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Sample records for transistor memory cell

  1. 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)

  2. 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...

  3. Homogeneous-oxide stack in IGZO thin-film transistors for multi-level-cell NAND memory application

    Science.gov (United States)

    Ji, Hao; Wei, Yehui; Zhang, Xinlei; Jiang, Ran

    2017-11-01

    A nonvolatile charge-trap-flash memory that is based on amorphous indium-gallium-zinc-oxide thin film transistors was fabricated with a homogeneous-oxide structure for a multi-level-cell application. All oxide layers, i.e., tunneling layer, charge trapping layer, and blocking layer, were fabricated with Al2O3 films. The fabrication condition (including temperature and deposition method) of the charge trapping layer was different from those of the other oxide layers. This device demonstrated a considerable large memory window of 4 V between the states fully erased and programmed with the operation voltage less than 14 V. This kind of device shows a good prospect for multi-level-cell memory applications.

  4. 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.

  5. Gold nanoparticle-pentacene memory-transistors

    OpenAIRE

    Novembre , Christophe; Guerin , David; Lmimouni , Kamal; Gamrat , Christian; Vuillaume , Dominique

    2008-01-01

    We demonstrate an organic memory-transistor device based on a pentacene-gold nanoparticles active layer. Gold (Au) nanoparticles are immobilized on the gate dielectric (silicon dioxide) of a pentacene transistor by an amino-terminated self-assembled monolayer. Under the application of writing and erasing pulses on the gate, large threshold voltage shift (22 V) and on/off drain current ratio of ~3E4 are obtained. The hole field-effect mobility of the transistor is similar in the on and off sta...

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

    Huffman, James Douglas

    2001-11-01

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

  8. Ferroelectric-gate field effect transistor memories device physics and applications

    CERN Document Server

    Ishiwara, Hiroshi; Okuyama, Masanori; Sakai, Shigeki; Yoon, Sung-Min

    2016-01-01

    This book provides comprehensive coverage of the materials characteristics, process technologies, and device operations for memory field-effect transistors employing inorganic or organic ferroelectric thin films. This transistor-type ferroelectric memory has interesting fundamental device physics and potentially large industrial impact. Among the various applications of ferroelectric thin films, the development of nonvolatile ferroelectric random access memory (FeRAM) has progressed most actively since the late 1980s and has achieved modest mass production levels for specific applications since 1995. There are two types of memory cells in ferroelectric nonvolatile memories. One is the capacitor-type FeRAM and the other is the field-effect transistor (FET)-type FeRAM. Although the FET-type FeRAM claims ultimate scalability and nondestructive readout characteristics, the capacitor-type FeRAMs have been the main interest for the major semiconductor memory companies, because the ferroelectric FET has fatal handic...

  9. P-channel differential multiple-time programmable memory cells by laterally coupled floating metal gate fin field-effect transistors

    Science.gov (United States)

    Wang, Tai-Min; Chien, Wei-Yu; Hsu, Chia-Ling; Lin, Chrong Jung; King, Ya-Chin

    2018-04-01

    In this paper, we present a new differential p-channel multiple-time programmable (MTP) memory cell that is fully compatible with advanced 16 nm CMOS fin field-effect transistors (FinFET) logic processes. This differential MTP cell stores complementary data in floating gates coupled by a slot contact structure, which make different read currents possible on a single cell. In nanoscale CMOS FinFET logic processes, the gate dielectric layer becomes too thin to retain charges inside floating gates for nonvolatile data storage. By using a differential architecture, the sensing window of the cell can be extended and maintained by an advanced blanket boost scheme. The charge retention problem in floating gate cells can be improved by periodic restoring lost charges when significant read window narrowing occurs. In addition to high programming efficiency, this p-channel MTP cells also exhibit good cycling endurance as well as disturbance immunity. The blanket boost scheme can remedy the charge loss problem under thin gate dielectrics.

  10. Light programmable organic transistor memory device based on hybrid dielectric

    Science.gov (United States)

    Ren, Xiaochen; Chan, Paddy K. L.

    2013-09-01

    We have fabricated the transistor memory devices based on SiO2 and polystyrene (PS) hybrid dielectric. The trap states densities with different semiconductors have been investigated and a maximum 160V memory window between programming and erasing is realized. For DNTT based transistor, the trapped electron density is limited by the number of mobile electrons in semiconductor. The charge transport mechanism is verified by light induced Vth shift effect. Furthermore, in order to meet the low operating power requirement of portable electronic devices, we fabricated the organic memory transistor based on AlOx/self-assembly monolayer (SAM)/PS hybrid dielectric, the effective capacitance of hybrid dielectric is 210 nF cm-2 and the transistor can reach saturation state at -3V gate bias. The memory window in transfer I-V curve is around 1V under +/-5V programming and erasing bias.

  11. A Vertical Organic Transistor Architecture for Fast Nonvolatile Memory.

    Science.gov (United States)

    She, Xiao-Jian; Gustafsson, David; Sirringhaus, Henning

    2017-02-01

    A new device architecture for fast organic transistor memory is developed, based on a vertical organic transistor configuration incorporating high-performance ambipolar conjugated polymers and unipolar small molecules as the transport layers, to achieve reliable and fast programming and erasing of the threshold voltage shift in less than 200 ns. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Suppressing the memory state of floating gate transistors with repeated femtosecond laser backside irradiations

    Science.gov (United States)

    Chambonneau, Maxime; Souiki-Figuigui, Sarra; Chiquet, Philippe; Della Marca, Vincenzo; Postel-Pellerin, Jérémy; Canet, Pierre; Portal, Jean-Michel; Grojo, David

    2017-04-01

    We demonstrate that infrared femtosecond laser pulses with intensity above the two-photon ionization threshold of crystalline silicon induce charge transport through the tunnel oxide in floating gate Metal-Oxide-Semiconductor transistor devices. With repeated irradiations of Flash memory cells, we show how the laser-produced free-electrons naturally redistribute on both sides of the tunnel oxide until the electric field of the transistor is suppressed. This ability enables us to determine in a nondestructive, rapid and contactless way the flat band and the neutral threshold voltages of the tested device. The physical mechanisms including nonlinear ionization, quantum tunneling of free-carriers, and flattening of the band diagram are discussed for interpreting the experiments. The possibility to control the carriers in memory transistors with ultrashort pulses holds promises for fast and remote device analyses (reliability, security, and defectivity) and for considerable developments in the growing field of ultrafast microelectronics.

  13. Tunnel field-effect transistor charge-trapping memory with steep subthreshold slope and large memory window

    Science.gov (United States)

    Kino, Hisashi; Fukushima, Takafumi; Tanaka, Tetsu

    2018-04-01

    Charge-trapping memory requires the increase of bit density per cell and a larger memory window for lower-power operation. A tunnel field-effect transistor (TFET) can achieve to increase the bit density per cell owing to its steep subthreshold slope. In addition, a TFET structure has an asymmetric structure, which is promising for achieving a larger memory window. A TFET with the N-type gate shows a higher electric field between the P-type source and the N-type gate edge than the conventional FET structure. This high electric field enables large amounts of charges to be injected into the charge storage layer. In this study, we fabricated silicon-oxide-nitride-oxide-semiconductor (SONOS) memory devices with the TFET structure and observed a steep subthreshold slope and a larger memory window.

  14. 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).

  15. One bipolar transistor selector - One resistive random access memory device for cross bar memory array

    Science.gov (United States)

    Aluguri, R.; Kumar, D.; Simanjuntak, F. M.; Tseng, T.-Y.

    2017-09-01

    A bipolar transistor selector was connected in series with a resistive switching memory device to study its memory characteristics for its application in cross bar array memory. The metal oxide based p-n-p bipolar transistor selector indicated good selectivity of about 104 with high retention and long endurance showing its usefulness in cross bar RRAM devices. Zener tunneling is found to be the main conduction phenomena for obtaining high selectivity. 1BT-1R device demonstrated good memory characteristics with non-linearity of 2 orders, selectivity of about 2 orders and long retention characteristics of more than 105 sec. One bit-line pull-up scheme shows that a 650 kb cross bar array made with this 1BT1R devices works well with more than 10 % read margin proving its ability in future memory technology application.

  16. 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.

  17. Reprogrammable read only variable threshold transistor memory with isolated addressing buffer

    Science.gov (United States)

    Lodi, Robert J.

    1976-01-01

    A monolithic integrated circuit, fully decoded memory comprises a rectangular array of variable threshold field effect transistors organized into a plurality of multi-bit words. Binary address inputs to the memory are decoded by a field effect transistor decoder into a plurality of word selection lines each of which activates an address buffer circuit. Each address buffer circuit, in turn, drives a word line of the memory array. In accordance with the word line selected by the decoder the activated buffer circuit directs reading or writing voltages to the transistors comprising the memory words. All of the buffer circuits additionally are connected to a common terminal for clearing all of the memory transistors to a predetermined state by the application to the common terminal of a large magnitude voltage of a predetermined polarity. The address decoder, the buffer and the memory array, as well as control and input/output control and buffer field effect transistor circuits, are fabricated on a common substrate with means provided to isolate the substrate of the address buffer transistors from the remainder of the substrate so that the bulk clearing function of simultaneously placing all of the memory transistors into a predetermined state can be performed.

  18. Subthreshold-swing-adjustable tunneling-field-effect-transistor-based random-access memory for nonvolatile operation

    Science.gov (United States)

    Huh, In; Cheon, Woo Young; Choi, Woo Young

    2016-04-01

    A subthreshold-swing-adjustable tunneling-field-effect-transistor-based random-access memory (SAT RAM) has been proposed and fabricated for low-power nonvolatile memory applications. The proposed SAT RAM cell demonstrates adjustable subthreshold swing (SS) depending on stored information: small SS in the erase state ("1" state) and large SS in the program state ("0" state). Thus, SAT RAM cells can achieve low read voltage (Vread) with a large memory window in addition to the effective suppression of ambipolar behavior. These unique features of the SAT RAM are originated from the locally stored charge, which modulates the tunneling barrier width (Wtun) of the source-to-channel tunneling junction.

  19. 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.

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

    Science.gov (United States)

    Ogasawara, Ryosuke; Endoh, Tetsuo

    2018-04-01

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

  1. Organic field-effect transistor nonvolatile memories utilizing sputtered C nanoparticles as nano-floating-gate

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jie; Liu, Chang-Hai; She, Xiao-Jian; Sun, Qi-Jun; Gao, Xu; Wang, Sui-Dong, E-mail: wangsd@suda.edu.cn [Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou, Jiangsu 215123 (China)

    2014-10-20

    High-performance organic field-effect transistor nonvolatile memories have been achieved using sputtered C nanoparticles as the nano-floating-gate. The sputtered C nano-floating-gate is prepared with low-cost material and simple process, forming uniform and discrete charge trapping sites covered by a smooth and complete polystyrene layer. The devices show large memory window, excellent retention capability, and programming/reading/erasing/reading endurance. The sputtered C nano-floating-gate can effectively trap both holes and electrons, and it is demonstrated to be suitable for not only p-type but also n-type organic field-effect transistor nonvolatile memories.

  2. Organic field-effect transistor nonvolatile memories utilizing sputtered C nanoparticles as nano-floating-gate

    International Nuclear Information System (INIS)

    Liu, Jie; Liu, Chang-Hai; She, Xiao-Jian; Sun, Qi-Jun; Gao, Xu; Wang, Sui-Dong

    2014-01-01

    High-performance organic field-effect transistor nonvolatile memories have been achieved using sputtered C nanoparticles as the nano-floating-gate. The sputtered C nano-floating-gate is prepared with low-cost material and simple process, forming uniform and discrete charge trapping sites covered by a smooth and complete polystyrene layer. The devices show large memory window, excellent retention capability, and programming/reading/erasing/reading endurance. The sputtered C nano-floating-gate can effectively trap both holes and electrons, and it is demonstrated to be suitable for not only p-type but also n-type organic field-effect transistor nonvolatile memories.

  3. Modeling of strain effects on the device behaviors of ferroelectric memory field-effect transistors

    International Nuclear Information System (INIS)

    Yang, Feng; Hu, Guangda; Wu, Weibing; Yang, Changhong; Wu, Haitao; Tang, Minghua

    2013-01-01

    The influence of strains on the channel current–gate voltage behaviors and memory windows of ferroelectric memory field-effect transistors (FeMFETs) were studied using an improved model based on the Landau–Devonshire theory. ‘Channel potential–gate voltage’ ferroelectric polarization and silicon surface potential diagrams were constructed for strained single-domain BaTiO 3 FeMFETs. The compressive strains can increase (or decrease) the amplitude of transistor currents and enlarge memory windows. However, tensile strains only decrease the maximum value of transistor currents and compress memory windows. Mismatch strains were found to have a significant influence on the electrical behaviors of the devices, therefore, they must be considered in FeMFET device designing. (fast track communication)

  4. Surface engineering of ferroelectric polymer for the enhanced electrical performance of organic transistor memory

    Science.gov (United States)

    Kim, Do-Kyung; Lee, Gyu-Jeong; Lee, Jae-Hyun; Kim, Min-Hoi; Bae, Jin-Hyuk

    2018-05-01

    We suggest a viable surface control method to improve the electrical properties of organic nonvolatile memory transistors. For viable surface control, the surface of the ferroelectric insulator in the memory field-effect transistors was modified using a smooth-contact-curing process. For the modification of the ferroelectric polymer, during the curing of the ferroelectric insulators, the smooth surface of a soft elastomer contacts intimately with the ferroelectric surface. This smooth-contact-curing process reduced the surface roughness of the ferroelectric insulator without degrading its ferroelectric properties. The reduced roughness of the ferroelectric insulator increases the mobility of the organic field-effect transistor by approximately eight times, which results in a high memory on–off ratio and a low-voltage reading operation.

  5. Abnormal Multiple Charge Memory States in Exfoliated Few-Layer WSe2 Transistors.

    Science.gov (United States)

    Chen, Mikai; Wang, Yifan; Shepherd, Nathan; Huard, Chad; Zhou, Jiantao; Guo, L J; Lu, Wei; Liang, Xiaogan

    2017-01-24

    To construct reliable nanoelectronic devices based on emerging 2D layered semiconductors, we need to understand the charge-trapping processes in such devices. Additionally, the identified charge-trapping schemes in such layered materials could be further exploited to make multibit (or highly desirable analog-tunable) memory devices. Here, we present a study on the abnormal charge-trapping or memory characteristics of few-layer WSe 2 transistors. This work shows that multiple charge-trapping states with large extrema spacing, long retention time, and analog tunability can be excited in the transistors made from mechanically exfoliated few-layer WSe 2 flakes, whereas they cannot be generated in widely studied few-layer MoS 2 transistors. Such charge-trapping characteristics of WSe 2 transistors are attributed to the exfoliation-induced interlayer deformation on the cleaved surfaces of few-layer WSe 2 flakes, which can spontaneously form ambipolar charge-trapping sites. Our additional results from surface characterization, charge-retention characterization at different temperatures, and density functional theory computation strongly support this explanation. Furthermore, our research also demonstrates that the charge-trapping states excited in multiple transistors can be calibrated into consistent multibit data storage levels. This work advances the understanding of the charge memory mechanisms in layered semiconductors, and the observed charge-trapping states could be further studied for enabling ultralow-cost multibit analog memory devices.

  6. 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...

  7. The influence of nitride thickness variations on the switching speed of MNOS memory transistors

    DEFF Research Database (Denmark)

    Bruun, Erik

    1978-01-01

    The influence of nitride thickness variations on the switching speed of MNOS memory transistors is examined. The switching time constant is calculated as a function of the nitride thickness using a model of modified Fowler-Nordheim injection. The calculated characteristics compare well with measu......The influence of nitride thickness variations on the switching speed of MNOS memory transistors is examined. The switching time constant is calculated as a function of the nitride thickness using a model of modified Fowler-Nordheim injection. The calculated characteristics compare well...

  8. Memory operation devices based on light-illumination ambipolar carbon-nanotube thin-film-transistors

    Energy Technology Data Exchange (ETDEWEB)

    Aïssa, B., E-mail: aissab@emt.inrs.ca [Qatar Environment and Energy Research Institute (QEERI), Qatar Foundation, P.O. Box 5825, Doha (Qatar); Centre Energie, Matériaux et Télécommunications, INRS, 1650, Boulevard Lionel-Boulet Varennes, Quebec J3X 1S2 (Canada); Nedil, M. [Telebec Wireless Underground Communication Laboratory, UQAT, 675, 1ère Avenue, Val d' Or, Quebec J9P 1Y3 (Canada); Kroeger, J. [NanoIntegris & Raymor Nanotech, Raymor Industries Inc., 3765 La Vérendrye, Boisbriand, Quebec J7H 1R8 (Canada); Haddad, T. [Department of Mechanical Engineering, McGill University, Montreal, Quebec H3A 0B8 (Canada); Rosei, F. [Centre Energie, Matériaux et Télécommunications, INRS, 1650, Boulevard Lionel-Boulet Varennes, Quebec J3X 1S2 (Canada)

    2015-09-28

    We report the memory operation behavior of a light illumination ambipolar single-walled carbon nanotube thin film field-effect transistors devices. In addition to the high electronic-performance, such an on/off transistor-switching ratio of 10{sup 4} and an on-conductance of 18 μS, these memory devices have shown a high retention time of both hole and electron-trapping modes, reaching 2.8 × 10{sup 4} s at room temperature. The memory characteristics confirm that light illumination and electrical field can act as an independent programming/erasing operation method. This could be a fundamental step toward achieving high performance and stable operating nanoelectronic memory devices.

  9. Memory operation devices based on light-illumination ambipolar carbon-nanotube thin-film-transistors

    International Nuclear Information System (INIS)

    Aïssa, B.; Nedil, M.; Kroeger, J.; Haddad, T.; Rosei, F.

    2015-01-01

    We report the memory operation behavior of a light illumination ambipolar single-walled carbon nanotube thin film field-effect transistors devices. In addition to the high electronic-performance, such an on/off transistor-switching ratio of 10 4 and an on-conductance of 18 μS, these memory devices have shown a high retention time of both hole and electron-trapping modes, reaching 2.8 × 10 4  s at room temperature. The memory characteristics confirm that light illumination and electrical field can act as an independent programming/erasing operation method. This could be a fundamental step toward achieving high performance and stable operating nanoelectronic memory devices

  10. Transistor memory devices with large memory windows, using multi-stacking of densely packed, hydrophobic charge trapping metal nanoparticle array

    International Nuclear Information System (INIS)

    Cho, Ikjun; Cho, Jinhan; Kim, Beom Joon; Cho, Jeong Ho; Ryu, Sook Won

    2014-01-01

    Organic field-effect transistor (OFET) memories have rapidly evolved from low-cost and flexible electronics with relatively low-memory capacities to memory devices that require high-capacity memory such as smart memory cards or solid-state hard drives. Here, we report the high-capacity OFET memories based on the multilayer stacking of densely packed hydrophobic metal NP layers in place of the traditional transistor memory systems based on a single charge trapping layer. We demonstrated that the memory performances of devices could be significantly enhanced by controlling the adsorption isotherm behavior, multilayer stacking structure and hydrophobicity of the metal NPs. For this study, tetraoctylammonium (TOA)-stabilized Au nanoparticles (TOA-Au NPs ) were consecutively layer-by-layer (LbL) assembled with an amine-functionalized poly(amidoamine) dendrimer (PAD). The formed (PAD/TOA-Au NP ) n films were used as a multilayer stacked charge trapping layer at the interface between the tunneling dielectric layer and the SiO 2 gate dielectric layer. For a single Au NP layer (i.e. PAD/TOA-Au NP ) 1 ) with a number density of 1.82 × 10 12 cm −2 , the memory window of the OFET memory device was measured to be approximately 97 V. The multilayer stacked OFET memory devices prepared with four Au NP layers exhibited excellent programmable memory properties (i.e. a large memory window (ΔV th ) exceeding 145 V, a fast switching speed (1 μs), a high program/erase (P/E) current ratio (greater than 10 6 ) and good electrical reliability) during writing and erasing over a relatively short time scale under an operation voltage of 100 V applied at the gate. (paper)

  11. Ambipolar organic thin-film transistor-based nano-floating-gate nonvolatile memory

    International Nuclear Information System (INIS)

    Han, Jinhua; Wang, Wei; Ying, Jun; Xie, Wenfa

    2014-01-01

    An ambipolar organic thin-film transistor-based nano-floating-gate nonvolatile memory was demonstrated, with discrete distributed gold nanoparticles, tetratetracontane (TTC), pentacene as the floating-gate layer, tunneling layer, and active layer, respectively. The electron traps at the TTC/pentacene interface were significantly suppressed, which resulted in an ambipolar operation in present memory. As both electrons and holes were supplied in the channel and trapped in the floating-gate by programming/erasing operations, respectively, i.e., one type of charge carriers was used to overwrite the other, trapped, one, a large memory window, extending on both sides of the initial threshold voltage, was realized

  12. Ambipolar organic thin-film transistor-based nano-floating-gate nonvolatile memory

    Energy Technology Data Exchange (ETDEWEB)

    Han, Jinhua; Wang, Wei, E-mail: wwei99@jlu.edu.cn; Ying, Jun; Xie, Wenfa [State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, 2699 Qianjin Street, Changchun 130012 (China)

    2014-01-06

    An ambipolar organic thin-film transistor-based nano-floating-gate nonvolatile memory was demonstrated, with discrete distributed gold nanoparticles, tetratetracontane (TTC), pentacene as the floating-gate layer, tunneling layer, and active layer, respectively. The electron traps at the TTC/pentacene interface were significantly suppressed, which resulted in an ambipolar operation in present memory. As both electrons and holes were supplied in the channel and trapped in the floating-gate by programming/erasing operations, respectively, i.e., one type of charge carriers was used to overwrite the other, trapped, one, a large memory window, extending on both sides of the initial threshold voltage, was realized.

  13. Osteoblastic cells trigger gate currents on nanocrystalline diamond transistor

    Czech Academy of Sciences Publication Activity Database

    Ižák, Tibor; Krátká, Marie; Kromka, Alexander; Rezek, Bohuslav

    2015-01-01

    Roč. 129, May (2015), 95-99 ISSN 0927-7765 R&D Projects: GA ČR GAP108/12/0996 Grant - others:AVČR(CZ) M100101209 Institutional support: RVO:68378271 Keywords : field-effect transistors * nanocrystalline diamond * osteoblastic cells * leakage currents Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 3.902, year: 2015

  14. 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...

  15. Current-Induced Transistor Sensorics with Electrogenic Cells

    Directory of Open Access Journals (Sweden)

    Peter Fromherz

    2016-04-01

    Full Text Available The concepts of transistor recording of electroactive cells are considered, when the response is determined by a current-induced voltage in the electrolyte due to cellular activity. The relationship to traditional transistor recording, with an interface-induced response due to interactions with the open gate oxide, is addressed. For the geometry of a cell-substrate junction, the theory of a planar core-coat conductor is described with a one-compartment approximation. The fast electrical relaxation of the junction and the slow change of ion concentrations are pointed out. On that basis, various recording situations are considered and documented by experiments. For voltage-gated ion channels under voltage clamp, the effects of a changing extracellular ion concentration and the enhancement/depletion of ion conductances in the adherent membrane are addressed. Inhomogeneous ion conductances are crucial for transistor recording of neuronal action potentials. For a propagating action potential, the effects of an axon-substrate junction and the surrounding volume conductor are distinguished. Finally, a receptor-transistor-sensor is described, where the inhomogeneity of a ligand–activated ion conductance is achieved by diffusion of the agonist and inactivation of the conductance. Problems with regard to a development of reliable biosensors are mentioned.

  16. Ambipolar nonvolatile memory based on a quantum-dot transistor with a nanoscale floating gate

    International Nuclear Information System (INIS)

    Che, Yongli; Zhang, Yating; Song, Xiaoxian; Cao, Mingxuan; Zhang, Guizhong; Yao, Jianquan; Cao, Xiaolong; Dai, Haitao; Yang, Junbo

    2016-01-01

    Using only solution processing methods, we developed ambipolar quantum-dot (QD) transistor floating-gate memory (FGM) that uses Au nanoparticles as a floating gate. Because of the bipolarity of the active channel of PbSe QDs, the memory could easily trap holes or electrons in the floating gate by programming/erasing (P/E) operations, which could shift the threshold voltage both up and down. As a result, the memory exhibited good programmable memory characteristics: a large memory window (ΔV th  ∼ 15 V) and a long retention time (>10 5  s). The magnitude of ΔV th depended on both P/E voltages and the bias voltage (V DS ): ΔV th was a cubic function to V P/E and linearly depended on V DS . Therefore, this FGM based on a QD transistor is a promising alternative to its inorganic counterparts owing to its advantages of bipolarity, high mobility, low cost, and large-area production.

  17. Ambipolar nonvolatile memory based on a quantum-dot transistor with a nanoscale floating gate

    Energy Technology Data Exchange (ETDEWEB)

    Che, Yongli; Zhang, Yating, E-mail: yating@tju.edu.cn; Song, Xiaoxian; Cao, Mingxuan; Zhang, Guizhong; Yao, Jianquan [Institute of Laser and Opto-Electronics, College of Precision Instruments and Opto-Electronics Engineering, Tianjin University, Tianjin 300072 (China); Key Laboratory of Opto-Electronics Information Technology, Ministry of Education, Tianjin University, Tianjin 300072 (China); Cao, Xiaolong [Institute of Laser and Opto-Electronics, College of Precision Instruments and Opto-Electronics Engineering, Tianjin University, Tianjin 300072 (China); Key Laboratory of Opto-Electronics Information Technology, Ministry of Education, Tianjin University, Tianjin 300072 (China); College of Mechanical and Electronic Engineering, Shandong University of Science and Technology, Qingdao 266590 (China); Dai, Haitao [Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, School of Science, Tianjin University, Tianjin 300072 (China); Yang, Junbo [Center of Material Science, National University of Defense Technology, Changsha 410073 (China)

    2016-07-04

    Using only solution processing methods, we developed ambipolar quantum-dot (QD) transistor floating-gate memory (FGM) that uses Au nanoparticles as a floating gate. Because of the bipolarity of the active channel of PbSe QDs, the memory could easily trap holes or electrons in the floating gate by programming/erasing (P/E) operations, which could shift the threshold voltage both up and down. As a result, the memory exhibited good programmable memory characteristics: a large memory window (ΔV{sub th} ∼ 15 V) and a long retention time (>10{sup 5 }s). The magnitude of ΔV{sub th} depended on both P/E voltages and the bias voltage (V{sub DS}): ΔV{sub th} was a cubic function to V{sub P/E} and linearly depended on V{sub DS}. Therefore, this FGM based on a QD transistor is a promising alternative to its inorganic counterparts owing to its advantages of bipolarity, high mobility, low cost, and large-area production.

