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

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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.

The imaging performance of flash memory masks characterized with AIMS

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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

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

Data.gov (United States)

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...

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

Science.gov (United States)

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).

Doped SbTe phase change material in memory cells

NARCIS (Netherlands)

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

2009-01-01

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

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

Science.gov (United States)

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.

Modeling of SONOS Memory Cell Erase Cycle

Science.gov (United States)

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

2011-01-01

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

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

International Nuclear Information System (INIS)

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

2008-01-01

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

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

Science.gov (United States)

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...

Optimal proximity correction: application for flash memory design

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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)

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

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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)

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

International Nuclear Information System (INIS)

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)

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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.

Overview of emerging nonvolatile memory technologies.

Science.gov (United States)

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

2014-01-01

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

Overview of emerging nonvolatile memory technologies

Science.gov (United States)

2014-01-01

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

Graphene-quantum-dot nonvolatile charge-trap flash memories

International Nuclear Information System (INIS)

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)

Simple flash evaporator for making thin films of compounds

Energy Technology Data Exchange (ETDEWEB)

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.

Flash-Aware Page Replacement Algorithm

Directory of Open Access Journals (Sweden)

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.

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

International Nuclear Information System (INIS)

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.

Effects of tunnel oxide process on SONOS flash memory characteristics

International Nuclear Information System (INIS)

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.

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

Directory of Open Access Journals (Sweden)

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.

Characterizations of MoTiO5 flash memory devices with post-annealing

International Nuclear Information System (INIS)

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

Cell characteristics of a multiple alloy nano-dots memory structure

International Nuclear Information System (INIS)

Bea, Ji Chel; Lee, Kang-Wook; Tanaka, Tetsu; Koyanagi, Mitsumasa; Song, Yun Heub; Lee, Gae-Hun

2009-01-01

A multiple alloy metal nano-dots memory using FN tunneling was investigated in order to confirm its structural possibility for future flash memory. In this work, a multiple FePt nano-dots device with a high work function (∼5.2 eV) and extremely high dot density (∼1.2 × 10 13 cm −2 ) was fabricated. Its structural effect for multiple layers was evaluated and compared to the one with a single layer in terms of the cell characteristics and reliability. We confirm that MOS capacitor structures with two to four multiple FePt nano-dot layers provide a larger threshold voltage window and better retention characteristics. Furthermore, it was also revealed that several process parameters for block oxide and inter-tunnel oxide between the nano-dot layers are very important to improve the efficiency of electron injection into multiple nano-dots. From these results, it is expected that a multiple FePt nano-dots memory using Fowler–Nordheim (FN) tunneling could be a candidate structure for future flash memory

MoO3 trapping layers with CF4 plasma treatment in flash memory applications

International Nuclear Information System (INIS)

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

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

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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.

Environmental Effects on Data Retention in Flash Cells

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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.

Flash memory in embedded Java programs

DEFF Research Database (Denmark)

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...

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

Science.gov (United States)

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...

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

International Nuclear Information System (INIS)

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

System of ispFlash configuration

International Nuclear Information System (INIS)

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

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

Science.gov (United States)

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.

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

Science.gov (United States)

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

2015-07-01

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

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

Science.gov (United States)

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.

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

Energy Technology Data Exchange (ETDEWEB)

Campbell, Philip Montgomery; Wix, Steven D.

2017-04-01

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

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

Science.gov (United States)

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.

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

Science.gov (United States)

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

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

Science.gov (United States)

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.

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

Science.gov (United States)

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

2017-11-01

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

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

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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)

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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

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

Science.gov (United States)

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

Modélisation de Fautes et Test des Mémoires Flash

OpenAIRE

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...

Nanoscale memory devices

International Nuclear Information System (INIS)

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)

Nonvolatile memory design magnetic, resistive, and phase change

CERN Document Server

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,

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

Directory of Open Access Journals (Sweden)

Sparsh Mittal

2017-09-01

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

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

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

In2Ga2ZnO7 oxide semiconductor based charge trap device for NAND flash memory

Science.gov (United States)

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.

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

Science.gov (United States)

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

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

International Nuclear Information System (INIS)

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

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

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

International Nuclear Information System (INIS)

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

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

Science.gov (United States)

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

2018-05-01

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

Cuinse2 Thin Film For Solar Cell By Flash Evaporation

OpenAIRE

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...

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

International Nuclear Information System (INIS)

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

Memory T Cell Migration

OpenAIRE

Qianqian eZhang; Qianqian eZhang; Fadi G. Lakkis

2015-01-01

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

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

Science.gov (United States)

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.

Memory, microprocessor, and ASIC

CERN Document Server

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.

Non-volatile memories

CERN Document Server

Lacaze, Pierre-Camille

2014-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

International Nuclear Information System (INIS)

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.

Radiation hard memory cell and array thereof

International Nuclear Information System (INIS)

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

1978-01-01

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

The future of memory

Science.gov (United States)

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.

Nonvolatile Memory Technology for Space Applications

Science.gov (United States)

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

2010-01-01

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

The cellular memory disc of reprogrammed cells.

Science.gov (United States)

Anjamrooz, Seyed Hadi

2013-04-01

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

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

Science.gov (United States)

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

2018-05-01

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

Towards Terabit Memories

Science.gov (United States)

Hoefflinger, Bernd

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

Flexible NAND-Like Organic Ferroelectric Memory Array

NARCIS (Netherlands)

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

2014-01-01

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

Non-volatile memory based on the ferroelectric photovoltaic effect

Science.gov (United States)

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

2013-01-01

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

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

International Nuclear Information System (INIS)

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

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

Science.gov (United States)

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%.

Observers can reliably identify illusory flashes in the illusory flash paradigm

NARCIS (Netherlands)

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

Hot Flashes

Science.gov (United States)

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 ...

Asymptomatic memory CD8+ T cells

Science.gov (United States)

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

2014-01-01

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

CD4 T-Cell Memory Generation and Maintenance

Science.gov (United States)

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

2014-01-01

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

Phototoxic effects of commercial photographic flash lamp on rat eyes.

Science.gov (United States)

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.

A Josephson ternary associative memory cell

International Nuclear Information System (INIS)

Morisue, M.; Suzuki, K.

1989-01-01

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

Phase change memory

CERN Document Server

Qureshi, Moinuddin K

2011-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-06-24

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

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

Directory of Open Access Journals (Sweden)

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

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.

Science.gov (United States)

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.

Shape memory of human red blood cells.

Science.gov (United States)

Fischer, Thomas M

2004-05-01

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

Human T Cell Memory: A Dynamic View

Directory of Open Access Journals (Sweden)

Derek C. Macallan

2017-02-01

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

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

Science.gov (United States)

Hong, Augustin Jinwoo

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

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

Science.gov (United States)

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.

Memory T follicular helper CD4 T cells

Directory of Open Access Journals (Sweden)

J. Scott eHale

2015-02-01

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

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

Science.gov (United States)

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.

Flash Platform Examination

Science.gov (United States)

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

Measurements of SIMCON 3.1 LLRF control signal processing quality for VUV free-electron laser FLASH

Science.gov (United States)

Pietrasik, Rafal; Giergusiewicz, Wojciech; Jalmuzna, Wojciech; Pozniak, Krzysztof T.; Romaniuk, Ryszard S.; Simrock, Stefan

2006-10-01

The paper describes development of a new version of photonic and electronic control and measurement system for FLASH Laser under development in DESY Hamburg accelerator laboratory. The system is called SIMCON 3.1. and is a developmental continuation of previous systems SIMCON 1.0, SIMCON 2.1 and SIMCON 3.0. It differs from the previous systems by considerably bigger resources: 10 fast analog input channels, bigger FPGA chip with two power PC - CPU units, two multi-gigabit optical links, GbE interface, booting possibility from flash memory card. The PCB is done in VME mechanical and electrical standard. It is designed for usage in tests for FLASH Laser development.

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

Science.gov (United States)

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

2010-09-01

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

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

Directory of Open Access Journals (Sweden)

Jeremy A Sullivan

2012-02-01

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

Generation of memory B cells and their reactivation.

Science.gov (United States)

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

2018-05-01

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

MAP Detector for Flash Memory Without Accessing the Interfering Cells

DEFF Research Database (Denmark)

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

2018-01-01

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

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

Science.gov (United States)

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

2004-01-01

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

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

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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

2013-05-01

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

CD49b-dependent establishment of T helper cell memory.

Science.gov (United States)

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

2013-09-01

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

Measurements of a vortex transitional ndro Josephson memory cell

International Nuclear Information System (INIS)

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

1988-01-01

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

A vertically integrated capacitorless memory cell

International Nuclear Information System (INIS)

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

2013-01-01

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

Cuinse2 Thin Film For Solar Cell By Flash Evaporation

Directory of Open Access Journals (Sweden)

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.

Shape Memory of Human Red Blood Cells

OpenAIRE

Fischer, Thomas M.

2004-01-01

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

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

Directory of Open Access Journals (Sweden)

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.

Pro Android Flash

CERN Document Server

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

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

Science.gov (United States)

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.

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

Science.gov (United States)

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

2015-01-01

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

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

Directory of Open Access Journals (Sweden)

Michelle A E Jansen

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

Flash!

Science.gov (United States)

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.

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

OpenAIRE

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

2013-01-01

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

Interregional synaptic maps among engram cells underlie memory formation.

Science.gov (United States)

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

2018-04-27

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

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

Science.gov (United States)

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

2015-01-01

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

Professional Flash Lite Mobile Development

CERN Document Server

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

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

Directory of Open Access Journals (Sweden)

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.

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

Directory of Open Access Journals (Sweden)

Gonzalo Almanza

2010-06-01

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

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

CERN Document Server

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.

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

KAUST Repository

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.

Inadvertently programmed bits in Samsung 128 Mbit flash devices: a flaky investigation

Science.gov (United States)

Swift, G.

2002-01-01

JPL's X2000 avionics design pioneers new territory by specifying a non-volatile memory (NVM) board based on flash memories. The Samsung 128Mb device chosen was found to demonstrate bit errors (mostly program disturbs) and block-erase failures that increase with cycling. Low temperature, certain pseudo- random patterns, and, probably, higher bias increase the observable bit errors. An experiment was conducted to determine the wearout dependence of the bit errors to 100k cycles at cold temperature using flight-lot devices (some pre-irradiated). The results show an exponential growth rate, a wide part-to-part variation, and some annealing behavior.

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

Science.gov (United States)

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.

Electric-field-controlled interface dipole modulation for Si-based memory devices.

Science.gov (United States)

Miyata, Noriyuki

2018-05-31

Various nonvolatile memory devices have been investigated to replace Si-based flash memories or emulate synaptic plasticity for next-generation neuromorphic computing. A crucial criterion to achieve low-cost high-density memory chips is material compatibility with conventional Si technologies. In this paper, we propose and demonstrate a new memory concept, interface dipole modulation (IDM) memory. IDM can be integrated as a Si field-effect transistor (FET) based memory device. The first demonstration of this concept employed a HfO 2 /Si MOS capacitor where the interface monolayer (ML) TiO 2 functions as a dipole modulator. However, this configuration is unsuitable for Si-FET-based devices due to its large interface state density (D it ). Consequently, we propose, a multi-stacked amorphous HfO 2 /1-ML TiO 2 /SiO 2 IDM structure to realize a low D it and a wide memory window. Herein we describe the quasi-static and pulse response characteristics of multi-stacked IDM MOS capacitors and demonstrate flash-type and analog memory operations of an IDM FET device.

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

Science.gov (United States)

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

2017-01-01

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

CD4 T cell autophagy is integral to memory maintenance.

