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Sample records for flash memory cell

  1. A hybrid ferroelectric-flash memory cells

    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.

  2. Radiation damage in flash memory cells

    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

  3. NAND flash memory technologies

    Aritome, Seiichi

    2016-01-01

    This book discusses basic and advanced NAND flash memory technologies, including the principle of NAND flash, memory cell technologies, multi-bits cell technologies, scaling challenges of memory cell, reliability, and 3-dimensional cell as the future technology. Chapter 1 describes the background and early history of NAND flash. The basic device structures and operations are described in Chapter 2. Next, the author discusses the memory cell technologies focused on scaling in Chapter 3, and introduces the advanced operations for multi-level cells in Chapter 4. The physical limitations for scaling are examined in Chapter 5, and Chapter 6 describes the reliability of NAND flash memory. Chapter 7 examines 3-dimensional (3D) NAND flash memory cells and discusses the pros and cons in structure, process, operations, scalability, and performance. In Chapter 8, challenges of 3D NAND flash memory are dis ussed. Finally, in Chapter 9, the author summarizes and describes the prospect of technologies and market for the fu...

  4. Memristive behavior in a junctionless flash memory cell

    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.

  5. Non Volatile Flash Memory Radiation Tests

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

    2012-01-01

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

  6. MAP Detector for Flash Memory Without Accessing the Interfering Cells

    Yassine, Hachem; Badiu, Mihai Alin; Coon, Justin P.

    2018-01-01

    the latency cost of accessing the interfering cells. Specifically, we exploit the fact that adjacent cells have common interferers by modeling the system as an appropriate hidden Markov model. Then we use the sum-product (message-passing) algorithm to compute the marginal posterior probabilities of the stored...

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

    Richter, Detlev

    2014-01-01

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

  8. A Durable Flash Memory Search Tree

    Clay III, James; Wortman, Kevin

    2012-01-01

    We consider the task of optimizing the B-tree data structure, used extensively in operating systems and databases, for sustainable usage on multi-level flash memory. Empirical evidence shows that this new flash memory tree, or FM Tree, extends the operational lifespan of each block of flash memory by a factor of roughly 27 to 70 times, while still supporting logarithmic-time search tree operations.

  9. Method for programming a flash memory

    Brosky, Alexander R.; Locke, William N.; Maher, Conrado M.

    2016-08-23

    A method of programming a flash memory is described. The method includes partitioning a flash memory into a first group having a first level of write-protection, a second group having a second level of write-protection, and a third group having a third level of write-protection. The write-protection of the second and third groups is disabled using an installation adapter. The third group is programmed using a Software Installation Device.

  10. FPGA Flash Memory High Speed Data Acquisition

    Gonzalez, April

    2013-01-01

    The purpose of this research is to design and implement a VHDL ONFI Controller module for a Modular Instrumentation System. The goal of the Modular Instrumentation System will be to have a low power device that will store data and send the data at a low speed to a processor. The benefit of such a system will give an advantage over other purchased binary IP due to the capability of allowing NASA to re-use and modify the memory controller module. To accomplish the performance criteria of a low power system, an in house auxiliary board (Flash/ADC board), FPGA development kit, debug board, and modular instrumentation board will be jointly used for the data acquisition. The Flash/ADC board contains four, 1 MSPS, input channel signals and an Open NAND Flash memory module with an analog to digital converter. The ADC, data bits, and control line signals from the board are sent to an Microsemi/Actel FPGA development kit for VHDL programming of the flash memory WRITE, READ, READ STATUS, ERASE, and RESET operation waveforms using Libero software. The debug board will be used for verification of the analog input signal and be able to communicate via serial interface with the module instrumentation. The scope of the new controller module was to find and develop an ONFI controller with the debug board layout designed and completed for manufacture. Successful flash memory operation waveform test routines were completed, simulated, and tested to work on the FPGA board. Through connection of the Flash/ADC board with the FPGA, it was found that the device specifications were not being meet with Vdd reaching half of its voltage. Further testing showed that it was the manufactured Flash/ADC board that contained a misalignment with the ONFI memory module traces. The errors proved to be too great to fix in the time limit set for the project.

  11. A low-voltage flash memory cell utilizing the gate-injection program/erase method with a recessed channel structure

    Wu Dake; Huang Ru; Wang Pengfei; Tang Poren; Wang Yangyuan

    2008-01-01

    In this paper, a low-voltage recessed channel SONOS flash memory using the gate-injection program/erase method is proposed and investigated for NAND application. It is shown that the proposed flash memory can achieve 8 V lower programming voltage compared with planar flash memory, due to the effective capacitance coupling and the electric-field enhancement by combining the recessed channel structure and the gate-injection program/erase method. In addition, more than 30% larger threshold voltage window and improved short channel effects can be obtained in the proposed flash memory

  12. Transparent Flash Memory using Single Ta2O5 Layer for both Charge Trapping and Tunneling Dielectrics

    Hota, Mrinal Kanti

    2017-06-08

    We report reproducible multibit transparent flash memory in which a single solution-derived Ta2O5 layer is used simultaneously as charge trapping and tunneling layer. This is different from conventional flash cells, where two different dielectric layers are typically used. Under optimized programming/erasing operations, the memory device shows excellent programmable memory characteristics with a maximum memory window of ~10 V. Moreover, the flash memory device shows a stable 2-bit memory performance, good reliability, including data retention for more than 104 sec and endurance performance for more than 100 cycles. The use of a common charge trapping and tunneling layer can simplify advanced flash memory fabrication.

  13. Transparent Flash Memory using Single Ta2O5 Layer for both Charge Trapping and Tunneling Dielectrics

    Hota, Mrinal Kanti; Alshammari, Fwzah H.; Salama, Khaled N.; Alshareef, Husam N.

    2017-01-01

    We report reproducible multibit transparent flash memory in which a single solution-derived Ta2O5 layer is used simultaneously as charge trapping and tunneling layer. This is different from conventional flash cells, where two different dielectric layers are typically used. Under optimized programming/erasing operations, the memory device shows excellent programmable memory characteristics with a maximum memory window of ~10 V. Moreover, the flash memory device shows a stable 2-bit memory performance, good reliability, including data retention for more than 104 sec and endurance performance for more than 100 cycles. The use of a common charge trapping and tunneling layer can simplify advanced flash memory fabrication.

  14. Space Qualified, Radiation Hardened, Dense Monolithic Flash Memory, Phase II

    National Aeronautics and Space Administration — Space Micro proposes to build a radiation hardened by design (RHBD) flash memory, using a modified version of our RH-eDRAM Memory Controller to solve all the single...

  15. Error Characterization and Mitigation for 16Nm MLC NAND Flash Memory Under Total Ionizing Dose Effect

    Li, Yue (Inventor); Bruck, Jehoshua (Inventor)

    2018-01-01

    A data device includes a memory having a plurality of memory cells configured to store data values in accordance with a predetermined rank modulation scheme that is optional and a memory controller that receives a current error count from an error decoder of the data device for one or more data operations of the flash memory device and selects an operating mode for data scrubbing in accordance with the received error count and a program cycles count.

  16. The imaging performance of flash memory masks characterized with AIMS

    van Setten, Eelco; Wismans, Onno; Grim, Kees; Finders, Jo; Dusa, Mircea; Birkner, Robert; Richter, Rigo; Scherübl, Thomas

    2009-04-01

    Flash memory is an important driver of the lithography roadmap, with its dramatic acceleration in dimensional shrink, pushing for ever smaller feature sizes. The introduction of hyper-NA immersion lithography has brought the 45nm node and below within reach for memory makers using single exposure. At these feature sizes mask topology and the material properties of the film stack on the mask play an important role on imaging performance. Furthermore, the break up of the array pitch regularity in the NAND-type flash memory cell by two thick wordlines and a central space, leads to feature-center placement (overlay) errors, that are inherent to the design. An integral optimization approach is needed to mitigate these effects and to control both the CD and placement errors tightly. In this paper we will show that aerial image measurements at mask-level are useful for characterizing the gate layer of a NAND-Flash design before exposure. The aerial image measurements are performed with the AIMSTM 45-193i. and compared to CD measurements on the wafer obtained with an XT:1900Gi hyper-NA immersion system. An excellent correlation is demonstrated for feature-center placement errors and CD variations across the mask (see Figure 1) for several features in the gate layer down to 40nm half pitch. This shows the potential to use aerial image measurements at mask-level in combination with correction techniques on the photomask, like the CDC200 tool in combination with exposure tool correction techniques, such as DoseMapperTM, to improve both across field and across wafer CD uniformity of critical layers.

  17. Flash memory in embedded Java programs

    Korsholm, Stephan Erbs

    This paper introduces a Java execution environment with the capability for storing constant heap data in Flash, thus saving valuable RAM. The extension is motivated by the structure of three industrial applications which demonstrate the need for storing constant data in Flash on small embedded...

  18. Recovery of Flash Memories for Reliable Mobile Storages

    Daesung Moon

    2010-01-01

    Full Text Available As the mobile appliance is applied to many ubiquitous services and the importance of the information stored in it is increased, the security issue to protect the information becomes one of the major concerns. However, most previous researches focused only on the communication security, not the storage security. Especially, a flash memory whose operational characteristics are different from those of HDD is used increasingly as a storage device for the mobile appliance because of its resistance to physical shock and lower power requirement. In this paper, we propose a flash memory management scheme targeted for guaranteeing the data integrity of the mobile storage. By maintaining the old data specified during the recovery window, we can recover the old data when the mobile appliance is attacked. Also, to reduce the storage requirement for the recovery, we restrict the number of versions to be copied, called Degree of Integrity (DoI. Especially, we consider both the reclaim efficiency and the wear leveling which is a unique characteristic of the flash memory. Based on the performance evaluation, we confirm that the proposed scheme can be acceptable to many applications as a flash memory management scheme for improving data integrity.

  19. Multi-Level Bitmap Indexes for Flash Memory Storage

    Wu, Kesheng; Madduri, Kamesh; Canon, Shane

    2010-07-23

    Due to their low access latency, high read speed, and power-efficient operation, flash memory storage devices are rapidly emerging as an attractive alternative to traditional magnetic storage devices. However, tests show that the most efficient indexing methods are not able to take advantage of the flash memory storage devices. In this paper, we present a set of multi-level bitmap indexes that can effectively take advantage of flash storage devices. These indexing methods use coarsely binned indexes to answer queries approximately, and then use finely binned indexes to refine the answers. Our new methods read significantly lower volumes of data at the expense of an increased disk access count, thus taking full advantage of the improved read speed and low access latency of flash devices. To demonstrate the advantage of these new indexes, we measure their performance on a number of storage systems using a standard data warehousing benchmark called the Set Query Benchmark. We observe that multi-level strategies on flash drives are up to 3 times faster than traditional indexing strategies on magnetic disk drives.

  20. Flash memory management system and method utilizing multiple block list windows

    Chow, James (Inventor); Gender, Thomas K. (Inventor)

    2005-01-01

    The present invention provides a flash memory management system and method with increased performance. The flash memory management system provides the ability to efficiently manage and allocate flash memory use in a way that improves reliability and longevity, while maintaining good performance levels. The flash memory management system includes a free block mechanism, a disk maintenance mechanism, and a bad block detection mechanism. The free block mechanism provides efficient sorting of free blocks to facilitate selecting low use blocks for writing. The disk maintenance mechanism provides for the ability to efficiently clean flash memory blocks during processor idle times. The bad block detection mechanism provides the ability to better detect when a block of flash memory is likely to go bad. The flash status mechanism stores information in fast access memory that describes the content and status of the data in the flash disk. The new bank detection mechanism provides the ability to automatically detect when new banks of flash memory are added to the system. Together, these mechanisms provide a flash memory management system that can improve the operational efficiency of systems that utilize flash memory.

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

    Matsui, Chihiro; Kinoshita, Reika; Takeuchi, Ken

    2018-04-01

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

  2. Effects of tunnel oxide process on SONOS flash memory characteristics

    Li, Dong Hua; Park, Il Han; Yun, Jang-Gn; Park, Byung-Gook

    2010-01-01

    In this paper, various process conditions of tunnel oxides are applied in SONOS flash memory to investigate their effects on charge transport during the program/erase operations. We focus the key point of analysis on Fermi-level (E F ) variation at the interface of silicon substrate and tunnel oxide. The Si-O chemical bonding information which describes the interface oxidation states at the Si/SiO 2 is obtained by the core-level X-ray photoelectron spectroscopy (XPS). Moreover, relative E F position is determined by measuring the Si 2p energy shift from XPS spectrums. Experimental results from memory characteristic measurement show that MTO tunnel oxide structure exhibits faster erase speed, and larger memory window during P/E cycle compared to FTO and RTO tunnel oxide structures. Finally, we examine long-term charge retention characteristic and find that the memory windows of all the capacitors remain wider than 2 V after 10 5 s.

  3. A novel sourceline voltage compensation circuit for embedded NOR flash memory

    Zhang Shengbo; Yang Guangjun; Hu Jian; Xiao Jun

    2014-01-01

    A novel sourceline voltage compensation circuit for program operation in embedded flash memory is presented. With the sourceline voltage compensation circuit, the charge pump can modulate the output voltage according to the number of cells to be programmed with data “0”. So the IR drop on the sourceline decoding path is compensated, and a stable sourceline voltage can be obtained. In order to reduce the power dissipation in program operation, a bit-inversion program circuit is adopted. By using the bit-inversion program circuit, the cells programmed to data “0” are limited to half of the bits of a write data word, thus power dissipation in program operation is greatly reduced. A 1.8-V 8 × 64-kbits embedded NOR flash memory employing the two circuits has been integrated using a GSMC 0.18-μm 4-poly 4-metal CMOS process. (semiconductor integrated circuits)

  4. Ensuring the Trust of NAND Flash Memory: Going Beyond the Published Interface

    2016-03-17

    SSDs), in order to evaluate advanced Flash memory devices that are not available as individual components on the open market and for which no...measurable changes due to memory cell stress is shown in Figure 3 for a 42 nm SLC Samsung K9K8G08U0D device. Two logical pages were characterized... Samsung K9K8G08U0D device to change from a logical ‘0’ to a logical ‘1’ were measured. Three bits on the page were then fully programmed and erased

  5. Graphene-quantum-dot nonvolatile charge-trap flash memories

    Sin Joo, Soong; Kim, Jungkil; Seok Kang, Soo; Kim, Sung; Choi, Suk-Ho; Won Hwang, Sung

    2014-01-01

    Nonvolatile flash-memory capacitors containing graphene quantum dots (GQDs) of 6, 12, and 27 nm average sizes (d) between SiO 2 layers for use as charge traps have been prepared by sequential processes: ion-beam sputtering deposition (IBSD) of 10 nm SiO 2 on a p-type wafer, spin-coating of GQDs on the SiO 2 layer, and IBSD of 20 nm SiO 2 on the GQD layer. The presence of almost a single array of GQDs at a distance of ∼13 nm from the SiO 2 /Si wafer interface is confirmed by transmission electron microscopy and photoluminescence. The memory window estimated by capacitance–voltage curves is proportional to d for sweep voltages wider than  ± 3 V, and for d = 27 nm the GQD memories show a maximum memory window of 8 V at a sweep voltage of  ± 10 V. The program and erase speeds are largest at d = 12 and 27 nm, respectively, and the endurance and data-retention properties are the best at d = 27 nm. These memory behaviors can be attributed to combined effects of edge state and quantum confinement. (papers)

  6. Optimal proximity correction: application for flash memory design

    Chen, Y. O.; Huang, D. L.; Sung, K. T.; Chiang, J. J.; Yu, M.; Teng, F.; Chu, Lung; Rey, Juan C.; Bernard, Douglas A.; Li, Jiangwei; Li, Junling; Moroz, V.; Boksha, Victor V.

    1998-06-01

    Proximity Correction is the technology for which the most of IC manufacturers are committed already. The final intended result of correction is affected by many factors other than the optical characteristics of the mask-stepper system, such as photoresist exposure, post-exposure bake and development parameters, etch selectivity and anisotropy, and underlying topography. The most advanced industry and research groups already reported immediate need to consider wafer topography as one of the major components during a Proximity Correction procedure. In the present work we are discussing the corners rounding effect (which eventually cause electrical leakage) observed for the elements of Poly2 layer for a Flash Memory Design. It was found that the rounding originated by three- dimensional effects due to variation of photoresist thickness resulting from the non-planar substrate. Our major goal was to understand the reasons and correct corner rounding. As a result of this work highly effective layout correction methodology was demonstrated and manufacturable Depth Of Focus was achieved. Another purpose of the work was to demonstrate complete integration flow for a Flash Memory Design based on photolithography; deposition/etch; ion implantation/oxidation/diffusion; and device simulators.

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

    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

  8. Immersion and dry lithography monitoring for flash memories (after develop inspection and photo cell monitor) using a darkfield imaging inspector with advanced binning technology

    Parisi, P.; Mani, A.; Perry-Sullivan, C.; Kopp, J.; Simpson, G.; Renis, M.; Padovani, M.; Severgnini, C.; Piacentini, P.; Piazza, P.; Beccalli, A.

    2009-12-01

    After-develop inspection (ADI) and photo-cell monitoring (PM) are part of a comprehensive lithography process monitoring strategy. Capturing defects of interest (DOI) in the lithography cell rather than at later process steps shortens the cycle time and allows for wafer re-work, reducing overall cost and improving yield. Low contrast DOI and multiple noise sources make litho inspection challenging. Broadband brightfield inspectors provide the highest sensitivity to litho DOI and are traditionally used for ADI and PM. However, a darkfield imaging inspector has shown sufficient sensitivity to litho DOI, providing a high-throughput option for litho defect monitoring. On the darkfield imaging inspector, a very high sensitivity inspection is used in conjunction with advanced defect binning to detect pattern issues and other DOI and minimize nuisance defects. For ADI, this darkfield inspection methodology enables the separation and tracking of 'color variation' defects that correlate directly to CD variations allowing a high-sampling monitor for focus excursions, thereby reducing scanner re-qualification time. For PM, the darkfield imaging inspector provides sensitivity to critical immersion litho defects at a lower cost-of-ownership. This paper describes litho monitoring methodologies developed and implemented for flash devices for 65nm production and 45nm development using the darkfield imaging inspector.

  9. Asymmetric Programming: A Highly Reliable Metadata Allocation Strategy for MLC NAND Flash Memory-Based Sensor Systems

    Huang, Min; Liu, Zhaoqing; Qiao, Liyan

    2014-01-01

    While the NAND flash memory is widely used as the storage medium in modern sensor systems, the aggressive shrinking of process geometry and an increase in the number of bits stored in each memory cell will inevitably degrade the reliability of NAND flash memory. In particular, it's critical to enhance metadata reliability, which occupies only a small portion of the storage space, but maintains the critical information of the file system and the address translations of the storage system. Metadata damage will cause the system to crash or a large amount of data to be lost. This paper presents Asymmetric Programming, a highly reliable metadata allocation strategy for MLC NAND flash memory storage systems. Our technique exploits for the first time the property of the multi-page architecture of MLC NAND flash memory to improve the reliability of metadata. The basic idea is to keep metadata in most significant bit (MSB) pages which are more reliable than least significant bit (LSB) pages. Thus, we can achieve relatively low bit error rates for metadata. Based on this idea, we propose two strategies to optimize address mapping and garbage collection. We have implemented Asymmetric Programming on a real hardware platform. The experimental results show that Asymmetric Programming can achieve a reduction in the number of page errors of up to 99.05% with the baseline error correction scheme. PMID:25310473

  10. Asymmetric Programming: A Highly Reliable Metadata Allocation Strategy for MLC NAND Flash Memory-Based Sensor Systems

    Min Huang

    2014-10-01

    Full Text Available While the NAND flash memory is widely used as the storage medium in modern sensor systems, the aggressive shrinking of process geometry and an increase in the number of bits stored in each memory cell will inevitably degrade the reliability of NAND flash memory. In particular, it’s critical to enhance metadata reliability, which occupies only a small portion of the storage space, but maintains the critical information of the file system and the address translations of the storage system. Metadata damage will cause the system to crash or a large amount of data to be lost. This paper presents Asymmetric Programming, a highly reliable metadata allocation strategy for MLC NAND flash memory storage systems. Our technique exploits for the first time the property of the multi-page architecture of MLC NAND flash memory to improve the reliability of metadata. The basic idea is to keep metadata in most significant bit (MSB pages which are more reliable than least significant bit (LSB pages. Thus, we can achieve relatively low bit error rates for metadata. Based on this idea, we propose two strategies to optimize address mapping and garbage collection. We have implemented Asymmetric Programming on a real hardware platform. The experimental results show that Asymmetric Programming can achieve a reduction in the number of page errors of up to 99.05% with the baseline error correction scheme.

  11. Heavy Ion Irradiation Fluence Dependence for Single-Event Upsets of NAND Flash Memory

    Chen, Dakai; Wilcox, Edward; Ladbury, Raymond; Kim, Hak; Phan, Anthony; Seidleck, Christina; LaBel, Kenneth

    2016-01-01

    We investigated the single-event effect (SEE) susceptibility of the Micron 16 nm NAND flash, and found the single-event upset (SEU) cross section varied inversely with fluence. The SEU cross section decreased with increasing fluence. We attribute the effect to the variable upset sensitivities of the memory cells. The current test standards and procedures assume that SEU follow a Poisson process and do not take into account the variability in the error rate with fluence. Therefore, heavy ion irradiation of devices with variable upset sensitivity distribution using typical fluence levels may underestimate the cross section and on-orbit event rate.

  12. Flash!

    Schilling, Govert

    2002-04-01

    About three times a day our sky flashes with a powerful pulse of gamma ray bursts (GRB), invisible to human eyes but not to astronomers' instruments. The sources of this intense radiation are likely to be emitting, within the span of seconds or minutes, more energy than the sun will in its entire 10 billion years of life. Where these bursts originate, and how they come to have such incredible energies, is a mystery scientists have been trying to solve for three decades. The phenomenon has resisted study -- the flashes come from random directions in space and vanish without trace -- until very recently. In what could be called a cinematic conflation of Flash Gordon and The Hunt for Red October, Govert Schilling's Flash!: The Hunt for the Biggest Explosions in the Universe describes the exciting and ever-changing field of GRB research. Based on interviews with leading scientists, Flash! provides an insider's account of the scientific challenges involved in unravelling the enigmatic nature of GRBs. A science writer who has followed the drama from the very start, Schilling describes the ambition and jealousy, collegiality and competition, triumph and tragedy, that exists among those who have embarked on this recherche. Govert Schilling is a Dutch science writer and astronomy publicist. He is a contributing editor of Sky and Telescope magazine, and regularly writes for the news sections of Science and New Scientist. Schilling is the astronomy writer for de Volkskrant, one of the largest national daily newspapers in The Netherlands, and frequently talks about the Universe on Dutch radio broadcasts. He is the author of more than twenty popular astronomy books, and hundreds of newspaper and magazine articles on astronomy.

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

    Guo, Jiarong

    2017-04-01

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

  14. Doped SbTe phase change material in memory cells

    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)

  15. Highly scalable 3-D NAND-NOR hybrid-type dual bit per cell flash memory devices with an additional cut-off gate

    Cho, Seongjae; Shim, Wonbo; Park, Ilhan; Kim, Yoon; Park, Byunggook

    2010-01-01

    In this work, a nonvolatile memory (NVM) device of novel structure in 3 dimensions is introduced, and its operation physics is validated. It is based on a pillar structure in which two identical storage nodes are located for dual-bit operation. The two storage nodes on neighboring pillars are controlled by using one common control gate so that the space between silicon pillars can be further reduced. For compatibility with conventional memory operations, an additional cut-off gate is constructed under the common control gate. This is considered as the ultimate form for a 3-D nonvolatile memory device based on a double-gate structure. The underlying physics is explained, and the operational schemes are validated in various aspects by using a numerical device simulation. Also, critical issues in device design for higher reliability are discussed.

  16. Flash Memory Reliability: Read, Program, and Erase Latency Versus Endurance Cycling

    Heidecker, Jason

    2010-01-01

    This report documents the efforts and results of the fiscal year (FY) 2010 NASA Electronic Parts and Packaging Program (NEPP) task for nonvolatile memory (NVM) reliability. This year's focus was to measure latency (read, program, and erase) of NAND Flash memories and determine how these parameters drift with erase/program/read endurance cycling.

  17. A Fault-Tolerant Radiation-Robust Mass Storage Concept for Highly Scaled Flash Memory

    Fuchs, Cristian M.; Trinitis, Carsten; Appel, Nicolas; Langer, Martin

    2015-09-01

    Future spacemissions will require vast amounts of data to be stored and processed aboard spacecraft. While satisfying operational mission requirements, storage systems must guarantee data integrity and recover damaged data throughout the mission. NAND-flash memories have become popular for space-borne high performance mass memory scenarios, though future storage concepts will rely upon highly scaled flash or other memory technologies. With modern flash memory, single bit erasure coding and RAID based concepts are insufficient. Thus, a fully run-time configurable, high performance, dependable storage concept, requiring a minimal set of logic or software. The solution is based on composite erasure coding and can be adjusted for altered mission duration or changing environmental conditions.

  18. Heavy Ion Irradiation Fluence Dependence for Single-Event Upsets in a NAND Flash Memory

    Chen, Dakai; Wilcox, Edward; Ladbury, Raymond L.; Kim, Hak; Phan, Anthony; Seidleck, Christina; Label, Kenneth

    2016-01-01

    We investigated the single-event effect (SEE) susceptibility of the Micron 16 nm NAND flash, and found that the single-event upset (SEU) cross section varied inversely with cumulative fluence. We attribute the effect to the variable upset sensitivities of the memory cells. Furthermore, the effect impacts only single cell upsets in general. The rate of multiple-bit upsets remained relatively constant with fluence. The current test standards and procedures assume that SEU follow a Poisson process and do not take into account the variability in the error rate with fluence. Therefore, traditional SEE testing techniques may underestimate the on-orbit event rate for a device with variable upset sensitivity.

