of mesenchymal multipotent stromal cells on memory in animals with Alzheimer-type neurodegeneration.

    Science.gov (United States)

    Bobkova, N V; Poltavtseva, R A; Samokhin, A N; Sukhikh, G T

    2013-11-01

    Transplantation of human mesenchymal multipotent stromal cells improved spatial memory in bulbectomized mice with Alzheimer-type neurodegeneration. The positive effect was observed in 1 month after intracerebral transplantation and in 3 months after systemic injection of mesenchymal multipotent stromal cells. No cases of malignant transformation were noted. These findings indicate prospects of using mesenchymal multipotent stromal cells for the therapy of Alzheimer disease and the possibility of their systemic administration for attaining the therapeutic effect.

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

    Directory of Open Access Journals (Sweden)

    Zeyu Chen

    2017-09-01

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

  18. Low interleukin-2 concentration favors generation of early memory T cells over effector phenotypes during chimeric antigen receptor T-cell expansion.

    Science.gov (United States)

    Kaartinen, Tanja; Luostarinen, Annu; Maliniemi, Pilvi; Keto, Joni; Arvas, Mikko; Belt, Heini; Koponen, Jonna; Loskog, Angelica; Mustjoki, Satu; Porkka, Kimmo; Ylä-Herttuala, Seppo; Korhonen, Matti

    2017-06-01

    Adoptive T-cell therapy offers new options for cancer treatment. Clinical results suggest that T-cell persistence, depending on T-cell memory, improves efficacy. The use of interleukin (IL)-2 for in vitro T-cell expansion is not straightforward because it drives effector T-cell differentiation but does not promote the formation of T-cell memory. We have developed a cost-effective expansion protocol for chimeric antigen receptor (CAR) T cells with an early memory phenotype. Lymphocytes were transduced with third-generation lentiviral vectors and expanded using CD3/CD28 microbeads. The effects of altering the IL-2 supplementation (0-300 IU/mL) and length of expansion (10-20 days) on the phenotype of the T-cell products were analyzed. High IL-2 levels led to a decrease in overall generation of early memory T cells by both decreasing central memory T cells and augmenting effectors. T memory stem cells (T SCM , CD95 + CD45RO - CD45RA + CD27 + ) were present variably during T-cell expansion. However, their presence was not IL-2 dependent but was linked to expansion kinetics. CD19-CAR T cells generated in these conditions displayed in vitro antileukemic activity. In summary, production of CAR T cells without any cytokine supplementation yielded the highest proportion of early memory T cells, provided a 10-fold cell expansion and the cells were functionally potent. The number of early memory T cells in a T-cell preparation can be increased by simply reducing the amount of IL-2 and limiting the length of T-cell expansion, providing cells with potentially higher in vivo performance. These findings are significant for robust and cost-effective T-cell manufacturing. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  19. Understanding the slow depletion of memory CD4+ T cells in HIV infection.

    Directory of Open Access Journals (Sweden)

    Andrew Yates

    2007-05-01

    Full Text Available The asymptomatic phase of HIV infection is characterised by a slow decline of peripheral blood CD4(+ T cells. Why this decline is slow is not understood. One potential explanation is that the low average rate of homeostatic proliferation or immune activation dictates the pace of a "runaway" decline of memory CD4(+ T cells, in which activation drives infection, higher viral loads, more recruitment of cells into an activated state, and further infection events. We explore this hypothesis using mathematical models.Using simple mathematical models of the dynamics of T cell homeostasis and proliferation, we find that this mechanism fails to explain the time scale of CD4(+ memory T cell loss. Instead it predicts the rapid attainment of a stable set point, so other mechanisms must be invoked to explain the slow decline in CD4(+ cells.A runaway cycle in which elevated CD4(+ T cell activation and proliferation drive HIV production and vice versa cannot explain the pace of depletion during chronic HIV infection. We summarize some alternative mechanisms by which the CD4(+ memory T cell homeostatic set point might slowly diminish. While none are mutually exclusive, the phenomenon of viral rebound, in which interruption of antiretroviral therapy causes a rapid return to pretreatment viral load and T cell counts, supports the model of virus adaptation as a major force driving depletion.

  20. A novel whole-cell mechanism for long-term memory enhancement.

    Directory of Open Access Journals (Sweden)

    Iris Reuveni

    Full Text Available Olfactory-discrimination learning was shown to induce a profound long-lasting enhancement in the strength of excitatory and inhibitory synapses of pyramidal neurons in the piriform cortex. Notably, such enhancement was mostly pronounced in a sub-group of neurons, entailing about a quarter of the cell population. Here we first show that the prominent enhancement in the subset of cells is due to a process in which all excitatory synapses doubled their strength and that this increase was mediated by a single process in which the AMPA channel conductance was doubled. Moreover, using a neuronal-network model, we show how such a multiplicative whole-cell synaptic strengthening in a sub-group of cells that form a memory pattern, sub-serves a profound selective enhancement of this memory. Network modeling further predicts that synaptic inhibition should be modified by complex learning in a manner that much resembles synaptic excitation. Indeed, in a subset of neurons all GABAA-receptors mediated inhibitory synapses also doubled their strength after learning. Like synaptic excitation, Synaptic inhibition is also enhanced by two-fold increase of the single channel conductance. These findings suggest that crucial learning induces a multiplicative increase in strength of all excitatory and inhibitory synapses in a subset of cells, and that such an increase can serve as a long-term whole-cell mechanism to profoundly enhance an existing Hebbian-type memory. This mechanism does not act as synaptic plasticity mechanism that underlies memory formation but rather enhances the response of already existing memory. This mechanism is cell-specific rather than synapse-specific; it modifies the channel conductance rather than the number of channels and thus has the potential to be readily induced and un-induced by whole-cell transduction mechanisms.

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

    Science.gov (United States)

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

    2013-11-13

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

  2. Evaluation of profile and functionality of memory T cells in pulmonary tuberculosis.

    Science.gov (United States)

    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

  3. The role of natural killer T cells in dendritic cell licensing, cross-priming and memory CD8+ T cell generation

    Directory of Open Access Journals (Sweden)

    Catherine eGottschalk

    2015-07-01

    Full Text Available New vaccination strategies focus on achieving CD8+ T cell (CTL immunity rather than on induction of protective antibody responses. While the requirement of CD4+ T (Th cell help in dendritic cell (DC activation and licensing, and in CTL memory induction has been described in several disease models, CTL responses may occur in a Th cell help independent manner. Natural Killer T cells (NKT cells can substitute for Th cell help and license DC as well. NKT cells produce a broad spectrum of Th1 and Th2 cytokines, thereby inducing a similar set of costimulatory molecules and cytokines in DC. This form of licensing differs from Th cell help by inducing other chemokines: while Th cell licensed DC produce CCR5 ligands, NKT cell-licensed DC produce CCL17 which attracts CCR4+ CD8+ T cells for subsequent activation. It has recently been shown that iNKT cells do not only enhance immune responses against bacterial pathogens or parasites, but also play a role in viral infections. The inclusion of NKT cell ligands in Influenza virus vaccines enhanced memory CTL generation and protective immunity in a mouse model. This review will focus on the role of iNKT cells in the cross-talk with cross-priming DC and memory CD8+ T cell formation.

  4. Effects of Asiatic Acid on Spatial Working Memory and Cell Proliferation in the Adult Rat Hippocampus

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    Apiwat Sirichoat

    2015-10-01

    Full Text Available Asiatic acid is a pentacyclic triterpene from Centella asiatica. Previous studies have reported that asiatic acid exhibits antioxidant and neuroprotective activities in cell culture. It also prevents memory deficits in animal models. The objective of this study was to investigate the relationship between spatial working memory and changes in cell proliferation within the hippocampus after administration of asiatic acid to male Spraque-Dawley rats. Control rats received vehicle (propylene glycol while treated rats received asiatic acid (30 mg/kg orally for 14 or 28 days. Spatial memory was determined using the novel object location (NOL test. In animals administered asiatic acid for both 14 and 28 days, the number of Ki-67 positive cells in the subgranular zone of the dentate gyrus was significantly higher than in control animals. This was associated with a significant increase in their ability to discriminate between novel and familiar object locations in a novel object discrimination task, a hippocampus-dependent spatial memory test. Administration of asiatic acid also significantly increased doublecortin (DCX and Notch1 protein levels in the hippocampus. These findings demonstrate that asiatic acid treatment may be a potent cognitive enhancer which improves hippocampal-dependent spatial memory, likely by increasing hippocampal neurogenesis.

  5. SPATIAL MEMORY IMPAIRMENT AND HIPPOCAMPAL CELL LOSS INDUCED BY OKADAIC ACID (EXPERIMENTAL STUDY).

    Science.gov (United States)

    Chighladze, M; Dashniani, M; Beselia, G; Kruashvili, L; Naneishvili, T

    2016-01-01

    In the present study, we evaluated and compared effect of intracerebroventricular (ICV) and intrahippocampal bilateral microinjection of okadaic acid (OA) on spatial memory function assessed in one day water maze paradigm and hippocampal structure in rats. Rats were divided in following groups: Control(icv) - rats injected with ICV and aCSF; Control(hipp) - rats injected intrahippocampally with aCSF; OAicv - rats injected with ICV and OA; OAhipp - rats injected intrahippocampally with OA. Nissl staining of hippocampal sections showed that the pyramidal cell loss in OAhipp group is significantly higher than that in the OAicv. The results of behavioral experiments showed that ICV or intrahippocampal bilateral microinjection of OA did not affect learning process and short-term spatial memory but induced impairment in spatial long-term memory assessed in probe test performance 24 h after training. OA-induced spatial memory impairment may be attributed to the hippocampal cell death. Based on these results OA induced memory deficit and hippocampal cell loss in rat may be considered as a potential animal model for preclinical evaluation of antidementic drug activity.

  6. Transplanted Bone Marrow Mesenchymal Stem Cells Improve Memory in Rat Models of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Parvin Babaei

    2012-01-01

    Full Text Available The present study aims to evaluate the effect of bone marrow mesenchymal stem cells (MSCs grafts on cognition deficit in chemically and age-induced Alzheimer's models of rats. In the first experiments aged animals (30 months were tested in Morris water maze (MWM and divided into two groups: impaired memory and unimpaired memory. Impaired groups were divided into two groups and cannulated bilaterally at the CA1 of the hippocampus for delivery of mesenchymal stem cells (500×103/ and PBS (phosphate buffer saline. In the second experiment, Ibotenic acid (Ibo was injected bilaterally into the nucleus basalis magnocellularis (NBM of young rats (3 months and animals were tested in MWM. Then, animals with memory impairment received the following treatments: MSCs (500×103/ and PBS. Two months after the treatments, cognitive recovery was assessed by MWM in relearning paradigm in both experiments. Results showed that MSCs treatment significantly increased learning ability and memory in both age- and Ibo-induced memory impairment. Adult bone marrow mesenchymal stem cells show promise in treating cognitive decline associated with aging and NBM lesions.

  7. The relation between T-cell expression of LFA-1 and immunological memory

    DEFF Research Database (Denmark)

    Hviid, L; Odum, N; Theander, T G

    1993-01-01

    Antibodies against isotypes of the leucocyte common antigen (LCA, CD45) can be used to identify largely reciprocal subsets of human peripheral T cells, characterized by differential ability to respond to recall antigen in vitro. The transition from naive, unprimed T cells to memory cells capable...... of responding to recall stimulating has been associated with a switch in surface expression of CD45 from the CD45RA isotype to CD45RO. It has been proposed that this transition is accompanied by the coordinated up-regulation of a number of cell-surface molecules involved in cellular adhesion and/or activation......, including the leucocyte function-associated antigens (LFA). In the present study we have examined the expression of LFA-1 on subsets of human peripheral T cells, and related it to the expression of markers of cellular activation and CD45 isotypes, and thus to immunological memory. Our results suggest...

  8. High-performance and low-power rewritable SiOx 1 kbit one diode-one resistor crossbar memory array.

    Science.gov (United States)

    Wang, Gunuk; Lauchner, Adam C; Lin, Jian; Natelson, Douglas; Palem, Krishna V; Tour, James M

    2013-09-14

    An entire 1-kilobit crossbar device based upon SiOx resistive memories with integrated diodes has been made. The SiOx -based one diode-one resistor device system has promise to satisfy the prerequisite conditions for next generation non-volatile memory applications. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Circulating CXCR5+CD4+ T Follicular-Like Helper Cell and Memory B Cell Responses to Human Papillomavirus Vaccines

    Science.gov (United States)

    Matsui, Ken; Adelsberger, Joseph W.; Kemp, Troy J.; Baseler, Michael W.; Ledgerwood, Julie E.; Pinto, Ligia A.

    2015-01-01

    Through the interaction of T follicular helper (Tfh) cells and B cells, efficacious vaccines can generate high-affinity, pathogen-neutralizing antibodies, and memory B cells. Using CXCR5, CXCR3, CCR6, CCR7, PD1, and ICOS as markers, Tfh-like cells can be identified in the circulation and be classified into three functionally distinct subsets that are PD1+ICOS+, PD1+ ICOS-, or PD1-ICOS-. We used these markers to identify different subsets of CXCR5+CD4+ Tfh-like cells in response to highly immunogenic and efficacious vaccines for human papillomaviruses (HPV): Cervarix and Gardasil. In this small study, we used PBMC samples from 11 Gardasil recipients, and 8 Cervarix recipients from the Vaccine Research Center 902 Study to examine the induction of circulating Tfh-like cells and IgD-CD38HiCD27+ memory B cells by flow cytometry. PD1+ICOS+ CXCR3+CCR6-CXCR5+CD4+ (Tfh1-like) cells were induced and peaked on Day (D) 7 post-first vaccination, but not as much on D7 post-third vaccination. We also observed a trend toward increase in PD1+ICOS+ CXCR3-CCR6-CXCR5+CD4+ (Tfh2-like) cells for both vaccines, and PD1+ICOS+ CXCR3-CCR6+CXCR5+CD4+ (Tfh17-like) subset was induced by Cervarix post-first vaccination. There were also minimal changes in the other cellular subsets. In addition, Cervarix recipients had more memory B cells post-first vaccination than did Gardasil recipients at D14 and D30. We found frequencies of memory B cells at D30 correlated with anti-HPV16 and 18 antibody titers from D30, and the induction levels of memory B cells at D30 and PD1+ICOS+Tfh1-like cells at D7 post-first vaccination correlated for Cervarix. Our study showed that induction of circulating CXCR5+CD4+ Tfh-like subsets can be detected following immunization with HPV vaccines, and potentially be useful as a marker of immunogenicity of vaccines. However, further investigations should be extended to different cohorts with larger sample size to better understand the functions of these T cells, as well as

  10. Tissue-resident memory CD8+ T cells continuously patrol skin epithelia to quickly recognize local antigen

    NARCIS (Netherlands)

    Ariotti, S.; Beltman, J.B.; Chodaczek, G.; Hoekstra, M.E.; van Beek, A.E.; Gomez-Eerland, R.; Ritsma, L.; van Rheenen, J.; Maree, A.F.; Zal, T.; de Boer, R.J.; Haanen, J.B.; Schumacher, T.N.

    2012-01-01

    Recent work has demonstrated that following the clearance of infection a stable population of memory T cells remains present in peripheral organs and contributes to the control of secondary infections. However, little is known about how tissue-resident memory T cells behave in situ and how they

  11. Diet-induced obesity does not impact the generation and maintenance of primary memory CD8 T cells.

    Science.gov (United States)

    Khan, Shaniya H; Hemann, Emily A; Legge, Kevin L; Norian, Lyse A; Badovinac, Vladimir P

    2014-12-15

    The extent to which obesity compromises the differentiation and maintenance of protective memory CD8 T cell responses and renders obese individuals susceptible to infection remains unknown. In this study, we show that diet-induced obesity did not impact the maintenance of pre-existing memory CD8 T cells, including acquisition of a long-term memory phenotype (i.e., CD27(hi), CD62L(hi), KLRG1(lo)) and function (i.e., cytokine production, secondary expansion, and memory CD8 T cell-mediated protection). Additionally, obesity did not influence the differentiation and maintenance of newly evoked memory CD8 T cell responses in inbred and outbred hosts generated in response to different types of systemic (LCMV, L. monocytogenes) and/or localized (influenza virus) infections. Interestingly, the rate of naive-to-memory CD8 T cell differentiation after a peptide-coated dendritic cell immunization was similar in lean and obese hosts, suggesting that obesity-associated inflammation, unlike pathogen- or adjuvant-induced inflammation, did not influence the development of endogenous memory CD8 T cell responses. Therefore, our studies reveal that the obese environment does not influence the development or maintenance of memory CD8 T cell responses that are either primed before or after obesity is established, a surprising notion with important implications for future studies aiming to elucidate the role obesity plays in host susceptibility to infections. Copyright © 2014 by The American Association of Immunologists, Inc.

  12. Evaluation of non-volatile metabolites in beer stored at high temperature and utility as an accelerated method to predict flavour stability.

    Science.gov (United States)

    Heuberger, Adam L; Broeckling, Corey D; Sedin, Dana; Holbrook, Christian; Barr, Lindsay; Kirkpatrick, Kaylyn; Prenni, Jessica E

    2016-06-01

    Flavour stability is vital to the brewing industry as beer is often stored for an extended time under variable conditions. Developing an accelerated model to evaluate brewing techniques that affect flavour stability is an important area of research. Here, we performed metabolomics on non-volatile compounds in beer stored at 37 °C between 1 and 14 days for two beer types: an amber ale and an India pale ale. The experiment determined high temperature to influence non-volatile metabolites, including the purine 5-methylthioadenosine (5-MTA). In a second experiment, three brewing techniques were evaluated for improved flavour stability: use of antioxidant crowns, chelation of pro-oxidants, and varying plant content in hops. Sensory analysis determined the hop method was associated with improved flavour stability, and this was consistent with reduced 5-MTA at both regular and high temperature storage. Future studies are warranted to understand the influence of 5-MTA on flavour and aging within different beer types. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Voltage control of metal-insulator transition and non-volatile ferroelastic switching of resistance in VOx/PMN-PT heterostructures.

    Science.gov (United States)

    Nan, Tianxiang; Liu, Ming; Ren, Wei; Ye, Zuo-Guang; Sun, Nian X

    2014-08-04

    The central challenge in realizing electronics based on strongly correlated electronic states, or 'Mottronics', lies in finding an energy efficient way to switch between the distinct collective phases with a control voltage in a reversible and reproducible manner. In this work, we demonstrate that a voltage-impulse-induced ferroelastic domain switching in the (011)-oriented 0.71Pb(Mg1/3Nb2/3)O3-0.29PbTiO3 (PMN-PT) substrates allows a robust non-volatile tuning of the metal-insulator transition in the VOx films deposited onto them. In such a VOx/PMN-PT heterostructure, the unique two-step electric polarization switching covers up to 90% of the entire poled area and contributes to a homogeneous in-plane anisotropic biaxial strain, which, in turn, enables the lattice changes and results in the suppression of metal-insulator transition in the mechanically coupled VOx films by 6 K with a resistance change up to 40% over a broad range of temperature. These findings provide a framework for realizing in situ and non-volatile tuning of strain-sensitive order parameters in strongly correlated materials, and demonstrate great potentials in delivering reconfigurable, compactable, and energy-efficient electronic devices.

  14. Deficiency in memory B cell compartment in a patient with infertility and recurrent pregnancy losses.

    Science.gov (United States)

    Sung, N; Byeon, H J; Garcia, M D Salazar; Skariah, A; Wu, L; Dambaeva, S; Beaman, K; Gilman-Sachs, A; Kwak-Kim, J

    2016-11-01

    Alterations in normal balance of B cell subsets have been reported in various rheumatic diseases. In this study, we report a woman with a history of recurrent pregnancy losses (RPL) and infertility who had low levels of memory B cells. A 35-year-old woman with a history of RPL and infertility was demonstrated to have increased peripheral blood CD19+ B cells with persistently low levels of memory B cell subsets. Prior to the frozen donor egg transfer cycle, prednisone and intravenous immunoglobulin G (IVIg) treatment was initiated and patient achieved dichorionic diamniotic twin pregnancies. During pregnancy, proportion (%) of switched memory B cells CD27+IgD- increased, while percent of total CD19+ B cells and CD27-IgD+ naive B cells were gradually decreased with a high dose IVIg treatment. She developed cervical incompetence at 20 weeks of gestation, received a Cesarean section at 32 weeks of gestation due to preterm labor, and delivered twin babies. B cell subset abnormalities may be associated with infertility, RPL and preterm labor, and further investigation is needed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Fluoxetine prevents the memory deficits and reduction in hippocampal cell proliferation caused by valproic acid.