Science.gov (United States)

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

2018-04-13

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

Nanographene charge trapping memory with a large memory window

International Nuclear Information System (INIS)

Meng, Jianling; Yang, Rong; Zhao, Jing; He, Congli; Wang, Guole; Shi, Dongxia; Zhang, Guangyu

2015-01-01

Nanographene is a promising alternative to metal nanoparticles or semiconductor nanocrystals for charge trapping memory. In general, a high density of nanographene is required in order to achieve high charge trapping capacity. Here, we demonstrate a strategy of fabrication for a high density of nanographene for charge trapping memory with a large memory window. The fabrication includes two steps: (1) direct growth of continuous nanographene film; and (2) isolation of the as-grown film into high-density nanographene by plasma etching. Compared with directly grown isolated nanographene islands, abundant defects and edges are formed in nanographene under argon or oxygen plasma etching, i.e. more isolated nanographene islands are obtained, which provides more charge trapping sites. As-fabricated nanographene charge trapping memory shows outstanding memory properties with a memory window as wide as ∼9 V at a relative low sweep voltage of ±8 V, program/erase speed of ∼1 ms and robust endurance of >1000 cycles. The high-density nanographene charge trapping memory provides an outstanding alternative for downscaling technology beyond the current flash memory. (paper)

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

Science.gov (United States)

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

2011-10-15

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

Flash grundkursus

DEFF Research Database (Denmark)

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...

NRAM: a disruptive carbon-nanotube resistance-change memory

Science.gov (United States)

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.

A Scalable and Highly Configurable Cache-Aware Hybrid Flash Translation Layer

Directory of Open Access Journals (Sweden)

Jalil Boukhobza

2014-03-01

Full Text Available This paper presents a cache-aware configurable hybrid flash translation layer (FTL, named CACH-FTL. It was designed based on the observation that most state-of­­-the-art flash-specific cache systems above FTLs flush groups of pages belonging to the same data block. CACH-FTL relies on this characteristic to optimize flash write operations placement, as large groups of pages are flushed to a block-mapped region, named BMR, whereas small groups are buffered into a page-mapped region, named PMR. Page group placement is based on a configurable threshold defining the limit under which it is more cost-effective to use page mapping (PMR and wait for grouping more pages before flushing to the BMR. CACH-FTL is scalable in terms of mapping table size and flexible in terms of Input/Output (I/O workload support. CACH-FTL performs very well, as the performance difference with the ideal page-mapped FTL is less than 15% in most cases and has a mean of 4% for the best CACH-FTL configurations, while using at least 78% less memory for table mapping storage on RAM.

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.

Science.gov (United States)

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

The Effect of Shape Memory on Red Blood Cell Motions

Science.gov (United States)

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

2013-11-01

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

High flash point electrolyte for use in lithium-ion batteries

Energy Technology Data Exchange (ETDEWEB)

Isken, P.; Dippel, C.; Schmitz, R.; Schmitz, R.W.; Kunze, M.; Passerini, S.; Winter, M. [Institute of Physical Chemistry, Westfaelische Wilhelms-University Muenster, Corrensstrasse 28/30, 48149 Muenster (Germany); Lex-Balducci, A., E-mail: a.lex-balducci@uni-muenster.de [Institute of Physical Chemistry, Westfaelische Wilhelms-University Muenster, Corrensstrasse 28/30, 48149 Muenster (Germany)

2011-09-01

Highlights: > Substitution of linear carbonates in conventional electrolytes with adiponitrile allows the realization of high flash point electrolytes. > EC:ADN based electrolytes display a higher anodic stability than a conventional electrolyte based on EC:DEC. > Graphite and NCM electrodes used in combination with the EC:ADN based electrolyte display a performance comparable with that of conventional electrolytes. - Abstract: The high flash point solvent adiponitrile (ADN) was investigated as co-solvent with ethylene carbonate (EC) for use as lithium-ion battery electrolyte. The flash point of this solvent mixture was more than 110 deg. C higher than that of conventional electrolyte solutions involving volatile linear carbonate components, such as diethyl carbonate (DEC) or dimethyl carbonate (DMC). The electrolyte based on EC:ADN (1:1 wt) with lithium tetrafluoroborate (LiBF{sub 4}) displayed a conductivity of 2.6 mS cm{sup -1} and no aluminum corrosion. In addition, it showed higher anodic stability on a Pt electrode than the standard electrolyte 1 M lithium hexafluorophosphate (LiPF{sub 6}) in EC:DEC (3:7 wt). Graphite/Li half cells using this electrolyte showed excellent rate capability up to 5C and good cycling stability (more than 98% capacity retention after 50 cycles at 1C). Additionally, the electrolyte was investigated in NCM/Li half cells. The cells were able to reach a capacity of 104 mAh g{sup -1} at 5C and capacity retention of more than 97% after 50 cycles. These results show that an electrolyte with a considerably increased flash point with respect to common electrolyte systems comprising linear carbonates, could be realized without any negative effects on the electrochemical performance in Li-half cells.

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

International Nuclear Information System (INIS)

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)

Associative memory cells and their working principle in the brain

Science.gov (United States)

Wang, Jin-Hui; Cui, Shan

2018-01-01

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

Learning Flash CS4 Professional

CERN Document Server

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.

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

Science.gov (United States)

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

2018-05-01

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

Flashing oscillation in pool water

International Nuclear Information System (INIS)

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

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

KAUST Repository

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

2013-01-01

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

Flashing subdiffusive ratchets in viscoelastic media

International Nuclear Information System (INIS)

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)

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

KAUST Repository

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

New memory devices based on the proton transfer process

Science.gov (United States)

Wierzbowska, Małgorzata

2016-01-01

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

Hot flashes and sleep in women.

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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.)

LOCAL IMMUNITY BY TISSUE-RESIDENT CD8+ MEMORY T CELLS

Directory of Open Access Journals (Sweden)

Thomas eGebhardt

2012-11-01

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

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

DEFF Research Database (Denmark)

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

2011-01-01

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

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

KAUST Repository

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

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

Science.gov (United States)

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

2016-01-05

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

Flash-Type Discrimination

Science.gov (United States)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

Directory of Open Access Journals (Sweden)

Martin Prlic

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

The October 2014 United States Treasury bond flash crash and the contributory effect of mini flash crashes.

Directory of Open Access Journals (Sweden)

Zachary S Levine

Full Text Available We investigate the causal uncertainty surrounding the flash crash in the U.S. Treasury bond market on October 15, 2014, and the unresolved concern that no clear link has been identified between the start of the flash crash at 9:33 and the opening of the U.S. equity market at 9:30. We consider the contributory effect of mini flash crashes in equity markets, and find that the number of equity mini flash crashes in the three-minute window between market open and the Treasury Flash Crash was 2.6 times larger than the number experienced in any other three-minute window in the prior ten weekdays. We argue that (a this statistically significant finding suggests that mini flash crashes in equity markets both predicted and contributed to the October 2014 U.S. Treasury Bond Flash Crash, and (b mini-flash crashes are important phenomena with negative externalities that deserve much greater scholarly attention.

The October 2014 United States Treasury bond flash crash and the contributory effect of mini flash crashes.

Science.gov (United States)

Levine, Zachary S; Hale, Scott A; Floridi, Luciano

2017-01-01

We investigate the causal uncertainty surrounding the flash crash in the U.S. Treasury bond market on October 15, 2014, and the unresolved concern that no clear link has been identified between the start of the flash crash at 9:33 and the opening of the U.S. equity market at 9:30. We consider the contributory effect of mini flash crashes in equity markets, and find that the number of equity mini flash crashes in the three-minute window between market open and the Treasury Flash Crash was 2.6 times larger than the number experienced in any other three-minute window in the prior ten weekdays. We argue that (a) this statistically significant finding suggests that mini flash crashes in equity markets both predicted and contributed to the October 2014 U.S. Treasury Bond Flash Crash, and (b) mini-flash crashes are important phenomena with negative externalities that deserve much greater scholarly attention.

The charge storage characteristics of ZrO2 nanocrystallite-based charge trap nonvolatile memory

International Nuclear Information System (INIS)

Tang Zhen-Jie; Li Rong; Yin Jiang

2013-01-01

ZrO 2 nanocrystallite-based charge trap flash memory capacitors incorporating a (ZrO 2 ) 0.6 (SiO 2 ) 0.4 pseudobinary high-k oxide film as the charge trapping layer were prepared and investigated. The precipitation reaction in the charge trapping layer, forming ZrO 2 nanocrystallites during rapid thermal annealing, was investigated by transmission electron microscopy and X-ray diffraction. It was observed that a ZrO 2 nanocrystallite-based memory capacitor after post-annealing at 850 °C for 60 s exhibits a maximum memory window of about 6.8 V, good endurance and a low charge loss of ∼25% over a period of 10 years (determined by extrapolating the charge loss curve measured experimentally), even at 85 °C. Such 850 °C-annealed memory capacitors appear to be candidates for future nonvolatile flash memory device applications

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

Energy Technology Data Exchange (ETDEWEB)

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.)

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

Science.gov (United States)

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

Mutational analysis of FLASH and PTPN13 genes in colorectal carcinomas.

Science.gov (United States)

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.

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

Science.gov (United States)

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

2017-02-01

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

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

Science.gov (United States)

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.

Cell-assembly coding in several memory processes.

Science.gov (United States)

Sakurai, Y

1998-01-01

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

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

Science.gov (United States)

Shedlock, Devon J.; Shen, Hao

2003-04-01

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

B Cell Intrinsic Mechanisms Constraining IgE Memory

Directory of Open Access Journals (Sweden)

Brice Laffleur

2017-11-01

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

DIRCM FLASH Flight Tests

National Research Council Canada - National Science Library

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...

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

Science.gov (United States)

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

2013-01-01

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

Unpredictable visual changes cause temporal memory averaging.

Science.gov (United States)

Ohyama, Junji; Watanabe, Katsumi

2007-09-01

Various factors influence the perceived timing of visual events. Yet, little is known about the ways in which transient visual stimuli affect the estimation of the timing of other visual events. In the present study, we examined how a sudden color change of an object would influence the remembered timing of another transient event. In each trial, subjects saw a green or red disk travel in circular motion. A visual flash (white frame) occurred at random times during the motion sequence. The color of the disk changed either at random times (unpredictable condition), at a fixed time relative to the motion sequence (predictable condition), or it did not change (no-change condition). The subjects' temporal memory of the visual flash in the predictable condition was as veridical as that in the no-change condition. In the unpredictable condition, however, the flash was reported to occur closer to the timing of the color change than actual timing. Thus, an unpredictable visual change distorts the temporal memory of another visual event such that the remembered moment of the event is closer to the timing of the unpredictable visual change.

From silicon to organic nanoparticle memory devices.

Science.gov (United States)

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.