  19. Enhanced memory performance by tailoring the microstructural evolution of (ZrO{sub 2}){sub 0.6}(SiO{sub 2}){sub 0.4} charge trapping layer in the nanocrystallites-based charge trap flash memory cells

    Tang, Zhenjie; Xu, Hanni; Xia, Yidong; Yin, Jiang; Li, Aidong; Liu, Zhiguo [Nanjing University, Department of Materials Science and Engineering and National Laboratory of Solid State Microstructures, Nanjing (China); Zhu, Xinhua [Nanjing University, Department of Physics and National and Laboratory of Solid State Microstructures, Nanjing (China); Yan, Feng [Nanjing University, School of Electronics Science and Engineering, Nanjing (China)

    2012-07-15

    ZrO{sub 2} nanocrystallites based charge trap memory cells by incorporating a (ZrO{sub 2}){sub 0.6}(SiO{sub 2}){sub 0.4} film as a charge trapping layer and amorphous Al{sub 2}O{sub 3} as tunneling and blocking layer were prepared and investigated. The precipitation reaction in charge trapping layer forming ZrO{sub 2} nanocrystallites during rapid thermal annealing was investigated by transmission electron microscopy. The density and size of ZrO{sub 2} nanocrystallites are the critical factors for controlling the charge storage characteristics. The ZrO{sub 2} nanocrystallites based memory cells after postannealing at 800 C for 60 s exhibit the best electrical characteristics and a low charge loss {proportional_to}5 % after 10{sup 5} write/erase cycles operation. (orig.)

  20. 76 FR 40931 - In the Matter of Certain Flash Memory and Products Containing Same; Notice of Commission...

    2011-07-12

    ... INTERNATIONAL TRADE COMMISSION [Inv. No. 337-TA-685] In the Matter of Certain Flash Memory and... for importation, and the sale within the United States after importation of certain flash memory and... other agreements, written or oral, express or implied, between the parties concerning the subject matter...

  1. Modeling of SONOS Memory Cell Erase Cycle

    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.

  2. Threshold voltage variation depending on single grain boundary and stored charges in an adjacent cell for vertical silicon–oxide–nitride–oxide–silicon NAND flash memory

    Oh, Hyeongwan; Kim, Jiwon; Baek, Rock-Hyun; Lee, Jeong-Soo

    2018-04-01

    The effects of single grain boundary (SGB) position and stored electron charges in an adjacent cell in silicon–oxide–nitride–oxide–silicon (SONOS) structures on the variations of threshold voltage (V th) were investigated using technology computer-aided design (TCAD) simulation. As the bit line voltage increases, the SGB position causing the maximum V th variation was shifted from the center to the source side in the channel, owing to the drain-induced grain barrier lowering effect. When the SGB is located in the spacer region, the potential interaction from both the SGB and the stored electron charges in the adjacent cell becomes significant and thus resulting in larger V th variation. In contrast, when the SGB is located at the center of the channel, the peak position of potential barrier is shifted to the center, so that the influence of the adjacent cell is diminished. As the gate length is scaled down to 20 nm, the influence of stored charges in adjacent cells becomes significant, resulting in larger V th variations.

  3. Environmental Effects on Data Retention in Flash Cells

    Katz, Rich; Flowers, David; Bergevin, Keith

    2017-01-01

    Flash technology is being utilized in fuzed munition applications and, based on the development of digital logic devices in the commercial world, usage of flash technology will increase. Antifuse technology, prevalent in non-volatile field programmable gate arrays (FPGAs), will eventually be phased out as new devices have not been developed for approximately a decade. The reliance on flash technology presents a long-term reliability issue for both DoD and NASA safety- and mission-critical applications. A thorough understanding of the data retention failure modes and statistics associated with Flash data retention is of vital concern to the fuze safety community. A key retention parameter for a flash cell is the threshold voltage (VTH), which is an indirect indicator of the amount of charge stored on the cells floating gate. This paper will present the results of our on-going tests: long-term storage at 150 C for a small population of devices, neutron radiation exposure, electrostatic discharge (ESD) testing, and the trends of large populations (over 300 devices for each condition) exposed to three difference temperatures: 25 C, 125 C, and 150 C.

  4. Performance analysis of three-dimensional-triple-level cell and two-dimensional-multi-level cell NAND flash hybrid solid-state drives

    Sakaki, Yukiya; Yamada, Tomoaki; Matsui, Chihiro; Yamaga, Yusuke; Takeuchi, Ken

    2018-04-01

    In order to improve performance of solid-state drives (SSDs), hybrid SSDs have been proposed. Hybrid SSDs consist of more than two types of NAND flash memories or NAND flash memories and storage-class memories (SCMs). However, the cost of hybrid SSDs adopting SCMs is more expensive than that of NAND flash only SSDs because of the high bit cost of SCMs. This paper proposes unique hybrid SSDs with two-dimensional (2D) horizontal multi-level cell (MLC)/three-dimensional (3D) vertical triple-level cell (TLC) NAND flash memories to achieve higher cost-performance. The 2D-MLC/3D-TLC hybrid SSD achieves up to 31% higher performance than the conventional 2D-MLC/2D-TLC hybrid SSD. The factors of different performance between the proposed hybrid SSD and the conventional hybrid SSD are analyzed by changing its block size, read/write/erase latencies, and write unit of 3D-TLC NAND flash memory, by means of a transaction-level modeling simulator.

  5. Space Qualified, Radiation Hardened, Dense Monolithic Flash Memory, Phase I

    National Aeronautics and Space Administration — Radiation hardened nonvolatile memories for space is still primarily confined to EEPROM. There is high density effective or cost effective NVM solution available to...

  6. MoO3 trapping layers with CF4 plasma treatment in flash memory applications

    Kao, Chuyan Haur; Chen, Hsiang; Chen, Su-Zhien; Chen, Chian Yu; Lo, Kuang-Yu; Lin, Chun Han

    2014-01-01

    Highlights: • MoO 3 -based flash memories have been fabricated. • CF4 plasma treatment could enhance good memory performance. • Material analyses confirm that plasma treatment eliminated defects. • Fluorine atoms might fix the dangling bonds. - Abstract: In this research, we used MoO 3 with CF 4 plasma treatment as charge trapping layer in metal-oxide-high-k -oxide-Si-type memory. We analyzed material properties and electrical characteristics with multiple analyses. The plasma treatment could increase the trapping density, reduce the leakage current, expand band gap, and passivate the defect to enhance the memory performance. The MoO 3 charge trapping layer memory with suitable CF 4 plasma treatment is promising for future nonvolatile memory applications

  7. Quick-low-density parity check and dynamic threshold voltage optimization in 1X nm triple-level cell NAND flash memory with comprehensive analysis of endurance, retention-time, and temperature variation

    Doi, Masafumi; Tokutomi, Tsukasa; Hachiya, Shogo; Kobayashi, Atsuro; Tanakamaru, Shuhei; Ning, Sheyang; Ogura Iwasaki, Tomoko; Takeuchi, Ken

    2016-08-01

    NAND flash memory’s reliability degrades with increasing endurance, retention-time and/or temperature. After a comprehensive evaluation of 1X nm triple-level cell (TLC) NAND flash, two highly reliable techniques are proposed. The first proposal, quick low-density parity check (Quick-LDPC), requires only one cell read in order to accurately estimate a bit-error rate (BER) that includes the effects of temperature, write and erase (W/E) cycles and retention-time. As a result, 83% read latency reduction is achieved compared to conventional AEP-LDPC. Also, W/E cycling is extended by 100% compared with conventional Bose-Chaudhuri-Hocquenghem (BCH) error-correcting code (ECC). The second proposal, dynamic threshold voltage optimization (DVO) has two parts, adaptive V Ref shift (AVS) and V TH space control (VSC). AVS reduces read error and latency by adaptively optimizing the reference voltage (V Ref) based on temperature, W/E cycles and retention-time. AVS stores the optimal V Ref’s in a table in order to enable one cell read. VSC further improves AVS by optimizing the voltage margins between V TH states. DVO reduces BER by 80%.

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

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

    2008-01-01

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

  9. Modeling of apparent activation energy and lifetime estimation in NAND flash memory

    Lee, Kyunghwan; Shin, Hyungcheol; Kang, Myounggon; Hwang, Yuchul

    2015-01-01

    Misunderstanding apparent activation energy (E aa ) can cause serious error in lifetime predictions. In this paper, the E aa is investigated for sub 20 nm NAND flash memory. In a high-temperature (HT) regime, the interface trap (N it ) recovery mechanism has the greatest impact on the charge loss. However, the values of E aa and E a(Nit) have a wide difference. Also, the lifetime of the device cannot be estimated by the Arrhenius model due to the E aa roll-off behavior. For the first time, we reveal the origin of abnormal characteristics on E aa and derive a mathematical formula for E aa as a function of each E a(mechanism) in NAND flash memory. Using the proposed E aa equation, the accurate lifetime for the device is estimated. (paper)

  10. Cuinse2 Thin Film For Solar Cell By Flash Evaporation

    A.H. Soepardjo

    2009-01-01

    Deposition of thin films for material solar cell CuInSe2 are relatively simple. In this research mainly focused on the use of flash evaporation method, and the material created can then be characterized by optical and electrical properties. The optical characterization is done by X-ray Diffraction (XRD), Energy Dispersive Spectroscopy (EDS), and transmission and reflection by UV-VIS spectrophotometry. Electrical characterization is done by utilizing the Hall effect equipment. From these chara...

  11. TID and SEE Response of an Advanced Samsung 4G NAND Flash Memory

    Oldham, Timothy R.; Friendlich, M.; Howard, J. W.; Berg, M. D.; Kim, H. S.; Irwin, T. L.; LaBel, K. A.

    2007-01-01

    Initial total ionizing dose (TID) and single event heavy ion test results are presented for an unhardened commercial flash memory, fabricated with 63 nm technology. Results are that the parts survive to a TID of nearly 200 krad (SiO2), with a tractable soft error rate of about 10(exp -l2) errors/bit-day, for the Adams Ten Percent Worst Case Environment.

  12. Characterization of nitride hole lateral transport in a charge trap flash memory by using a random telegraph signal method

    Liu, Yu-Heng; Jiang, Cheng-Min; Lin, Hsiao-Yi; Wang, Tahui; Tsai, Wen-Jer; Lu, Tao-Cheng; Chen, Kuang-Chao; Lu, Chih-Yuan

    2017-07-01

    We use a random telegraph signal method to investigate nitride trapped hole lateral transport in a charge trap flash memory. The concept of this method is to utilize an interface oxide trap and its associated random telegraph signal as an internal probe to detect a local channel potential change resulting from nitride charge lateral movement. We apply different voltages to the drain of a memory cell and vary a bake temperature in retention to study the electric field and temperature dependence of hole lateral movement in a nitride. Thermal energy absorption by trapped holes in lateral transport is characterized. Mechanisms of hole lateral transport in retention are investigated. From the measured and modeled results, we find that thermally assisted trap-to-band tunneling is a major trapped hole emission mechanism in nitride hole lateral transport.

  13. Analysis of the X-ray microbeam test result of the flash memories

    Yan Yihua; Ding Lili; Chen Wei; Guo Hongxia; Guo Xiaoqiang; Lin Dongsheng; Zhang Keying; Zhang Fengqi; Deng Yuliang; Fan Ruyu

    2013-01-01

    Background: The failure phenomenon is difficult to analyze for the flash memories when the whole chip is exposed to irradiation since both the memory array and the peripheral circuits might be degraded. Purpose: In order to detect the radiation susceptibility and corresponding phenomenon of the related circuits that included in the flash memories, the X-ray microbeam is used as the radiation source instead of 60 Co. Methods: The failure phenomenon is studied respectively when the memory array, decoder circuits, the charge pump circuits as well as the I/O circuits are exposed to radiation. The errors are mapped according to the logical address and the failure mechanism is analyzed based on the circuits. Results: Irradiated on the memory .array win lead to regularly distributed 0→1 bit flips, while only 1→0 are found when the row decoder is under exposure. Degradation of the charge pump circuits would lead to the erase/program functional failure. Conclusions: The results suggest that the X-ray microbeam radiation test is a good method for detecting the radiation susceptibility of the integrated circuits that contains lots of circuit modules. (authors)

  14. An integrated lithography concept with application on 45-nm ½ pitch flash memory devices

    Dusa, Mircea; Engelen, Andre; Finders, Jo

    2006-03-01

    It is well accepted to judge imaging capability of an exposure tool primarily on printing equal line-spaces, at a minimum ½ pitch. Further on, combining line-space minimum ½ pitches with scanner maximum NA, defines the process k I. From a lithographer viewpoint, flash memory device is the perfect candidate to achieve lowest k I lithography for a given NA. This is justified by flash layout specific, with regular and relative simple 1-D topology of the critical layers that look like line-space gratings. In reality, flash layout presents a subtle topology and cannot be considered a simple 1-D line-space problem. Uniqueness to flash layout is the array-end zones, where pattern regularity is broken up by features with dimensions and separation of n x ½ pitch, where n is an integer number that we used in this work to manipulate litho process latitudes. Integrated lithography concept seeks to tweak flash pattern details and tune it with scanner control parameters. We introduce feature-center placement through focus and dose as the metric to characterize a cross-coupling phenomena occurring between adjacent features located at array-end of typical flash poly wordline layer. We comparedthe metric behavior with usual litho process window parameters and identified interactions with scanner CDU control parameters. We show how feature-center placement errors are direct functions of optical and physical characteristics of mask materials, attenuated PSM or binary, and of layout array-end topology. Imaging at extreme low-k I, effects from layout specifics and mask materials are best characterized by full vector, rigorous EM simulation, instead of scalar approach, typically used for OPC treatment. Predicted CDU performance of 1.2NA scanner, based on integrated lithography concept, matched very well the experimental results in printing 45nm ½ pitch flash wordline layer. Results show that 1.2NA scanner, operating at 0.28 k I could be an effective lithography solution for 45nm

  15. Memory T Cell Migration

    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...

  16. Characterizations of MoTiO5 flash memory devices with post-annealing

    Kao, Chyuan Haur; Chen, Hsiang; Chen, Su Zhien; Chen, Yu Jie; Chu, Yu Cheng

    2014-01-01

    In this study, high-K MoTiO 5 dielectrics were applied as charge trapping layers in fabricated metal-oxide-high-K MoTiO 5 -oxide-Si-type memory devices. Among the applied MoTiO 5 trapping layer treatment conditions, annealing at 900 °C yielded devices that exhibited superior memory performance, such as a larger memory window and faster programming/erasing speed. Multiple material analyses, namely X-ray diffraction, X-ray photoelectron spectroscopy, and atomic force microscopy, confirmed that annealing at 900 °C can improve the material quality as a result of crystallization. The fabricated MoTiO 5 -based memory devices show potential for future commercial memory device applications. - Highlights: • MoTiO5-based flash memories have been fabricated. • MoTiO5 trapping layers could be formed by co-sputtering. • MoTiO5 layers with annealing exhibited a good memory performance. • Multiple material analyses confirm that annealing enhanced crystallization

  17. Chemical-Vapor-Deposited Graphene as Charge Storage Layer in Flash Memory Device

    W. J. Liu

    2016-01-01

    Full Text Available We demonstrated a flash memory device with chemical-vapor-deposited graphene as a charge trapping layer. It was found that the average RMS roughness of block oxide on graphene storage layer can be significantly reduced from 5.9 nm to 0.5 nm by inserting a seed metal layer, which was verified by AFM measurements. The memory window is 5.6 V for a dual sweep of ±12 V at room temperature. Moreover, a reduced hysteresis at the low temperature was observed, indicative of water molecules or −OH groups between graphene and dielectric playing an important role in memory windows.

  18. Fault-tolerant NAND-flash memory module for next-generation scientific instruments

    Lange, Tobias; Michel, Holger; Fiethe, Björn; Michalik, Harald; Walter, Dietmar

    2015-10-01

    Remote sensing instruments on today's space missions deliver a high amount of data which is typically evaluated on ground. Especially for deep space missions the telemetry downlink is very limited which creates the need for the scientific evaluation and thereby a reduction of data volume already on-board the spacecraft. A demanding example is the Polarimetric and Helioseismic Imager (PHI) instrument on Solar Orbiter. To enable on-board offline processing for data reduction, the instrument has to be equipped with a high capacity memory module. The module is based on non-volatile NAND-Flash technology, which requires more advanced operation than volatile DRAM. Unlike classical mass memories, the module is integrated into the instrument and allows readback of data for processing. The architecture and safe operation of such kind of memory module is described in the following paper.

  19. 75 FR 82071 - In the Matter of Certain Flash Memory Chips and Products Containing Same; Notice of Commission...

    2010-12-29

    ... Memory Chips and Products Containing Same; Notice of Commission Decision Not To Review the ALJ's Final... flash memory chips and products containing the same by reason of infringement of various claims of... practices or exploits the '877 patent does not exist, nor is such an industry in the process of being...

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

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

    2008-03-01

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

  1. The influence of Ti doping and annealing on Ce_2Ti_2O_7 flash memory devices

    Kao, Chyuan Haur; Chen, Su Zhien; Luo, Yang; Chiu, Wang Ting; Chiu, Shih Wei; Chen, I Chien; Lin, Chan-Yu; Chen, Hsiang

    2017-01-01

    Highlights: • Ce_2Ti_2O_7 flash memories have been fabricated. • Material quality can be improved by annealing. • The memory performance can be enhanced by Ti doping. • Ti doping and annealing can reinforce crystallization. - Abstract: In this research, a CeO_2 film with Ti doping was used as a trapping layer in metal oxide high-K-oxide-Si (MOHOS)-type memory devices. Since incorporation of Ti atoms into the film could fix dangling bonds and defects, the Ce_2Ti_2O_7 trapping layer with annealing treatment could have a larger memory window and a faster programming/erasing speed. To confirm the origin, multiple material analyses indicate that annealing at an appropriate temperature and Ti doping could enhance crystallization. The Ce_2Ti_2O_7-based memory device is promising for future industrial flash memory applications.

  2. Fast neutron irradiation tests of flash memories used in space environment at the ISIS spallation neutron source

    C. Andreani

    2018-02-01

    Full Text Available This paper presents a neutron accelerated study of soft errors in advanced electronic devices used in space missions, i.e. Flash memories performed at the ChipIr and VESUVIO beam lines at the ISIS spallation neutron source. The two neutron beam lines are set up to mimic the space environment spectra and allow neutron irradiation tests on Flash memories in the neutron energy range above 10 MeV and up to 800 MeV. The ISIS neutron energy spectrum is similar to the one occurring in the atmospheric as well as in space and planetary environments, with intensity enhancements varying in the range 108- 10 9 and 106- 10 7 respectively. Such conditions are suitable for the characterization of the atmospheric, space and planetary neutron radiation environments, and are directly applicable for accelerated tests of electronic components as demonstrated here in benchmark measurements performed on flash memories.

  3. Fast neutron irradiation tests of flash memories used in space environment at the ISIS spallation neutron source

    Andreani, C.; Senesi, R.; Paccagnella, A.; Bagatin, M.; Gerardin, S.; Cazzaniga, C.; Frost, C. D.; Picozza, P.; Gorini, G.; Mancini, R.; Sarno, M.

    2018-02-01

    This paper presents a neutron accelerated study of soft errors in advanced electronic devices used in space missions, i.e. Flash memories performed at the ChipIr and VESUVIO beam lines at the ISIS spallation neutron source. The two neutron beam lines are set up to mimic the space environment spectra and allow neutron irradiation tests on Flash memories in the neutron energy range above 10 MeV and up to 800 MeV. The ISIS neutron energy spectrum is similar to the one occurring in the atmospheric as well as in space and planetary environments, with intensity enhancements varying in the range 108- 10 9 and 106- 10 7 respectively. Such conditions are suitable for the characterization of the atmospheric, space and planetary neutron radiation environments, and are directly applicable for accelerated tests of electronic components as demonstrated here in benchmark measurements performed on flash memories.

  4. Performance improvement of charge trap flash memory by using a composition-modulated high-k trapping layer

    Tang Zhen-Jie; Li Rong; Yin Jiang

    2013-01-01

    A composition-modulated (HfO 2 ) x (Al 2 O3) 1−x charge trapping layer is proposed for charge trap flash memory by controlling the Al atom content to form a peak and valley shaped band gap. It is found that the memory device using the composition-modulated (HfO 2 ) x (Al 2 O 3 ) 1−x as the charge trapping layer exhibits a larger memory window of 11.5 V, improves data retention even at high temperature, and enhances the program/erase speed. Improvements of the memory characteristics are attributed to the special band-gap structure resulting from the composition-modulated trapping layer. Therefore, the composition-modulated charge trapping layer may be useful in future nonvolatile flash memory device application. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

  5. Cuinse2 Thin Film For Solar Cell By Flash Evaporation

    A.H. Soepardjo

    2009-11-01

    Full Text Available Deposition of thin films for material solar cell CuInSe2 are relatively simple. In this research mainly focused on the use of flash evaporation method, and the material created can then be characterized by optical and electrical properties. The optical characterization is done by X-ray Diffraction (XRD, Energy Dispersive Spectroscopy (EDS, and transmission and reflection by UV-VIS spectrophotometry. Electrical characterization is done by utilizing the Hall effect equipment. From these characterization, the atomic structure, absorption coefficient, energy gap, material type, composition of each elements and the mobility of CuInSe2 can be measured and determined. During process evaporation were carried out at substrate temperatures the range between 20ºC-415ºC.

  6. PIYAS-Proceeding to Intelligent Service Oriented Memory Allocation for Flash Based Data Centric Sensor Devices in Wireless Sensor Networks

    Sanam Shahla Rizvi

    2009-12-01

    Full Text Available Flash memory has become a more widespread storage medium for modern wireless devices because of its effective characteristics like non-volatility, small size, light weight, fast access speed, shock resistance, high reliability and low power consumption. Sensor nodes are highly resource constrained in terms of limited processing speed, runtime memory, persistent storage, communication bandwidth and finite energy. Therefore, for wireless sensor networks supporting sense, store, merge and send schemes, an efficient and reliable file system is highly required with consideration of sensor node constraints. In this paper, we propose a novel log structured external NAND flash memory based file system, called Proceeding to Intelligent service oriented memorY Allocation for flash based data centric Sensor devices in wireless sensor networks (PIYAS. This is the extended version of our previously proposed PIYA [1]. The main goals of the PIYAS scheme are to achieve instant mounting and reduced SRAM space by keeping memory mapping information to a very low size of and to provide high query response throughput by allocation of memory to the sensor data by network business rules. The scheme intelligently samples and stores the raw data and provides high in-network data availability by keeping the aggregate data for a longer period of time than any other scheme has done before. We propose effective garbage collection and wear-leveling schemes as well. The experimental results show that PIYAS is an optimized memory management scheme allowing high performance for wireless sensor networks.

  7. PIYAS-proceeding to intelligent service oriented memory allocation for flash based data centric sensor devices in wireless sensor networks.

    Rizvi, Sanam Shahla; Chung, Tae-Sun

    2010-01-01

    Flash memory has become a more widespread storage medium for modern wireless devices because of its effective characteristics like non-volatility, small size, light weight, fast access speed, shock resistance, high reliability and low power consumption. Sensor nodes are highly resource constrained in terms of limited processing speed, runtime memory, persistent storage, communication bandwidth and finite energy. Therefore, for wireless sensor networks supporting sense, store, merge and send schemes, an efficient and reliable file system is highly required with consideration of sensor node constraints. In this paper, we propose a novel log structured external NAND flash memory based file system, called Proceeding to Intelligent service oriented memorY Allocation for flash based data centric Sensor devices in wireless sensor networks (PIYAS). This is the extended version of our previously proposed PIYA [1]. The main goals of the PIYAS scheme are to achieve instant mounting and reduced SRAM space by keeping memory mapping information to a very low size of and to provide high query response throughput by allocation of memory to the sensor data by network business rules. The scheme intelligently samples and stores the raw data and provides high in-network data availability by keeping the aggregate data for a longer period of time than any other scheme has done before. We propose effective garbage collection and wear-leveling schemes as well. The experimental results show that PIYAS is an optimized memory management scheme allowing high performance for wireless sensor networks.

  8. Sentinel 2 MMFU: The first European Mass Memory System Based on NAND-Flash Storage Technology

    Staehle, M.; Cassel, M.; Lonsdorfer, U.; Gliem, F.; Walter, D.; Fichna, T.

    2011-08-01

    Sentinel-2 is the multispectral optical mission of the EU-ESA GMES (Global Monitoring for Environment and Security) program, currently under development by Astrium-GmbH in Friedrichshafen (Germany) for a launch in 2013. The mission features a 490 Mbit/s optical sensor operating at high duty cycles, requiring in turn a large 2.4 Tbit on-board storage capacity.The required storage capacity motivated the selection of the NAND-Flash technology which was already secured by a lengthy period (2004-2009) of detailed testing, analysis and qualification by Astrium GmbH, IDA and ESTEC. The mass memory system is currently being realized by Astrium GmbH.

  9. An Analysis of MARSIS Radar Flash Memory Data from Lunae Planum, Mars: Searching for Subsurface Structures.

    Caprarelli, G.; Orosei, R.; Mastrogiuseppe, M.; Cartacci, M.