  18. 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.

  19. The MONOS memory transistor: application in a radiation-hard nonvolatile RAM

    International Nuclear Information System (INIS)

    Brown, W.D.

    1985-01-01

    The MONOS (metal-oxide-nitride-oxide-silicon) device is a prime candidate for use as the nonvolatile memory element in a radiation-hardened RAM (random-access memory). The endurance, retention and radiation properties of MONOS memory transistors have been studied as a function of post nitride deposition annealing. Following the nitride layer deposition, all devices were subjected to an 800 0 C oxidation step and some were then annealed at 900 0 C in nitrogen. The nitrogen anneal produces an increase in memory window size of approximately 40%. The memory window center of the annealed devices is shifted toward more positive voltages and is more stable with endurance cycling. Endurance cycling to 10 9 cycles produces a 20% increase in memory window size and a 60% increase in decay rate. For a radiation total dose of 10 6 rads (Si), the memory window size is essentially unchanged and the decay rate increases approximately 13%. A combination of 10 9 cycles and 10 6 rads (Si) reduces the decades of retention (in sec) from 6.3 to 4.3 for a +- 23-V 16-μsec write/erase pulse. (author)

  20. 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.

  1. Characteristics of Reduced Graphene Oxide Quantum Dots for a Flexible Memory Thin Film Transistor.

    Science.gov (United States)

    Kim, Yo-Han; Lee, Eun Yeol; Lee, Hyun Ho; Seo, Tae Seok

    2017-05-17

    Reduced graphene oxide quantum dot (rGOQD) devices in formats of capacitor and thin film transistor (TFT) were demonstrated and examined as the first trial to achieve nonambipolar channel property. In addition, through a gold nanoparticle (Au NP) layer embedded between the rGOQD active channel and dielectric layer, memory capacitor and TFT performances were realized by capacitance-voltage (C-V) hysteresis and gate program, erase, and reprogram biases. First, capacitor structure of the rGOQD memory device was constructed to examine memory charging effect featured in hysteretic C-V behavior with a 30 nm dielectric layer of cross-linked poly(vinyl alcohol). For the intervening Au NP charging layer, self-assembled monolayer (SAM) formation of the Au NP was executed to utilize electrostatic interaction by a dip-coating process under ambient environments with a conformal fabrication uniformity. Second, the rGOQD memory TFT device was also constructed in the same format of the Au NPs SAMs on a flexible substrate. Characteristics of the rGOQD TFT output showed novel saturation curves unlike typical graphene-based TFTs. However, The rGOQD TFT device reveals relatively low on/off ratio of 10 1 and mobility of 5.005 cm 2 /V·s. For the memory capacitor, the flat-band voltage shift (ΔV FB ) was measured as 3.74 V for ±10 V sweep, and for the memory TFT, the threshold voltage shift (ΔV th ) by the Au NP charging was detected as 7.84 V. In summary, it was concluded that the rGOQD memory device could accomplish an ideal graphene-based memory performance, which could have provided a wide memory window and saturated output characteristics.

  2. Photovoltaic Cells Improvised With Used Bipolar Junction Transistors

    International Nuclear Information System (INIS)

    Akintayo, J. A

    2002-01-01

    The understanding of the underlying principle that the solar cell consists of a p-n junction is exploited to adapt the basic NPN or PNP Bipolar Junction Transistors (BJT) to serve as solar cells. In this mode the in improvised solar cell have employed just the emitter and the base sections with an intact emitter/base junction as the active PN area. The improvised devices tested screened and sorted are wired up in strings, blocks and modules. The photovoltaic modules realised tested as close replica of solar cells with output voltage following insolation level. Further work need be done on the modules to make them generate usable levels of output voltage and current

  3. 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 ...

  4. Organic Electrochemical Transistors for the Detection of Cell Surface Glycans.

    Science.gov (United States)

    Chen, Lizhen; Fu, Ying; Wang, Naixiang; Yang, Anneng; Li, Yuanzhe; Wu, Jie; Ju, Huangxian; Yan, Feng

    2018-05-23

    Cell surface glycans play critical roles in diverse biological processes, such as cell-cell communication, immunity, infection, development, and differentiation. Their expressions are closely related to cancer growth and metastasis. This work demonstrates an organic electrochemical transistor (OECT)-based biosensor for the detection of glycan expression on living cancer cells. Herein, mannose on human breast cancer cells (MCF-7) as the target glycan model, poly dimethyl diallyl ammonium chloride-multiwall carbon nanotubes (PDDA-MWCNTs) as the loading interface, concanavalin A (Con A) with active mannose binding sites, aptamer and horseradish peroxidase co-immobilized gold nanoparticles (HRP-aptamer-Au NPs) as specific nanoprobes are used to fabricate the OECT biosensor. In this strategy, PDDA-MWCNT interfaces can enhance the loading of Con A, and the target cells can be captured through Con A via active mannose binding sites. Thus, the expression of cell surface can be reflected by the amount of cells captured on the gate. Specific nanoprobes are introduced to the captured cells to produce an OECT signal because of the reduction of hydrogen peroxide catalyzed by HRP conjugated on Au nanoparticles, while the aptamer on nanoprobes can selectively recognize the MCF-7 cells. It is reasonable that more target cells are captured on the gate electrode, more HRP-nanoprobes are loaded thus a larger signal response. The device shows an obvious response to MCF-7 cells down to 10 cells/μL and can be used to selectively monitor the change of mannose expression on cell surfaces upon a treatment with the N-glycan inhibitor. The OECT-based biosensor is promising for the analysis of glycan expressions on the surfaces of different types of cells.

  5. Spike-timing dependent plasticity in a transistor-selected resistive switching memory

    International Nuclear Information System (INIS)

    Ambrogio, S; Balatti, S; Nardi, F; Facchinetti, S; Ielmini, D

    2013-01-01

    In a neural network, neuron computation is achieved through the summation of input signals fed by synaptic connections. The synaptic activity (weight) is dictated by the synchronous firing of neurons, inducing potentiation/depression of the synaptic connection. This learning function can be supported by the resistive switching memory (RRAM), which changes its resistance depending on the amplitude, the pulse width and the bias polarity of the applied signal. This work shows a new synapse circuit comprising a MOS transistor as a selector and a RRAM as a variable resistance, displaying spike-timing dependent plasticity (STDP) similar to the one originally experienced in biological neural networks. We demonstrate long-term potentiation and long-term depression by simulations with an analytical model of resistive switching. Finally, the experimental demonstration of the new STDP scheme is presented. (paper)

  6. Boost Up Carrier Mobility for Ferroelectric Organic Transistor Memory via Buffering Interfacial Polarization Fluctuation

    Science.gov (United States)

    Sun, Huabin; Wang, Qijing; Li, Yun; Lin, Yen-Fu; Wang, Yu; Yin, Yao; Xu, Yong; Liu, Chuan; Tsukagoshi, Kazuhito; Pan, Lijia; Wang, Xizhang; Hu, Zheng; Shi, Yi

    2014-11-01

    Ferroelectric organic field-effect transistors (Fe-OFETs) have been attractive for a variety of non-volatile memory device applications. One of the critical issues of Fe-OFETs is the improvement of carrier mobility in semiconducting channels. In this article, we propose a novel interfacial buffering method that inserts an ultrathin poly(methyl methacrylate) (PMMA) between ferroelectric polymer and organic semiconductor layers. A high field-effect mobility (μFET) up to 4.6 cm2 V-1 s-1 is obtained. Subsequently, the programming process in our Fe-OFETs is mainly dominated by the switching between two ferroelectric polarizations rather than by the mobility-determined charge accumulation at the channel. Thus, the ``reading'' and ``programming'' speeds are significantly improved. Investigations show that the polarization fluctuation at semiconductor/insulator interfaces, which affect the charge transport in conducting channels, can be suppressed effectively using our method.

  7. Organic electrochemical transistors for cell-based impedance sensing

    International Nuclear Information System (INIS)

    Rivnay, Jonathan; Ramuz, Marc; Hama, Adel; Huerta, Miriam; Owens, Roisin M.; Leleux, Pierre

    2015-01-01

    Electrical impedance sensing of biological systems, especially cultured epithelial cell layers, is now a common technique to monitor cell motion, morphology, and cell layer/tissue integrity for high throughput toxicology screening. Existing methods to measure electrical impedance most often rely on a two electrode configuration, where low frequency signals are challenging to obtain for small devices and for tissues with high resistance, due to low current. Organic electrochemical transistors (OECTs) are conducting polymer-based devices, which have been shown to efficiently transduce and amplify low-level ionic fluxes in biological systems into electronic output signals. In this work, we combine OECT-based drain current measurements with simultaneous measurement of more traditional impedance sensing using the gate current to produce complex impedance traces, which show low error at both low and high frequencies. We apply this technique in vitro to a model epithelial tissue layer and show that the data can be fit to an equivalent circuit model yielding trans-epithelial resistance and cell layer capacitance values in agreement with literature. Importantly, the combined measurement allows for low biases across the cell layer, while still maintaining good broadband signal

  8. Homo-junction ferroelectric field-effect-transistor memory device using solution-processed lithium-doped zinc oxide thin films

    KAUST Repository

    Nayak, Pradipta K.; Caraveo-Frescas, J. A.; Bhansali, Unnat. S.; Alshareef, Husam N.

    2012-01-01

    High performance homo-junction field-effect transistor memory devices were prepared using solution processed transparent lithium-doped zinc oxide thin films for both the ferroelectric and semiconducting active layers. A highest field-effect mobility

  9. 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

  10. Homo-junction ferroelectric field-effect-transistor memory device using solution-processed lithium-doped zinc oxide thin films

    Science.gov (United States)

    Nayak, Pradipta K.; Caraveo-Frescas, J. A.; Bhansali, Unnat. S.; Alshareef, H. N.

    2012-06-01

    High performance homo-junction field-effect transistor memory devices were prepared using solution processed transparent lithium-doped zinc oxide thin films for both the ferroelectric and semiconducting active layers. A highest field-effect mobility of 8.7 cm2/Vs was obtained along with an Ion/Ioff ratio of 106. The ferroelectric thin film transistors showed a low sub-threshold swing value of 0.19 V/dec and a significantly reduced device operating voltage (±4 V) compared to the reported hetero-junction ferroelectric transistors, which is very promising for low-power non-volatile memory applications.

  11. Insights into operation of planar tri-gate tunnel field effect transistor for dynamic memory application

    Science.gov (United States)

    Navlakha, Nupur; Kranti, Abhinav

    2017-07-01

    Insights into device physics and operation through the control of energy barriers are presented for a planar tri-gate Tunnel Field Effect Transistor (TFET) based dynamic memory. The architecture consists of a double gate (G1) at the source side and a single gate (G2) at the drain end of the silicon film. Dual gates (G1) effectively enhance the tunneling based read mechanism through the enhanced coupling and improved electrostatic control over the channel. The single gate (G2) controls the holes in the potential barrier induced through the proper selection of bias and workfunction. The results indicate that the planar tri-gate achieves optimum performance evaluated in terms of two composite metrics (M1 and M2), namely, product of (i) Sense Margin (SM) and Retention Time (RT) i.e., M1 = SM × RT and (ii) Sense Margin and Current Ratio (CR) i.e., M2 = SM × CR. The regulation of barriers created by the gates (G1 and G2) through the optimal use of device parameters leads to better performance metrics, with significant improvement at scaled lengths as compared to other tunneling based dynamic memory architectures. The investigation shows that lengths of G1, G2 and lateral spacing can be scaled down to 25 nm, 50 nm, and 30 nm, respectively, while achieving reasonable values for (M1, M2). The work demonstrates a systematic approach to showcase the advancement in TFET based Dynamic Random Access Memory (DRAM) through the use of planar tri-gate topology at a lower bias value. The concept, design, and operation of planar tri-gate architecture provide valuable viewpoints for TFET based DRAM.

  12. Memory and learning behaviors mimicked in nanogranular SiO2-based proton conductor gated oxide-based synaptic transistors.

    Science.gov (United States)

    Wan, Chang Jin; Zhu, Li Qiang; Zhou, Ju Mei; Shi, Yi; Wan, Qing

    2013-11-07

    In neuroscience, signal processing, memory and learning function are established in the brain by modifying ionic fluxes in neurons and synapses. Emulation of memory and learning behaviors of biological systems by nanoscale ionic/electronic devices is highly desirable for building neuromorphic systems or even artificial neural networks. Here, novel artificial synapses based on junctionless oxide-based protonic/electronic hybrid transistors gated by nanogranular phosphorus-doped SiO2-based proton-conducting films are fabricated on glass substrates by a room-temperature process. Short-term memory (STM) and long-term memory (LTM) are mimicked by tuning the pulse gate voltage amplitude. The LTM process in such an artificial synapse is due to the proton-related interfacial electrochemical reaction. Our results are highly desirable for building future neuromorphic systems or even artificial networks via electronic elements.

  13. A light-stimulated synaptic transistor with synaptic plasticity and memory functions based on InGaZnO_x–Al_2O_3 thin film structure

    International Nuclear Information System (INIS)

    Li, H. K.; Chen, T. P.; Liu, P.; Zhang, Q.; Hu, S. G.; Liu, Y.; Lee, P. S.

    2016-01-01

    In this work, a synaptic transistor based on the indium gallium zinc oxide (IGZO)–aluminum oxide (Al_2O_3) thin film structure, which uses ultraviolet (UV) light pulses as the pre-synaptic stimulus, has been demonstrated. The synaptic transistor exhibits the behavior of synaptic plasticity like the paired-pulse facilitation. In addition, it also shows the brain's memory behaviors including the transition from short-term memory to long-term memory and the Ebbinghaus forgetting curve. The synapse-like behavior and memory behaviors of the transistor are due to the trapping and detrapping processes of the holes, which are generated by the UV pulses, at the IGZO/Al_2O_3 interface and/or in the Al_2O_3 layer.

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

    Science.gov (United States)

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

    2017-04-01

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

  15. 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)

  16. Solution-Processed Wide-Bandgap Organic Semiconductor Nanostructures Arrays for Nonvolatile Organic Field-Effect Transistor Memory.

    Science.gov (United States)

    Li, Wen; Guo, Fengning; Ling, Haifeng; Liu, Hui; Yi, Mingdong; Zhang, Peng; Wang, Wenjun; Xie, Linghai; Huang, Wei

    2018-01-01

    In this paper, the development of organic field-effect transistor (OFET) memory device based on isolated and ordered nanostructures (NSs) arrays of wide-bandgap (WBG) small-molecule organic semiconductor material [2-(9-(4-(octyloxy)phenyl)-9H-fluoren-2-yl)thiophene]3 (WG 3 ) is reported. The WG 3 NSs are prepared from phase separation by spin-coating blend solutions of WG 3 /trimethylolpropane (TMP), and then introduced as charge storage elements for nonvolatile OFET memory devices. Compared to the OFET memory device with smooth WG 3 film, the device based on WG 3 NSs arrays exhibits significant improvements in memory performance including larger memory window (≈45 V), faster switching speed (≈1 s), stable retention capability (>10 4 s), and reliable switching properties. A quantitative study of the WG 3 NSs morphology reveals that enhanced memory performance is attributed to the improved charge trapping/charge-exciton annihilation efficiency induced by increased contact area between the WG 3 NSs and pentacene layer. This versatile solution-processing approach to preparing WG 3 NSs arrays as charge trapping sites allows for fabrication of high-performance nonvolatile OFET memory devices, which could be applicable to a wide range of WBG organic semiconductor materials. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Liquid–Solid Dual-Gate Organic Transistors with Tunable Threshold Voltage for Cell Sensing

    KAUST Repository

    Zhang, Yu

    2017-10-17

    Liquid electrolyte-gated organic field effect transistors and organic electrochemical transistors have recently emerged as powerful technology platforms for sensing and simulation of living cells and organisms. For such applications, the transistors are operated at a gate voltage around or below 0.3 V because prolonged application of a higher voltage bias can lead to membrane rupturing and cell death. This constraint often prevents the operation of the transistors at their maximum transconductance or most sensitive regime. Here, we exploit a solid–liquid dual-gate organic transistor structure, where the threshold voltage of the liquid-gated conduction channel is controlled by an additional gate that is separated from the channel by a metal-oxide gate dielectric. With this design, the threshold voltage of the “sensing channel” can be linearly tuned in a voltage window exceeding 0.4 V. We have demonstrated that the dual-gate structure enables a much better sensor response to the detachment of human mesenchymal stem cells. In general, the capability of tuning the optimal sensing bias will not only improve the device performance but also broaden the material selection for cell-based organic bioelectronics.

  18. Liquid-Solid Dual-Gate Organic Transistors with Tunable Threshold Voltage for Cell Sensing.

    Science.gov (United States)

    Zhang, Yu; Li, Jun; Li, Rui; Sbircea, Dan-Tiberiu; Giovannitti, Alexander; Xu, Junling; Xu, Huihua; Zhou, Guodong; Bian, Liming; McCulloch, Iain; Zhao, Ni

    2017-11-08

    Liquid electrolyte-gated organic field effect transistors and organic electrochemical transistors have recently emerged as powerful technology platforms for sensing and simulation of living cells and organisms. For such applications, the transistors are operated at a gate voltage around or below 0.3 V because prolonged application of a higher voltage bias can lead to membrane rupturing and cell death. This constraint often prevents the operation of the transistors at their maximum transconductance or most sensitive regime. Here, we exploit a solid-liquid dual-gate organic transistor structure, where the threshold voltage of the liquid-gated conduction channel is controlled by an additional gate that is separated from the channel by a metal-oxide gate dielectric. With this design, the threshold voltage of the "sensing channel" can be linearly tuned in a voltage window exceeding 0.4 V. We have demonstrated that the dual-gate structure enables a much better sensor response to the detachment of human mesenchymal stem cells. In general, the capability of tuning the optimal sensing bias will not only improve the device performance but also broaden the material selection for cell-based organic bioelectronics.

  19. Investigation of 6T SRAM memory circuit using high-k dielectrics based nano scale junctionless transistor

    Science.gov (United States)

    Charles Pravin, J.; Nirmal, D.; Prajoon, P.; Mohan Kumar, N.; Ajayan, J.

    2017-04-01

    In this paper the Dual Metal Surround Gate Junctionless Transistor (DMSGJLT) has been implemented with various high-k dielectric. The leakage current in the device is analysed in detail by obtaining the band structure for different high-k dielectric material. It is noticed that with increasing dielectric constant the device provides more resistance for the direct tunnelling of electron in off state. The gate oxide capacitance also shows 0.1 μF improvement with Hafnium Oxide (HfO2) than Silicon Oxide (SiO2). This paved the way for a better memory application when high-k dielectric is used. The Six Transistor (6T) Static Random Access Memory (SRAM) circuit implemented shows 41.4% improvement in read noise margin for HfO2 than SiO2. It also shows 37.49% improvement in write noise margin and 30.16% improvement in hold noise margin for HfO2 than SiO2.

  20. Effects of thickness and geometric variations in the oxide gate stack on the nonvolatile memory behaviors of charge-trap memory thin-film transistors

    Science.gov (United States)

    Bak, Jun Yong; Kim, So-Jung; Byun, Chun-Won; Pi, Jae-Eun; Ryu, Min-Ki; Hwang, Chi Sun; Yoon, Sung-Min

    2015-09-01

    Device designs of charge-trap oxide memory thin-film transistors (CTM-TFTs) were investigated to enhance their nonvolatile memory performances. The first strategy was to optimize the film thicknesses of the tunneling and charge-trap (CT) layers in order to meet requirements of both higher operation speed and longer retention time. While the program speed and memory window were improved for the device with a thinner tunneling layer, a long retention time was obtained only for the device with a tunneling layer thicker than 5 nm. The carrier concentration and charge-trap densities were optimized in the 30-nm-thick CT layer. It was observed that 10-nm-thick tunneling, 30-nm-thick CT, and 50-nm-thick blocking layers were the best configuration for our proposed CTM-TFTs, where a memory on/off margin higher than 107 was obtained, and a memory margin of 6.6 × 103 was retained even after the lapse of 105 s. The second strategy was to examine the effects of the geometrical relations between the CT and active layers for the applications of memory elements embedded in circuitries. The CTM-TFTs fabricated without an overlap between the CT layer and the drain electrode showed an enhanced program speed by the reduced parasitic capacitance. The drain-bias disturbance for the memory off-state was effectively suppressed even when a higher read-out drain voltage was applied. Appropriate device design parameters, such as the film thicknesses of each component layer and the geometrical relations between them, can improve the memory performances and expand the application fields of the proposed CTM-TFTs.

  1. 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].

  2. Effect of tunneling layers on the performances of floating-gate based organic thin-film transistor nonvolatile memories

    International Nuclear Information System (INIS)

    Wang, Wei; Han, Jinhua; Ying, Jun; Xiang, Lanyi; Xie, Wenfa

    2014-01-01

    Two types of floating-gate based organic thin-film transistor nonvolatile memories (FG-OTFT-NVMs) were demonstrated, with poly(methyl methacrylate co glycidyl methacrylate) (P(MMA-GMA)) and tetratetracontane (TTC) as the tunneling layer, respectively. Their device performances were measured and compared. In the memory with a P(MMA-GMA) tunneling layer, typical unipolar hole transport was obtained with a relatively small mobility of 0.16 cm 2 /V s. The unidirectional shift of turn-on voltage (V on ) due to only holes trapped/detrapped in/from the floating gate resulted in a small memory window of 12.5 V at programming/erasing voltages (V P /V E ) of ±100 V and a nonzero reading voltage. Benefited from the well-ordered molecule orientation and the trap-free surface of TTC layer, a considerably high hole mobility of 1.7 cm 2 /V s and a visible feature of electrons accumulated in channel and trapped in floating-gate were achieved in the memory with a TTC tunneling layer. High hole mobility resulted in a high on current and a large memory on/off ratio of 600 at the V P /V E of ±100 V. Both holes and electrons were injected into floating-gate and overwritten each other, which resulted in a bidirectional V on shift. As a result, an enlarged memory window of 28.6 V at the V P /V E of ±100 V and a zero reading voltage were achieved. Based on our results, a strategy is proposed to optimize FG-OTFT-NVMs by choosing a right tunneling layer to improve the majority carrier mobility and realize ambipolar carriers injecting and trapping in the floating-gate.

  3. Effect of tunneling layers on the performances of floating-gate based organic thin-film transistor nonvolatile memories

    Science.gov (United States)

    Wang, Wei; Han, Jinhua; Ying, Jun; Xiang, Lanyi; Xie, Wenfa

    2014-09-01

    Two types of floating-gate based organic thin-film transistor nonvolatile memories (FG-OTFT-NVMs) were demonstrated, with poly(methyl methacrylate co glycidyl methacrylate) (P(MMA-GMA)) and tetratetracontane (TTC) as the tunneling layer, respectively. Their device performances were measured and compared. In the memory with a P(MMA-GMA) tunneling layer, typical unipolar hole transport was obtained with a relatively small mobility of 0.16 cm2/V s. The unidirectional shift of turn-on voltage (Von) due to only holes trapped/detrapped in/from the floating gate resulted in a small memory window of 12.5 V at programming/erasing voltages (VP/VE) of ±100 V and a nonzero reading voltage. Benefited from the well-ordered molecule orientation and the trap-free surface of TTC layer, a considerably high hole mobility of 1.7 cm2/V s and a visible feature of electrons accumulated in channel and trapped in floating-gate were achieved in the memory with a TTC tunneling layer. High hole mobility resulted in a high on current and a large memory on/off ratio of 600 at the VP/VE of ±100 V. Both holes and electrons were injected into floating-gate and overwritten each other, which resulted in a bidirectional Von shift. As a result, an enlarged memory window of 28.6 V at the VP/VE of ±100 V and a zero reading voltage were achieved. Based on our results, a strategy is proposed to optimize FG-OTFT-NVMs by choosing a right tunneling layer to improve the majority carrier mobility and realize ambipolar carriers injecting and trapping in the floating-gate.

  4. 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

  5. Direct probing of electron and hole trapping into nano-floating-gate in organic field-effect transistor nonvolatile memories

    Energy Technology Data Exchange (ETDEWEB)

    Cui, Ze-Qun; Wang, Shun; Chen, Jian-Mei; Gao, Xu; Dong, Bin, E-mail: wangsd@suda.edu.cn, E-mail: chilf@suda.edu.cn, E-mail: bdong@suda.edu.cn; Chi, Li-Feng, E-mail: wangsd@suda.edu.cn, E-mail: chilf@suda.edu.cn, E-mail: bdong@suda.edu.cn; Wang, Sui-Dong, E-mail: wangsd@suda.edu.cn, E-mail: chilf@suda.edu.cn, E-mail: bdong@suda.edu.cn [Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou, Jiangsu 215123 (China)

    2015-03-23

    Electron and hole trapping into the nano-floating-gate of a pentacene-based organic field-effect transistor nonvolatile memory is directly probed by Kelvin probe force microscopy. The probing is straightforward and non-destructive. The measured surface potential change can quantitatively profile the charge trapping, and the surface characterization results are in good accord with the corresponding device behavior. Both electrons and holes can be trapped into the nano-floating-gate, with a preference of electron trapping than hole trapping. The trapped charge quantity has an approximately linear relation with the programming/erasing gate bias, indicating that the charge trapping in the device is a field-controlled process.