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

Science.gov (United States)

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

2017-05-01

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

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

Directory of Open Access Journals (Sweden)

Souheil-Antoine Younes

2011-10-01

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

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

Science.gov (United States)

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

2015-02-24

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

Flashing inception in flowing liquids

International Nuclear Information System (INIS)

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

Statistical Evolution of the Lightning Flash

Science.gov (United States)

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

New memory devices based on the proton transfer process

International Nuclear Information System (INIS)

Wierzbowska, Małgorzata

2016-01-01

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

Distributed Shared Memory for the Cell Broadband Engine (DSMCBE)

DEFF Research Database (Denmark)

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

2009-01-01

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

PD-1 Blockade Expands Intratumoral Memory T Cells

DEFF Research Database (Denmark)

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

2016-01-01

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

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

Science.gov (United States)

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

2011-01-01

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

Menopausal Hot Flashes and White Matter Hyperintensities

Science.gov (United States)

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

Foundation Flash CS4 for Designers

CERN Document Server

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

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

Science.gov (United States)

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

2015-01-01

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

Experimental Comparison of 2-3MV X-Ray Sources for Flash Radiography

International Nuclear Information System (INIS)

MENGE, PETER RICHARD; JOHNSON, DAVID LEE; MAENCHEN, JOHN E.; OLSON, CRAIG L.; ROVANG, DEAN C.; DROEMER, D.; HUNT, E.; OLIVER, BRYAN VELTEN; ROSE, DAVID VINCENT; WELCH, DALE ROBERT

2002-01-01

High-brightness flash x-ray sources are needed for penetrating dynamic radiography for a variety of applications. Various bremsstrahlung source experiments have been conducted on the TriMeV accelerator (3MV, 60 Ω 20 ns) to determine the best diode and focusing configuration in the 2-3 MV range. Three classes of candidate diodes were examined: gas cell focusing, magnetically immersed, and rod pinch. The best result for the gas cell diode was 6 rad at 1 meter from the source with a 5 mm diameter x-ray spot. Using a 0.5 mm diameter cathode immersed in a 17 T solenoidal magnetic field, the best shot produced 4.1 rad with a 2.9 mm spot. The rod pinch diode demonstrated very reproducible radiographic spots between 0.75 and 0.8 mm in diameter, producing 1.2 rad. This represents a factor of eight improvement in the TriMeV flash radiographic capability above the original gas cell diode to a figure of merit (dose/spot diameter) > 1.8 rad/mm. These results clearly show the rod pinch diode to be the choice x-ray source for flash radiography at 2-3 M V

Detection of Malicious Flash Banner Advertisements

Directory of Open Access Journals (Sweden)

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.

Memory control by the B cell antigen receptor.

Science.gov (United States)

Engels, Niklas; Wienands, Jürgen

2018-05-01

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

Design of SMART alarm system using main memory database

International Nuclear Information System (INIS)

Jang, Kue Sook; Seo, Yong Seok; Park, Keun Oak; Lee, Jong Bok; Kim, Dong Hoon

2001-01-01

To achieve design goal of SMART alarm system, first of all we have to decide on how to handle and manage alarm information and how to use database. So this paper analyses concepts and deficiencies of main memory database applied in real time system. And this paper sets up structure and processing principles of main memory database using nonvolatile memory such as flash memory and develops recovery strategy and process board structures using these. Therefore this paper shows design of SMART alarm system is suited functions and requirements

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

Science.gov (United States)

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

2009-01-01

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

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

Directory of Open Access Journals (Sweden)

Grégoire Lauvau

2016-09-01

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

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

Science.gov (United States)

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

2018-05-11

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

On multiphase negative flash for ideal solutions

DEFF Research Database (Denmark)

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...

Measuring hot flash phenomenonology using ambulatory prospective digital diaries

Science.gov (United States)

Fisher, William I.; Thurston, Rebecca C.

2016-01-01

Objective This study provides the description, protocol, and results from a novel prospective ambulatory digital hot flash phenomenon diary. Methods This study included 152 midlife women with daily hot flashes who completed an ambulatory electronic hot flash diary continuously for the waking hours of 3 consecutive days. In this diary, women recorded their hot flashes and accompanying characteristics and associations as the hot flashes occurred. Results Self-reported hot flash severity on the digital diaries indicated that the majority of hot flashes were rated as mild (41.3%) or moderate (43.7%). Severe (13.1%) and very severe (1.8%) hot flashes were less common. Hot flash bother ratings were rated as mild (43%), or moderate (33.5%), with fewer hot flashes reported bothersome (17.5%) or very bothersome (6%). The majority of hot flashes were reported as occurring on the on the face (78.9%), neck (74.7%), and chest (61.3%). Prickly skin was reported concurrently with 32% of hot flashes, 7% with anxiety and 5% with nausea. A novel finding, 38% of hot flashes were accompanied by a premonitory aura. Conclusion A prospective electronic digital hot flash diary allows for a more precise quantitation of hot flashes while overcoming many of the limitations of commonly employed retrospective questionnaires and paper diaries. Unique insights into the phenomenology, loci and associated characteristics of hot flashes were obtained using this device. The digital hot flash phenomenology diary is recommended for future ambulatory studies of hot flashes as a prospective measure of the hot flash experience. PMID:27404030

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

Directory of Open Access Journals (Sweden)

Katie L. Reagin

2018-01-01

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

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

Directory of Open Access Journals (Sweden)

Zeyu Chen

2017-09-01

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

Low power and reliable SRAM memory cell and array design

CERN Document Server

Ishibashi, Koichiro

2011-01-01

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

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

Science.gov (United States)

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

2013-03-28

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

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

Directory of Open Access Journals (Sweden)

Jan P. Böttcher

2013-03-01

Full Text Available Development of CD8+ T cell (CTL immunity or tolerance is linked to the conditions during T cell priming. Dendritic cells (DCs matured during inflammation generate effector/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.

Memory CD8+ T cells protect dendritic cells from CTL killing

NARCIS (Netherlands)

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

2008-01-01

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

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

KAUST Repository

Meister, Stefan

2011-04-26

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 switching in PCM devices motivate the need to further study its fundamental properties. However, many investigations treat PCM cells as black boxes; nanostructural changes inside the devices remain hidden. Here, using in situ transmission electron microscopy, we observe real-time nanostructural changes in lateral Ge2Sb2Te5 (GST) PCM bridges during switching. We find that PCM devices with similar resistances can exhibit distinct threshold switching behaviors due to the different initial distribution of nanocrystalline and amorphous domains, explaining variability of switching behaviors of PCM cells in the literature. Our findings show a direct correlation between nanostructure and switching behavior, providing important guidelines in the design and operation of future PCM devices with improved endurance and lower variability. © 2011 American Chemical Society.

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

Science.gov (United States)

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.

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

Science.gov (United States)

Weinberg, Adriana; Huang, Sharon; Moscicki, Anna-Barbara; Saah, Afred; Levin, Myron J

2018-04-24

To determine the magnitude and persistence of quadrivalent human papillomavirus (HPV)16 and HPV18 B-cell and T-cell memory after three or four doses of quadrivalent HPV vaccine (QHPV) in HIV-infected children. Seventy-four HIV-infected children immunized with four doses and 23 with three doses of QHPV had HPV16 and HPV18 IgG B-cell and IFNγ and IL2 T-cell ELISPOT performed at 2, 3.5 and 4-5 years after the last dose. HPV16 and HPV18 T-cell responses were similar in both treatment groups, with higher responses to HPV16 vs. HPV18. These HPV T-cell responses correlated with HIV disease characteristics at the study visits. Global T-cell function declined over time as measured by nonspecific mitogenic stimulation. B-cell memory was similar across treatment groups and HPV genotypes. There was a decline in HPV-specific B-cell memory over time that reached statistical significance for HPV16 in the four-dose group. B-cell and T-cell memory did not significantly differ after either three or four doses of QHPV in HIV-infected children. The clinical consequences of decreasing global T-cell function and HPV B-cell memory over time in HIV-infected children requires further investigation.

Flashing inception in flowing liquids

International Nuclear Information System (INIS)

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

Advanced error-prediction LDPC with temperature compensation for highly reliable SSDs

Science.gov (United States)

Tokutomi, Tsukasa; Tanakamaru, Shuhei; Iwasaki, Tomoko Ogura; Takeuchi, Ken

2015-09-01

To improve the reliability of NAND Flash memory based solid-state drives (SSDs), error-prediction LDPC (EP-LDPC) has been proposed for multi-level-cell (MLC) NAND Flash memory (Tanakamaru et al., 2012, 2013), which is effective for long retention times. However, EP-LDPC is not as effective for triple-level cell (TLC) NAND Flash memory, because TLC NAND Flash has higher error rates and is more sensitive to program-disturb error. Therefore, advanced error-prediction LDPC (AEP-LDPC) has been proposed for TLC NAND Flash memory (Tokutomi et al., 2014). AEP-LDPC can correct errors more accurately by precisely describing the error phenomena. In this paper, the effects of AEP-LDPC are investigated in a 2×nm TLC NAND Flash memory with temperature characterization. Compared with LDPC-with-BER-only, the SSD's data-retention time is increased by 3.4× and 9.5× at room-temperature (RT) and 85 °C, respectively. Similarly, the acceptable BER is increased by 1.8× and 2.3×, respectively. Moreover, AEP-LDPC can correct errors with pre-determined tables made at higher temperatures to shorten the measurement time before shipping. Furthermore, it is found that one table can cover behavior over a range of temperatures in AEP-LDPC. As a result, the total table size can be reduced to 777 kBytes, which makes this approach more practical.

High frequency electromechanical memory cells based on telescoping carbon nanotubes.

Science.gov (United States)

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

2010-07-01

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

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

Science.gov (United States)

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

2012-01-01

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

The mutagenic potential of high flash aromatic naphtha.

Science.gov (United States)

Schreiner, C A; Edwards, D A; McKee, R H; Swanson, M; Wong, Z A; Schmitt, S; Beatty, P

1989-06-01

Catalytic reforming is a refining process that converts naphthenes to aromatics by dehydrogenation to make higher octane gasoline blending components. A portion of this wide boiling range hydrocarbon stream can be separated by distillation and used for other purposes. One such application is a mixture of predominantly 9-carbon aromatic molecules (C9 aromatics, primarily isomers of ethyltoluene and trimethylbenzene), which is removed and used as a solvent--high-flash aromatic naphtha. A program was initiated to assess the toxicological properties of high-flash aromatic naphtha since there may be human exposure through inhalation or external body contact. The current study was conducted partly to assess the potential for mutagenic activity and also to assist in an assessment of carcinogenic potential. The specific tests utilized included the Salmonella/mammalian microsome mutagenicity assay, the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) forward mutation assay in CHO cells, in vitro chromosome aberration and sister chromatid exchange (SCE) assays in CHO cells, and an in vivo chromosome aberration assay in rat bone marrow.

GeckoFTL: Scalable Flash Translation Techniques For Very Large Flash Devices

DEFF Research Database (Denmark)

Dayan, Niv; Bonnet, Philippe; Idreos, Stratos

2016-01-01

The volume of metadata needed by a flash translation layer (FTL) is proportional to the storage capacity of a flash device. Ideally, this metadata should reside in the device's integrated RAM to enable fast access. However, as flash devices scale to terabytes, the necessary volume of metadata...... thereby harming performance and device lifetime. In this paper, we identify a key component of the metadata called the Page Validity Bitmap (PVB) as the bottleneck. PVB is used by the garbage-collectors of state-of-the-art FTLs to keep track of which physical pages in the device are invalid. PVB...... constitutes 95% of the FTL's RAM-resident metadata, and recovering PVB after power fails takes a significant proportion of the overall recovery time. To solve this problem, we propose a page-associative FTL called GeckoFTL, whose central innovation is replacing PVB with a new data structure called Logarithmic...