    2017-12-01

    Lunae Planum is a Martian plain measuring approximately 1000 km in width and 2000 km in length, centered at coordinates 294°E-11°N. MOLA elevations range from +2500 m to +500 m in the south, gently sloping northward to -500 m. The plain is part of a belt of terrains located between the southern highlands and the northern lowlands, that are transitional in character (e.g., by elevation, age and morphology). These transitional terrains are poorly understood, in part because of their relative lack of major geomorphological features. They record however a very significant part of Mars's geologic history. The most evident features on Lunae Planum's Hesperian surface are regularly spaced, longitudinally striking, wrinkle ridges. These indicate the presence of blind thrust faults cutting through thick stacks of layers of volcanic or sedimentary rocks. The presence of fluidized ejecta craters scattered all over the region suggests also the presence of ice or volatiles in the subsurface. In a preliminary study of Lunae Planum's subsurface we used the Mars Express ground penetrating radar MARSIS dataset [1], in order to detect reflectors that could indicate the presence of fault planes or layering. Standard radargrams however, provided no evidence of changes in value of dielectric constant that could indicate possible geologic discontinuities or stratification of physically diverse materials. We thus started a new investigation based on processing of raw MARSIS data. Here we report on the preliminary results of this study. We searched the MARSIS archive for raw data stored in flash memory. When operating with flash storage, the radar collects 2 frequency bands along-track covering a distance = 100-250 km, depending on the orbiter altitude [2]. We found flash memory data from 24 orbits over the area. We processed the data focusing radar returns in off-nadir directions, to maximize the likelihood of detecting sloping subsurface structures, including those striking parallel

  10. High performance SONOS flash memory with in-situ silicon nanocrystals embedded in silicon nitride charge trapping layer

    Lim, Jae-Gab; Yang, Seung-Dong; Yun, Ho-Jin; Jung, Jun-Kyo; Park, Jung-Hyun; Lim, Chan; Cho, Gyu-seok; Park, Seong-gye; Huh, Chul; Lee, Hi-Deok; Lee, Ga-Won

    2018-02-01

    In this paper, SONOS-type flash memory device with highly improved charge-trapping efficiency is suggested by using silicon nanocrystals (Si-NCs) embedded in silicon nitride (SiNX) charge trapping layer. The Si-NCs were in-situ grown by PECVD without additional post annealing process. The fabricated device shows high program/erase speed and retention property which is suitable for multi-level cell (MLC) application. Excellent performance and reliability for MLC are demonstrated with large memory window of ∼8.5 V and superior retention characteristics of 7% charge loss for 10 years. High resolution transmission electron microscopy image confirms the Si-NC formation and the size is around 1-2 nm which can be verified again in X-ray photoelectron spectroscopy (XPS) where pure Si bonds increase. Besides, XPS analysis implies that more nitrogen atoms make stable bonds at the regular lattice point. Photoluminescence spectra results also illustrate that Si-NCs formation in SiNx is an effective method to form deep trap states.

  11. Total Ionizing Dose Influence on the Single Event Effect Sensitivity in Samsung 8Gb NAND Flash Memories

    Edmonds, Larry D.; Irom, Farokh; Allen, Gregory R.

    2017-08-01

    A recent model provides risk estimates for the deprogramming of initially programmed floating gates via prompt charge loss produced by an ionizing radiation environment. The environment can be a mixture of electrons, protons, and heavy ions. The model requires several input parameters. This paper extends the model to include TID effects in the control circuitry by including one additional parameter. Parameters intended to produce conservative risk estimates for the Samsung 8 Gb SLC NAND flash memory are given, subject to some qualifications.

  12. Al203 thin films on Silicon and Germanium substrates for CMOS and flash memory applications

    Gopalan, Sundararaman; Dutta, Shibesh; Ramesh, Sivaramakrishnan; Prathapan, Ragesh; Sreehari G., S.

    2017-07-01

    As scaling of device dimensions has continued, it has become necessary to replace traditional SiO2 with high dielectric constant materials in the conventional CMOS devices. In addition, use of metal gate electrodes and Germanium substrates may have to be used in order to address leakage and mobility issues. Al2O3 is one of the potential candidates both for CMOS and as a blocking dielectric for Flash memory applications owing to its low leakage. In this study, the effects of sputtering conditions and post-deposition annealing conditions on the electrical and reliability characteristics of MOS capacitors using Al2O3 films on Si and Ge substrates with Aluminium gate electrodes have been presented. It was observed that higher sputtering power resulted in larger flat-band voltage (Vfb) shifts, more hysteresis, higher interface state density (Dit) and a poorer reliability. Wit was also found that while a short duration high temperature annealing improves film characteristics, a long duration anneal even at 800C was found to be detrimental to MOS characteristics. Finally, the electronic conduction mechanism in Al2O3 films was also studied. It was observed that the conduction mechanism varied depending on the annealing condition, thickness of film and electric field.

  13. Atomic-layer deposited IrO2 nanodots for charge-trap flash-memory devices

    Choi, Sangmoo; Cha, Young-Kwan; Seo, Bum-Seok; Park, Sangjin; Park, Ju-Hee; Shin, Sangmin; Seol, Kwang Soo; Park, Jong-Bong; Jung, Young-Soo; Park, Youngsoo; Park, Yoondong; Yoo, In-Kyeong; Choi, Suk-Ho

    2007-01-01

    Charge-trap flash- (CTF) memory structures have been fabricated by employing IrO 2 nanodots (NDs) grown by atomic-layer deposition. A band of isolated IrO 2 NDs of about 3 nm lying almost parallel to Si/SiO 2 interface is confirmed by transmission electron microscopy and x-ray photoelectron spectroscopy. The memory device with IrO 2 NDs shows much larger capacitance-voltage (C-V) hysteresis and memory window compared with the control sample without IrO 2 NDs. After annealing at 800 deg. C for 20 min, the ND device shows almost no change in the width of C-V hysteresis and the ND distribution. These results indicate that the IrO 2 NDs embedded in SiO 2 can be utilized as thermally stable, discrete charge traps, promising for metal oxide-ND-based CTF memory devices

  14. Simple flash evaporator for making thin films of compounds

    Hemanadhan, M.; Bapanayya, Ch.; Agarwal, S. C. [Department of Physics, Indian Institute of Technology, Kanpur 208016 (India)

    2010-07-15

    A simple and compact arrangement for flash evaporation is described. It uses a cell phone vibrator for powder dispensing that can be incorporated into a vacuum deposition chamber without any major alterations. The performance of the flash evaporation system is checked by making thin films of the optical memory chalcogenide glass Ge{sub 2}Sb{sub 2}Te{sub 5} (GST). Energy dispersive x-ray analysis shows that the flash evaporation preserves the stoichiometry in thin films.

  15. Human sensory-evoked responses differ coincident with either "fusion-memory" or "flash-memory", as shown by stimulus repetition-rate effects

    Baird Bill

    2006-02-01

    Full Text Available Abstract Background: A new method has been used to obtain human sensory evoked-responses whose time-domain waveforms have been undetectable by previous methods. These newly discovered evoked-responses have durations that exceed the time between the stimuli in a continuous stream, thus causing an overlap which, up to now, has prevented their detection. We have named them "A-waves", and added a prefix to show the sensory system from which the responses were obtained (visA-waves, audA-waves, somA-waves. Results: When A-waves were studied as a function of stimulus repetition-rate, it was found that there were systematic differences in waveshape at repetition-rates above and below the psychophysical region in which the sensation of individual stimuli fuse into a continuity. The fusion phenomena is sometimes measured by a "Critical Fusion Frequency", but for this research we can only identify a frequency-region [which we call the STZ (Sensation-Transition Zone]. Thus, the A-waves above the STZ differed from those below the STZ, as did the sensations. Study of the psychophysical differences in auditory and visual stimuli, as shown in this paper, suggest that different stimulus features are detected, and remembered, at stimulation rates above and below STZ. Conclusion: The results motivate us to speculate that: 1 Stimulus repetition-rates above the STZ generate waveforms which underlie "fusion-memory" whereas rates below the STZ show neuronal processing in which "flash-memory" occurs. 2 These two memories differ in both duration and mechanism, though they may occur in the same cell groups. 3 The differences in neuronal processing may be related to "figure" and "ground" differentiation. We conclude that A-waves provide a novel measure of neural processes that can be detected on the human scalp, and speculate that they may extend clinical applications of evoked response recordings. If A-waves also occur in animals, it is likely that A-waves will provide

  16. Human sensory-evoked responses differ coincident with either "fusion-memory" or "flash-memory", as shown by stimulus repetition-rate effects

    Jewett, Don L; Hart, Toryalai; Larson-Prior, Linda J; Baird, Bill; Olson, Marram; Trumpis, Michael; Makayed, Katherine; Bavafa, Payam

    2006-01-01

    Background: A new method has been used to obtain human sensory evoked-responses whose time-domain waveforms have been undetectable by previous methods. These newly discovered evoked-responses have durations that exceed the time between the stimuli in a continuous stream, thus causing an overlap which, up to now, has prevented their detection. We have named them "A-waves", and added a prefix to show the sensory system from which the responses were obtained (visA-waves, audA-waves, somA-waves). Results: When A-waves were studied as a function of stimulus repetition-rate, it was found that there were systematic differences in waveshape at repetition-rates above and below the psychophysical region in which the sensation of individual stimuli fuse into a continuity. The fusion phenomena is sometimes measured by a "Critical Fusion Frequency", but for this research we can only identify a frequency-region [which we call the STZ (Sensation-Transition Zone)]. Thus, the A-waves above the STZ differed from those below the STZ, as did the sensations. Study of the psychophysical differences in auditory and visual stimuli, as shown in this paper, suggest that different stimulus features are detected, and remembered, at stimulation rates above and below STZ. Conclusion: The results motivate us to speculate that: 1) Stimulus repetition-rates above the STZ generate waveforms which underlie "fusion-memory" whereas rates below the STZ show neuronal processing in which "flash-memory" occurs. 2) These two memories differ in both duration and mechanism, though they may occur in the same cell groups. 3) The differences in neuronal processing may be related to "figure" and "ground" differentiation. We conclude that A-waves provide a novel measure of neural processes that can be detected on the human scalp, and speculate that they may extend clinical applications of evoked response recordings. If A-waves also occur in animals, it is likely that A-waves will provide new methods for

  17. Program scheme using common source lines in channel stacked NAND flash memory with layer selection by multilevel operation

    Kim, Do-Bin; Kwon, Dae Woong; Kim, Seunghyun; Lee, Sang-Ho; Park, Byung-Gook

    2018-02-01

    To obtain high channel boosting potential and reduce a program disturbance in channel stacked NAND flash memory with layer selection by multilevel (LSM) operation, a new program scheme using boosted common source line (CSL) is proposed. The proposed scheme can be achieved by applying proper bias to each layer through its own CSL. Technology computer-aided design (TCAD) simulations are performed to verify the validity of the new method in LSM. Through TCAD simulation, it is revealed that the program disturbance characteristics is effectively improved by the proposed scheme.

  18. In2Ga2ZnO7 oxide semiconductor based charge trap device for NAND flash memory

    Hwang, Eun Suk; Kim, Jun Shik; Jeon, Seok Min; Lee, Seung Jun; Jang, Younjin; Cho, Deok-Yong; Hwang, Cheol Seong

    2018-04-01

    The programming characteristics of charge trap flash memory device adopting amorphous In2Ga2ZnO7 (a-IGZO) oxide semiconductors as channel layer were evaluated. Metal-organic chemical vapor deposition (MOCVD) and RF-sputtering processes were used to grow a 45 nm thick a-IGZO layer on a 20 nm thick SiO2 (blocking oxide)/p++-Si (control gate) substrate, where 3 nm thick atomic layer deposited Al2O3 (tunneling oxide) and 5 nm thick low-pressure CVD Si3N4 (charge trap) layers were intervened between the a-IGZO and substrate. Despite the identical stoichiometry and other physicochemical properties of the MOCVD and sputtered a-IGZO, a much faster programming speed of MOCVD a-IGZO was observed. A comparable amount of oxygen vacancies was found in both MOCVD and sputtered a-IGZO, confirmed by x-ray photoelectron spectroscopy and bias-illumination-instability test measurements. Ultraviolet photoelectron spectroscopy analysis revealed a higher Fermi level (E F) of the MOCVD a-IGZO (∼0.3 eV) film than that of the sputtered a-IGZO, which could be ascribed to the higher hydrogen concentration in the MOCVD a-IGZO film. Since the programming in a flash memory device is governed by the tunneling of electrons from the channel to charge trapping layer, the faster programming performance could be the result of a higher E F of MOCVD a-IGZO.

  19. Radiation hard memory cell and array thereof

    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

  20. 3D NAND Flash Based on Planar Cells

    Andrea Silvagni

    2017-10-01

    Full Text Available In this article, the transition from 2D NAND to 3D NAND is first addressed, and the various 3D NAND architectures are compared. The article carries out a comparison of 3D NAND architectures that are based on a “punch-and-plug” process—with gate-all-around (GAA cell devices—against architectures that are based on planar cell devices. The differences and similarities between the two classes of architectures are highlighted. The differences between architectures using floating-gate (FG and charge-trap (CT devices are also considered. Although the current production of 3D NAND is based on GAA cell devices, it is suggested that architectures with planar cell devices could also be viable for mass production.

  1. Simulation of trapping properties of high κ material as the charge storage layer for flash memory application

    Yeo, Yee Ngee; Wang Yingqian; Samanta, Santanu Kumar; Yoo, Won Jong; Samudra, Ganesh; Gao, Dongyue; Chong, Chee Ching

    2006-01-01

    We investigated the trapping properties of high κ material as the charge storage layer in non-volatile flash memory devices using a two-dimensional device simulator, Medici. The high κ material is sandwiched between two silicon oxide layers, resulting in the Silicon-Oxide-High κ-Oxide-Silicon (SOHOS) structure. The trap energy levels of the bulk electron traps in high κ material were determined. The programming and erasing voltage and time using Fowler Nordheim tunneling were estimated by simulation. The effect of deep level traps on erasing was investigated. Also, the effect of bulk traps density, thickness of block oxide and thickness of high κ material on the threshold voltage of the device was simulated

  2. Multi-layered metal nanocrystals in a sol-gel spin-on-glass matrix for flash memory applications

    Huang, Meiyu Stella [Department of Chemical and Biomolecular Engineering, National University of Singapore, Block E5, 4 Engineering Drive 4, 117576 (Singapore); Globalfoundries Singapore Pte Ltd, 60 Woodlands Industrial Park D, 738406 (Singapore); Suresh, Vignesh [Department of Chemical and Biomolecular Engineering, National University of Singapore, Block E5, 4 Engineering Drive 4, 117576 (Singapore); Agency for Science, Technology and Research - A*Star, Institute of Materials Research and Engineering (IMRE), #08-03, 2 Fusionopolis Way, Innovis, 138634 (Singapore); Chan, Mei Yin [School of Materials Science and Engineering (MSE), Nanyang Technological University (NTU), 50 Nanyang Avenue, 639798 (Singapore); Ma, Yu Wei [Globalfoundries Singapore Pte Ltd, 60 Woodlands Industrial Park D, 738406 (Singapore); Lee, Pooi See [School of Materials Science and Engineering (MSE), Nanyang Technological University (NTU), 50 Nanyang Avenue, 639798 (Singapore); Krishnamoorthy, Sivashankar [Agency for Science, Technology and Research - A*Star, Institute of Materials Research and Engineering (IMRE), #08-03, 2 Fusionopolis Way, Innovis, 138634 (Singapore); Science et Analyse des Materiaux Unit (SAM), Centre de Recherche Public-Gabriel Lippmann, 41, rue du Brill, Belvaux, 4422 (Luxembourg); Srinivasan, M.P., E-mail: srinivasan.madapusi@rmit.edu.au [Department of Chemical and Biomolecular Engineering, National University of Singapore, Block E5, 4 Engineering Drive 4, 117576 (Singapore); School of Engineering, RMIT University, Building 10, Level 11, Room 14, 376-392 Swanston Street, Melbourne, Victoria, 3001 (Australia)

    2017-01-15

    A simple and low-cost process of embedding metal nanocrystals as charge storage centers within a dielectric is demonstrated to address leakage issues associated with the scaling of the tunnelling oxide in flash memories. Metal nanocrystals with high work functions (nickel, platinum and palladium) were prepared as embedded species in methyl siloxane spin-on-glass (SOG) films on silicon substrates. Sub-10 nm-sized, well-isolated, uniformly distributed, multi-layered nanocrystals with high particle densities (10{sup 11}–10{sup 12} cm{sup −2}) were formed in the films by thermal curing of the spin-coated SOG films containing the metal precursors. Capacitance-Voltage measurements performed on metal-insulator-semiconductor capacitors with the SOG films show that the presence of metal nanocrystals enhanced the memory window of the films to 2.32 V at low operating voltages of ±5 V. These SOG films demonstrated the ability to store both holes and electrons. Capacitance-time measurements show good charge retention of more than 75% after 10{sup 4} s of discharging. This work demonstrates the applicability of the low-cost in-situ sol-gel preparation in contrast to conventional methods that involve multiple and expensive processing steps. - Highlights: • Sub-10 nm sized, well-isolated, uniformly distributed nanoparticle based charge trap memories. • Preparation of multi-layer high work function metal nanocrystals at low cost. • Large memory window of 2.32 V at low operating voltages of ±5 V. • Good charge retention of more than 90% and 75% after 10{sup 3} and 10{sup 4} s of discharging respectively. • Use of a 3 nm thick tunnelling oxide in compliance with ITRS specifications.

  3. Multi-layered metal nanocrystals in a sol-gel spin-on-glass matrix for flash memory applications

    Huang, Meiyu Stella; Suresh, Vignesh; Chan, Mei Yin; Ma, Yu Wei; Lee, Pooi See; Krishnamoorthy, Sivashankar; Srinivasan, M.P.

    2017-01-01

    A simple and low-cost process of embedding metal nanocrystals as charge storage centers within a dielectric is demonstrated to address leakage issues associated with the scaling of the tunnelling oxide in flash memories. Metal nanocrystals with high work functions (nickel, platinum and palladium) were prepared as embedded species in methyl siloxane spin-on-glass (SOG) films on silicon substrates. Sub-10 nm-sized, well-isolated, uniformly distributed, multi-layered nanocrystals with high particle densities (10"1"1–10"1"2 cm"−"2) were formed in the films by thermal curing of the spin-coated SOG films containing the metal precursors. Capacitance-Voltage measurements performed on metal-insulator-semiconductor capacitors with the SOG films show that the presence of metal nanocrystals enhanced the memory window of the films to 2.32 V at low operating voltages of ±5 V. These SOG films demonstrated the ability to store both holes and electrons. Capacitance-time measurements show good charge retention of more than 75% after 10"4 s of discharging. This work demonstrates the applicability of the low-cost in-situ sol-gel preparation in contrast to conventional methods that involve multiple and expensive processing steps. - Highlights: • Sub-10 nm sized, well-isolated, uniformly distributed nanoparticle based charge trap memories. • Preparation of multi-layer high work function metal nanocrystals at low cost. • Large memory window of 2.32 V at low operating voltages of ±5 V. • Good charge retention of more than 90% and 75% after 10"3 and 10"4 s of discharging respectively. • Use of a 3 nm thick tunnelling oxide in compliance with ITRS specifications.

  4. Hot Flashes

    Hot flashes Overview Hot flashes are sudden feelings of warmth, which are usually most intense over the face, neck and chest. Your skin might redden, as if you're blushing. Hot flashes can also cause sweating, and if you ...

  5. 76 FR 55417 - In the Matter of Certain Dynamic Random Access Memory and Nand Flash Memory Devices and Products...

    2011-09-07

    ... Bldg. 3F, 2-1 Yaesu 2- chome Chuo-ku, Tokyo 104-0028, Japan. Elpida Memory (USA) Inc., 1175 Sonora..., Round Rock, TX 78682. Hewlett-Packard Company, 3000 Hanover Street, Palo Alto, CA 94304. Kingston...

  6. Improved charge trapping properties by embedded graphene oxide quantum-dots for flash memory application

    Jia, Xinlei; Yan, Xiaobing; Wang, Hong; Yang, Tao; Zhou, Zhenyu; Zhao, Jianhui

    2018-06-01

    In this work, we have investigated two kinds of charge trapping memory devices with Pd/Al2O3/ZnO/SiO2/p-Si and Pd/Al2O3/ZnO/graphene oxide quantum-dots (GOQDs)/ZnO/SiO2/p-Si structure. Compared with the single ZnO sample, the memory window of the ZnO-GOQDs-ZnO sample reaches a larger value (more than doubled) of 2.7 V under the sweeping gate voltage ± 7 V, indicating a better charge storage capability and the significant charge trapping effects by embedding the GOQDs trapping layer. The ZnO-GOQDs-ZnO devices have better date retention properties with the high and low capacitances loss of ˜ 1.1 and ˜ 6.9%, respectively, as well as planar density of the trapped charges of 1.48 × 1012 cm- 2. It is proposed that the GOQDs play an important role in the outstanding memory characteristics due to the deep quantum potential wells and the discrete distribution of the GOQDs. The long date retention time might have resulted from the high potential barrier which suppressed both the back tunneling and the leakage current. Intercalating GOQDs in the memory device is a promising method to realize large memory window, low-power consumption and excellent retention properties.

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

    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.

  8. Focusing of megaampere electron beam in gas cell for production of flash X-ray source

    Zinchenko, Vl; Chlenov, A M; Shiyan, V D [Research Institute of Scientific Instruments, Turaevo-Lytkarino (Russian Federation)

    1997-12-31

    One of important problems to be solved in the development of an intense source of flash X-rays is the choice of the optimum design of the high-current diode at the exit of the electron accelerator. The results of numerical investigations of megaampere relativistic electron beam (REB) generation and focusing in a compound diode are discussed. The diode consists of a vacuum field-emission annular cathode, a planar anode, and a gas cell inserted between the anode foil and the target. (author). 2 figs., 5 refs.

  9. The influence of Ti doping and annealing on Ce{sub 2}Ti{sub 2}O{sub 7} flash memory devices

    Kao, Chyuan Haur [Department of Electronic Engineering, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan Dist., Taoyuan City 33302, Taiwan, ROC (China); Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, Taiwan, ROC (China); Department of Electronic Engineering, Ming Chi University of Technology, Taiwan, ROC (China); Chen, Su Zhien [Department of Electronic Engineering, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan Dist., Taoyuan City 33302, Taiwan, ROC (China); Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, Taiwan, ROC (China); Luo, Yang; Chiu, Wang Ting; Chiu, Shih Wei; Chen, I Chien [Department of Applied Materials and Optoelectronic Engineering, National Chi Nan University, No. 1, University Rd., Puli, Nantou Country 54561, Taiwan, ROC (China); Lin, Chan-Yu [Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, Taiwan, ROC (China); Chen, Hsiang, E-mail: hchen@ncnu.edu.tw [Department of Applied Materials and Optoelectronic Engineering, National Chi Nan University, No. 1, University Rd., Puli, Nantou Country 54561, Taiwan, ROC (China)

    2017-02-28

    Highlights: • Ce{sub 2}Ti{sub 2}O{sub 7} flash memories have been fabricated. • Material quality can be improved by annealing. • The memory performance can be enhanced by Ti doping. • Ti doping and annealing can reinforce crystallization. - Abstract: In this research, a CeO{sub 2} film with Ti doping was used as a trapping layer in metal oxide high-K-oxide-Si (MOHOS)-type memory devices. Since incorporation of Ti atoms into the film could fix dangling bonds and defects, the Ce{sub 2}Ti{sub 2}O{sub 7} trapping layer with annealing treatment could have a larger memory window and a faster programming/erasing speed. To confirm the origin, multiple material analyses indicate that annealing at an appropriate temperature and Ti doping could enhance crystallization. The Ce{sub 2}Ti{sub 2}O{sub 7}-based memory device is promising for future industrial flash memory applications.

  10. InAs quantum dots as charge storing elements for applications in flash memory devices

    Islam, Sk Masiul; Biswas, Pranab [Materials Science Centre, Indian Institute of Technology, Kharagpur 721 302 (India); Banerji, P., E-mail: pallab@matsc.iitkgp.ernet.in [Materials Science Centre, Indian Institute of Technology, Kharagpur 721 302 (India); Chakraborty, S. [Applied Materials Science Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Sector-I, Kolkata 700 064 (India)

    2015-08-15

    Graphical abstract: - Highlights: • Catalyst-free growth of InAs quantum dots was carried out on high-k ZrO{sub 2}. • Memory device with InAs quantum dots as charge storage nodes are fabricated. • Superior memory window, low leakage and reasonably good retention were observed. • Carrier transport phenomena are explained in both program and erase operations. - Abstract: InAs quantum dots (QDs) were grown by metal organic chemical vapor deposition technique to use them as charge storage nodes. Uniform QDs were formed with average diameter 5 nm and height 5–10 nm with a density of 2 × 10{sup 11} cm{sup −2}. The QDs were grown on high-k dielectric layer (ZrO{sub 2}), which was deposited onto ultra-thin GaP passivated p-GaAs (1 0 0) substrate. A charge storage device with the structure Metal/ZrO{sub 2}/InAs QDs/ZrO{sub 2}/(GaP)GaAs/Metal was fabricated. The devices containing InAs QDs exhibit superior memory window, low leakage current density along with reasonably good charge retention. A suitable electronic band diagram corresponding to programming and erasing operations was proposed to explain the operation.

  11. The cellular memory disc of reprogrammed cells.

    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].

  12. A Josephson ternary associative memory cell

    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

  13. FLASH knockdown sensitizes cells to Fas-mediated apoptosis via down-regulation of the anti-apoptotic proteins, MCL-1 and Cflip short.

    Song Chen

    Full Text Available FLASH (FLICE-associated huge protein or CASP8AP2 is a large multifunctional protein that is involved in many cellular processes associated with cell death and survival. It has been reported to promote apoptosis, but we show here that depletion of FLASH in HT1080 cells by siRNA interference can also accelerate the process. As shown previously, depletion of FLASH halts growth by down-regulating histone biosynthesis and arrests the cell cycle in S-phase. FLASH knockdown followed by stimulating the cells with Fas ligand or anti-Fas antibodies was found to be associated with a more rapid cleavage of PARP, accelerated activation of caspase-8 and the executioner caspase-3 and rapid progression to cellular disintegration. As is the case for most anti-apoptotic proteins, FLASH was degraded soon after the onset of apoptosis. Depletion of FLASH also resulted in the reduced intracellular levels of the anti-apoptotic proteins, MCL-1 and the short isoform of cFLIP. FLASH knockdown in HT1080 mutant cells defective in p53 did not significantly accelerate Fas mediated apoptosis indicating that the effect was dependent on functional p53. Collectively, these results suggest that under some circumstances, FLASH suppresses apoptosis.

  14. Asymptomatic memory CD8+ T cells

    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

  15. Photodynamic Therapy for Cancer Cells Using a Flash Wave Light Xenon Lamp

    Kimura, Makoto; Kashikura, Kasumi; Yokoi, Satomi; Koiwa, Yumiko; Tokuoka, Yoshikazu; Kawashima, Norimichi

    We determined photodynamic therapy (PDT) efficacy using a flash wave (FW) and a continuous wave (CW) light, of which the fluence rate was 70 W/cm2, for murine thymic lymphoma cells (EL-4) cultivated in vitro. The irradiation frequency and the pulse width of the FW light were in the range of 1-32 Hz and less than one millisecond, respectively. 5-Aminolevulinic acid-induced protoporphyrin IX (ALA-PpIX) was used as a photosensitizer. When EL-4 with ALA administration was irradiated by the light for 4 h (irradiation fluence: 1.0J/cm2), the survival rate of EL-4 by the FW light was lower than that by the CW light, except for the FW light with irradiation frequency of 32 Hz, and decreased gradually with decreasing irradiation frequency. Moreover, the FW light, especially at lower irradiation frequency, was superior to the CW light for the generation of singlet oxygen in an aqueous PpIX solution. Therefore, thehigher PDT efficacy for EL-4 of the FW light would be caused by the greater generation of singlet oxygen in the cells.