    Science.gov (United States)

    Welbat, Jariya Umka; Sangrich, Preeyanuch; Sirichoat, Apiwat; Chaisawang, Pornthip; Chaijaroonkhanarak, Wunnee; Prachaney, Parichat; Pannangrong, Wanassanun; Wigmore, Peter

    2016-12-01

    Valproic acid (VPA), a commonly used antiepileptic drug, has been reported to cause cognitive impairments in patients. In a previous study, using a rodent model, we showed that VPA treatment impaired cognition which was associated with a reduction in the cell proliferation required for hippocampal neurogenesis. The antidepressant fluoxetine has been shown to increase hippocampal neurogenesis and to reverse the memory deficits found in a number of pathological conditions. In the present study we investigated the protective effects of fluoxetine treatment against the impairments in memory and hippocampal cell proliferation produced by VPA. Male Sprague Dawley rats received daily treatment with fluoxetine (10mg/kg) by oral gavage for 21days. Some rats were co-administered with VPA (300mg/kg, twice daily i.p. injections) for 14days from day 8 to day 21 of the fluoxetine treatment. Spatial memory was tested using the novel object location (NOL) test. The number of proliferating cells present in the sub granular zone of the dentate gyrus was quantified using Ki67 immunohistochemistry at the end of the experiment. Levels of the receptor Notch1, the neurotrophic factor BDNF and the neural differentiation marker DCX were determined by Western blotting. VPA-treated rats showed memory deficits, a decrease in the number of proliferating cells in the sub granular zone and decreases in the levels of Notch1 and BDNF but not DCX compared to control animals. These changes in behavior, cell proliferation and Notch1 and BDNF were prevented in animals which had received both VPA and fluoxetine. Rats receiving fluoxetine alone did not show a significant difference in the number of proliferating cells or behavior compared to controls. These results demonstrated that the spatial memory deficits and reduction of cell proliferation produced by VPA can be ameliorated by the simultaneous administration of the antidepressant fluoxetine. Crown Copyright © 2016. Published by Elsevier B

  16. Human Memory B Cells Targeting Staphylococcus aureus Exotoxins Are Prevalent with Skin and Soft Tissue Infection

    Directory of Open Access Journals (Sweden)

    Adam J. Pelzek

    2018-03-01

    Full Text Available Staphylococcus aureus is a Gram-positive opportunistic pathogen that causes superficial and invasive infections in the hospital and community. High mortality from infection emphasizes the need for improved methods for prevention and treatment. Although S. aureus possesses an arsenal of virulence factors that contribute to evasion of host defenses, few studies have examined long-term humoral and B-cell responses. Adults with acute-phase skin and soft tissue infections were recruited; blood samples were obtained; and S. aureus isolates, including methicillin-resistant strains, were subjected to genomic sequence analysis. In comparisons of acute-phase sera with convalescent-phase sera, a minority (37.5% of patients displayed 2-fold or greater increases in antibody titers against three or more S. aureus antigens, whereas nearly half exhibited no changes, despite the presence of toxin genes in most infecting strains. Moreover, enhanced antibody responses waned over time, which could reflect a defect in B-cell memory or long-lived plasma cells. However, memory B cells reactive with a range of S. aureus antigens were prevalent at both acute-phase and convalescent-phase time points. While some memory B cells exhibited toxin-specific binding, those cross-reactive with structurally related leucocidin subunits were dominant across patients, suggesting the targeting of conserved epitopes. Memory B-cell reactivity correlated with serum antibody levels for selected S. aureus exotoxins, suggesting a relationship between the cellular and humoral compartments. Overall, although there was no global defect in the representation of anti-S. aureus memory B cells, there was evidence of restrictions in the range of epitopes recognized, which may suggest potential therapeutic approaches for augmenting host defenses.

  17. Memory of Natural Killer Cells: A New Chance against Mycobacterium tuberculosis?

    Directory of Open Access Journals (Sweden)

    José Alberto Choreño Parra

    2017-08-01

    Full Text Available Natural killer (NK cells are lymphocytes of the innate immune system, which play an important role in the initial defense against a wide variety of pathogens, including viruses and intracellular bacteria. NK cells produce cytokines that enhance immune responses directed toward pathogens and also exert cytotoxic activity against infected cells, thereby eliminating the reservoir of infection. Their role in defense against Mycobacterium tuberculosis (Mtb has been recently studied, and there is increasing evidence that highlight the importance of NK cell function during pulmonary tuberculosis (PTB, especially in the absence of optimal T-cell responses. Additionally, in the last years, it has been observed that NK cells mediate secondary responses against antigens to which they were previously exposed, an ability classically attributed to lymphocytes of the adaptive branch of immunity. This phenomenon, called “innate memory,” could have important implications in the efforts to develop therapies and vaccines to improve the initial phases of immune reactions against different microorganisms, especially those to which there is not yet available vaccines to prevent infection, as is the case for tuberculosis. Therefore, the possibility of inducing memory-like NK cells ready to act prior to contact with Mtb or during the earliest stages of infection becomes quite interesting. However, our understanding of the mechanisms of innate memory remains incomplete. Here, we review recent literature about the mechanisms involved in the formation and maintenance of NK cell memory and the role of these cells in the immune response during tuberculosis. Finally, we discuss if the current evidence is sufficient to substantiate that NK cells exert more rapid and robust secondary responses after consecutive encounters with Mtb.

  18. Tissue-resident memory T cells in tissue homeostasis, persistent infection, and cancer surveillance.

    Science.gov (United States)

    Gebhardt, Thomas; Palendira, Umaimainthan; Tscharke, David C; Bedoui, Sammy

    2018-05-01

    A large proportion of memory T cells disseminated throughout the body are non-recirculating cells whose maintenance and function is regulated by tissue-specific environmental cues. These sessile cells are referred to as tissue-resident memory T (T RM ) cells and similar populations of non-recirculating cells also exist among unconventional T cells and innate lymphocyte cells. The pool of T RM cells is highly diverse with respect to anatomical positioning, phenotype, molecular regulation and effector function. Nevertheless, certain transcriptional programs are shared and appear as important unifying features for the overall population of T RM cells and tissue-resident lymphocytes. It is now widely appreciated that T RM cells are a critical component of our immune defense by acting as peripheral sentinels capable of rapidly mobilizing protective tissue immunity upon pathogen recognition. This function is of particular importance in anatomical sites that are not effectively surveilled by blood-borne memory T cells in absence of inflammation, such as neuronal tissues or epithelial compartments in skin and mucosae. Focusing on the well-characterized subtype of CD8 +  CD69 +  CD103 + T RM cells, we will review current concepts on the generation, persistence and function of T RM cells and will summarize commonly used tools to study these cells. Furthermore, we will discuss accumulating data that emphasize localized T RM responses as an important determinant of tissue homeostasis and immune defense in the context of microbiota-immune interactions, persistent infections and cancer surveillance. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. 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

    Science.gov (United States)

    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

  20. Quantitative Analysis of Memristance Defined Exponential Model for Multi-bits Titanium Dioxide Memristor Memory Cell

    Directory of Open Access Journals (Sweden)

    DAOUD, A. A. D.

    2016-05-01

    Full Text Available The ability to store multiple bits in a single memristor based memory cell is a key feature for high-capacity memory packages. Studying multi-bit memristor circuits requires high accuracy in modelling the memristance change. A memristor model based on a novel definition of memristance is proposed. A design of a single memristor memory cell using the proposed model for the platinum electrodes titanium dioxide memristor is illustrated. A specific voltage pulse is used with varying its parameters (amplitude or pulse width to store different number of states in a single memristor. New state variation parameters associated with the utilized model are provided and their effects on write and read processes of memristive multi-states are analysed. PSPICE simulations are also held, and they show a good agreement with the data obtained from the analysis.

  1. CD73 expression identifies a subset of IgM+ antigen-experienced cells with memory attributes that is T cell and CD40 signalling dependent.

    Science.gov (United States)

    D'Souza, Lucas; Gupta, Sneh Lata; Bal, Vineeta; Rath, Satyajit; George, Anna

    2017-12-01

    B-cell memory was long characterized as isotype-switched, somatically mutated and germinal centre (GC)-derived. However, it is now clear that the memory pool is a complex mixture that includes unswitched and unmutated cells. Further, expression of CD73, CD80 and CD273 has allowed the categorization of B-cell memory into multiple subsets, with combinatorial expression of the markers increasing with GC progression, isotype-switching and acquisition of somatic mutations. We have extended these findings to determine whether these markers can be used to identify IgM memory phenotypically as arising from T-dependent versus T-independent responses. We report that CD73 expression identifies a subset of antigen-experienced IgM + cells that share attributes of functional B-cell memory. This subset is reduced in the spleens of T-cell-deficient and CD40-deficient mice and in mixed marrow chimeras made with mutant and wild-type marrow, the proportion of CD73 + IgM memory is restored in the T-cell-deficient donor compartment but not in the CD40-deficient donor compartment, indicating that CD40 ligation is involved in its generation. We also report that CD40 signalling supports optimal expression of CD73 on splenic T cells and age-associated B cells (ABCs), but not on other immune cells such as neutrophils, marginal zone B cells, peritoneal cavity B-1 B cells and regulatory T and B cells. Our data indicate that in addition to promoting GC-associated memory generation during B-cell differentiation, CD40-signalling can influence the composition of the unswitched memory B-cell pool. They also raise the possibility that a fraction of ABCs may represent T-cell-dependent IgM memory. © 2017 John Wiley & Sons Ltd.

  2. Tissue-specific B-cell dysfunction and generalized memory B-cell loss during acute SIV infection.

    Directory of Open Access Journals (Sweden)

    Sandrine Peruchon

    Full Text Available BACKGROUND: Primary HIV-infected patients display severe and irreversible damage to different blood B-cell subsets which is not restored by highly efficient anti-retroviral therapy (HAART. Because longitudinal investigations of primary HIV-infection is limited by the availability of lymphoid organs, we studied the tissue-specific B-cell dysfunctions in acutely simian immunodeficiency virus (SIV mac251-infected Cynomolgus macaques. METHODS AND FINDINGS: Experiments were performed on three groups of macaques infected for 14, 21 or 28 days and on three groups of animals treated with HAART for two-weeks either initiated at 4 h, 7 or 14 days post-infection (p.i.. We have simultaneously compared changes in B-cell phenotypes and functions and tissue organization of B-cell areas in various lymphoid organs. We showed that SIV induced a steady decline in SIgG-expressing memory (SIgD(-CD27(+ B-cells in spleen and lymph nodes during the first 4 weeks of infection, concomitant to selective homing/sequestration of B-cells to the small intestine and spleen. SIV non-specific Ig production was transiently increased before D14p.i., whereas SIV-specific Ig production was only detectable after D14p.i., coinciding with the presence of CD8(+ T-cells and IgG-expressing plasma cells within germinal centres. Transient B-cell apoptosis on D14p.i. and commitment to terminal differentiation contributed to memory B-cell loss. HAART abrogated B-cell apoptosis, homing to the small intestine and SIV-specific Ig production but had minimal effect on early Ig production, increased B-cell proportions in spleen and loss of memory B-cells. Therefore, virus-B-cell interactions and SIV-induced inflammatory cytokines may differently contribute to early B-cell dysfunction and impaired SIV/HIV-specific antibody response. CONCLUSIONS: These data establish tissue-specific impairments in B-cell trafficking and functions and a generalized and steady memory B-cell loss in secondary lymphoid

  3. NK Cell-Mediated Regulation of Protective Memory Responses against Intracellular Ehrlichial Pathogens.

    Directory of Open Access Journals (Sweden)

    Samar Habib

    Full Text Available Ehrlichiae are gram-negative obligate intracellular bacteria that cause potentially fatal human monocytic ehrlichiosis. We previously showed that natural killer (NK cells play a critical role in host defense against Ehrlichia during primary infection. However, the contribution of NK cells to the memory response against Ehrlichia remains elusive. Primary infection of C57BL/6 mice with Ehrlichia muris provides long-term protection against a second challenge with the highly virulent Ixodes ovatus Ehrlichia (IOE, which ordinarily causes fatal disease in naïve mice. Here, we show that the depletion of NK cells in E. muris-primed mice abrogates the protective memory response against IOE. Approximately, 80% of NK cell-depleted E. muris-primed mice succumbed to lethal IOE infection on days 8-10 after IOE infection, similar to naïve mice infected with the same dose of IOE. The lack of a recall response in NK cell-depleted mice correlated with an increased bacterial burden, extensive liver injury, decreased frequency of Ehrlichia-specific IFN-γ-producing memory CD4+ and CD8+ T-cells, and a low titer of Ehrlichia-specific antibodies. Intraperitoneal infection of mice with E. muris resulted in the production of IL-15, IL-12, and IFN-γ as well as an expansion of activated NKG2D+ NK cells. The adoptive transfer of purified E. muris-primed hepatic and splenic NK cells into Rag2-/-Il2rg-/- recipient mice provided protective immunity against challenge with E. muris. Together, these data suggest that E. muris-induced memory-like NK cells, which contribute to the protective, recall response against Ehrlichia.

  4. Excess influx of Zn(2+) into dentate granule cells affects object recognition memory via attenuated LTP.

    Science.gov (United States)

    Suzuki, Miki; Fujise, Yuki; Tsuchiya, Yuka; Tamano, Haruna; Takeda, Atsushi

    2015-08-01

    The influx of extracellular Zn(2+) into dentate granule cells is nonessential for dentate gyrus long-term potentiation (LTP) and the physiological significance of extracellular Zn(2+) dynamics is unknown in the dentate gyrus. Excess increase in extracellular Zn(2+) in the hippocampal CA1, which is induced with excitation of zincergic neurons, induces memory deficit via excess influx of Zn(2+) into CA1 pyramidal cells. In the present study, it was examined whether extracellular Zn(2+) induces object recognition memory deficit via excess influx of Zn(2+) into dentate granule cells. KCl (100 mM, 2 µl) was locally injected into the dentate gyrus. The increase in intracellular Zn(2+) in dentate granule cells induced with high K(+) was blocked by co-injection of CaEDTA and CNQX, an extracellular Zn(2+) chelator and an AMPA receptor antagonist, respectively, suggesting that high K(+) increases the influx of Zn(2+) into dentate granule cells via AMPA receptor activation. Dentate gyrus LTP induction was attenuated 1 h after KCl injection into the dentate gyrus and also attenuated when KCl was injected 5 min after the induction. Memory deficit was induced when training of object recognition test was performed 1 h after KCl injection into the dentate gyrus and also induced when KCl was injected 5 min after the training. High K(+)-induced impairments of LTP and memory were rescued by co-injection of CaEDTA. These results indicate that excess influx of Zn(2+) into dentate granule cells via AMPA receptor activation affects object recognition memory via attenuated LTP induction. Even in the dentate gyrus where is scarcely innervated by zincergic neurons, it is likely that extracellular Zn(2+) homeostasis is strictly regulated for cognition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Past matrix stiffness primes epithelial cells and regulates their future collective migration through a mechanical memory.

    Science.gov (United States)

    Nasrollahi, Samila; Walter, Christopher; Loza, Andrew J; Schimizzi, Gregory V; Longmore, Gregory D; Pathak, Amit

    2017-11-01

    During morphogenesis and cancer metastasis, grouped cells migrate through tissues of dissimilar stiffness. Although the influence of matrix stiffness on cellular mechanosensitivity and motility are well-recognized, it remains unknown whether these matrix-dependent cellular features persist after cells move to a new microenvironment. Here, we interrogate whether priming of epithelial cells by a given matrix stiffness influences their future collective migration on a different matrix - a property we refer to as the 'mechanical memory' of migratory cells. To prime cells on a defined matrix and track their collective migration onto an adjoining secondary matrix of dissimilar stiffness, we develop a modular polyacrylamide substrate through step-by-step polymerization of different PA compositions. We report that epithelial cells primed on a stiff matrix migrate faster, display higher actomyosin expression, form larger focal adhesions, and retain nuclear YAP even after arriving onto a soft secondary matrix, as compared to their control behavior on a homogeneously soft matrix. Priming on a soft ECM causes a reverse effect. The depletion of YAP dramatically reduces this memory-dependent migration. Our results present a previously unidentified regulation of mechanosensitive collective cell migration by past matrix stiffness, in which mechanical memory depends on YAP activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. A colitogenic memory CD4+ T cell population mediates gastrointestinal graft-versus-host disease

    Science.gov (United States)

    Zhou, Vivian; Agle, Kimberle; Chen, Xiao; Beres, Amy; Komorowski, Richard; Belle, Ludovic; Taylor, Carolyn; Zhu, Fenlu; Haribhai, Dipica; Williams, Calvin B.; Verbsky, James; Blumenschein, Wendy; Sadekova, Svetlana; Bowman, Eddie; Ballantyne, Christie; Weaver, Casey; Serody, David A.; Vincent, Benjamin; Serody, Jonathan; Cua, Daniel J.; Drobyski, William R.

    2016-01-01

    Damage to the gastrointestinal tract is a major cause of morbidity and mortality in graft-versus-host disease (GVHD) and is attributable to T cell–mediated inflammation. In this work, we identified a unique CD4+ T cell population that constitutively expresses the β2 integrin CD11c and displays a biased central memory phenotype and memory T cell transcriptional profile, innate-like properties, and increased expression of the gut-homing molecules α4β7 and CCR9. Using several complementary murine GVHD models, we determined that adoptive transfer and early accumulation of β2 integrin–expressing CD4+ T cells in the gastrointestinal tract initiated Th1-mediated proinflammatory cytokine production, augmented pathological damage in the colon, and increased mortality. The pathogenic effect of this CD4+ T cell population critically depended on coexpression of the IL-23 receptor, which was required for maximal inflammatory effects. Non–Foxp3-expressing CD4+ T cells produced IL-10, which regulated colonic inflammation and attenuated lethality in the absence of functional CD4+Foxp3+ T cells. Thus, the coordinate expression of CD11c and the IL-23 receptor defines an IL-10–regulated, colitogenic memory CD4+ T cell subset that is poised to initiate inflammation when there is loss of tolerance and breakdown of mucosal barriers. PMID:27500496

  7. Skin-resident memory CD4+ T cells enhance protection against Leishmania major infection.

    Science.gov (United States)

    Glennie, Nelson D; Yeramilli, Venkata A; Beiting, Daniel P; Volk, Susan W; Weaver, Casey T; Scott, Phillip

    2015-08-24

    Leishmaniasis causes a significant disease burden worldwide. Although Leishmania-infected patients become refractory to reinfection after disease resolution, effective immune protection has not yet been achieved by human vaccines. Although circulating Leishmania-specific T cells are known to play a critical role in immunity, the role of memory T cells present in peripheral tissues has not been explored. Here, we identify a population of skin-resident Leishmania-specific memory CD4+ T cells. These cells produce IFN-γ and remain resident in the skin when transplanted by skin graft onto naive mice. They function to recruit circulating T cells to the skin in a CXCR3-dependent manner, resulting in better control of the parasites. Our findings are the first to demonstrate that CD4+ TRM cells form in response to a parasitic infection, and indicate that optimal protective immunity to Leishmania, and thus the success of a vaccine, may depend on generating both circulating and skin-resident memory T cells. © 2015 Glennie et al.

  8. Basic principles of STT-MRAM cell operation in memory arrays

    International Nuclear Information System (INIS)

    Khvalkovskiy, A V; Apalkov, D; Watts, S; Chepulskii, R; Beach, R S; Ong, A; Tang, X; Driskill-Smith, A; Lottis, D; Chen, E; Nikitin, V; Krounbi, M; Butler, W H; Visscher, P B

    2013-01-01

    For reliable operation, individual cells of an STT-MRAM memory array must meet specific requirements on their performance. In this work we review some of these requirements and discuss the fundamental physical principles of STT-MRAM operation, covering the range from device level to chip array performance, and methodology for its development. (paper)

  9. The Memories of NK Cells: Innate-Adaptive Immune Intrinsic Crosstalk.

    Science.gov (United States)

    Gabrielli, Sara; Ortolani, Claudio; Del Zotto, Genny; Luchetti, Francesca; Canonico, Barbara; Buccella, Flavia; Artico, Marco; Papa, Stefano; Zamai, Loris

    2016-01-01

    Although NK cells are considered part of the innate immune system, a series of evidences has demonstrated that they possess characteristics typical of the adaptive immune system. These NK adaptive features, in particular their memory-like functions, are discussed from an ontogenetic and evolutionary point of view.

  10. The Memories of NK Cells: Innate-Adaptive Immune Intrinsic Crosstalk

    Directory of Open Access Journals (Sweden)

    Sara Gabrielli

    2016-01-01

    Full Text Available Although NK cells are considered part of the innate immune system, a series of evidences has demonstrated that they possess characteristics typical of the adaptive immune system. These NK adaptive features, in particular their memory-like functions, are discussed from an ontogenetic and evolutionary point of view.

  11. Nanostructure-property relations for phase-change random access memory (PCRAM) line cells

    NARCIS (Netherlands)

    Kooi, B. J.; Oosthoek, J. L. M.; Verheijen, M. A.; Kaiser, M.; Jedema, F. J.; Gravesteijn, D. J.

    2012-01-01

    Phase-change random access memory (PCRAM) cells have been studied extensively using electrical characterization and rather limited by detailed structure characterization. The combination of these two characterization techniques has hardly been exploited and it is the focus of the present work.

  12. Increased memory phenotypes of CD4+ and CD8+ T cells in ...

    African Journals Online (AJOL)

    Conclusions: Children with SCA in Tanzania show an absolute increase in all leukocyte types, including lymphocytes, with skewing of both CD4+ and CD8+ T cells towards the memory phenotypes. These findings provide insights on the development of adaptive immunity which may have implications on vaccine ...

  13. B Cells Negatively Regulate the Establishment of CD49b(+)T-bet(+) Resting Memory T Helper Cells in the Bone Marrow.

    Science.gov (United States)

    Hojyo, Shintaro; Sarkander, Jana; Männe, Christian; Mursell, Mathias; Hanazawa, Asami; Zimmel, David; Zhu, Jinfang; Paul, William E; Fillatreau, Simon; Löhning, Max; Radbruch, Andreas; Tokoyoda, Koji

    2016-01-01

    During an immune reaction, some antigen-experienced CD4 T cells relocate from secondary lymphoid organs (SLOs) to the bone marrow (BM) in a CD49b-dependent manner and reside and rest there as professional memory CD4 T cells. However, it remains unclear how the precursors of BM memory CD4 T cells are generated in the SLOs. While several studies have so far shown that B cell depletion reduces the persistence of memory CD4 T cells in the spleen, we here show that B cell depletion enhances the establishment of memory CD4 T cells in the BM and that B cell transfer conversely suppresses it. Interestingly, the number of antigen-experienced CD4 T cells in the BM synchronizes the number of CD49b(+)T-bet(+) antigen-experienced CD4 T cells in the spleen. CD49b(+)T-bet(+) antigen-experienced CD4 T cells preferentially localize in the red pulp area of the spleen and the BM in a T-bet-independent manner. We suggest that B cells negatively control the generation of CD49b(+)T-bet(+) precursors of resting memory CD4 T cells in the spleen and may play a role in bifurcation of activated effector and resting memory CD4 T cell lineages.

  14. B cells negatively regulate the establishment of CD49b+T-bet+ resting memory T helper cells in the bone marrow

    Directory of Open Access Journals (Sweden)

    Shintaro eHojyo

    2016-02-01

    Full Text Available During an immune reaction, some antigen-experienced CD4 T cells relocate from secondary lymphoid organs (SLOs to the bone marrow (BM in a CD49b-dependent manner and reside and rest there as professional memory CD4 T cells. However, it remains unclear how the precursors of BM memory CD4 T cells are generated in the SLOs. While several studies have so far shown that B cell depletion reduces the persistence of memory CD4 T cells in the spleen, we here show that B cell depletion enhances the establishment of memory CD4 T cells in the BM and that B cell transfer conversely suppresses it. Interestingly, the number of antigen-experienced CD4 T cells in the BM synchronizes the number of CD49b+T-bet+ antigen-experienced CD4 T cells in the spleen. CD49b+T-bet+ antigen-experienced CD4 T cells preferentially localize in the red pulp area of the spleen and the BM in a T-bet-independent manner. We suggest that B cells negatively control the generation of CD49b+T-bet+ precursors of resting memory CD4 T cells in the spleen and may play a role in bifurcation of activated effector and resting memory CD4 T cell lineages.