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

Directory of Open Access Journals (Sweden)

Angela Fuery

Full Text Available Carrier-specific T cell and polysaccharide-specific B cell memory responses are not well characterised in infants following glyco-conjugate vaccination. We aimed to determine if the number of Meningococcal (Men C- and Y- specific memory B cells and; number and quality of Tetanus Toxoid (TT carrier-specific memory CD4+ T cells are associated with polysaccharide-specific IgG post HibMenCY-TT vaccination. Healthy infants received HibMenCY-TT vaccine at 2, 4 and 6 months with a booster at 12 months. Peripheral blood mononuclear cells were isolated and polysaccharide-specific memory B cells enumerated using ELISpot. TT-specific memory CD4+ T cells were detected and phenotyped based on CD154 expression and intracellular TNF-α, IL-2 and IFN-γ expression following stimulation. Functional polysaccharide-specific IgG titres were measured using the serum bactericidal activity (SBA assay. Polysaccharide-specific Men C- but not Men Y- specific memory B cell frequencies pre-boost (12 months were significantly associated with post-boost (13 months SBA titres. Regression analysis showed no association between memory B cell frequencies post-priming (at 6 or 7 months and SBA at 12 months or 13 months. TT-specific CD4+ T cells were detected at frequencies between 0.001 and 0.112 as a percentage of CD3+ T cells, but their numbers were not associated with SBA titres. There were significant negative associations between SBA titres at M13 and cytokine expression at M7 and M12.Induction of persistent polysaccharide-specific memory B cells prior to boosting is an important determinant of secondary IgG responses in infants. However, polysaccharide-specific functional IgG responses appear to be independent of the number and quality of circulating carrier-specific CD4+ T cells after priming.

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

Science.gov (United States)

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

2014-08-01

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

An Analysis of Total Lightning Flash Rates Over Florida

Science.gov (United States)

Mazzetti, Thomas O.; Fuelberg, Henry E.

2017-12-01

Although Florida is known as the "Sunshine State", it also contains the greatest lightning flash densities in the United States. Flash density has received considerable attention in the literature, but lightning flash rate has received much less attention. We use data from the Earth Networks Total Lightning Network (ENTLN) to produce a 5 year (2010-2014) set of statistics regarding total flash rates over Florida and adjacent regions. Instead of tracking individual storms, we superimpose a 0.2° × 0.2° grid over the study region and count both cloud-to-ground (CG) and in-cloud (IC) flashes over 5 min intervals. Results show that the distribution of total flash rates is highly skewed toward small values, whereas the greatest rate is 185 flashes min-1. Greatest average annual flash rates ( 3 flashes min-1) are located near Orlando. The southernmost peninsula, North Florida, and the Florida Panhandle exhibit smaller average annual flash rates ( 1.5 flashes min-1). Large flash rates > 100 flashes min-1 can occur during any season, at any time during the 24 h period, and at any location within the domain. However, they are most likely during the afternoon and early evening in East Central Florida during the spring and summer months.

A global flash flood forecasting system

Science.gov (United States)

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

Flash CS4: The Missing Manual

CERN Document Server

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.

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

OpenAIRE

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

2009-01-01

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

Single-cell atomic quantum memory for light

International Nuclear Information System (INIS)

Opatrny, Tomas

2006-01-01

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

NAFFS: network attached flash file system for cloud storage on portable consumer electronics

Science.gov (United States)

Han, Lin; Huang, Hao; Xie, Changsheng

Cloud storage technology has become a research hotspot in recent years, while the existing cloud storage services are mainly designed for data storage needs with stable high speed Internet connection. Mobile Internet connections are often unstable and the speed is relatively low. These native features of mobile Internet limit the use of cloud storage in portable consumer electronics. The Network Attached Flash File System (NAFFS) presented the idea of taking the portable device built-in NAND flash memory as the front-end cache of virtualized cloud storage device. Modern portable devices with Internet connection have built-in more than 1GB NAND Flash, which is quite enough for daily data storage. The data transfer rate of NAND flash device is much higher than mobile Internet connections[1], and its non-volatile feature makes it very suitable as the cache device of Internet cloud storage on portable device, which often have unstable power supply and intermittent Internet connection. In the present work, NAFFS is evaluated with several benchmarks, and its performance is compared with traditional network attached file systems, such as NFS. Our evaluation results indicate that the NAFFS achieves an average accessing speed of 3.38MB/s, which is about 3 times faster than directly accessing cloud storage by mobile Internet connection， and offers a more stable interface than that of directly using cloud storage API. Unstable Internet connection and sudden power off condition are tolerable, and no data in cache will be lost in such situation.

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

Science.gov (United States)

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

2017-06-05

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

Flashing coupled density wave oscillation

International Nuclear Information System (INIS)

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.)

How Polycomb-Mediated Cell Memory Deals With a Changing Environment

KAUST Repository

Marasca, Federica

2018-03-09

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

How Polycomb-Mediated Cell Memory Deals With a Changing Environment

KAUST Repository

Marasca, Federica; Bodega, Beatrice; Orlando, Valerio

2018-01-01

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

Flash CS5 The Missing Manual

CERN Document Server

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

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

International Nuclear Information System (INIS)

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

2006-01-01

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

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

Science.gov (United States)

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.

Novel conformal organic antireflective coatings for advanced I-line lithography

Science.gov (United States)

Deshpande, Shreeram V.; Nowak, Kelly A.; Fowler, Shelly; Williams, Paul; Arjona, Mikko

2001-08-01

Flash memory chips are playing a critical role in semiconductor devices due to increased popularity of hand held electronic communication devices such as cell phones and PDAs (personal Digital Assistants). Flash memory offers two primary advantages in semiconductor devices. First, it offers flexibility of in-circuit programming capability to reduce the loss from programming errors and to significantly reduce commercialization time to market for new devices. Second, flash memory has a double density memory capability through stacked gate structures which increases the memory capability and thus saves significantly on chip real estate. However, due to stacked gate structures the requirements for manufacturing of flash memory devices are significantly different from traditional memory devices. Stacked gate structures also offer unique challenges to lithographic patterning materials such as Bottom Anti-Reflective Coating (BARC) compositions used to achieve CD control and to minimize standing wave effect in photolithography. To be applicable in flash memory manufacturing a BARC should form a conformal coating on high topography of stacked gate features as well as provide the normal anti-reflection properties for CD control. In this paper we report on a new highly conformal advanced i-line BARC for use in design and manufacture of flash memory devices. Conformal BARCs being significantly thinner in trenches than the planarizing BARCs offer the advantage of reducing BARC overetch and thus minimizing resist thickness loss.

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

Directory of Open Access Journals (Sweden)

Matthew D Martin

2015-10-01

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

Research of coal flash hydropyrolysis

Energy Technology Data Exchange (ETDEWEB)

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.

Emerging memory technologies design, architecture, and applications

CERN Document Server

2014-01-01

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

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

Science.gov (United States)

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

2017-06-01

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

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

Directory of Open Access Journals (Sweden)

Iris Reuveni

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

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

Directory of Open Access Journals (Sweden)

Russell Kate

2008-08-01

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

A nanowire magnetic memory cell based on a periodic magnetic superlattice

International Nuclear Information System (INIS)

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

2005-01-01

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

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

Science.gov (United States)

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

2011-01-01

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

Bipolar cloud-to-ground lightning flash observations

Science.gov (United States)

Saba, Marcelo M. F.; Schumann, Carina; Warner, Tom A.; Helsdon, John H.; Schulz, Wolfgang; Orville, Richard E.

2013-10-01

lightning is usually defined as a lightning flash where the current waveform exhibits a polarity reversal. There are very few reported cases of cloud-to-ground (CG) bipolar flashes using only one channel in the literature. Reports on this type of bipolar flashes are not common due to the fact that in order to confirm that currents of both polarities follow the same channel to the ground, one necessarily needs video records. This study presents five clear observations of single-channel bipolar CG flashes. High-speed video and electric field measurement observations are used and analyzed. Based on the video images obtained and based on previous observations of positive CG flashes with high-speed cameras, we suggest that positive leader branches which do not participate in the initial return stroke of a positive cloud-to-ground flash later generate recoil leaders whose negative ends, upon reaching the branch point, traverse the return stroke channel path to the ground resulting in a subsequent return stroke of opposite polarity.

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

Science.gov (United States)

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.

Atypical and classical memory B cells produce Plasmodium falciparum neutralizing antibodies

DEFF Research Database (Denmark)

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

2013-01-01

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

Modelling and mitigation of Flash Crashes

OpenAIRE

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....

Electro-optical muzzle flash detection

Science.gov (United States)

Krieg, Jürgen; Eisele, Christian; Seiffer, Dirk

2016-10-01

Localizing a shooter in a complex scenario is a difficult task. Acoustic sensors can be used to detect blast waves. Radar technology permits detection of the projectile. A third method is to detect the muzzle flash using electro-optical devices. Detection of muzzle flash events is possible with focal plane arrays, line and single element detectors. In this paper, we will show that the detection of a muzzle flash works well in the shortwave infrared spectral range. Important for the acceptance of an operational warning system in daily use is a very low false alarm rate. Using data from a detector with a high sampling rate the temporal signature of a potential muzzle flash event can be analyzed and the false alarm rate can be reduced. Another important issue is the realization of an omnidirectional view required on an operational level. It will be shown that a combination of single element detectors and simple optics in an appropriate configuration is a capable solution.

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

Science.gov (United States)

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

2005-01-01

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

On the shape memory of red blood cells

Science.gov (United States)

Cordasco, Daniel; Bagchi, Prosenjit

2017-04-01

Red blood cells (RBCs) undergo remarkably large deformations when subjected to external forces but return to their biconcave discoid resting shape as the forces are withdrawn. In many experiments, such as when RBCs are subjected to a shear flow and undergo the tank-treading motion, the membrane elements are also displaced from their original (resting) locations along the cell surface with respect to the cell axis, in addition to the cell being deformed. A shape memory is said to exist if after the flow is stopped the RBC regains its biconcave shape and the membrane elements also return to their original locations. The shape memory of RBCs was demonstrated by Fischer ["Shape memory of human red blood cells," Biophys. J. 86, 3304-3313 (2004)] using shear flow go-and-stop experiments. Optical tweezer and micropipette based stretch-relaxation experiments do not reveal the complete shape memory because while the RBC may be deformed, the membrane elements are not significantly displaced from their original locations with respect to the cell axis. Here we present the first three-dimensional computational study predicting the complete shape memory of RBCs using shear flow go-and-stop simulations. The influence of different parameters, namely, membrane shear elasticity and bending rigidity, membrane viscosity, cytoplasmic and suspending fluid viscosity, as well as different stress-free states of the RBC is studied. For all cases, the RBCs always exhibit shape memory. The complete recovery of the RBC in shear flow go-and-stop simulations occurs over a time that is orders of magnitude longer than that for optical tweezer and micropipette based relaxations. The response is also observed to be more complex and composed of widely disparate time scales as opposed to only one time scale that characterizes the optical tweezer and micropipette based relaxations. We observe that the recovery occurs in three phases: a rapid compression of the RBC immediately after the flow is stopped

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

Directory of Open Access Journals (Sweden)

Megan E Schmidt

2018-01-01

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

RELATIONSHIP BETWEEN FLASH POINTS OF SOME BINARY ...

African Journals Online (AJOL)

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.

CellSs: Scheduling Techniques to Better Exploit Memory Hierarchy

Directory of Open Access Journals (Sweden)

Pieter Bellens

2009-01-01

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

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

Science.gov (United States)

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

2016-01-01

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

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

Science.gov (United States)

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

2018-03-01

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

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

Science.gov (United States)

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

2011-01-01

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

Resistive Switching of Ta2O5-Based Self-Rectifying Vertical-Type Resistive Switching Memory

Science.gov (United States)

Ryu, Sungyeon; Kim, Seong Keun; Choi, Byung Joon

2018-01-01

To efficiently increase the capacity of resistive switching random-access memory (RRAM) while maintaining the same area, a vertical structure similar to a vertical NAND flash structure is needed. In addition, the sneak-path current through the half-selected neighboring memory cell should be mitigated by integrating a selector device with each RRAM cell. In this study, an integrated vertical-type RRAM cell and selector device was fabricated and characterized. Ta2O5 as the switching layer and TaOxNy as the selector layer were used to preliminarily study the feasibility of such an integrated device. To make the side contact of the bottom electrode with active layers, a thick Al2O3 insulating layer was placed between the Pt bottom electrode and the Ta2O5/TaOxNy stacks. Resistive switching phenomena were observed under relatively low currents (below 10 μA) in this vertical-type RRAM device. The TaOxNy layer acted as a nonlinear resistor with moderate nonlinearity. Its low-resistance-state and high-resistance-state were well retained up to 1000 s.