  16. Shape Memory of Human Red Blood Cells

    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...

  17. Improved speed and data retention characteristics in flash memory using a stacked HfO2/Ta2O5 charge-trapping layer

    Zheng, Zhiwei; Huo, Zongliang; Zhang, Manhong; Zhu, Chenxin; Liu, Jing; Liu, Ming

    2011-01-01

    This paper reports the simultaneous improvements in erase speed and data retention characteristics in flash memory using a stacked HfO 2 /Ta 2 O 5 charge-trapping layer. In comparison to a memory capacitor with a single HfO 2 trapping layer, the erase speed of a memory capacitor with a stacked HfO 2 /Ta 2 O 5 charge-trapping layer is 100 times faster and its memory window is enlarged from 2.7 to 4.8 V for the same ±16 V sweeping voltage range. With the same initial window of ΔV FB = 4 V, the device with a stacked HfO 2 /Ta 2 O 5 charge-trapping layer has a 3.5 V extrapolated 10-year retention window, while the control device with a single HfO 2 trapping layer has only 2.5 V for the extrapolated 10-year window. The present results demonstrate that the device with the stacked HfO 2 /Ta 2 O 5 charge-trapping layer has a strong potential for future high-performance nonvolatile memory application

  18. Human T Cell Memory: A Dynamic View

    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.

  19. Analysis of Conduction and Charging Mechanisms in Atomic Layer Deposited Multilayered HfO2/Al2O3 Stacks for Use in Charge Trapping Flash Memories

    Nenad Novkovski

    2018-01-01

    Full Text Available Method for characterization of electrical and trapping properties of multilayered high permittivity stacks for use in charge trapping flash memories is proposed. Application of the method to the case of multilayered HfO2/Al2O3 stacks is presented. By applying our previously developed comprehensive model for MOS structures containing high-κ dielectrics on the J-V characteristics measured in the voltage range without marked degradation and charge trapping (from −3 V to +3 V, several parameters of the structure connected to the interfacial layer and the conduction mechanisms have been extracted. We found that the above analysis gives precise information on the main characteristics and the quality of the injection layer. C-V characteristics of stressed (with write and erase pulses structures recorded in a limited range of voltages between −1 V and +1 V (where neither significant charge trapping nor visible degradation of the structures is expected to occur were used in order to provide measures of the effect of stresses with no influence of the measurement process. Both trapped charge and the distribution of interface states have been determined using modified Terman method for fresh structures and for structures stressed with write and erase cycles. The proposed method allows determination of charge trapping and interface state with high resolution, promising a precise characterization of multilayered high permittivity stacks for use in charge trapping flash memories.

  20. Shape memory of human red blood cells.

    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.

  1. A vertically integrated capacitorless memory cell

    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)

  2. Cell characteristics of a multiple alloy nano-dots memory structure

    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

  3. Flash grundkursus

    Jensen, Henrik

    2008-01-01

    Flash er et programmeringssprog  og kan som sådant ikke noget i sig selv. Kursets mål er, at give den studerende et grundlæggende kendskab til Flash, så det kan bruges til præsentationer på skærm og til produktion af hjemmesider. På kurset arbejdes der med billede, grafik, lyd, video og interakti...

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

    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...

  5. Early Detection of Baby-Rain-Cell Aloft in a Severe Storm and Risk Projection for Urban Flash Flood

    Eiichi Nakakita

    2017-01-01

    Full Text Available In July 2008, five people were killed by a tragic flash flood caused by a local torrential heavy rainfall in a short time in Toga River. From this tragic accident, we realized that a system which can detect hazardous rain-cells in the earlier stage is strongly needed and would provide an additional 5 to 10 min for evacuation. By analyzing this event, we verified that a first radar echo aloft, by volume scan observation, is a practical and important sign for early warning of flash flood, and we named a first echo as a “baby-rain-cell” of Guerrilla-heavy rainfall. Also, we found a vertical vorticity criterion for identifying hazardous rain-cells and developed a heavy rainfall prediction system that has the important feature of not missing any hazardous rain-cell. Being able to detect heavy rainfall by 23.6 min on average before it reaches the ground, this system is implemented in XRAIN in the Kinki area. Additionally, to resolve the relationship between baby-rain-cell growth and vorticity behavior, we carried out an analysis of vorticity inside baby-rain-cells and verified that a pair of positive and negative vertical vortex tubes as well as an updraft between them existed in a rain-cell in the early stage.

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

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

    2015-06-24

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

  7. Overview of emerging nonvolatile memory technologies.

    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

  8. Overview of emerging nonvolatile memory technologies

    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

  9. Pregnancy persistently affects memory T cell populations

    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

  10. Damage to UV-sensitive cells by short UV in photographic flashes

    Menezes, S.; Monteiro, C.

    1996-01-01

    Light emitted by electronic photographic flash units is shown to damage bacteria and human skin fibroblasts deficient in repair systems, with survival curves very similar to those produced by 254 nm short UV. The lesions induced by these flashes are as photorepairable by the photolyase enzyme as those induced by 254 nm UV and result in equivalent survival rates. Biological dosimetry performed with microorganisms highly sensitive to UV (Escherichia coli K12 AB2480, deficient in excision and recombinational-dependent repair systems and Bacillus subtilis UVSSP spores, deficient in excision and in a specific spore repair process) revealed that each 1 ms flash of light from the photographic unit used in this work contained the equivalent of 0.25 J m -2 of 254 nm UV, when measured at a distance of 7.0 cm. This dose of UV was found to be lethal to both repair-deficient E. coli bacteria and repair-deficient human skin fibroblasts obtained from xeroderma pigmentosum donors, as well as mutagenic in B/r wild-type and HCR-mutant bacteria. (Author)

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

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

    2003-01-01

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

  12. Measurements of a vortex transitional ndro Josephson memory cell

    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

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

    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.

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

    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.

  15. Engrampigenetics: Epigenetics of engram memory cells.

    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.

  16. Flash evaporator

    1997-01-01

    A device and method for flash evaporating a reagent includes an evaporation chamber that houses a dome on which evaporation occurs. The dome is solid and of high thermal conductivity and mass, and may be heated to a temperature sufficient to vaporize a specific reagent. The reagent is supplied from an external source to the dome through a nozzle, and may be supplied as a continuous stream, as a shower, and as discrete drops. A carrier gas may be introduced into the evaporation chamber and cre...

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

    Campbell, Philip Montgomery; Wix, Steven D.

    2017-04-01

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

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

    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.

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

    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.

  20. CD4 T-Cell Memory Generation and Maintenance

    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

  1. Thermal diffusivity measurements of molten salts using a three-layered cell by the laser flash method

    Ohta, Hiromichi; Ogura, Gaku; Waseda, Yoshio; Suzuki, Mustumi

    1990-10-01

    A simple cell and easy data processing are described for measuring the thermal diffusivity of a liquid sample at high temperatures using the laser flash method. A cell consists of a liquid sample sandwiched by two metallic plates. The front surface of one metallic plate is exposed to a single pulse of beam laser and the resulting temperature rise of the back surface of the other metallic plate is measured. The logarithmic analysis proposed by James using the initial time region of the temperature response curve of a two layered cell system has been extended to apply to the present three layered cell system in order to estimate the thermal diffusivity value of a liquid sample. Measurements of distilled water and methanol were made first and the results were found to be in good agreement with the reference data. Then, the thermal diffusivities of molten NaNO3 at 593-660 K and of molten KNO3 at 621-694 K were determined and the results also appear to agree reasonably well with those reported in the literature.

  2. System of ispFlash configuration

    Bourrion, Olivier

    2003-01-01

    The aim of this module is to allow the use of FPGA components instead of EPLD components which for an equivalent or even inferior capacity are more expensive. For instance, the idea is to replace CPLD components having 512 macro-cells by one FPGA spartan II of Xilinx. However, due to the configuration's volatility, one configuration means is needed to put under voltage. A solution appears to be the using of a high capacity Flash memory coupled to a CPLD of small size to comply with the FPGA configuration protocol; also, one has to provide an in situ configuration means for this memory. Obviously, a product having an equivalent functionality already exists, since Xilinx and ALTERA supply PROMs of serial configuration. Unfortunately, they are expensive and a dealer is implied while the FLASH, the small CPLD and the FPGA spartan II are currently available. In conclusion, by using this assembly, which requires a small supplementary surface and a delay of upmost 240 ms (for the largest FPGA 1 Mbit), one obtains a solution cheaper and more performing than an EPLD of high capacity

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

    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.

  4. Model-assisted template extraction SRAF application to contact holes patterns in high-end flash memory device fabrication

    Seoud, Ahmed; Kim, Juhwan; Ma, Yuansheng; Jayaram, Srividya; Hong, Le; Chae, Gyu-Yeol; Lee, Jeong-Woo; Park, Dae-Jin; Yune, Hyoung-Soon; Oh, Se-Young; Park, Chan-Ha

    2018-03-01

    Sub-resolution assist feature (SRAF) insertion techniques have been effectively used for a long time now to increase process latitude in the lithography patterning process. Rule-based SRAF and model-based SRAF are complementary solutions, and each has its own benefits, depending on the objectives of applications and the criticality of the impact on manufacturing yield, efficiency, and productivity. Rule-based SRAF provides superior geometric output consistency and faster runtime performance, but the associated recipe development time can be of concern. Model-based SRAF provides better coverage for more complicated pattern structures in terms of shapes and sizes, with considerably less time required for recipe development, although consistency and performance may be impacted. In this paper, we introduce a new model-assisted template extraction (MATE) SRAF solution, which employs decision tree learning in a model-based solution to provide the benefits of both rule-based and model-based SRAF insertion approaches. The MATE solution is designed to automate the creation of rules/templates for SRAF insertion, and is based on the SRAF placement predicted by model-based solutions. The MATE SRAF recipe provides optimum lithographic quality in relation to various manufacturing aspects in a very short time, compared to traditional methods of rule optimization. Experiments were done using memory device pattern layouts to compare the MATE solution to existing model-based SRAF and pixelated SRAF approaches, based on lithographic process window quality, runtime performance, and geometric output consistency.

  5. Combined mask and illumination scheme optimization for robust contact patterning on 45nm technology node flash memory devices

    Vaglio Pret, Alessandro; Capetti, Gianfranco; Bollin, Maddalena; Cotti, Gina; De Simone, Danilo; Cantù, Pietro; Vaccaro, Alessandro; Soma, Laura

    2008-03-01

    Immersion Lithography is the most important technique for extending optical lithography's capabilities and meeting the requirements of Semiconductor Roadmap. The introduction of immersion tools has recently allowed the development of 45nm technology node in single exposure. Nevertheless the usage of hyper-high NA scanners (NA > 1), some levels still remain very critical to be imaged with sufficient process performances. For memory devices, contact mask is for sure the most challenging layer. Aim of this paper is to present the lithographic assessment of 193nm contact holes process, with k I value of ~0.30 using NA 1.20 immersion lithography (minimum pitch is 100nm). Different issues will be reported, related to mask choices (Binary or Attenuated Phase Shift) and illuminator configurations. First phase of the work will be dedicated to a preliminary experimental screening on a simple test case in order to reduce the variables in the following optimization sections. Based on this analysis we will discard X-Y symmetrical illuminators (Annular, C-Quad) due to poor contrast. Second phase will be dedicated to a full simulation assessment. Different illuminators will be compared, with both mask type and several mask biases. From this study, we will identify some general trends of lithography performances that can be used for the fine tuning of the RET settings. The last phase of the work will be dedicated to find the sensitivity trends for one of the analyzed illuminators. In particular we study the effect of Numerical Aperture, mask bias in both X and Y direction and poles sigma ring-width and centre.

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

    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.

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

    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.

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

    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...

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

    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.

  10. MemFlash device: floating gate transistors as memristive devices for neuromorphic computing

    Riggert, C.; Ziegler, M.; Schroeder, D.; Krautschneider, W. H.; Kohlstedt, H.

    2014-10-01

    Memristive devices are promising candidates for future non-volatile memory applications and mixed-signal circuits. In the field of neuromorphic engineering these devices are especially interesting to emulate neuronal functionality. Therefore, new materials and material combinations are currently investigated, which are often not compatible with Si-technology processes. The underlying mechanisms of the device often remain unclear and are paired with low device endurance and yield. These facts define the current most challenging development tasks towards a reliable memristive device technology. In this respect, the MemFlash concept is of particular interest. A MemFlash device results from a diode configuration wiring scheme of a floating gate transistor, which enables the persistent device resistance to be varied according to the history of the charge flow through the device. In this study, we investigate the scaling conditions of the floating gate oxide thickness with respect to possible applications in the field of neuromorphic engineering. We show that MemFlash cells exhibit essential features with respect to neuromorphic applications. In particular, cells with thin floating gate oxides show a limited synaptic weight growth together with low energy dissipation. MemFlash cells present an attractive alternative for state-of-art memresitive devices. The emulation of associative learning is discussed by implementing a single MemFlash cell in an analogue circuit.

  11. MemFlash device: floating gate transistors as memristive devices for neuromorphic computing

    Riggert, C; Ziegler, M; Kohlstedt, H; Schroeder, D; Krautschneider, W H

    2014-01-01

    Memristive devices are promising candidates for future non-volatile memory applications and mixed-signal circuits. In the field of neuromorphic engineering these devices are especially interesting to emulate neuronal functionality. Therefore, new materials and material combinations are currently investigated, which are often not compatible with Si-technology processes. The underlying mechanisms of the device often remain unclear and are paired with low device endurance and yield. These facts define the current most challenging development tasks towards a reliable memristive device technology. In this respect, the MemFlash concept is of particular interest. A MemFlash device results from a diode configuration wiring scheme of a floating gate transistor, which enables the persistent device resistance to be varied according to the history of the charge flow through the device. In this study, we investigate the scaling conditions of the floating gate oxide thickness with respect to possible applications in the field of neuromorphic engineering. We show that MemFlash cells exhibit essential features with respect to neuromorphic applications. In particular, cells with thin floating gate oxides show a limited synaptic weight growth together with low energy dissipation. MemFlash cells present an attractive alternative for state-of-art memresitive devices. The emulation of associative learning is discussed by implementing a single MemFlash cell in an analogue circuit. (paper)

  12. Systems-wide RNAi analysis of CASP8AP2/FLASH shows transcriptional deregulation of the replication-dependent histone genes and extensive effects on the transcriptome of colorectal cancer cells.

    Hummon, Amanda B; Pitt, Jason J; Camps, Jordi; Emons, Georg; Skube, Susan B; Huppi, Konrad; Jones, Tamara L; Beissbarth, Tim; Kramer, Frank; Grade, Marian; Difilippantonio, Michael J; Ried, Thomas; Caplen, Natasha J

    2012-01-04

    Colorectal carcinomas (CRC) carry massive genetic and transcriptional alterations that influence multiple cellular pathways. The study of proteins whose loss-of-function (LOF) alters the growth of CRC cells can be used to further understand the cellular processes cancer cells depend upon for survival. A small-scale RNAi screen of ~400 genes conducted in SW480 CRC cells identified several candidate genes as required for the viability of CRC cells, most prominently CASP8AP2/FLASH. To understand the function of this gene in maintaining the viability of CRC cells in an unbiased manner, we generated gene specific expression profiles following RNAi. Silencing of CASP8AP2/FLASH resulted in altered expression of over 2500 genes enriched for genes associated with cellular growth and proliferation. Loss of CASP8AP2/FLASH function was significantly associated with altered transcription of the genes encoding the replication-dependent histone proteins as a result of the expression of the non-canonical polyA variants of these transcripts. Silencing of CASP8AP2/FLASH also mediated enrichment of changes in the expression of targets of the NFκB and MYC transcription factors. These findings were confirmed by whole transcriptome analysis of CASP8AP2/FLASH silenced cells at multiple time points. Finally, we identified and validated that CASP8AP2/FLASH LOF increases the expression of neurofilament heavy polypeptide (NEFH), a protein recently linked to regulation of the AKT1/ß-catenin pathway. We have used unbiased RNAi based approaches to identify and characterize the function of CASP8AP2/FLASH, a protein not previously reported as required for cell survival. This study further defines the role CASP8AP2/FLASH plays in the regulating expression of the replication-dependent histones and shows that its LOF results in broad and reproducible effects on the transcriptome of colorectal cancer cells including the induction of expression of the recently described tumor suppressor gene NEFH.

  13. Memory T follicular helper CD4 T cells

    J. Scott eHale

    2015-02-01

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

  14. Generation of memory B cells and their reactivation.

    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.

  15. Flash-Aware Page Replacement Algorithm

    Guangxia Xu

    2014-01-01

    Full Text Available Due to the limited main memory resource of consumer electronics equipped with NAND flash memory as storage device, an efficient page replacement algorithm called FAPRA is proposed for NAND flash memory in the light of its inherent characteristics. FAPRA introduces an efficient victim page selection scheme taking into account the benefit-to-cost ratio for evicting each victim page candidate and the combined recency and frequency value, as well as the erase count of the block to which each page belongs. Since the dirty victim page often contains clean data that exist in both the main memory and the NAND flash memory based storage device, FAPRA only writes the dirty data within the victim page back to the NAND flash memory based storage device in order to reduce the redundant write operations. We conduct a series of trace-driven simulations and experimental results show that our proposed FAPRA algorithm outperforms the state-of-the-art algorithms in terms of page hit ratio, the number of write operations, runtime, and the degree of wear leveling.

  16. Performance enhancement in p-channel charge-trapping flash memory devices with Si/Ge super-lattice channel and band-to-band tunneling induced hot-electron injection

    Liu, Li-Jung; Chang-Liao, Kuei-Shu; Jian, Yi-Chuen; Wang, Tien-Ko; Tsai, Ming-Jinn

    2013-01-01

    P-channel charge-trapping flash memory devices with Si, SiGe, and Si/Ge super-lattice channel are investigated in this work. A Si/Ge super-lattice structure with extremely low roughness and good crystal structure is obtained by precisely controlling the epitaxy thickness of Ge layer. Both programming and erasing (P/E) speeds are significantly improved by employing this Si/Ge super-lattice channel. Moreover, satisfactory retention and excellent endurance characteristics up to 10 6 P/E cycles with 3.8 V memory window show that the degradation on reliability properties is negligible when super-lattice channel is introduced. - Highlights: ► A super-lattice structure is proposed to introduce more Ge content into channel. ► Super-lattice structure possesses low roughness and good crystal structure. ► P-channel flash devices with Si, SiGe, and super-lattice channel are investigated. ► Programming/erasing speeds are significantly improved. ► Reliability properties can be kept for device with super-lattice channel

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

    Wang, Jin-Hui; Cui, Shan

    2018-01-01

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

  18. DIRCM FLASH Flight Tests

    Molocher, Bernhard; Kaltenecker, Anton; Thum-Jaeger, Andrea; Regensburger, Martin; Formery, Martin

    2005-01-01

    .... FLASH operation is as follows: After handover following an alarm from the missile warning system FLASH enters autonomous passive tracking mode for tracking a missiles and sending a laser beam onto the missile...

  19. Tumor cells and memory T cells converge at glycolysis

    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

  20. Flash Platform Examination

    2011-03-01

    than would be performed in software”[108]. Uro Tinic, one of the Flash player’s engineers, further clarifies exactly what Flash player 10 hardware...www.adobe.com/products/flashplayer/features/ (Access date: 28 Sep 2009). [109] Uro , T. What Does GPU Acceleration Mean? (online), http...133] Shorten, A. (2009), Design to Development: Flash Catalyst to Flash Builder, In Proceedings of Adobe Max 2009, Los Angeles, CA. 142 DRDC

  1. PD-1 Blockade Expands Intratumoral Memory T Cells

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

    2016-01-01

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

  2. A stacked memory device on logic 3D technology for ultra-high-density data storage

    Kim, Jiyoung; Hong, Augustin J; Kim, Sung Min; Shin, Kyeong-Sik; Song, Emil B; Hwang, Yongha; Xiu, Faxian; Galatsis, Kosmas; Chui, Chi On; Candler, Rob N; Wang, Kang L; Choi, Siyoung; Moon, Joo-Tae

    2011-01-01

    We have demonstrated, for the first time, a novel three-dimensional (3D) memory chip architecture of stacked-memory-devices-on-logic (SMOL) achieving up to 95% of cell-area efficiency by directly building up memory devices on top of front-end CMOS devices. In order to realize the SMOL, a unique 3D Flash memory device and vertical integration structure have been successfully developed. The SMOL architecture has great potential to achieve tera-bit level memory density by stacking memory devices vertically and maximizing cell-area efficiency. Furthermore, various emerging devices could replace the 3D memory device to develop new 3D chip architectures.

  3. A stacked memory device on logic 3D technology for ultra-high-density data storage

    Kim, Jiyoung; Hong, Augustin J; Kim, Sung Min; Shin, Kyeong-Sik; Song, Emil B; Hwang, Yongha; Xiu, Faxian; Galatsis, Kosmas; Chui, Chi On; Candler, Rob N; Wang, Kang L [Device Research Laboratory, Department of Electrical Engineering, University of California, Los Angeles, CA 90095 (United States); Choi, Siyoung; Moon, Joo-Tae, E-mail: hbt100@ee.ucla.edu [Advanced Technology Development Team and Process Development Team, Memory R and D Center, Samsung Electronics Co. Ltd (Korea, Republic of)

    2011-06-24

    We have demonstrated, for the first time, a novel three-dimensional (3D) memory chip architecture of stacked-memory-devices-on-logic (SMOL) achieving up to 95% of cell-area efficiency by directly building up memory devices on top of front-end CMOS devices. In order to realize the SMOL, a unique 3D Flash memory device and vertical integration structure have been successfully developed. The SMOL architecture has great potential to achieve tera-bit level memory density by stacking memory devices vertically and maximizing cell-area efficiency. Furthermore, various emerging devices could replace the 3D memory device to develop new 3D chip architectures.

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

    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.

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

    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.

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

    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.

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

    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.

  8. CELLS v1.0: updated and parallelized version of an electrical scheme to simulate multiple electrified clouds and flashes over large domains

    C. Barthe

    2012-01-01

    Full Text Available The paper describes the fully parallelized electrical scheme CELLS which is suitable to simulate explicitly electrified storm systems on parallel computers. Our motivation here is to show that a cloud electricity scheme can be developed for use on large grids with complex terrain. Large computational domains are needed to perform real case meteorological simulations with many independent convective cells.

    The scheme computes the bulk electric charge attached to each cloud particle and hydrometeor. Positive and negative ions are also taken into account. Several parametrizations of the dominant non-inductive charging process are included and an inductive charging process as well. The electric field is obtained by inverting the Gauss equation with an extension to terrain-following coordinates. The new feature concerns the lightning flash scheme which is a simplified version of an older detailed sequential scheme. Flashes are composed of a bidirectional leader phase (vertical extension from the triggering point and a phase obeying a fractal law (with horizontal extension on electrically charged zones. The originality of the scheme lies in the way the branching phase is treated to get a parallel code.

    The complete electrification scheme is tested for the 10 July 1996 STERAO case and for the 21 July 1998 EULINOX case. Flash characteristics are analysed in detail and additional sensitivity experiments are performed for the STERAO case. Although the simulations were run for flat terrain conditions, they show that the model behaves well on multiprocessor computers. This opens a wide area of application for this electrical scheme with the next objective of running real meterological case on large domains.

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

    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.

  10. Single-cell atomic quantum memory for light

    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

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

    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.

  12. Pro Android Flash

    Chin, Stephen; Campesato, Oswald

    2011-01-01

    Did you know you can take your Flash skills beyond the browser, allowing you to make apps for Android, iOS and the BlackBerry Tablet OS? Build dynamic apps today starting with the easy-to-use Android smartphones and tablets. Then, take your app to other platforms without writing native code. Pro Android Flash is the definitive guide to building Flash and other rich Internet applications (RIAs) on the Android platform. It covers the most popular RIA frameworks for Android developers - Flash and Flex - and shows how to build rich, immersive user experiences on both Android smartphones and tablet

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

    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.

  14. Systems-wide RNAi analysis of CASP8AP2/FLASH shows transcriptional deregulation of the replication-dependent histone genes and extensive effects on the transcriptome of colorectal cancer cells

    Hummon Amanda B

    2012-01-01

    Full Text Available Abstract Background Colorectal carcinomas (CRC carry massive genetic and transcriptional alterations that influence multiple cellular pathways. The study of proteins whose loss-of-function (LOF alters the growth of CRC cells can be used to further understand the cellular processes cancer cells depend upon for survival. Results A small-scale RNAi screen of ~400 genes conducted in SW480 CRC cells identified several candidate genes as required for the viability of CRC cells, most prominently CASP8AP2/FLASH. To understand the function of this gene in maintaining the viability of CRC cells in an unbiased manner, we generated gene specific expression profiles following RNAi. Silencing of CASP8AP2/FLASH resulted in altered expression of over 2500 genes enriched for genes associated with cellular growth and proliferation. Loss of CASP8AP2/FLASH function was significantly associated with altered transcription of the genes encoding the replication-dependent histone proteins as a result of the expression of the non-canonical polyA variants of these transcripts. Silencing of CASP8AP2/FLASH also mediated enrichment of changes in the expression of targets of the NFκB and MYC transcription factors. These findings were confirmed by whole transcriptome analysis of CASP8AP2/FLASH silenced cells at multiple time points. Finally, we identified and validated that CASP8AP2/FLASH LOF increases the expression of neurofilament heavy polypeptide (NEFH, a protein recently linked to regulation of the AKT1/ß-catenin pathway. Conclusions We have used unbiased RNAi based approaches to identify and characterize the function of CASP8AP2/FLASH, a protein not previously reported as required for cell survival. This study further defines the role CASP8AP2/FLASH plays in the regulating expression of the replication-dependent histones and shows that its LOF results in broad and reproducible effects on the transcriptome of colorectal cancer cells including the induction of

  15. Flash-Type Discrimination

    Koshak, William J.