  6. Direct probing of electron and hole trapping into nano-floating-gate in organic field-effect transistor nonvolatile memories

    International Nuclear Information System (INIS)

    Cui, Ze-Qun; Wang, Shun; Chen, Jian-Mei; Gao, Xu; Dong, Bin; Chi, Li-Feng; Wang, Sui-Dong

    2015-01-01

    Electron and hole trapping into the nano-floating-gate of a pentacene-based organic field-effect transistor nonvolatile memory is directly probed by Kelvin probe force microscopy. The probing is straightforward and non-destructive. The measured surface potential change can quantitatively profile the charge trapping, and the surface characterization results are in good accord with the corresponding device behavior. Both electrons and holes can be trapped into the nano-floating-gate, with a preference of electron trapping than hole trapping. The trapped charge quantity has an approximately linear relation with the programming/erasing gate bias, indicating that the charge trapping in the device is a field-controlled process

  7. Dielectric relaxation dependent memory elements in pentacene/[6,6]-phenyl-C61-butyric acid methyl ester bi-layer field effect transistors

    Energy Technology Data Exchange (ETDEWEB)

    Park, Byoungnam

    2015-03-02

    We fabricate a pentacene/[6,6]-phenyl-C{sub 61}-butyric acid methyl ester (PCBM) bi-layer field effect transistor (FET) featuring large hysteresis that can be used as memory elements. Intentional introduction of excess electron traps in a PCBM layer by exposure to air caused large hysteresis in the FET. The memory window, characterized by the threshold voltage difference, increased upon exposure to air and this is attributed to an increase in the number of electron trapping centers and (or) an increase in the dielectric relaxation time in the underlying PCBM layer. Decrease in the electron conduction in the PCBM close to the SiO{sub 2} gate dielectric upon exposure to air is consistent with the increase in the dielectric relaxation time, ensuring that the presence of large hysteresis in the FET originates from electron trapping at the PCBM not at the pentacene. - Highlights: • Charge trapping-induced memory effect was clarified using transistors. • The memory window can be enhanced by controlling charge trapping mechanism. • Memory transistors can be optimized by controlling dielectric relaxation time.

  8. Proton induced single event upset cross section prediction for 0.15 μm six-transistor (6T) silicon-on-insulator static random access memories

    International Nuclear Information System (INIS)

    Li Lei; Zhou Wanting; Liu Huihua

    2012-01-01

    In this paper, an efficient physics-based method to estimate the saturated proton upset cross section for six-transistor (6T) silicon-on-insulator (SOI) static random access memory (SRAM) cells using layout and technology parameters is proposed. This method calculates the effects of radiation based on device physics. The simple method handles the problem with ease by SPICE simulations, which can be divided into two stages. At first, it uses a standard SPICE program to predict the cross section for recoiling heavy ions with linear energy transfer (LET) of 14 MeV-cm 2 /mg. Then, the predicted cross section for recoiling heavy ions with LET of 14 MeV-cm 2 /mg is used to estimate the saturated proton upset cross section for 6T SOI SRAM cells with a simple model. The calculated proton induced upset cross section based on this method is in good agreement with the test results of 6T SOI SRAM cells processed using 0.15 μm technology. (author)

  9. Molecular design and ordering effects in π-functional materials for transistor and solar cell applications

    KAUST Repository

    Beaujuge, Pierre

    2011-12-21

    Organic electronics are broadly anticipated to impact the development of flexible thin-film device technologies. Among these, solution-processable π-conjugated polymers and small molecules are proving particularly promising in field-effect transistors and bulk heterojunction solar cells. This Perspective analyzes some of the most exciting strategies recently suggested in the design and structural organization of π-functional materials for transistor and solar cell applications. Emphasis is placed on the interplay between molecular structure, self-assembling properties, nanoscale and mesoscale ordering, and device efficiency parameters. A critical look at the various approaches used to optimize both materials and device performance is provided to assist in the identification of new directions and further advances. © 2011 American Chemical Society.

  10. Using white noise to gate organic transistors for dynamic monitoring of cultured cell layers.

    Science.gov (United States)

    Rivnay, Jonathan; Leleux, Pierre; Hama, Adel; Ramuz, Marc; Huerta, Miriam; Malliaras, George G; Owens, Roisin M

    2015-06-26

    Impedance sensing of biological systems allows for monitoring of cell and tissue properties, including cell-substrate attachment, layer confluence, and the "tightness" of an epithelial tissue. These properties are critical for electrical detection of tissue health and viability in applications such as toxicological screening. Organic transistors based on conducting polymers offer a promising route to efficiently transduce ionic currents to attain high quality impedance spectra, but collection of complete impedance spectra can be time consuming (minutes). By applying uniform white noise at the gate of an organic electrochemical transistor (OECT), and measuring the resulting current noise, we are able to dynamically monitor the impedance and thus integrity of cultured epithelial monolayers. We show that noise sourcing can be used to track rapid monolayer disruption due to compounds which interfere with dynamic polymerization events crucial for maintaining cytoskeletal integrity, and to resolve sub-second alterations to the monolayer integrity.

  11. 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

  12. CMOS integration of high-k/metal gate transistors in diffusion and gate replacement (D&GR) scheme for dynamic random access memory peripheral circuits

    Science.gov (United States)

    Dentoni Litta, Eugenio; Ritzenthaler, Romain; Schram, Tom; Spessot, Alessio; O’Sullivan, Barry; Machkaoutsan, Vladimir; Fazan, Pierre; Ji, Yunhyuck; Mannaert, Geert; Lorant, Christophe; Sebaai, Farid; Thiam, Arame; Ercken, Monique; Demuynck, Steven; Horiguchi, Naoto

    2018-04-01

    Integration of high-k/metal gate stacks in peripheral transistors is a major candidate to ensure continued scaling of dynamic random access memory (DRAM) technology. In this paper, the CMOS integration of diffusion and gate replacement (D&GR) high-k/metal gate stacks is investigated, evaluating four different approaches for the critical patterning step of removing the N-type field effect transistor (NFET) effective work function (eWF) shifter stack from the P-type field effect transistor (PFET) area. The effect of plasma exposure during the patterning step is investigated in detail and found to have a strong impact on threshold voltage tunability. A CMOS integration scheme based on an experimental wet-compatible photoresist is developed and the fulfillment of the main device metrics [equivalent oxide thickness (EOT), eWF, gate leakage current density, on/off currents, short channel control] is demonstrated.

  13. Investigations on the effects of electrode materials on the device characteristics of ferroelectric memory thin film transistors fabricated on flexible substrates

    Science.gov (United States)

    Yang, Ji-Hee; Yun, Da-Jeong; Seo, Gi-Ho; Kim, Seong-Min; Yoon, Myung-Han; Yoon, Sung-Min

    2018-03-01

    For flexible memory device applications, we propose memory thin-film transistors using an organic ferroelectric poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)] gate insulator and an amorphous In-Ga-Zn-O (a-IGZO) active channel. The effects of electrode materials and their deposition methods on the characteristics of memory devices exploiting the ferroelectric field effect were investigated for the proposed ferroelectric memory thin-film transistors (Fe-MTFTs) at flat and bending states. It was found that the plasma-induced sputtering deposition and mechanical brittleness of the indium-tin oxide (ITO) markedly degraded the ferroelectric-field-effect-driven memory window and bending characteristics of the Fe-MTFTs. The replacement of ITO electrodes with metal aluminum (Al) electrodes prepared by plasma-free thermal evaporation greatly enhanced the memory device characteristics even under bending conditions owing to their mechanical ductility. Furthermore, poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate) (PEDOT:PSS) was introduced to achieve robust bending performance under extreme mechanical stress. The Fe-MTFTs using PEDOT:PSS source/drain electrodes were successfully fabricated and showed the potential for use as flexible memory devices. The suitable choice of electrode materials employed for the Fe-MTFTs is concluded to be one of the most important control parameters for highly functional flexible Fe-MTFTs.

  14. 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...

  15. 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.

  16. 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.

  17. The retention characteristics of nonvolatile SNOS memory transistors in a radiation environment: Experiment and model

    International Nuclear Information System (INIS)

    McWhorter, P.J.; Miller, S.L.; Dellin, T.A.; Axness, C.L.

    1987-01-01

    Experimental data and a model to accurately and quantitatively predict the data are presented for retention of SNOS memory devices over a wide range of dose rates. A wide range of SNOS stack geometries are examined. The model is designed to aid in screening nonvolatile memories for use in a radiation environment

  18. 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

  19. 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.

  20. High-Performance Nonvolatile Organic Field-Effect Transistor Memory Based on Organic Semiconductor Heterostructures of Pentacene/P13/Pentacene as Both Charge Transport and Trapping Layers.

    Science.gov (United States)

    Li, Wen; Guo, Fengning; Ling, Haifeng; Zhang, Peng; Yi, Mingdong; Wang, Laiyuan; Wu, Dequn; Xie, Linghai; Huang, Wei

    2017-08-01

    Nonvolatile organic field-effect transistor (OFET) memory devices based on pentacene/ N , N '-ditridecylperylene-3,4,9,10-tetracarboxylic diimide (P13)/pentacene trilayer organic heterostructures have been proposed. The discontinuous n-type P13 embedded in p-type pentacene layers can not only provide electrons in the semiconductor layer that facilitates electron trapping process; it also works as charge trapping sites, which is attributed to the quantum well-like pentacene/P13/pentacene organic heterostructures. The synergistic effects of charge trapping in the discontinuous P13 and the charge-trapping property of the poly(4-vinylphenol) (PVP) layer remarkably improve the memory performance. In addition, the trilayer organic heterostructures have also been successfully applied to multilevel and flexible nonvolatile memory devices. The results provide a novel design strategy to achieve high-performance nonvolatile OFET memory devices and allow potential applications for different combinations of various organic semiconductor materials in OFET memory.

  1. 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.

  2. 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)

  3. Material insights of HfO2-based integrated 1-transistor-1-resistor resistive random access memory devices processed by batch atomic layer deposition.

    Science.gov (United States)

    Niu, Gang; Kim, Hee-Dong; Roelofs, Robin; Perez, Eduardo; Schubert, Markus Andreas; Zaumseil, Peter; Costina, Ioan; Wenger, Christian

    2016-06-17

    With the continuous scaling of resistive random access memory (RRAM) devices, in-depth understanding of the physical mechanism and the material issues, particularly by directly studying integrated cells, become more and more important to further improve the device performances. In this work, HfO2-based integrated 1-transistor-1-resistor (1T1R) RRAM devices were processed in a standard 0.25 μm complementary-metal-oxide-semiconductor (CMOS) process line, using a batch atomic layer deposition (ALD) tool, which is particularly designed for mass production. We demonstrate a systematic study on TiN/Ti/HfO2/TiN/Si RRAM devices to correlate key material factors (nano-crystallites and carbon impurities) with the filament type resistive switching (RS) behaviours. The augmentation of the nano-crystallites density in the film increases the forming voltage of devices and its variation. Carbon residues in HfO2 films turn out to be an even more significant factor strongly impacting the RS behaviour. A relatively higher deposition temperature of 300 °C dramatically reduces the residual carbon concentration, thus leading to enhanced RS performances of devices, including lower power consumption, better endurance and higher reliability. Such thorough understanding on physical mechanism of RS and the correlation between material and device performances will facilitate the realization of high density and reliable embedded RRAM devices with low power consumption.

  4. Homo-junction ferroelectric field-effect-transistor memory device using solution-processed lithium-doped zinc oxide thin films

    KAUST Repository

    Nayak, Pradipta K.

    2012-06-22

    High performance homo-junction field-effect transistor memory devices were prepared using solution processed transparent lithium-doped zinc oxide thin films for both the ferroelectric and semiconducting active layers. A highest field-effect mobility of 8.7 cm2/Vs was obtained along with an Ion/Ioff ratio of 106. The ferroelectric thin filmtransistors showed a low sub-threshold swing value of 0.19 V/dec and a significantly reduced device operating voltage (±4 V) compared to the reported hetero-junction ferroelectrictransistors, which is very promising for low-power non-volatile memory applications.

  5. Photoresponse and photo-induced memory effect in the organic field-effect transistor based on AlOX nanoparticles at the interface of semiconductor/dielectric

    Science.gov (United States)

    Cheng, Yunfei; Wang, Wu

    2017-10-01

    In this work, the photoresponse and photo-induced memory effect were demonstrated in an organic field-effect transistor (OFET) with semiconductor pentacene and SiO2 as the active and gate dielectric layers, respectively. By inserting AlOX nanoparticles (NPs) at the interface of pentacene/SiO2, obvious enhancing photoresponse was obtained in the OFET with the maximum responsivity and photosensitivity of about 15 A/W and 100, respectively. Moreover, the stable photoinduced memory effect was achieved in the OFET, attributing to the photogenerated electrons captured by the interface traps of the AlOX NPs/SiO2.

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

    Science.gov (United States)

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

    2017-09-01

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

  7. Three-terminal heterojunction bipolar transistor solar cell for high-efficiency photovoltaic conversion.

    Science.gov (United States)

    Martí, A; Luque, A

    2015-04-22

    Here we propose, for the first time, a solar cell characterized by a semiconductor transistor structure (n/p/n or p/n/p) where the base-emitter junction is made of a high-bandgap semiconductor and the collector is made of a low-bandgap semiconductor. We calculate its detailed-balance efficiency limit and prove that it is the same one than that of a double-junction solar cell. The practical importance of this result relies on the simplicity of the structure that reduces the number of layers that are required to match the limiting efficiency of dual-junction solar cells without using tunnel junctions. The device naturally emerges as a three-terminal solar cell and can also be used as building block of multijunction solar cells with an increased number of junctions.

  8. 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...

  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. 1T1R Nonvolatile Memory with Al/TiO2/Au and Sol-Gel-Processed Insulator for Barium Zirconate Nickelate Gate in Pentacene Thin Film Transistor

    Directory of Open Access Journals (Sweden)

    Ke-Jing Lee

    2017-12-01

    Full Text Available A one-transistor and one-resistor (1T1R architecture with a resistive random access memory (RRAM cell connected to an organic thin-film transistor (OTFT device is successfully demonstrated to avoid the cross-talk issues of only one RRAM cell. The OTFT device, which uses barium zirconate nickelate (BZN as a dielectric layer, exhibits favorable electrical properties, such as a high field-effect mobility of 2.5 cm2/Vs, low threshold voltage of −2.8 V, and low leakage current of 10−12 A, for a driver in the 1T1R operation scheme. The 1T1R architecture with a TiO2-based RRAM cell connected with a BZN OTFT device indicates a low operation current (10 μA and reliable data retention (over ten years. This favorable performance of the 1T1R device can be attributed to the additional barrier heights introduced by using Ni (II acetylacetone as a substitute for acetylacetone, and the relatively low leakage current of a BZN dielectric layer. The proposed 1T1R device with low leakage current OTFT and excellent uniform resistance distribution of RRAM exhibits a good potential for use in practical low-power electronic applications.

  11. Direct visualization of polarization reversal of organic ferroelectric memory transistor by using charge modulated reflectance imaging

    Science.gov (United States)

    Otsuka, Takako; Taguchi, Dai; Manaka, Takaaki; Iwamoto, Mitsumasa

    2017-11-01

    By using the charge modulated reflectance (CMR) imaging technique, charge distribution in the pentacene organic field-effect transistor (OFET) with a ferroelectric gate insulator [P(VDF-TrFE)] was investigated in terms of polarization reversal of the P(VDF-TrFE) layer. We studied the polarization reversal process and the carrier spreading process in the OFET channel. The I-V measurement showed a hysteresis behavior caused by the spontaneous polarization of P(VDF-TrFE), but the hysteresis I-V curve changes depending on the applied drain bias, possibly due to the gradual shift of the polarization reversal position in the OFET channel. CMR imaging visualized the gradual shift of the polarization reversal position and showed that the electrostatic field formed by the polarization of P(VDF-TrFE) contributes to hole and electron injection into the pentacene layer and the carrier distribution is significantly dependent on the direction of the polarization. The polarization reversal position in the channel region is governed by the electrostatic potential, and it happens where the potential reaches the coercive voltage of P(VDF-TrFE). The transmission line model developed on the basis of the Maxwell-Wagner effect element analysis well accounts for this polarization reversal process in the OFET channel.

  12. Comparison Elements on STG DICE cell for Content-Addressable Memory and Simulation of Single-Event Transients

    Directory of Open Access Journals (Sweden)

    V. Ya. Stenin

    2017-06-01

    Full Text Available Comparison elements on base the STG DICE cell and the logical element “Exclusive OR” for a content-addressable memory were designed and simulated. The comparison element contains two identical joint groups of transistors that are spaced on the chip by the distance of four micrometers, so the loss of data in STG DICE cell practically excluded. On the characteristics of the new 65-nm CMOS comparison element, we predict the hardness of these item to single event rate (SER more to hundred times compared to elements on 6-transistors cells and the standard DICE cell with distances 0.5-0.6 μm between mutually sensitive nodes.

  13. Diazaisoindigo bithiophene and terthiophene copolymers for application in field-effect transistors and solar cells

    KAUST Repository

    Yue, Wan

    2017-06-10

    Two donor–acceptor conjugated polymers with azaisoindigo as acceptor units and bithiophene and terthiophene as donor units have been synthesized by Stille polymerization. These two polymers have been successfully applied in field-effect transistors and polymer solar cells. By changing the donor component of the conjugated polymer backbone from bithiophene to terthiophene, the density of thiophene in the backbone is increased, manifesting as a decrease in both ionization potential and in electron affinity. Therefore, the charge transport in field-effect transistors switches from ambipolar to predominantly hole transport behavior. PAIIDTT exhibits hole mobility up to 0.40 cm2/Vs and electron mobility of 0.02 cm2/Vs, whereas PAIIDTTT exhibits hole mobility of 0.62 cm2/Vs. Polymer solar cells were fabricated based on these two polymers as donors with PC61BM and PC71BM as acceptor where PAIIDTT shows a modest efficiency of 2.57% with a very low energy loss of 0.55 eV, while PAIIDTTT shows a higher efficiency of 6.16% with a higher energy loss of 0.74 eV. Our results suggest that azaisoindgo is a useful building block for the development of efficient polymer solar cells with further improvement possibility by tuning the alternative units on the polymer backbone. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017

  14. A light-stimulated synaptic transistor with synaptic plasticity and memory functions based on InGaZnO{sub x}–Al{sub 2}O{sub 3} thin film structure

    Energy Technology Data Exchange (ETDEWEB)

    Li, H. K.; Chen, T. P., E-mail: echentp@ntu.edu.sg; Liu, P.; Zhang, Q. [School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798 (Singapore); Hu, S. G. [School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798 (Singapore); State Key Laboratory of Electronic Thin Films and Integrated Devices, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054 (China); Liu, Y. [State Key Laboratory of Electronic Thin Films and Integrated Devices, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054 (China); Lee, P. S. [School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798 (Singapore)

    2016-06-28

    In this work, a synaptic transistor based on the indium gallium zinc oxide (IGZO)–aluminum oxide (Al{sub 2}O{sub 3}) thin film structure, which uses ultraviolet (UV) light pulses as the pre-synaptic stimulus, has been demonstrated. The synaptic transistor exhibits the behavior of synaptic plasticity like the paired-pulse facilitation. In addition, it also shows the brain's memory behaviors including the transition from short-term memory to long-term memory and the Ebbinghaus forgetting curve. The synapse-like behavior and memory behaviors of the transistor are due to the trapping and detrapping processes of the holes, which are generated by the UV pulses, at the IGZO/Al{sub 2}O{sub 3} interface and/or in the Al{sub 2}O{sub 3} layer.

  15. Review on thin-film transistor technology, its applications, and possible new applications to biological cells

    Science.gov (United States)

    Tixier-Mita, Agnès; Ihida, Satoshi; Ségard, Bertrand-David; Cathcart, Grant A.; Takahashi, Takuya; Fujita, Hiroyuki; Toshiyoshi, Hiroshi

    2016-04-01

    This paper presents a review on state-of-the-art of thin-film transistor (TFT) technology and its wide range of applications, not only in liquid crystal displays (TFT-LCDs), but also in sensing devices. The history of the evolution of the technology is first given. Then the standard applications of TFT-LCDs, and X-ray detectors, followed by state-of-the-art applications in the field of chemical and biochemical sensing are presented. TFT technology allows the fabrication of dense arrays of independent and transparent microelectrodes on large glass substrates. The potential of these devices as electrical substrates for biological cell applications is then described. The possibility of using TFT array substrates as new tools for electrical experiments on biological cells has been investigated for the first time by our group. Dielectrophoresis experiments and impedance measurements on yeast cells are presented here. Their promising results open the door towards new applications of TFT technology.

  16. 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

  17. An Investigation of Quantum Dot Super Lattice Use in Nonvolatile Memory and Transistors

    Science.gov (United States)

    Mirdha, P.; Parthasarathy, B.; Kondo, J.; Chan, P.-Y.; Heller, E.; Jain, F. C.

    2018-02-01

    Site-specific self-assembled colloidal quantum dots (QDs) will deposit in two layers only on p-type substrate to form a QD superlattice (QDSL). The QDSL structure has been integrated into the floating gate of a nonvolatile memory component and has demonstrated promising results in multi-bit storage, ease of fabrication, and memory retention. Additionally, multi-valued logic devices and circuits have been created by using QDSL structures which demonstrated ternary and quaternary logic. With increasing use of site-specific self-assembled QDSLs, fundamental understanding of silicon and germanium QDSL charge storage capability, self-assembly on specific surfaces, uniform distribution, and mini-band formation has to be understood for successful implementation in devices. In this work, we investigate the differences in electron charge storage by building metal-oxide semiconductor (MOS) capacitors and using capacitance and voltage measurements to quantify the storage capabilities. The self-assembly process and distribution density of the QDSL is done by obtaining atomic force microscopy (AFM) results on line samples. Additionally, we present a summary of the theoretical density of states in each of the QDSLs.

  18. 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

  19. 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.

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

    Science.gov (United States)

    Ochoa, A. Jr.

    1987-10-28

    In a random access memory cell, a resistance ''T'' decoupling network in each leg of the cell reduces random errors caused by the interaction of energetic ions with the semiconductor material forming the cell. The cell comprises two parallel legs each containing a series pair of complementary MOS transistors having a common gate connected to the node between the transistors of the opposite leg. The decoupling network in each leg is formed by a series pair of resistors between the transistors together with a third resistor interconnecting the junction between the pair of resistors and the gate of the transistor pair forming the opposite leg of the cell. 4 figs.

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

    Science.gov (United States)

    Ochoa, Jr., Agustin

    1989-01-01

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

  2. Asymmetric diketopyrrolopyrrole conjugated polymers for field-effect transistors and polymer solar cells processed from a non-chlorinated solvent

    NARCIS (Netherlands)

    Ji, Y.; Xiao, C.; Wang, Q.; Zhang, J.; Li, C.; Wu, Y.; Wei, Z.; Zhan, X.; Hu, W.; Wang, Z.; Janssen, R.A.J.; Li, W.W.

    2016-01-01

    Newly designed asymmetric diketopyrrolopyrrole conjugated polymers with two different aromatic substituents possess a hole mobility of 12.5 cm2 V−1 s−1 in field-effect transistors and a power conversion efficiency of 6.5% in polymer solar cells, when solution processed from a nonchlorinated

  3. Influence of non-adherent yeast cells on electrical characteristics of diamond-based field-effect transistors

    Czech Academy of Sciences Publication Activity Database

    Procházka, Václav; Cifra, Michal; Kulha, Pavel; Ižák, Tibor; Rezek, Bohuslav; Kromka, Alexander

    2017-01-01

    Roč. 395, Feb (2017), s. 214-219 ISSN 0169-4332 R&D Projects: GA ČR(CZ) GBP108/12/G108 Institutional support: RVO:68378271 ; RVO:67985882 Keywords : nanocrystalline diamond * yeast cells * field-effect transistor * transfer characteristics pH sensitivity Subject RIV: BO - Biophysics OBOR OECD: Biophysics Impact factor: 3.387, year: 2016

  4. Two transistor cluster DICE Cells with the minimum area for a hardened 28-nm CMOS and 65-nm SRAM layout design

    International Nuclear Information System (INIS)

    Stenin, V.Ya.; Stepanov, P.V.

    2015-01-01

    A hardened DICE cell layout design is based on the two spaced transistor clusters of the DICE cell each consisting of four transistors. The larger the distance between these two CMOS transistor clusters, the more robust the hardened DICE SRAM to Single Event Upsets. Some versions of the 28-nm and 65-nm DICE CMOS SRAM block composition have been suggested with minimum cluster distances of 2.27-2.32 mkm. The area of hardened 28-nm DICE CMOS cells is larger than the area of 28-nm 6T CMOS cells by a factor of 2.1 [ru

  5. Capacitorless one-transistor dynamic random-access memory based on asymmetric double-gate Ge/GaAs-heterojunction tunneling field-effect transistor with n-doped boosting layer and drain-underlap structure

    Science.gov (United States)

    Yoon, Young Jun; Seo, Jae Hwa; Kang, In Man

    2018-04-01

    In this work, we present a capacitorless one-transistor dynamic random-access memory (1T-DRAM) based on an asymmetric double-gate Ge/GaAs-heterojunction tunneling field-effect transistor (TFET) for DRAM applications. The n-doped boosting layer and gate2 drain-underlap structure is employed in the device to obtain an excellent 1T-DRAM performance. The n-doped layer inserted between the source and channel regions improves the sensing margin because of a high rate of increase in the band-to-band tunneling (BTBT) probability. Furthermore, because the gate2 drain-underlap structure reduces the recombination rate that occurs between the gate2 and drain regions, a device with a gate2 drain-underlap length (L G2_D-underlap) of 10 nm exhibited a longer retention performance. As a result, by applying the n-doped layer and gate2 drain-underlap structure, the proposed device exhibited not only a high sensing margin of 1.11 µA/µm but also a long retention time of greater than 100 ms at a temperature of 358 K (85 °C).