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

Directory of Open Access Journals (Sweden)

Cathy Steel

2011-04-01

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

Flash x-ray

International Nuclear Information System (INIS)

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

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

Directory of Open Access Journals (Sweden)

Paul U Cameron

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

Flash CS5.5 The Missing Manual

CERN Document Server

Grover, Chris

2011-01-01

You can build everything from simple animations to full-fledged iOS and Android apps with Flash CS5.5, but learning this complex program can be difficult-unless you have this fully updated, bestselling guide. Learn how to create gorgeous Flash effects even if you have no programming experience. With Flash CS5.5: The Missing Manual, you'll move from the basics to power-user tools with ease. Learn animation basics. Discover how to turn simple ideas into stunning animations.Master Flash's tools. Learn the animation and effects tools with clear explanations and hands-on examples.Use 3D effects. R

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

Directory of Open Access Journals (Sweden)

Shintaro eHojyo

2016-02-01

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

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

Science.gov (United States)

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

2016-11-29

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

Interfacial Redox Reactions Associated Ionic Transport in Oxide-Based Memories.

Science.gov (United States)

Younis, Adnan; Chu, Dewei; Shah, Abdul Hadi; Du, Haiwei; Li, Sean

2017-01-18

As an alternative to transistor-based flash memories, redox reactions mediated resistive switches are considered as the most promising next-generation nonvolatile memories that combine the advantages of a simple metal/solid electrolyte (insulator)/metal structure, high scalability, low power consumption, and fast processing. For cation-based memories, the unavailability of in-built mobile cations in many solid electrolytes/insulators (e.g., Ta 2 O 5 , SiO 2 , etc.) instigates the essential role of absorbed water in films to keep electroneutrality for redox reactions at counter electrodes. Herein, we demonstrate electrochemical characteristics (oxidation/reduction reactions) of active electrodes (Ag and Cu) at the electrode/electrolyte interface and their subsequent ions transportation in Fe 3 O 4 film by means of cyclic voltammetry measurements. By posing positive potentials on Ag/Cu active electrodes, Ag preferentially oxidized to Ag + , while Cu prefers to oxidize into Cu 2+ first, followed by Cu/Cu + oxidation. By sweeping the reverse potential, the oxidized ions can be subsequently reduced at the counter electrode. The results presented here provide a detailed understanding of the resistive switching phenomenon in Fe 3 O 4 -based memory cells. The results were further discussed on the basis of electrochemically assisted cations diffusions in the presence of absorbed surface water molecules in the film.

Hot Flashes amd Night Sweats (PDQ)

Science.gov (United States)

... 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 ...

"Know What to Do If You Encounter a Flash Flood": Mental Models Analysis for Improving Flash Flood Risk Communication and Public Decision Making.

Science.gov (United States)

Lazrus, Heather; Morss, Rebecca E; Demuth, Julie L; Lazo, Jeffrey K; Bostrom, Ann

2016-02-01

Understanding how people view flash flood risks can help improve risk communication, ultimately improving outcomes. This article analyzes data from 26 mental models interviews about flash floods with members of the public in Boulder, Colorado, to understand their perspectives on flash flood risks and mitigation. The analysis includes a comparison between public and professional perspectives by referencing a companion mental models study of Boulder-area professionals. A mental models approach can help to diagnose what people already know about flash flood risks and responses, as well as any critical gaps in their knowledge that might be addressed through improved risk communication. A few public interviewees mentioned most of the key concepts discussed by professionals as important for flash flood warning decision making. However, most interviewees exhibited some incomplete understandings and misconceptions about aspects of flash flood development and exposure, effects, or mitigation that may lead to ineffective warning decisions when a flash flood threatens. These include important misunderstandings about the rapid evolution of flash floods, the speed of water in flash floods, the locations and times that pose the greatest flash flood risk in Boulder, the value of situational awareness and environmental cues, and the most appropriate responses when a flash flood threatens. The findings point to recommendations for ways to improve risk communication, over the long term and when an event threatens, to help people quickly recognize and understand threats, obtain needed information, and make informed decisions in complex, rapidly evolving extreme weather events such as flash floods. © 2015 Society for Risk Analysis.

Flash sintering of ceramic materials

Science.gov (United States)

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.

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

Science.gov (United States)

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

2004-01-01

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

Evaluation of Flash Bainite in 4130 Steel

Science.gov (United States)

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

Physiologically assessed hot flashes and endothelial function among midlife women.

Science.gov (United States)

Thurston, Rebecca C; Chang, Yuefang; Barinas-Mitchell, Emma; Jennings, J Richard; von Känel, Roland; Landsittel, Doug P; Matthews, Karen A

2017-08-01

Hot flashes are experienced by most midlife women. Emerging data indicate that they may be associated with endothelial dysfunction. No studies have tested whether hot flashes are associated with endothelial function using physiologic measures of hot flashes. We tested whether physiologically assessed hot flashes were associated with poorer endothelial function. We also considered whether age modified associations. Two hundred seventy-two nonsmoking women reporting either daily hot flashes or no hot flashes, aged 40 to 60 years, and free of clinical cardiovascular disease, underwent ambulatory physiologic hot flash and diary hot flash monitoring; a blood draw; and ultrasound measurement of brachial artery flow-mediated dilation to assess endothelial function. Associations between hot flashes and flow-mediated dilation were tested in linear regression models controlling for lumen diameter, demographics, cardiovascular disease risk factors, and estradiol. In multivariable models incorporating cardiovascular disease risk factors, significant interactions by age (P hot flashes (beta [standard error] = -2.07 [0.79], P = 0.01), and more frequent physiologic hot flashes (for each hot flash: beta [standard error] = -0.10 [0.05], P = 0.03, multivariable) were associated with lower flow-mediated dilation. Associations were not accounted for by estradiol. Associations were not observed among the older women (age 54-60 years) or for self-reported hot flash frequency, severity, or bother. Among the younger women, hot flashes explained more variance in flow-mediated dilation than standard cardiovascular disease risk factors or estradiol. Among younger midlife women, frequent hot flashes were associated with poorer endothelial function and may provide information about women's vascular status beyond cardiovascular disease risk factors and estradiol.

Principles of arc flash protection

Energy Technology Data Exchange (ETDEWEB)

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.

Out of sight but not out of mind : The neurophysiology of iconic memory in the superior temporal sulcus

NARCIS (Netherlands)

Keysers, C; Xiao, DK; Foldiak, P; Perrett, DI

2005-01-01

Iconic memory, the short-lasting visual memory of a briefly flashed stimulus, is an important component of most models of visual perception. Here we investigate what physiological mechanisms underlie this capacity by showing rapid serial visual presentation (RSVP) sequences with and without

Flash flood forecasting, warning and risk management: the HYDRATE project

International Nuclear Information System (INIS)

Borga, M.; Anagnostou, E.N.; Bloeschl, G.; Creutin, J.-D.

2011-01-01

Highlights: → We characterize flash flood events in various regions of Europe. → We provide guidance to improve observations and monitoring of flash floods. → Flash floods are associated to orography and are influenced by initial soil moisture conditions. → Models for flash flood forecasting and flash flood hazard assessment are illustrated and discussed. → We examine implications for flood risk policy and discuss recommendations received from end users. - Abstract: The management of flash flood hazards and risks is a critical component of public safety and quality of life. Flash-floods develop at space and time scales that conventional observation systems are not able to monitor for rainfall and river discharge. Consequently, the atmospheric and hydrological generating mechanisms of flash-floods are poorly understood, leading to highly uncertain forecasts of these events. The objective of the HYDRATE project has been to improve the scientific basis of flash flood forecasting by advancing and harmonising a European-wide innovative flash flood observation strategy and developing a coherent set of technologies and tools for effective early warning systems. To this end, the project included actions on the organization of the existing flash flood data patrimony across Europe. The final aim of HYDRATE was to enhance the capability of flash flood forecasting in ungauged basins by exploiting the extended availability of flash flood data and the improved process understanding. This paper provides a review of the work conducted in HYDRATE with a special emphasis on how this body of research can contribute to guide the policy-life cycle concerning flash flood risk management.

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

Science.gov (United States)

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

2012-07-01

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

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

Science.gov (United States)

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

2016-11-01

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

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

Data.gov (United States)

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...

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

Science.gov (United States)

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

2014-11-19

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

Geographical distribution of hot flash frequencies: considering climatic influences.

Science.gov (United States)

Sievert, Lynnette Leidy; Flanagan, Erin K

2005-10-01

Laboratory studies suggest that hot flashes are triggered by small elevations in core body temperature acting within a reduced thermoneutral zone, i.e., the temperature range in which a woman neither shivers nor sweats. In the present study, it was hypothesized that women in different populations develop climate-specific thermoneutral zones, and ultimately, population-specific frequencies of hot flashes at menopause. Correlations were predicted between hot flash frequencies and latitude, elevation, and annual temperatures. Data on hot flash frequencies were drawn from 54 studies. Pearson correlation analyses and simple linear regressions were applied, first using all studies, and second using a subset of studies that included participants only to age 60 (n = 36). Regressions were repeated with all studies, controlling for method of hot flash assessment. When analyses were restricted to studies that included women up to age 60, average temperature of the coldest month was a significant predictor of hot flash frequency (P hottest and coldest temperatures was also a significant predictor (P coldest month, difference between hottest and coldest temperatures, and mean annual temperature were significant predictors of hot flash frequency. Women reported fewer hot flashes in warmer temperatures, and more hot flashes with increasing seasonality. These results suggest that acclimatization to coldest temperatures or sensitivity to seasonality may explain part of the population variation in hot flash frequency.

Organic flash cycles for efficient power production

Science.gov (United States)

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.

Ultra-Low Voltage Class AB Switched Current Memory Cell

DEFF Research Database (Denmark)

Igor, Mucha

1996-01-01

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

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

Directory of Open Access Journals (Sweden)

Francis Maina Ndungu

2009-12-01

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

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

Science.gov (United States)

Tonaco, Marcela M; Moreira, Jôsimar D; Nunes, Fernanda F C; Loures, Cristina M G; Souza, Larissa R; Martins, Janaina M; Silva, Henrique R; Porto, Arthur Henrique R; Toledo, Vicente Paulo C P; Miranda, Silvana S; Guimarães, Tânia Mara P D

2017-12-01

The cells T CD4+ T and CD8+ can be subdivided into phenotypes naïve, T of central memory, T of effector memory and effector, according to the expression of surface molecules CD45RO and CD27. The T lymphocytes are cells of long life with capacity of rapid expansion and function, after a new antigenic exposure. In tuberculosis, it was found that specific memory T cells are present, however, gaps remain about the role of such cells in the disease immunology. In this study, the phenotypic profile was analyzed and characterized the functionality of CD4+ T lymphocytes and CD8+ T cells of memory and effector, in response to specific stimuli in vitro, in patients with active pulmonary TB, compared to individuals with latent infection with Mycobacterium tuberculosis the ones treated with pulmonary TB. It was observed that the group of patients with active pulmonary tuberculosis was the one which presented the highest proportion of cells T CD4+ of central memory IFN-ɣ+ e TNF-α+, suggesting that in TB, these T of central memory cells would have a profile of protective response, being an important target of study for the development of more effective vaccines; this group also developed lower proportion of CD8+ T effector lymphocytes than the others, a probable cause of specific and less effective response against the bacillus in these individuals; the ones treated for pulmonary tuberculosis were those who developed higher proportion of T CD4+ of memory central IL-17+ cells, indicating that the stimulation of long duration, with high antigenic load, followed by elimination of the pathogen, contribute to more significant generation of such cells; individuals with latent infection by M. tuberculosis and treated for pulmonary tuberculosis, showed greater response of CD8+ T effector lymphocytes IFN-ɣ+ than the controls, suggesting that these cells, as well as CD4+ T lymphocytes, have crucial role of protection against M. tuberculosis. These findings have contributed to a better

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

Directory of Open Access Journals (Sweden)

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.