  15. Switching speed in resistive random access memories (RRAMS) based on plastic semiconductor

    NARCIS (Netherlands)

    Rocha, P.R.F.; Gomes, H.L.; Kiazadeh, A.; Chen, Qian; Leeuw, de D.M.; Meskers, S.C.J.

    2011-01-01

    This work addresses non-volatile memories based on metal-oxide polymer diodes. We make a thorough investigation into the static and dynamic behavior. Current-voltage characteristics with varying voltage ramp speed demonstrate that the internal capacitive double-layer structure inhibits the switching

  16. Intégration de matériaux à forte permittivité électrique (High-k) dans les mémoires non-volatiles pour les générations sub-45nm

    OpenAIRE

    Bocquet , Marc

    2009-01-01

    Flash memory is today a major element for the development of the portable electronics which require more and more memory capability at low cost (netbook, cell phones, PDA, USB sticks...). In order to maintain it for the years to come, it is necessary to continue improving this technology. Also, the integration of High-k materials and the use of trap charge memories are strongly envisaged. This PhD focuses on the integration and the electrical study (fixed charge, trapping, leakage currents......

  17. The memory effect of a pentacene field-effect transistor with a polarizable gate dielectric

    Science.gov (United States)

    Unni, K. N. N.; de Bettignies, Remi; Dabos-Seignon, Sylvie; Nunzi, Jean-Michel

    2004-06-01

    The nonvolatile transistor memory element is an interesting topic in organic electronics. In this case a memory cell consists of only one device where the stored information is written as a gate insulator polarization by a gate voltage pulse and read by the channel conductance control with channel voltage pulse without destruction of the stored information. Therefore such transistor could be the base of non-volatile non-destructively readable computer memory of extremely high density. Also devices with polarizable gate dielectrics can function more effectively in certain circuits. The effective threshold voltage Vt can be brought very close to zero, for applications where the available gate voltage is limited. Resonant and adaptive circuits can be tuned insitu by polarizing the gates. Poly(vinylidene fluoride), PVDF and its copolymer with trifluoroethylene P(VDF-TrFE) are among the best known and most widely used ferroelectric polymers. In this manuscript, we report new results of an organic FET, fabricated with pentacene as the active material and P(VDF-TrFE) as the gate insulator. Application of a writing voltage of -50 V for short duration results in significant change in the threshold voltage and remarkable increase in the drain current. The memory effect is retained over a period of 20 hours.

  18. Thin PZT-Based Ferroelectric Capacitors on Flexible Silicon for Nonvolatile Memory Applications

    KAUST Repository

    Ghoneim, Mohamed T.

    2015-04-24

    A flexible version of traditional thin lead zirconium titanate ((Pb1.1Zr0.48Ti0.52O3)-(PZT)) based ferroelectric random access memory (FeRAM) on silicon shows record performance in flexible arena. The thin PZT layer requires lower operational voltages to achieve coercive electric fields, reduces the sol-gel coating cycles required (i.e., more cost-effective), and, fabrication wise, is more suitable for further scaling of lateral dimensions to the nano-scale due to the larger feature size-to-depth aspect ratio (critical for ultra-high density non-volatile memory applications). Utilizing the inverse proportionality between substrate\\'s thickness and its flexibility, traditional PZT based FeRAM on silicon is transformed through a transfer-less manufacturable process into a flexible form that matches organic electronics\\' flexibility while preserving the superior performance of silicon CMOS electronics. Each memory cell in a FeRAM array consists of two main elements; a select/access transistor, and a storage ferroelectric capacitor. Flexible transistors on silicon have already been reported. In this work, we focus on the storage ferroelectric capacitors, and report, for the first time, its performance after transformation into a flexible version, and assess its key memory parameters while bent at 0.5 cm minimum bending radius.

  19. Expansion of mycobacterium-reactive gamma delta T cells by a subset of memory helper T cells.

    Science.gov (United States)

    Vila, L M; Haftel, H M; Park, H S; Lin, M S; Romzek, N C; Hanash, S M; Holoshitz, J

    1995-04-01

    Human gamma delta T cells expressing the V gamma 9/V delta 2 T-cell receptor have been previously found to proliferate in response to certain microorganisms and to expand throughout life, presumably because of extrathymic activation by foreign antigens. In vitro expansion of V gamma 9/V delta 2 cells by mycobacteria has been previously shown to be dependent on accessory cells. In order to gain an insight into the mechanisms involved in the expansion of these cells, we have undertaken to identify the peripheral blood subset of cells on which proliferation of V gamma 9/V delta 2 cells in response to mycobacteria is dependent. Contrary to their role in antigen presentation to alpha beta T cells, professional antigen-presenting cells, such as monocytes, B cells, and dendritic cells, were unable to provide the cellular support for the expansion of V gamma 9/V delta 2 cells. Selective depletion of T-cell subsets, as well as the use of highly purified T-cell populations, indicated that the only subset of peripheral blood cells that could expand V gamma 9/V delta 2 cells were CD4+ CD45RO+ CD7- alpha beta T cells. These cells underwent distinct intracellular signaling events after stimulation with the mycobacterial antigen. Expansion of V gamma 9/V delta 2 cells by alpha beta T cells was dependent on cell-cell contact. This is the first evidence that a small subset of the memory helper T-cell population is exclusively responsible for the peripheral expansion of V gamma 9/V delta 2 cells. These data illustrate a unique aspect of antigen recognition by gamma delta T cells and provide new means to study their immune defense role.

  20. Writing to and reading from a nano-scale crossbar memory based on memristors

    International Nuclear Information System (INIS)

    Vontobel, Pascal O; Robinett, Warren; Kuekes, Philip J; Stewart, Duncan R; Straznicky, Joseph; Stanley Williams, R

    2009-01-01

    We present a design study for a nano-scale crossbar memory system that uses memristors with symmetrical but highly nonlinear current-voltage characteristics as memory elements. The memory is non-volatile since the memristors retain their state when un-powered. In order to address the nano-wires that make up this nano-scale crossbar, we use two coded demultiplexers implemented using mixed-scale crossbars (in which CMOS-wires cross nano-wires and in which the crosspoint junctions have one-time configurable memristors). This memory system does not utilize the kind of devices (diodes or transistors) that are normally used to isolate the memory cell being written to and read from in conventional memories. Instead, special techniques are introduced to perform the writing and the reading operation reliably by taking advantage of the nonlinearity of the type of memristors used. After discussing both writing and reading strategies for our memory system in general, we focus on a 64 x 64 memory array and present simulation results that show the feasibility of these writing and reading procedures. Besides simulating the case where all device parameters assume exactly their nominal value, we also simulate the much more realistic case where the device parameters stray around their nominal value: we observe a degradation in margins, but writing and reading is still feasible. These simulation results are based on a device model for memristors derived from measurements of fabricated devices in nano-scale crossbars using Pt and Ti nano-wires and using oxygen-depleted TiO 2 as the switching material.

  1. A non-destructive crossbar architecture of multi-level memory-based resistor

    Science.gov (United States)

    Sahebkarkhorasani, Seyedmorteza

    Nowadays, researchers are trying to shrink the memory cell in order to increase the capacity of the memory system and reduce the hardware costs. In recent years, there has been a revolution in electronics by using fundamentals of physics to build a new memory for computer application in order to increase the capacity and decrease the power consumption. Increasing the capacity of the memory causes a growth in the chip area. From 1971 to 2012 semiconductor manufacturing process improved from 6mum to 22 mum. In May 2008, S.Williams stated that "it is time to stop shrinking". In his paper, he declared that the process of shrinking memory element has recently become very slow and it is time to use another alternative in order to create memory elements [9]. In this project, we present a new design of a memory array using the new element named Memristor [3]. Memristor is a two-terminal passive electrical element that relates the charge and magnetic flux to each other. The device remained unknown since 1971 when it was discovered by Chua and introduced as the fourth fundamental passive element like capacitor, inductor and resistor [3]. Memristor has a dynamic resistance and it can retain its previous value even after disconnecting the power supply. Due to this interesting behavior of the Memristor, it can be a good replacement for all of the Non-Volatile Memories (NVMs) in the near future. Combination of this newly introduced element with the nanowire crossbar architecture would be a great structure which is called Crossbar Memristor. Some frameworks have recently been introduced in literature that utilized Memristor crossbar array, but there are many challenges to implement the Memristor crossbar array due to fabrication and device limitations. In this work, we proposed a simple design of Memristor crossbar array architecture which uses input feedback in order to preserve its data after each read operation.

  2. Disruptive effect of Dzyaloshinskii-Moriya interaction on the magnetic memory cell performance

    Energy Technology Data Exchange (ETDEWEB)

    Sampaio, J.; Cubukcu, M.; Cros, V.; Reyren, N., E-mail: nicolas.reyren@thalesgroup.com [Unité Mixte de Physique, CNRS, Thales, Univ. Paris-Sud, Université Paris-Saclay, 91767, Palaiseau (France); Khvalkovskiy, A. V. [Samsung Electronics, Semiconductor R& D Center (Grandis), San Jose, California 95134 (United States); Moscow Institute of Physics and Technology, State University, Moscow 141700 (Russian Federation); Kuteifan, M.; Lomakin, V. [Department of Electrical and Computer Engineering, University of California at San Diego, La Jolla, California 92093-0407 (United States); Apalkov, D. [Samsung Electronics, Semiconductor R& D Center (Grandis), San Jose, California 95134 (United States)

    2016-03-14

    In order to increase the thermal stability of a magnetic random access memory cell, materials with high spin-orbit interaction are often introduced in the storage layer. As a side effect, a strong Dzyaloshinskii-Moriya interaction (DMI) may arise in such systems. Here, we investigate the impact of DMI on the magnetic cell performance, using micromagnetic simulations. We find that DMI strongly promotes non-uniform magnetization states and non-uniform switching modes of the magnetic layer. It appears to be detrimental for both the thermal stability of the cell and its switching current, leading to considerable deterioration of the cell performance even for a moderate DMI amplitude.

  3. AMPKα1: a glucose sensor that controls CD8 T-cell memory.

    Science.gov (United States)

    Rolf, Julia; Zarrouk, Marouan; Finlay, David K; Foretz, Marc; Viollet, Benoit; Cantrell, Doreen A

    2013-04-01

    The adenosine monophosphate-activated protein kinase (AMPK) is activated by antigen receptor signals and energy stress in T cells. In many cell types, AMPK can maintain energy homeostasis and can enforce quiescence to limit energy demands. We consequently evaluated the importance of AMPK for controlling the transition of metabolically active effector CD8 T lymphocytes to the metabolically quiescent catabolic memory T cells during the contraction phase of the immune response. We show that AMPKα1 activates rapidly in response to the metabolic stress caused by glucose deprivation of CD8 cytotoxic T lymphocytes (CTLs). Moreover, AMPKα1 restrains mammalian target of rapamycin complex 1 activity under conditions of glucose stress. AMPKα1 activity is dispensable for proliferation and differentiation of CTLs. However, AMPKα1 is required for in vivo survival of CTLs following withdrawal of immune stimulation. AMPKα1(null) T cells also show a striking defect in their ability to generate memory CD8 T-cell responses during Listeria monocytogenes infection. These results show that AMPKα1 monitors energy stress in CTLs and controls CD8 T-cell memory. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. CD8 T cell memory to a viral pathogen requires trans cosignaling between HVEM and BTLA.

    Directory of Open Access Journals (Sweden)

    Rachel Flynn

    Full Text Available Defining the molecular interactions required to program activated CD8 T cells to survive and become memory cells may allow us to understand how to augment anti-viral immunity. HVEM (herpes virus entry mediator is a member of the tumor necrosis factor receptor (TNFR family that interacts with ligands in the TNF family, LIGHT and Lymphotoxin-α, and in the Ig family, B and T lymphocyte attenuator (BTLA and CD160. The Ig family members initiate inhibitory signaling when engaged with HVEM, but may also activate survival gene expression. Using a model of vaccinia virus infection, we made the unexpected finding that deficiency in HVEM or BTLA profoundly impaired effector CD8 T cell survival and development of protective immune memory. Mixed adoptive transfer experiments indicated that BTLA expressed in CD8α+ dendritic cells functions as a trans-activating ligand that delivers positive co-signals through HVEM expressed in T cells. Our data demonstrate a critical role of HVEM-BTLA bidirectional cosignaling system in antiviral defenses by driving the differentiation of memory CD8 T cells.

  5. T Cell Responses: Naive to Memory and Everything in Between

    Science.gov (United States)

    Pennock, Nathan D.; White, Jason T.; Cross, Eric W.; Cheney, Elizabeth E.; Tamburini, Beth A.; Kedl, Ross M.

    2013-01-01

    The authors describe the actions that take place in T cells because of their amazing capacity to proliferate and adopt functional roles aimed at clearing a host of an infectious agent. There is a drastic decline in the T cell population once the primary response is over and the infection is terminated. What remains afterward is a population of T…

  6. MAP Detector for Flash Memory Without Accessing the Interfering Cells

    DEFF Research Database (Denmark)

    Yassine, Hachem; Badiu, Mihai Alin; Coon, Justin P.

    2018-01-01

    the latency cost of accessing the interfering cells. Specifically, we exploit the fact that adjacent cells have common interferers by modeling the system as an appropriate hidden Markov model. Then we use the sum-product (message-passing) algorithm to compute the marginal posterior probabilities of the stored...

  7. De novo alloreactive memory CD8+ T cells develop following allogeneic challenge when CNI immunosuppression is delayed.

    Science.gov (United States)

    Hart-Matyas, M; Gareau, A J; Hirsch, G M; Lee, T D G

    2015-01-01

    Allospecific memory T cells are a recognized threat to the maintenance of solid-organ transplants. Limited information exists regarding the development of alloreactive memory T cells when post-transplant immunosuppression is present. The clinical practice of delaying calcineurin inhibitor (CNI) initiation post-transplant may permit the development of a de novo allospecific memory population. We investigated the development of de novo allospecific memory CD8+ T cells following the introduction of CNI immunosuppression in a murine model using allogeneic cell priming. Recipient mice alloprimed with splenocytes from fully mismatched donors received cyclosporine (CyA), initiated at 0, 2, 6, or 10days post-prime. Splenocytes from recipients were analyzed by flow cytometry or enzyme-linked immunosorbent assay for evidence of memory cell formation. Memory and effector CD8+ T cell development was prevented when CyA was initiated at 0day or 2days post-prime (p0.05). Delaying CyA up to 6days or later post-prime permits the development of functional de novo allospecific memory CD8+ T cells. The development of this potentially detrimental T cell population in patients could be prevented by starting CNI immunosuppression early post-transplant. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. A Content-Addressable Memory structure using quantum cells in nanotechnology with energy dissipation analysis

    Science.gov (United States)

    Sadoghifar, Ali; Heikalabad, Saeed Rasouli

    2018-05-01

    Quantum-dot cellular automata is one of the recent new technologies at the nanoscale that can be a suitable replacement for CMOS technology. The circuits constructed in QCA technology have desirable features such as low power consumption, high speed and small size. These features can be more distinct in memory structures. In this paper, we design a new structure for content addressable memory cell in QCA. For this purpose, first, a unique gate is introduced for mask operation in QCA and then this gate is used to improve the performance of CAM. These structures are evaluated with QCADesigner simulator.

  9. Low-resistivity C54-TiSi2 as a sidewall-confinement nanoscale electrode for three-dimensional vertical resistive memory

    KAUST Repository

    Duran Retamal, Jose Ramon; Kang, Chen-Fang; Yang, Po-Kang; Lee, Chuan-Pei; Lien, Der-Hsien; Ho, Chih-Hsiang; He, Jr-Hau

    2014-01-01

    A three-dimensional (3D) double-layer HfO2-based vertical-resistive random access memory (VRRAM) with low-resistivity C54-TiSi2 as horizontal electrodes is demonstrated using complementary metal-oxide semiconductor processing. The electrical measurements show bipolar resistive switching by using C54-TiSi2 as electrodes for resistive switching (RS) applications. The statistical analysis exhibits cycle-to-cycle and cell-to-cell stable non-volatile properties with robust endurance (100 cycles) and long term data retention (104s), suggesting that the ultrathin sidewall of C54-TiSi2 nanoscale electrodes serve to confine and stabilize the random nature of the conducting nanofilaments. The superior RS characteristics demonstrated here highlight the applicability of C54-TiSi2 sidewall-confinement nanoscale electrodes to VRRAM.

  10. Low-resistivity C54-TiSi2 as a sidewall-confinement nanoscale electrode for three-dimensional vertical resistive memory

    KAUST Repository

    Duran Retamal, Jose Ramon

    2014-11-03

    A three-dimensional (3D) double-layer HfO2-based vertical-resistive random access memory (VRRAM) with low-resistivity C54-TiSi2 as horizontal electrodes is demonstrated using complementary metal-oxide semiconductor processing. The electrical measurements show bipolar resistive switching by using C54-TiSi2 as electrodes for resistive switching (RS) applications. The statistical analysis exhibits cycle-to-cycle and cell-to-cell stable non-volatile properties with robust endurance (100 cycles) and long term data retention (104s), suggesting that the ultrathin sidewall of C54-TiSi2 nanoscale electrodes serve to confine and stabilize the random nature of the conducting nanofilaments. The superior RS characteristics demonstrated here highlight the applicability of C54-TiSi2 sidewall-confinement nanoscale electrodes to VRRAM.

  11. IGF1-Dependent Synaptic Plasticity of Mitral Cells in Olfactory Memory during Social Learning.

    Science.gov (United States)

    Liu, Zhihui; Chen, Zijun; Shang, Congping; Yan, Fei; Shi, Yingchao; Zhang, Jiajing; Qu, Baole; Han, Hailin; Wang, Yanying; Li, Dapeng; Südhof, Thomas C; Cao, Peng

    2017-07-05

    During social transmission of food preference (STFP), mice form long-term memory of food odors presented by a social partner. How does the brain associate a social context with odor signals to promote memory encoding? Here we show that odor exposure during STFP, but not unconditioned odor exposure, induces glomerulus-specific long-term potentiation (LTP) of synaptic strength selectively at the GABAergic component of dendrodendritic synapses of granule and mitral cells in the olfactory bulb. Conditional deletion of synaptotagmin-10, the Ca 2+ sensor for IGF1 secretion from mitral cells, or deletion of IGF1 receptor in the olfactory bulb prevented the socially relevant GABAergic LTP and impaired memory formation after STFP. Conversely, the addition of IGF1 to acute olfactory bulb slices elicited the GABAergic LTP in mitral cells by enhancing postsynaptic GABA receptor responses. Thus, our data reveal a synaptic substrate for a socially conditioned long-term memory that operates at the level of the initial processing of sensory information. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. MicroRNA-21 preserves the fibrotic mechanical memory of mesenchymal stem cells.

    Science.gov (United States)

    Li, Chen Xi; Talele, Nilesh P; Boo, Stellar; Koehler, Anne; Knee-Walden, Ericka; Balestrini, Jenna L; Speight, Pam; Kapus, Andras; Hinz, Boris

    2017-03-01

    Expansion on stiff culture substrates activates pro-fibrotic cell programs that are retained by mechanical memory. Here, we show that priming on physiologically soft silicone substrates suppresses fibrogenesis and desensitizes mesenchymal stem cells (MSCs) against subsequent mechanical activation in vitro and in vivo, and identify the microRNA miR-21 as a long-term memory keeper of the fibrogenic program in MSCs. During stiff priming, miR-21 levels were gradually increased by continued regulation through the acutely mechanosensitive myocardin-related transcription factor-A (MRTF-A/MLK-1) and remained high over 2 weeks after removal of the mechanical stimulus. Knocking down miR-21 once by the end of the stiff-priming period was sufficient to erase the mechanical memory and sensitize MSCs to subsequent exposure to soft substrates. Soft priming and erasing mechanical memory following cell culture expansion protects MSCs from fibrogenesis in the host wound environment and increases the chances for success of MSC therapy in tissue-repair applications.

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

    Science.gov (United States)

    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

  14. Functional, Antigen-Specific Stem Cell Memory (TSCM CD4+ T Cells Are Induced by Human Mycobacterium tuberculosis Infection

    Directory of Open Access Journals (Sweden)

    Cheleka A. M. Mpande

    2018-03-01

    Full Text Available BackgroundMaintenance of long-lasting immunity is thought to depend on stem cell memory T cells (TSCM, which have superior self-renewing capacity, longevity and proliferative potential compared with central memory (TCM or effector (TEFF T cells. Our knowledge of TSCM derives primarily from studies of virus-specific CD8+ TSCM. We aimed to determine if infection with Mycobacterium tuberculosis (M. tb, the etiological agent of tuberculosis, generates antigen-specific CD4+ TSCM and to characterize their functional ontology.MethodsWe studied T cell responses to natural M. tb infection in a longitudinal adolescent cohort of recent QuantiFERON-TB Gold (QFT converters and three cross-sectional QFT+ adult cohorts; and to bacillus Calmette–Guerin (BCG vaccination in infants. M. tb and/or BCG-specific CD4 T cells were detected by flow cytometry using major histocompatibility complex class II tetramers bearing Ag85, CFP-10, or ESAT-6 peptides, or by intracellular cytokine staining. Transcriptomic analyses of M. tb-specific tetramer+ CD4+ TSCM (CD45RA+ CCR7+ CD27+ were performed by microfluidic qRT-PCR, and functional and phenotypic characteristics were confirmed by measuring expression of chemokine receptors, cytotoxic molecules and cytokines using flow cytometry.ResultsM. tb-specific TSCM were not detected in QFT-negative persons. After QFT conversion frequencies of TSCM increased to measurable levels and remained detectable thereafter, suggesting that primary M. tb infection induces TSCM cells. Gene expression (GE profiling of tetramer+ TSCM showed that these cells were distinct from bulk CD4+ naïve T cells (TN and shared features of bulk TSCM and M. tb-specific tetramer+ TCM and TEFF cells. These TSCM were predominantly CD95+ and CXCR3+, markers typical of CD8+ TSCM. Tetramer+ TSCM expressed significantly higher protein levels of CCR5, CCR6, CXCR3, granzyme A, granzyme K, and granulysin than bulk TN and TSCM cells. M. tb-specific TSCM were also

  15. Magnetic vortex racetrack memory

    Energy Technology Data Exchange (ETDEWEB)

    Geng, Liwei D.; Jin, Yongmei M., E-mail: ymjin@mtu.edu

    2017-02-01

    We report a new type of racetrack memory based on current-controlled movement of magnetic vortices in magnetic nanowires with rectangular cross-section and weak perpendicular anisotropy. Data are stored through the core polarity of vortices and each vortex carries a data bit. Besides high density, non-volatility, fast data access, and low power as offered by domain wall racetrack memory, magnetic vortex racetrack memory has additional advantages of no need for constrictions to define data bits, changeable information density, adjustable current magnitude for data propagation, and versatile means of ultrafast vortex core switching. By using micromagnetic simulations, current-controlled motion of magnetic vortices in cobalt nanowire is demonstrated for racetrack memory applications. - Highlights: • Advance fundamental knowledge of current-driven magnetic vortex phenomena. • Report appealing new magnetic racetrack memory based on current-controlled magnetic vortices in nanowires. • Provide a novel approach to adjust current magnitude for data propagation. • Overcome the limitations of domain wall racetrack memory.