    2010-01-01

    This viewgraph presentation describes the significant progress made in the flash-type discrimination algorithm development. The contents include: 1) Highlights of Progress for GLM-R3 Flash-Type discrimination Algorithm Development; 2) Maximum Group Area (MGA) Data; 3) Retrieval Errors from Simulations; and 4) Preliminary Global-scale Retrieval.

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

    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...

  17. Cell-assembly coding in several memory processes.

    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.

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

    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.

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

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

    2015-07-01

    Today the influence of non-volatile solid-state memories on persons' lives has become more prominent because of their non-volatility, low data latency, and high robustness. As a pioneering technology that is representative of non-volatile solidstate memories, flash memory has recently seen widespread application in many areas ranging from electronic appliances, such as cell phones and digital cameras, to external storage devices such as universal serial bus (USB) memory. Moreover, owing to its large storage capacity, it is expected that in the near future, flash memory will replace hard-disk drives as a dominant technology in the mass storage market, especially because of recently emerging solid-state drives. However, the rapid growth of the global digital data has led to the need for flash memories to have larger storage capacity, thus requiring a further downscaling of the cell size. Such a miniaturization is expected to be extremely difficult because of the well-known scaling limit of flash memories. It is therefore necessary to either explore innovative technologies that can extend the areal density of flash memories beyond the scaling limits, or to vigorously develop alternative non-volatile solid-state memories including ferroelectric random-access memory, magnetoresistive random-access memory, phase-change random-access memory, and resistive random-access memory. In this paper, we review the physical principles of flash memories and their technical challenges that affect our ability to enhance the storage capacity. We then present a detailed discussion of novel technologies that can extend the storage density of flash memories beyond the commonly accepted limits. In each case, we subsequently discuss the physical principles of these new types of non-volatile solid-state memories as well as their respective merits and weakness when utilized for data storage applications. Finally, we predict the future prospects for the aforementioned solid-state memories for

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

    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.

  1. Memory control by the B cell antigen receptor.

    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.

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

    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.

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

    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...

  4. CellSs: Scheduling Techniques to Better Exploit Memory Hierarchy

    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.

  5. Nanoscale memory devices

    Chung, Andy; Deen, Jamal; Lee, Jeong-Soo; Meyyappan, M

    2010-01-01

    This article reviews the current status and future prospects for the use of nanomaterials and devices in memory technology. First, the status and continuing scaling trends of the flash memory are discussed. Then, a detailed discussion on technologies trying to replace flash in the near-term is provided. This includes phase change random access memory, Fe random access memory and magnetic random access memory. The long-term nanotechnology prospects for memory devices include carbon-nanotube-based memory, molecular electronics and memristors based on resistive materials such as TiO 2 . (topical review)

  6. B Cell Intrinsic Mechanisms Constraining IgE Memory

    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.

  7. Floods and Flash Flooding

    Floods and flash flooding Now is the time to determine your area’s flood risk. If you are not sure whether you ... If you are in a floodplain, consider buying flood insurance. Do not drive around barricades. If your ...

  8. Superior PSZ-SOD Gap-Fill Process Integration Using Ultra-Low Dispensation Amount in STI for 28 nm NAND Flash Memory and Beyond

    Chun Chi Lai

    2015-01-01

    Full Text Available The gap-fill performance and process of perhydropolysilazane-based inorganic spin-on dielectric (PSZ-SOD film in shallow trench isolation (STI with the ultra-low dispensation amount of PSZ-SOD solution have been investigated in this study. A PSZ-SOD film process includes liner deposition, PSZ-SOD coating, and furnace curing. For liner deposition, hydrophilic property is required to improve the contact angle and gap-fill capability of PSZ-SOD coating. Prior to PSZ-SOD coating, the additional treatment on liner surface is beneficial for the fluidity of PSZ-SOD solution. The superior film thickness uniformity and gap-fill performance of PSZ-SOD film are achieved due to the improved fluidity of PSZ-SOD solution. Following that up, the low dispensation rate of PSZ-SOD solution leads to more PSZ-SOD filling in the trenches. After PSZ-SOD coating, high thermal curing process efficiently promotes PSZ-SOD film conversion into silicon oxide. Adequate conversion from PSZ-SOD into silicon oxide further increases the etching resistance inside the trenches. Integrating the above sequence of optimized factors, void-free gap-fill and well-controlled STI recess uniformity are achieved even when the PSZ-SOD solution dispensation volume is reduced 3 to 6 times compared with conventional condition for the 28 nm node NAND flash and beyond.

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

    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

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

    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.

  11. Influence of post-annealing on the electrical properties of metal/oxide/silicon nitride/oxide/silicon capacitors for flash memories

    Kim, Hee Dong; An, Ho-Myoung; Kim, Kyoung Chan; Seo, Yu Jeong; Kim, Tae Geun

    2008-01-01

    We report the effect of post-annealing on the electrical properties of metal/oxide/silicon nitride/oxide/silicon (MONOS) capacitors. Four samples, namely as-deposited and annealed at 750, 850 and 950 °C for 30 s in nitrogen ambient by a rapid thermal process, were prepared and characterized for comparison. The best performance with the largest memory window of 4.4 V and the fastest program speed of 10 ms was observed for the sample annealed at 850 °C. In addition, the highest traps density of 6.84 × 10 18 cm −3 was observed with ideal trap distributions for the same sample by capacitance–voltage (C–V) measurement. These results indicate that the memory traps in the ONO structure can be engineered by post-annealing to improve the electrical properties of the MONOS device

  12. Cellular memory and, hematopoietic stem cell aging

    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

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

    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

  14. Memory, microprocessor, and ASIC

    Chen, Wai-Kai

    2003-01-01

    System Timing. ROM/PROM/EPROM. SRAM. Embedded Memory. Flash Memories. Dynamic Random Access Memory. Low-Power Memory Circuits. Timing and Signal Integrity Analysis. Microprocessor Design Verification. Microprocessor Layout Method. Architecture. ASIC Design. Logic Synthesis for Field Programmable Gate Array (EPGA) Technology. Testability Concepts and DFT. ATPG and BIST. CAD Tools for BIST/DFT and Delay Faults.

  15. Memory

    ... 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 ...

  16. 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.

    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.

  17. Modélisation de Fautes et Test des Mémoires Flash

    Ginez , Olivier

    2007-01-01

    Flash memories more and more occurs in complex integrated circuits designed for portable electronic devices and dominate the area of such circuits. The lack of defects within these memories is therefore one the key elements of the production yield for manufacturers of these types of applications. However, the high integration density and the complexity of the fabrication process make these Flash memories more and more prone to manufacturing defects. To exhibit the failures that affect the fun...

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

    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.

  19. Methyltransferases mediate cell memory of a genotoxic insult.

    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.

  20. Interactions of numerical and temporal stimulus characteristics on the control of response location by brief flashes of light.

    Fetterman, J Gregor; Killeen, P Richard

    2011-09-01

    Pigeons pecked on three keys, responses to one of which could be reinforced after 3 flashes of the houselight, to a second key after 6, and to a third key after 12. The flashes were arranged according to variable-interval schedules. Response allocation among the keys was a function of the number of flashes. When flashes were omitted, transitions occurred very late. Increasing flash duration produced a leftward shift in the transitions along a number axis. Increasing reinforcement probability produced a leftward shift, and decreasing reinforcement probability produced a rightward shift. Intermixing different flash rates within sessions separated allocations: Faster flash rates shifted the functions sooner in real time, but later in terms of flash count, and conversely for slower flash rates. A model of control by fading memories of number and time was proposed.

  1. Professional Flash Lite Mobile Development

    Anderson, J G

    2010-01-01

    Discover how to create Flash Lite mobile apps from the ground up. Adobe Flash is an ideal choice for developing rich interactive content for "Flash-enabled" mobile devices; and with this book, you'll learn how to create unique applications with Flash Lite. Through a series of code samples and extensive example applications, you'll explore the core concepts, key features, and best practices of the Flash Lite player. Coverage reveals various ways to develop Flash mobile content, create applications with a cross-platform programming framework based on the Model, View and Controller conc

  2. On the shape memory of red blood cells

    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

  3. Timing in a FLASH

    Hoek, M.; Cardinali, M.; Corell, O.; Dickescheid, M.; Ferretti B., M. I.; Lauth, W.; Schlimme, B. S.; Sfienti, C.; Thiel, M.

    2017-12-01

    A prototype detector, called FLASH (Fast Light Acquiring Start Hodoscope), was built to provide precise Time-of-Flight (TOF) measurements and reference timestamps for detector setups at external beam lines. Radiator bars, made of synthetic fused silica, were coupled to a fast MCP-PMT with 64 channels and read out with custom electronics using Time-over-Threshold (TOT) for signal characterization. The TRB3 system, a high-precision TDC implemented in an FPGA, was used as data acquisition system. The performance of a system consisting of two FLASH units was investigated at a dedicated test experiment at the Mainz Microtron (MAMI) accelerator using its 855 MeV electron beam. The TOT measurement enabled time walk corrections and an overall TOF resolution of ∼70 ps could be achieved which translates into a resolution of ∼50 ps per FLASH unit. The intrinsic resolution of the frontend electronics including the TDC was measured to be less than 25 ps.

  4. Foundation Flash Cartoon Animation

    Jones, Tim; Rosson, Allan S

    2008-01-01

    One of Flash s most common uses is still animation for cartoons, games, advertising etc, and this book takes a fresh look at the topic, breaking it down pre-production, production, and post production, and looking at each section in detail, and covering topics such as storyboarding, character libraries and camera mechanics like no Flash book has before. The book is written by members of the Emmy award winning ANIMAX team, who have created work for clients such as Disney, AOL, Fox, WWE, ESPN, and Sesame workshop. This book is an opportunity for them to share their secrets, and is written to sui

  5. Flash x-ray

    Johnson, Q.; Pellinen, D.

    1976-01-01

    The complementary techniques of flash x-ray radiography (FXR) and flash x-ray diffraction (FXD) provide access to a unique domain in nondestructive materials testing. FXR is useful in studies of macroscopic properties during extremely short time intervals, and FXD, the newer technique, is used in studies of microscopic properties. Although these techniques are similar in many respects, there are some substantial differences. FXD generally requires low-voltage, line-radiation sources and extremely accurate timing; FXR is usually less demanding. Phenomena which can be profitably studied by FXR often can also be studied by FXD to permit a complete materials characterization

  6. Theory of optical flashes

    London, R.A.

    1983-01-01

    The theory of optical flashes created by x- and γ-ray burst heating of stars in binaries is reviewed. Calculations of spectra due to steady-state x-ray reprocessing and estimates of the fundamental time scales for the non-steady case are discussed. The results are applied to the extant optical data from x-ray and γ-ray bursters. Finally, I review predictions of flashes from γ-ray bursters detectable by a state of the art all-sky optical monitor

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

    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

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

    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...

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

    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.

  10. Learning Flash CS4 Professional

    Shupe, Rich

    2009-01-01

    Learning Flash CS4 Professional offers beginners and intermediate Flash developers a unique introduction to the latest version of Adobe's powerful multimedia application. This easy-to-read book is loaded with full-color examples and hands-on tasks to help you master Flash CS4's new motion editor, integrated 3D system, and character control using the new inverse kinematics bones animation system. No previous Flash experience is necessary.

  11. Jaan Toomik Flash Artis

    1999-01-01

    1999. a. mai-juuni 'Flash Artis' on ajakirja Eesti korrespondendi Ando Keskküla artikkel Jaan Toomikust. Jaan Toomik on kutsutud esinema Londoni The Photographers' Gallery grupinäitusele, tema videot 'Father and Son' näidatakse Londonis avataval näitusel 'Near and Elsewhere' 11.-24. juunini

  12. Inessa Josing Flash Artis

    1999-01-01

    'Flash Art'i' 1998. a. nov.-dets. numbris Rosa Martínezi artiklis suvisest Manifesta II näitusest Luxembourg'is on positiivselt mainitud ka Inessa Josingut. Illustratsiooniks toodud seitsmest fotost ühel on I. Josingu aknakujundus 'What Must I Do to be Saved?'

  13. Evaluating Non-In-Place Update Techniques for Flash-Based Transaction Processing Systems

    Wang, Yongkun; Goda, Kazuo; Kitsuregawa, Masaru

    Recently, flash memory is emerging as the storage device. With price sliding fast, the cost per capacity is approaching to that of SATA disk drives. So far flash memory has been widely deployed in consumer electronics even partly in mobile computing environments. For enterprise systems, the deployment has been studied by many researchers and developers. In terms of the access performance characteristics, flash memory is quite different from disk drives. Without the mechanical components, flash memory has very high random read performance, whereas it has a limited random write performance because of the erase-before-write design. The random write performance of flash memory is comparable with or even worse than that of disk drives. Due to such a performance asymmetry, naive deployment to enterprise systems may not exploit the potential performance of flash memory at full blast. This paper studies the effectiveness of using non-in-place-update (NIPU) techniques through the IO path of flash-based transaction processing systems. Our deliberate experiments using both open-source DBMS and commercial DBMS validated the potential benefits; x3.0 to x6.6 performance improvement was confirmed by incorporating non-in-place-update techniques into file system without any modification of applications or storage devices.

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

    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.

  15. Photobinding of tiaprofenic acid and suprofen to proteins and cells: a combined study using radiolabeling, antibodies and laser flash photolysis of model bichromophores.

    Castell, J V; Hernández, D; Gómez-Lechón, M J; Lahoz, A; Miranda, M A; Morera, I M; Pérez-Prieto, J; Sarabia, Z

    1998-11-01

    Drug photoallergy is a matter of current concern. It involves the formation of drug-protein photoadducts (photoantigens) that may ultimately trigger an immunological response. Tyrosine residues appear to be key binding sites in proteins. The present work has investigated the photobinding of tiaprofenic and (TPA) and the closely related isomer suprofen (SUP) to proteins and cells by means of radioactive labelling and drug-directed antibodies. To ascertain whether preassociation with the protein may play a role in photoreactivity, two model bichromophoric compounds (TPA-Tyr and SUP-Tyr) have been prepared and studied by laser flash photolysis. The results of this work show that (a) TPA and SUP photobind to proteins with similar efficiencies, (b) both drugs form photoadducts that share a basic common structure, as they are recognized by the same antibody and (c) drug-protein preassociation must play a key role in photoreactivity, as indicated by the dramatic decrease in the triplet state lifetimes of the model bichromophores compared to the parent drugs.

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

    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. ...

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

    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

  18. Phototoxic effects of commercial photographic flash lamp on rat eyes.

    Inoue, Makoto; Shinoda, Kei; Ohde, Hisao; Tezuka, Keiji; Hida, Tetsuo

    2006-11-01

    To determine whether exposure of the cornea and retina of rats to flashes from a commercial photographic flash lamp is phototoxic. Sprague-Dawley rats were exposed to 10, 100, or 1,000 flashes of the OPTICAM 16M photographic flash lamp (Fujikoeki, Japan) placed 0.1, 1, or 3 m from the eyes. Corneal damage was assessed by a fluorescein staining score, and the retinal damage by eletroretinography (ERG) and histology before and 24 h after exposure. Exposure of the eyes to 1,000 flashes at 0.1 m increased the fluorescein staining score significantly (P = 0.009, the Mann-Whitney test). Scanning electron microscopy (SEM) of the cornea showed a detachment of the epithelial cells from the surface after this exposure. The amplitude of the a-wave was decreased significantly by 23.0% (P = 0.026) of the amplitude before the exposure, and the b-wave by 19.7% (P = 0.0478) following 1,000 flashes at 0.1 m but not by the other exposures. TUNEL-positive cells were present in the outer nuclear layer only after the extreme exposure, but no significant decrease in retinal thickness was seen under any condition. The fluorescein staining score and ERGs recovered to control levels within 1 week. Light exposure to a photographic flash lamp does not induce damage to the cornea and retina except when they are exposed to 1,000 flashes at 0.1 m.

  19. On the nature of rainfall in dry climate: Space-time patterns of convective rain cells over the Dead Sea region and their relations with synoptic state and flash flood generation

    Belachsen, Idit; Marra, Francesco; Peleg, Nadav; Morin, Efrat

    2017-04-01

    Space-time patterns of rainfall are important climatic characteristics that influence runoff generation and flash flood magnitude. Their derivation requires high-resolution measurements to adequately represent the rainfall distribution, and is best provided by remote sensing tools. This need is further emphasized in dry climate regions, where rainfall is scarce and, often, local and highly variable. Our research is focused on understanding the nature of rainfall events in the dry Dead Sea region (Eastern Mediterranean) by identifying and characterizing the spatial structure and the dynamics of convective storm cores (known as rain cells). To do so, we take advantage of 25 years of corrected and gauge-adjusted weather radar data. A statistical analysis of convective rain-cells spatial and temporal characteristics was performed with respect to synoptic pattern, geographical location, and flash flood generation. Rain cells were extracted from radar data using a cell segmentation method and a tracking algorithm and were divided into rain events. A total of 10,500 rain cells, 2650 cell tracks and 424 rain events were elicited. Rain cell properties, such as mean areal and maximal rain intensity, area, life span, direction and speed, were derived. Rain events were clustered, according to several ERA-Interim atmospheric parameters, and associated with three main synoptic patterns: Cyprus Low, Low to the East of the study region and Active Red Sea Trough. The first two originate from the Mediterranean Sea, while the third is an extension of the African monsoon. On average, the convective rain cells in the region are 90 km2 in size, moving from West to East in 13 ms-1 and living 18 minutes. Several significant differences between rain cells of the various synoptic types were observed. In particular, Active Red Sea Trough rain cells are characterized by higher rain intensities and lower speeds, suggesting a higher flooding potential for small catchments. The north

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

    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

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

    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

  2. Detection of charge storage on molecular thin films of tris(8-hydroxyquinoline) aluminum (Alq3) by Kelvin force microscopy: a candidate system for high storage capacity memory cells.

    Paydavosi, Sarah; Aidala, Katherine E; Brown, Patrick R; Hashemi, Pouya; Supran, Geoffrey J; Osedach, Timothy P; Hoyt, Judy L; Bulović, Vladimir

    2012-03-14

    Retention and diffusion of charge in tris(8-hydroxyquinoline) aluminum (Alq(3)) molecular thin films are investigated by injecting electrons and holes via a biased conductive atomic force microscopy tip into the Alq(3) films. After the charge injection, Kelvin force microscopy measurements reveal minimal changes with time in the spatial extent of the trapped charge domains within Alq(3) films, even for high hole and electron densities of >10(12) cm(-2). We show that this finding is consistent with the very low mobility of charge carriers in Alq(3) thin films (<10(-7) cm(2)/(Vs)) and that it can benefit from the use of Alq(3) films as nanosegmented floating gates in flash memory cells. Memory capacitors using Alq(3) molecules as the floating gate are fabricated and measured, showing durability over more than 10(4) program/erase cycles and the hysteresis window of up to 7.8 V, corresponding to stored charge densities as high as 5.4 × 10(13) cm(-2). These results demonstrate the potential for use of molecular films in high storage capacity nonvolatile memory cells. © 2012 American Chemical Society

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

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

    2017-06-05

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

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

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

    2013-09-01

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

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

    Paul U Cameron

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

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

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

    2011-01-01

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

  7. Non-volatile memories

    Lacaze, Pierre-Camille

    2014-01-01

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

  8. Physics Flash August 2016

    Kippen, Karen Elizabeth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-08-25

    Physics Flash is the newsletter for the Physics Division at Los Alamos National Laboratory. This newsletter is for August 2016. The following topics are covered: "Accomplishments in the Trident Laser Facility", "David Meyerhofer elected as chair-elect APS Nominating Committee", "HAWC searches for gamma rays from dark matter", "Proton Radiography Facility commissions electromagnetic magnifier", and "Cosmic ray muon computed tomography of spent nuclear fuel in dry storage casks."

  9. The lightning flash

    Cooray, Vernon

    2014-01-01

    With contributions from today's leading lightning engineers and researchers, this updated 2nd edition of Vernon Cooray's classic text, The Lightning Flash provides the reader with an essential introduction to lightning and its impact on electrical and electronic equipment. Providing the reader with a thorough background into almost every aspect of lightning and its impact on electrical and electronic equipment, this new edition is updated throughout and features eight new chapters that bring the science up to date.

  10. Deconstructing continuous flash suppression

    Yang, Eunice; Blake, Randolph

    2012-01-01

    In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in co...

  11. Coherent imaging at FLASH

    Chapman, H N; Bajt, S; Duesterer, S; Treusch, R; Barty, A; Benner, W H; Bogan, M J; Frank, M; Hau-Riege, S P; Woods, B W; Boutet, S; Cavalleri, A; Hajdu, J; Iwan, B; Seibert, M M; Timneanu, N; Marchesini, S; Sakdinawat, A; Sokolowski-Tinten, K

    2009-01-01

    We have carried out high-resolution single-pulse coherent diffractive imaging at the FLASH free-electron laser. The intense focused FEL pulse gives a high-resolution low-noise coherent diffraction pattern of an object before that object turns into a plasma and explodes. In particular we are developing imaging of biological specimens beyond conventional radiation damage resolution limits, developing imaging of ultrafast processes, and testing methods to characterize and perform single-particle imaging.

  12. Physics Flash December 2016

    Kippen, Karen Elizabeth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). ADEPS Communications

    2016-12-01

    This is the December 2016 issue of Physics Flash, the newsletter of the Physics Division of Los Alamos National Laboratory (LANL). In this issue, the following topics are covered: Novel liquid helium technique to aid highly sensitive search for a neutron electrical dipole moment; Silverleaf: Prototype Red Sage experiments performed at Q-site; John L. Kline named 2016 APS Fellow; Physics students in the news; First Entropy Engine quantum random number generator hits the market; and celebrating service.

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

    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.

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

    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

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

    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

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

    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....

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

    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.

    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

    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. Nonvolatile memory design magnetic, resistive, and phase change

    Li, Hai

    2011-01-01

    The manufacture of flash memory, which is the dominant nonvolatile memory technology, is facing severe technical barriers. So much so, that some emerging technologies have been proposed as alternatives to flash memory in the nano-regime. Nonvolatile Memory Design: Magnetic, Resistive, and Phase Changing introduces three promising candidates: phase-change memory, magnetic random access memory, and resistive random access memory. The text illustrates the fundamental storage mechanism of these technologies and examines their differences from flash memory techniques. Based on the latest advances,

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

    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

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

    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

  3. Crystal growth within a phase change memory cell.

    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.

  4. Eight-logic memory cell based on multiferroic junctions

    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)

  5. Flashing inception in flowing liquids

    Jones, O.C. Jr.

    1979-01-01

    The inception of net vaporization in flashing flows is examined. It is suggested that the flashing inception can be expressed as two additive effects. One is due to the static decompression which is a function of the spinodal limit and also of the expansion rate. The other effect which is a function of Reynolds number and flashing index, is due to the turbulent fluctuations of the flowing liquid. It is shown that by taking a three standard deviation band on the turbulent velocity fluctuations, an adequate representation of the inverse mass flux effect on flashing inception for existing data is obtained

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

    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. Modular Electronics for Flash Memory Production

    2011-12-28

    DEFENSE TECHNICAL INFORMATION CENTER ImuM ktkUmlimäj DTICfhas determined on oc öf^H AJI that this Technical Document has the Distribution...the second harmonic (8I2/8V2), and a normalization to remove the scale of the measured current. The red dashed lines represent notable vibrational...superimposed as red dashed lines. The agreement between the two spectroscopies is conclusive that we have successfully put our OPE derivative into the gap

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

    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.

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

    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.

  10. Flash X-ray

    Sato, Eiichi

    2003-01-01

    Generation of quasi-monochromatic X-ray by production of weakly ionized line plasma (flash X-ray), high-speed imaging by the X-ray and high-contrast imaging by the characteristic X-ray absorption are described. The equipment for the X-ray is consisted from the high-voltage power supply and condenser, turbo molecular pump, and plasma X-ray tube. The tube has a long linear anticathode to produce the line plasma and flash X-ray at 20 kA current at maximum. X-ray spectrum is measured by the imaging plate equipped in the computed radiography system after diffracted by a LiF single crystal bender. Cu anticathode generates sharp peaks of K X-ray series. The tissue images are presented for vertebra, rabbit ear and heart, and dog heart by X-ray fluoroscopy with Ce anticathode. Generation of K-orbit characteristic X-ray with extremely low bremsstrahung is to be attempted for medical use. (N.I.)

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

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

    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.

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

    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.

  14. 1Protein Energy Malnutrition Impairs Homeostatic Proliferation of Memory CD8 T cells

    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

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

    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.

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

    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.

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

    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.

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

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

    2013-01-01

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

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

    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

    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

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

    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

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

    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.

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

    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.

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

    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

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

    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...

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

    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

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

    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.

  9. Laser-flash calorimetry

    Takahashi, Y.; Nakamura, J.-I.

    1982-01-01

    The heat capacity of vanadium has been measured by laser-flash calorimetry in the temperature region from 80 to 1000 K. The results are compared with available low- and high-temperature heat capacities, and revised thermodynamic values of vanadium are given. No heat-capacity anomaly has been found in the pure vanadium sample over the temperature range investigated, while a small heat-capacity discontinuity, less than 1.2 J.K -1 .mol -1 , has been observed at 220 to 230 K on the same sample but electropolished before measurement. This anomaly disappeared after annealing at 1000 K in vacuo for 1 h and is attributable to the introduction of a small amount of hydrogen during electropolishing. (author)

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

    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. Flashing oscillation in pool water

    Takamasa, Tomoji; Kondo, Koichi; Hazuku, Tatsuya

    1996-01-01

    This paper presents an experimental study of high-pressure saturated water discharging into the pool water. The purpose of the experiment is to clarify the phenomena that occur in blow-down of high-pressure saturated water from the pressure vessel into the water-filled containment in the case of a wall-crack accident or a LOCA in an advanced reactor. The results revealed that a flashing oscillation (FO) occurs when high-pressure saturated water discharges into the pool water, under specified experimental settings. The range of the flashing oscillates between a point very close to and some distance from the vent hole. The pressures in the vent tube and pool water vary according to the flashing oscillation. The pressure oscillation and frequency of flashing position might be caused by the balancing action between the supply of saturated water, flashing at the control volume and its condensation on the steam-water interface. A linear analysis was conducted using a spherical flashing bubble model. The period of the flashing oscillation in the experiments can be explained by theoretical analysis

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

    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.