An optically transparent and flexible memory with embedded gold nanoparticles in a polymethylsilsesquioxane dielectric

International Nuclear Information System (INIS)

Ooi, P.C.; Aw, K.C.; Gao, W.; Razak, K.A.

2013-01-01

In this work, we demonstrated a simple fabrication route towards an optically transparent and flexible memory device. The device is simple and consists of a metal/insulator/semiconductor structure; namely MIS. The preliminary MIS study with gold nanoparticles embedded between the polymethylsilsesquioxane layers was fabricated on p-Si substrate and the capacitance versus voltage measurements confirmed the charge trapped capability of the fabricated MIS memory device. Subsequently, an optically transparent and flexible MIS memory device made from indium–tin-oxide coated polyethylene terephthalate substrate and pentacene was used to replace the opaque p-Si substrate as the active layer. Current versus voltage (I–V) plot of the transparent and flexible device shows the presence of hysteresis. In an I–V plot, three distinct regions have been identified and the transport mechanisms are explained. The fabricated optically transparent and mechanically flexible MIS memory device can be programmed and erased multiple times, similar to a flash memory. Mechanical characterization to determine the robustness of the flexible memory device was also conducted but failed to establish any relationship in this preliminary work as the effect was random. Hence, more work is needed to understand the reliability of this device, especially when they are subjected to mechanical stress. - Highlights: ► An optically transparent and mechanically flexible memory is presented. ► Electrical characteristics show reprogrammable memory similar to flash memory. ► Transport mechanisms are proposed and explained. ► Mechanical bending tests are conducted

An optically transparent and flexible memory with embedded gold nanoparticles in a polymethylsilsesquioxane dielectric

Energy Technology Data Exchange (ETDEWEB)

Ooi, P.C. [Mechanical Engineering, The University of Auckland (New Zealand); Aw, K.C., E-mail: k.aw@auckland.ac.nz [Mechanical Engineering, The University of Auckland (New Zealand); Gao, W. [Chemical and Materials Engineering, The University of Auckland (New Zealand); Razak, K.A. [School of Materials and Mineral Resources Engineering, Universiti Sains (Malaysia); NanoBiotechnology Research and Innovation, INFORMM, Universiti Sains (Malaysia)

2013-10-01

In this work, we demonstrated a simple fabrication route towards an optically transparent and flexible memory device. The device is simple and consists of a metal/insulator/semiconductor structure; namely MIS. The preliminary MIS study with gold nanoparticles embedded between the polymethylsilsesquioxane layers was fabricated on p-Si substrate and the capacitance versus voltage measurements confirmed the charge trapped capability of the fabricated MIS memory device. Subsequently, an optically transparent and flexible MIS memory device made from indium–tin-oxide coated polyethylene terephthalate substrate and pentacene was used to replace the opaque p-Si substrate as the active layer. Current versus voltage (I–V) plot of the transparent and flexible device shows the presence of hysteresis. In an I–V plot, three distinct regions have been identified and the transport mechanisms are explained. The fabricated optically transparent and mechanically flexible MIS memory device can be programmed and erased multiple times, similar to a flash memory. Mechanical characterization to determine the robustness of the flexible memory device was also conducted but failed to establish any relationship in this preliminary work as the effect was random. Hence, more work is needed to understand the reliability of this device, especially when they are subjected to mechanical stress. - Highlights: ► An optically transparent and mechanically flexible memory is presented. ► Electrical characteristics show reprogrammable memory similar to flash memory. ► Transport mechanisms are proposed and explained. ► Mechanical bending tests are conducted.

Construction and performance of large flash chambers

International Nuclear Information System (INIS)

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

Production of bio-oils from wood by flash pyrolysis; Herstellung von Bio-Oelen aus Holz in einer Flash-Pyrolyseanlage

Energy Technology Data Exchange (ETDEWEB)

Meier, D; Ollesch, T [Bundesforschungsanstalt fuer Forst- und Holzwirtschaft, Hamburg (Germany). Inst. fuer Holzchemie und Chemische Technologie des Holzes; Gerdes, C; Kaminsky, W [Hamburg Univ. (Germany). Inst. fuer Technische und Makromolekulare Chemie (ITMCh)

1998-09-01

Flash pyrolysis is a medium-temperature process (around 475 C) in which biomass is heated up rapidly in the absence of oxygen. The pyrolysis products are cooled down rapidly, condensing into a reddish-brown liquid with around half the calorific value of a conventional heating oil. In contrast to conventional charcoal production, flash pyrolysis is a modern process whose process parameters enure high liquid yields. Modern fluidized-bed reactors for flash pyrolysis of biomass tend to have high heating rates and short times of residue. In the `Hamburg process`, fluidized-bed reactors are used successfully for pyrolysis of plastics. A flash pyrolysis plant for biomass treatment was constructed in cooperation with Hamburg University with funds provided by the `Bundesstiftung Umwelt`. This contribution describes the first series of experiments, mass balances and oil analyses using beech wood as material to be pyrolyzed. (orig./SR) [Deutsch] Flash-Pyrolyse ist ein Mitteltemperatur-Prozess (ca. 475 C), in dem Biomasse unter Sauerstoffausschluss sehr schnell erhitzt wird. Die entstehenden Pyrolyseprodukte werden schnell abgekuehlt und kondensieren zu einer roetlich-braunen Fluessigkeit, die etwa die Haelfte des Heizwertes eines konventionellen Heizoeles besitzt. Flash-Pyrolyse ist, im Gegensatz zur konventionellen Holzverkohlung, ein modernes Verfahren, dessen spezielle Verfahrensparameter hohe Fluessigausbeuten ermoeglichen. Hohe Aufheizraten, verbunden mit kurzen Verweilzeiten, werden mit stationaeren Wirbelbettreaktoren erzielt die gegenwaertig vorwiegend fuer die Flash-Pyrolyse von Biomasse eingesetzt werden. Im `Hamburger Verfahren` haben sich Wirbelbettreaktoren im Bereich der Kunststoffpyrolyse bewaehrt. Daher wurde in Zusammenarbeit mit der Universitaet Hamburg und finanzieller Foerderung der Bundesstiftung Umwelt eine Flash-Pyrolyseanlage fuer Biomasse gebaut: In dieser Arbeit werden erste Versuchsreihen, Massenbilanzen und Oelanalysen aus der Pyrolyse von

Theory of optical flashes

International Nuclear Information System (INIS)

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

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

Science.gov (United States)

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

2014-01-01

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

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

Science.gov (United States)

Takamura, Shiki

2018-01-01

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

The Evolution and Structure of Extreme Optical Lightning Flashes.

Science.gov (United States)

Peterson, Michael; Rudlosky, Scott; Deierling, Wiebke

2017-12-27

This study documents the composition, morphology, and motion of extreme optical lightning flashes observed by the Lightning Imaging Sensor (LIS). The furthest separation of LIS events (groups) in any flash is 135 km (89 km), the flash with the largest footprint had an illuminated area of 10,604 km 2 , and the most dendritic flash has 234 visible branches. The longest-duration convective LIS flash lasted 28 s and is overgrouped and not physical. The longest-duration convective-to-stratiform propagating flash lasted 7.4 s, while the longest-duration entirely stratiform flash lasted 4.3 s. The longest series of nearly consecutive groups in time lasted 242 ms. The most radiant recorded LIS group (i.e., "superbolt") is 735 times more radiant than the average group. Factors that impact these optical measures of flash morphology and evolution are discussed. While it is apparent that LIS can record the horizontal development of the lightning channel in some cases, radiative transfer within the cloud limits the flash extent and level of detail measured from orbit. These analyses nonetheless suggest that lightning imagers such as LIS and Geostationary Lightning Mapper can complement ground-based lightning locating systems for studying physical lightning phenomena across large geospatial domains.

Timing in a FLASH

Science.gov (United States)

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.

A Comparative Study of Reduced-Variables-Based Flash and Conventional Flash

DEFF Research Database (Denmark)

Yan, Wei; Stenby, Erling Halfdan; Michelsen, Michael Locht

2013-01-01

) with zero binary-interaction parameters (BIPs) and later generalized to situations with nonzero-BIP matrices. Most of the studies in the last decade suggest that the reduced-variables methods are much more efficient than the conventional flash method. However, Haugen and Beckner (2011) questioned...... with the conventional minimization-based flash. A test with the use of the SPE 3 example (Kenyon and Behie 1987) showed that the best reduction in time was less than 20% for the extreme situation of 25 components and just one row/column with nonzero BIPs. A better performance can be achieved by a simpler implementation...... directly using the sparsity of the BIP matrix....

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

International Nuclear Information System (INIS)

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

2014-01-01

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

An unusual characteristic "flower-like" pattern: flash suppressor burns.

Science.gov (United States)

Gurcan, Altun

2012-04-01

The case on contact shots from firearms with a flash suppressor is rare. When a rifle fitted with a flash suppressor is fired, the emerging soot-laden gas in the barrel escapes from the slits of the flash suppressor. If the shot is contact or near contact, the flash suppressor will produce a characteristic "flower-like" pattern of seared, blackened zones around the entrance. This paper presents the injury pattern of the flash suppressor in a 29-year-old man who committed suicide with a G3 automatic infantry rifle.

Working memory biasing of visual perception without awareness.

Science.gov (United States)

Pan, Yi; Lin, Bingyuan; Zhao, Yajun; Soto, David

2014-10-01

Previous research has demonstrated that the contents of visual working memory can bias visual processing in favor of matching stimuli in the scene. However, the extent to which such top-down, memory-driven biasing of visual perception is contingent on conscious awareness remains unknown. Here we showed that conscious awareness of critical visual cues is dispensable for working memory to bias perceptual selection mechanisms. Using the procedure of continuous flash suppression, we demonstrated that "unseen" visual stimuli during interocular suppression can gain preferential access to awareness if they match the contents of visual working memory. Strikingly, the very same effect occurred even when the visual cue to be held in memory was rendered nonconscious by masking. Control experiments ruled out the alternative accounts of repetition priming and different detection criteria. We conclude that working memory biases of visual perception can operate in the absence of conscious awareness.

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

Science.gov (United States)

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

2018-05-31

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

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

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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.

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

Science.gov (United States)

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

2017-11-01

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

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

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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

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

Science.gov (United States)

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

2016-08-01

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

Critical flashing flows in nozzles with subcooled inlet conditions

International Nuclear Information System (INIS)

Abuaf, N.; Jones, O.C. Jr.; Wu, B.J.C.