  16. CD27 instructs CD4+ T cells to provide help for the memory CD8+ T cell response after protein immunization

    NARCIS (Netherlands)

    Xiao, Yanling; Peperzak, Victor; Keller, Anna M.; Borst, Jannie

    2008-01-01

    For optimal quality, memory CD8(+) T cells require CD4(+) T cell help. We have examined whether CD4(+) T cells require CD27 to deliver this help, in a model of intranasal OVA protein immunization. CD27 deficiency reduced the capacity of CD4(+) T cells to support Ag-specific CD8(+) T cell

  17. Resistive switching effect in the planar structure of all-printed, flexible and rewritable memory device based on advanced 2D nanocomposite of graphene quantum dots and white graphene flakes

    International Nuclear Information System (INIS)

    Rehman, Muhammad Muqeet; Siddiqui, Ghayas Uddin; Kim, Sowon; Choi, Kyung Hyun

    2017-01-01

    Pursuit of the most appropriate materials and fabrication methods is essential for developing a reliable, rewritable and flexible memory device. In this study, we have proposed an advanced 2D nanocomposite of white graphene (hBN) flakes embedded with graphene quantum dots (GQDs) as the functional layer of a flexible memory device owing to their unique electrical, chemical and mechanical properties. Unlike the typical sandwich type structure of a memory device, we developed a cost effective planar structure, to simplify device fabrication and prevent sneak current. The entire device fabrication was carried out using printing technology followed by encapsulation in an atomically thin layer of aluminum oxide (Al 2 O 3 ) for protection against environmental humidity. The proposed memory device exhibited attractive bipolar switching characteristics of high switching ratio, large electrical endurance and enhanced lifetime, without any crosstalk between adjacent memory cells. The as-fabricated device showed excellent durability for several bending cycles at various bending diameters without any degradation in bistable resistive states. The memory mechanism was deduced to be conductive filamentary; this was validated by illustrating the temperature dependence of bistable resistive states. Our obtained results pave the way for the execution of promising 2D material based next generation flexible and non-volatile memory (NVM) applications. (paper)

  18. Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells.

    Science.gov (United States)

    Kawalekar, Omkar U; O'Connor, Roddy S; Fraietta, Joseph A; Guo, Lili; McGettigan, Shannon E; Posey, Avery D; Patel, Prachi R; Guedan, Sonia; Scholler, John; Keith, Brian; Snyder, Nathaniel W; Snyder, Nathaniel; Blair, Ian A; Blair, Ian; Milone, Michael C; June, Carl H

    2016-02-16

    Chimeric antigen receptors (CARs) redirect T cell cytotoxicity against cancer cells, providing a promising approach to cancer immunotherapy. Despite extensive clinical use, the attributes of CAR co-stimulatory domains that impact persistence and resistance to exhaustion of CAR-T cells remain largely undefined. Here, we report the influence of signaling domains of coreceptors CD28 and 4-1BB on the metabolic characteristics of human CAR T cells. Inclusion of 4-1BB in the CAR architecture promoted the outgrowth of CD8(+) central memorycells that had significantly enhanced respiratory capacity, increased fatty acid oxidation and enhanced mitochondrial biogenesis. In contrast, CAR T cells with CD28 domains yielded effector memory cells with a genetic signature consistent with enhanced glycolysis. These results provide, at least in part, a mechanistic insight into the differential persistence of CAR-T cells expressing 4-1BB or CD28 signaling domains in clinical trials and inform the design of future CAR T cell therapies. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Memory window engineering of Ta2O5-x oxide-based resistive switches via incorporation of various insulating frames

    Science.gov (United States)

    Lee, Ah Rahm; Baek, Gwang Ho; Kim, Tae Yoon; Ko, Won Bae; Yang, Seung Mo; Kim, Jongmin; Im, Hyun Sik; Hong, Jin Pyo

    2016-07-01

    Three-dimensional (3D) stackable memory frames, including nano-scaled crossbar arrays, are one of the most reliable building blocks to meet the demand of high-density non-volatile memory electronics. However, their utilization has the disadvantage of introducing issues related to sneak paths, which can negatively impact device performance. We address the enhancement of complementary resistive switching (CRS) features via the incorporation of insulating frames as a generic approach to extend their use; here, a Pt/Ta2O5-x/Ta/Ta2O5-x/Pt frame is chosen as the basic CRS cell. The incorporation of Ta/Ta2O5-x/Ta or Pt/amorphous TaN/Pt insulting frames into the basic CRS cell ensures the appreciably advanced memory features of CRS cells including higher on/off ratios, improved read margins, and increased selectivity without reliability degradation. Experimental observations identified that a suitable insulating frame is crucial for adjusting the abrupt reset events of the switching element, thereby facilitating the enhanced electrical characteristics of CRS cells that are suitable for practical applications.

  20. Fast Response, Open-Celled Porous, Shape Memory Effect Actuators with Integrated Attachments

    Science.gov (United States)

    Jardine, Andrew Peter (Inventor)

    2015-01-01

    This invention relates to the exploitation of porous foam articles exhibiting the Shape Memory Effect as actuators. Each foam article is composed of a plurality of geometric shapes, such that some geometric shapes can fit snugly into or around rigid mating connectors that attach the Shape Memory foam article intimately into the load path between a static structure and a moveable structure. The foam is open-celled, composed of a plurality of interconnected struts whose mean diameter can vary from approximately 50 to 500 microns. Gases and fluids flowing through the foam transfer heat rapidly with the struts, providing rapid Shape Memory Effect transformations. Embodiments of porous foam articles as torsional actuators and approximately planar structures are disposed. Simple, integral connection systems exploiting the ability to supply large loads to a structure, and that can also supply hot and cold gases and fluids to effect rapid actuation are also disposed.

  1. Enhanced resistive switching and multilevel behavior in bilayered HfAlO/HfAlO{sub x} structures for non-volatile memory applications

    Energy Technology Data Exchange (ETDEWEB)

    Faita, F. L., E-mail: fabriciofaita@gmail.com [Centre of Physics, University of Minho, Campus de Gualtar, 4710-057 Braga (Portugal); Departamento de Física, Universidade Federal de Santa Catarina, Campus Trindade, 88040-900 Florianópolis, SC (Brazil); Silva, J. P. B., E-mail: josesilva@fisica.uminho.pt [Centre of Physics, University of Minho, Campus de Gualtar, 4710-057 Braga (Portugal); IFIMUP and IN-Institute of Nanoscience and Nanotechnology, Departamento de Física e Astronomia, Faculdade de Ciências da Universidade do Porto, 4169-007 Porto (Portugal); Pereira, M.; Gomes, M. J. M. [Centre of Physics, University of Minho, Campus de Gualtar, 4710-057 Braga (Portugal)

    2015-12-14

    In this work, hafnium aluminum oxide (HfAlO) thin films were deposited by ion beam sputtering deposition technique on Si substrate. The presence of oxygen vacancies in the HfAlO{sub x} layer deposited in oxygen deficient environment is evidenced from the photoluminescence spectra. Furthermore, HfAlO(oxygen rich)/HfAlO{sub x}(oxygen poor) bilayer structures exhibit multilevel resistive switching (RS), and the switching ratio becomes more prominent with increasing the HfAlO layer thickness. The bilayer structure with HfAlO/HfAlO{sub x} thickness of 30/40 nm displays the enhanced multilevel resistive switching characteristics, where the high resistance state/intermediate resistance state (IRS) and IRS/low resistance state resistance ratios are ≈10{sup 2} and ≈5 × 10{sup 5}, respectively. The switching mechanisms in the bilayer structures were investigated by the temperature dependence of the three resistance states. This study revealed that the multilevel RS is attributed to the coupling of ionic conduction and the metallic conduction, being the first associated to the formation and rupture of conductive filaments related to oxygen vacancies and the second with the formation of a metallic filament. Moreover, the bilayer structures exhibit good endurance and stability in time.

  2. Simultaneous Microwave Extraction and Separation of Volatile and Non-Volatile Organic Compounds of Boldo Leaves. From Lab to Industrial Scale

    Directory of Open Access Journals (Sweden)

    Loïc Petigny

    2014-04-01

    Full Text Available Microwave extraction and separation has been used to increase the concentration of the extract compared to the conventional method with the same solid/liquid ratio, reducing extraction time and separate at the same time Volatile Organic Compounds (VOC from non-Volatile Organic Compounds (NVOC of boldo leaves. As preliminary study, a response surface method has been used to optimize the extraction of soluble material and the separation of VOC from the plant in laboratory scale. The results from the statistical analysis revealed that the optimized conditions were: microwave power 200 W, extraction time 56 min and solid liquid ratio of 7.5% of plants in water. Lab scale optimized microwave method is compared to conventional distillation, and requires a power/mass ratio of 0.4 W/g of water engaged. This power/mass ratio is kept in order to upscale from lab to pilot plant.

  3. Analysis of drugs of forensic interest with capillary zone electrophoresis/time-of-flight mass spectrometry based on the use of non-volatile buffers.

    Science.gov (United States)

    Gottardo, Rossella; Mikšík, Ivan; Aturki, Zeineb; Sorio, Daniela; Seri, Catia; Fanali, Salvatore; Tagliaro, Franco

    2012-02-01

    The present work is aimed at investigating the influence of the background electrolyte composition and concentration on the separation efficiency and resolution and mass spectrometric detection of illicit drugs in a capillary zone electrophoresis-electrospray ionization-time of flight mass spectrometry (CZE-ESI-TOF MS) system. The effect of phosphate, borate and Tris buffers on the separation and mass spectrometry response of a mixture of 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, methadone, cocaine, morphine, codeine and 6-monoacetylmorphine was studied, in comparison with a reference ammonium formate separation buffer. Inorganic non-volatile borate and Tris buffers proved hardly suitable for capillary electrophoresis-mass spectrometry (CE-MS) analysis, but quite unexpectedly ammonium phosphate buffers showed good separation and ionization performances for all the analytes tested. Applications of this method to real samples of hair from drug addicts are also provided. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. A Simultaneous Analytical Method to Profile Non-Volatile Components with Low Polarity Elucidating Differences Between Tobacco Leaves Using Atmospheric Pressure Chemical Ionization Mass Spectrometry Detection

    Directory of Open Access Journals (Sweden)

    Ishida Naoyuki

    2016-04-01

    Full Text Available A comprehensive analytical method using liquid chromatography atmospheric pressure chemical ionization mass spectrometry detector (LC/APCI-MSD was developed to determine key non-volatile components with low polarity elucidating holistic difference among tobacco leaves. Nonaqueous reversed-phase chromatography (NARPC using organic solvent ensured simultaneous separation of various components with low polarity in tobacco resin. Application of full-scan mode to APCI-MSD hyphenated with NARPC enabled simultaneous detection of numerous intense product ions given by APCI interface. Parameters for data processing to filter, feature and align peaks were adjusted in order to strike a balance between comprehensiveness and reproducibility in analysis. 63 types of components such as solanesols, chlorophylls, phytosterols, triacylglycerols, solanachromene and others were determined on total ion chromatograms according to authentic components, wavelength spectrum and mass spectrum. The whole area of identified entities among the ones detected on total ion chromatogram reached to over 60% and major entities among those identified showed favorable linearity of determination coefficient of over 0.99. The developed method and data processing procedure were therefore considered feasible for subsequent multivariate analysis. Data matrix consisting of a number of entities was then subjected to principal component analysis (PCA and hierarchical clustering analysis. Cultivars of tobacco leaves were distributed far from each cultivar on PCA score plot and each cluster seemed to be characterized by identified non-volatile components with low polarity. While fluecured Virginia (FCV was loaded by solanachromene, phytosterol esters and triacylglycerols, free phytosterols and chlorophylls loaded Burley (BLY and Oriental (ORI respectively. Consequently the whole methodology consisting of comprehensive method and data processing procedure proved useful to determine key

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

    Directory of Open Access Journals (Sweden)

    Nicola L Bird

    Full Text Available 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.

  6. Granule cell dispersion is associated with memory impairment in right mesial temporal lobe epilepsy.

    Science.gov (United States)

    Neves, Rafael Scarpa da Costa; de Souza Silva Tudesco, Ivanda; Jardim, Anaclara Prada; Caboclo, Luís Otávio Sales Ferreira; Lancellotti, Carmen; Ferrari-Marinho, Taíssa; Hamad, Ana Paula; Marinho, Murilo; Centeno, Ricardo Silva; Cavalheiro, Esper Abrão; Scorza, Carla Alessandra; Yacubian, Elza Márcia Targas

    2012-11-01

    We analyzed the association of granule cell dispersion (GCD) with memory performance, clinical data and surgical outcome in a series of patients with mesial temporal lobe epilepsy (MTLE) and mesial temporal sclerosis (MTS). Hippocampal specimens from 54 patients with MTLE (27 patients with right MTLE and 27 with left MTLE) and unilateral MTS, who were separated into GCD and no-GCD groups and thirteen controls were studied. Quantitative neuropathological evaluation was performed using hippocampal sections stained with NeuN. Patients' neuropsychological measures, clinical data, type of MTS and surgical outcome were reviewed. GCD occurred in 28 (51.9%) patients. No correlation between GCD and MTS pattern, clinical data or surgical outcome was found. The presence of GCD was correlated with worse visuospatial memory performance in right MTLE, but not with memory performance in left MTLE. GCD may be related to memory impairment in right MTLE-MTS patients. However, the role of GCD in memory function is not precisely defined. Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  7. Regulatory role for the memory B cell as suppressor-inducer of feedback control

    International Nuclear Information System (INIS)

    Kennedy, M.W.; Thomas, D.B.

    1983-01-01

    A regulatory role is proposed for the antigen-responsive B cell, as suppressor-inducer of feedback control during the secondary response in vivo. In a double adoptive transfer of memory cells primed to a thymus-dependent antigen from one irradiated host to another, antigen-specific suppressors are generated after a critical time in the primary recipient, able to entirely ablate a secondary anti-hapten response. Positive cell selection in the fluorescence-activated cell sorter confirmed that suppression was mediated by an Lyt-2+ T cell; however, positively selected B cells were also inhibitory and able to induce suppressors in a carrier-specific manner: B hapten induced suppressors in a carrier-primed population, and B carrier induced suppressors in a hapten-carrier population. At the peak of the antibody response in the primary host, memory B cells and their progeny were unable to differentiate further to plasma cells due to their intrinsic suppressor-inducer activity, but this autoregulatory circuit could be severed by adoptive transfer to carrier-primed, X-irradiated recipients

  8. Human Infant Memory B Cell and CD4+ T Cell Responses to HibMenCY-TT Glyco-Conjugate Vaccine.

    Directory of Open Access Journals (Sweden)

    Angela Fuery

    Full Text Available Carrier-specific T cell and polysaccharide-specific B cell memory responses are not well characterised in infants following glyco-conjugate vaccination. We aimed to determine if the number of Meningococcal (Men C- and Y- specific memory B cells and; number and quality of Tetanus Toxoid (TT carrier-specific memory CD4+ T cells are associated with polysaccharide-specific IgG post HibMenCY-TT vaccination. Healthy infants received HibMenCY-TT vaccine at 2, 4 and 6 months with a booster at 12 months. Peripheral blood mononuclear cells were isolated and polysaccharide-specific memory B cells enumerated using ELISpot. TT-specific memory CD4+ T cells were detected and phenotyped based on CD154 expression and intracellular TNF-α, IL-2 and IFN-γ expression following stimulation. Functional polysaccharide-specific IgG titres were measured using the serum bactericidal activity (SBA assay. Polysaccharide-specific Men C- but not Men Y- specific memory B cell frequencies pre-boost (12 months were significantly associated with post-boost (13 months SBA titres. Regression analysis showed no association between memory B cell frequencies post-priming (at 6 or 7 months and SBA at 12 months or 13 months. TT-specific CD4+ T cells were detected at frequencies between 0.001 and 0.112 as a percentage of CD3+ T cells, but their numbers were not associated with SBA titres. There were significant negative associations between SBA titres at M13 and cytokine expression at M7 and M12.Induction of persistent polysaccharide-specific memory B cells prior to boosting is an important determinant of secondary IgG responses in infants. However, polysaccharide-specific functional IgG responses appear to be independent of the number and quality of circulating carrier-specific CD4+ T cells after priming.

  9. Curtailed T-cell activation curbs effector differentiation and generates CD8+ T cells with a naturally-occurring memory stem cell phenotype.

    Science.gov (United States)

    Zanon, Veronica; Pilipow, Karolina; Scamardella, Eloise; De Paoli, Federica; De Simone, Gabriele; Price, David A; Martinez Usatorre, Amaia; Romero, Pedro; Mavilio, Domenico; Roberto, Alessandra; Lugli, Enrico

    2017-09-01

    Human T memory stem (T SCM ) cells with superior persistence capacity and effector functions are emerging as important players in the maintenance of long-lived T-cell memory and are thus considered an attractive population to be used in adoptive transfer-based immunotherapy of cancer. However, the molecular signals regulating their generation remain poorly defined. Here we show that curtailed T-cell receptor stimulation curbs human effector CD8 + T-cell differentiation and allows the generation of CD45RO - CD45RA + CCR7 + CD27 + CD95 + -phenotype cells from highly purified naïve T-cell precursors, resembling naturally-occurring human T SCM . These cells proliferate extensively in vitro and in vivo, express low amounts of effector-associated genes and transcription factors and undergo considerable self-renewal in response to IL-15 while retaining effector differentiation potential. Such a phenotype is associated with a lower number of mitochondria compared to highly-activated effector T cells committed to terminal differentiation. These results shed light on the molecular signals that are required to generate long-lived memory T cells with potential application in adoptive cell transfer immunotherapy. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co.KGaA, Weinheim.

  10. Diet-induced obesity in mice reduces the maintenance of influenza-specific CD8+ memory T cells.

    Science.gov (United States)

    Karlsson, Erik A; Sheridan, Patricia A; Beck, Melinda A

    2010-09-01

    Obesity has been associated with increasing the risk for type 2 diabetes and heart disease, but its influence on the immune response to viral infection is understudied. Memory T cells generated during a primary influenza infection are important for protection against subsequent influenza exposures. Previously, we have demonstrated that diet-induced obese (DIO) mice have increased morbidity and mortality following secondary influenza infection compared with lean mice. To determine whether the problem resided in a failure to maintain functional, influenza-specific CD8(+) memory T cells, male DIO and lean mice were infected with influenza X-31. At 84 d postinfection, DIO mice had a 10% reduction in memory T cell numbers. This reduction may have resulted from significantly reduced memory T cell expression of interleukin 2 receptor beta (IL-2R beta, CD122), but not IL-7 receptor alpha (CD127), which are both required for memory cell maintenance. Peripheral leptin resistance in the DIO mice may be a contributing factor to the impairment. Indeed, leptin receptor mRNA expression was significantly reduced in the lungs of obese mice, whereas suppressor of cytokine signaling (Socs)1 and Socs3 mRNA expression were increased. It is imperative to understand how the obese state alters memory T cells, because impairment in maintenance of functional memory responses has important implications for vaccine efficacy in an obese population.

  11. Protection against Pertussis in Humans Correlates to Elevated Serum Antibodies and Memory B Cells

    Directory of Open Access Journals (Sweden)

    Valentina Marcellini

    2017-09-01

    Full Text Available Pertussis is a respiratory infection caused by Bordetella pertussis that may be particularly severe and even lethal in the first months of life when infants are still too young to be vaccinated. Adults and adolescents experience mild symptoms and are the source of infection for neonates. Adoptive maternal immunity does not prevent pertussis in the neonate. We compared the specific immune response of mothers of neonates diagnosed with pertussis and mothers of control children. We show that women have pre-existing pertussis-specific antibodies and memory B cells and react against the infection with a recall response increasing the levels specific serum IgG, milk IgA, and the frequency of memory B cells of all isotypes. Thus, the maternal immune system is activated in response to pertussis and effectively prevents the disease indicating that the low levels of pre-formed serum antibodies are insufficient for protection. For this reason, memory B cells play a major role in the adult defense. The results of this study suggest that new strategies for vaccine design should aim at increasing long-lived plasma cells and their antibodies.

  12. Every breath you take: the impact of environment on resident memory CD8 T cells in the lung.

    Science.gov (United States)

    Shane, Hillary L; Klonowski, Kimberly D

    2014-01-01

    Resident memory T cells (TRM) are broadly defined as a population of T cells, which persist in non-lymphoid sites long-term, do not re-enter the circulation, and are distinct from central memory T cells (TCM) and circulating effector memory T cells (TEM). Recent studies have described populations of TRM cells in the skin, gut, lungs, and nervous tissue. However, it is becoming increasingly clear that the specific environment in which the TRM reside can further refine their phenotypical and functional properties. Here, we focus on the TRM cells that develop following respiratory infection and reside in the lungs and the lung airways. Specifically, we will review recent studies that have described some of the requirements for establishment of TRM cells in these tissues, and the defining characteristics of TRM in the lungs and lung airways. With continual bombardment of the respiratory tract by both pathogenic and environmental antigens, dynamic fluctuations in the local milieu including homeostatic resources and niche restrictions can impact TRM longevity. Beyond a comprehensive characterization of lung TRM cells, special attention will be placed on studies, which have defined how the microenvironment of the lung influences memory T cell survival at this site. As memory T cell populations in the lung airways are requisite for protection yet wane numerically over time, developing a comprehensive picture of factors which may influence TRM development and persistence at these sites is important for improving T cell-based vaccine design.