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

    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.

  14. Flashing coupled density wave oscillation

    Jiang Shengyao; Wu Xinxin; Zhang Youjie

    1997-07-01

    The experiment was performed on the test loop (HRTL-5), which simulates the geometry and system design of the 5 MW reactor. The phenomenon and mechanism of different kinds of two-phase flow instabilities, namely geyser instability, flashing instability and flashing coupled density wave instability are described. The especially interpreted flashing coupled density wave instability has never been studied well, it is analyzed by using a one-dimensional non-thermo equilibrium two-phase flow drift model computer code. Calculations are in good agreement with the experiment results. (5 refs.,5 figs., 1 tab.)

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

    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

  16. Memories.

    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,…

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

    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.

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

    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

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

    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.

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

    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

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

    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

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

    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.

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

    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.

  4. Observers can reliably identify illusory flashes in the illusory flash paradigm

    Erp, J.B.F. van; Philippi, T.G.; Werkhoven, P.

    2013-01-01

    In the illusory flash paradigm, a single flash may be experienced as two flashes when accompanied by two beeps or taps, and two flashes may be experienced as a single flash when accompanied by one beep or tap. The classic paradigm restricts responses to '1' and '2' (2-AFC), ignoring possible

  5. Flashing inception in flowing liquids

    Jones, O.C. Jr.

    1980-01-01

    The inception of net vaporization in flashing flows is examined. It is suggested that the flashing inception can be expressed as two additive effects. One is due to the static decompression which is a function of the initial temperature and also the expansion rate. The other effect which is a function of Reynolds number and flashing index, is due to the turbulent fluctuations of the flowing liquid. It is shown that by taking a three standard deviation band on the turbulent velocity fluctuations, an adequate representation of the inverse mass flux effect on flashing inception for existing data is obtained. The turbulence effects are combined with the correlation of Alamgir and Lienhard to provide predictive methods recommended for the case where both static and convective decompression effects exist

  6. Research of coal flash hydropyrolysis

    Zhu, Z.; Zhu, H.; Wu, Y.; Tang, L.; Cheng, L.; Xu, Z. [East China University of Science and Technology, Shanghai (China)

    2001-02-01

    Using x-ray photoelectron spectroscopy (XPS) analyses the organic sufur of seven different Chinese coals and their semi-cokes from flash hydropyrolysis were studied. The results showed that the organic sulfur in coal was alkyal sulfur and thiophene with the peak of XPS located in 163.1-163.5 eV and 164.1-164.5 eV. The relative thiophene content in coal increased with the coal rank. The type of organic sulfur in semi-coke in flash hydropyrolysis was generally thiophene species; its XPS peak also located in 164.1-164.5 eV, and was in accord with its corresponding coal. Total alkyl sulfur and some thiophene sulfur were removed during the flash hydropyrolysis process. The alkyl sulfur had very high activity in hydrogenation reaction. Flash hydropyrolysis was an important new clean-coal technique and had notable desulfurization effect. 13 refs., 2 figs., 4 tabs.

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

    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.

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

    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.

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

    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.

  10. New flash mixing

    Sackmann, I.

    1980-01-01

    It was found that even for stars evolved away from the red giant branch, a new mixing of nucleo-synthesis products from the hydrogen-burning shells into surface layers was possible, from the penetration of the contaminated intershell region with the H- and He-ionization convection zones. This is due to the helium shell flash driving an immense expansion of an inner carbon pocket, namely, by a factor of 12,000 in radius, a drop in density of about 10 12 , and a cooling of inner pockets normally near 10 8 K to 23,000 K. The surface would be enriched in carbon ( 12 C), helium ( 4 He), and s-process elements, but not significantly in nitrogen ( 14 N), oxygen ( 16 O), or the isotope 13 C. This new type of mixing might provide the missing clue for FG Sagittae. Such a mixing had been suggested by the observations of FG Sagittae, but had been unexplainable by theory up to now

  11. Deconstructing continuous flash suppression.

    Yang, Eunice; Blake, Randolph

    2012-03-08

    In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in contrast detection thresholds) as a function of the visual features of the stimulus being suppressed and the stimulus evoking suppression, namely, the popular "Mondrian" CFS stimulus (N. Tsuchiya & C. Koch, 2005). First, we found that CFS differentially suppresses the spatial components of the suppressed stimulus: Observers' sensitivity for stimuli of relatively low spatial frequency or cardinally oriented features was more strongly impaired in comparison to high spatial frequency or obliquely oriented stimuli. Second, we discovered that this feature-selective bias primarily arises from the spatiotemporal structure of the CFS stimulus, particularly within information residing in the low spatial frequency range and within the smooth rather than abrupt luminance changes over time. These results imply that this CFS stimulus operates by selectively attenuating certain classes of low-level signals while leaving others to be potentially encoded during suppression. These findings underscore the importance of considering the contribution of low-level features in stimulus-driven effects that are reported under CFS.

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

    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....

  13. Flashing subdiffusive ratchets in viscoelastic media

    Kharchenko, Vasyl; Goychuk, Igor

    2012-01-01

    We study subdiffusive ratchet transport in periodically and randomly flashing potentials. A central Brownian particle is elastically coupled to the surrounding auxiliary Brownian quasi-particles, which account for the influence of the viscoelastic environment. Similar to standard dynamical modeling of Brownian motion, the external force influences only the motion of the central particle, not affecting directly the environmental degrees of freedom. Just a handful of auxiliary Brownian particles suffices to model subdiffusion over many temporal decades. Time modulation of the potential violates the symmetry of thermal detailed balance and induces an anomalous subdiffusive current which exhibits a remarkably small dispersion at low temperatures, as well as a number of other surprising features such as saturation at low temperatures, and multiple inversions of the transport direction upon a change of the driving frequency in the non-adiabatic regime. It is shown that the subdiffusive current is finite at zero temperature for random flashing and can be finite for periodic flashing for a certain frequency window. Our study generalizes classical Brownian motors towards operating in sticky viscoelastic environments such as the cytosol of biological cells or dense polymer solutions. (paper)

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

    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...

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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

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

    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 ...

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

    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

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

    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.

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

    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.

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

    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...

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

    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.

  19. Flashing light in microalgae biotechnology.

    Abu-Ghosh, Said; Fixler, Dror; Dubinsky, Zvy; Iluz, David

    2016-03-01

    Flashing light can enhance photosynthesis and improve the quality and quantity of microalgal biomass, as it can increase the products of interest by magnitudes. Therefore, the integration of flashing light effect into microalgal cultivation systems should be considered. However, microalgae require a balanced mix of the light/dark cycle for higher growth rates, and respond to light intensity differently according to the pigments acquired or lost during the growth. This review highlights recently published results on flashing light effect on microalgae and its applications in biotechnology, as well as the recently developed bioreactors designed to fulfill this effect. It also discusses how this knowledge can be applied in selecting the optimal light frequencies and intensities with specific technical properties for increasing biomass production and/or the yield of the chemicals of interest by microalgae belonging to different genera. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Principles of arc flash protection

    Hirschmann, R. B.

    2003-04-01

    Recent developments in NFPA 70E, the electrical safety standards in the United States and Canada, designed to provide for a safe industrial work environment, are discussed. The emphasis in this instance is on arc explosions. Development of an arc flash protective program is discussed under various major components of an electrical safety program. These are: appropriate qualifications and training for workers, safe work practices, appropriate hazard assessment practices for any task exceeding 50V where there is the potential of an arc flash accident, flash protection equipment commensurate with the hazard associated with the task to be performed, layering in protective clothing over all body surfaces, and strict adherence to rules regarding use of safety garments and equipment.

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

    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....

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

    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.

  3. Flash sintering of ceramic materials

    Dancer, C. E. J.

    2016-10-01

    During flash sintering, ceramic materials can sinter to high density in a matter of seconds while subjected to electric field and elevated temperature. This process, which occurs at lower furnace temperatures and in shorter times than both conventional ceramic sintering and field-assisted methods such as spark plasma sintering, has the potential to radically reduce the power consumption required for the densification of ceramic materials. This paper reviews the experimental work on flash sintering methods carried out to date, and compares the properties of the materials obtained to those produced by conventional sintering. The flash sintering process is described for oxides of zirconium, yttrium, aluminium, tin, zinc, and titanium; silicon and boron carbide, zirconium diboride, materials for solid oxide fuel applications, ferroelectric materials, and composite materials. While experimental observations have been made on a wide range of materials, understanding of the underlying mechanisms responsible for the onset and latter stages of flash sintering is still elusive. Elements of the proposed theories to explain the observed behaviour include extensive Joule heating throughout the material causing thermal runaway, arrested by the current limitation in the power supply, and the formation of defect avalanches which rapidly and dramatically increase the sample conductivity. Undoubtedly, the flash sintering process is affected by the electric field strength, furnace temperature and current density limit, but also by microstructural features such as the presence of second phase particles or dopants and the particle size in the starting material. While further experimental work and modelling is still required to attain a full understanding capable of predicting the success of the flash sintering process in different materials, the technique non-etheless holds great potential for exceptional control of the ceramic sintering process.

  4. Quick Guide to Flash Catalyst

    Elmansy, Rafiq

    2011-01-01

    How do you transform user interface designs created in Photoshop or Illustrator into interactive web pages? It's easier than you think. This guide shows you how to use Adobe Flash Catalyst to create interactive UIs and website wireframes for Rich Internet Applications-without writing a single line of code. Ideal for web designers, this book introduces Flash Catalyst basics with detailed step-by-step instructions and screenshots that illustrate every part of the process. You'll learn hands-on how to turn your static design or artwork into working user interfaces that can be implemented in Fla

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

    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.

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

    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.

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

    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.

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

    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.

  9. Hot Flashes amd Night Sweats (PDQ)

    ... Professionals Questions to Ask about Your Treatment Research Hot Flashes and Night Sweats (PDQ®)–Patient Version Overview ... quality of life in many patients with cancer. Hot flashes and night sweats may be side effects ...

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

    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.

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

    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.

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

    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

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

    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.

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

    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.

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

    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.

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

    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

  17. Detection of Malicious Flash Banner Advertisements

    Kirill Alekseevich Samosadnyy

    2014-09-01

    Full Text Available The paper addresses the problem of detecting malicious flash advertisements. As a result, detection method based on dynamic analysis that modify flash application and execute it in Adobe Flash player is proposed and evaluated on synthetic and real world examples.

  18. Flash CS4: The Missing Manual

    Grover, Chris

    2008-01-01

    Unlock the power of Flash and bring gorgeous animations to life onscreen. Flash CS4: The Missing Manual includes a complete primer on animation, a guided tour of the program's tools and capabilities, lots of new illustrations, and more details on working with video. Beginners will learn to use the software in no time, and experienced Flash designers will improve their skills.

  19. RELATIONSHIP BETWEEN FLASH POINTS OF SOME BINARY ...

    B. S. Chandravanshi

    Miscellaneous binary blends containing solvent neutral-150 (SN-150), ... viscosity, the flash point test has always been a standard part of a lubricant's specification. ... between structure and flash points of organic compounds [5-12] and fuels [13, 14]. ... in binary mixtures, the gaps between flash points would be high enough.

  20. Jaan Toomik ajakirjas Flash Art

    1999-01-01

    Kunstiajakirja "Flash Art" maikuu numbris Ando Keskküla artikkel, mis annab ülevaate J. Toomiku loomingust ja peatub pikemalt tema olulisematel töödel. 10. juunist J. Toomiku isiknäitus Londoni fotograafide galeriis. Eksponeeritud video "Uisutaja"

  1. Ingmar Muusikuse foto Flash Artis

    1999-01-01

    Flash Arti 1999. a. oktoobrinumbris virtuaalse näituse rubriigis Ando Keskküla artikkel radikaalsemast eesti kunstist ja kunstielust postsotsialistlikul ajastul. Illustratsiooniks Liina Siibi fotokompositsioonid, Ingmar Muusikuse foto Raoul Kurvitza, Ene-Liis Semperi ja Kiwa Eesti Panga performance'ist

  2. Undergraduate Separations Utilizing Flash Chromatography

    Horowitz, G.

    2000-02-01

    This article describes the procedures used to carry out four flash chromatography experiments: the isolation of the carotenes, chlorophylls and xanthophylls from a spinach extract; the separation of ß-carotene from tetraphenyl cyclopentadienone; the isolation of (+) and (-) carvone from caraway and spearmint oil; and the purification of benzil from benzoin. Apparatus used is nonbreakable, easy to use, and inexpensive.

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

    Catherine eGottschalk

    2015-07-01

    Full Text Available New vaccination strategies focus on achieving CD8+ T cell (CTL immunity rather than on induction of protective antibody responses. While the requirement of CD4+ T (Th cell help in dendritic cell (DC activation and licensing, and in CTL memory induction has been described in several disease models, CTL responses may occur in a Th cell help independent manner. Natural Killer T cells (NKT cells can substitute for Th cell help and license DC as well. NKT cells produce a broad spectrum of Th1 and Th2 cytokines, thereby inducing a similar set of costimulatory molecules and cytokines in DC. This form of licensing differs from Th cell help by inducing other chemokines: while Th cell licensed DC produce CCR5 ligands, NKT cell-licensed DC produce CCL17 which attracts CCR4+ CD8+ T cells for subsequent activation. It has recently been shown that iNKT cells do not only enhance immune responses against bacterial pathogens or parasites, but also play a role in viral infections. The inclusion of NKT cell ligands in Influenza virus vaccines enhanced memory CTL generation and protective immunity in a mouse model. This review will focus on the role of iNKT cells in the cross-talk with cross-priming DC and memory CD8+ T cell formation.

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

    Apiwat Sirichoat

    2015-10-01

    Full Text Available Asiatic acid is a pentacyclic triterpene from Centella asiatica. Previous studies have reported that asiatic acid exhibits antioxidant and neuroprotective activities in cell culture. It also prevents memory deficits in animal models. The objective of this study was to investigate the relationship between spatial working memory and changes in cell proliferation within the hippocampus after administration of asiatic acid to male Spraque-Dawley rats. Control rats received vehicle (propylene glycol while treated rats received asiatic acid (30 mg/kg orally for 14 or 28 days. Spatial memory was determined using the novel object location (NOL test. In animals administered asiatic acid for both 14 and 28 days, the number of Ki-67 positive cells in the subgranular zone of the dentate gyrus was significantly higher than in control animals. This was associated with a significant increase in their ability to discriminate between novel and familiar object locations in a novel object discrimination task, a hippocampus-dependent spatial memory test. Administration of asiatic acid also significantly increased doublecortin (DCX and Notch1 protein levels in the hippocampus. These findings demonstrate that asiatic acid treatment may be a potent cognitive enhancer which improves hippocampal-dependent spatial memory, likely by increasing hippocampal neurogenesis.

  5. SPATIAL MEMORY IMPAIRMENT AND HIPPOCAMPAL CELL LOSS INDUCED BY OKADAIC ACID (EXPERIMENTAL STUDY).

    Chighladze, M; Dashniani, M; Beselia, G; Kruashvili, L; Naneishvili, T

    2016-01-01

    In the present study, we evaluated and compared effect of intracerebroventricular (ICV) and intrahippocampal bilateral microinjection of okadaic acid (OA) on spatial memory function assessed in one day water maze paradigm and hippocampal structure in rats. Rats were divided in following groups: Control(icv) - rats injected with ICV and aCSF; Control(hipp) - rats injected intrahippocampally with aCSF; OAicv - rats injected with ICV and OA; OAhipp - rats injected intrahippocampally with OA. Nissl staining of hippocampal sections showed that the pyramidal cell loss in OAhipp group is significantly higher than that in the OAicv. The results of behavioral experiments showed that ICV or intrahippocampal bilateral microinjection of OA did not affect learning process and short-term spatial memory but induced impairment in spatial long-term memory assessed in probe test performance 24 h after training. OA-induced spatial memory impairment may be attributed to the hippocampal cell death. Based on these results OA induced memory deficit and hippocampal cell loss in rat may be considered as a potential animal model for preclinical evaluation of antidementic drug activity.

  6. Transplanted Bone Marrow Mesenchymal Stem Cells Improve Memory in Rat Models of Alzheimer's Disease

    Parvin Babaei

    2012-01-01

    Full Text Available The present study aims to evaluate the effect of bone marrow mesenchymal stem cells (MSCs grafts on cognition deficit in chemically and age-induced Alzheimer's models of rats. In the first experiments aged animals (30 months were tested in Morris water maze (MWM and divided into two groups: impaired memory and unimpaired memory. Impaired groups were divided into two groups and cannulated bilaterally at the CA1 of the hippocampus for delivery of mesenchymal stem cells (500×103/ and PBS (phosphate buffer saline. In the second experiment, Ibotenic acid (Ibo was injected bilaterally into the nucleus basalis magnocellularis (NBM of young rats (3 months and animals were tested in MWM. Then, animals with memory impairment received the following treatments: MSCs (500×103/ and PBS. Two months after the treatments, cognitive recovery was assessed by MWM in relearning paradigm in both experiments. Results showed that MSCs treatment significantly increased learning ability and memory in both age- and Ibo-induced memory impairment. Adult bone marrow mesenchymal stem cells show promise in treating cognitive decline associated with aging and NBM lesions.

  7. The relation between T-cell expression of LFA-1 and immunological memory

    Hviid, L; Odum, N; Theander, T G

    1993-01-01

    Antibodies against isotypes of the leucocyte common antigen (LCA, CD45) can be used to identify largely reciprocal subsets of human peripheral T cells, characterized by differential ability to respond to recall antigen in vitro. The transition from naive, unprimed T cells to memory cells capable...... of responding to recall stimulating has been associated with a switch in surface expression of CD45 from the CD45RA isotype to CD45RO. It has been proposed that this transition is accompanied by the coordinated up-regulation of a number of cell-surface molecules involved in cellular adhesion and/or activation......, including the leucocyte function-associated antigens (LFA). In the present study we have examined the expression of LFA-1 on subsets of human peripheral T cells, and related it to the expression of markers of cellular activation and CD45 isotypes, and thus to immunological memory. Our results suggest...

  8. Circulating CXCR5+CD4+ T Follicular-Like Helper Cell and Memory B Cell Responses to Human Papillomavirus Vaccines

    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

  9. Tissue-resident memory CD8+ T cells continuously patrol skin epithelia to quickly recognize local antigen

    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

  10. Diet-induced obesity does not impact the generation and maintenance of primary memory CD8 T cells.

    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.

  11. Deficiency in memory B cell compartment in a patient with infertility and recurrent pregnancy losses.

    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.

  12. Fluoxetine prevents the memory deficits and reduction in hippocampal cell proliferation caused by valproic acid.

    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

  13. Human Memory B Cells Targeting Staphylococcus aureus Exotoxins Are Prevalent with Skin and Soft Tissue Infection

    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.

  14. Memory of Natural Killer Cells: A New Chance against Mycobacterium tuberculosis?

    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.

  15. Tissue-resident memory T cells in tissue homeostasis, persistent infection, and cancer surveillance.

    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.

  16. 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

    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

  17. Quantitative Analysis of Memristance Defined Exponential Model for Multi-bits Titanium Dioxide Memristor Memory Cell

    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.

  18. CD73 expression identifies a subset of IgM+ antigen-experienced cells with memory attributes that is T cell and CD40 signalling dependent.

    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.

  19. Speeding up the flash calculations in two-phase compositional flow simulations - The application of sparse grids

    Wu, Yuanqing

    2015-03-01

    Flash calculations have become a performance bottleneck in the simulation of compositional flow in subsurface reservoirs. We apply a sparse grid surrogate model to substitute the flash calculation and thus try to remove the bottleneck from the reservoir simulation. So instead of doing a flash calculation in each time step of the simulation, we just generate a sparse grid approximation of all possible results of the flash calculation before the reservoir simulation. Then we evaluate the constructed surrogate model to approximate the values of the flash calculation results from this surrogate during the simulations. The execution of the true flash calculation has been shifted from the online phase during the simulation to the offline phase before the simulation. Sparse grids are known to require only few unknowns in order to obtain good approximation qualities. In conjunction with local adaptivity, sparse grids ensure that the accuracy of the surrogate is acceptable while keeping the memory usage small by only storing a minimal amount of values for the surrogate. The accuracy of the sparse grid surrogate during the reservoir simulation is compared to the accuracy of using a surrogate based on regular Cartesian grids and the original flash calculation. The surrogate model improves the speed of the flash calculations and the simulation of the whole reservoir. In an experiment, it is shown that the speed of the online flash calculations is increased by about 2000 times and as a result the speed of the reservoir simulations has been enhanced by 21 times in the best conditions.

  20. Tissue-specific B-cell dysfunction and generalized memory B-cell loss during acute SIV infection.

    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

  1. Foundation Flash CS4 for Designers

    Green, Tom

    2008-01-01

    In this book, you'll learn:* How to create effective animations using the new Motion Editor and animation tools * How to use the new 3D features to animate objects in 3D space * Best-practice tips and techniques from some of the top Flash practitioners on the planet * How to create captioned video and full-screen video, and deploy HD video using Flash * Techniques for using the Flash UI components as well as XML documents to create stunning,interactive presentations If you're a Flash designer looking for a solid overview of Flash CS4, this book is for you. Through the use of solid and practica

  2. NK Cell-Mediated Regulation of Protective Memory Responses against Intracellular Ehrlichial Pathogens.

    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.

  3. Excess influx of Zn(2+) into dentate granule cells affects object recognition memory via attenuated LTP.

    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.

  4. Past matrix stiffness primes epithelial cells and regulates their future collective migration through a mechanical memory.

    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.

  5. A colitogenic memory CD4+ T cell population mediates gastrointestinal graft-versus-host disease

    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

  6. Skin-resident memory CD4+ T cells enhance protection against Leishmania major infection.

    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.

  7. Thin film electroluminescent cells on the basis of Ce-doped CaGa2S4 and SrGa2S4 prepared by flash evaporation method

    Gambarov, E.; Bayramov, A.; Kato, A.; Iida, S.

    2006-01-01

    Ce-doped CaGa 2 S 4 and SrGa 2 S 4 thin film electroluminescent (TFEL) devices were prepared for the first time on the basis of films deposited by flash evaporation method. Significant crystallization, stoichiometry improvement of the films and increase of photoluminescence intensity were found after annealing in H 2 S and O 2 gas stream. EL spectra of the cells exhibited the characteristic double-band emission similar to that seen for Ce 3+ activated CaGa 2 S 4 and SrGa 2 S 4 films under photon excitation. Applied voltage and frequency dependences of the electroluminescence were studied. Low voltage operation as low as 20 V was observed for these cells. Luminance of about 4 cd/m 2 at 100 V operating voltage with 2.5 kHz frequency was achieved for the TFEL cell with films annealed in O 2 gas stream. (copyright 2006 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  8. Basic principles of STT-MRAM cell operation in memory arrays

    Khvalkovskiy, A V; Apalkov, D; Watts, S; Chepulskii, R; Beach, R S; Ong, A; Tang, X; Driskill-Smith, A; Lottis, D; Chen, E; Nikitin, V; Krounbi, M; Butler, W H; Visscher, P B

    2013-01-01

    For reliable operation, individual cells of an STT-MRAM memory array must meet specific requirements on their performance. In this work we review some of these requirements and discuss the fundamental physical principles of STT-MRAM operation, covering the range from device level to chip array performance, and methodology for its development. (paper)

  9. The Memories of NK Cells: Innate-Adaptive Immune Intrinsic Crosstalk.

    Gabrielli, Sara; Ortolani, Claudio; Del Zotto, Genny; Luchetti, Francesca; Canonico, Barbara; Buccella, Flavia; Artico, Marco; Papa, Stefano; Zamai, Loris

    2016-01-01

    Although NK cells are considered part of the innate immune system, a series of evidences has demonstrated that they possess characteristics typical of the adaptive immune system. These NK adaptive features, in particular their memory-like functions, are discussed from an ontogenetic and evolutionary point of view.

  10. The Memories of NK Cells: Innate-Adaptive Immune Intrinsic Crosstalk

    Sara Gabrielli

    2016-01-01

    Full Text Available Although NK cells are considered part of the innate immune system, a series of evidences has demonstrated that they possess characteristics typical of the adaptive immune system. These NK adaptive features, in particular their memory-like functions, are discussed from an ontogenetic and evolutionary point of view.

  11. Nanostructure-property relations for phase-change random access memory (PCRAM) line cells

    Kooi, B. J.; Oosthoek, J. L. M.; Verheijen, M. A.; Kaiser, M.; Jedema, F. J.; Gravesteijn, D. J.

    2012-01-01

    Phase-change random access memory (PCRAM) cells have been studied extensively using electrical characterization and rather limited by detailed structure characterization. The combination of these two characterization techniques has hardly been exploited and it is the focus of the present work.

  12. Increased memory phenotypes of CD4+ and CD8+ T cells in ...

    Conclusions: Children with SCA in Tanzania show an absolute increase in all leukocyte types, including lymphocytes, with skewing of both CD4+ and CD8+ T cells towards the memory phenotypes. These findings provide insights on the development of adaptive immunity which may have implications on vaccine ...

  13. B Cells Negatively Regulate the Establishment of CD49b(+)T-bet(+) Resting Memory T Helper Cells in the Bone Marrow.

    Hojyo, Shintaro; Sarkander, Jana; Männe, Christian; Mursell, Mathias; Hanazawa, Asami; Zimmel, David; Zhu, Jinfang; Paul, William E; Fillatreau, Simon; Löhning, Max; Radbruch, Andreas; Tokoyoda, Koji

    2016-01-01

    During an immune reaction, some antigen-experienced CD4 T cells relocate from secondary lymphoid organs (SLOs) to the bone marrow (BM) in a CD49b-dependent manner and reside and rest there as professional memory CD4 T cells. However, it remains unclear how the precursors of BM memory CD4 T cells are generated in the SLOs. While several studies have so far shown that B cell depletion reduces the persistence of memory CD4 T cells in the spleen, we here show that B cell depletion enhances the establishment of memory CD4 T cells in the BM and that B cell transfer conversely suppresses it. Interestingly, the number of antigen-experienced CD4 T cells in the BM synchronizes the number of CD49b(+)T-bet(+) antigen-experienced CD4 T cells in the spleen. CD49b(+)T-bet(+) antigen-experienced CD4 T cells preferentially localize in the red pulp area of the spleen and the BM in a T-bet-independent manner. We suggest that B cells negatively control the generation of CD49b(+)T-bet(+) precursors of resting memory CD4 T cells in the spleen and may play a role in bifurcation of activated effector and resting memory CD4 T cell lineages.