1983-01-01

Examination of a large number of experiments dealing with flashing flows in converging and converging-diverging nozzles reveals that knowledge of the flashing inception point is the key to the prediction of critical flow rates. An extension of the static flashing inception correlation of Jones [16] and Alamgir and Lienhard [17] to flowing systems has allowed the determination of the location of flashing inception in nozzle flows with subcooled inlet conditions. It is shown that in all the experiments examined with subcooled inlet regardless of the degree of inlet subcooling, flashing inception invariably occurred very close to the throat. A correlation is given to predict flashing inception in both pipes and nozzles which matches all data available, but is lacking verification in intermediate nozzle geometries where turbulence may be important. A consequence of this behavior is that the critical mass flux may be correlated to the pressure difference between the nozzle inlet and flashing inception, through a single phase liquid discharge coefficient and an accurate prediction of the flashing inception pressure at the throat. Comparison with the available experiments indicate that the predicted mass fluxes are within 5 percent of the measurements

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

Directory of Open Access Journals (Sweden)

José Alberto Choreño Parra

2017-08-01

Full Text Available Natural killer (NK cells are lymphocytes of the innate immune system, which play an important role in the initial defense against a wide variety of pathogens, including viruses and intracellular bacteria. NK cells produce cytokines that enhance immune responses directed toward pathogens and also exert cytotoxic activity against infected cells, thereby eliminating the reservoir of infection. Their role in defense against Mycobacterium tuberculosis (Mtb has been recently studied, and there is increasing evidence that highlight the importance of NK cell function during pulmonary tuberculosis (PTB, especially in the absence of optimal T-cell responses. Additionally, in the last years, it has been observed that NK cells mediate secondary responses against antigens to which they were previously exposed, an ability classically attributed to lymphocytes of the adaptive branch of immunity. This phenomenon, called “innate memory,” could have important implications in the efforts to develop therapies and vaccines to improve the initial phases of immune reactions against different microorganisms, especially those to which there is not yet available vaccines to prevent infection, as is the case for tuberculosis. Therefore, the possibility of inducing memory-like NK cells ready to act prior to contact with Mtb or during the earliest stages of infection becomes quite interesting. However, our understanding of the mechanisms of innate memory remains incomplete. Here, we review recent literature about the mechanisms involved in the formation and maintenance of NK cell memory and the role of these cells in the immune response during tuberculosis. Finally, we discuss if the current evidence is sufficient to substantiate that NK cells exert more rapid and robust secondary responses after consecutive encounters with Mtb.

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

Directory of Open Access Journals (Sweden)

Emma C Reilly

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

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

OpenAIRE

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

2014-01-01

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

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

Directory of Open Access Journals (Sweden)

Jin-Hui Wang

2018-01-01

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

A Testable Design Method for Memories by Boundary Scan Technique

Directory of Open Access Journals (Sweden)

Qiao Guo-Hui

2016-01-01

Full Text Available This paper presents a design for test the embedded flash in an object System-on-a-chip (SoC. The feature of the Flash TAP (Test Access Port complies with the IEEE std.1149.1, and it can select different scan chains and other control registers for other test. By the trade-off between the test time and the circuit area, an IST (In System Test circuit is designed in the SoC. Experiment results on the embedded memory have shown that the proposed method costs small testing timing by the use of IST.

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

Science.gov (United States)

D'Souza, Lucas; Gupta, Sneh Lata; Bal, Vineeta; Rath, Satyajit; George, Anna

2017-12-01

B-cell memory was long characterized as isotype-switched, somatically mutated and germinal centre (GC)-derived. However, it is now clear that the memory pool is a complex mixture that includes unswitched and unmutated cells. Further, expression of CD73, CD80 and CD273 has allowed the categorization of B-cell memory into multiple subsets, with combinatorial expression of the markers increasing with GC progression, isotype-switching and acquisition of somatic mutations. We have extended these findings to determine whether these markers can be used to identify IgM memory phenotypically as arising from T-dependent versus T-independent responses. We report that CD73 expression identifies a subset of antigen-experienced IgM + cells that share attributes of functional B-cell memory. This subset is reduced in the spleens of T-cell-deficient and CD40-deficient mice and in mixed marrow chimeras made with mutant and wild-type marrow, the proportion of CD73 + IgM memory is restored in the T-cell-deficient donor compartment but not in the CD40-deficient donor compartment, indicating that CD40 ligation is involved in its generation. We also report that CD40 signalling supports optimal expression of CD73 on splenic T cells and age-associated B cells (ABCs), but not on other immune cells such as neutrophils, marginal zone B cells, peritoneal cavity B-1 B cells and regulatory T and B cells. Our data indicate that in addition to promoting GC-associated memory generation during B-cell differentiation, CD40-signalling can influence the composition of the unswitched memory B-cell pool. They also raise the possibility that a fraction of ABCs may represent T-cell-dependent IgM memory. © 2017 John Wiley & Sons Ltd.

Frequency and seasonality of flash floods in Slovenia

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Trobec Tajan

2017-01-01

Full Text Available The purpose of this paper is to assess and analyse the dynamics of flash flooding events in Slovenia. The paper examines in particular the frequency of flash floods and their seasonal distribution. The methodology is based on the analysis of historical records and modern flood data. The results of a long-term frequency analysis of 138 flash floods that occurred between 1550 and 2015 are presented. Because of the lack of adequate historical flood data prior to 1950 the main analysis is based on data for the periodbetween1951 and2015, while the analysis of data for the period between1550 and1950 is added as a supplement to the main analysis. Analysis of data for the period after 1950 shows that on average 1.3 flash floods occur each year in Slovenia. The linear trend for the number of flash floods is increasing but is not statistically significant. Despite the fact that the majority of Slovenian rivers have one of the peaks in spring and one of the lows in summer, 90% of flash floods actually occur during meteorological summer or autumn - i.e. between June and November, which shows that discharge regimes and flood regimes are not necessarily related. Because of the lack of flood records from the more distant past as well as the large variability of flash flood events in the last several decades, we cannot provide a definitive answer to the question about possible changes in their frequency and seasonality by relying solely on the detected trends. Nevertheless, considering the results of analysis and future climate change scenarios the frequency of flash floods in Slovenia could increase while the period of flash flood occurrence could be extended.

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

Institute of Scientific and Technical Information of China (English)

无

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.

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

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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.

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

International Nuclear Information System (INIS)

Kim, Tae-Hyun; Park, Jea-Gun

2013-01-01

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

Spatial-temporal characteristics of lightning flash size in a supercell storm

Science.gov (United States)

Zhang, Zhixiao; Zheng, Dong; Zhang, Yijun; Lu, Gaopeng

2017-11-01

The flash sizes of a supercell storm, in New Mexico on October 5, 2004, are studied using the observations from the New Mexico Lightning Mapping Array and the Albuquerque, New Mexico, Doppler radar (KABX). First, during the temporal evolution of the supercell, the mean flash size is anti-correlated with the flash rate, following a unary power function, with a correlation coefficient of - 0.87. In addition, the mean flash size is linearly correlated with the area of reflectivity > 30 dBZ at 5 km normalized by the flash rate, with a correlation coefficient of 0.88. Second, in the horizontal, flash size increases along the direction from the region near the convection zone to the adjacent forward anvil. The region of minimum flash size usually corresponds to the region of maximum flash initiation and extent density. The horizontal correspondence between the mean flash size and the flash extent density can also be fitted by a unary power function, and the correlation coefficient is > 0.5 in 50% of the radar volume scans. Furthermore, the quality of fit is positively correlated to the convective intensity. Third, in the vertical direction, the height of the maximum flash initiation density is close to the height of maximum flash extent density, but corresponds to the height where the mean flash size is relatively small. In the discussion, the distribution of the small and dense charge regions when and where convection is vigorous in the storm, is deduced to be responsible for the relationship that flash size is temporally and spatially anti-correlated with flash rate and density, and the convective intensity.

Menopausal Hot Flashes and Carotid Intima Media Thickness Among Midlife Women.

Science.gov (United States)

Thurston, Rebecca C; Chang, Yuefang; Barinas-Mitchell, Emma; Jennings, J Richard; Landsittel, Doug P; Santoro, Nanette; von Känel, Roland; Matthews, Karen A

2016-12-01

There has been a longstanding interest in the role of menopause and its correlates in the development of cardiovascular disease (CVD) in women. Menopausal hot flashes are experienced by most midlife women; emerging data link hot flashes to CVD risk indicators. We tested whether hot flashes, measured via state-of-the-art physiologic methods, were associated with greater subclinical atherosclerosis as assessed by carotid ultrasound. We considered the role of CVD risk factors and estradiol concentrations in these associations. A total of 295 nonsmoking women free of clinical CVD underwent ambulatory physiologic hot flash assessments; a blood draw; and carotid ultrasound measurement of intima media thickness and plaque. Associations between hot flashes and subclinical atherosclerosis were tested in regression models controlling for CVD risk factors and estradiol. More frequent physiologic hot flashes were associated with higher carotid intima media thickness (for each additional hot flash: β [SE]=0.004 [0.001]; P=0.0001; reported hot flash: β [SE]=0.008 [0.002]; P=0.002, multivariable) and plaque (eg, for each additional hot flash, odds ratio [95% confidence interval] plaque index ≥2=1.07 [1.003-1.14]; P=0.04, relative to no plaque, multivariable] among women reporting daily hot flashes; associations were not accounted for by CVD risk factors or by estradiol. Among women reporting hot flashes, hot flashes accounted for more variance in intima media thickness than most CVD risk factors. Among women reporting daily hot flashes, frequent hot flashes may provide information about a woman's vascular status beyond standard CVD risk factors and estradiol. Frequent hot flashes may mark a vulnerable vascular phenotype among midlife women. © 2016 American Heart Association, Inc.

Flood hazard assessment in areas prone to flash flooding

Science.gov (United States)

Kvočka, Davor; Falconer, Roger A.; Bray, Michaela

2016-04-01

Contemporary climate projections suggest that there will be an increase in the occurrence of high-intensity rainfall events in the future. These precipitation extremes are usually the main cause for the emergence of extreme flooding, such as flash flooding. Flash floods are among the most unpredictable, violent and fatal natural hazards in the world. Furthermore, it is expected that flash flooding will occur even more frequently in the future due to more frequent development of extreme weather events, which will greatly increase the danger to people caused by flash flooding. This being the case, there will be a need for high resolution flood hazard maps in areas susceptible to flash flooding. This study investigates what type of flood hazard assessment methods should be used for assessing the flood hazard to people caused by flash flooding. Two different types of flood hazard assessment methods were tested: (i) a widely used method based on an empirical analysis, and (ii) a new, physically based and experimentally calibrated method. Two flash flood events were considered herein, namely: the 2004 Boscastle flash flood and the 2007 Železniki flash flood. The results obtained in this study suggest that in the areas susceptible to extreme flooding, the flood hazard assessment should be conducted using methods based on a mechanics-based analysis. In comparison to standard flood hazard assessment methods, these physically based methods: (i) take into account all of the physical forces, which act on a human body in floodwater, (ii) successfully adapt to abrupt changes in the flow regime, which often occur for flash flood events, and (iii) rapidly assess a flood hazard index in a relatively short period of time.

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

Directory of Open Access Journals (Sweden)

Yang Yee

2004-07-01

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

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

DEFF Research Database (Denmark)

Mucha, Igor

1999-01-01

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

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

Science.gov (United States)

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

2015-12-01

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

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

International Nuclear Information System (INIS)

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

1974-01-01

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

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

Science.gov (United States)

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

2013-01-01

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

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

International Nuclear Information System (INIS)

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.

uFlip: Understanding Flash IO Patterns

DEFF Research Database (Denmark)

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...