  13. Every breath you take: The impact of environment on resident memory CD8 T cells in the lung

    Directory of Open Access Journals (Sweden)

    Hillary eShane

    2014-07-01

    Full Text Available Resident memory T cells (TRM are broadly defined as a population of T cells which persist in non-lymphoid sites long term, do not re-enter the circulation, and are distinct from central memory T cells (TCM and circulating effector memory T cells (TEM. Recent studies have described populations of TRM cells in the skin, gut, lungs and nervous tissue. However, it is becoming increasingly clear that the specific environment in which the TRM reside can further refine their phenotypical and functional properties. Here, we focus on the TRM cells that develop following respiratory infection and reside in the lungs and the lung airways. Specifically, we will review recent studies that have described some of the requirements for establishment of TRM cells in these tissues, and the defining characteristics of TRM in the lungs and lung airways. With continual bombardment of the respiratory tract by both pathogenic and environmental antigens, dynamic fluctuations in the local milieu including homeostatic resources and niche restrictions can impact TRM longevity. Beyond a comprehensive characterization of lung TRM cells, special attention will be placed on studies which have defined how the microenvironment of the lung influences memory T cell survival at this site. As memory T cell populations in the lung airways are requisite for protection yet wane numerically over time, developing a comprehensive picture of factors which may influence TRM development and persistence at these sites is important for improving T cell-based vaccine design.

  14. A dual-docking microfluidic cell migration assay (D2-Chip) for testing neutrophil chemotaxis and the memory effect.

    Science.gov (United States)

    Yang, Ke; Wu, Jiandong; Xu, Guoqing; Xie, Dongxue; Peretz-Soroka, Hagit; Santos, Susy; Alexander, Murray; Zhu, Ling; Zhang, Michael; Liu, Yong; Lin, Francis

    2017-04-18

    Chemotaxis is a classic mechanism for guiding cell migration and an important topic in both fundamental cell biology and health sciences. Neutrophils are a widely used model to study eukaryotic cell migration and neutrophil chemotaxis itself can lead to protective or harmful immune actions to the body. While much has been learnt from past research about how neutrophils effectively navigate through a chemoattractant gradient, many interesting questions remain unclear. For example, while it is tempting to model neutrophil chemotaxis using the well-established biased random walk theory, the experimental proof was challenged by the cell's highly persistent migrating nature. A special experimental design is required to test the key predictions from the random walk model. Another question that has interested the cell migration community for decades concerns the existence of chemotactic memory and its underlying mechanism. Although chemotactic memory has been suggested in various studies, a clear quantitative experimental demonstration will improve our understanding of the migratory memory effect. Motivated by these questions, we developed a microfluidic cell migration assay (so-called dual-docking chip or D 2 -Chip) that can test both the biased random walk model and the memory effect for neutrophil chemotaxis on a single chip enabled by multi-region gradient generation and dual-region cell alignment. Our results provide experimental support for the biased random walk model and chemotactic memory for neutrophil chemotaxis. Quantitative data analyses provide new insights into neutrophil chemotaxis and memory by making connections to entropic disorder, cell morphology and oscillating migratory response.

  15. Persistence of memory B-cell and T-cell responses to the quadrivalent HPV vaccine in HIV-infected children.

    Science.gov (United States)

    Weinberg, Adriana; Huang, Sharon; Moscicki, Anna-Barbara; Saah, Afred; Levin, Myron J

    2018-04-24

    To determine the magnitude and persistence of quadrivalent human papillomavirus (HPV)16 and HPV18 B-cell and T-cell memory after three or four doses of quadrivalent HPV vaccine (QHPV) in HIV-infected children. Seventy-four HIV-infected children immunized with four doses and 23 with three doses of QHPV had HPV16 and HPV18 IgG B-cell and IFNγ and IL2 T-cell ELISPOT performed at 2, 3.5 and 4-5 years after the last dose. HPV16 and HPV18 T-cell responses were similar in both treatment groups, with higher responses to HPV16 vs. HPV18. These HPV T-cell responses correlated with HIV disease characteristics at the study visits. Global T-cell function declined over time as measured by nonspecific mitogenic stimulation. B-cell memory was similar across treatment groups and HPV genotypes. There was a decline in HPV-specific B-cell memory over time that reached statistical significance for HPV16 in the four-dose group. B-cell and T-cell memory did not significantly differ after either three or four doses of QHPV in HIV-infected children. The clinical consequences of decreasing global T-cell function and HPV B-cell memory over time in HIV-infected children requires further investigation.

  16. Capacitor-less memory cell fabricated on nano-scale strained Si on a relaxed SiGe layer-on-insulator

    International Nuclear Information System (INIS)

    Kim, Tae-Hyun; Park, Jea-Gun

    2013-01-01

    We investigated the combined effect of the strained Si channel and hole confinement on the memory margin enhancement for a capacitor-less memory cell fabricated on nano-scale strained Si on a relaxed SiGe layer-on-insulator (ε-Si SGOI). The memory margin for the ε-Si SGOI capacitor-less memory cell was higher than that of the memory cell fabricated on an unstrained Si-on-insulator (SOI) and increased with increasing Ge concentration of the relaxed SiGe layer; i.e. the memory margin for the ε-Si SGOI capacitor-less memory cell (138.6 µA) at a 32 at% Ge concentration was 3.3 times higher than the SOI capacitor-less memory cell (43 µA). (paper)

  17. Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection

    Science.gov (United States)

    Lalor, Stephen J.; Leech, John M.; O’Keeffe, Kate M.; Mac Aogáin, Micheál; O’Halloran, Dara P.; Lacey, Keenan A.; Tavakol, Mehri; Hearnden, Claire H.; Fitzgerald-Hughes, Deirdre; Humphreys, Hilary; Fennell, Jérôme P.; van Wamel, Willem J.; Foster, Timothy J.; Geoghegan, Joan A.; Lavelle, Ed C.; Rogers, Thomas R.; McLoughlin, Rachel M.

    2015-01-01

    Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S. aureus peritonitis, we demonstrated that prior exposure to S. aureus enhanced IFNγ responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naïve mice. Translating these findings, we found that S. aureus antigen-specific Th1 cells were also significantly expanded during human S. aureus bloodstream infection (BSI). These Th1 cells were CD45RO+, indicative of a memory phenotype. Thus, exposure to S. aureus induces memory Th1 cells in mice and humans, identifying Th1 cells as potential S. aureus vaccine targets. Consequently, we developed a model vaccine comprising staphylococcal clumping factor A, which we demonstrate to be an effective human T cell antigen, combined with the Th1-driving adjuvant CpG. This novel Th1-inducing vaccine conferred significant protection during S. aureus infection in mice. This study notably advances our understanding of S. aureus cellular immunity, and demonstrates for the first time that a correlate of S. aureus protective immunity identified in mice may be relevant in humans. PMID:26539822

  18. Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection.

    LENUS (Irish Health Repository)

    Brown, Aisling F

    2015-01-01

    Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S. aureus peritonitis, we demonstrated that prior exposure to S. aureus enhanced IFNγ responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naïve mice. Translating these findings, we found that S. aureus antigen-specific Th1 cells were also significantly expanded during human S. aureus bloodstream infection (BSI). These Th1 cells were CD45RO+, indicative of a memory phenotype. Thus, exposure to S. aureus induces memory Th1 cells in mice and humans, identifying Th1 cells as potential S. aureus vaccine targets. Consequently, we developed a model vaccine comprising staphylococcal clumping factor A, which we demonstrate to be an effective human T cell antigen, combined with the Th1-driving adjuvant CpG. This novel Th1-inducing vaccine conferred significant protection during S. aureus infection in mice. This study notably advances our understanding of S. aureus cellular immunity, and demonstrates for the first time that a correlate of S. aureus protective immunity identified in mice may be relevant in humans.

  19. Associations of unilateral whisker and olfactory signals induce synapse formation and memory cell recruitment in bilateral barrel cortices: cellular mechanism for unilateral training toward bilateral memory

    Directory of Open Access Journals (Sweden)

    Zilong Gao

    2016-12-01

    Full Text Available Somatosensory signals and operative skills learned by unilateral limbs can be retrieved bilaterally. In terms of cellular mechanism underlying this unilateral learning toward bilateral memory, we hypothesized that associative memory cells in bilateral cortices and synapse innervations between them were produced. In the examination of this hypothesis, we have observed that paired unilateral whisker and odor stimulations led to odorant-induced whisker motions in bilateral sides, which were attenuated by inhibiting the activity of barrel cortices. In the mice that showed bilateral cross-modal responses, the neurons in both sides of barrel cortices became to encode this new odor signal alongside the innate whisker signal. Axon projections and synapse formations from the barrel cortex, which was co-activated with the piriform cortex, toward its contralateral barrel cortex were upregulated. Glutamatergic synaptic transmission in bilateral barrel cortices was upregulated and GABAergic synaptic transmission was downregulated. The associative activations of the sensory cortices facilitate new axon projection, glutamatergic synapse formation and GABAergic synapse downregulation, which drive the neurons to be recruited as associative memory cells in the bilateral cortices. Our data reveals the productions of associative memory cells and synapse innervations in bilateral sensory cortices for unilateral training toward bilateral memory.

  20. Field-effect transistor memories based on ferroelectric polymers

    Science.gov (United States)

    Zhang, Yujia; Wang, Haiyang; Zhang, Lei; Chen, Xiaomeng; Guo, Yu; Sun, Huabin; Li, Yun

    2017-11-01

    Field-effect transistors based on ferroelectrics have attracted intensive interests, because of their non-volatile data retention, rewritability, and non-destructive read-out. In particular, polymeric materials that possess ferroelectric properties are promising for the fabrications of memory devices with high performance, low cost, and large-area manufacturing, by virtue of their good solubility, low-temperature processability, and good chemical stability. In this review, we discuss the material characteristics of ferroelectric polymers, providing an update on the current development of ferroelectric field-effect transistors (Fe-FETs) in non-volatile memory applications. Program supported partially by the NSFC (Nos. 61574074, 61774080), NSFJS (No. BK20170075), and the Open Partnership Joint Projects of NSFC-JSPS Bilateral Joint Research Projects (No. 61511140098).

  1. Characterization of the metabolic phenotype of rapamycin-treated CD8+ T cells with augmented ability to generate long-lasting memory cells.

    Directory of Open Access Journals (Sweden)

    Shan He

    Full Text Available BACKGROUND: Cellular metabolism plays a critical role in regulating T cell responses and the development of memory T cells with long-term protections. However, the metabolic phenotype of antigen-activated T cells that are responsible for the generation of long-lived memory cells has not been characterized. DESIGN AND METHODS: Using lymphocytic choriomeningitis virus (LCMV peptide gp33-specific CD8(+ T cells derived from T cell receptor transgenic mice, we characterized the metabolic phenotype of proliferating T cells that were activated and expanded in vitro in the presence or absence of rapamycin, and determined the capability of these rapamycin-treated T cells to generate long-lived memory cells in vivo. RESULTS: Antigen-activated CD8(+ T cells treated with rapamycin gave rise to 5-fold more long-lived memory T cells in vivo than untreated control T cells. In contrast to that control T cells only increased glycolysis, rapamycin-treated T cells upregulated both glycolysis and oxidative phosphorylation (OXPHOS. These rapamycin-treated T cells had greater ability than control T cells to survive withdrawal of either glucose or growth factors. Inhibition of OXPHOS by oligomycin significantly reduced the ability of rapamycin-treated T cells to survive growth factor withdrawal. This effect of OXPHOS inhibition was accompanied with mitochondrial hyperpolarization and elevation of reactive oxygen species that are known to be toxic to cells. CONCLUSIONS: Our findings indicate that these rapamycin-treated T cells may represent a unique cell model for identifying nutrients and signals critical to regulating metabolism in both effector and memory T cells, and for the development of new methods to improve the efficacy of adoptive T cell cancer therapy.

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

    Science.gov (United States)

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

    2018-05-15

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

  3. Demonstration of Novel Sampling Techniques for Measurement of Turbine Engine Volatile and Non-Volatile Particulate Matter (PM) Emissions

    Science.gov (United States)

    2015-12-30

    emissions demonstration . 46 6 Figure 24. T63 engine with extension pipe to direct exhaust outside of the test cell for exhaust sampling with tip...to assess their effectiveness in conditioning turbine engine exhaust for total PM emissions measurements. Both were designed to promote the... effectively control and mitigate PM emissions. Aircraft PM is formed in the engine combustor due to incomplete combustion of fuel, and in the

  4. Ultra-Low Power Memory Design in Scaled Technology Nodes

    DEFF Research Database (Denmark)

    Zeinali, Behzad

    that the proposed SRAM reduces access time and leakage current by 40% and 20%, respectively, compared to the standard 8T-SRAM cell without any degradation in read and write margins. The second solution is an asymmetric Schottky barrier device, which can mitigate the read–write conflict of the 6T-SRAM cell in scaled...... technology nodes i.e. sub-50 nm. The 6T-SRAM designed based on the proposed device shows 18% leakage reduction and 54%, 6.6% and 3.1X improvement in read margin, write margin and write time, respectively, compared to the conventional 6T-SRAM cell. To address the standby power issue of SRAMs in scaled...... technology nodes, this thesis also investigates emerging non-volatile spintronics memories. In this respect, STT-MRAMs and SOT-MRAMs are studied and their design challenges are explored. To improve the read performance of STT-MRAMs, a novel non-destructive self-reference sensing scheme is proposed enabling...

  5. Cerebral Giant Cells are Necessary for the Formation and Recall of Memory of Conditioned Taste Aversion in Lymnaea.

    Science.gov (United States)

    Sunada, Hiroshi; Lukowiak, Ken; Ito, Etsuro

    2017-02-01

    The pond snail Lymnaea stagnalis can acquire conditioned taste aversion (CTA) as a long-term memory. CTA is caused by the temporal pairing of a stimulus, such as sucrose (the conditioned stimulus; CS), with another stimulus, such as electric shock (the unconditioned stimulus; US). Previous studies have demonstrated changes in both cellular and molecular properties in a pair of neurons known as the cerebral giant cells (CGCs), suggesting that these neurons play a key role in CTA. Here we examined the necessity of the pair of CGC somata for the learning, memory formation and memory recall of CTA by using the soma ablation technique. There was no difference in the feeding response elicited by the CS before and after ablation of the CGC somata. Ablation of the CGC somata before taste-aversion training resulted in the learning acquisition, but the memory formation was not observed 24 h later. We next asked whether memory was present when the CGC somata were ablated 24 h after taste-aversion training. The memory was present before performing the somata ablation. However, when we tested snails five days after somata ablation, the memory recall was not present. Together the data show that: 1) the somata of the CGCs are not necessary for learning acquisition; 2) the somata are necessary for memory formation; and 3) the somata are necessary for memory recall. That is, these results demonstrate that the CGCs function in the long-term memory of CTA in Lymnaea.

  6. A multi-level capacitor-less memory cell fabricated on a nano-scale strained silicon-on-insulator

    International Nuclear Information System (INIS)

    Park, Jea-Gun; Kim, Seong-Je; Shin, Mi-Hee; Song, Seung-Hyun; Shim, Tae-Hun; Chung, Sung-Woong; Enomoto, Hirofumi

    2011-01-01

    A multi-level capacitor-less memory cell was fabricated with a fully depleted n-metal-oxide-semiconductor field-effect transistor on a nano-scale strained silicon channel on insulator (FD sSOI n-MOSFET). The 0.73% biaxial tensile strain in the silicon channel of the FD sSOI n-MOSFET enhanced the effective electron mobility to ∼ 1.7 times that with an unstrained silicon channel. This thereby enables both front- and back-gate cell operations, demonstrating eight-level volatile memory-cell operation with a 1 ms retention time and 12 μA memory margin. This is a step toward achieving a terabit volatile memory cell.

  7. Material Engineering for Phase Change Memory

    Science.gov (United States)

    Cabrera, David M.

    As semiconductor devices continue to scale downward, and portable consumer electronics become more prevalent there is a need to develop memory technology that will scale with devices and use less energy, while maintaining performance. One of the leading prototypical memories that is being investigated is phase change memory. Phase change memory (PCM) is a non-volatile memory composed of 1 transistor and 1 resistor. The resistive structure includes a memory material alloy which can change between amorphous and crystalline states repeatedly using current/voltage pulses of different lengths and magnitudes. The most widely studied PCM materials are chalcogenides - Germanium-Antimony-Tellerium (GST) with Ge2Sb2Te3 and Germanium-Tellerium (GeTe) being some of the most popular stochiometries. As these cells are scaled downward, the current/voltage needed to switch these materials becomes comparable to the voltage needed to sense the cell's state. The International Roadmap for Semiconductors aims to raise the threshold field of these devices from 66.6 V/mum to be at least 375 V/mum for the year 2024. These cells are also prone to resistance drift between states, leading to bit corruption and memory loss. Phase change material properties are known to influence PCM device performance such as crystallization temperature having an effect on data retention and litetime, while resistivity values in the amorphous and crystalline phases have an effect on the current/voltage needed to write/erase the cell. Addition of dopants is also known to modify the phase change material parameters. The materials G2S2T5, GeTe, with dopants - nitrogen, silicon, titanium, and aluminum oxide and undoped Gallium-Antimonide (GaSb) are studied for these desired characteristics. Thin films of these compositions are deposited via physical vapor deposition at IBM Watson Research Center. Crystallization temperatures are investigated using time resolved x-ray diffraction at Brookhaven National Laboratory

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

    Science.gov (United States)

    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

  9. Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility

    Science.gov (United States)

    Seumois, Grégory; Chavez, Lukas; Gerasimova, Anna; Lienhard, Matthias; Omran, Nada; Kalinke, Lukas; Vedanayagam, Maria; Ganesan, Asha Purnima V; Chawla, Ashu; Djukanović, Ratko; Ansel, K Mark; Peters, Bjoern; Rao, Anjana; Vijayanand, Pandurangan

    2014-01-01

    A characteristic feature of asthma is the aberrant accumulation, differentiation or function of memory CD4+ T cells that produce type 2 cytokines (TH2 cells). By mapping genome-wide histone modification profiles for subsets of T cells isolated from peripheral blood of healthy and asthmatic individuals, we identified enhancers with known and potential roles in the normal differentiation of human TH1 cells and TH2 cells. We discovered disease-specific enhancers in T cells that differ between healthy and asthmatic individuals. Enhancers that gained the histone H3 Lys4 dimethyl (H3K4me2) mark during TH2 cell development showed the highest enrichment for asthma-associated single nucleotide polymorphisms (SNPs), which supported a pathogenic role for TH2 cells in asthma. In silico analysis of cell-specific enhancers revealed transcription factors, microRNAs and genes potentially linked to human TH2 cell differentiation. Our results establish the feasibility and utility of enhancer profiling in well-defined populations of specialized cell types involved in disease pathogenesis. PMID:24997565

  10. The effects of cell phone conversations on the attention and memory of bystanders.

    Science.gov (United States)

    Galván, Veronica V; Vessal, Rosa S; Golley, Matthew T

    2013-01-01

    The pervasive use of cell phones impacts many people-both cell phone users and bystanders exposed to conversations. This study examined the effects of overhearing a one-sided (cell phone) conversation versus a two-sided conversation on attention and memory. In our realistic design, participants were led to believe they were participating in a study examining the relationship between anagrams and reading comprehension. While the participant was completing an anagram task, the researcher left the room and participants overheard a scripted conversation, either two confederates talking with each other or one confederate talking on a cell phone. Upon the researcher's return, the participant took a recognition memory task with words from the conversation, and completed a questionnaire measuring the distracting nature of the conversation. Participants who overheard the one-sided conversation rated the conversation as significantly higher in distractibility than those who overheard the two-sided conversation. Also, participants in the one-sided condition scored higher on the recognition task. In particular they were more confident and accurate in their responses to words from the conversation than participants in the two-sided condition. However, participants' scores on the anagram task were not significantly different between conditions. As in real world situations, individual participants could pay varying amounts of attention to the conversation since they were not explicitly instructed to ignore it. Even though the conversation was irrelevant to the anagram task and contained less words and noise, one-sided conversations still impacted participants' self-reported distractibility and memory, thus showing people are more attentive to cell phone conversations than two-sided conversations. Cell phone conversations may be a common source of distraction causing negative consequences in workplace environments and other public places.

  11. Altered distribution of peripheral blood memory B cells in humans chronically infected with Trypanosoma cruzi.

    Science.gov (United States)

    Fernández, Esteban R; Olivera, Gabriela C; Quebrada Palacio, Luz P; González, Mariela N; Hernandez-Vasquez, Yolanda; Sirena, Natalia María; Morán, María L; Ledesma Patiño, Oscar S; Postan, Miriam

    2014-01-01

    Numerous abnormalities of the peripheral blood T cell compartment have been reported in human chronic Trypanosoma cruzi infection and related to prolonged antigenic stimulation by persisting parasites. Herein, we measured circulating lymphocytes of various phenotypes based on the differential expression of CD19, CD4, CD27, CD10, IgD, IgM, IgG and CD138 in a total of 48 T. cruzi-infected individuals and 24 healthy controls. Infected individuals had decreased frequencies of CD19+CD27+ cells, which positively correlated with the frequencies of CD4+CD27+ cells. The contraction of CD19+CD27+ cells was comprised of IgG+IgD-, IgM+IgD- and isotype switched IgM-IgD- memory B cells, CD19+CD10+CD27+ B cell precursors and terminally differentiated CD19+CD27+CD138+ plasma cells. Conversely, infected individuals had increased proportions of CD19+IgG+CD27-IgD- memory and CD19+IgM+CD27-IgD+ transitional/naïve B cells. These observations prompted us to assess soluble CD27, a molecule generated by the cleavage of membrane-bound CD27 and used to monitor systemic immune activation. Elevated levels of serum soluble CD27 were observed in infected individuals with Chagas cardiomyopathy, indicating its potentiality as an immunological marker for disease progression in endemic areas. In conclusion, our results demonstrate that chronic T. cruzi infection alters the distribution of various peripheral blood B cell subsets, probably related to the CD4+ T cell deregulation process provoked by the parasite in humans.