  6. 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)

  7. 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

  8. EDITORIAL: Reigniting innovation in the transistor Reigniting innovation in the transistor

    Science.gov (United States)

    Demming, Anna

    2012-09-01

    behaviour in devices fabricated from chemically reduced graphene oxide. The work provided an important step forward for graphene electronics, which has been hampered by difficulties in scaling up the mechanical exfoliation techniques required to produce the high-quality graphene often needed for functioning devices [8]. In Sweden, researchers have developed a transistor design that they fabricate using standard III-V parallel processing, which also has great promise for scaling up production. Their transistor is based on a vertical array of InAs nanowires, which provide high electron mobility and the possibility of high-speed and low-power operation [9]. Different fabrication techniques and design parameters can influence the properties of transistors. Researchers in Belgium used a new method based on high-vacuum scanning spreading resistance microscopy to study the effect of diameter on carrier profile in nanowire transistors [10]. They then used experimental data and simulations to gain a better understanding of how this influenced the transistor performance. In Japan, Y Ohno and colleagues at Nagoya University have reported how atomic layer deposition of an insulating layer of HfO2 on carbon nanotube field effect transistors can change the carrier from p-type to n-type [11]. Carrier type switching—'ambipolar behaviour'—and hysteresis of carbon nanotube network transistors can make achieving reliable device performance challenging. However studies have also suggested that the hysteretic properties may be exploited in non-volatile memory applications. A collaboration of researchers in Italy and the US demonstrated transistor and memory cell behaviour in a system based on a carbon nanotube network [13]. Their device had relatively fast programming, good endurance and the charge retention was successfully enhanced by limiting exposure to air. Progress in understanding transistor behaviour has inspired other innovations in device applications. Nanowires are notoriously

  9. Theoretical results on the tandem junction solar cell based on its Ebers-Moll transistor model

    Science.gov (United States)

    Goradia, C.; Vaughn, J.; Baraona, C. R.

    1980-01-01

    A one-dimensional theoretical model of the tandem junction solar cell (TJC) with base resistivity greater than about 1 ohm-cm and under low level injection has been derived. This model extends a previously published conceptual model which treats the TJC as an npn transistor. The model gives theoretical expressions for each of the Ebers-Moll type currents of the illuminated TJC and allows for the calculation of the spectral response, I(sc), V(oc), FF and eta under variation of one or more of the geometrical and material parameters and 1MeV electron fluence. Results of computer calculations based on this model are presented and discussed. These results indicate that for space applications, both a high beginning of life efficiency, greater than 15% AM0, and a high radiation tolerance can be achieved only with thin (less than 50 microns) TJC's with high base resistivity (greater than 10 ohm-cm).

  10. Thin-film-transistor array: an exploratory attempt for high throughput cell manipulation using electrowetting principle

    Science.gov (United States)

    Shaik, F. Azam; Cathcart, G.; Ihida, S.; Lereau-Bernier, M.; Leclerc, E.; Sakai, Y.; Toshiyoshi, H.; Tixier-Mita, A.

    2017-05-01

    In lab-on-a-chip (LoC) devices, microfluidic displacement of liquids is a key component. electrowetting on dielectric (EWOD) is a technique to move fluids, with the advantage of not requiring channels, pumps or valves. Fluids are discretized into droplets on microelectrodes and moved by applying an electric field via the electrodes to manipulate the contact angle. Micro-objects, such as biological cells, can be transported inside of these droplets. However, the design of conventional microelectrodes, made by standard micro-fabrication techniques, fixes the path of the droplets, and limits the reconfigurability of paths and thus limits the parallel processing of droplets. In that respect, thin film transistor (TFT) technology presents a great opportunity as it allows infinitely reconfigurable paths, with high parallelizability. We propose here to investigate the possibility of using TFT array devices for high throughput cell manipulation using EWOD. A COMSOL based 2D simulation coupled with a MATLAB algorithm was used to simulate the contact angle modulation, displacement and mixing of droplets. These simulations were confirmed by experimental results. The EWOD technique was applied to a droplet of culture medium containing HepG2 carcinoma cells and demonstrated no negative effects on the viability of the cells. This confirms the possibility of applying EWOD techniques to cellular applications, such as parallel cell analysis.

  11. Thin-film-transistor array: an exploratory attempt for high throughput cell manipulation using electrowetting principle

    International Nuclear Information System (INIS)

    Shaik, F Azam; Cathcart, G; Toshiyoshi, H; Tixier-Mita, A; Ihida, S; Sakai, Y; Lereau-Bernier, M; Leclerc, E

    2017-01-01

    In lab-on-a-chip (LoC) devices, microfluidic displacement of liquids is a key component. electrowetting on dielectric (EWOD) is a technique to move fluids, with the advantage of not requiring channels, pumps or valves. Fluids are discretized into droplets on microelectrodes and moved by applying an electric field via the electrodes to manipulate the contact angle. Micro-objects, such as biological cells, can be transported inside of these droplets. However, the design of conventional microelectrodes, made by standard micro-fabrication techniques, fixes the path of the droplets, and limits the reconfigurability of paths and thus limits the parallel processing of droplets. In that respect, thin film transistor (TFT) technology presents a great opportunity as it allows infinitely reconfigurable paths, with high parallelizability. We propose here to investigate the possibility of using TFT array devices for high throughput cell manipulation using EWOD. A COMSOL based 2D simulation coupled with a MATLAB algorithm was used to simulate the contact angle modulation, displacement and mixing of droplets. These simulations were confirmed by experimental results. The EWOD technique was applied to a droplet of culture medium containing HepG2 carcinoma cells and demonstrated no negative effects on the viability of the cells. This confirms the possibility of applying EWOD techniques to cellular applications, such as parallel cell analysis. (paper)

  12. Nonvolatile memory thin film transistors using CdSe/ZnS quantum dot-poly(methyl methacrylate) composite layer formed by a two-step spin coating technique

    Science.gov (United States)

    Chen, Ying-Chih; Huang, Chun-Yuan; Yu, Hsin-Chieh; Su, Yan-Kuin

    2012-08-01

    The nonvolatile memory thin film transistors (TFTs) using a core/shell CdSe/ZnS quantum dot (QD)-poly(methyl methacrylate) (PMMA) composite layer as the floating gate have been demonstrated, with the device configuration of n+-Si gate/SiO2 insulator/QD-PMMA composite layer/pentacene channel/Au source-drain being proposed. To achieve the QD-PMMA composite layer, a two-step spin coating technique was used to successively deposit QD-PMMA composite and PMMA on the insulator. After the processes, the variation of crystal quality and surface morphology of the subsequent pentacene films characterized by x-ray diffraction spectra and atomic force microscopy was correlated to the two-step spin coating. The crystalline size of pentacene was improved from 147.9 to 165.2 Å, while the degree of structural disorder was decreased from 4.5% to 3.1% after the adoption of this technique. In pentacene-based TFTs, the improvement of the performance was also significant, besides the appearances of strong memory characteristics. The memory behaviors were attributed to the charge storage/discharge effect in QD-PMMA composite layer. Under the programming and erasing operations, programmable memory devices with the memory window (Δ Vth) = 23 V and long retention time were obtained.

  13. High‐Performance Nonvolatile Organic Field‐Effect Transistor Memory Based on Organic Semiconductor Heterostructures of Pentacene/P13/Pentacene as Both Charge Transport and Trapping Layers

    Science.gov (United States)

    Li, Wen; Guo, Fengning; Ling, Haifeng; Zhang, Peng; Wang, Laiyuan; Wu, Dequn

    2017-01-01

    Nonvolatile organic field‐effect transistor (OFET) memory devices based on pentacene/N,N′‐ditridecylperylene‐3,4,9,10‐tetracarboxylic diimide (P13)/pentacene trilayer organic heterostructures have been proposed. The discontinuous n‐type P13 embedded in p‐type pentacene layers can not only provide electrons in the semiconductor layer that facilitates electron trapping process; it also works as charge trapping sites, which is attributed to the quantum well‐like pentacene/P13/pentacene organic heterostructures. The synergistic effects of charge trapping in the discontinuous P13 and the charge‐trapping property of the poly(4‐vinylphenol) (PVP) layer remarkably improve the memory performance. In addition, the trilayer organic heterostructures have also been successfully applied to multilevel and flexible nonvolatile memory devices. The results provide a novel design strategy to achieve high‐performance nonvolatile OFET memory devices and allow potential applications for different combinations of various organic semiconductor materials in OFET memory. PMID:28852619

  14. Band-to-band tunneling field effect transistor for low power logic and memory applications: Design, fabrication and characterization

    Science.gov (United States)

    Mookerjea, Saurabh A.

    Over the past decade the microprocessor clock frequency has hit a plateau. The main reason for this has been the inability to follow constant electric field scaling, which requires the transistor supply voltage to be scaled down as the transistor dimensions are reduced. Scaling the supply voltage down reduces the dynamic power quadratically but increases the static leakage power exponentially due to non-scalability of threshold voltage of the transistor, which is required to maintain the same ON state performance. This limitation in supply voltage scaling is directly related to MOSFET's (Metal Oxide Semiconductor Field Effect Transistor) sub-threshold slope (SS) limitation of 60 mV/dec at room temperature. Thus novel device design/materials are required that would allow the transistor to switch with sub-threshold slopes steeper than 60 mV/dec at room temperature, thus facilitating supply voltage scaling. Recently, a new class of devices known as super-steep slope (SSswitching behavior of TFET is studied through mixed-mode numerical simulations. The significance of correct benchmarking methodology to estimate the effective drive current and capacitance in TFET is highlighted and compared with MOSFET. This is followed by the fabrication details of homo-junction TFET. Analysis of the electrical characteristics of homo-junction TFET gives key insight into its device operation and identifies the critical factors that impact its performance. In order to boost the ON current, the design and fabrication of hetero-junction TFET is also presented.

  15. 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.

  16. Evolution of the MOS transistor - From conception to VLSI

    International Nuclear Information System (INIS)

    Sah, C.T.

    1988-01-01

    Historical developments of the metal-oxide-semiconductor field-effect-transistor (MOSFET) during the last sixty years are reviewed, from the 1928 patent disclosures of the field-effect conductivity modulation concept and the semiconductor triodes structures proposed by Lilienfeld to the 1947 Shockley-originated efforts which led to the laboratory demonstration of the modern silicon MOSFET thirty years later in 1960. A survey is then made of the milestones of the past thirty years leading to the latest submicron silicon logic CMOS (Complementary MOS) and BICMOS (Bipolar-Junction-Transistor CMOS combined) arrays and the three-dimensional and ferroelectric extensions of Dennard's one-transistor dynamic random access memory (DRAM) cell. Status of the submicron lithographic technologies (deep ultra-violet light, X-ray, electron-beam) are summarized. Future trends of memory cell density and logic gate speed are projected. Comparisons of the switching speed of the silicon MOSFET with that of silicon bipolar and GaAs field-effect transistors are reviewed. Use of high-temperature superconducting wires and GaAs-on-Si monolithic semiconductor optical clocks to break the interconnect-wiring delay barrier is discussed. Further needs in basic research and mathematical modeling on the failure mechanisms in submicron silicon transistors at high electric fields (hot electron effects) and in interconnection conductors at high current densities and low as well as high electric fields (electromigration) are indicated

  17. 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.

  18. Transistor data book

    International Nuclear Information System (INIS)

    1988-03-01

    It introduces how to use this book. It lists transistor data and index, which are Type No, Cross index, Germanium PNP low power transistors, silicon NPN low power transistors, Germanium PNP high power transistors, Switching transistors, transistor arrays, Miscellaneous transistors, types with U.S military specifications, direct replacement transistors, suggested replacement transistors, schematic drawings, outline drawings, device number keys and manufacturer's logos.

  19. High reliable and stable organic field-effect transistor nonvolatile memory with a poly(4-vinyl phenol) charge trapping layer based on a pn-heterojunction active layer

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Lanyi; Ying, Jun; Han, Jinhua; Zhang, Letian, E-mail: zlt@jlu.edu.cn, E-mail: wwei99@jlu.edu.cn; Wang, Wei, E-mail: zlt@jlu.edu.cn, E-mail: wwei99@jlu.edu.cn [State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, 2699 Qianjin Street, Changchun 130012 (China)

    2016-04-25

    In this letter, we demonstrate a high reliable and stable organic field-effect transistor (OFET) based nonvolatile memory (NVM) with a polymer poly(4-vinyl phenol) (PVP) as the charge trapping layer. In the unipolar OFETs, the inreversible shifts of the turn-on voltage (V{sub on}) and severe degradation of the memory window (ΔV{sub on}) at programming (P) and erasing (E) voltages, respectively, block their application in NVMs. The obstacle is overcome by using a pn-heterojunction as the active layer in the OFET memory, which supplied a holes and electrons accumulating channel at the supplied P and E voltages, respectively. Both holes and electrons transferring from the channels to PVP layer and overwriting the trapped charges with an opposite polarity result in the reliable bidirectional shifts of V{sub on} at P and E voltages, respectively. The heterojunction OFET exhibits excellent nonvolatile memory characteristics, with a large ΔV{sub on} of 8.5 V, desired reading (R) voltage at 0 V, reliable P/R/E/R dynamic endurance over 100 cycles and a long retention time over 10 years.

  20. Nanowire field effect transistors principles and applications

    CERN Document Server

    Jeong, Yoon-Ha

    2014-01-01

    “Nanowire Field Effect Transistor: Basic Principles and Applications” places an emphasis on the application aspects of nanowire field effect transistors (NWFET). Device physics and electronics are discussed in a compact manner, together with the p-n junction diode and MOSFET, the former as an essential element in NWFET and the latter as a general background of the FET. During this discussion, the photo-diode, solar cell, LED, LD, DRAM, flash EEPROM and sensors are highlighted to pave the way for similar applications of NWFET. Modeling is discussed in close analogy and comparison with MOSFETs. Contributors focus on processing, electrostatic discharge (ESD) and application of NWFET. This includes coverage of solar and memory cells, biological and chemical sensors, displays and atomic scale light emitting diodes. Appropriate for scientists and engineers interested in acquiring a working knowledge of NWFET as well as graduate students specializing in this subject.

  1. 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.

  2. 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.

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

    Science.gov (United States)

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

    2018-04-01

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

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

    Science.gov (United States)

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

    2018-04-01

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

  5. 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

  6. 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.

  7. Diazaisoindigo bithiophene and terthiophene copolymers for application in field-effect transistors and solar cells

    KAUST Repository

    Yue, Wan; Li, Cheng; Tian, Xuelin; Li, Weiwei; Neophytou, Marios; Chen, Hu; Du, Weiyuan; Jellett, Cameron; Chen, Hung-Yang; Onwubiko, Ada; McCulloch, Iain

    2017-01-01

    Two donor–acceptor conjugated polymers with azaisoindigo as acceptor units and bithiophene and terthiophene as donor units have been synthesized by Stille polymerization. These two polymers have been successfully applied in field-effect transistors

  8. 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.

  9. Graphene quantum dot (GQD)-induced photovoltaic and photoelectric memory elements in a pentacene/GQD field effect transistor as a probe of functional interface

    Science.gov (United States)

    Kim, Youngjun; Cho, Seongeun; Kim, Hyeran; Seo, Soonjoo; Lee, Hyun Uk; Lee, Jouhahn; Ko, Hyungduk; Chang, Mincheol; Park, Byoungnam

    2017-09-01

    Electric field-induced charge trapping and exciton dissociation were demonstrated at a penatcene/grapheme quantum dot (GQD) interface using a bottom contact bi-layer field effect transistor (FET) as an electrical nano-probe. Large threshold voltage shift in a pentacene/GQD FET in the dark arises from field-induced carrier trapping in the GQD layer or GQD-induced trap states at the pentacene/GQD interface. As the gate electric field increases, hysteresis characterized by the threshold voltage shift depending on the direction of the gate voltage scan becomes stronger due to carrier trapping associated with the presence of a GQD layer. Upon illumination, exciton dissociation and gate electric field-induced charge trapping simultaneously contribute to increase the threshold voltage window, which can potentially be exploited for photoelectric memory and/or photovoltaic devices through interface engineering.

  10. Effect of ZnO channel thickness on the device behaviour of nonvolatile memory thin film transistors with double-layered gate insulators of Al2O3 and ferroelectric polymer

    International Nuclear Information System (INIS)

    Yoon, Sung-Min; Yang, Shin-Hyuk; Ko Park, Sang-Hee; Jung, Soon-Won; Cho, Doo-Hee; Byun, Chun-Won; Kang, Seung-Youl; Hwang, Chi-Sun; Yu, Byoung-Gon

    2009-01-01

    Poly(vinylidene fluoride trifluoroethylene) and ZnO were employed for nonvolatile memory thin film transistors as ferroelectric gate insulator and oxide semiconducting channel layers, respectively. It was proposed that the thickness of the ZnO layer be carefully controlled for realizing the lower programming voltage, because the serially connected capacitor by the formation of a fully depleted ZnO channel had a critical effect on the off programming voltage. The fabricated memory transistor with Al/P(VDF-TrFE) (80 nm)/Al 2 O 3 (4 nm)/ZnO (5 nm) exhibits encouraging behaviour such as a memory window of 3.8 V at the gate voltage of -10 to 12 V, and 10 7 on/off ratio, and a gate leakage current of 10 -11 A.

  11. 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

  12. Silicon nanowire transistors

    CERN Document Server

    Bindal, Ahmet

    2016-01-01

    This book describes the n and p-channel Silicon Nanowire Transistor (SNT) designs with single and dual-work functions, emphasizing low static and dynamic power consumption. The authors describe a process flow for fabrication and generate SPICE models for building various digital and analog circuits. These include an SRAM, a baseband spread spectrum transmitter, a neuron cell and a Field Programmable Gate Array (FPGA) platform in the digital domain, as well as high bandwidth single-stage and operational amplifiers, RF communication circuits in the analog domain, in order to show this technology’s true potential for the next generation VLSI. Describes Silicon Nanowire (SNW) Transistors, as vertically constructed MOS n and p-channel transistors, with low static and dynamic power consumption and small layout footprint; Targets System-on-Chip (SoC) design, supporting very high transistor count (ULSI), minimal power consumption requiring inexpensive substrates for packaging; Enables fabrication of different types...

  13. Copper atomic-scale transistors.

    Science.gov (United States)

    Xie, Fangqing; Kavalenka, Maryna N; Röger, Moritz; Albrecht, Daniel; Hölscher, Hendrik; Leuthold, Jürgen; Schimmel, Thomas

    2017-01-01

    We investigated copper as a working material for metallic atomic-scale transistors and confirmed that copper atomic-scale transistors can be fabricated and operated electrochemically in a copper electrolyte (CuSO 4 + H 2 SO 4 ) in bi-distilled water under ambient conditions with three microelectrodes (source, drain and gate). The electrochemical switching-on potential of the atomic-scale transistor is below 350 mV, and the switching-off potential is between 0 and -170 mV. The switching-on current is above 1 μA, which is compatible with semiconductor transistor devices. Both sign and amplitude of the voltage applied across the source and drain electrodes ( U bias ) influence the switching rate of the transistor and the copper deposition on the electrodes, and correspondingly shift the electrochemical operation potential. The copper atomic-scale transistors can be switched using a function generator without a computer-controlled feedback switching mechanism. The copper atomic-scale transistors, with only one or two atoms at the narrowest constriction, were realized to switch between 0 and 1 G 0 ( G 0 = 2e 2 /h; with e being the electron charge, and h being Planck's constant) or 2 G 0 by the function generator. The switching rate can reach up to 10 Hz. The copper atomic-scale transistor demonstrates volatile/non-volatile dual functionalities. Such an optimal merging of the logic with memory may open a perspective for processor-in-memory and logic-in-memory architectures, using copper as an alternative working material besides silver for fully metallic atomic-scale transistors.

  14. Unijunction transistors

    International Nuclear Information System (INIS)

    1981-01-01

    The electrical characteristics of unijunction transistors can be modified by irradiation with electron beams in excess of 400 KeV and at a dose rate of 10 13 to 10 16 e/cm 2 . Examples are given of the effect of exposing the emitter-base junctions of transistors to such lattice defect causing radiation for a time sufficient to change the valley current of the transistor. (U.K.)

  15. 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.

  16. 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...

  17. Conditional Dispersive Readout of a CMOS Single-Electron Memory Cell

    Science.gov (United States)

    Schaal, S.; Barraud, S.; Morton, J. J. L.; Gonzalez-Zalba, M. F.

    2018-05-01

    Quantum computers require interfaces with classical electronics for efficient qubit control, measurement, and fast data processing. Fabricating the qubit and the classical control layer using the same technology is appealing because it will facilitate the integration process, improving feedback speeds and offering potential solutions to wiring and layout challenges. Integrating classical and quantum devices monolithically, using complementary metal-oxide-semiconductor (CMOS) processes, enables the processor to profit from the most mature industrial technology for the fabrication of large-scale circuits. We demonstrate a CMOS single-electron memory cell composed of a single quantum dot and a transistor that locks charge on the quantum-dot gate. The single-electron memory cell is conditionally read out by gate-based dispersive sensing using a lumped-element L C resonator. The control field-effect transistor (FET) and quantum dot are fabricated on the same chip using fully depleted silicon-on-insulator technology. We obtain a charge sensitivity of δ q =95 ×10-6e Hz-1 /2 when the quantum-dot readout is enabled by the control FET, comparable to results without the control FET. Additionally, we observe a single-electron retention time on the order of a second when storing a single-electron charge on the quantum dot at millikelvin temperatures. These results demonstrate first steps towards time-based multiplexing of gate-based dispersive readout in CMOS quantum devices opening the path for the development of an all-silicon quantum-classical processor.

  18. 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.

  19. Low-voltage operating flexible ferroelectric organic field-effect transistor nonvolatile memory with a vertical phase separation P(VDF-TrFE-CTFE)/PS dielectric

    Science.gov (United States)

    Xu, Meili; Xiang, Lanyi; Xu, Ting; Wang, Wei; Xie, Wenfa; Zhou, Dayu

    2017-10-01

    Future flexible electronic systems require memory devices combining low-power operation and mechanical bendability. However, high programming/erasing voltages, which are universally needed to switch the storage states in previously reported ferroelectric organic field-effect transistor (Fe-OFET) nonvolatile memories (NVMs), severely prevent their practical applications. In this work, we develop a route to achieve a low-voltage operating flexible Fe-OFET NVM. Utilizing vertical phase separation, an ultrathin self-organized poly(styrene) (PS) buffering layer covers the surface of the ferroelectric polymer layer by one-step spin-coating from their blending solution. The ferroelectric polymer with a low coercive field contributes to low-voltage operation in the Fe-OFET NVM. The polymer PS contributes to the improvement of mobility, attributing to screening the charge scattering and decreasing the surface roughness. As a result, a high performance flexible Fe-OFET NVM is achieved at the low P/E voltages of ±10 V, with a mobility larger than 0.2 cm2 V-1 s-1, a reliable P/E endurance over 150 cycles, stable data storage retention capability over 104 s, and excellent mechanical bending durability with a slight performance degradation after 1000 repetitive tensile bending cycles at a curvature radius of 5.5 mm.

  20. Nonvolatile memory thin-film transistors using biodegradable chicken albumen gate insulator and oxide semiconductor channel on eco-friendly paper substrate.

    Science.gov (United States)

    Kim, So-Jung; Jeon, Da-Bin; Park, Jung-Ho; Ryu, Min-Ki; Yang, Jong-Heon; Hwang, Chi-Sun; Kim, Gi-Heon; Yoon, Sung-Min

    2015-03-04

    Nonvolatile memory thin-film transistors (TFTs) fabricated on paper substrates were proposed as one of the eco-friendly electronic devices. The gate stack was composed of chicken albumen gate insulator and In-Ga-Zn-O semiconducting channel layers. All the fabrication processes were performed below 120 °C. To improve the process compatibility of the synthethic paper substrate, an Al2O3 thin film was introduced as adhesion and barrier layers by atomic layer deposition. The dielectric properties of biomaterial albumen gate insulator were also enhanced by the preparation of Al2O3 capping layer. The nonvolatile bistabilities were realized by the switching phenomena of residual polarization within the albumen thin film. The fabricated device exhibited a counterclockwise hysteresis with a memory window of 11.8 V, high on/off ratio of approximately 1.1 × 10(6), and high saturation mobility (μsat) of 11.5 cm(2)/(V s). Furthermore, these device characteristics were not markedly degraded even after the delamination and under the bending situration. When the curvature radius was set as 5.3 cm, the ION/IOFF ratio and μsat were obtained to be 5.9 × 10(6) and 7.9 cm(2)/(V s), respectively.

  1. Nonvolatile ferroelectric memory based on PbTiO3 gated single-layer MoS2 field-effect transistor

    Science.gov (United States)

    Shin, Hyun Wook; Son, Jong Yeog

    2018-01-01

    We fabricated ferroelectric non-volatile random access memory (FeRAM) based on a field effect transistor (FET) consisting of a monolayer MoS2 channel and a ferroelectric PbTiO3 (PTO) thin film of gate insulator. An epitaxial PTO thin film was deposited on a Nb-doped SrTiO3 (Nb:STO) substrate via pulsed laser deposition. A monolayer MoS2 sheet was exfoliated from a bulk crystal and transferred to the surface of the PTO/Nb:STO. Structural and surface properties of the PTO thin film were characterized by X-ray diffraction and atomic force microscopy, respectively. Raman spectroscopy analysis was performed to identify the single-layer MoS2 sheet on the PTO/Nb:STO. We obtained mobility value (327 cm2/V·s) of the MoS2 channel at room temperature. The MoS2-PTO FeRAM FET showed a wide memory window with 17 kΩ of resistance variation which was attributed to high remnant polarization of the epitaxially grown PTO thin film. According to the fatigue resistance test for the FeRAM FET, however, the resistance states gradually varied during the switching cycles of 109. [Figure not available: see fulltext.

  2. Superconducting transistor

    International Nuclear Information System (INIS)

    Gray, K.E.

    1978-01-01

    A three film superconducting tunneling device, analogous to a semiconductor transistor, is presented, including a theoretical description and experimental results showing a current gain of four. Much larger current gains are shown to be feasible. Such a development is particularly interesting because of its novelty and the striking analogies with the semiconductor junction transistor

  3. Measurements of dose with individual FAMOS transistors

    Energy Technology Data Exchange (ETDEWEB)

    Scheick, L.Z.; McNulty, P.J.; Roth, D.R.; Davis, M.G.; Mason, B.E.

    1999-12-01

    A new method is described for measuring the doses absorbed by microstructures from an exposure to ionizing radiation. The decrease in the duration of UltraViolet light (UV) exposure required to erase each cell of a commercial UltraViolet erasable Programmable Read Only Memory (UVPROM) correlates with the dose absorbed by the floating gate of that transistor. This technique facilitates analysis of the microdose distribution across the array and the occurrence of Single Event Upset (SEU) like anomalous shifts due to rare large energy-deposition events.