  14. B cells negatively regulate the establishment of CD49b+T-bet+ resting memory T helper cells in the bone marrow

    Shintaro eHojyo

    2016-02-01

    Full Text Available During an immune reaction, some antigen-experienced CD4 T cells relocate from secondary lymphoid organs (SLOs to the bone marrow (BM in a CD49b-dependent manner and reside and rest there as professional memory CD4 T cells. However, it remains unclear how the precursors of BM memory CD4 T cells are generated in the SLOs. While several studies have so far shown that B cell depletion reduces the persistence of memory CD4 T cells in the spleen, we here show that B cell depletion enhances the establishment of memory CD4 T cells in the BM and that B cell transfer conversely suppresses it. Interestingly, the number of antigen-experienced CD4 T cells in the BM synchronizes the number of CD49b+T-bet+ antigen-experienced CD4 T cells in the spleen. CD49b+T-bet+ antigen-experienced CD4 T cells preferentially localize in the red pulp area of the spleen and the BM in a T-bet-independent manner. We suggest that B cells negatively control the generation of CD49b+T-bet+ precursors of resting memory CD4 T cells in the spleen and may play a role in bifurcation of activated effector and resting memory CD4 T cell lineages.

  15. Dual-functional Memory and Threshold Resistive Switching Based on the Push-Pull Mechanism of Oxygen Ions

    Huang, Yi-Jen; Chao, Shih-Chun; Lien, Der-Hsien; Wen, Cheng-Yen; He, Jr-Hau; Lee, Si-Chen

    2016-01-01

    The combination of nonvolatile memory switching and volatile threshold switching functions of transition metal oxides in crossbar memory arrays is of great potential for replacing charge-based flash memory in very-large-scale integration. Here, we

  16. On multiphase negative flash for ideal solutions

    Yan, Wei; Stenby, Erling Halfdan

    2012-01-01

    simpler than the corresponding normal flash algorithm. Unlike normal flash, multiphase negative flash for ideal solutions can diverge if the feasible domain for phase amounts is not closed. This can be judged readily during the iteration process. The algorithm can also be extended to the partial negative......There is a recent interest to solve multiphase negative flash problems where the phase amounts can be negative for normal positive feed composition. Solving such a negative flash problem using successive substitution needs an inner loop for phase distribution calculation at constant fugacity...... coefficients. It is shown that this inner loop, named here as multiphase negative flash for ideal solutions, can be solved either by Michelsen's algorithm for multiphase normal flash, or by its variation which uses F−1 phase amounts as independent variables. In either case, the resulting algorithm is actually...

  17. Expansion of mycobacterium-reactive gamma delta T cells by a subset of memory helper T cells.

    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.

  18. Disruptive effect of Dzyaloshinskii-Moriya interaction on the magnetic memory cell performance

    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.

  19. AMPKα1: a glucose sensor that controls CD8 T-cell memory.

    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.

  20. CD8 T cell memory to a viral pathogen requires trans cosignaling between HVEM and BTLA.

    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.

  1. T Cell Responses: Naive to Memory and Everything in Between

    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…

  2. De novo alloreactive memory CD8+ T cells develop following allogeneic challenge when CNI immunosuppression is delayed.

    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.

  3. Phase change memory

    Qureshi, Moinuddin K

    2011-01-01

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

  4. Spurious dispersion effects at FLASH

    Prat, Eduard

    2009-07-01

    The performance of the Free-Electron Laser (FEL) process imposes stringent demands on the transverse trajectory and size of the electron beam. Since transverse dispersion changes off-energy particle trajectories and increases the effective beam size, dispersion must be controlled. This thesis treats the concept of dispersion in linacs, and analyses the impact of dispersion on the electron beam and on the FEL process. It presents generation mechanisms for spurious dispersion, quantifying its importance for FLASH (Free-electron Laser in Hamburg) and the XFEL (European X-ray Free-Electron Laser). A method for measuring and correcting dispersion and its implementation in FLASH is described. Experiments of dispersion e ects on the transverse beam quality and on the FEL performance are presented. (orig.)

  5. Flash x-ray cinematography

    Stein, W.E.

    1976-01-01

    Experiments intended to provide an overview of the potential capabilities and limitations of flash x-ray cinematography as a diagnostic technique for a Fast Reactor Safety Test Facility are described. The results provide estimates of the x-ray pulse intensity required to obtain adequate radiographs of an array of fuel pins in a typical reactor configuration. An estimate of the upper limit on the pulse duration imposed by the reactor background radiation was also determined. X-ray cinematography has been demonstrated at a repetition rate limited only by the recording equipment on hand at the time of these measurements. These preliminary results indicate that flash x-ray cinematography of the motion of fuel in a Fast Reactor Test Facility is technically feasible

  6. Spurious dispersion effects at FLASH

    Prat, Eduard

    2009-07-15

    The performance of the Free-Electron Laser (FEL) process imposes stringent demands on the transverse trajectory and size of the electron beam. Since transverse dispersion changes off-energy particle trajectories and increases the effective beam size, dispersion must be controlled. This thesis treats the concept of dispersion in linacs, and analyses the impact of dispersion on the electron beam and on the FEL process. It presents generation mechanisms for spurious dispersion, quantifying its importance for FLASH (Free-electron Laser in Hamburg) and the XFEL (European X-ray Free-Electron Laser). A method for measuring and correcting dispersion and its implementation in FLASH is described. Experiments of dispersion e ects on the transverse beam quality and on the FEL performance are presented. (orig.)

  7. A Content-Addressable Memory structure using quantum cells in nanotechnology with energy dissipation analysis

    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.

  8. IGF1-Dependent Synaptic Plasticity of Mitral Cells in Olfactory Memory during Social Learning.

    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.

  9. MicroRNA-21 preserves the fibrotic mechanical memory of mesenchymal stem cells.

    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.

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

    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

  11. Functional, Antigen-Specific Stem Cell Memory (TSCM CD4+ T Cells Are Induced by Human Mycobacterium tuberculosis Infection

    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

  12. Towards Terabit Memories

    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. CD27 instructs CD4+ T cells to provide help for the memory CD8+ T cell response after protein immunization

    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

  14. Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells.

    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.

  15. Hot flashes and sleep in women.

    Moe, Karen E

    2004-12-01

    Sleep disturbances during menopause are often attributed to nocturnal hot flashes and 'sweats' associated with changing hormone patterns. This paper is a comprehensive critical review of the research on the relationship between sleep disturbance and hot flashes in women. Numerous studies have found a relationship between self-reported hot flashes and sleep complaints. However, hot flash studies using objective sleep assessment techniques such as polysomnography, actigraphy, or quantitative analysis of the sleep EEG are surprisingly scarce and have yielded somewhat mixed results. Much of this limited evidence suggests that hot flashes are associated with objectively identified sleep disruption in at least some women. At least some of the negative data may be due to methodological issues such as reliance upon problematic self-reports of nocturnal hot flashes and a lack of concurrent measures of hot flashes and sleep. The recent development of a reliable and non-intrusive method for objectively identifying hot flashes during the night should help address the need for substantial additional research in this area. Several areas of clinical relevance are described, including the effects of discontinuing combined hormone therapy (estrogen plus progesterone) or estrogen-only therapy, the possibility of hot flashes continuing for many years after menopause, and the link between hot flashes and depression.

  16. Fast Response, Open-Celled Porous, Shape Memory Effect Actuators with Integrated Attachments

    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.

  17. Structural and electrical characterization of phase‐change memory line cells

    Oosthoek, Jasper

    2014-01-01

    De afgelopen tien jaar is Flash geheugen veel toegepast in o.a. USB sticks en later ook in smartphones en tablets. Een geheugentype waarvan verwacht werd dat ze Flash zou kunnen vervangen is Phase-change RAM of PRAM. NXP, dat toendertijd nog bekend stond als Philips Semiconductors, introduceerde het

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

    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.

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

    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.

  20. Granule cell dispersion is associated with memory impairment in right mesial temporal lobe epilepsy.

    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.

  1. Regulatory role for the memory B cell as suppressor-inducer of feedback control

    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

  2. Human Infant Memory B Cell and CD4+ T Cell Responses to HibMenCY-TT Glyco-Conjugate Vaccine.

    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.

  3. Curtailed T-cell activation curbs effector differentiation and generates CD8+ T cells with a naturally-occurring memory stem cell phenotype.

    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.

  4. Flexible NAND-Like Organic Ferroelectric Memory Array

    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

  5. Diet-induced obesity in mice reduces the maintenance of influenza-specific CD8+ memory T cells.

    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.

  6. The future of memory

    Marinella, M.

    In the not too distant future, the traditional memory and storage hierarchy of may be replaced by a single Storage Class Memory (SCM) device integrated on or near the logic processor. Traditional magnetic hard drives, NAND flash, DRAM, and higher level caches (L2 and up) will be replaced with a single high performance memory device. The Storage Class Memory paradigm will require high speed (read/write), excellent endurance (> 1012), nonvolatility (retention > 10 years), and low switching energies (memory (PCM). All of these devices show potential well beyond that of current flash technologies and research efforts are underway to improve the endurance, write speeds, and scalabilities to be on-par with DRAM. This progress has interesting implications for space electronics: each of these emerging device technologies show excellent resistance to the types of radiation typically found in space applications. Commercially developed, high density storage class memory-based systems may include a memory that is physically radiation hard, and suitable for space applications without major shielding efforts. This paper reviews the Storage Class Memory concept, emerging memory devices, and possible applicability to radiation hardened electronics for space.

  7. Protection against Pertussis in Humans Correlates to Elevated Serum Antibodies and Memory B Cells

    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.

  8. Every breath you take: the impact of environment on resident memory CD8 T cells in the lung.

    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.

  9. Every breath you take: The impact of environment on resident memory CD8 T cells in the lung

    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.

  10. A dual-docking microfluidic cell migration assay (D2-Chip) for testing neutrophil chemotaxis and the memory effect.

    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.

  11. Persistence of memory B-cell and T-cell responses to the quadrivalent HPV vaccine in HIV-infected children.

    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.

  12. Evaluation of Flash Bainite in 4130 Steel

    2011-07-01

    Technical Report ARWSB-TR-11011 Evaluation of Flash Bainite in 4130 Steel G. Vigilante M. Hespos S. Bartolucci...4. TITLE AND SUBTITLE Evaluation of Flash Bainite in 4130 Steel 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...need to be addressed, the Flash Bainite processing of 4130 steel demonstrates promise for applications needing a combination of high strength with

  13. Construction and performance of large flash chambers

    Taylor, F.E.; Bogert, D.; Fisk, R.; Stutte, L.; Walker, J.K.; Wolfson, J.; Abolins, M.; Ernwein, J.; Owen, D.; Lyons, T.

    1979-01-01

    The construction and performance of 12' x 12' flash chambers used in a 340 ton neutrino detector under construction at Fermilab is described. The flash chambers supply digital information with a spatial resolution of 0.2'', and are used to finely sample the shower development of the reaction products of neutrino interactions. The flash chambers are easy and inexpensive to build and are electronically read out

  14. Menopausal Hot Flashes and White Matter Hyperintensities

    Thurston, Rebecca C.; Aizenstein, Howard J.; Derby, Carol A.; Sejdić, Ervin; Maki, Pauline M.

    2015-01-01

    Objective Hot flashes are the classic menopausal symptom. Emerging data links hot flashes to cardiovascular disease (CVD) risk, yet how hot flashes are related to brain health is poorly understood. We examined the relationship between hot flashes - measured via physiologic monitor and self-report - and white matter hyperintensities (WMH) among midlife women. Methods Twenty midlife women ages 40-60 without clinical CVD, with their uterus and both ovaries, and not taking hormone therapy were recruited. Women underwent 24 hours of ambulatory physiologic and diary hot flash monitoring to quantify hot flashes; magnetic resonance imaging to assess WMH burden; 72 hours of actigraphy and questionnaires to quantify sleep; and a blood draw, questionnaires, and physical measures to quantify demographics and CVD risk factors. Test of a priori hypotheses regarding relations between physiologically-monitored and self-reported wake and sleep hot flashes and WMH were conducted in linear regression models. Results More physiologically-monitored hot flashes during sleep were associated with greater WMH, controlling for age, race, and body mass index [beta(standard error)=.0002 (.0001), p=.03]. Findings persisted controlling for sleep characteristics and additional CVD risk factors. No relations were observed for self-reported hot flashes. Conclusions More physiologically-monitored hot flashes during sleep were associated with greater WMH burden among midlife women free of clinical CVD. Results suggest that relations between hot flashes and CVD risk observed in the periphery may extend to the brain. Future work should consider the unique role of sleep hot flashes in brain health. PMID:26057822

  15. Modelling and mitigation of Flash Crashes

    Fry, John; Serbera, Jean-Philippe

    2017-01-01

    The algorithmic trading revolution has had a dramatic effect upon markets. Trading has become faster, and in some ways more efficient, though potentially at the cost higher volatility and increased uncertainty. Stories of predatory trading and flash crashes constitute a new financial reality. Worryingly, highly capitalised stocks may be particularly vulnerable to flash crashes. Amid fears of high-risk technology failures in the global financial system we develop a model for flash crashes....

  16. Capacitor-less memory cell fabricated on nano-scale strained Si on a relaxed SiGe layer-on-insulator

    Kim, Tae-Hyun; Park, Jea-Gun

    2013-01-01

    We investigated the combined effect of the strained Si channel and hole confinement on the memory margin enhancement for a capacitor-less memory cell fabricated on nano-scale strained Si on a relaxed SiGe layer-on-insulator (ε-Si SGOI). The memory margin for the ε-Si SGOI capacitor-less memory cell was higher than that of the memory cell fabricated on an unstrained Si-on-insulator (SOI) and increased with increasing Ge concentration of the relaxed SiGe layer; i.e. the memory margin for the ε-Si SGOI capacitor-less memory cell (138.6 µA) at a 32 at% Ge concentration was 3.3 times higher than the SOI capacitor-less memory cell (43 µA). (paper)

  17. Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection

    Lalor, Stephen J.; Leech, John M.; O’Keeffe, Kate M.; Mac Aogáin, Micheál; O’Halloran, Dara P.; Lacey, Keenan A.; Tavakol, Mehri; Hearnden, Claire H.; Fitzgerald-Hughes, Deirdre; Humphreys, Hilary; Fennell, Jérôme P.; van Wamel, Willem J.; Foster, Timothy J.; Geoghegan, Joan A.; Lavelle, Ed C.; Rogers, Thomas R.; McLoughlin, Rachel M.

    2015-01-01

    Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S. aureus peritonitis, we demonstrated that prior exposure to S. aureus enhanced IFNγ responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naïve mice. Translating these findings, we found that S. aureus antigen-specific Th1 cells were also significantly expanded during human S. aureus bloodstream infection (BSI). These Th1 cells were CD45RO+, indicative of a memory phenotype. Thus, exposure to S. aureus induces memory Th1 cells in mice and humans, identifying Th1 cells as potential S. aureus vaccine targets. Consequently, we developed a model vaccine comprising staphylococcal clumping factor A, which we demonstrate to be an effective human T cell antigen, combined with the Th1-driving adjuvant CpG. This novel Th1-inducing vaccine conferred significant protection during S. aureus infection in mice. This study notably advances our understanding of S. aureus cellular immunity, and demonstrates for the first time that a correlate of S. aureus protective immunity identified in mice may be relevant in humans. PMID:26539822

  18. Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection.

    Brown, Aisling F

    2015-01-01

    Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S. aureus peritonitis, we demonstrated that prior exposure to S. aureus enhanced IFNγ responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naïve mice. Translating these findings, we found that S. aureus antigen-specific Th1 cells were also significantly expanded during human S. aureus bloodstream infection (BSI). These Th1 cells were CD45RO+, indicative of a memory phenotype. Thus, exposure to S. aureus induces memory Th1 cells in mice and humans, identifying Th1 cells as potential S. aureus vaccine targets. Consequently, we developed a model vaccine comprising staphylococcal clumping factor A, which we demonstrate to be an effective human T cell antigen, combined with the Th1-driving adjuvant CpG. This novel Th1-inducing vaccine conferred significant protection during S. aureus infection in mice. This study notably advances our understanding of S. aureus cellular immunity, and demonstrates for the first time that a correlate of S. aureus protective immunity identified in mice may be relevant in humans.

  19. Digital Device Architecture and the Safe Use of Flash Devices in Munitions

    Katz, Richard B.; Flowers, David; Bergevin, Keith

    2017-01-01

    Flash technology is being utilized in fuzed munition applications and, based on the development of digital logic devices in the commercial world, usage of flash technology will increase. Digital devices of interest to designers include flash-based microcontrollers and field programmable gate arrays (FPGAs). Almost a decade ago, a study was undertaken to determine if flash-based microcontrollers could be safely used in fuzes and, if so, how should such devices be applied. The results were documented in the Technical Manual for the Use of Logic Devices in Safety Features. This paper will first review the Technical Manual and discuss the rationale behind the suggested architectures for microcontrollers and a brief review of the concern about data retention in flash cells. An architectural feature in the microcontroller under study will be discussed and its use will show how to screen for weak or failed cells during manufacture, storage, or immediately prior to use. As was done for microcontrollers a decade ago, architectures for a flash-based FPGA will be discussed, showing how it can be safely used in fuzes. Additionally, architectures for using non-volatile (including flash-based) storage will be discussed for SRAM-based FPGAs.

  20. 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

    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.

  1. Flash CS5 The Missing Manual

    Grover, Chris

    2010-01-01

    Once you know how to use Flash, you can create everything from simple animations to high-end desktop applications, but it's a complex tool that can be difficult to master on your own-unless you have this Missing Manual. This book will help you learn all you need to know about Flash CS5 to create animations that bring your ideas to life. Learn animation basics. Find everything you need to know to get started with FlashMaster the Flash tools. Learn the animation and effects toolset, with clear explanations and hands-on examplesUse 3D effects. Rotate and put objects in motion in three dimensions

  2. Search Engine Optimization for Flash Best Practices for Using Flash on the Web

    Perkins, Todd

    2009-01-01

    Search Engine Optimization for Flash dispels the myth that Flash-based websites won't show up in a web search by demonstrating exactly what you can do to make your site fully searchable -- no matter how much Flash it contains. You'll learn best practices for using HTML, CSS and JavaScript, as well as SWFObject, for building sites with Flash that will stand tall in search rankings.

  3. The haptic and the visual flash-lag effect and the role of flash characteristics.

    Knut Drewing

    Full Text Available When a short flash occurs in spatial alignment with a moving object, the moving object is seen ahead the stationary one. Similar to this visual "flash-lag effect" (FLE it has been recently observed for the haptic sense that participants judge a moving hand to be ahead a stationary hand when judged at the moment of a short vibration ("haptic flash" that is applied when the two hands are spatially aligned. We further investigated the haptic FLE. First, we compared participants' performance in two isosensory visual or haptic conditions, in which moving object and flash were presented only in a single modality (visual: sphere and short color change, haptic: hand and vibration, and two bisensory conditions, in which the moving object was presented in both modalities (hand aligned with visible sphere, but the flash was presented only visually or only haptically. The experiment aimed to disentangle contributions of the flash's and the objects' modalities to the FLEs in haptics versus vision. We observed a FLE when the flash was visually displayed, both when the moving object was visual and visuo-haptic. Because the position of a visual flash, but not of an analogue haptic flash, is misjudged relative to a same visuo-haptic moving object, the difference between visual and haptic conditions can be fully attributed to characteristics of the flash. The second experiment confirmed that a haptic FLE can be observed depending on flash characteristics: the FLE increases with decreasing intensity of the flash (slightly modulated by flash duration, which had been previously observed for vision. These findings underline the high relevance of flash characteristics in different senses, and thus fit well with the temporal-sampling framework, where the flash triggers a high-level, supra-modal process of position judgement, the time point of which further depends on the processing time of the flash.

  4. Characterization of the metabolic phenotype of rapamycin-treated CD8+ T cells with augmented ability to generate long-lasting memory cells.

    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.

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

    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.

  6. Cerebral Giant Cells are Necessary for the Formation and Recall of Memory of Conditioned Taste Aversion in Lymnaea.

    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.

  7. A multi-level capacitor-less memory cell fabricated on a nano-scale strained silicon-on-insulator

    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.

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

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

    2018-01-01

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

  9. Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility

    Seumois, Grégory; Chavez, Lukas; Gerasimova, Anna; Lienhard, Matthias; Omran, Nada; Kalinke, Lukas; Vedanayagam, Maria; Ganesan, Asha Purnima V; Chawla, Ashu; Djukanović, Ratko; Ansel, K Mark; Peters, Bjoern; Rao, Anjana; Vijayanand, Pandurangan

    2014-01-01

    A characteristic feature of asthma is the aberrant accumulation, differentiation or function of memory CD4+ T cells that produce type 2 cytokines (TH2 cells). By mapping genome-wide histone modification profiles for subsets of T cells isolated from peripheral blood of healthy and asthmatic individuals, we identified enhancers with known and potential roles in the normal differentiation of human TH1 cells and TH2 cells. We discovered disease-specific enhancers in T cells that differ between healthy and asthmatic individuals. Enhancers that gained the histone H3 Lys4 dimethyl (H3K4me2) mark during TH2 cell development showed the highest enrichment for asthma-associated single nucleotide polymorphisms (SNPs), which supported a pathogenic role for TH2 cells in asthma. In silico analysis of cell-specific enhancers revealed transcription factors, microRNAs and genes potentially linked to human TH2 cell differentiation. Our results establish the feasibility and utility of enhancer profiling in well-defined populations of specialized cell types involved in disease pathogenesis. PMID:24997565

  10. Mitochondrial flash as a novel biomarker of mitochondrial respiration in the heart.

    Gong, Guohua; Liu, Xiaoyun; Zhang, Huiliang; Sheu, Shey-Shing; Wang, Wang

    2015-10-01

    Mitochondrial respiration through electron transport chain (ETC) activity generates ATP and reactive oxygen species in eukaryotic cells. The modulation of mitochondrial respiration in vivo or under physiological conditions remains elusive largely due to the lack of appropriate approach to monitor ETC activity in a real-time manner. Here, we show that ETC-coupled mitochondrial flash is a novel biomarker for monitoring mitochondrial respiration under pathophysiological conditions in cultured adult cardiac myocyte and perfused beating heart. Through real-time confocal imaging, we follow the frequency of a transient bursting fluorescent signal, named mitochondrial flash, from individual mitochondria within intact cells expressing a mitochondrial matrix-targeted probe, mt-cpYFP (mitochondrial-circularly permuted yellow fluorescent protein). This mt-cpYFP recorded mitochondrial flash has been shown to be composed of a major superoxide signal with a minor alkalization signal within the mitochondrial matrix. Through manipulating physiological substrates for mitochondrial respiration, we find a close coupling between flash frequency and the ETC electron flow, as measured by oxygen consumption rate in cardiac myocyte. Stimulating electron flow under physiological conditions increases flash frequency. On the other hand, partially block or slowdown electron flow by inhibiting the F0F1 ATPase, which represents a pathological condition, transiently increases then decreases flash frequency. Limiting electron entrance at complex I by knocking out Ndufs4, an assembling subunit of complex I, suppresses mitochondrial flash activity. These results suggest that mitochondrial electron flow can be monitored by real-time imaging of mitochondrial flash. The mitochondrial flash frequency could be used as a novel biomarker for mitochondrial respiration under physiological and pathological conditions. Copyright © 2015 the American Physiological Society.

  11. The effects of cell phone conversations on the attention and memory of bystanders.

    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.

  12. Altered distribution of peripheral blood memory B cells in humans chronically infected with Trypanosoma cruzi.

    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.

  13. Altered distribution of peripheral blood memory B cells in humans chronically infected with Trypanosoma cruzi.

    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.

  14. FinFET memory cell improvements for higher immunity against single event upsets

    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

  15. Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells

    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

  16. Rh-flash acquisition card

    Bourrion, O.

    2003-01-01

    The rh-flash card main purpose is to convert and store the image of the analog data present at input into an output buffer, namely in a given timing window besides a stop signal (like a digital oscilloscope). It is conceived in VME format 1U wide with an additional connector. Novelty of this card is its ability to sample at a high frequency, due to flash coders, and this at a high repetition rate. To do that the card allows the storage of the data considered 'useful' and that is done by storing only the data exceeding a certain threshold. This can be useful for instance for viewing peaks in a spectrum, and obtaining their relative location. The goal is to stock and process the data sampled before and after the arrival of a stop signal (what entails a storage depth). A threshold is defined and any peak exceeding its level will really be stored in the output buffer which is readable through the VME bus. The peak values will be stored as well as m preceding and n subsequent values (both programmable). Obviously, if the threshold is zero the system of data processing is off and all data will be stored. The document is structured on six sections titled: 1. Description; 2. Specifications; 3. Explaining the design of channels; 4. Explaining the shared part of the design; 5. Addressing (→ user guide); 6. Software precautions. (author)

  17. NO signatures from lightning flashes

    Stith, J.; Dye, J.; Ridley, B.; Laroche, P.; Defer, E.; Baumann, K.; Hübler, G.; Zerr, R.; Venticinque, M.

    1999-07-01

    In situ measurements of cloud properties, NO, and other trace gases were made in active thunderstorms by two research aircraft. Concurrent measurements from a three-dimensional (3-D) VHF interferometer and the 2-D National Lightning Detection Network were used to determine lightning frequency and location. The CHILL Doppler radar and the NOAA-WP-3D Orion X band Doppler radar were also used to measure storm characteristics. Two case studies from the (STERAO) Stratosphere-Troposphere Experiments: Radiation, Aerosols, and Ozone project in northeastern Colorado during the summer of 1996 are presented. Narrow spikes (0.11-0.96 km across), containing up to 19 ppbv of NO, were observed in the storms. Most were located in or downwind of electrically active regions where the NO produced by lightning would be expected. However, it was difficult to correlate individual flashes with NO spikes. A simple model of the plume of NO from lightning is used to estimate NO production from the mean mixing ratio measured in these spikes. The estimates range from 2.0×1020 to 1.0×1022 molecules of NO per meter of flash length.