  12. Altered distribution of peripheral blood memory B cells in humans chronically infected with Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Esteban R Fernández

    Full Text Available Numerous abnormalities of the peripheral blood T cell compartment have been reported in human chronic Trypanosoma cruzi infection and related to prolonged antigenic stimulation by persisting parasites. Herein, we measured circulating lymphocytes of various phenotypes based on the differential expression of CD19, CD4, CD27, CD10, IgD, IgM, IgG and CD138 in a total of 48 T. cruzi-infected individuals and 24 healthy controls. Infected individuals had decreased frequencies of CD19+CD27+ cells, which positively correlated with the frequencies of CD4+CD27+ cells. The contraction of CD19+CD27+ cells was comprised of IgG+IgD-, IgM+IgD- and isotype switched IgM-IgD- memory B cells, CD19+CD10+CD27+ B cell precursors and terminally differentiated CD19+CD27+CD138+ plasma cells. Conversely, infected individuals had increased proportions of CD19+IgG+CD27-IgD- memory and CD19+IgM+CD27-IgD+ transitional/naïve B cells. These observations prompted us to assess soluble CD27, a molecule generated by the cleavage of membrane-bound CD27 and used to monitor systemic immune activation. Elevated levels of serum soluble CD27 were observed in infected individuals with Chagas cardiomyopathy, indicating its potentiality as an immunological marker for disease progression in endemic areas. In conclusion, our results demonstrate that chronic T. cruzi infection alters the distribution of various peripheral blood B cell subsets, probably related to the CD4+ T cell deregulation process provoked by the parasite in humans.

  13. FinFET memory cell improvements for higher immunity against single event upsets

    Science.gov (United States)

    Sajit, Ahmed Sattar

    The 21st century is witnessing a tremendous demand for transistors. Life amenities have incorporated the transistor in every aspect of daily life, ranging from toys to rocket science. Day by day, scaling down the transistor is becoming an imperious necessity. However, it is not a straightforward process; instead, it faces overwhelming challenges. Due to these scaling changes, new technologies, such as FinFETs for example, have emerged as alternatives to the conventional bulk-CMOS technology. FinFET has more control over the channel, therefore, leakage current is reduced. FinFET could bridge the gap between silicon devices and non-silicon devices. The semiconductor industry is now incorporating FinFETs in systems and subsystems. For example, Intel has been using them in their newest processors, delivering potential saving powers and increased speeds to memory circuits. Memory sub-systems are considered a vital component in the digital era. In memory, few rows are read or written at a time, while the most rows are static; hence, reducing leakage current increases the performance. However, as a transistor shrinks, it becomes more vulnerable to the effects from radioactive particle strikes. If a particle hits a node in a memory cell, the content might flip; consequently, leading to corrupting stored data. Critical fields, such as medical and aerospace, where there are no second chances and cannot even afford to operate at 99.99% accuracy, has induced me to find a rigid circuit in a radiated working environment. This research focuses on a wide spectrum of memories such as 6T SRAM, 8T SRAM, and DICE memory cells using FinFET technology and finding the best platform in terms of Read and Write delay, susceptibility level of SNM, RSNM, leakage current, energy consumption, and Single Event Upsets (SEUs). This research has shown that the SEU tolerance that 6T and 8T FinFET SRAMs provide may not be acceptable in medical and aerospace applications where there is a very high

  14. Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells

    Science.gov (United States)

    Watanabe, Rei; Gehad, Ahmed; Yang, Chao; Campbell, Laura; Teague, Jessica E.; Schlapbach, Christoph; Elco, Christopher; Huang, Victor; Matos, Tiago R.; Kupper, Thomas S.; Clark, Rachael A.

    2015-01-01

    The skin of an adult human contains approximately 20 billion memory T cells. Epithelial barrier tissues are infiltrated by a combination of resident and recirculating T cells in mice but the relative proportions and functional activities of resident versus recirculating T cells have not been evaluated in human skin. We discriminated resident from recirculating T cells in human engrafted mice and lymphoma patients using alemtuzumab, a medication that depletes recirculating T cells from skin, and then analyzed these T cell populations in healthy human skin. All non-recirculating resident memory T cells (TRM) expressed CD69, but the majority were CD4+, CD103− and located in the dermis, in contrast to studies in mice. Both CD4+ and CD8+ CD103+ TRM were enriched in the epidermis, had potent effector functions and had a limited proliferative capacity compared to CD103− TRM. TRM of both types had more potent effector functions than recirculating T cells. Induction of CD103 on human T cells was enhanced by keratinocyte contact, depended on TGFβ and was independent of T cell keratinocyte adhesive interactions. We observed two distinct populations of recirculating T cells, CCR7+/L-selectin+ central memory T cells (TCM) and CCR7+/L-selectin− T cells, which we term migratory memory T cells (TMM). Circulating skin-tropic TMM were intermediate in cytokine production between TCM and effector memory T cells. In patients with cutaneous T cell lymphoma, malignant TCM and TMM induced distinct inflammatory skin lesions and TMM were depleted more slowly from skin after alemtuzumab, suggesting TMM may recirculate more slowly. In summary, human skin is protected by four functionally distinct populations of T cells, two resident and two recirculating, with differing territories of migration and distinct functional activities. PMID:25787765

  15. Effect of human bone marrow mesenchymal stromal cells on cytokine production by peripheral blood naive, memory, and effector T cells.

    Science.gov (United States)

    Laranjeira, Paula; Pedrosa, Monia; Pedreiro, Susana; Gomes, Joana; Martinho, Antonio; Antunes, Brigida; Ribeiro, Tania; Santos, Francisco; Trindade, Helder; Paiva, Artur

    2015-01-05

    The different distribution of T cells among activation/differentiation stages in immune disorders may condition the outcome of mesenchymal stromal cell (MSC)-based therapies. Indeed, the effect of MSCs in the different functional compartments of T cells is not completely elucidated. We investigated the effect of human bone marrow MSCs on naturally occurring peripheral blood functional compartments of CD4(+) and CD8(+) T cells: naive, central memory, effector memory, and effector compartments. For that, mononuclear cells (MNCs) stimulated with phorbol myristate acetate (PMA) plus ionomycin were cultured in the absence/presence of MSCs. The percentage of cells expressing tumor necrosis factor-alpha (TNF-α), interferon gamma (IFNγ), and interleukin-2 (IL-2), IL-17, IL-9, and IL-6 and the amount of cytokine produced were assessed by flow cytometry. mRNA levels of IL-4, IL-10, transforming growth factor-beta (TGF-β), and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) in purified CD4(+) and CD8(+) T cells, and phenotypic and mRNA expression changes induced by PMA + ionomycin stimulation in MSCs, were also evaluated. MSCs induced the reduction of the percentage of CD4(+) and CD8(+) T cells producing TNF-α, IFNγ, and IL-2 in all functional compartments, except for naive IFNγ(+)CD4(+) T cells. This inhibitory effect differentially affected CD4(+) and CD8(+) T cells as well as the T-cell functional compartments; remarkably, different cytokines showed distinct patterns of inhibition regarding both the percentage of producing cells and the amount of cytokine produced. Likewise, the percentages of IL-17(+), IL-17(+)TNF-α(+), and IL-9(+) within CD4(+) and CD8(+) T cells and of IL-6(+)CD4(+) T cells were decreased in MNC-MSC co-cultures. MSCs decreased IL-10 and increased IL-4 mRNA expression in stimulated CD4(+) and CD8(+) T cells, whereas TGF-β was reduced in CD8(+) and augmented in CD4(+) T cells, with no changes for CTLA4. Finally, PMA

  16. Cell characteristics of a multiple alloy nano-dots memory structure

    International Nuclear Information System (INIS)

    Bea, Ji Chel; Lee, Kang-Wook; Tanaka, Tetsu; Koyanagi, Mitsumasa; Song, Yun Heub; Lee, Gae-Hun

    2009-01-01

    A multiple alloy metal nano-dots memory using FN tunneling was investigated in order to confirm its structural possibility for future flash memory. In this work, a multiple FePt nano-dots device with a high work function (∼5.2 eV) and extremely high dot density (∼1.2 × 10 13 cm −2 ) was fabricated. Its structural effect for multiple layers was evaluated and compared to the one with a single layer in terms of the cell characteristics and reliability. We confirm that MOS capacitor structures with two to four multiple FePt nano-dot layers provide a larger threshold voltage window and better retention characteristics. Furthermore, it was also revealed that several process parameters for block oxide and inter-tunnel oxide between the nano-dot layers are very important to improve the efficiency of electron injection into multiple nano-dots. From these results, it is expected that a multiple FePt nano-dots memory using Fowler–Nordheim (FN) tunneling could be a candidate structure for future flash memory

  17. Atypical memory B cells in human chronic infectious diseases: An interim report.

    Science.gov (United States)

    Portugal, Silvia; Obeng-Adjei, Nyamekye; Moir, Susan; Crompton, Peter D; Pierce, Susan K

    2017-11-01

    Immunological memory is a remarkable phenomenon in which survival of an initial infection by a pathogen leads to life-long protection from disease upon subsequent exposure to that same pathogen. For many infectious diseases, long-lived protective humoral immunity is induced after only a single infection in a process that depends on the generation of memory B cells (MBCs) and long-lived plasma cells. However, over the past decade it has become increasingly evident that many chronic human infectious diseases to which immunity is not readily established, including HIV-AIDS, malaria and TB, are associated with fundamental alterations in the composition and functionality of MBC compartments. A common feature of these diseases appears to be a large expansion of what have been termed exhausted B cells, tissue-like memory B cells or atypical memory B cells (aMBCs) that, for simplicity's sake, we refer to here as aMBCs. It has been suggested that chronic immune activation and inflammation drive the expansion of aMBCs and that in some way aMBCs contribute to deficiencies in the acquisition of immunity in chronic infectious diseases. Although aMBCs are heterogeneous both within individuals and between diseases, they have several features in common including low expression of the cell surface markers that define classical MBCs in humans including CD21 and CD27 and high expression of genes not usually expressed by classical MBCs including T-bet, CD11c and a variety of inhibitory receptors, notably members of the FcRL family. Another distinguishing feature is their greatly diminished ability to be stimulated through their B cell receptors to proliferate, secrete cytokines or produce antibodies. In this review, we describe our current understanding of the phenotypic markers of aMBCs, their specificity in relation to the disease-causing pathogen, their functionality, the drivers of their expansion in chronic infections and their life span. We briefly summarize the features of a

  18. Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells

    NARCIS (Netherlands)

    Watanabe, Rei; Gehad, Ahmed; Yang, Chao; Scott, Laura L.; Teague, Jessica E.; Schlapbach, Christoph; Elco, Christopher P.; Huang, Victor; Matos, Tiago R.; Kupper, Thomas S.; Clark, Rachael A.

    2015-01-01

    The skin of an adult human contains about 20 billion memory T cells. Epithelial barrier tissues are infiltrated by a combination of resident and recirculating T cells in mice, but the relative proportions and functional activities of resident versus recirculating T cells have not been evaluated in

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

    NARCIS (Netherlands)

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

    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

  20. Search for Non-Volatile Components with Low Polarity Characterizing Tobacco Leaves Using Liquid Chromatography / Atmospheric Pressure Chemical Ionization Mass Spectrometry Detector

    Directory of Open Access Journals (Sweden)

    Ishida Naoyuki

    2015-06-01

    Full Text Available Alors que les regards se sont principalement tournés sur les composants à faible polarité dans la résine de feuilles de tabac en raison de leur lien probable avec le goût et l’arôme des produits du tabac, l’absence d’une méthode praticable et d’un outil analytique a longtemps fait obstacle à l’identification des composants non-volatils à faible polarité. L’auteur a, en l’occurrence, porté son attention sur l’analyse recourant à la chromatographie en phase inverse non aqueuse couplée à un détecteur à barrettes de photodiodes et à un détecteur de spectrométrie de masse par ionisation chimique à pression atmosphérique. Cette analyse fut considérée applicable à la séparation des composants nonvolatils significatifs mais inconnus. Son application a permis, avec succès, de séparer, détecter et quantifier simultanément plus de 100 composants non-volatils présentant des polarités faibles et différenciées. Ces composantes furent, entre autres, des solanésols, des triacylglycérides, des phytostérols et des chlorophylles. Cependant, les données concernant les différences de composition parmi les diverses feuilles de tabac demeurent encore partielles et basées sur une analyse ciblée plutôt que globales et basées sur une analyse exhaustive. Aucune étude n’a été, à ce jour, accomplie qui recense les composants essentiels permettant de distinguer, parmi les feuilles de tabac, les différents goûts, arômes, variétés, cultivars, processus de séchage et régions de culture. Par conséquent, toutes les données de quantification ont été consolidées dans le but de former une matrice multidimensionnelle complète et ont subi un traitement statistique qui a mis en exergue les catégories et les composants-clés des diverses feuilles de tabac grâce à une analyse en composantes principales et une classification hiérarchique. Les feuilles de tabac ont, dans un premier temps, été ventilées en

  1. Generation mechanism of RANKL(+) effector memory B cells: relevance to the pathogenesis of rheumatoid arthritis.

    Science.gov (United States)

    Ota, Yuri; Niiro, Hiroaki; Ota, Shun-Ichiro; Ueki, Naoko; Tsuzuki, Hirofumi; Nakayama, Tsuyoshi; Mishima, Koji; Higashioka, Kazuhiko; Jabbarzadeh-Tabrizi, Siamak; Mitoma, Hiroki; Akahoshi, Mitsuteru; Arinobu, Yojiro; Kukita, Akiko; Yamada, Hisakata; Tsukamoto, Hiroshi; Akashi, Koichi

    2016-03-16

    The efficacy of B cell-depleting therapies for rheumatoid arthritis underscores antibody-independent functions of effector B cells such as cognate T-B interactions and production of pro-inflammatory cytokines. Receptor activator of nuclear factor κB ligand (RANKL) is a key cytokine involved in bone destruction and is highly expressed in synovial fluid B cells in patients with rheumatoid arthritis. In this study we sought to clarify the generation mechanism of RANKL(+) effector B cells and their impacts on osteoclast differentiation. Peripheral blood and synovial fluid B cells from healthy controls and patients with rheumatoid arthritis were isolated using cell sorter. mRNA expression of RANKL, osteoprotegerin, tumor necrosis factor (TNF)-α, and Blimp-1 was analyzed by quantitative real-time polymerase chain reaction. Levels of RANKL, CD80, CD86, and CXCR3 were analyzed using flow cytometry. Functional analysis of osteoclastogenesis was carried out in the co-culture system using macrophage RAW264 reporter cells. RANKL expression was accentuated in CD80(+)CD86(+) B cells, a highly activated B-cell subset more abundantly observed in patients with rheumatoid arthritis. Upon activation via B-cell receptor and CD40, switched-memory B cells predominantly expressed RANKL, which was further augmented by interferon-γ (IFN-γ) but suppressed by interleukin-21. Strikingly, IFN-γ also enhanced TNF-α expression, while it strongly suppressed osteoprotegerin expression in B cells. IFN-γ increased the generation of CXCR3(+)RANKL(+) effector B cells, mimicking the synovial B cell phenotype in patients with rheumatoid arthritis. Finally, RANKL(+) effector B cells in concert with TNF-α facilitated osteoclast differentiation in vitro. Our current findings have shed light on the generation mechanism of pathogenic RANKL(+) effector B cells that would be an ideal therapeutic target for rheumatoid arthritis in the future.

  2. Aborted germinal center reactions and B cell memory by follicular T cells specific for a B cell receptor V region peptide.

    Science.gov (United States)

    Heiser, Ryan A; Snyder, Christopher M; St Clair, James; Wysocki, Lawrence J

    2011-07-01

    A fundamental problem in immunoregulation is how CD4(+) T cells react to immunogenic peptides derived from the V region of the BCR that are created by somatic mechanisms, presented in MHC II, and amplified to abundance by B cell clonal expansion during immunity. BCR neo Ags open a potentially dangerous avenue of T cell help in violation of the principle of linked Ag recognition. To analyze this issue, we developed a murine adoptive transfer model using paired donor B cells and CD4 T cells specific for a BCR-derived peptide. BCR peptide-specific T cells aborted ongoing germinal center reactions and impeded the secondary immune response. Instead, they induced the B cells to differentiate into short-lived extrafollicular plasmablasts that secreted modest quantities of Ig. These results uncover an immunoregulatory process that restricts the memory pathway to B cells that communicate with CD4 T cells via exogenous foreign Ag.

  3. miRNA profiling of naive, effector and memory CD8 T cells.

    Directory of Open Access Journals (Sweden)

    Haoquan Wu

    Full Text Available microRNAs have recently emerged as master regulators of gene expression during development and cell differentiation. Although profound changes in gene expression also occur during antigen-induced T cell differentiation, the role of miRNAs in the process is not known. We compared the miRNA expression profiles between antigen-specific naïve, effector and memory CD8+ T cells using 3 different methods--small RNA cloning, miRNA microarray analysis and real-time PCR. Although many miRNAs were expressed in all the T cell subsets, the frequency of 7 miRNAs (miR-16, miR-21, miR-142-3p, miR-142-5p, miR-150, miR-15b and let-7f alone accounted for approximately 60% of all miRNAs, and their expression was several fold higher than the other expressed miRNAs. Global downregulation of miRNAs (including 6/7 dominantly expressed miRNAs was observed in effector T cells compared to naïve cells and the miRNA expression levels tended to come back up in memory T cells. However, a few miRNAs, notably miR-21 were higher in effector and memory T cells compared to naïve T cells. These results suggest that concomitant with profound changes in gene expression, miRNA profile also changes dynamically during T cell differentiation. Sequence analysis of the cloned mature miRNAs revealed an extensive degree of end polymorphism. While 3'end polymorphisms dominated, heterogeneity at both ends, resembling drosha/dicer processing shift was also seen in miR-142, suggesting a possible novel mechanism to generate new miRNA and/or to diversify miRNA target selection. Overall, our results suggest that dynamic changes in the expression of miRNAs may be important for the regulation of gene expression during antigen-induced T cell differentiation. Our study also suggests possible novel mechanisms for miRNA biogenesis and function.

  4. Splenectomy alters distribution and turnover but not numbers or protective capacity of de novo generated memory CD8 T cells.

    Directory of Open Access Journals (Sweden)

    Marie eKim

    2014-11-01

    Full Text Available The spleen is a highly compartmentalized lymphoid organ that allows for efficient antigen presentation and activation of immune responses. Additionally, the spleen itself functions to remove senescent red blood cells, filter bacteria, and sequester platelets. Splenectomy, commonly performed after blunt force trauma or splenomegaly, has been shown to increase risk of certain bacterial and parasitic infections years after removal of the spleen. Although previous studies report defects in memory B cells and IgM titers in splenectomized patients, the effect of splenectomy on CD8 T cell responses and memory CD8 T cell function remains ill defined. Using TCR-transgenic P14 cells, we demonstrate that homeostatic proliferation and representation of pathogen-specific memory CD8 T cells in the blood are enhanced in splenectomized compared to sham surgery mice. Surprisingly, despite the enhanced turnover, splenectomized mice displayed no changes in total memory CD8 T cell numbers nor impaired protection against lethal dose challenge with Listeria monocytogenes. Thus, our data suggest that memory CD8 T cell maintenance and function remain intact in the absence of the spleen.

  5. Chatting in the face of the eyewitness: The impact of extraneous cell-phone conversation on memory for a perpetrator

    OpenAIRE

    Skelton, Faye.; Marsh, John.; Patel, Kruali.; Labonte, Katherine.; Threadgold, Emma.; Fodarella, Cristina.; Thorley, Rachel.; Battersby, Kirsty.; Frowd, Charlie.; Ball, Linden.; Vachon, Francois.

    2017-01-01

    Cell-phone conversation is ubiquitous within public spaces. The current study investigates whether ignored cell-phone conversation impairs eyewitness memory for a perpetrator. Participants viewed a video of a staged-crime in the presence of one side of a comprehensible cell-phone conversation (meaningful halfalogue), two sides of a comprehensible cell-phone conversation (meaningful dialogue), one side of an incomprehensible cell-phone conversation (meaningless halfalogue) or quiet. Between 24...

  6. Differences between naive and memory T cell phenotype in Malawian and UK adolescents: a role for Cytomegalovirus?

    Directory of Open Access Journals (Sweden)

    Wallace Diana

    2008-10-01

    Full Text Available Abstract Background Differences in degree of environmental exposure to antigens in early life have been hypothesized to lead to differences in immune status in individuals from different populations, which may have implications for immune responses in later years. Methods Venous blood from HIV-negative adolescents and blood from the umbilical cords of babies, born to HIV-negative women, post-delivery was collected and analysed using flow cytometry. T cell phenotype was determined from peripheral blood lymphocytes and cytomegalovirus (CMV seropositivity was assessed by ELISA in adolescents. Results HIV-negative Malawian adolescents were shown to have a lower percentage of naïve T cells (CD45RO-CD62Lhi CD11alo, a higher proportion of memory T cells and a higher percentage of CD28- memory (CD28-CD45RO+ T cells compared to age-matched UK adolescents. Malawian adolescents also had a lower percentage of central memory (CD45RA-CCR7+ T cells and a higher percentage of stable memory (CD45RA+CCR7- T cells than UK adolescents. All of the adolescents tested in Malawi were seropositive for CMV (59/59, compared to 21/58 (36% of UK adolescents. CMV seropositivity in the UK was associated with a reduced percentage of naïve T cells and an increased percentage of CD28- memory T cells in the periphery. No differences in the proportions of naïve and memory T cell populations were observed in cord blood samples from the two sites. Conclusion It is likely that these differences between Malawian and UK adolescents reflect a greater natural exposure to various infections, including CMV, in the African environment and may imply differences in the ability of these populations to induce and maintain immunological memory to vaccines and natural infections.