  4. Measurements of dose with individual FAMOS transistors

    International Nuclear Information System (INIS)

    Scheick, L.Z.; McNulty, P.J.; Roth, D.R.; Davis, M.G.; Mason, B.E.

    1999-01-01

    A new method is described for measuring the doses absorbed by microstructures from an exposure to ionizing radiation. The decrease in the duration of UltraViolet light (UV) exposure required to erase each cell of a commercial UltraViolet erasable Programmable Read Only Memory (UVPROM) correlates with the dose absorbed by the floating gate of that transistor. This technique facilitates analysis of the microdose distribution across the array and the occurrence of Single Event Upset (SEU) like anomalous shifts due to rare large energy-deposition events

  5. 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.

  6. Saddle-fin cell transistors with oxide etch rate control by using tilted ion implantation (TIS-fin) for sub-50-nm DRAMs

    International Nuclear Information System (INIS)

    Yoo, Min Soo; Choi, Kang Sik; Sun, Woo Kyung

    2010-01-01

    As DRAM cell pitch size decreases, the need for a high performance transistor is increasing. Though saddle-fin (S-fin) transistors have superior characteristics, S-fin transistors are well known to be more sensitive to process variation. To make uniform S-fin transistors, for the first time, we developed a new fin formation method using tilted ion implantation along the wordline direction after a recess gate etch. Due to the increased etch rate of the oxide film by ion implantation damage, fins are made at the bottom channel of the recess gate after wet etching. The resulting tilt implanted saddle-fin (TIS-fin) transistor has remarkably improved characteristics, such as ∼8% subthreshold swing (SS) and a 40% drain induced barrier lowering (DIBL) decrease. Especially, the TIS-fin with a neutral dopant has a reduced threshold voltage (Vth) variation within a wafer (<100 mV), which is comparable with that of a mass-produced sphere-shaped recessed channel array transistor (SRCAT).

  7. 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.

  8. Influence of non-adherent yeast cells on electrical characteristics of diamond-based field-effect transistors

    Energy Technology Data Exchange (ETDEWEB)

    Procházka, Václav, E-mail: prochazkav@fzu.cz [Faculty of Electrical Engineering, Czech Technical University in Prague, Technická 2, 16627 Prague (Czech Republic); Institute of Physics, The Czech Academy of Sciences, Cukrovarnická 10/112, 162 00 Prague (Czech Republic); Cifra, Michal [Institute of Photonics and Electronics, The Czech Academy of Sciences, Chaberská 57, 182 51 Prague (Czech Republic); Kulha, Pavel [Faculty of Electrical Engineering, Czech Technical University in Prague, Technická 2, 16627 Prague (Czech Republic); Institute of Physics, The Czech Academy of Sciences, Cukrovarnická 10/112, 162 00 Prague (Czech Republic); Ižák, Tibor [Institute of Physics, The Czech Academy of Sciences, Cukrovarnická 10/112, 162 00 Prague (Czech Republic); Rezek, Bohuslav [Faculty of Electrical Engineering, Czech Technical University in Prague, Technická 2, 16627 Prague (Czech Republic); Institute of Physics, The Czech Academy of Sciences, Cukrovarnická 10/112, 162 00 Prague (Czech Republic); Kromka, Alexander [Institute of Physics, The Czech Academy of Sciences, Cukrovarnická 10/112, 162 00 Prague (Czech Republic); Faculty of Civil Engineering, Czech Technical University in Prague, Thákurova 7, 16629 Prague (Czech Republic)

    2017-02-15

    Highlights: • Interaction of non-adherent yeast cells with H-terminated diamond described. • Effect of cell culture solutions on H-diamond SGFET (positive potential shifts). • H-diamond sensitive to metabolic activity of yeast cells (negative potential shift). - Abstract: Diamond thin films provide unique features as substrates for cell cultures and as bio-electronic sensors. Here we employ solution-gated field effect transistors (SGFET) based on nanocrystalline diamond thin films with H-terminated surface which exhibits the sub-surface p-type conductive channel. We study an influence of yeast cells (Saccharomyces cerevisiae) on electrical characteristics of the diamond SGFETs. Two different cell culture solutions (sucrose and yeast peptone dextrose–YPD) are used, with and without the cells. We have found that transfer characteristics of the SGFETs exhibit a negative shift of the gate voltage by −26 mV and −42 mV for sucrose and YPD with cells in comparison to blank solutions without the cells. This effect is attributed to a local pH change in close vicinity of the H-terminated diamond surface due to metabolic processes of the yeast cells. The pH sensitivity of the diamond-based SGFETs, the role of cell and protein adhesion on the gate surface and the role of negative surface charge of yeast cells on the SGFETs electrical characteristics are discussed as well.

  9. Influence of non-adherent yeast cells on electrical characteristics of diamond-based field-effect transistors

    International Nuclear Information System (INIS)

    Procházka, Václav; Cifra, Michal; Kulha, Pavel; Ižák, Tibor; Rezek, Bohuslav; Kromka, Alexander

    2017-01-01

    Highlights: • Interaction of non-adherent yeast cells with H-terminated diamond described. • Effect of cell culture solutions on H-diamond SGFET (positive potential shifts). • H-diamond sensitive to metabolic activity of yeast cells (negative potential shift). - Abstract: Diamond thin films provide unique features as substrates for cell cultures and as bio-electronic sensors. Here we employ solution-gated field effect transistors (SGFET) based on nanocrystalline diamond thin films with H-terminated surface which exhibits the sub-surface p-type conductive channel. We study an influence of yeast cells (Saccharomyces cerevisiae) on electrical characteristics of the diamond SGFETs. Two different cell culture solutions (sucrose and yeast peptone dextrose–YPD) are used, with and without the cells. We have found that transfer characteristics of the SGFETs exhibit a negative shift of the gate voltage by −26 mV and −42 mV for sucrose and YPD with cells in comparison to blank solutions without the cells. This effect is attributed to a local pH change in close vicinity of the H-terminated diamond surface due to metabolic processes of the yeast cells. The pH sensitivity of the diamond-based SGFETs, the role of cell and protein adhesion on the gate surface and the role of negative surface charge of yeast cells on the SGFETs electrical characteristics are discussed as well.

  10. 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

  11. 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

  12. A 1T Dynamic Random Access Memory Cell Based on Gated Thyristor with Surrounding Gate Structure for High Scalability.

    Science.gov (United States)

    Kim, Hyungjin; Kim, Sihyun; Kim, Hyun-Min; Lee, Kitae; Kim, Sangwan; Pak, Byung-Gook

    2018-09-01

    In this study, we investigate a one-transistor (1T) dynamic random access memory (DRAM) cell based on a gated-thyristor device utilizing voltage-driven bistability to enable high-speed operations. The structural feature of the surrounding gate using a sidewall provides high scalability with regard to constructing an array architecture of the proposed devices. In addition, the operation mechanism, I-V characteristics, DRAM operations, and bias dependence are analyzed using a commercial device simulator. Unlike conventional 1T DRAM cells utilizing the floating body effect, excess carriers which are required to be stored to make two different states are not generated but injected from the n+ cathode region, giving the device high-speed operation capabilities. The findings here indicate that the proposed DRAM cell offers distinct advantages in terms of scalability and high-speed operations.

  13. 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...

  14. Non-Faradaic electrical impedimetric investigation of the interfacial effects of neuronal cell growth and differentiation on silicon nanowire transistors.

    Science.gov (United States)

    Lin, Shu-Ping; Vinzons, Lester U; Kang, Yu-Shan; Lai, Tung-Yen

    2015-05-13

    Silicon nanowire field-effect transistor (SiNW FET) devices have been interfaced with cells; however, their application for noninvasive, real-time monitoring of interfacial effects during cell growth and differentiation on SiNW has not been fully explored. Here, we cultured rat adrenal pheochromocytoma (PC12) cells, a type of neural progenitor cell, directly on SiNW FET devices to monitor cell adhesion during growth and morphological changes during neuronal differentiation for a period of 5-7 d. Monitoring was performed by measuring the non-Faradaic electrical impedance of the cell-SiNW FET system using a precision LCR meter. Our SiNW FET devices exhibited changes in impedance parameters during cell growth and differentiation because of the negatively charged cell membrane, seal resistance, and membrane capacitance at the cell/SiNW interface. It was observed that during both PC12 cell growth and neuronal differentiation, the impedance magnitude increased and the phase shifted to more negative values. However, impedance changes during cell growth already plateaued 3 d after seeding, while impedance changes continued until the last observation day during differentiation. Our results also indicate that the frequency shift to above 40 kHz after growth factor induction resulted from a larger coverage of cell membrane on the SiNWs due to distinctive morphological changes according to vinculin staining. Encapsulation of PC12 cells in a hydrogel scaffold resulted in a lack of trend in impedance parameters and confirmed that impedance changes were due to the cells. Moreover, cytolysis of the differentiated PC12 cells led to significant changes in impedance parameters. Equivalent electrical circuits were used to analyze the changes in impedance values during cell growth and differentiation. The technique employed in this study can provide a platform for performing investigations of growth-factor-induced progenitor cell differentiation.

  15. Transistor Effect in Improperly Connected Transistors.

    Science.gov (United States)

    Luzader, Stephen; Sanchez-Velasco, Eduardo

    1996-01-01

    Discusses the differences between the standard representation and a realistic representation of a transistor. Presents an experiment that helps clarify the explanation of the transistor effect and shows why transistors should be connected properly. (JRH)

  16. 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.

  17. Organic electrochemical transistors

    Science.gov (United States)

    Rivnay, Jonathan; Inal, Sahika; Salleo, Alberto; Owens, Róisín M.; Berggren, Magnus; Malliaras, George G.

    2018-02-01

    Organic electrochemical transistors (OECTs) make effective use of ion injection from an electrolyte to modulate the bulk conductivity of an organic semiconductor channel. The coupling between ionic and electronic charges within the entire volume of the channel endows OECTs with high transconductance compared with that of field-effect transistors, but also limits their response time. The synthetic tunability, facile deposition and biocompatibility of organic materials make OECTs particularly suitable for applications in biological interfacing, printed logic circuitry and neuromorphic devices. In this Review, we discuss the physics and the mechanism of operation of OECTs, focusing on their identifying characteristics. We highlight organic materials that are currently being used in OECTs and survey the history of OECT technology. In addition, form factors, fabrication technologies and applications such as bioelectronics, circuits and memory devices are examined. Finally, we take a critical look at the future of OECT research and development.

  18. Organic electrochemical transistors

    KAUST Repository

    Rivnay, Jonathan

    2018-01-16

    Organic electrochemical transistors (OECTs) make effective use of ion injection from an electrolyte to modulate the bulk conductivity of an organic semiconductor channel. The coupling between ionic and electronic charges within the entire volume of the channel endows OECTs with high transconductance compared with that of field-effect transistors, but also limits their response time. The synthetic tunability, facile deposition and biocompatibility of organic materials make OECTs particularly suitable for applications in biological interfacing, printed logic circuitry and neuromorphic devices. In this Review, we discuss the physics and the mechanism of operation of OECTs, focusing on their identifying characteristics. We highlight organic materials that are currently being used in OECTs and survey the history of OECT technology. In addition, form factors, fabrication technologies and applications such as bioelectronics, circuits and memory devices are examined. Finally, we take a critical look at the future of OECT research and development.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. The supply voltage scaled dependency of the recovery of single event upset in advanced complementary metal—oxide—semiconductor static random-access memory cells

    International Nuclear Information System (INIS)

    Li Da-Wei; Qin Jun-Rui; Chen Shu-Ming

    2013-01-01

    Using computer-aided design three-dimensional simulation technology, the supply voltage scaled dependency of the recovery of single event upset and charge collection in static random-access memory cells are investigated. It reveals that the recovery linear energy transfer threshold decreases with the supply voltage reducing, which is quite attractive for dynamic voltage scaling and subthreshold circuit radiation-hardened design. Additionally, the effect of supply voltage on charge collection is also investigated. It is concluded that the supply voltage mainly affects the bipolar gain of the parasitical bipolar junction transistor (BJT) and the existence of the source plays an important role in supply voltage variation. (geophysics, astronomy, and astrophysics)

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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...

  13. Record Endurance for Single-Walled Carbon Nanotube–Based Memory Cell

    Directory of Open Access Journals (Sweden)

    Yang Y

    2010-01-01

    Full Text Available Abstract We study memory devices consisting of single-walled carbon nanotube transistors with charge storage at the SiO2/nanotube interface. We show that this type of memory device is robust, withstanding over 105 operating cycles, with a current drive capability up to 10−6 A at 20 mV drain bias, thus competing with state-of-the-art Si-devices. We find that the device performance depends on temperature and pressure, while both endurance and data retention are improved in vacuum.

  14. 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.

  15. Copolymer semiconductors comprising thiazolothiazole or benzobisthiazole, or benzobisoxazole electron acceptor subunits, and electron donor subunits, and their uses in transistors and solar cells

    Science.gov (United States)

    Jenekhe, Samson A; Subramaniyan, Selvam; Ahmed, Eilaf; Xin, Hao; Kim, Felix Sunjoo

    2014-10-28

    The inventions disclosed, described, and/or claimed herein relate to copolymers comprising copolymers comprising electron accepting A subunits that comprise thiazolothiazole, benzobisthiazole, or benzobisoxazoles rings, and electron donating subunits that comprise certain heterocyclic groups. The copolymers are useful for manufacturing organic electronic devices, including transistors and solar cells. The invention also relates to certain synthetic precursors of the copolymers. Methods for making the copolymers and the derivative electronic devices are also described.

  16. 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.

  17. 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

  18. Electrically programmable-erasable In-Ga-Zn-O thin-film transistor memory with atomic-layer-deposited Al2O3/Pt nanocrystals/Al2O3 gate stack

    Directory of Open Access Journals (Sweden)

    Shi-Bing Qian

    2015-12-01

    Full Text Available Amorphous indium-gallium-zinc oxide (a-IGZO thin-film transistor (TFT memory is very promising for transparent and flexible system-on-panel displays; however, electrical erasability has always been a severe challenge for this memory. In this article, we demonstrated successfully an electrically programmable-erasable memory with atomic-layer-deposited Al2O3/Pt nanocrystals/Al2O3 gate stack under a maximal processing temperature of 300 oC. As the programming voltage was enhanced from 14 to 19 V for a constant pulse of 0.2 ms, the threshold voltage shift increased significantly from 0.89 to 4.67 V. When the programmed device was subjected to an appropriate pulse under negative gate bias, it could return to the original state with a superior erasing efficiency. The above phenomena could be attributed to Fowler-Nordheim tunnelling of electrons from the IGZO channel to the Pt nanocrystals during programming, and inverse tunnelling of the trapped electrons during erasing. In terms of 0.2-ms programming at 16 V and 350-ms erasing at −17 V, a large memory window of 3.03 V was achieved successfully. Furthermore, the memory exhibited stable repeated programming/erasing (P/E characteristics and good data retention, i.e., for 2-ms programming at 14 V and 250-ms erasing at −14 V, a memory window of 2.08 V was still maintained after 103 P/E cycles, and a memory window of 1.1 V was retained after 105 s retention time.

  19. Electrically programmable-erasable In-Ga-Zn-O thin-film transistor memory with atomic-layer-deposited Al{sub 2}O{sub 3}/Pt nanocrystals/Al{sub 2}O{sub 3} gate stack

    Energy Technology Data Exchange (ETDEWEB)

    Qian, Shi-Bing; Zhang, Wen-Peng; Liu, Wen-Jun; Ding, Shi-Jin, E-mail: sjding@fudan.edu.cn [State Key Laboratory of ASIC and System, School of Microelectronics, Fudan University, Shanghai 200433 (China)

    2015-12-15

    Amorphous indium-gallium-zinc oxide (a-IGZO) thin-film transistor (TFT) memory is very promising for transparent and flexible system-on-panel displays; however, electrical erasability has always been a severe challenge for this memory. In this article, we demonstrated successfully an electrically programmable-erasable memory with atomic-layer-deposited Al{sub 2}O{sub 3}/Pt nanocrystals/Al{sub 2}O{sub 3} gate stack under a maximal processing temperature of 300 {sup o}C. As the programming voltage was enhanced from 14 to 19 V for a constant pulse of 0.2 ms, the threshold voltage shift increased significantly from 0.89 to 4.67 V. When the programmed device was subjected to an appropriate pulse under negative gate bias, it could return to the original state with a superior erasing efficiency. The above phenomena could be attributed to Fowler-Nordheim tunnelling of electrons from the IGZO channel to the Pt nanocrystals during programming, and inverse tunnelling of the trapped electrons during erasing. In terms of 0.2-ms programming at 16 V and 350-ms erasing at −17 V, a large memory window of 3.03 V was achieved successfully. Furthermore, the memory exhibited stable repeated programming/erasing (P/E) characteristics and good data retention, i.e., for 2-ms programming at 14 V and 250-ms erasing at −14 V, a memory window of 2.08 V was still maintained after 10{sup 3} P/E cycles, and a memory window of 1.1 V was retained after 10{sup 5} s retention time.

  20. Liquid–Solid Dual-Gate Organic Transistors with Tunable Threshold Voltage for Cell Sensing

    KAUST Repository

    Zhang, Yu; Li, Jun; Li, Rui; Sbircea, Dan-Tiberiu; Giovannitti, Alexander; Xu, Junling; Xu, Huihua; Zhou, Guodong; Bian, Liming; McCulloch, Iain; Zhao, Ni

    2017-01-01

    mesenchymal stem cells. In general, the capability of tuning the optimal sensing bias will not only improve the device performance but also broaden the material selection for cell-based organic bioelectronics.

  1. 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.

  2. 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

  3. 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

  4. 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 ...

  5. 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.

  6. 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.

  7. 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.

  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. Anthradithiophene-Containing Copolymers for Thin-Film Transistors and Photovoltaic Cells

    KAUST Repository

    Jiang, Ying; Okamoto, Toshihiro; Becerril, Hector A.; Hong, Sanghyun; Tang, Ming Lee; Mayer, Alex C.; Parmer, Jack E.; McGehee, Michael D.; Bao, Zhenan

    2010-01-01

    compatible with fullerenes, acceptor material commonly used in bulk heterojunction (BHJ) photovoltaic cells. The polymers exhibit high film absorption coefficients of 105 cm-1, an order of magnitude higher than previously reported anthradithiophene

  10. 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

  11. 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...

  12. Recent progress in photoactive organic field-effect transistors.

    Science.gov (United States)

    Wakayama, Yutaka; Hayakawa, Ryoma; Seo, Hoon-Seok

    2014-04-01

    Recent progress in photoactive organic field-effect transistors (OFETs) is reviewed. Photoactive OFETs are divided into light-emitting (LE) and light-receiving (LR) OFETs. In the first part, LE-OFETs are reviewed from the viewpoint of the evolution of device structures. Device performances have improved in the last decade with the evolution of device structures from single-layer unipolar to multi-layer ambipolar transistors. In the second part, various kinds of LR-OFETs are featured. These are categorized according to their functionalities: phototransistors, non-volatile optical memories, and photochromism-based transistors. For both, various device configurations are introduced: thin-film based transistors for practical applications, single-crystalline transistors to investigate fundamental physics, nanowires, multi-layers, and vertical transistors based on new concepts.

  13. Recent progress in photoactive organic field-effect transistors

    International Nuclear Information System (INIS)

    Wakayama, Yutaka; Hayakawa, Ryoma; Seo, Hoon-Seok

    2014-01-01

    Recent progress in photoactive organic field-effect transistors (OFETs) is reviewed. Photoactive OFETs are divided into light-emitting (LE) and light-receiving (LR) OFETs. In the first part, LE-OFETs are reviewed from the viewpoint of the evolution of device structures. Device performances have improved in the last decade with the evolution of device structures from single-layer unipolar to multi-layer ambipolar transistors. In the second part, various kinds of LR-OFETs are featured. These are categorized according to their functionalities: phototransistors, non-volatile optical memories, and photochromism-based transistors. For both, various device configurations are introduced: thin-film based transistors for practical applications, single-crystalline transistors to investigate fundamental physics, nanowires, multi-layers, and vertical transistors based on new concepts. (review)

  14. Transistor challenges - A DRAM perspective

    International Nuclear Information System (INIS)

    Faul, Juergen W.; Henke, Dietmar

    2005-01-01

    Key challenges of the transistor scaling from a DRAM perspective will be reviewed. Both, array transistors as well as DRAM support devices face challenges that differ essentially from high performance logic device scaling. As a major difference, retention time and standby current requirements characterize special boundary conditions in the DRAM device design. Array device scaling is determined by a chip size driven aggressive node scaling. To continue scaling, major innovations need to be introduced into state-of-the-art planar array transistors. Alternatively, non planar device concepts will have to be evaluated. Support device design for DRAMs is driven by today's market demand for increased chip performances at little to no extra cost. Major innovations are required to continue that path. Besides this strive for performance increase, special limitations for 'on pitch' circuits at the array edge will come up due to the aggressive cell size scaling

  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. Impact of regioregularity on thin-film transistor and photovoltaic cell performances of pentacene-containing polymers

    KAUST Repository

    Jiang, Ying; Hong, Sanghyun; Oh, Joon Hak; Mondal, Rajib; Okamoto, Toshihiro; Verploegen, Eric; Toney, Michael F.; McGehee, Michael D.; Bao, Zhenan

    2012-01-01

    Regioregular pentacene-containing polymers were synthesized with alkylated bithiophene (BT) and cyclopentadithiophene (CPDT) as comonomers. Among them, 2,9-conjugated polymers PnBT-2,9 and PnCPDT-2,9 achieved the best performance in transistor

  18. 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. ...

  19. 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

  20. Anthradithiophene-Containing Copolymers for Thin-Film Transistors and Photovoltaic Cells

    KAUST Repository

    Jiang, Ying

    2010-08-10

    We synthesized anthradithiophene-cyclopentadithiophene conjugated copolymers via Stille coupling. The anthradithiophene core was verified to be superior in stability compared to pentacene toward Diels-Alder cycloaddition and therefore more compatible with fullerenes, acceptor material commonly used in bulk heterojunction (BHJ) photovoltaic cells. The polymers exhibit high film absorption coefficients of 105 cm-1, an order of magnitude higher than previously reported anthradithiophene-dialkylfluorene copolymers. Short-circuit currents exceeding 5 mA/cm2 and a BHJ device efficiency close to 1% were achieved when device morphology was improved with diiodooctane as a solvent additive. This is the highest power conversion efficiency achieved by an acene-containing polymer so far. © 2010 American Chemical Society.

  1. Flexible NAND-Like Organic Ferroelectric Memory Array

    NARCIS (Netherlands)

    Kam, B.; Ke, T.H.; Chasin, A.; Tyagi, M.; Cristoferi, C.; Tempelaars, K.; Breemen, A.J.J.M. van; Myny, K.; Schols, S.; Genoe, J.; Gelinck, G.H.; Heremans, P.

    2014-01-01

    We present a memory array of organic ferroelectric field-effect transistors (OFeFETs) on flexible substrates. The OFeFETs are connected serially, similar to the NAND architecture of flash memory, which offers the highest memory density of transistor memories. We demonstrate a reliable addressing

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. Impact of regioregularity on thin-film transistor and photovoltaic cell performances of pentacene-containing polymers

    KAUST Repository

    Jiang, Ying

    2012-01-01

    Regioregular pentacene-containing polymers were synthesized with alkylated bithiophene (BT) and cyclopentadithiophene (CPDT) as comonomers. Among them, 2,9-conjugated polymers PnBT-2,9 and PnCPDT-2,9 achieved the best performance in transistor and photovoltaic devices respectively. The former achieved the most highly ordered structures in thin films, yielding ambipolar transistor behavior with hole and electron mobilities up to 0.03 and 0.02 cm 2 V -1 s -1 on octadecylsilane-treated substrates. The latter achieved photovoltaic power conversion efficiencies up to 0.33%. The impact of regioregularity and direction of conjugation-extension (2,9 vs. 2,10), on thin-film order and device performance has been demonstrated for the pentacene-containing polymers for the first time, providing insight towards future functional material design. © 2012 The Royal Society of Chemistry.

  10. 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.

  11. Doped Organic Transistors.

    Science.gov (United States)

    Lüssem, Björn; Keum, Chang-Min; Kasemann, Daniel; Naab, Ben; Bao, Zhenan; Leo, Karl

    2016-11-23

    Organic field-effect transistors hold the promise of enabling low-cost and flexible electronics. Following its success in organic optoelectronics, the organic doping technology is also used increasingly in organic field-effect transistors. Doping not only increases device performance, but it also provides a way to fine-control the transistor behavior, to develop new transistor concepts, and even improve the stability of organic transistors. This Review summarizes the latest progress made in the understanding of the doping technology and its application to organic transistors. It presents the most successful doping models and an overview of the wide variety of materials used as dopants. Further, the influence of doping on charge transport in the most relevant polycrystalline organic semiconductors is reviewed, and a concise overview on the influence of doping on transistor behavior and performance is given. In particular, recent progress in the understanding of contact doping and channel doping is summarized.

  12. 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

  13. SOI Transistor measurement techniques using body contacted transistors

    International Nuclear Information System (INIS)

    Worley, E.R.; Williams, R.

    1989-01-01

    Measurements of body contacted SOI transistors are used to isolate parameters of the back channel and island edge transistor. Properties of the edge and back channel transistor have been measured before and after X-ray irradiation (ARACOR). The unique properties of the edge transistor are shown to be a result of edge geometry as confirmed by a two dimensional transistor simulator

  14. 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

  15. 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....

  16. Performance report for Stanford/SLAC Microstore Analog Memory Unit

    International Nuclear Information System (INIS)

    Freytag, D.R.; Walker, J.T.

    1984-09-01

    Tests of a newly developed Analog Memory Unit (AMU) are described. The device contains 256 analog storage cells consisting of pass transistors, a storage capacitor and a differential read out buffer. By addressing the storage cells sequentially, the shape of the signal present at the input can be recorded in time. Fast response and good amplitude resolution were the design goals for the development. Measurements on individual devices will be presented and the status of hybridized subsystems containing eight AMUs discussed

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. Overview of emerging nonvolatile memory technologies.