  18. Effect of human bone marrow mesenchymal stromal cells on cytokine production by peripheral blood naive, memory, and effector T cells.

    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

  19. Atypical memory B cells in human chronic infectious diseases: An interim report.

    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

  20. Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells

    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

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

    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

  2. In Situ Transmission Electron Microscopy Observation of Nanostructural Changes in Phase-Change Memory

    Meister, Stefan; Kim, SangBum; Cha, Judy J.; Wong, H.-S. Philip; Cui, Yi

    2011-01-01

    Phase-change memory (PCM) has been researched extensively as a promising alternative to flash memory. Important studies have focused on its scalability, switching speed, endurance, and new materials. Still, reliability issues and inconsistent

  3. Generation mechanism of RANKL(+) effector memory B cells: relevance to the pathogenesis of rheumatoid arthritis.

    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.

  4. Aborted germinal center reactions and B cell memory by follicular T cells specific for a B cell receptor V region peptide.

    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.

  5. uFlip: Understanding Flash IO Patterns

    Bouganim, Luc; Jonsson, Bjørn; Bonnet, Philippe

    2009-01-01

    want to establish what kind of IOs should be favored (or avoided) when designing algorithms and architectures for flash-based systems. In this paper, we focus on flash IO patterns, that capture relevant distribution of IOs in time and space, and our goal is to quantify their performance. We define uFLIP...

  6. Au Contraire: Gifted in a Flash (Mob)

    Delisle, James R.

    2012-01-01

    A "flash mob" is defined by Wikipedia as "a large group of people who assemble suddenly in a public place, perform an unusual and pointless act for a brief time, then disperse." Fueled by social media and Smartphones, flash mobs have been used, primarily, as entertaining diversions by addicted techies with (apparently) tons of time on their hands.…

  7. miRNA profiling of naive, effector and memory CD8 T cells.

    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.

  8. Splenectomy alters distribution and turnover but not numbers or protective capacity of de novo generated memory CD8 T cells.

    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.

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

    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.

  10. FLASH Interface; a GUI for managing runtime parameters in FLASH simulations

    Walker, Christopher; Tzeferacos, Petros; Weide, Klaus; Lamb, Donald; Flocke, Norbert; Feister, Scott

    2017-10-01

    We present FLASH Interface, a novel graphical user interface (GUI) for managing runtime parameters in simulations performed with the FLASH code. FLASH Interface supports full text search of available parameters; provides descriptions of each parameter's role and function; allows for the filtering of parameters based on categories; performs input validation; and maintains all comments and non-parameter information already present in existing parameter files. The GUI can be used to edit existing parameter files or generate new ones. FLASH Interface is open source and was implemented with the Electron framework, making it available on Mac OSX, Windows, and Linux operating systems. The new interface lowers the entry barrier for new FLASH users and provides an easy-to-use tool for experienced FLASH simulators. U.S. Department of Energy (DOE), NNSA ASC/Alliances Center for Astrophysical Thermonuclear Flashes, U.S. DOE NNSA ASC through the Argonne Institute for Computing in Science, U.S. National Science Foundation.

  11. Chatting in the face of the eyewitness: The impact of extraneous cell-phone conversation on memory for a perpetrator

    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?

    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. Therapeutic limitations in tumor-specific CD8+ memory T cell engraftment

    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

  14. Organic flash cycles for efficient power production

    Ho, Tony; Mao, Samuel S.; Greif, Ralph

    2016-03-15

    This disclosure provides systems, methods, and apparatus related to an Organic Flash Cycle (OFC). In one aspect, a modified OFC system includes a pump, a heat exchanger, a flash evaporator, a high pressure turbine, a throttling valve, a mixer, a low pressure turbine, and a condenser. The heat exchanger is coupled to an outlet of the pump. The flash evaporator is coupled to an outlet of the heat exchanger. The high pressure turbine is coupled to a vapor outlet of the flash evaporator. The throttling valve is coupled to a liquid outlet of the flash evaporator. The mixer is coupled to an outlet of the throttling valve and to an outlet of the high pressure turbine. The low pressure turbine is coupled to an outlet of the mixer. The condenser is coupled to an outlet of the low pressure turbine and to an inlet of the pump.

  15. Glucose-induced metabolic memory in Schwann cells: prevention by PPAR agonists.

    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. Sizing of SRAM Cell with Voltage Biasing Techniques for Reliability Enhancement of Memory and PUF Functions

    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.

  17. Intelligent structures based on the improved activation of shape memory polymers using Peltier cells

    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

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

    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)

  19. Human cerebrospinal fluid contains CD4+ memory T cells expressing gut- or skin-specific trafficking determinants: relevance for immunotherapy

    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.

  20. IFN-Gamma-Dependent and Independent Mechanisms of CD4+ Memory T Cell-Mediated Protection from Listeria Infection

    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.

  1. Engagement of NKG2D on bystander memory CD8 T cells promotes increased immunopathology following Leishmania major infection.

    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.

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

    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.

  3. NRAM: a disruptive carbon-nanotube resistance-change memory

    Gilmer, D. C.; Rueckes, T.; Cleveland, L.

    2018-04-01

    Advanced memory technology based on carbon nanotubes (CNTs) (NRAM) possesses desired properties for implementation in a host of integrated systems due to demonstrated advantages of its operation including high speed (nanotubes can switch state in picoseconds), high endurance (over a trillion), and low power (with essential zero standby power). The applicable integrated systems for NRAM have markets that will see compound annual growth rates (CAGR) of over 62% between 2018 and 2023, with an embedded systems CAGR of 115% in 2018-2023 (http://bccresearch.com/pressroom/smc/bcc-research-predicts:-nram-(finally)-to-revolutionize-computer-memory). These opportunities are helping drive the realization of a shift from silicon-based to carbon-based (NRAM) memories. NRAM is a memory cell made up of an interlocking matrix of CNTs, either touching or slightly separated, leading to low or higher resistance states respectively. The small movement of atoms, as opposed to moving electrons for traditional silicon-based memories, renders NRAM with a more robust endurance and high temperature retention/operation which, along with high speed/low power, is expected to blossom in this memory technology to be a disruptive replacement for the current status quo of DRAM (dynamic RAM), SRAM (static RAM), and NAND flash memories.

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

    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.

  5. Projection specificity in heterogeneous locus coeruleus cell populations: implications for learning and memory

    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

  6. A dense voltage-mode Josephson memory cell insensitive to systematic variations in critical current density

    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

  7. Terrestrial gamma-ray flashes

    Marisaldi, Martino; Fuschino, Fabio; Labanti, Claudio; Tavani, Marco; Argan, Andrea; Del Monte, Ettore; Longo, Francesco; Barbiellini, Guido; Giuliani, Andrea; Trois, Alessio; Bulgarelli, Andrea; Gianotti, Fulvio; Trifoglio, Massimo

    2013-08-01

    Lightning and thunderstorm systems in general have been recently recognized as powerful particle accelerators, capable of producing electrons, positrons, gamma-rays and neutrons with energies as high as several tens of MeV. In fact, these natural systems turn out to be the highest energy and most efficient natural particle accelerators on Earth. Terrestrial Gamma-ray Flashes (TGFs) are millisecond long, very intense bursts of gamma-rays and are one of the most intriguing manifestation of these natural accelerators. Only three currently operative missions are capable of detecting TGFs from space: the RHESSI, Fermi and AGILE satellites. In this paper we review the characteristics of TGFs, including energy spectrum, timing structure, beam geometry and correlation with lightning, and the basic principles of the associated production models. Then we focus on the recent AGILE discoveries concerning the high energy extension of the TGF spectrum up to 100 MeV, which is difficult to reconcile with current theoretical models.

  8. Terrestrial gamma-ray flashes

    Marisaldi, Martino; Fuschino, Fabio; Labanti, Claudio; Tavani, Marco; Argan, Andrea; Del Monte, Ettore; Longo, Francesco; Barbiellini, Guido; Giuliani, Andrea; Trois, Alessio; Bulgarelli, Andrea; Gianotti, Fulvio; Trifoglio, Massimo

    2013-01-01

    Lightning and thunderstorm systems in general have been recently recognized as powerful particle accelerators, capable of producing electrons, positrons, gamma-rays and neutrons with energies as high as several tens of MeV. In fact, these natural systems turn out to be the highest energy and most efficient natural particle accelerators on Earth. Terrestrial Gamma-ray Flashes (TGFs) are millisecond long, very intense bursts of gamma-rays and are one of the most intriguing manifestation of these natural accelerators. Only three currently operative missions are capable of detecting TGFs from space: the RHESSI, Fermi and AGILE satellites. In this paper we review the characteristics of TGFs, including energy spectrum, timing structure, beam geometry and correlation with lightning, and the basic principles of the associated production models. Then we focus on the recent AGILE discoveries concerning the high energy extension of the TGF spectrum up to 100 MeV, which is difficult to reconcile with current theoretical models

  9. EEHG at FLASH and DELTA

    Molo, Robert; Hoener, Markus; Huck, Holger; Hacker, Kirsten; Khan, Shaukat; Schick, Andreas; Ungelenk, Peter; Zeinalzadeh, Maryam [Center for Synchrotron Radiation (DELTA), TU Dortmund University (Germany); Meulen, Peter van der; Salen, Peter [Stockholm University (Sweden); Angelova Hamberg, Gergana; Ziemann, Volker [Uppsala University (Sweden)

    2013-07-01

    The echo-enabled harmonic generation (EEHG) scheme utilizes two modulators with two magnetic chicanes in order to generate an electron density modulation with high harmonic content. In contrast to free-electron lasers (FEL) based on self-amplified spontaneous emission (SASE), the radiation of an EEHG FEL has better longitudinal coherence and is naturally synchronized with an external laser, which is advantageous for pump-probe applications. At the free-electron laser in Hamburg (FLASH), an EEHG experiment is currently under preparation. The short-pulse facility at DELTA (a 1.5-GeV synchrotron light source operated by the TU Dortmund University) based on coherent harmonic generation (CHG) will be upgraded using the EEHG technique in order to reach shorter wavelengths.

  10. [Nikola Tesla: flashes of inspiration].

    Villarejo-Galende, Albero; Herrero-San Martín, Alejandro

    2013-01-16

    Nikola Tesla (1856-1943) was one of the greatest inventors in history and a key player in the revolution that led to the large-scale use of electricity. He also made important contributions to such diverse fields as x-rays, remote control, radio, the theory of consciousness or electromagnetism. In his honour, the international unit of magnetic induction was named after him. Yet, his fame is scarce in comparison with that of other inventors of the time, such as Edison, with whom he had several heated arguments. He was a rather odd, reserved person who lived for his inventions, the ideas for which came to him in moments of inspiration. In his autobiography he relates these flashes with a number of neuropsychiatric manifestations, which can be seen to include migraine auras, synaesthesiae, obsessions and compulsions.

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

    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.

  12. Statistical Evolution of the Lightning Flash

    Zoghzoghy, F. G.; Cohen, M.; Said, R.; Inan, U. S.

    2012-12-01

    Natural lightning is one of the most fascinating and powerful electrical processes on Earth. To date, the physics behind this natural phenomenon are not fully understood, due primarily to the difficulty of obtaining measurements inside thunderstorms and to the wide range of timescales involved (from nanoseconds to seconds). Our aim is to use accurate lightning geo-location data from the National Lightning Detection Network (NLDN) to study statistical patterns in lightning, taking advantage of the fact that millions of lightning flashes occur around the globe every day. We present two sets of results, one involving the patterns of flashes in a storm, and a second involving the patterns of strokes in a flash. These patterns can provide a surrogate measure of the timescales and the spatial extents of the underlying physical processes. First, we study the timescales of charge buildup inside thunderstorms. We find that, following a lightning flash, the probability of another neighboring flash decreases and takes tens of seconds to recover. We find that this suppression effect is a function of flash type, stroke peak current, cloud-to-ground (CG) stroke multiplicity, and other lightning and geographical parameters. We find that the probabilities of subsequent flashes are more suppressed following oceanic lightning, or following flashes with higher peak currents and/or higher multiplicities (for CG flashes). Second, we use NLDN data to study the evolution of the strokes within a CG flash. A CG flash typically includes multiple return strokes, which can occur in the same channel or in multiple channels within a few kilometers. We cluster NLDN stroke data into flashes and produce the probability density function of subsequent strokes as a function of distance and time-delays relative to the previous stroke. Using this technique, we investigate processes which occur during the CG lightning flash with nanosecond to millisecond timescales. For instance, our results suggest

  13. CD8 Memory Cells Develop Unique DNA Repair Mechanisms Favoring Productive Division.

    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.

  14. Memory-guided sensory comparisons in the prefrontal cortex: contribution of putative pyramidal cells and interneurons.

    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.

  15. CCR6 is expressed on an IL-10-producing, autoreactive memory T cell population with context-dependent regulatory function.

    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.

  16. From sensorimotor learning to memory cells in prefrontal and temporal association cortex: a neurocomputational study of disembodiment.

    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

  17. Local Inflammatory Cues Regulate Differentiation and Persistence of CD8+ Tissue-Resident Memory T Cells

    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.

  18. Selective Expansion of Memory CD4+ T cells By Mitogenic Human CD28 Generates Inflammatory Cytokines and Regulatory T cells

    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

  19. Tissue-Resident Memory CD8+ T Cells: From Phenotype to Function

    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.

  20. Radiation-induced alterations in murine lymphocyte homing patterns. II. Recovery and function of memory cells in LBN rats

    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

  1. Mucosal immunization in macaques upregulates the innate APOBEC 3G anti-viral factor in CD4(+) memory T cells.

    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.

  2. Identifying long-term memory B-cells in vaccinated children despite waning antibody levels specific for Bordetella pertussis proteins.

    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.

  3. Incomplete effector/memory differentiation of antigen-primed CD8+ T cells in gene gun DNA-vaccinated mice

    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...

  4. Concept of rewritable organic ferroelectric random access memory in two lateral transistors-in-one cell architecture

    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)

  5. Increased degradation of ATP is driven by memory regulatory T cells in kidney transplantation tolerance.

    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.

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

    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.

  7. Plasmablasts During Acute Dengue Infection Represent a Small Subset of a Broader Virus-specific Memory B Cell Pool

    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.

  8. Nicotinic modulation of hippocampal cell signaling and associated effects on learning and memory.

    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.

  9. An SEU tolerant memory cell derived from fundamental studies of SEU mechanisms in SRAM

    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

  10. Write/erase time of nanoseconds in quantum dot based memory structures

    Nowozin, Tobias; Marent, Andreas; Geller, Martin; Bimberg, Dieter

    2008-01-01

    We have developed a novel charge-storage memory concept based on III-V semiconductor quantum dots (QDs) which has a number of fundamental advantages over conventional Si/SiO 2 floating gate memories (Flash): material-tunable and voltage-tunable barriers for improved intrinsic speed and/or storage time and high endurance. To investigate the potential of this new memory concept we have determined intrinsic write/erase times in memory structures based on InAs/GaAs and GaSb/GaAs QDs using capacitance-voltage spectroscopy. We measured a write time below 15 ns independent of the localization energy (i.e. the storage time) of the QDs. This write time is more than three orders of magnitude faster than in a Flash cell and already below the write time of a dynamic random access memory (DRAM). The erase time was determined to be 42 ns for InAs/GaAs QDs and 1.5 ms for GaSb/GaAs QDs for applied electric fields of 166 kV/cm and 206 kV/cm, respectively. From these results we derive an erase time of 1 ns in GaSb QDs for an electric field of 330 kV/cm

  11. Nonvolatile Memory Technology for Space Applications

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

    2010-01-01

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

  12. Antigen and Memory CD8 T Cells: Were They Both Right?

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

    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.

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

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

    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.

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

    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.

  1. MR colonography with fecal tagging: comparison between 2D turbo FLASH and 3D FLASH sequences

    Papanikolaou, Nickolas; Grammatikakis, John; Maris, Thomas; Prassopoulos, Panos; Gourtsoyiannis, Nicholas; Lauenstein, Thomas

    2003-01-01

    The objective of this study was to compare inversion recovery turbo 2D fast low-angle shot (FLASH) and 3D FLASH sequences for fecal-tagged MR colonography studies. Fifteen consecutive patients with indications for colonoscopy underwent MR colonography with fecal tagging. An inversion recovery turbo-FLASH sequence was applied and compared in terms of artifacts presence, efficiency for masking residual stool, and colonic wall conspicuity with a fat-saturated 3D FLASH sequence. Both sequences were acquired following administration of paramagnetic contrast agent. Contrast-to-noise ratio and relative contrast between colonic wall and lumen were calculated and compared for both sequences. Turbo 2D FLASH provided fewer artifacts, higher efficiency for masking the residual stool, and colonic wall conspicuity equivalent to 3D FLASH. An inversion time of 10 ms provided homogeneously low signal intensity of the colonic lumen. Contrast to noise between colonic wall and lumen was significantly higher in the 3D FLASH images, whereas differences in relative contrast were not statistically significant. An optimized inversion-recovery 2D turbo-FLASH sequence provides better fecal tagging results and should be added to the 3D FLASH sequence when designing dark-lumen MR colonography examination protocols. (orig.)

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

    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.

  3. A global flash flood forecasting system

    Baugh, Calum; Pappenberger, Florian; Wetterhall, Fredrik; Hewson, Tim; Zsoter, Ervin

    2016-04-01

    The sudden and devastating nature of flash flood events means it is imperative to provide early warnings such as those derived from Numerical Weather Prediction (NWP) forecasts. Currently such systems exist on basin, national and continental scales in Europe, North America and Australia but rely on high resolution NWP forecasts or rainfall-radar nowcasting, neither of which have global coverage. To produce global flash flood forecasts this work investigates the possibility of using forecasts from a global NWP system. In particular we: (i) discuss how global NWP can be used for flash flood forecasting and discuss strengths and weaknesses; (ii) demonstrate how a robust evaluation can be performed given the rarity of the event; (iii) highlight the challenges and opportunities in communicating flash flood uncertainty to decision makers; and (iv) explore future developments which would significantly improve global flash flood forecasting. The proposed forecast system uses ensemble surface runoff forecasts from the ECMWF H-TESSEL land surface scheme. A flash flood index is generated using the ERIC (Enhanced Runoff Index based on Climatology) methodology [Raynaud et al., 2014]. This global methodology is applied to a series of flash floods across southern Europe. Results from the system are compared against warnings produced using the higher resolution COSMO-LEPS limited area model. The global system is evaluated by comparing forecasted warning locations against a flash flood database of media reports created in partnership with floodlist.com. To deal with the lack of objectivity in media reports we carefully assess the suitability of different skill scores and apply spatial uncertainty thresholds to the observations. To communicate the uncertainties of the flash flood system output we experiment with a dynamic region-growing algorithm. This automatically clusters regions of similar return period exceedence probabilities, thus presenting the at-risk areas at a spatial

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

    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.

  5. From silicon to organic nanoparticle memory devices.

    Tsoukalas, D

    2009-10-28

    After introducing the operational principle of nanoparticle memory devices, their current status in silicon technology is briefly presented in this work. The discussion then focuses on hybrid technologies, where silicon and organic materials have been combined together in a nanoparticle memory device, and finally concludes with the recent development of organic nanoparticle memories. The review is focused on the nanoparticle memory concept as an extension of the current flash memory device. Organic nanoparticle memories are at a very early stage of research and have not yet found applications. When this happens, it is expected that they will not directly compete with mature silicon technology but will find their own areas of application.

  6. Flash spectroscopy of purple membrane.

    Xie, A H; Nagle, J F; Lozier, R H

    1987-04-01

    Flash spectroscopy data were obtained for purple membrane fragments at pH 5, 7, and 9 for seven temperatures from 5 degrees to 35 degrees C, at the magic angle for actinic versus measuring beam polarizations, at fifteen wavelengths from 380 to 700 nm, and for about five decades of time from 1 microsecond to completion of the photocycle. Signal-to-noise ratios are as high as 500. Systematic errors involving beam geometries, light scattering, absorption flattening, photoselection, temperature fluctuations, partial dark adaptation of the sample, unwanted actinic effects, and cooperativity were eliminated, compensated for, or are shown to be irrelevant for the conclusions. Using nonlinear least squares techniques, all data at one temperature and one pH were fitted to sums of exponential decays, which is the form required if the system obeys conventional first-order kinetics. The rate constants obtained have well behaved Arrhenius plots. Analysis of the residual errors of the fitting shows that seven exponentials are required to fit the data to the accuracy of the noise level.

  7. Improving Flash Flood Prediction in Multiple Environments

    Broxton, P. D.; Troch, P. A.; Schaffner, M.; Unkrich, C.; Goodrich, D.; Wagener, T.; Yatheendradas, S.

    2009-12-01

    Flash flooding is a major concern in many fast responding headwater catchments . There are many efforts to model and to predict these flood events, though it is not currently possible to adequately predict the nature of flash flood events with a single model, and furthermore, many of these efforts do not even consider snow, which can, by itself, or in combination with rainfall events, cause destructive floods. The current research is aimed at broadening the applicability of flash flood modeling. Specifically, we will take a state of the art flash flood model that is designed to work with warm season precipitation in arid environments, the KINematic runoff and EROSion model (KINEROS2), and combine it with a continuous subsurface flow model and an energy balance snow model. This should improve its predictive capacity in humid environments where lateral subsurface flow significantly contributes to streamflow, and it will make possible the prediction of flooding events that involve rain-on-snow or rapid snowmelt. By modeling changes in the hydrologic state of a catchment before a flood begins, we can also better understand the factors or combination of factors that are necessary to produce large floods. Broadening the applicability of an already state of the art flash flood model, such as KINEROS2, is logical because flash floods can occur in all types of environments, and it may lead to better predictions, which are necessary to preserve life and property.

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

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

    2013-04-01

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

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

    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.

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

    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.

  11. Time Correlations of Lightning Flash Sequences in Thunderstorms Revealed by Fractal Analysis

    Gou, Xueqiang; Chen, Mingli; Zhang, Guangshu

    2018-01-01

    By using the data of lightning detection and ranging system at the Kennedy Space Center, the temporal fractal and correlation of interevent time series of lightning flash sequences in thunderstorms have been investigated with Allan factor (AF), Fano factor (FF), and detrended fluctuation analysis (DFA) methods. AF, FF, and DFA methods are powerful tools to detect the time-scaling structures and correlations in point processes. Totally 40 thunderstorms with distinguishing features of a single-cell storm and apparent increase and decrease in the total flash rate were selected for the analysis. It is found that the time-scaling exponents for AF (αAF) and FF (αFF) analyses are 1.62 and 0.95 in average, respectively, indicating a strong time correlation of the lightning flash sequences. DFA analysis shows that there is a crossover phenomenon—a crossover timescale (τc) ranging from 54 to 195 s with an average of 114 s. The occurrence of a lightning flash in a thunderstorm behaves randomly at timescales τc but shows strong time correlation at scales >τc. Physically, these may imply that the establishment of an extensive strong electric field necessary for the occurrence of a lightning flash needs a timescale >τc, which behaves strongly time correlated. But the initiation of a lightning flash within a well-established extensive strong electric field may involve the heterogeneities of the electric field at a timescale τc, which behave randomly.

  12. Mutational analysis of FLASH and PTPN13 genes in colorectal carcinomas.

    Jeong, Eun Goo; Lee, Sung Hak; Yoo, Nam Jin; Lee, Sug Hyung

    2008-01-01

    The Fas-Fas ligand system is considered a major pathway for induction of apoptosis in cells and tissues. FLASH was identified as a pro-apoptotic protein that transmits apoptosis signal during Fas-mediated apoptosis. PTPN13 interacts with Fas and functions as both suppressor and inducer of Fas-mediated apoptosis. There are polyadenine tracts in both FLASH (A8 and A9 in exon 8) and PTPN13 (A8 in exon 7) genes that could be frameshift mutation targets in colorectal carcinomas. Because genes encoding proteins in Fas-mediated apoptosis frequently harbor somatic mutations in cancers, we explored the possibility as to whether mutations of FLASH and PTPN13 are a feature of colorectal carcinomas. We analysed human FLASH in exon 8 and PTPN13 in exon 7 for the detection of somatic mutations in 103 colorectal carcinomas by a polymerase chain reaction (PCR)- based single-strand conformation polymorphism (SSCP). We detected two mutations in FLASH gene, but none in PTPN13 gene. However, the two mutations were not frameshift (deletion or insertion) mutations in the polyadenine tracts of FLASH. The two mutations consisted of a deletion mutation (c.3734-3737delAGAA) and a missense mutation (c.3703A>C). These data indicate that frameshift mutation in the polyadenine tracts in both FLASH and PTPN13 genes is rare in colorectal carcinomas. Also, the data suggest that both FLASH and PTPN13 mutations in the polyadenine tracts may not have a crucial role in the pathogenesis of colorectal carcinomas.

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

    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.

    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

    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.

    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

    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

    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. An improved lightning flash rate parameterization developed from Colorado DC3 thunderstorm data for use in cloud-resolving chemical transport models

    Basarab, B. M.; Rutledge, S. A.; Fuchs, B. R.

    2015-09-01

    Accurate prediction of total lightning flash rate in thunderstorms is important to improve estimates of nitrogen oxides (NOx) produced by lightning (LNOx) from the storm scale to the global scale. In this study, flash rate parameterization schemes from the literature are evaluated against observed total flash rates for a sample of 11 Colorado thunderstorms, including nine storms from the Deep Convective Clouds and Chemistry (DC3) experiment in May-June 2012. Observed flash rates were determined using an automated algorithm that clusters very high frequency radiation sources emitted by electrical breakdown in clouds and detected by the northern Colorado lightning mapping array. Existing schemes were found to inadequately predict flash rates and were updated based on observed relationships between flash rate and simple storm parameters, yielding significant improvement. The most successful updated scheme predicts flash rate based on the radar-derived mixed-phase 35 dBZ echo volume. Parameterizations based on metrics for updraft intensity were also updated but were found to be less reliable predictors of flash rate for this sample of storms. The 35 dBZ volume scheme was tested on a data set containing radar reflectivity volume information for thousands of isolated convective cells in different regions of the U.S. This scheme predicted flash rates to within 5.8% of observed flash rates on average. These results encourage the application of this scheme to larger radar data sets and its possible implementation into cloud-resolving models.

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

    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