  7. Therapeutic limitations in tumor-specific CD8+ memory T cell engraftment

    International Nuclear Information System (INIS)

    Bathe, Oliver F; Dalyot-Herman, Nava; Malek, Thomas R

    2003-01-01

    Adoptive immunotherapy with cytotoxic T lymphocytes (CTL) represents an alternative approach to treating solid tumors. Ideally, this would confer long-term protection against tumor. We previously demonstrated that in vitro-generated tumor-specific CTL from the ovalbumin (OVA)-specific OT-I T cell receptor transgenic mouse persisted long after adoptive transfer as memory T cells. When recipient mice were challenged with the OVA-expressing E.G7 thymoma, tumor growth was delayed and sometimes prevented. The reasons for therapeutic failures were not clear. OT-I CTL were adoptively transferred to C57BL/6 mice 21 – 28 days prior to tumor challenge. At this time, the donor cells had the phenotypical and functional characteristics of memory CD8+ T cells. Recipients which developed tumor despite adoptive immunotherapy were analyzed to evaluate the reason(s) for therapeutic failure. Dose-response studies demonstrated that the degree of tumor protection was directly proportional to the number of OT-I CTL adoptively transferred. At a low dose of OT-I CTL, therapeutic failure was attributed to insufficient numbers of OT-I T cells that persisted in vivo, rather than mechanisms that actively suppressed or anergized the OT-I T cells. In recipients of high numbers of OT-I CTL, the E.G7 tumor that developed was shown to be resistant to fresh OT-I CTL when examined ex vivo. Furthermore, these same tumor cells no longer secreted a detectable level of OVA. In this case, resistance to immunotherapy was secondary to selection of clones of E.G7 that expressed a lower level of tumor antigen. Memory engraftment with tumor-specific CTL provides long-term protection against tumor. However, there are several limitations to this immunotherapeutic strategy, especially when targeting a single antigen. This study illustrates the importance of administering large numbers of effectors to engraft sufficiently efficacious immunologic memory. It also demonstrates the importance of targeting several

  8. Glucose-induced metabolic memory in Schwann cells: prevention by PPAR agonists.

    Science.gov (United States)

    Kim, Esther S; Isoda, Fumiko; Kurland, Irwin; Mobbs, Charles V

    2013-09-01

    A major barrier in reversing diabetic complications is that molecular and pathologic effects of elevated glucose persist despite normalization of glucose, a phenomenon referred to as metabolic memory. In the present studies we have investigated the effects of elevated glucose on Schwann cells, which are implicated in diabetic neuropathy. Using quantitative PCR arrays for glucose and fatty acid metabolism, we have found that chronic (>8 wk) 25 mM high glucose induces a persistent increase in genes that promote glycolysis, while inhibiting those that oppose glycolysis and alternate metabolic pathways such as fatty acid metabolism, the pentose phosphate pathway, and trichloroacetic acid cycle. These sustained effects were associated with decreased peroxisome proliferator-activated receptor (PPAR)γ binding and persistently increased reactive oxygen species, cellular NADH, and altered DNA methylation. Agonists of PPARγ and PPARα prevented select effects of glucose-induced gene expression. These observations suggest that Schwann cells exhibit features of metabolic memory that may be regulated at the transcriptional level. Furthermore, targeting PPAR may prevent metabolic memory and the development of diabetic complications.

  9. Sizing of SRAM Cell with Voltage Biasing Techniques for Reliability Enhancement of Memory and PUF Functions

    Directory of Open Access Journals (Sweden)

    Chip-Hong Chang

    2016-08-01

    Full Text Available Static Random Access Memory (SRAM has recently been developed into a physical unclonable function (PUF for generating chip-unique signatures for hardware cryptography. The most compelling issue in designing a good SRAM-based PUF (SPUF is that while maximizing the mismatches between the transistors in the cross-coupled inverters improves the quality of the SPUF, this ironically also gives rise to increased memory read/write failures. For this reason, the memory cells of existing SPUFs cannot be reused as storage elements, which increases the overheads of cryptographic system where long signatures and high-density storage are both required. This paper presents a novel design methodology for dual-mode SRAM cell optimization. The design conflicts are resolved by using word-line voltage modulation, dynamic voltage scaling, negative bit-line and adaptive body bias techniques to compensate for reliability degradation due to transistor downsizing. The augmented circuit-level techniques expand the design space to achieve a good solution to fulfill several otherwise contradicting key design qualities for both modes of operation, as evinced by our statistical analysis and simulation results based on complementary metal–oxide–semiconductor (CMOS 45 nm bulk Predictive Technology Model.

  10. Intelligent structures based on the improved activation of shape memory polymers using Peltier cells

    International Nuclear Information System (INIS)

    Díaz Lantada, Andrés; Lafont Morgado, Pilar; Muñoz Sanz, José Luis; Muñoz García, Julio; Munoz-Guijosa, Juan Manuel; Echávarri Otero, Javier

    2010-01-01

    This study is focused on obtaining intelligent structures manufactured from shape memory polymers possessing the ability to change their geometry in successive or 'step-by-step' actions. This objective has been reached by changing the conventionally used shape memory activation systems (heating resistance, laser or induction heating). The solution set out consists in using Peltier cells as a heating system capable of heating (and activating) a specific zone of the device in the first activation, while the opposite zone keeps its original geometry. By carefully reversing the polarity of the electrical supply to the Peltier cell, in the second activation, the as yet unchanged zone is activated while the already changed zone in the first activation remains unaltered. We have described the criteria for the selection, calibration and design of this alternative heating (activation) system based on the thermoelectric effect, together with the development of different 'proof of concept' prototypes that have enabled us to validate the concepts put forward, as well as suggest future improvements for 'intelligent' shape memory polymer-based devices

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  12. Human cerebrospinal fluid contains CD4+ memory T cells expressing gut- or skin-specific trafficking determinants: relevance for immunotherapy

    Directory of Open Access Journals (Sweden)

    Campbell James J

    2006-07-01

    Full Text Available Abstract Background Circulating memory T cells can be divided into tissue-specific subsets, which traffic through distinct tissue compartments during physiologic immune surveillance, based on their expression of adhesion molecules and chemokine receptors. We reasoned that a bias (either enrichment or depletion of CSF T cell expression of known organ-specific trafficking determinants might suggest that homing of T cells to the subarachnoid space could be governed by a CNS-specific adhesion molecule or chemokine receptor. Results The expression of cutaneous leukocyte antigen (CLA and CC-chemokine receptor 4 (CCR4; associated with skin-homing as well as the expression of integrin α4β7 and CCR9 (associated with gut-homing was analyzed on CD4+ memory T cells in CSF from individuals with non-inflammatory neurological diseases using flow cytometry. CSF contained similar proportions of CD4+ memory T cells expressing CLA, CCR4, integrin α4β7 and CCR9 as paired blood samples. Conclusion The results extend our previous findings that antigen-experienced CD4+ memory T cells traffic through the CSF in proportion to their abundance in the peripheral circulation. Furthermore, the ready access of skin- and gut-homing CD4+ memory T cells to the CNS compartment via CSF has implications for the mechanisms of action of immunotherapeutic strategies, such as oral tolerance or therapeutic immunization, where immunogens are administered using an oral or subcutaneous route.

  13. IFN-Gamma-Dependent and Independent Mechanisms of CD4+ Memory T Cell-Mediated Protection from Listeria Infection

    Directory of Open Access Journals (Sweden)

    Stephanie M. Meek

    2018-02-01

    Full Text Available While CD8+ memory T cells can promote long-lived protection from secondary exposure to intracellular pathogens, less is known regarding the direct protective mechanisms of CD4+ T cells. We utilized a prime/boost model in which mice are initially exposed to an acutely infecting strain of lymphocytic choriomeningitis virus (LCMV, followed by a heterologous rechallenge with Listeria monocytogenes recombinantly expressing the MHC Class II-restricted LCMV epitope, GP61–80 (Lm-gp61. We found that heterologous Lm-gp61 rechallenge resulted in robust activation of CD4+ memory T cells and that they were required for rapid bacterial clearance. We further assessed the relative roles of TNF and IFNγ in the direct anti-bacterial function of CD4+ memory T cells. We found that disruption of TNF resulted in a complete loss of protection mediated by CD4+ memory T cells, whereas disruption of IFNγ signaling to macrophages results in only a partial loss of protection. The protective effect mediated by CD4+ T cells corresponded to the rapid accumulation of pro-inflammatory macrophages in the spleen and an altered inflammatory environment in vivo. Overall, we conclude that protection mediated by CD4+ memory T cells from heterologous Listeria challenge is most directly dependent on TNF, whereas IFNγ only plays a minor role.

  14. Engagement of NKG2D on bystander memory CD8 T cells promotes increased immunopathology following Leishmania major infection.

    Directory of Open Access Journals (Sweden)

    Erika J Crosby

    2014-02-01

    Full Text Available One of the hallmarks of adaptive immunity is the development of a long-term pathogen specific memory response. While persistent memory T cells certainly impact the immune response during a secondary challenge, their role in unrelated infections is less clear. To address this issue, we utilized lymphocytic choriomeningitis virus (LCMV and Listeria monocytogenes immune mice to investigate whether bystander memory T cells influence Leishmania major infection. Despite similar parasite burdens, LCMV and Listeria immune mice exhibited a significant increase in leishmanial lesion size compared to mice infected with L. major alone. This increased lesion size was due to a severe inflammatory response, consisting not only of monocytes and neutrophils, but also significantly more CD8 T cells. Many of the CD8 T cells were LCMV specific and expressed gzmB and NKG2D, but unexpectedly expressed very little IFN-γ. Moreover, if CD8 T cells were depleted in LCMV immune mice prior to challenge with L. major, the increase in lesion size was lost. Strikingly, treating with NKG2D blocking antibodies abrogated the increased immunopathology observed in LCMV immune mice, showing that NKG2D engagement on LCMV specific memory CD8 T cells was required for the observed phenotype. These results indicate that bystander memory CD8 T cells can participate in an unrelated immune response and induce immunopathology through an NKG2D dependent mechanism without providing increased protection.

  15. Autoreactive effector/memory CD4+ and CD8+ T cells infiltrating grafted and endogenous islets in diabetic NOD mice exhibit similar T cell receptor usage.

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    Ramiro Diz

    Full Text Available Islet transplantation provides a "cure" for type 1 diabetes but is limited in part by recurrent autoimmunity mediated by β cell-specific CD4(+ and CD8(+ T cells. Insight into the T cell receptor (TCR repertoire of effector T cells driving recurrent autoimmunity would aid the development of immunotherapies to prevent islet graft rejection. Accordingly, we used a multi-parameter flow cytometry strategy to assess the TCR variable β (Vβ chain repertoires of T cell subsets involved in autoimmune-mediated rejection of islet grafts in diabetic NOD mouse recipients. Naïve CD4(+ and CD8(+ T cells exhibited a diverse TCR repertoire, which was similar in all tissues examined in NOD recipients including the pancreas and islet grafts. On the other hand, the effector/memory CD8(+ T cell repertoire in the islet graft was dominated by one to four TCR Vβ chains, and specific TCR Vβ chain usage varied from recipient to recipient. Similarly, islet graft- infiltrating effector/memory CD4(+ T cells expressed a limited number of prevalent TCR Vβ chains, although generally TCR repertoire diversity was increased compared to effector/memory CD8(+ T cells. Strikingly, the majority of NOD recipients showed an increase in TCR Vβ12-bearing effector/memory CD4(+ T cells in the islet graft, most of which were proliferating, indicating clonal expansion. Importantly, TCR Vβ usage by effector/memory CD4(+ and CD8(+ T cells infiltrating the islet graft exhibited greater similarity to the repertoire found in the pancreas as opposed to the draining renal lymph node, pancreatic lymph node, or spleen. Together these results demonstrate that effector/memory CD4(+ and CD8(+ T cells mediating autoimmune rejection of islet grafts are characterized by restricted TCR Vβ chain usage, and are similar to T cells that drive destruction of the endogenous islets.

  16. Acetylation of the Cd8 Locus by KAT6A Determines Memory T Cell Diversity

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    Dane M. Newman

    2016-09-01

    Full Text Available How functionally diverse populations of pathogen-specific killer T cells are generated during an immune response remains unclear. Here, we propose that fine-tuning of CD8αβ co-receptor levels via histone acetylation plays a role in lineage fate. We show that lysine acetyltransferase 6A (KAT6A is responsible for maintaining permissive Cd8 gene transcription and enabling robust effector responses during infection. KAT6A-deficient CD8+ T cells downregulated surface CD8 co-receptor expression during clonal expansion, a finding linked to reduced Cd8α transcripts and histone-H3 lysine 9 acetylation of the Cd8 locus. Loss of CD8 expression in KAT6A-deficient T cells correlated with reduced TCR signaling intensity and accelerated contraction of the effector-like memory compartment, whereas the long-lived memory compartment appeared unaffected, a result phenocopied by the removal of the Cd8 E8I enhancer element. These findings suggest a direct role of CD8αβ co-receptor expression and histone acetylation in shaping functional diversity within the cytotoxic T cell pool.

  17. Projection specificity in heterogeneous locus coeruleus cell populations: implications for learning and memory

    Science.gov (United States)

    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

  18. A dense voltage-mode Josephson memory cell insensitive to systematic variations in critical current density

    International Nuclear Information System (INIS)

    Bradley, P.; Van Duzer, T.

    1985-01-01

    A destructive read-out (DRO) memory cell using three Josephson junctions has been devised whose operation depends only on the ratio of critical currents and application of the proper read/write voltages. The effects of run-to-run and across-thewafer variations in I /SUB c/ are minimized since all three junctions for a given cell are quite close to each other. Additional advantages are: immunity from flux trapping, high circuit density, and fast switching. Since destructive read-out is generally undesirable, a self-rewriting scheme is necessary. Rows and columns of cells with drivers and sense circuits, as well as small memory arrays and decoders have been simulated on SPICE. Power dissipation of cells and bias circuits for a 1K-bit RAM is estimated at about 2 mW. Inclusion of peripheral circuitry raises this by as much as a factor of five depending on the driving scheme and speed desired. Estimated access time is appreciably less than a nanosecond. Preliminary experimental investigations are reported

  19. Changes in B Cell Populations and Merozoite Surface Protein-1-Specific Memory B Cell Responses after Prolonged Absence of Detectable P. falciparum Infection.

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    Cyrus Ayieko

    Full Text Available Clinical immunity to malaria declines in the absence of repeated parasite exposure. However, little is known about how B cell populations and antigen-specific memory B cells change in the absence of P. falciparum infection. A successful indoor residual insecticide spraying campaign in a highland area of western Kenya, led to an absence of blood-stage P. falciparum infection between March 2007 and April 2008. We assessed memory B cell responses in 45 adults at the beginning (April 2008 and end (April 2009 of a subsequent 12-month period during which none of the adults had evidence of asymptomatic parasitemia or clinical disease. Antibodies and memory B cells to the 42-kDa portion of the merozoite surface protein-1 (MSP-142 were measured using ELISA and ELISPOT assays, respectively. B cell populations were characterized by flow cytometry. From 2008 to 2009, the prevalence of MSP-142-specific memory B cells (45% vs. 55%, respectively, P = 0.32 or antibodies (91% vs. 82%, respectively, P = 0.32 did not differ significantly, although specific individuals did change from positive to negative and vice versa, particularly for memory B cells, suggesting possible low-level undetected parasitemia may have occurred in some individuals. The magnitude of MSP-142-specific memory B cells and levels of antibodies to MSP-142 also did not differ from 2008 to 2009 (P>0.10 for both. However, from 2008 to 2009 the proportions of both class-switched atypical (CD19+IgD-CD27-CD21-IgM- and class-switched activated (CD19+IgD-CD27+CD21-IgM- memory B cells decreased (both P<0.001. In contrast, class-switched resting classical memory B cells (CD19+IgD-CD27+CD21+IgM- increased (P<0.001. In this area of seasonal malaria transmission, a one- year absence of detectable P. falciparum infection was not associated with changes in the prevalence or level of MSP-142 specific memory B cells, but was associated with major changes in overall memory B cell subsets.

  20. Spironolactone release from liquisolid formulations prepared with Capryol™ 90, Solutol® HS-15 and Kollicoat® SR 30 D as non-volatile liquid vehicles.

    Science.gov (United States)

    Elkordy, Amal Ali; Tan, Xin Ning; Essa, Ebtessam Ahmed

    2013-02-01

    The purpose of the study is to enhance dissolution of spironolactone as a model hydrophobic drug through application of liquisolid technology. Spironolactone is prepared as liquisolid formulations, and its dissolution property is evaluated and compared to that of conventional spironolactone tablets and pure spironolactone. Three non-volatile liquid vehicles were used in the design of spironolactone liquisolid formulations, Capryol™ 90, Synperonic® PE/L61 in combination with Solutol® HS-15 at a ratio of 1:1, and Kollicoat® SR 30 D. Spironolactone liquisolid formulations were tested according to British Pharmacopoeia (BP) quality control tests. Furthermore, the prepared liquisolid powder formulations were evaluated via differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR) and scanning electron microscopy. Also, liquisolid formulations were subjected to testing of storage stability at high relative humidity. The results indicated that most of liquisolid tablets met the BP requirements. Dissolution results indicate that release of spironolactone was significantly increased (PSolutol® HS-15 showed highest dissolution. DSC thermograms from liquisolid formulations revealed that drug endothermic peak was disappeared after processing. Dissolution, DSC and FT-IR data after storage demonstrated that there were no significant changes in the formulations after storage. In conclusion, the liquid vehicles used within spironolactone liquisolid formulations enhanced drug dissolution rate. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Volatile and non-volatile radiolysis products in irradiated multilayer coextruded food-packaging films containing a buried layer of recycled low-density polyethylene.

    Science.gov (United States)

    Chytiri, S; Goulas, A E; Badeka, A; Riganakos, K A; Kontominas, M G

    2005-12-01

    The effects of gamma-irradiation (5-60 kGy) on radiolysis products and sensory changes of experimental five-layer food-packaging films were determined. Films contained a middle buried layer of recycled low-density polyethylene (LDPE) comprising 25-50% by weight (bw) of the multilayer structure. Respective films containing 100% virgin LDPE as the buried layer were used as controls. Under realistic polymer/food simulant contact conditions during irradiation, a large number of primary and secondary radiolysis products (hydrocarbons, aldehydes, ketones, alcohols, carboxylic acids) were produced. These compounds were detected in the food simulant after contact with all films tested, even at the lower absorbed doses of 5 and 10 kGy (approved doses for food preservation). The type and concentration of radiolysis products increased progressively with increasing dose. Generally, there were no significant differences in radiolysis products between samples containing a buried layer of recycled LDPE and those containing virgin LDPE (all absorbed doses), indicating the good barrier properties of external virgin polymer layers. Volatile and non-volatile compounds produced during irradiation affected the sensory properties of potable water after contact with packaging films. Taste transfer to water was observed mainly at higher doses and was more noticeable for multilayer structures containing recycled LDPE, even though differences were slight.

  2. CD8 Memory Cells Develop Unique DNA Repair Mechanisms Favoring Productive Division.

    Science.gov (United States)

    Galgano, Alessia; Barinov, Aleksandr; Vasseur, Florence; de Villartay, Jean-Pierre; Rocha, Benedita

    2015-01-01

    Immune responses are efficient because the rare antigen-specific naïve cells are able to proliferate extensively and accumulate upon antigen stimulation. Moreover, differentiation into memory cells actually increases T cell accumulation, indicating improved productive division in secondary immune responses. These properties raise an important paradox: how T cells may survive the DNA lesions necessarily induced during their extensive division without undergoing transformation. We here present the first data addressing the DNA damage responses (DDRs) of CD8 T cells in vivo during exponential expansion in primary and secondary responses in mice. We show that during exponential division CD8 T cells engage unique DDRs, which are not present in other exponentially dividing cells, in T lymphocytes after UV or X irradiation or in non-metastatic tumor cells. While in other cell types a single DDR pathway is affected, all DDR pathways and cell cycle checkpoints are affected in dividing CD8 T cells. All DDR pathways collapse in secondary responses in the absence of CD4 help. CD8 T cells are driven to compulsive suicidal divisions preventing the propagation of DNA lesions. In contrast, in the presence of CD4 help all the DDR pathways are up regulated, resembling those present in metastatic tumors. However, this up regulation is present only during the expansion phase; i.e., their dependence on antigen stimulation prevents CD8 transformation. These results explain how CD8 T cells maintain genome integrity in spite of their extensive division, and highlight the fundamental role of DDRs in the efficiency of CD8 immune responses.

  3. Memory-guided sensory comparisons in the prefrontal cortex: contribution of putative pyramidal cells and interneurons.

    Science.gov (United States)

    Hussar, Cory R; Pasternak, Tatiana

    2012-02-22

    Comparing two stimuli that occur at different times demands the coordination of bottom-up and top-down processes. It has been hypothesized that the dorsolateral prefrontal (PFC) cortex, the likely source of top-down cortical influences, plays a key role in such tasks, contributing to both maintenance and sensory comparisons. We examined this hypothesis by recording from the PFC of monkeys comparing directions of two moving stimuli, S1 and S2, separated by a memory delay. We determined the contribution of the two principal cell types to these processes by classifying neurons into broad-spiking (BS) putative pyramidal cells and narrow-spiking (NS) putative local interneurons. During the delay, BS cells were more likely to exhibit anticipatory modulation and represent the remembered direction. While this representation was transient, appearing at different times in different neurons, it weakened when direction was not task relevant, suggesting its utility. During S2, both putative cell types showed comparison-related activity modulations. These modulations were of two types, each carried by different neurons, which either preferred trials with stimuli moving in the same direction or trials with stimuli of different directions. These comparison effects were strongly correlated with choice, suggesting their role in circuitry underlying decision making. These results provide the first demonstration of distinct contributions made by principal cell types to memory-guided perceptual decisions. During sensory stimulation both cell types represent behaviorally relevant stimulus features contributing to comparison and decision-related activity. However in the absence of sensory stimulation, putative pyramidal cells dominated, carrying information about the elapsed time and the preceding direction.

  4. CCR6 is expressed on an IL-10-producing, autoreactive memory T cell population with context-dependent regulatory function.