    Science.gov (United States)

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

    2014-01-01

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

  2. Overview of emerging nonvolatile memory technologies

    Science.gov (United States)

    2014-01-01

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

  3. 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

  4. 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.

  5. 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)

  6. 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.

  7. Liquid crystals for organic transistors (Conference Presentation)

    Science.gov (United States)

    Hanna, Jun-ichi; Iino, Hiroaki

    2016-09-01

    Liquid crystals are a new type of organic semiconductors exhibiting molecular orientation in self-organizing manner, and have high potential for device applications. In fact, various device applications have been proposed so far, including photosensors, solar cells, light emitting diodes, field effect transistors, and so on.. However, device performance in those fabricated with liquid crystals is less than those of devices fabricated with conventional materials in spite of unique features of liquid crystals. Here we discuss how we can utilize the liquid crystallinity in organic transistors and how we can overcome conventional non-liquid crystalline organic transistor materials. Then, we demonstrate high performance organic transistors fabricated with a smectic E liquid crystal of Ph-BTBT-10, which show high mobility of over 10cm2/Vs and high thermal durability of over 200oC in OFETs fabricated with its spin-coated polycrystalline thin films.

  8. Multiple-channel detection of cellular activities by ion-sensitive transistors

    Science.gov (United States)

    Machida, Satoru; Shimada, Hideto; Motoyama, Yumi

    2018-04-01

    An ion-sensitive field-effect transistor to record cellular activities was demonstrated. This field-effect transistor (bio transistor) includes cultured cells on the gate insulator instead of gate electrode. The bio transistor converts a change in potential underneath the cells into variation of the drain current when ion channels open. The bio transistor has high detection sensitivity to even minute variations in potential utilizing a subthreshold swing region. To open ion channels, a reagent solution (acetylcholine) was added to a human-originating cell cultured on the bio transistor. The drain current was successfully decreased with the addition of acetylcholine. Moreover, we attempted to detect the opening of ion channels using a multiple-channel measurement circuit containing several bio transistors. As a consequence, the drain current distinctly decreased only after the addition of acetylcholine. We confirmed that this measurement system including bio transistors enables to observation of cellular activities sensitively and simultaneously.

  9. 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.

  10. 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.

  11. 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.)

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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...

  2. A highly symmetrical 10 transistor 2-read/write dual-port static random access memory bitcell design in 28 nm high-k/metal-gate planar bulk CMOS technology

    Science.gov (United States)

    Ishii, Yuichiro; Tanaka, Miki; Yabuuchi, Makoto; Sawada, Yohei; Tanaka, Shinji; Nii, Koji; Lu, Tien Yu; Huang, Chun Hsien; Sian Chen, Shou; Tse Kuo, Yu; Lung, Ching Cheng; Cheng, Osbert

    2018-04-01

    We propose a highly symmetrical 10 transistor (10T) 2-read/write (2RW) dual-port (DP) static random access memory (SRAM) bitcell in 28 nm high-k/metal-gate (HKMG) planar bulk CMOS. It replaces the conventional 8T 2RW DP SRAM bitcell without any area overhead. It significantly improves the robustness of process variations and an asymmetric issue between the true and bar bitline pairs. Measured data show that read current (I read) and read static noise margin (SNM) are respectively boosted by +20% and +15 mV by introducing the proposed bitcell with enlarged pull-down (PD) and pass-gate (PG) N-channel MOSs (NMOSs). The minimum operating voltage (V min) of the proposed 256 kbit 10T DP SRAM is 0.53 V in the TT process, 25 °C under the worst access condition with read/write disturbances, and improved by 90 mV (15%) compared with the conventional one.

  3. 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

  4. 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.

  5. 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.

  6. Measurement of Rapid Amiloride-Dependent pH Changes at the Cell Surface Using a Proton-Sensitive Field-Effect Transistor.

    Science.gov (United States)

    Schaffhauser, Daniel; Fine, Michael; Tabata, Miyuki; Goda, Tatsuro; Miyahara, Yuji

    2016-03-30

    We present a novel method for the rapid measurement of pH fluxes at close proximity to the surface of the plasma membrane in mammalian cells using an ion-sensitive field-effect transistor (ISFET). In conjuction with an efficient continuous superfusion system, the ISFET sensor was capable of recording rapid changes in pH at the cells' surface induced by intervals of ammonia loading and unloading, even when using highly buffered solutions. Furthermore, the system was able to isolate physiologically relevant signals by not only detecting the transients caused by ammonia loading and unloading, but display steady-state signals as would be expected by a proton transport-mediated influence on the extracellular proton-gradient. Proof of concept was demonstrated through the use of 5-(N-ethyl-N-isopropyl)amiloride (EIPA), a small molecule inhibitor of sodium/hydrogen exchangers (NHE). As the primary transporter responsible for proton balance during cellular regulation of pH, non-electrogenic NHE transport is notoriously difficult to detect with traditional methods. Using the NHE positive cell lines, Chinese hamster ovary (CHO) cells and NHE3-reconstituted mouse skin fibroblasts (MSF), the sensor exhibited a significant response to EIPA inhibition, whereas NHE-deficient MSF cells were unaffected by application of the inhibitor.

  7. 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

  8. 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

  9. 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.

  10. 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.

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

    Science.gov (United States)

    Sasaki, Taro; Endoh, Tetsuo

    2018-04-01

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

  12. 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.

  13. 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

  14. 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,…

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Silicon heterojunction transistor

    International Nuclear Information System (INIS)

    Matsushita, T.; Oh-uchi, N.; Hayashi, H.; Yamoto, H.

    1979-01-01

    SIPOS (Semi-insulating polycrystalline silicon) which is used as a surface passivation layer for highly reliable silicon devices constitutes a good heterojunction for silicon. P- or B-doped SIPOS has been used as the emitter material of a heterojunction transistor with the base and collector of silicon. An npn SIPOS-Si heterojunction transistor showing 50 times the current gain of an npn silicon homojunction transistor has been realized by high-temperature treatments in nitrogen and low-temperature annealing in hydrogen or forming gas

  6. 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....

  7. 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...

  8. 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.

  9. 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.

  10. Copper (I) Selenocyanate (CuSeCN) as a Novel Hole-Transport Layer for Transistors, Organic Solar Cells, and Light-Emitting Diodes

    KAUST Repository

    Wijeyasinghe, Nilushi; Tsetseris, Leonidas; Regoutz, Anna; Sit, Wai-Yu; Fei, Zhuping; Du, Tian; Wang, Xuhua; McLachlan, Martyn A.; Vourlias, George; Patsalas, Panos A.; Payne, David J.; Heeney, Martin; Anthopoulos, Thomas D.

    2018-01-01

    The synthesis and characterization of copper (I) selenocyanate (CuSeCN) and its application as a solution-processable hole-transport layer (HTL) material in transistors, organic light-emitting diodes, and solar cells are reported. Density-functional theory calculations combined with X-ray photoelectron spectroscopy are used to elucidate the electronic band structure, density of states, and microstructure of CuSeCN. Solution-processed layers are found to be nanocrystalline and optically transparent (>94%), due to the large bandgap of ≥3.1 eV, with a valence band maximum located at −5.1 eV. Hole-transport analysis performed using field-effect measurements confirms the p-type character of CuSeCN yielding a hole mobility of 0.002 cm2 V−1 s−1. When CuSeCN is incorporated as the HTL material in organic light-emitting diodes and organic solar cells, the resulting devices exhibit comparable or improved performance to control devices based on commercially available poly(3,4-ethylenedioxythiophene):polystyrene sulfonate as the HTL. This is the first report on the semiconducting character of CuSeCN and it highlights the tremendous potential for further developments in the area of metal pseudohalides.

  11. Chalcogenophene comonomer comparison in small band gap diketopyrrolopyrrole-based conjugated polymers for high-performing field-effect transistors and organic solar cells

    KAUST Repository

    Ashraf, Raja Shahid

    2015-01-28

    The design, synthesis, and characterization of a series of diketopyrrolopyrrole-based copolymers with different chalcogenophene comonomers (thiophene, selenophene, and tellurophene) for use in field-effect transistors and organic photovoltaic devices are reported. The effect of the heteroatom substitution on the optical, electrochemical, and photovoltaic properties and charge carrier mobilities of these polymers is discussed. The results indicate that by increasing the size of the chalcogen atom (S < Se < Te), polymer band gaps are narrowed mainly due to LUMO energy level stabilization. In addition, the larger heteroatomic size also increases intermolecular heteroatom-heteroatom interactions facilitating the formation of polymer aggregates leading to enhanced field-effect mobilities of 1.6 cm2/(V s). Bulk heterojunction solar cells based on the chalcogenophene polymer series blended with fullerene derivatives show good photovoltaic properties, with power conversion efficiencies ranging from 7.1-8.8%. A high photoresponse in the near-infrared (NIR) region with excellent photocurrents above 20 mA cm-2 was achieved for all polymers, making these highly efficient low band gap polymers promising candidates for use in tandem solar cells. (Graph Presented).

  12. Copper (I) Selenocyanate (CuSeCN) as a Novel Hole-Transport Layer for Transistors, Organic Solar Cells, and Light-Emitting Diodes

    KAUST Repository

    Wijeyasinghe, Nilushi

    2018-02-01

    The synthesis and characterization of copper (I) selenocyanate (CuSeCN) and its application as a solution-processable hole-transport layer (HTL) material in transistors, organic light-emitting diodes, and solar cells are reported. Density-functional theory calculations combined with X-ray photoelectron spectroscopy are used to elucidate the electronic band structure, density of states, and microstructure of CuSeCN. Solution-processed layers are found to be nanocrystalline and optically transparent (>94%), due to the large bandgap of ≥3.1 eV, with a valence band maximum located at −5.1 eV. Hole-transport analysis performed using field-effect measurements confirms the p-type character of CuSeCN yielding a hole mobility of 0.002 cm2 V−1 s−1. When CuSeCN is incorporated as the HTL material in organic light-emitting diodes and organic solar cells, the resulting devices exhibit comparable or improved performance to control devices based on commercially available poly(3,4-ethylenedioxythiophene):polystyrene sulfonate as the HTL. This is the first report on the semiconducting character of CuSeCN and it highlights the tremendous potential for further developments in the area of metal pseudohalides.

  13. 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.

  14. 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.

  15. Organic electrochemical transistors

    KAUST Repository

    Rivnay, Jonathan; Inal, Sahika; Salleo, Alberto; Owens, Ró isí n M.; Berggren, Magnus; Malliaras, George G.

    2018-01-01

    Organic electrochemical transistors (OECTs) make effective use of ion injection from an electrolyte to modulate the bulk conductivity of an organic semiconductor channel. The coupling between ionic and electronic charges within the entire volume

  16. Vertical organic transistors.

    Science.gov (United States)

    Lüssem, Björn; Günther, Alrun; Fischer, Axel; Kasemann, Daniel; Leo, Karl

    2015-11-11

    Organic switching devices such as field effect transistors (OFETs) are a key element of future flexible electronic devices. So far, however, a commercial breakthrough has not been achieved because these devices usually lack in switching speed (e.g. for logic applications) and current density (e.g. for display pixel driving). The limited performance is caused by a combination of comparatively low charge carrier mobilities and the large channel length caused by the need for low-cost structuring. Vertical Organic Transistors are a novel technology that has the potential to overcome these limitations of OFETs. Vertical Organic Transistors allow to scale the channel length of organic transistors into the 100 nm regime without cost intensive structuring techniques. Several different approaches have been proposed in literature, which show high output currents, low operation voltages, and comparatively high speed even without sub-μm structuring technologies. In this review, these different approaches are compared and recent progress is highlighted.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. A spiking neuron circuit based on a carbon nanotube transistor

    International Nuclear Information System (INIS)

    Chen, C-L; Kim, K; Truong, Q; Shen, A; Li, Z; Chen, Y

    2012-01-01

    A spiking neuron circuit based on a carbon nanotube (CNT) transistor is presented in this paper. The spiking neuron circuit has a crossbar architecture in which the transistor gates are connected to its row electrodes and the transistor sources are connected to its column electrodes. An electrochemical cell is incorporated in the gate of the transistor by sandwiching a hydrogen-doped poly(ethylene glycol)methyl ether (PEG) electrolyte between the CNT channel and the top gate electrode. An input spike applied to the gate triggers a dynamic drift of the hydrogen ions in the PEG electrolyte, resulting in a post-synaptic current (PSC) through the CNT channel. Spikes input into the rows trigger PSCs through multiple CNT transistors, and PSCs cumulate in the columns and integrate into a ‘soma’ circuit to trigger output spikes based on an integrate-and-fire mechanism. The spiking neuron circuit can potentially emulate biological neuron networks and their intelligent functions. (paper)

  12. Flexible Proton-Gated Oxide Synaptic Transistors on Si Membrane.

    Science.gov (United States)

    Zhu, Li Qiang; Wan, Chang Jin; Gao, Ping Qi; Liu, Yang Hui; Xiao, Hui; Ye, Ji Chun; Wan, Qing

    2016-08-24

    Ion-conducting materials have received considerable attention for their applications in fuel cells, electrochemical devices, and sensors. Here, flexible indium zinc oxide (InZnO) synaptic transistors with multiple presynaptic inputs gated by proton-conducting phosphorosilicate glass-based electrolyte films are fabricated on ultrathin Si membranes. Transient characteristics of the proton gated InZnO synaptic transistors are investigated, indicating stable proton-gating behaviors. Short-term synaptic plasticities are mimicked on the proposed proton-gated synaptic transistors. Furthermore, synaptic integration regulations are mimicked on the proposed synaptic transistor networks. Spiking logic modulations are realized based on the transition between superlinear and sublinear synaptic integration. The multigates coupled flexible proton-gated oxide synaptic transistors may be interesting for neuroinspired platforms with sophisticated spatiotemporal information processing.

  13. 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

  14. S,N-Heteroacene-Based Copolymers for Highly Efficient Organic Field Effect Transistors and Organic Solar Cells: Critical Impact of Aromatic Subunits in the Ladder π-System.

    Science.gov (United States)

    Chung, Chin-Lung; Chen, Hsieh-Chih; Yang, Yun-Siou; Tung, Wei-Yao; Chen, Jian-Wei; Chen, Wen-Chang; Wu, Chun-Guey; Wong, Ken-Tsung

    2018-02-21

    Three novel donor-acceptor alternating polymers containing ladder-type pentacyclic heteroacenes (PBo, PBi, and PT) are synthesized, characterized, and further applied to organic field effect transistors (OFETs) and polymer solar cells. Significant aspects of quinoidal characters, electrochemical properties, optical absorption, frontier orbitals, backbone coplanarity, molecular orientation, charge carrier mobilities, morphology discrepancies, and the corresponding device performances are notably different with various heteroarenes. PT exhibits a stronger quinoidal mesomeric structure, linear and coplanar conformation, smooth surface morphology, and better bimodal crystalline structures, which is beneficial to extend the π-conjugation and promotes charge transport via 3-D transport pathways and in consequence improves overall device performances. Organic photovoltaics based on the PT polymer achieve a power conversion efficiency of 6.04% along with a high short-circuit current density (J SC ) of 14.68 mA cm -2 , and a high hole mobility of 0.1 cm 2 V -1 s -1 is fulfilled in an OFET, which is superior to those of its counterparts, PBi and PBo.

  15. Bis(thienothiophenyl) diketopyrrolopyrrole-based conjugated polymers with various branched alkyl side chains and their applications in thin-film transistors and polymer solar cells.

    Science.gov (United States)

    Shin, Jicheol; Park, Gi Eun; Lee, Dae Hee; Um, Hyun Ah; Lee, Tae Wan; Cho, Min Ju; Choi, Dong Hoon

    2015-02-11

    New thienothiophene-flanked diketopyrrolopyrrole and thiophene-containing π-extended conjugated polymers with various branched alkyl side-chains were successfully synthesized. 2-Octyldodecyl, 2-decyltetradecyl, 2-tetradecylhexadecyl, 2-hexadecyloctadecyl, and 2-octadecyldocosyl groups were selected as the side-chain moieties and were anchored to the N-positions of the thienothiophene-flanked diketopyrrolopyrrole unit. All five polymers were found to be soluble owing to the bulkiness of the side chains. The thin-film transistor based on the 2-tetradecylhexadecyl-substituted polymer showed the highest hole mobility of 1.92 cm2 V(-1) s(-1) due to it having the smallest π-π stacking distance between the polymer chains, which was determined by grazing incidence X-ray diffraction. Bulk heterojunction polymer solar cells incorporating [6,6]-phenyl-C71-butyric acid methyl ester as the n-type molecule and the additive 1,8-diiodooctane (1 vol %) were also constructed from the synthesized polymers without thermal annealing; the device containing the 2-octyldodecyl-substituted polymer exhibited the highest power conversion efficiency of 5.8%. Although all the polymers showed similar physical properties, their device performance was clearly influenced by the sizes of the branched alkyl side-chain groups.

  16. 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.

  17. 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.

  18. 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...

  19. Empirical study of the metal-nitride-oxide-semiconductor device characteristics deduced from a microscopic model of memory traps

    International Nuclear Information System (INIS)

    Ngai, K.L.; Hsia, Y.

    1982-01-01

    A graded-nitride gate dielectric metal-nitride-oxide-semiconductor (MNOS) memory transistor exhibiting superior device characteristics is presented and analyzed based on a qualitative microscopic model of the memory traps. The model is further reviewed to interpret some generic properties of the MNOS memory transistors including memory window, erase-write speed, and the retention-endurance characteristic features

  20. 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....

  1. 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.

  2. 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.

  3. Diode, transistor & fet circuits manual

    CERN Document Server

    Marston, R M

    2013-01-01

    Diode, Transistor and FET Circuits Manual is a handbook of circuits based on discrete semiconductor components such as diodes, transistors, and FETS. The book also includes diagrams and practical circuits. The book describes basic and special diode characteristics, heat wave-rectifier circuits, transformers, filter capacitors, and rectifier ratings. The text also presents practical applications of associated devices, for example, zeners, varicaps, photodiodes, or LEDs, as well as it describes bipolar transistor characteristics. The transistor can be used in three basic amplifier configuration

  4. 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.

  5. 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.

  6. Ferroelectric field-effect transistors based on solution-processed electrochemically exfoliated graphene

    Science.gov (United States)

    Heidler, Jonas; Yang, Sheng; Feng, Xinliang; Müllen, Klaus; Asadi, Kamal

    2018-06-01

    Memories based on graphene that could be mass produced using low-cost methods have not yet received much attention. Here we demonstrate graphene ferroelectric (dual-gate) field effect transistors. The graphene has been obtained using electrochemical exfoliation of graphite. Field-effect transistors are realized using a monolayer of graphene flakes deposited by the Langmuir-Blodgett protocol. Ferroelectric field effect transistor memories are realized using a random ferroelectric copolymer poly(vinylidenefluoride-co-trifluoroethylene) in a top gated geometry. The memory transistors reveal ambipolar behaviour with both electron and hole accumulation channels. We show that the non-ferroelectric bottom gate can be advantageously used to tune the on/off ratio.

  7. 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.

  8. Electron irradiation of power transistors

    International Nuclear Information System (INIS)

    Hower, P.L.; Fiedor, R.J.

    1982-01-01

    A method for reducing storage time and gain parameters in a semiconductor transistor includes the step of subjecting the transistor to electron irradiation of a dosage determined from measurements of the parameters of a test batch of transistors. Reduction of carrier lifetime by proton bombardment and gold doping is mentioned as an alternative to electron irradiation. (author)

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. Effects of Asiatic Acid on Spatial Working Memory and Cell Proliferation in the Adult Rat Hippocampus

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. 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.

  20. 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...

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. Memory Applications Using Resonant Tunneling Diodes

    Science.gov (United States)

    Shieh, Ming-Huei

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

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. Accelerating the life of transistors

    International Nuclear Information System (INIS)

    Qi Haochun; Lü Changzhi; Zhang Xiaoling; Xie Xuesong

    2013-01-01

    Choosing small and medium power switching transistors of the NPN type in a 3DK set as the study object, the test of accelerating life is conducted in constant temperature and humidity, and then the data are statistically analyzed with software developed by ourselves. According to degradations of such sensitive parameters as the reverse leakage current of transistors, the lifetime order of transistors is about more than 10 4 at 100 °C and 100% relative humidity (RH) conditions. By corrosion fracture of transistor outer leads and other failure modes, with the failure truncated testing, the average lifetime rank of transistors in different distributions is extrapolated about 10 3 . Failure mechanism analyses of degradation of electrical parameters, outer lead fracture and other reasons that affect transistor lifetime are conducted. The findings show that the impact of external stress of outer leads on transistor reliability is more serious than that of parameter degradation. (semiconductor devices)

  14. 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

  15. 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.

  16. Nanophotonic quantum computer based on atomic quantum transistor

    International Nuclear Information System (INIS)

    Andrianov, S N; Moiseev, S A

    2015-01-01

    We propose a scheme of a quantum computer based on nanophotonic elements: two buses in the form of nanowaveguide resonators, two nanosized units of multiatom multiqubit quantum memory and a set of nanoprocessors in the form of photonic quantum transistors, each containing a pair of nanowaveguide ring resonators coupled via a quantum dot. The operation modes of nanoprocessor photonic quantum transistors are theoretically studied and the execution of main logical operations by means of them is demonstrated. We also discuss the prospects of the proposed nanophotonic quantum computer for operating in high-speed optical fibre networks. (quantum computations)

  17. Nanophotonic quantum computer based on atomic quantum transistor

    Energy Technology Data Exchange (ETDEWEB)

    Andrianov, S N [Institute of Advanced Research, Academy of Sciences of the Republic of Tatarstan, Kazan (Russian Federation); Moiseev, S A [Kazan E. K. Zavoisky Physical-Technical Institute, Kazan Scientific Center, Russian Academy of Sciences, Kazan (Russian Federation)

    2015-10-31

    We propose a scheme of a quantum computer based on nanophotonic elements: two buses in the form of nanowaveguide resonators, two nanosized units of multiatom multiqubit quantum memory and a set of nanoprocessors in the form of photonic quantum transistors, each containing a pair of nanowaveguide ring resonators coupled via a quantum dot. The operation modes of nanoprocessor photonic quantum transistors are theoretically studied and the execution of main logical operations by means of them is demonstrated. We also discuss the prospects of the proposed nanophotonic quantum computer for operating in high-speed optical fibre networks. (quantum computations)

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. Vertical organic transistors

    International Nuclear Information System (INIS)

    Lüssem, Björn; Günther, Alrun; Fischer, Axel; Kasemann, Daniel; Leo, Karl

    2015-01-01

    Organic switching devices such as field effect transistors (OFETs) are a key element of future flexible electronic devices. So far, however, a commercial breakthrough has not been achieved because these devices usually lack in switching speed (e.g. for logic applications) and current density (e.g. for display pixel driving). The limited performance is caused by a combination of comparatively low charge carrier mobilities and the large channel length caused by the need for low-cost structuring. Vertical Organic Transistors are a novel technology that has the potential to overcome these limitations of OFETs. Vertical Organic Transistors allow to scale the channel length of organic transistors into the 100 nm regime without cost intensive structuring techniques. Several different approaches have been proposed in literature, which show high output currents, low operation voltages, and comparatively high speed even without sub-μm structuring technologies. In this review, these different approaches are compared and recent progress is highlighted. (topical review)

  3. Photosensitive graphene transistors.

    Science.gov (United States)

    Li, Jinhua; Niu, Liyong; Zheng, Zijian; Yan, Feng

    2014-08-20

    High performance photodetectors play important roles in the development of innovative technologies in many fields, including medicine, display and imaging, military, optical communication, environment monitoring, security check, scientific research and industrial processing control. Graphene, the most fascinating two-dimensional material, has demonstrated promising applications in various types of photodetectors from terahertz to ultraviolet, due to its ultrahigh carrier mobility and light absorption in broad wavelength range. Graphene field effect transistors are recognized as a type of excellent transducers for photodetection thanks to the inherent amplification function of the transistors, the feasibility of miniaturization and the unique properties of graphene. In this review, we will introduce the applications of graphene transistors as photodetectors in different wavelength ranges including terahertz, infrared, visible, and ultraviolet, focusing on the device design, physics and photosensitive performance. Since the device properties are closely related to the quality of graphene, the devices based on graphene prepared with different methods will be addressed separately with a view to demonstrating more clearly their advantages and shortcomings in practical applications. It is expected that highly sensitive photodetectors based on graphene transistors will find important applications in many emerging areas especially flexible, wearable, printable or transparent electronics and high frequency communications. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. 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)

  5. 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.

  6. 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.

  7. 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.

  8. 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 ...

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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…

  16. 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...

  17. 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.

  18. High-performance solution-processed polymer ferroelectric field-effect transistors

    NARCIS (Netherlands)

    Naber, RCG; Tanase, C; Blom, PWM; Gelinck, GH; Marsman, AW; Touwslager, FJ; Setayesh, S; De Leeuw, DM; Naber, Ronald C.G.; Gelinck, Gerwin H.; Marsman, Albert W.; Touwslager, Fred J.

    We demonstrate a rewritable, non-volatile memory device with flexible plastic active layers deposited from solution. The memory device is a ferroelectric field-effect transistor (FeFET) made with a ferroelectric fluoropolymer and a bisalkoxy-substituted poly(p-phenylene vinylene) semiconductor

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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.

  6. Non-invasive screening for Alzheimer's disease by sensing salivary sugar using Drosophila cells expressing gustatory receptor (Gr5a) immobilized on an extended gate ion-sensitive field-effect transistor (EG-ISFET) biosensor.