    Science.gov (United States)

    Rivino, Laura; Gruarin, Paola; Häringer, Barbara; Steinfelder, Svenja; Lozza, Laura; Steckel, Bodo; Weick, Anja; Sugliano, Elisa; Jarrossay, David; Kühl, Anja A; Loddenkemper, Christoph; Abrignani, Sergio; Sallusto, Federica; Lanzavecchia, Antonio; Geginat, Jens

    2010-03-15

    Interleukin (IL)-10 produced by regulatory T cell subsets is important for the prevention of autoimmunity and immunopathology, but little is known about the phenotype and function of IL-10-producing memory T cells. Human CD4(+)CCR6(+) memory T cells contained comparable numbers of IL-17- and IL-10-producing cells, and CCR6 was induced under both Th17-promoting conditions and upon tolerogenic T cell priming with transforming growth factor (TGF)-beta. In normal human spleens, the majority of CCR6(+) memory T cells were in the close vicinity of CCR6(+) myeloid dendritic cells (mDCs), and strikingly, some of them were secreting IL-10 in situ. Furthermore, CCR6(+) memory T cells produced suppressive IL-10 but not IL-2 upon stimulation with autologous immature mDCs ex vivo, and secreted IL-10 efficiently in response to suboptimal T cell receptor (TCR) stimulation with anti-CD3 antibodies. However, optimal TCR stimulation of CCR6(+) T cells induced expression of IL-2, interferon-gamma, CCL20, and CD40L, and autoreactive CCR6(+) T cell lines responded to various recall antigens. Notably, we isolated autoreactive CCR6(+) T cell clones with context-dependent behavior that produced IL-10 with autologous mDCs alone, but that secreted IL-2 and proliferated upon stimulation with tetanus toxoid. We propose the novel concept that a population of memory T cells, which is fully equipped to participate in secondary immune responses upon recognition of a relevant recall antigen, contributes to the maintenance of tolerance under steady-state conditions.

  5. From sensorimotor learning to memory cells in prefrontal and temporal association cortex: a neurocomputational study of disembodiment.

    Science.gov (United States)

    Pulvermüller, Friedemann; Garagnani, Max

    2014-08-01

    Memory cells, the ultimate neurobiological substrates of working memory, remain active for several seconds and are most commonly found in prefrontal cortex and higher multisensory areas. However, if correlated activity in "embodied" sensorimotor systems underlies the formation of memory traces, why should memory cells emerge in areas distant from their antecedent activations in sensorimotor areas, thus leading to "disembodiment" (movement away from sensorimotor systems) of memory mechanisms? We modelled the formation of memory circuits in six-area neurocomputational architectures, implementing motor and sensory primary, secondary and higher association areas in frontotemporal cortices along with known between-area neuroanatomical connections. Sensorimotor learning driven by Hebbian neuroplasticity led to formation of cell assemblies distributed across the different areas of the network. These action-perception circuits (APCs) ignited fully when stimulated, thus providing a neural basis for long-term memory (LTM) of sensorimotor information linked by learning. Subsequent to ignition, activity vanished rapidly from APC neurons in sensorimotor areas but persisted in those in multimodal prefrontal and temporal areas. Such persistent activity provides a mechanism for working memory for actions, perceptions and symbols, including short-term phonological and semantic storage. Cell assembly ignition and "disembodied" working memory retreat of activity to multimodal areas are documented in the neurocomputational models' activity dynamics, at the level of single cells, circuits, and cortical areas. Memory disembodiment is explained neuromechanistically by APC formation and structural neuroanatomical features of the model networks, especially the central role of multimodal prefrontal and temporal cortices in bridging between sensory and motor areas. These simulations answer the "where" question of cortical working memory in terms of distributed APCs and their inner structure

  6. Local Inflammatory Cues Regulate Differentiation and Persistence of CD8+ Tissue-Resident Memory T Cells

    Directory of Open Access Journals (Sweden)

    Tessa Bergsbaken

    2017-04-01

    Full Text Available Many pathogens initiate infection at mucosal surfaces, and tissue-resident memory T (Trm cells play an important role in protective immunity, yet the tissue-specific signals that regulate Trm differentiation are poorly defined. During Yersinia infection, CD8+ T cell recruitment to areas of inflammation within the intestine is required for differentiation of the CD103−CD69+ Trm subset. Intestinal proinflammatory microenvironments have elevated interferon (IFN-β and interleukin-12 (IL-12, which regulated Trm markers, including CD103. Type I interferon-receptor- or IL-12-receptor-deficient T cells functioned similarly to wild-type (WT cells during infection; however, the inability of T cells to respond to inflammation resulted in defective differentiation of CD103−CD69+ Trm cells and reduced Trm persistence. Intestinal macrophages were the main producers of IFN-β and IL-12 during infection, and deletion of CCR2+ IL-12-producing cells reduced the size of the CD103− Trm population. These data indicate that intestinal inflammation drives phenotypic diversity and abundance of Trm cells for optimal tissue-specific immunity.

  7. Integration of ammonia-plasma-functionalized graphene nanodiscs as charge trapping centers for nonvolatile memory applications

    KAUST Repository

    Wang, Jer-Chyi

    2016-11-23

    Graphene nanodiscs (GNDs), functionalized using NH3 plasma, as charge trapping sites (CTSs) for non-volatile memory applications have been investigated in this study. The fabrication process relies on the patterning of Au nanoparticles (Au-NPs), whose thicknesses are tuned to adjust the GND density and size upon etching. A GND density as high as 8 × 1011 cm−2 and a diameter of approximately 20 nm are achieved. The functionalization of GNDs by NH3 plasma creates Nsingle bondH+ functional groups that act as CTSs, as observed by Raman and Fourier transform infrared spectroscopy. This inherently enhances the density of CTSs in the GNDs, as a result, the memory window becomes more than 2.4 V and remains stable after 104 operating cycles. The charge loss is less than 10% for a 10-year data retention testing, making this low-temperature process suitable for low-cost non-volatile memory applications on flexible substrates.

  8. A new approach for two-terminal electronic memory devices - Storing information on silicon nanowires

    Science.gov (United States)

    Saranti, Konstantina; Alotaibi, Sultan; Paul, Shashi

    2016-06-01

    The work described in this paper focuses on the utilisation of silicon nanowires as the information storage element in flash-type memory devices. Silicon nanostructures have attracted attention due to interesting electrical and optical properties, and their potential integration into electronic devices. A detailed investigation of the suitability of silicon nanowires as the charge storage medium in two-terminal non-volatile memory devices are presented in this report. The deposition of the silicon nanostructures was carried out at low temperatures (less than 400 °C) using a previously developed a novel method within our research group. Two-terminal non-volatile (2TNV) memory devices and metal-insulator-semiconductor (MIS) structures containing the silicon nanowires were fabricated and an in-depth study of their characteristics was carried out using current-voltage and capacitance techniques.

  9. Selective Expansion of Memory CD4+ T cells By Mitogenic Human CD28 Generates Inflammatory Cytokines and Regulatory T cells

    Science.gov (United States)

    Singh, Manisha; Basu, Sreemanti; Camell, Christina; Couturier, Jacob; Nudelman, Rodolfo J.; Medina, Miguel A.; Rodgers, John R.; Lewis, Dorothy E.

    2009-01-01

    Co-stimulatory signals are important for development of effector and regulatory T cells. In this case, CD28 signaling is usually considered inert in the absence of signaling through the TCR. By contrast, mitogenic rat CD28 mAbs reportedly expand regulatory T cells without TCR stimulation. We found that a commercially available human CD28 mAb (ANC28) stimulated PBMCs without TCR co-ligation or cross-linking; ANC28 selectively expanded CD4+CD25+FoxP3−(T effector) and CD4+CD25+FoxP3+ (Treg) cells. ANC28 stimulated the CD45RO+ CD4+ (memory) population whereas CD45RA+CD4+ (naïve) cells did not respond. ANC28 also induced inflammatory cytokines. Treg induced by ANC28 retain the Treg phenotype longer than did co-stimulated Treg. Treg induced by ANC28 suppressed CD25− T cells through a contact-dependent mechanism. Purity influenced the response of CD4+CD25+ cells because bead-purified CD4+CD25+ cells (85–90% pure) responded strongly to ANC28, whereas 98% pure FACS-sorted CD4+CD25 bright (T-reg) did not respond. Purified CD4+CD25int cells responded similarly to the bead-purified CD4+CD25+ cells. Thus, pre-activated CD4+ T cells (CD25int) respond to ANC28 rather than Treg (CD25bright). The ability of ANC28 to expand both effectors producing inflammatory cytokines as well as suppressive regulatory T cells might be useful for ex vivo expansion of therapeutic T cells. PMID:18446791

  10. Tissue-Resident Memory CD8+ T Cells: From Phenotype to Function

    Directory of Open Access Journals (Sweden)

    David J. Topham

    2018-03-01

    Full Text Available Tissue-resident memory CD8+ T cells are an important first line of defense from infection in peripheral non-lymphoid tissues, such as the mucosal tissues of the respiratory, digestive, and urogenital tracts. This memory T cell subset is established late during resolution of primary infection of those tissues, has a distinct genetic signature, and is often defined by the cell surface expression of CD69, CD103, CD49a, and CD44 in both mouse and human studies. The stimuli that program or imprint the unique gene expression and cell surface phenotypes on TRM are beginning to be defined, but much work remains to be done. It is not clear, for example, when and where the TRM precursors receive these signals, and there is evidence that supports imprinting in both the lymph node and the peripheral tissue sites. In most studies, expression of CD49a, CD103, and CD69 on T cells in the tissues appears relatively late in the response, suggesting there are precise environmental cues that are not present at the height of the acute response. CD49a and CD103 are not merely biomarkers of TRM, they confer substrate specificities for cell adhesion to collagen and E-cadherin, respectively. Yet, little attention has been paid to how expression affects the positioning of TRM in the peripheral tissues. CD103 and CD49a are not mutually exclusive, and not always co-expressed, although whether they can compensate for one another is unknown. In fact, they may define different subsets of TRM in certain tissues. For instance, while CD49a+CD8+ memory T cells can be found in almost all peripheral tissues, CD103 appears to be more restricted. In this review, we discuss the evidence for how these hallmarks of TRM affect positioning of T cells in peripheral sites, how CD49a and CD103 differ in expression and function, and why they are important for immune protection conferred by TRM in mucosal tissues such as the respiratory tract.

  11. Radiation-induced alterations in murine lymphocyte homing patterns. II. Recovery and function of memory cells in LBN rats

    International Nuclear Information System (INIS)

    Crouse, D.A.; Feldbush, T.L.; Evans, T.C.

    1978-01-01

    Suspensions of lymph node cells from dinitrophenylated bovine gamma globulin (DNP-BGG)-immune LBN F 1 hybrid rats (Lewis X Brown Norway) were prepared, irradiated, and injected intravenously into unirradiated syngeneic intermediate hosts and irradiated syngeneic adoptive controls. After allowance of 24 hr for homing to occur, the intermediate hosts were killed and cell preparations from the lymph nodes and spleen were injected intravenously into separate irradiated LBN final host groups. All control and experimental groups were challenged (DNP-BGG saline iv) 24 hr after the injection of the lymphoid cells. Rats were bled on Days 7, 11, and 14 after challenge and the antigen-binding capacity (ABC) of the serum was determined. After correction for the fraction of the total cell population transferred from the intermediate host, the peak ABC of the final hosts was related to the number of memory cells present. It was thus possible to determine the relative distribution of the memory cell population to the spleen and lymph nodes of the intermediate hosts. In the intermediate control animals, irradiated memory cells provided a secondary antibody response which was delayed but not suppressed when compared to unirradiated cells. In intermediate hosts, the homing of lymph node memory cells to the spleen and lymph nodes was significantly reduced by an exposure to 200 R of x radiation

  12. Mucosal immunization in macaques upregulates the innate APOBEC 3G anti-viral factor in CD4(+) memory T cells.

    Science.gov (United States)

    Wang, Yufei; Bergmeier, Lesley A; Stebbings, Richard; Seidl, Thomas; Whittall, Trevor; Singh, Mahavir; Berry, Neil; Almond, Neil; Lehner, Thomas

    2009-02-05

    APOBEC3G is an innate intracellular anti-viral factor which deaminates retroviral cytidine to uridine. In vivo studies of APOBEC3G (A3G) were carried out in rhesus macaques, following mucosal immunization with SIV antigens and CCR5 peptides, linked to the 70kDa heat shock protein. A progressive increase in A3G mRNA was elicited in PBMC after each immunization (p<0.0002 to p< or =0.02), which was maintained for at least 17 weeks. Analysis of memory T cells showed a significant increase in A3G mRNA and protein in CD4(+)CCR5(+) memory T cells in circulating (p=0.0001), splenic (p=0.0001), iliac lymph nodes (p=0.002) and rectal (p=0.01) cells of the immunized compared with unimmunized macaques. Mucosal challenge with SIVmac 251 showed a significant increase in A3G mRNA in the CD4(+)CCR5(+) circulating cells (p<0.01) and the draining iliac lymph node cells (p<0.05) in the immunized uninfected macaques, consistent with a protective effect exerted by A3G. The results suggest that mucosal immunization in a non-human primate can induce features of a memory response to an innate anti-viral factor in CCR5(+)CD4(+) memory and CD4(+)CD95(+)CCR7(-) effector memory T cells.

  13. Transparent Memory For Harsh Electronics

    KAUST Repository

    Ho, C. H.

    2017-03-14

    As a new class of non-volatile memory, resistive random access memory (RRAM) offers not only superior electronic characteristics, but also advanced functionalities, such as transparency and radiation hardness. However, the environmental tolerance of RRAM is material-dependent, and therefore the materials used must be chosen carefully in order to avoid instabilities and performance degradation caused by the detrimental effects arising from environmental gases and ionizing radiation. In this work, we demonstrate that AlN-based RRAM displays excellent performance and environmental stability, with no significant degradation to the resistance ratio over a 100-cycle endurance test. Moreover, transparent RRAM (TRRAM) based on AlN also performs reliably under four different harsh environmental conditions and 2 MeV proton irradiation fluences, ranging from 1011 to 1015 cm-2. These findings not only provide a guideline for TRRAM design, but also demonstrate the promising applicability of AlN TRRAM for future transparent harsh electronics.

  14. Identifying long-term memory B-cells in vaccinated children despite waning antibody levels specific for Bordetella pertussis proteins.

    Science.gov (United States)

    Hendrikx, Lotte H; Oztürk, Kemal; de Rond, Lia G H; Veenhoven, Reinier H; Sanders, Elisabeth A M; Berbers, Guy A M; Buisman, Anne-Marie

    2011-02-04

    Whooping cough is a respiratory disease caused by Bordetella pertussis. Since the 1950s in developed countries pertussis vaccinations are included in the national immunization program. However, antibody levels rapidly wane after both whole cell and acellular pertussis vaccination. Therefore protection against pertussis may depend largely on long-term B- and T-cell immunities. We investigated long-term pertussis-specific memory B-cell responses in children who were primed at infant age with the Dutch wP-vaccine (ISRCTN65428640). Purified B-cells were characterized by FACS-analysis and after polyclonal stimulation memory B-cells were detected by ELISPOT-assays specific for pertussis toxin, filamentous haemagglutinin, pertactin and tetanus. In addition, plasma IgG levels directed to the same antigens were measured by a fluorescent bead-based multiplex immunoassay. Two and 3 years after wP priming as well as 2 and 5 years after the aP booster at the age of 4, low plasma IgG levels to the pertussis proteins were found. At the same time, however pertussis protein-specific memory B-cells could be detected and their number increased with age. The number of tetanus-specific memory B-cells was similar in all age groups, whereas IgG-tetanus levels were high 2 years after tetanus booster compared to pre- and 5 years post-booster levels. This study shows the presence of long-term pertussis protein-specific memory B-cells in children despite waning antibody levels after vaccination, which suggests that memory B-cells in addition to antibodies may contribute to protection against pertussis. Copyright © 2010 Elsevier Ltd. All rights reserved.

  15. Incomplete effector/memory differentiation of antigen-primed CD8+ T cells in gene gun DNA-vaccinated mice

    DEFF Research Database (Denmark)

    Bartholdy, Christina; Stryhn, Anette; Hansen, Nils Jacob Vest

    2003-01-01

    DNA vaccination is an efficient way to induce CD8+ T cell memory, but it is still unclear to what extent such memory responses afford protection in vivo. To study this, we induced CD8+ memory responses directed towards defined viral epitopes, using DNA vaccines encoding immunodominant MHC class I......-restricted epitopes of lymphocytic choriomeningitis virus covalently linked to beta2-microglobulin. This vaccine construct primed for a stronger recall response than did a more conventional minigene construct. Despite this, vaccinated mice were only protected against systemic infection whereas protection against...... sites. Thus, our DNA vaccine induces a long-lived memory CD8+ T cell population that provides efficient protection against high-dose systemic infection. However, viral replication in solid non-lymphoid organs is not curtailed sufficiently fast to prevent significant virus-induced inflammation. Our...

  16. Concept of rewritable organic ferroelectric random access memory in two lateral transistors-in-one cell architecture

    International Nuclear Information System (INIS)

    Kim, Min-Hoi; Lee, Gyu Jeong; Keum, Chang-Min; Lee, Sin-Doo

    2014-01-01

    We propose a concept of rewritable ferroelectric random access memory (RAM) with two lateral organic transistors-in-one cell architecture. Lateral integration of a paraelectric organic field-effect transistor (OFET), being a selection transistor, and a ferroelectric OFET as a memory transistor is realized using a paraelectric depolarizing layer (PDL) which is patterned on a ferroelectric insulator by transfer-printing. For the selection transistor, the key roles of the PDL are to reduce the dipolar strength and the surface roughness of the gate insulator, leading to the low memory on–off ratio and the high switching on–off current ratio. A new driving scheme preventing the crosstalk between adjacent memory cells is also demonstrated for the rewritable operation of the ferroelectric RAM. (paper)

  17. Increased degradation of ATP is driven by memory regulatory T cells in kidney transplantation tolerance.

    Science.gov (United States)

    Durand, Maxim; Dubois, Florian; Dejou, Cécile; Durand, Eugénie; Danger, Richard; Chesneau, Mélanie; Brosseau, Carole; Guerif, Pierrick; Soulillou, Jean-Paul; Degauque, Nicolas; Eliaou, Jean-François; Giral, Magali; Bonnefoy, Nathalie; Brouard, Sophie

    2018-05-01

    Regulatory T cells were recently proposed as the central actor in operational tolerance after renal transplantation. Tolerant patients harbor increased FoxP3hi memory Treg frequency and increased demethylation in the Foxp3 Treg-specific demethylated region when compared to stable kidney recipients and exhibit greater memory Treg suppressive capacities and higher expression of the ectonucleotidase CD39. However, in this particular and unique situation the mechanisms of action of Tregs were not identified. Thus, we analyzed the ability of memory Tregs to degrade extracellular ATP in tolerant patients, healthy volunteers, and patients with stable graft function under immunosuppression and determined the role of immunosuppressive drugs on this process. The conserved proportion of memory Tregs leads to the establishment of a pro-tolerogenic balance in operationally tolerant patients. Memory Tregs in tolerant patients display normal capacity to degrade extracellular ATP/ADP. In contrast, memory Tregs from patients with stable graft function do not have this ability. Finally, in vitro, immunosuppressive drugs may favor the lower proportion of memory Tregs in stable patients, but they have no effect on CD39-dependent ATP degradation and do not explain memory Treg lack of extracellular ATP/ADP degradation ability. Thus, intrinsic active regulatory mechanisms may act long after immunosuppressive drug arrest in operationally tolerant patients and may contribute to kidney allograft tolerance via the maintenance of CD39 Treg function. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

  19. Plasmablasts During Acute Dengue Infection Represent a Small Subset of a Broader Virus-specific Memory B Cell Pool

    Directory of Open Access Journals (Sweden)

    Ramapraba Appanna

    2016-10-01

    Full Text Available Dengue is endemic in tropical countries worldwide and the four dengue virus serotypes often co-circulate. Infection with one serotype results in high titers of cross-reactive antibodies produced by plasmablasts, protecting temporarily against all serotypes, but impairing protective immunity in subsequent infections. To understand the development of these plasmablasts, we analyzed virus-specific B cell properties in patients during acute disease and at convalescence. Plasmablasts were unrelated to classical memory cells expanding in the blood during early recovery. We propose that only a small subset of memory B cells is activated as plasmablasts during repeat infection and that plasmablast responses are not representative of the memory B cell repertoire after dengue infection.

  20. Nicotinic modulation of hippocampal cell signaling and associated effects on learning and memory.

    Science.gov (United States)

    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.

  1. An SEU tolerant memory cell derived from fundamental studies of SEU mechanisms in SRAM

    International Nuclear Information System (INIS)

    Weaver, H.T.; Axness, C.L.; McBrayer, J.D.; Browning, J.S.; Fu, J.S.; Ochoa, A. Jr.; Koga, R.

    1987-01-01

    A new single event upset (SEU) hardening concept, an LRAM cell, is demonstrated theoretically and experimentally. Decoupling resistors in the LRAM are used only to protect against the short n-channel transient; longer persisting pulses are reduced in magnitude by a voltage divider, a basically new concept for SEU protection. In such a design, smaller resistors provide SEU tolerance, allowing higher performance, hardened memories. As basis for the LRAM idea, techniques were developed to measure time constants for ion induced voltage transients in conventional static random access memories, SRAM. Time constants of 0.8 and 6.3 nsec were measured for transients following strikes at the n- and p-channel drains, respectively - primary areas of SEU sensitivity. These data are the first transient time measurements on full memory chips and the large difference is fundamental to the LRAM concept. Test structures of the new design exhibit equivalent SEU tolerance with resistors 5-to-10 times smaller than currently used in SRAM. Our advanced transport-plus-circuit numerical simulations of the SEU process predicted this result and account for the LRAM experiments, as well as a variety of experiments on conventional SRAM

  2. Three-terminal resistive switching memory in a transparent vertical-configuration device

    International Nuclear Information System (INIS)

    Ungureanu, Mariana; Llopis, Roger; Casanova, Fèlix; Hueso, Luis E.

    2014-01-01

    The resistive switching phenomenon has attracted much attention recently for memory applications. It describes the reversible change in the resistance of a dielectric between two non-volatile states by the application of electrical pulses. Typical resistive switching memories are two-terminal devices formed by an oxide layer placed between two metal electrodes. Here, we report on the fabrication and operation of a three-terminal resistive switching memory that works as a reconfigurable logic component and offers an increased logic density on chip. The three-terminal memory device we present is transparent and could be further incorporated in transparent computing electronic technologies

  3. Antigen and Memory CD8 T Cells: Were They Both Right?

    Directory of Open Access Journals (Sweden)

    Epelman Slava

    2007-06-01

    Full Text Available Picture yourself as a researcher in immunology. To begin your project, you ask a question: Do CD8 T cells require antigen to maintain a memory response? This question is of prime importance to numerous me