    Science.gov (United States)

    Lau, Hui-Chong; Lee, In-Kyu; Ko, Pan-Woo; Lee, Ho-Won; Huh, Jeung-Soo; Cho, Won-Ju; Lim, Jeong-Ok

    2015-01-01

    Body fluids are often used as specimens for medical diagnosis. With the advent of advanced analytical techniques in biotechnology, the diagnostic potential of saliva has been the focus of many studies. We recently reported the presence of excess salivary sugars, in patients with Alzheimer's disease (AD). In the present study, we developed a highly sensitive, cell-based biosensor to detect trehalose levels in patient saliva. The developed biosensor relies on the overexpression of sugar sensitive gustatory receptors (Gr5a) in Drosophila cells to detect the salivary trehalose. The cell-based biosensor was built on the foundation of an improved extended gate ion-sensitive field-effect transistor (EG-ISFET). Using an EG-ISFET, instead of a traditional ion-sensitive field-effect transistor (ISFET), resulted in an increase in the sensitivity and reliability of detection. The biosensor was designed with the gate terminals segregated from the conventional ISFET device. This design allows the construction of an independent reference and sensing region for simultaneous and accurate measurements of samples from controls and patients respectively. To investigate the efficacy of the cell-based biosensor for AD screening, we collected 20 saliva samples from each of the following groups: participants diagnosed with AD, participants diagnosed with Parkinson's disease (PD), and a control group composed of healthy individuals. We then studied the response generated from the interaction of the salivary trehalose of the saliva samples and the Gr5a in the immobilized cells on an EG-ISFET sensor. The cell-based biosensor significantly distinguished salivary sugar, trehalose of the AD group from the PD and control groups. Based on these findings, we propose that salivary trehalose, might be a potential biomarker for AD and could be detected using our cell-based EG-ISFET biosensor. The cell-based EG-ISFET biosensor provides a sensitive and direct approach for salivary sugar detection and

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Junctionless Cooper pair transistor

    Energy Technology Data Exchange (ETDEWEB)

    Arutyunov, K. Yu., E-mail: konstantin.yu.arutyunov@jyu.fi [National Research University Higher School of Economics , Moscow Institute of Electronics and Mathematics, 101000 Moscow (Russian Federation); P.L. Kapitza Institute for Physical Problems RAS , Moscow 119334 (Russian Federation); Lehtinen, J.S. [VTT Technical Research Centre of Finland Ltd., Centre for Metrology MIKES, P.O. Box 1000, FI-02044 VTT (Finland)

    2017-02-15

    Highlights: • Junctionless Cooper pair box. • Quantum phase slips. • Coulomb blockade and gate modulation of the Coulomb gap. - Abstract: Quantum phase slip (QPS) is the topological singularity of the complex order parameter of a quasi-one-dimensional superconductor: momentary zeroing of the modulus and simultaneous 'slip' of the phase by ±2π. The QPS event(s) are the dynamic equivalent of tunneling through a conventional Josephson junction containing static in space and time weak link(s). Here we demonstrate the operation of a superconducting single electron transistor (Cooper pair transistor) without any tunnel junctions. Instead a pair of thin superconducting titanium wires in QPS regime was used. The current–voltage characteristics demonstrate the clear Coulomb blockade with magnitude of the Coulomb gap modulated by the gate potential. The Coulomb blockade disappears above the critical temperature, and at low temperatures can be suppressed by strong magnetic field.

  12. Mesoscopic photon heat transistor

    DEFF Research Database (Denmark)

    Ojanen, T.; Jauho, Antti-Pekka

    2008-01-01

    We show that the heat transport between two bodies, mediated by electromagnetic fluctuations, can be controlled with an intermediate quantum circuit-leading to the device concept of a mesoscopic photon heat transistor (MPHT). Our theoretical analysis is based on a novel Meir-Wingreen-Landauer-typ......We show that the heat transport between two bodies, mediated by electromagnetic fluctuations, can be controlled with an intermediate quantum circuit-leading to the device concept of a mesoscopic photon heat transistor (MPHT). Our theoretical analysis is based on a novel Meir......-Wingreen-Landauer-type of conductance formula, which gives the photonic heat current through an arbitrary circuit element coupled to two dissipative reservoirs at finite temperatures. As an illustration we present an exact solution for the case when the intermediate circuit can be described as an electromagnetic resonator. We discuss...

  13. 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

  14. AM06: the Associative Memory chip for the Fast TracKer in the upgraded ATLAS detector

    CERN Document Server

    Liberali, Valentino; The ATLAS collaboration

    2018-01-01

    This paper describes the AM06 chip, a highly parallel processor for pattern recognition in high energy physics. AM06 contains memory banks that store up to 2^17 patterns made up of 8x18 bit words and integrates SER/DES IP blocks for 2.4 Gb/s IO to avoid routing congestion. AM06 combines custom memory arrays, standard logic cells and IP blocks within a 168 mm^2 silicon area with 421 million transistors and can perform bitwise comparisons at 1.6 Pbit/s, consuming ~2 fJ/bit per comparison thanks to the optimized design based on the XORAM cells.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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)

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. Modeling of charge transport in ion bipolar junction transistors.

    Science.gov (United States)

    Volkov, Anton V; Tybrandt, Klas; Berggren, Magnus; Zozoulenko, Igor V

    2014-06-17

    Spatiotemporal control of the complex chemical microenvironment is of great importance to many fields within life science. One way to facilitate such control is to construct delivery circuits, comprising arrays of dispensing outlets, for ions and charged biomolecules based on ionic transistors. This allows for addressability of ionic signals, which opens up for spatiotemporally controlled delivery in a highly complex manner. One class of ionic transistors, the ion bipolar junction transistors (IBJTs), is especially attractive for these applications because these transistors are functional at physiological conditions and have been employed to modulate the delivery of neurotransmitters to regulate signaling in neuronal cells. Further, the first integrated complementary ionic circuits were recently developed on the basis of these ionic transistors. However, a detailed understanding of the device physics of these transistors is still lacking and hampers further development of components and circuits. Here, we report on the modeling of IBJTs using Poisson's and Nernst-Planck equations and the finite element method. A two-dimensional model of the device is employed that successfully reproduces the main characteristics of the measurement data. On the basis of the detailed concentration and potential profiles provided by the model, the different modes of operation of the transistor are analyzed as well as the transitions between the different modes. The model correctly predicts the measured threshold voltage, which is explained in terms of membrane potentials. All in all, the results provide the basis for a detailed understanding of IBJT operation. This new knowledge is employed to discuss potential improvements of ion bipolar junction transistors in terms of miniaturization and device parameters.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. Dosimetric properties of MOS transistors

    International Nuclear Information System (INIS)

    Peter, I.; Frank, G.

    1977-01-01

    The performance of MOS transistors as gamma detectors has been tested. The dosimeter sensitivity has proved to be independent on the doses ranging from 10 3 to 10 6 R, and gamma energy of 137 Cs, 60 Co - sources and 5 - 18 MeV electrons. Fading of the space charge trapped by the SiO 2 layer of the transistor has appeared to be neglegible at room temperature after 400 hrs. The isochronous annealing in the temperature range of 40-260 deg C had a more substantial effect on the space charge of the transistor irradiated with 18 MeV electrons than on the 137 Cs gamma-irradiated transistors. This proved a repeated use of γ-dosemeters. MOS transistors are concluded to be promising for gamma dosimetry [ru

  20. 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

  1. 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

  2. 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

  3. Leakage characterization of top select transistor for program disturbance optimization in 3D NAND flash

    Science.gov (United States)

    Zhang, Yu; Jin, Lei; Jiang, Dandan; Zou, Xingqi; Zhao, Zhiguo; Gao, Jing; Zeng, Ming; Zhou, Wenbin; Tang, Zhaoyun; Huo, Zongliang

    2018-03-01

    In order to optimize program disturbance characteristics effectively, a characterization approach that measures top select transistor (TSG) leakage from bit-line is proposed to quantify TSG leakage under program inhibit condition in 3D NAND flash memory. Based on this approach, the effect of Vth modulation of two-cell TSG on leakage is evaluated. By checking the dependence of leakage and corresponding program disturbance on upper and lower TSG Vth, this approach is validated. The optimal Vth pattern with high upper TSG Vth and low lower TSG Vth has been suggested for low leakage current and high boosted channel potential. It is found that upper TSG plays dominant role in preventing drain induced barrier lowering (DIBL) leakage from boosted channel to bit-line, while lower TSG assists to further suppress TSG leakage by providing smooth potential drop from dummy WL to edge of TSG, consequently suppressing trap assisted band-to-band tunneling current (BTBT) between dummy WL and TSG.

  4. Flexible Electronics: Integration Processes for Organic and Inorganic Semiconductor-Based Thin-Film Transistors

    Directory of Open Access Journals (Sweden)

    Fábio F. Vidor

    2015-07-01

    Full Text Available Flexible and transparent electronics have been studied intensively during the last few decades. The technique establishes the possibility of fabricating innovative products, from flexible displays to radio-frequency identification tags. Typically, large-area polymeric substrates such as polypropylene (PP or polyethylene terephthalate (PET are used, which produces new requirements for the integration processes. A key element for flexible and transparent electronics is the thin-film transistor (TFT, as it is responsible for the driving current in memory cells, digital circuits or organic light-emitting devices (OLEDs. In this paper, we discuss some fundamental concepts of TFT technology. Additionally, we present a comparison between the use of the semiconducting organic small-molecule pentacene and inorganic nanoparticle semiconductors in order to integrate TFTs suitable for flexible electronics. Moreover, a technique for integration with a submicron resolution suitable for glass and foil substrates is presented.

  5. 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.

  6. 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.

  7. Spin Hall effect transistor

    Czech Academy of Sciences Publication Activity Database

    Wunderlich, Joerg; Park, B.G.; Irvine, A.C.; Zarbo, Liviu; Rozkotová, E.; Němec, P.; Novák, Vít; Sinova, Jairo; Jungwirth, Tomáš

    2010-01-01

    Roč. 330, č. 6012 (2010), s. 1801-1804 ISSN 0036-8075 R&D Projects: GA AV ČR KAN400100652; GA MŠk LC510 EU Projects: European Commission(XE) 215368 - SemiSpinNet Grant - others:AV ČR(CZ) AP0801 Program:Akademická prémie - Praemium Academiae Institutional research plan: CEZ:AV0Z10100521 Keywords : spin Hall effect * spintronics * spin transistor Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 31.364, year: 2010

  8. 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.

  9. 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.

  10. 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.

  11. 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...

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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)

  18. 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.

  19. 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.

  20. 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.

  1. Autoreactive effector/memory CD4+ and CD8+ T cells infiltrating grafted and endogenous islets in diabetic NOD mice exhibit similar T cell receptor usage.

    Directory of Open Access Journals (Sweden)

    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.

  2. Physical limits of silicon transistors and circuits

    International Nuclear Information System (INIS)

    Keyes, Robert W

    2005-01-01

    A discussion on transistors and electronic computing including some history introduces semiconductor devices and the motivation for miniaturization of transistors. The changing physics of field-effect transistors and ways to mitigate the deterioration in performance caused by the changes follows. The limits of transistors are tied to the requirements of the chips that carry them and the difficulties of fabricating very small structures. Some concluding remarks about transistors and limits are presented

  3. Acetylation of the Cd8 Locus by KAT6A Determines Memory T Cell Diversity

    Directory of Open Access Journals (Sweden)

    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.

  4. 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

  5. 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

  6. Changes in B Cell Populations and Merozoite Surface Protein-1-Specific Memory B Cell Responses after Prolonged Absence of Detectable P. falciparum Infection.

    Directory of Open Access Journals (Sweden)

    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.

  7. Architecture and performance of radiation-hardened 64-bit SOS/MNOS memory

    International Nuclear Information System (INIS)

    Kliment, D.C.; Ronen, R.S.; Nielsen, R.L.; Seymour, R.N.; Splinter, M.R.

    1976-01-01

    This paper discusses the circuit architecture and performance of a nonvolatile 64-bit MNOS memory fabricated on silicon on sapphire (SOS). The circuit is a test vehicle designed to demonstrate the feasibility of a high-performance, high-density, radiation-hardened MNOS/SOS memory. The array is organized as 16 words by 4 bits and is fully decoded. It utilizes a two-(MNOS) transistor-per-bit cell and differential sensing scheme and is realized in PMOS static resistor load logic. The circuit was fabricated and tested as both a fast write random access memory (RAM) and an electrically alterable read only memory (EAROM) to demonstrate design and process flexibility. Discrete device parameters such as retention, circuit electrical characteristics, and tolerance to total dose and transient radiation are presented

  8. 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.

  9. 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.

  10. 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.

  11. Programmable automated transistor test system

    International Nuclear Information System (INIS)

    Truong, L.V.; Sundberg, G.R.

    1986-01-01

    The paper describes a programmable automated transistor test system (PATTS) and its utilization to evaluate bipolar transistors and Darlingtons, and such MOSFET and special types as can be accommodated with the PATTS base-drive. An application of a pulsed power technique at low duty cycles in a non-destructive test is used to examine the dynamic switching characteristic curves of power transistors. Data collection, manipulation, storage, and output are operator interactive but are guided and controlled by the system software. In addition a library of test data is established on disks, tapes, and hard copies for future reference

  12. 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

  13. 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.

  14. Operational method of a ferroelectric (Fe)-NAND flash memory array

    International Nuclear Information System (INIS)

    Wang, Shouyu; Takahashi, Mitue; Li, Qiu-Hong; Sakai, Shigeki; Takeuchi, Ken

    2009-01-01

    Operations of arrayed ferroelectric (Fe)-NAND flash memory cells: erase, program and read were demonstrated for the first time using a small cell array of four word lines by two NAND strings. The memory cells and select-gate transistors were all n-channel Pt/SrBi 2 Ta 2 O 9 /Hf-Al-O/Si ferroelectric-gate field effect transistors. The erase was performed by applying 10 µs wide 7 V pulses to n- and p-wells. The program was performed by applying 10 µs wide 7 V pulses to selected word lines. Accumulated read currents of 51 programmed patterns in the Fe-NAND flash memory cell array successfully showed distribution of the two distinguishable '0' and '1' states. The margin between the two states became wider by applying a verification technique in programming a cell out of the eight. Retention times of bit-line currents were obtained over 33 h for both the '0' and '1' states in a program pattern

  15. 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

  16. 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.

  17. 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

  18. Non-invasive screening for Alzheimer's disease by sensing salivary sugar using Drosophila cells expressing gustatory receptor (Gr5a immobilized on an extended gate ion-sensitive field-effect transistor (EG-ISFET biosensor.

    Directory of Open Access Journals (Sweden)

    Hui-Chong Lau

    Full Text Available Body fluids are often used as specimens for medical diagnosis. With the advent of advanced analytical techniques in biotechnology, the diagnostic potential of saliva has been the focus of many studies. We recently reported the presence of excess salivary sugars, in patients with Alzheimer's disease (AD. In the present study, we developed a highly sensitive, cell-based biosensor to detect trehalose levels in patient saliva. The developed biosensor relies on the overexpression of sugar sensitive gustatory receptors (Gr5a in Drosophila cells to detect the salivary trehalose. The cell-based biosensor was built on the foundation of an improved extended gate ion-sensitive field-effect transistor (EG-ISFET. Using an EG-ISFET, instead of a traditional ion-sensitive field-effect transistor (ISFET, resulted in an increase in the sensitivity and reliability of detection. The biosensor was designed with the gate terminals segregated from the conventional ISFET device. This design allows the construction of an independent reference and sensing region for simultaneous and accurate measurements of samples from controls and patients respectively. To investigate the efficacy of the cell-based biosensor for AD screening, we collected 20 saliva samples from each of the following groups: participants diagnosed with AD, participants diagnosed with Parkinson's disease (PD, and a control group composed of healthy individuals. We then studied the response generated from the interaction of the salivary trehalose of the saliva samples and the Gr5a in the immobilized cells on an EG-ISFET sensor. The cell-based biosensor significantly distinguished salivary sugar, trehalose of the AD group from the PD and control groups. Based on these findings, we propose that salivary trehalose, might be a potential biomarker for AD and could be detected using our cell-based EG-ISFET biosensor. The cell-based EG-ISFET biosensor provides a sensitive and direct approach for salivary sugar

  19. 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.

  20. 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.

  1. 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...

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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 medical fields. In chronologic order, you digest the literature, but unfortunately, you hit a major stumbling block in the 1990s. The crux of the problem is that which so often happens in science: two well-recognized, capable groups emerge with diametrically opposed conclusions, leaving you pondering which set of wellcontrolled data to believe. Fortunately, years later, a surprising group of articles sheds light on this mystery and subtly reconciles these two positions.

  8. Characterisation of retention properties of charge-trapping memory cells at low temperatures

    International Nuclear Information System (INIS)

    Yurchuk, E; Bollmann, J; Mikolajick, T

    2009-01-01

    The density of states of deep level centers in silicon oxynitride layer of SONOS memory cells are calculated from temperature dependent retention measurement. The dominating charge loss mechanisms are direct trap-to-band tunneling (TB) and thermally stimulated emission (TE). Retention measurements at low temperatures (80 - 300K) will be dominated by TE from more 'shallow' traps with energies below 1eV and by TB. Taking into account both independent and rival processes the density of states could be calculated self consisting. The results are in excellent agreement with elsewhere published data.

  9. Characterisation of retention properties of charge-trapping memory cells at low temperatures

    Science.gov (United States)

    Yurchuk, E.; Bollmann, J.; Mikolajick, T.

    2009-09-01

    The density of states of deep level centers in silicon oxynitride layer of SONOS memory cells are calculated from temperature dependent retention measurement. The dominating charge loss mechanisms are direct trap-to-band tunneling (TB) and thermally stimulated emission (TE). Retention measurements at low temperatures (80 - 300K) will be dominated by TE from more "shallow" traps with energies below 1eV and by TB. Taking into account both independent and rival processes the density of states could be calculated self consisting. The results are in excellent agreement with elsewhere published data.

  10. FAST TRACK COMMUNICATION: Eight-logic memory cell based on multiferroic junctions

    Science.gov (United States)

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

    2009-04-01

    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.

  11. T-cell help permits memory CD8(+) T-cell inflation during cytomegalovirus latency.

    Science.gov (United States)

    Walton, Senta M; Torti, Nicole; Mandaric, Sanja; Oxenius, Annette

    2011-08-01

    CD4(+) T cells are implied to sustain CD8(+) T-cell responses during persistent infections. As CD4(+) T cells are often themselves antiviral effectors, they might shape CD8(+) T-cell responses via help or via controlling antigen load. We used persistent murine CMV (MCMV) infection to dissect the impact of CD4(+) T cells on virus-specific CD8(+) T cells, distinguishing between increased viral load in the absence of CD4(+) T cells and CD4(+) T-cell-mediated helper mechanisms. Absence of T-helper cells was associated with sustained lytic MCMV replication and led to a slow and gradual reduction of the size and function of the MCMV-specific CD8(+) T-cell pool. However, when virus replication was controlled in the absence of CD4(+) T cells, CD8(+) T-cell function was comparably impaired, but in addition CD8(+) T-cell inflation, a hallmark of CMV infection, was completely abolished. Thus, CD8(+) T-cell inflation during latent CMV infection is strongly dependent on CD4(+) T-cell helper functions, which can partially be compensated by ongoing lytic viral replication in the absence of CD4(+) T cells. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Short neuropeptide F acts as a functional neuromodulator for olfactory memory in Kenyon cells of Drosophila mushroom bodies.

    Science.gov (United States)

    Knapek, Stephan; Kahsai, Lily; Winther, Asa M E; Tanimoto, Hiromu; Nässel, Dick R

    2013-03-20

    In insects, many complex behaviors, including olfactory memory, are controlled by a paired brain structure, the so-called mushroom bodies (MB). In Drosophila, the development, neuroanatomy, and function of intrinsic neurons of the MB, the Kenyon cells, have been well characterized. Until now, several potential neurotransmitters or neuromodulators of Kenyon cells have been anatomically identified. However, whether these neuroactive substances of the Kenyon cells are functional has not been clarified yet. Here we show that a neuropeptide precursor gene encoding four types of short neuropeptide F (sNPF) is required in the Kenyon cells for appetitive olfactory memory. We found that activation of Kenyon cells by expressing a thermosensitive cation channel (dTrpA1) leads to a decrease in sNPF immunoreactivity in the MB lobes. Targeted expression of RNA interference against the sNPF precursor in Kenyon cells results in a highly significant knockdown of sNPF levels. This knockdown of sNPF in the Kenyon cells impairs sugar-rewarded olfactory memory. This impairment is not due to a defect in the reflexive sugar preference or odor response. Consistently, knockdown of sNPF receptors outside the MB causes deficits in appetitive memory. Altogether, these results suggest that sNPF is a functional neuromodulator released by Kenyon cells.

  13. Transistor and integrated circuit manufacture

    International Nuclear Information System (INIS)

    Colman, D.

    1978-01-01

    This invention relates to the manufacture of transistors and integrated circuits by ion bombardment techniques and is particularly, but not exclusively, of value in the manufacture of so-called integrated injection logic circuitry. (author)

  14. High transconductance organic electrochemical transistors

    Science.gov (United States)

    Khodagholy, Dion; Rivnay, Jonathan; Sessolo, Michele; Gurfinkel, Moshe; Leleux, Pierre; Jimison, Leslie H.; Stavrinidou, Eleni; Herve, Thierry; Sanaur, Sébastien; Owens, Róisín M.; Malliaras, George G.

    2013-07-01

    The development of transistors with high gain is essential for applications ranging from switching elements and drivers to transducers for chemical and biological sensing. Organic transistors have become well-established based on their distinct advantages, including ease of fabrication, synthetic freedom for chemical functionalization, and the ability to take on unique form factors. These devices, however, are largely viewed as belonging to the low-end of the performance spectrum. Here we present organic electrochemical transistors with a transconductance in the mS range, outperforming transistors from both traditional and emerging semiconductors. The transconductance of these devices remains fairly constant from DC up to a frequency of the order of 1 kHz, a value determined by the process of ion transport between the electrolyte and the channel. These devices, which continue to work even after being crumpled, are predicted to be highly relevant as transducers in biosensing applications.

  15. Organic tunnel field effect transistors

    KAUST Repository

    Tietze, Max Lutz; Lussem, Bjorn; Liu, Shiyi

    2017-01-01

    Various examples are provided for organic tunnel field effect transistors (OTFET), and methods thereof. In one example, an OTFET includes a first intrinsic layer (i-layer) of organic semiconductor material disposed over a gate insulating layer

  16. High transconductance organic electrochemical transistors

    Science.gov (United States)

    Khodagholy, Dion; Rivnay, Jonathan; Sessolo, Michele; Gurfinkel, Moshe; Leleux, Pierre; Jimison, Leslie H.; Stavrinidou, Eleni; Herve, Thierry; Sanaur, Sébastien; Owens, Róisín M.; Malliaras, George G.

    2013-01-01

    The development of transistors with high gain is essential for applications ranging from switching elements and drivers to transducers for chemical and biological sensing. Organic transistors have become well-established based on their distinct advantages, including ease of fabrication, synthetic freedom for chemical functionalization, and the ability to take on unique form factors. These devices, however, are largely viewed as belonging to the low-end of the performance spectrum. Here we present organic electrochemical transistors with a transconductance in the mS range, outperforming transistors from both traditional and emerging semiconductors. The transconductance of these devices remains fairly constant from DC up to a frequency of the order of 1 kHz, a value determined by the process of ion transport between the electrolyte and the channel. These devices, which continue to work even after being crumpled, are predicted to be highly relevant as transducers in biosensing applications. PMID:23851620

  17. Transistor and integrated circuit manufacture

    Energy Technology Data Exchange (ETDEWEB)

    Colman, D

    1978-09-27

    This invention relates to the manufacture of transistors and integrated circuits by ion bombardment techniques and is particularly, but not exclusively, of value in the manufacture of so-called integrated injection logic circuitry.

  18. Mycobacterium tuberculosis-specific memory NKT cells in patients with tuberculous pleurisy.

    Science.gov (United States)

    Li, Zitao; Yang, Binyan; Zhang, Yannan; Ma, Jiangjun; Chen, Xinchun; Lao, Suihua; Li, Baiqing; Wu, Changyou

    2014-11-01

    Natural killer T (NKT) cells from mouse and human play a protective role in the immune responses against the infection of Mycobacterium tuberculosis. However, the characteristic of CD3(+)TCRvβ11(+) NKT cells at the local site of M. tuberculosis infection remains poorly defined. In the present study, we found that the numbers of CD3(+)TCRvβ11(+) NKT cells in pleural fluid mononuclear cells (PFMCs) were significantly lower than those in peripheral blood mononuclear cells (PBMCs). However, CD3(+)TCRvβ11(+) NKT cells from PFMCs spontaneously expressed high levels of CD69 and CD25 and effector memory phenotypes of CD45RO(high)CD62L(low)CCR7(low). After stimulation with the antigens of M. tuberculosis, CD3(+)TCRvβ11(+) NKT cells from PFMCs produced high levels of IFN-γ. Sorted CD3(+)TCRvβ11(+) NKT cells from PFMCs cultured with antigen presenting cells (APCs) produced IFN-γ protein and mRNA. The production of IFN-γ could be completely inhibited by AG490 and Wortmannin. In addition, CD3(+)TCRvβ11(+) NKT cells from PFMCs expressed higher levels of Fas (CD95), FasL (CD178) and perforin but lower levels of granzyme B compared with those from PBMCs. Taken together, our data demonstrated for the first time that M. tuberculosis-specific CD3(+)TCRvβ11(+) NKT cells participated in the local immune responses against M. tuberculosis through the production of IFN-γ and the secretion of cytolytic molecules.

  19. Dosimetric properties of MOS transistors

    International Nuclear Information System (INIS)

    Frank, H.; Petr, I.

    1977-01-01

    The structure of MOS transistors is described and their characteristics given. The experiments performed and data in the literature show the following dosimetric properties of MOS transistors: while for low gamma doses the transistor response to exposure is linear, it shows saturation for higher doses (exceeding 10 3 Gy in tissue). The response is independent of the energy of radiation and of the dose rate (within 10 -2 to 10 5 Gy/s). The spontaneous reduction with time of the spatial charge captured by the oxide layer (fading) is small and acceptable from the point of view of dosimetry. Curves are given of isochronous annealing of the transistors following irradiation with 137 Cs and 18 MeV electrons for different voltages during irradiation. The curves show that in MOS transistors irradiated with high-energy electrons the effect of annealing is less than in transistors irradiated with 137 Cs. In view of the requirement of using higher temperatures (approx. 400 degC) for the complete ''erasing'' of the captured charge, unsealed systems must be used for dosimetric purposes. The effect was also studied of neutron radiation, proton radiation and electron radiation on the MOS transistor structure. For MOS transistor irradiation with 14 MeV neutrons from a neutron generator the response was 4% of that for gamma radiation at the same dose equivalent. The effect of proton radiation was studied as related to the changes in MOS transistor structure during space flights. The response curve shapes are similar to those of gamma radiation curves. The effect of electron radiation on the MOS structure was studied by many authors. The experiments show that for each thickness of the SiO 2 layer an electron energy exists at which the size of the charge captured in SiO 2 is the greatest. All data show that MOS transistors are promising for radiation dosimetry. The main advantage of MOS transistors as gamma dosemeters is the ease and speed of evaluation, low sensitivity to neutron

  20. Planar-Processed Polymer Transistors.

    Science.gov (United States)

    Xu, Yong; Sun, Huabin; Shin, Eul-Yong; Lin, Yen-Fu; Li, Wenwu; Noh, Yong-Young

    2016-10-01

    Planar-processed polymer transistors are proposed where the effective charge injection and the split unipolar charge transport are all on the top surface of the polymer film, showing ideal device characteristics with unparalleled performance. This technique provides a great solution to the problem of fabrication limitations, the ambiguous operating principle, and the performance improvements in practical applications of conjugated-polymer transistors. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Impact of infant and preschool pertussis vaccinations on memory B-cell responses in children at 4 years of age.

    Science.gov (United States)

    Hendrikx, Lotte H; de Rond, Lia G H; Oztürk, Kemal; Veenhoven, Reinier H; Sanders, Elisabeth A M; Berbers, Guy A M; Buisman, Anne-Marie

    2011-08-05

    Whooping cough, caused by Bordetella pertussis, is reemerging in the vaccinated population. Antibody levels to pertussis antigens wane rapidly after both whole-cell (wP) and acellular pertussis (aP) vaccination and protection may largely depend on long-term B- and T-cell immunity. We studied the effect of wP and aP infant priming at 2, 3, 4 and 11 months according to the Dutch immunization program on pertussis-specific memory B-cell responses before and after a booster vaccination with either a high- or low-pertussis dose vaccine at 4 years of age. 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 and pertactin. Before and after the booster, higher memory B-cell responses were measured in aP primed children compared with wP primed children. In contrast with antibody levels, no dose-effect was observed on the numbers of memory B-cell responses. In aP primed children a fifth high-dose aP vaccination tended to induce even lower memory B-cell responses than a low-dose aP booster. In both wP and aP primed children, the number of memory B-cells increased after the booster and correlated with the pertussis-specific antibody concentrations and observed affinity maturation. This study indicates that aP vaccinations in the first year of life induce higher pertussis-specific memory B-cell responses in children 4 years of age compared with Dutch wP primary vaccinations. Since infant aP vaccinations have improved protection against whooping cough in children despite waning antibody levels, this suggests that an enhanced memory B-cell pool induction may have an important role in protection. However, the pertussis-dose of the preschool booster needs to be considered depending on the vaccine used for priming to optimize long-term protection against whooping cough. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Magnetophoretic transistors in a tri-axial magnetic field.

    Science.gov (United States)

    Abedini-Nassab, Roozbeh; Joh, Daniel Y; Albarghouthi, Faris; Chilkoti, Ashutosh; Murdoch, David M; Yellen, Benjamin B

    2016-10-18

    The ability to direct and sort individual biological and non-biological particles into spatially addressable locations is fundamentally important to the emerging field of single cell biology. Towards this goal, we demonstrate a new class of magnetophoretic transistors, which can switch single magnetically labeled cells and magnetic beads between different paths in a microfluidic chamber. Compared with prior work on magnetophoretic transistors driven by a two-dimensional in-plane rotating field, the addition of a vertical magnetic field bias provides significant advantages in preventing the formation of particle clumps and in better replicating the operating principles of circuits in general. However, the three-dimensional driving field requires a complete redesign of the magnetic track geometry and switching electrodes. We have solved this problem by developing several types of transistor geometries which can switch particles between two different tracks by either presenting a local energy barrier or by repelling magnetic objects away from a given track, hereby denoted as "barrier" and "repulsion" transistors, respectively. For both types of transistors, we observe complete switching of magnetic objects with currents of ∼40 mA, which is consistent over a range of particle sizes (8-15 μm). The switching efficiency was also tested at various magnetic field strengths (50-90 Oe) and driving frequencies (0.1-0.6 Hz); however, we again found that the device performance only weakly depended on these parameters. These findings support the use of these novel transistor geometries to form circuit architectures in which cells can be placed in defined locations and retrieved on demand.

  3. Distinct kinetics of memory B-cell and plasma-cell responses in peripheral blood following a blood-stage Plasmodium chabaudi infection in mice.

    Directory of Open Access Journals (Sweden)

    Eunice W Nduati

    2010-11-01

    Full Text Available B cell and plasma cell responses take place in lymphoid organs, but because of the inaccessibility of these organs, analyses of human responses are largely performed using peripheral blood mononuclear cells (PBMC. To determine whether PBMC are a useful source of memory B cells and plasma cells in malaria, and whether they reflect Plasmodium-specific B cell responses in spleen or bone marrow, we have investigated these components of the humoral response in PBMC using a model of Plasmodium chabaudi blood-stage infections in C57BL/6 mice. We detected memory B cells, defined as isotype-switched IgD(- IgM(- CD19(+ B cells, and low numbers of Plasmodium chabaudi Merozoite Surface Protein-1 (MSP1-specific memory B cells, in PBMC at all time points sampled for up to 90 days following primary or secondary infection. By contrast, we only detected CD138(+ plasma cells and MSP1-specific antibody-secreting cells within a narrow time frame following primary (days 10 to 25 or secondary (day 10 infection. CD138(+ plasma cells in PBMC at these times expressed CD19, B220 and MHC class II, suggesting that they were not dislodged bone-marrow long-lived plasma cells, but newly differentiated migratory plasmablasts migrating to the bone marrow; thus reflective of an ongoing or developing immune response. Our data indicates that PBMC can be a useful source for malaria-specific memory B cells and plasma cells, but extrapolation of the results to human malaria infections suggests that timing of sampling, particularly for plasma cells, may be critical. Studies should therefore include multiple sampling points, and at times of infection/immunisation when the B-cell phenotypes of interest are likely to be found in peripheral blood.

  4. Pattern imprinting in deep sub-micron static random access memories induced by total dose irradiation

    International Nuclear Information System (INIS)

    Zheng Qi-Wen; Yu Xue-Feng; Cui Jiang-Wei; Guo Qi; Ren Di-Yuan; Cong Zhong-Chao; Zhou Hang

    2014-01-01

    Pattern imprinting in deep sub-micron static random access memories (SRAMs) during total dose irradiation is investigated in detail. As the dose accumulates, the data pattern of memory cells loading during irradiation is gradually imprinted on their background data pattern. We build a relationship between the memory cell's static noise margin (SNM) and the background data, and study the influence of irradiation on the probability density function of ΔSNM, which is the difference between two data sides' SNMs, to discuss the reason for pattern imprinting. Finally, we demonstrate that, for micron and deep sub-micron devices, the mechanism of pattern imprinting is the bias-dependent threshold shift of the transistor, but for a deep sub-micron device the shift results from charge trapping in the shallow trench isolation (STI) oxide rather than from the gate oxide of the micron-device. (condensed matter: structural, mechanical, and thermal properties)

  5. Pattern imprinting in deep sub-micron static random access memories induced by total dose irradiation

    Science.gov (United States)

    Zheng, Qi-Wen; Yu, Xue-Feng; Cui, Jiang-Wei; Guo, Qi; Ren, Di-Yuan; Cong, Zhong-Chao; Zhou, Hang

    2014-10-01

    Pattern imprinting in deep sub-micron static random access memories (SRAMs) during total dose irradiation is investigated in detail. As the dose accumulates, the data pattern of memory cells loading during irradiation is gradually imprinted on their background data pattern. We build a relationship between the memory cell's static noise margin (SNM) and the background data, and study the influence of irradiation on the probability density function of ΔSNM, which is the difference between two data sides' SNMs, to discuss the reason for pattern imprinting. Finally, we demonstrate that, for micron and deep sub-micron devices, the mechanism of pattern imprinting is the bias-dependent threshold shift of the transistor, but for a deep sub-micron device the shift results from charge trapping in the shallow trench isolation (STI) oxide rather than from the gate oxide of the micron-device.

  6. Flexible conductive-bridging random-access-memory cell vertically stacked with top Ag electrode, PEO, PVK, and bottom Pt electrode

    Science.gov (United States)

    Seung, Hyun-Min; Kwon, Kyoung-Cheol; Lee, Gon-Sub; Park, Jea-Gun

    2014-10-01

    Flexible conductive-bridging random-access-memory (RAM) cells were fabricated with a cross-bar memory cell stacked with a top Ag electrode, conductive polymer (poly(n-vinylcarbazole): PVK), electrolyte (polyethylene oxide: PEO), bottom Pt electrode, and flexible substrate (polyethersulfone: PES), exhibiting the bipolar switching behavior of resistive random access memory (ReRAM). The cell also exhibited bending-fatigue-free nonvolatile memory characteristics: i.e., a set voltage of 1.0 V, a reset voltage of -1.6 V, retention time of >1 × 105 s with a memory margin of 9.2 × 105, program/erase endurance cycles of >102 with a memory margin of 8.4 × 105, and bending-fatigue-free cycles of ˜1 × 103 with a memory margin (Ion/Ioff) of 3.3 × 105.

  7. Fluorescently labeled dengue viruses as probes to identify antigen-specific memory B cells by multiparametric flow cytometry.

    Science.gov (United States)

    Woda, Marcia; Mathew, Anuja

    2015-01-01

    Low frequencies of memory B cells in the peripheral blood make it challenging to measure the functional and phenotypic characteristics of this antigen experienced subset of B cells without in vitro culture. To date, reagents are lacking to measure ex vivo frequencies of dengue virus (DENV)-specific memory B cells. We wanted to explore the possibility of using fluorescently labeled DENV as probes to detect antigen-specific memory B cells in the peripheral blood of DENV immune individuals. Alexa Fluor dye-labeled DENV yielded viable virus that could be stored at -80°C for long periods of time. Using a careful gating strategy and methods to decrease non-specific binding, we were able to identify a small frequency of B cells from dengue immune individuals that bound labeled DENV. Sorted DENV(+) B cells from immune, but not naïve donors secreted antibodies that bound DENV after in vitro stimulation. Overall, Alexa Fluor dye-labeled DENVs are useful reagents to enable the detection and characterization of memory B cells in DENV immune individuals. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Radiation effect on silicon transistors in mixed neutrons-gamma environment

    Science.gov (United States)

    Assaf, J.; Shweikani, R.; Ghazi, N.

    2014-10-01

    The effects of gamma and neutron irradiations on two different types of transistors, Junction Field Effect Transistor (JFET) and Bipolar Junction Transistor (BJT), were investigated. Irradiation was performed using a Syrian research reactor (RR) (Miniature Neutron Source Reactor (MNSR)) and a gamma source (Co-60 cell). For RR irradiation, MCNP code was used to calculate the absorbed dose received by the transistors. The experimental results showed an overall decrease in the gain factors of the transistors after irradiation, and the JFETs were more resistant to the effects of radiation than BJTs. The effect of RR irradiation was also greater than that of gamma source for the same dose, which could be because neutrons could cause more damage than gamma irradiation.

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

    Science.gov (United States)

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

    2013-04-01

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

  10. A Public Database of Memory and Naive B-Cell Receptor Sequences.

    Directory of Open Access Journals (Sweden)

    William S DeWitt

    Full Text Available The vast diversity of B-cell receptors (BCR and secreted antibodies enables the recognition of, and response to, a wide range of epitopes, but this diversity has also limited our understanding of humoral immunity. We present a public database of more than 37 million unique BCR sequences from three healthy adult donors that is many fold deeper than any existing resource, together with a set of online tools designed to facilitate the visualization and analysis of the annotated data. We estimate the clonal diversity of the naive and memory B-cell repertoires of healthy individuals, and provide a set of examples that illustrate the utility of the database, including several views of the basic properties of immunoglobulin heavy chain sequences, such as rearrangement length, subunit usage, and somatic hypermutation positions and dynamics.

  11. A Public Database of Memory and Naive B-Cell Receptor Sequences.

    Science.gov (United States)

    DeWitt, William S; Lindau, Paul; Snyder, Thomas M; Sherwood, Anna M; Vignali, Marissa; Carlson, Christopher S; Greenberg, Philip D; Duerkopp, Natalie; Emerson, Ryan O; Robins, Harlan S

    2016-01-01

    The vast diversity of B-cell receptors (BCR) and secreted antibodies enables the recognition of, and response to, a wide range of epitopes, but this diversity has also limited our understanding of humoral immunity. We present a public database of more than 37 million unique BCR sequences from three healthy adult donors that is many fold deeper than any existing resource, together with a set of online tools designed to facilitate the visualization and analysis of the annotated data. We estimate the clonal diversity of the naive and memory B-cell repertoires of healthy individuals, and provide a set of examples that illustrate the utility of the database, including several views of the basic properties of immunoglobulin heavy chain sequences, such as rearrangement length, subunit usage, and somatic hypermutation positions and dynamics.

  12. Modeling of bias-induced changes of organic field-effect transistor characteristics

    NARCIS (Netherlands)

    Sharma, A.

    2011-01-01

    Organic semiconductors offer exciting possibilities in developing new types of solar cells, photodetectors, light emitting diodes and field-effect transistors. Important advantages of organic semiconducting materials over their inorganic counterparts are their chemical tunability, their low weight,

  13. Human dendritic cells sequentially matured with CD4+ T cells as a secondary signal favor CTL and long-term T memory cell responses

    Directory of Open Access Journals (Sweden)

    Thomas Simon

    2012-01-01

    Full Text Available Dendritic cells (DCs are professional antigen-presenting cells involved in the control and initiation of immune responses. In vivo, DCs exposed at the periphery to maturation stimuli migrate to lymph nodes, where they receive secondary signals from CD4+ T helper cells. These DCs become able to initiate CD8+ cytotoxic T lymphocyte (CTL responses. However, in vitro investigations concerning human monocyte-derived DCs have never focused on their functional properties after such sequential maturation. Here, we studied human DC phenotypes and functions according to this sequential exposure to maturation stimuli. As first signals, we used TNF-α/polyI:C mimicking inflammatory and pathogen stimuli and, as second signals, we compared activated CD4+ T helper cells to a combination of CD40-L/ IFN-γ. Our results show that a sequential activation with activated CD4+ T cells dramatically increased the maturation of DCs in terms of their phenotype and cytokine secretion compared to DCs activated with maturation stimuli delivered simultaneously. Furthermore, this sequential maturation led to the induction of CTL with a long-term effector and central memory phenotypes. Thus, sequential delivery of maturation stimuli, which includes CD4+ T cells, should be considered in the future to improve the induction of long-term CTL memory in DC-based immunotherapy.

  14. Human dendritic cells sequentially matured with CD4(+) T cells as a secondary signal favor CTL and long-term T memory cell responses.

    Science.gov (United States)

    Simon, Thomas; Tanguy-Royer, Séverine; Royer, Pierre-Joseph; Boisgerault, Nicolas; Frikeche, Jihane; Fonteneau, Jean-François; Grégoire, Marc

    2012-01-01

    Dendritic cells (DCs) are professional antigen-presenting cells involved in the control and initiation of immune responses. In vivo, DCs exposed at the periphery to maturation stimuli migrate to lymph nodes, where they receive secondary signals from CD4+ T helper cells. These DCs become able to initiate CD8+ cytotoxic T lymphocyte (CTL) responses. However, in vitro investigations concerning human monocyte-derived DCs have never focused on their functional properties after such sequential maturation. Here, we studied human DC phenotypes and functions according to this sequential exposure to maturation stimuli. As first signals, we used TNF-α/polyI:C mimicking inflammatory and pathogen stimuli and, as second signals, we compared activated CD4+ T helper cells to a combination of CD40-L/ IFN-γ. Our results show that a sequential activation with activated CD4+ T cells dramatically increased the maturation of DCs in terms of their phenotype and cytokine secretion compared to DCs activated with maturation stimuli delivered simultaneously. Furthermore, this sequential maturation led to the induction of CTL with a long-term effector and central memory phenotypes. Thus, sequential delivery of maturation stimuli, which includes CD4+ T cells, should be considered in the future to improve the induction of long-term CTL memory in DC-based immunotherapy.

  15. Accessory signals in T-T cell interactions between antigen- and alloantigen-specific, human memory T cells generated in vitro

    DEFF Research Database (Denmark)

    Odum, N; Ryder, L P; Georgsen, J

    1990-01-01

    The potential of activated HLA class II-positive T cells as antigen-/alloantigen-presenting cells remains controversial. In our model system we use in vitro-primed, HLA class II-specific T cells of the memory T-cell phenotype, CD4+, CD29+ (4B4+), and CD45RO+ (UCHL-1). We have previously shown......), or a calcium ionophore (A23187) enabled Ta to elicit alloantigen-specific memory T-cell responses and to present purified protein derivative (PPD) to PPD-specific T-cell lines. The addition of irradiated, Epstein-Barr virus-transformed B-cell lines (EBV-LCL) (but not their supernatants) had a similar but less...

  16. Selective Memory to Apoptotic Cell-Derived Self-Antigens with Implications for Systemic Lupus Erythematosus Development.

    Science.gov (United States)

    Duhlin, Amanda; Chen, Yunying; Wermeling, Fredrik; Sedimbi, Saikiran K; Lindh, Emma; Shinde, Rahul; Halaby, Marie Jo; Kaiser, Ylva; Winqvist, Ola; McGaha, Tracy L; Karlsson, Mikael C I

    2016-10-01

    Autoimmune diseases are characterized by pathogenic immune responses to self-antigens. In systemic lupus erythematosus (SLE), many self-antigens are found in apoptotic cells (ACs), and defects in removal of ACs from the body are linked to a risk for developing SLE. This includes pathological memory that gives rise to disease flares. In this study, we investigated how memory to AC-derived self-antigens develops and the contribution of self-memory to the development of lupus-related pathology. Multiple injections of ACs without adjuvant into wild-type mice induce a transient primary autoimmune response without apparent anti-nuclear Ab reactivity or kidney pathology. Interestingly, as the transient Ab response reached baseline, a single boost injection fully recalled the immune response to ACs, and this memory response was furthermore transferable into naive mice. Additionally, the memory response contains elements of pathogenicity, accompanied by selective memory to selective Ags. Thus, we provide evidence for a selective self-memory that underlies progression of the response to self-antigens with implications for SLE development therapy. Copyright © 2016 by The American Association of Immunologists, Inc.

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

    OpenAIRE

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

    2015-01-01

    CD8(+) T cells directed against conserved viral regions elicit broad immunity against distinct influenza viruses, promote rapid virus elimination and enhanced host recovery. The influenza neuraminidase inhibitor, oseltamivir, is prescribed for therapy and prophylaxis, although it remains unclear how the drug impacts disease severity and establishment of effector and memory CD8(+) T cell immunity. We dissected the effects of oseltamivir on viral replication, inflammation, acute CD8(+) T cell r...

  18. Mechanism for resistive switching in chalcogenide-based electrochemical metallization memory cells

    Directory of Open Access Journals (Sweden)

    Fei Zhuge

    2015-05-01

    Full Text Available It has been reported that in chalcogenide-based electrochemical metallization (ECM memory cells (e.g., As2S3:Ag, GeS:Cu, and Ag2S, the metal filament grows from the cathode (e.g., Pt and W towards the anode (e.g., Cu and Ag, whereas filament growth along the opposite direction has been observed in oxide-based ECM cells (e.g., ZnO, ZrO2, and SiO2. The growth direction difference has been ascribed to a high ion diffusion coefficient in chalcogenides in comparison with oxides. In this paper, upon analysis of OFF state I–V characteristics of ZnS-based ECM cells, we find that the metal filament grows from the anode towards the cathode and the filament rupture and rejuvenation occur at the cathodic interface, similar to the case of oxide-based ECM cells. It is inferred that in ECM cells based on the chalcogenides such as As2S3:Ag, GeS:Cu, and Ag2S, the filament growth from the cathode towards the anode is due to the existence of an abundance of ready-made mobile metal ions in the chalcogenides rather than to the high ion diffusion coefficient.

  19. Freestanding Artificial Synapses Based on Laterally Proton-Coupled Transistors on Chitosan Membranes.

    Science.gov (United States)

    Liu, Yang Hui; Zhu, Li Qiang; Feng, Ping; Shi, Yi; Wan, Qing

    2015-10-07

    Freestanding synaptic transistors are fabricated on solution-processed chitosan membranes. A short-term memory to long-term memory transition is observed due to proton-related electrochemical doping under repeated pulse stimulus. Moreover, freestanding artificial synaptic devices with multiple presynaptic inputs are investigated, and spiking logic operation and logic modulation are realized. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. 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)

  1. Maintained LTP and Memory Are Lost by Zn2+ Influx into Dentate Granule Cells, but Not Ca2+ Influx.

    Science.gov (United States)

    Takeda, Atsushi; Tamano, Haruna; Hisatsune, Marie; Murakami, Taku; Nakada, Hiroyuki; Fujii, Hiroaki

    2018-02-01

    The idea that maintained LTP and memory are lost by either increase in intracellular Zn 2+ in dentate granule cells or increase in intracellular Ca 2+ was examined to clarify significance of the increases induced by excess synapse excitation. Both maintained LTP and space memory were impaired by injection of high K + into the dentate gyrus, but rescued by co-injection of CaEDTA, which blocked high K + -induced increase in intracellular Zn 2+ but not high K + -induced increase in intracellular Ca 2+ . High K + -induced disturbances of LTP and intracellular Zn 2+ are rescued by co-injection of 6-cyano-7-nitroquinoxakine-2,3-dione, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist, but not by co-injection of blockers of NMDA receptors, metabotropic glutamate receptors, and voltage-dependent calcium channels. Furthermore, AMPA impaired maintained LTP and the impairment was also rescued by co-injection of CaEDTA, which blocked increase in intracellular Zn 2+ , but not increase in intracellular Ca 2+ . NMDA and glucocorticoid, which induced Zn 2+ release from the internal stores, did not impair maintained LTP. The present study indicates that increase in Zn 2+ influx into dentate granule cells through AMPA receptors loses maintained LTP and memory. Regulation of Zn 2+ influx into dentate granule cells is more critical for not only memory acquisition but also memory retention than that of Ca 2+ influx.

  2. In vivo proliferation of naïve and memory influenza-specific CD8(+) T cells

    DEFF Research Database (Denmark)

    Flynn, K J; Riberdy, J M; Christensen, Jan Pravsgaard

    1999-01-01

    days. The greatly expanded population of CD8(+)NPP(+) memory T cells in the lymphoid tissue of secondarily challenged mice declines progressively in mean prevalence over the ensuing 100 days, despite the fact that at least some of these lymphocytes continue to cycle. The recall of cell......The virus-specific CD8(+) T cell response has been analyzed through the development, effector, and recovery phases of primary and secondary influenza pneumonia. Apparently, most, if not all, memory T cells expressing clonotypic receptors that bind a tetrameric complex of influenza nucleoprotein (NP......)(366-374) peptide+H-2D(b) (NPP) are induced to divide during the course of this localized respiratory infection. The replicative phase of the recall response ends about the time that virus can no longer be recovered from the lung, whereas some primary CD8(+)NPP(+) T cells may proliferate for a few more...

  3. History-dependent excitability as a single-cell substrate of transient memory for information discrimination.

    Directory of Open Access Journals (Sweden)

    Fabiano Baroni

    Full Text Available Neurons react differently to incoming stimuli depending upon their previous history of stimulation. This property can be considered as a single-cell substrate for transient memory, or context-dependent information processing: depending upon the current context that the neuron "sees" through the subset of the network impinging on it in the immediate past, the same synaptic event can evoke a postsynaptic spike or just a subthreshold depolarization. We propose a formal definition of History-Dependent Excitability (HDE as a measure of the propensity to firing in any moment in time, linking the subthreshold history-dependent dynamics with spike generation. This definition allows the quantitative assessment of the intrinsic memory for different single-neuron dynamics and input statistics. We illustrate the concept of HDE by considering two general dynamical mechanisms: the passive behavior of an Integrate and Fire (IF neuron, and the inductive behavior of a Generalized Integrate and Fire (GIF neuron with subthreshold damped oscillations. This framework allows us to characterize the sensitivity of different model neurons to the detailed temporal structure of incoming stimuli. While a neuron with intrinsic oscillations discriminates equally well between input trains with the same or different frequency, a passive neuron discriminates better between inputs with different frequencies. This suggests that passive neurons are better suited to rate-based computation, while neurons with subthreshold oscillations are advantageous in a temporal coding scheme. We also address the influence of intrinsic properties in single-cell processing as a function of input statistics, and show that intrinsic oscillations enhance discrimination sensitivity at high input rates. Finally, we discuss how the recognition of these cell-specific discrimination properties might further our understanding of neuronal network computations and their relationships to the distribution and

  4. Logarithmic current-measuring transistor circuits

    DEFF Research Database (Denmark)

    Højberg, Kristian Søe

    1967-01-01

    Describes two transistorized circuits for the logarithmic measurement of small currents suitable for nuclear reactor instrumentation. The logarithmic element is applied in the feedback path of an amplifier, and only one dual transistor is used as logarithmic diode and temperature compensating...... transistor. A simple one-amplifier circuit is compared with a two-amplifier system. The circuits presented have been developed in connexion with an amplifier using a dual m.o.s. transistor input stage with diode-protected gates....

  5. Distributed amplifier using Josephson vortex flow transistors

    International Nuclear Information System (INIS)

    McGinnis, D.P.; Beyer, J.B.; Nordman, J.E.

    1986-01-01

    A wide-band traveling wave amplifier using vortex flow transistors is proposed. A vortex flow transistor is a long Josephson junction used as a current controlled voltage source. The dual nature of this device to the field effect transistor is exploited. A circuit model of this device is proposed and a distributed amplifier utilizing 50 vortex flow transistors is predicted to have useful gain to 100 GHz