Exploring Branded Flash Mobs : A study of the impact of branded flash mobs on consumer behavior and consumer experience

OpenAIRE

Grant, Philip

2014-01-01

The desire of every marketer is to develop and maintain strong customer relationships. One way this can be accomplished is through effective advertising. Marketers have recently begun to brand flash mobs as a way to effectuate strong brand relationships. Even so, it is unclear whether or not the branding of flash mobs supports or frustrates this pursuit. Therefore, the goal of this thesis is to help marketers understand the potential impact that branded flash mobs may have on consumer behavio...

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

Science.gov (United States)

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

2017-04-01

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

Automated Studies of Continuing Current in Lightning Flashes

Science.gov (United States)

Martinez-Claros, Jose

Continuing current (CC) is a continuous luminosity in the lightning channel that lasts longer than 10 ms following a lightning return stroke to ground. Lightning flashes following CC are associated with direct damage to power lines and are thought to be responsible for causing lightning-induced forest fires. The development of an algorithm that automates continuing current detection by combining NLDN (National Lightning Detection Network) and LEFA (Langmuir Electric Field Array) datasets for CG flashes will be discussed. The algorithm was applied to thousands of cloud-to-ground (CG) flashes within 40 km of Langmuir Lab, New Mexico measured during the 2013 monsoon season. It counts the number of flashes in a single minute of data and the number of return strokes of an individual lightning flash; records the time and location of each return stroke; performs peak analysis on E-field data, and uses the slope of interstroke interval (ISI) E-field data fits to recognize whether continuing current (CC) exists within the interval. Following CC detection, duration and magnitude are measured. The longest observed C in 5588 flashes was 631 ms. The performance of the algorithm (vs. human judgement) was checked on 100 flashes. At best, the reported algorithm is "correct" 80% of the time, where correct means that multiple stations agree with each other and with a human on both the presence and duration of CC. Of the 100 flashes that were validated against human judgement, 62% were hybrid. Automated analysis detects the first but misses the second return stroke in many cases where the second return stroke is followed by long CC. This problem is also present in human interpretation of field change records.

Foundation Flash Cartoon Animation

CERN Document Server

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

Structural and electrical characterization of phase‐change memory line cells

NARCIS (Netherlands)

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

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

Directory of Open Access Journals (Sweden)

Shan He

Full Text Available BACKGROUND: Cellular metabolism plays a critical role in regulating T cell responses and the development of memory T cells with long-term protections. However, the metabolic phenotype of antigen-activated T cells that are responsible for the generation of long-lived memory cells has not been characterized. DESIGN AND METHODS: Using lymphocytic choriomeningitis virus (LCMV peptide gp33-specific CD8(+ T cells derived from T cell receptor transgenic mice, we characterized the metabolic phenotype of proliferating T cells that were activated and expanded in vitro in the presence or absence of rapamycin, and determined the capability of these rapamycin-treated T cells to generate long-lived memory cells in vivo. RESULTS: Antigen-activated CD8(+ T cells treated with rapamycin gave rise to 5-fold more long-lived memory T cells in vivo than untreated control T cells. In contrast to that control T cells only increased glycolysis, rapamycin-treated T cells upregulated both glycolysis and oxidative phosphorylation (OXPHOS. These rapamycin-treated T cells had greater ability than control T cells to survive withdrawal of either glucose or growth factors. Inhibition of OXPHOS by oligomycin significantly reduced the ability of rapamycin-treated T cells to survive growth factor withdrawal. This effect of OXPHOS inhibition was accompanied with mitochondrial hyperpolarization and elevation of reactive oxygen species that are known to be toxic to cells. CONCLUSIONS: Our findings indicate that these rapamycin-treated T cells may represent a unique cell model for identifying nutrients and signals critical to regulating metabolism in both effector and memory T cells, and for the development of new methods to improve the efficacy of adoptive T cell cancer therapy.

Weak positive cloud-to-ground flashes in Northeastern Colorado

Science.gov (United States)

Lopez, Raul E.; Maier, Michael W.; Garcia-Miguel, Juan A.; Holle, Ronald L.

1991-01-01

The frequency distributions of the peak magnetic field associated with the first detected return stroke of positive and negative cloud-to-ground (CG) flashes were studied using lightning data from northeastern Colorado. These data were obtained during 1985 with a medium-to-high gain network of three direction finders (DF's). The median signal strength of positive flashes was almost two times that of the negatives for flashes within 300 km of the DF's, which have an inherent detection-threshold bias that tends to discriminate against weak signals. This bias increases with range, and affects the detection of positive and negative flashes in different ways, because of the differing character of their distributions. Positive flashes appear to have a large percentage of signals clustered around very weak values that are lost to the medium-to-high gain Colorado Detection System very quickly with increasing range. The resulting median for positive signals could thus appear to be much larger than the median for negative signals, which are more clustered around intermediate values. When only flashes very close to the DF's are considered, however, the two distributions have almost identical medians. The large percentage of weak positive signals detected close to the DF's has not been explored previously. They have been suggested to come from intracloud discharges and thus are improperly classified as CG flashes. Evidence in hand, points to their being real positive, albeit weak CG flashes. Whether or not they are real positive ground flashes, it is important to be aware of their presence in data from magnetic DF networks.

Flash hydropyrolysis of bituminous coal . III. Research on flash hydropyrolysis tar

Energy Technology Data Exchange (ETDEWEB)

Dong, M.; Zhu, Z.; He, Y.; Ding, N.; Tang, L. [East China University of Science and Technology, Shanghai (China)

2000-02-01

Tar sample obtained by flash hydropyrolysis (FHP) from Dongshen coal at high pressure entrained reactor was investigated. An effect of flash hydropyrolysis temperature on the main components in tar was studied and the quality of the tar was compared with high temperature coke oven tar. The results showed that: the yields of liquid hydrocarbon in FHP tar were more than 15%, which is twofold of that in coke oven tar; the FHP tar has high oil fraction and low pitch; high phenol components and pure condensed polycyclic aromatic hydrocarbon, and low aliphatic hydrocarbon. The components of the FHP tar were simpler than that of high temperature coke oven tar. Therefore, FHP has improved the quantity and quality of tar. 11 refs., 3 figs., 5 tabs.

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

Science.gov (United States)

Zanon, Veronica; Pilipow, Karolina; Scamardella, Eloise; De Paoli, Federica; De Simone, Gabriele; Price, David A; Martinez Usatorre, Amaia; Romero, Pedro; Mavilio, Domenico; Roberto, Alessandra; Lugli, Enrico

2017-09-01

Human T memory stem (T SCM ) cells with superior persistence capacity and effector functions are emerging as important players in the maintenance of long-lived T-cell memory and are thus considered an attractive population to be used in adoptive transfer-based immunotherapy of cancer. However, the molecular signals regulating their generation remain poorly defined. Here we show that curtailed T-cell receptor stimulation curbs human effector CD8 + T-cell differentiation and allows the generation of CD45RO - CD45RA + CCR7 + CD27 + CD95 + -phenotype cells from highly purified naïve T-cell precursors, resembling naturally-occurring human T SCM . These cells proliferate extensively in vitro and in vivo, express low amounts of effector-associated genes and transcription factors and undergo considerable self-renewal in response to IL-15 while retaining effector differentiation potential. Such a phenotype is associated with a lower number of mitochondria compared to highly-activated effector T cells committed to terminal differentiation. These results shed light on the molecular signals that are required to generate long-lived memory T cells with potential application in adoptive cell transfer immunotherapy. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co.KGaA, Weinheim.

Improving Flash Flood Prediction in Multiple Environments

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

Christopher J. Haines

2013-05-01

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

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

Science.gov (United States)

Verhoeven, D; Sankaran, S; Dandekar, S

2007-08-01

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

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

Science.gov (United States)

Li, Chen Xi; Talele, Nilesh P; Boo, Stellar; Koehler, Anne; Knee-Walden, Ericka; Balestrini, Jenna L; Speight, Pam; Kapus, Andras; Hinz, Boris

2017-03-01

Expansion on stiff culture substrates activates pro-fibrotic cell programs that are retained by mechanical memory. Here, we show that priming on physiologically soft silicone substrates suppresses fibrogenesis and desensitizes mesenchymal stem cells (MSCs) against subsequent mechanical activation in vitro and in vivo, and identify the microRNA miR-21 as a long-term memory keeper of the fibrogenic program in MSCs. During stiff priming, miR-21 levels were gradually increased by continued regulation through the acutely mechanosensitive myocardin-related transcription factor-A (MRTF-A/MLK-1) and remained high over 2 weeks after removal of the mechanical stimulus. Knocking down miR-21 once by the end of the stiff-priming period was sufficient to erase the mechanical memory and sensitize MSCs to subsequent exposure to soft substrates. Soft priming and erasing mechanical memory following cell culture expansion protects MSCs from fibrogenesis in the host wound environment and increases the chances for success of MSC therapy in tissue-repair applications.

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

DEFF Research Database (Denmark)

Nannarelli, Alberto; Taylor, Jonathan

2016-01-01

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

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

Directory of Open Access Journals (Sweden)

Cyrus Ayieko

Full Text Available Clinical immunity to malaria declines in the absence of repeated parasite exposure. However, little is known about how B cell populations and antigen-specific memory B cells change in the absence of P. falciparum infection. A successful indoor residual insecticide spraying campaign in a highland area of western Kenya, led to an absence of blood-stage P. falciparum infection between March 2007 and April 2008. We assessed memory B cell responses in 45 adults at the beginning (April 2008 and end (April 2009 of a subsequent 12-month period during which none of the adults had evidence of asymptomatic parasitemia or clinical disease. Antibodies and memory B cells to the 42-kDa portion of the merozoite surface protein-1 (MSP-142 were measured using ELISA and ELISPOT assays, respectively. B cell populations were characterized by flow cytometry. From 2008 to 2009, the prevalence of MSP-142-specific memory B cells (45% vs. 55%, respectively, P = 0.32 or antibodies (91% vs. 82%, respectively, P = 0.32 did not differ significantly, although specific individuals did change from positive to negative and vice versa, particularly for memory B cells, suggesting possible low-level undetected parasitemia may have occurred in some individuals. The magnitude of MSP-142-specific memory B cells and levels of antibodies to MSP-142 also did not differ from 2008 to 2009 (P>0.10 for both. However, from 2008 to 2009 the proportions of both class-switched atypical (CD19+IgD-CD27-CD21-IgM- and class-switched activated (CD19+IgD-CD27+CD21-IgM- memory B cells decreased (both P<0.001. In contrast, class-switched resting classical memory B cells (CD19+IgD-CD27+CD21+IgM- increased (P<0.001. In this area of seasonal malaria transmission, a one- year absence of detectable P. falciparum infection was not associated with changes in the prevalence or level of MSP-142 specific memory B cells, but was associated with major changes in overall memory B cell subsets.

Flash flood modelling for ungauged catchments

Science.gov (United States)

Garambois, P.-A.; Roux, H.; Larnier, K.; Dartus, D.

2012-04-01

Flash flood is a very intense and quick hydrologic response of a catchment to rainfall. This phenomenon has a high spatial-temporal variability as its generating storm, often hitting small catchments (few km2). Data collected by (Gaume et al. 2009) about 500 flash floods over the last 50 years showed that they could occur everywhere in Europe and more often in the Mediterranean regions, Alpine regions and continental Europe. Given the small spatial-temporal scales and high variability of flash floods, their prediction remains a hard exercise as the necessary data are often scarce. Flash flood prediction on ungauged catchments is one of the challenges of hydrological modelling as defined by (Sivapalan et al. 2003). Several studies have been headed up with the MARINE model (Modélisation de l'Anticipation du Ruissellement et des Inondations pour des évèNements Extrêmes) for the Gard region (France), (Roux et al. 2011), (Castaings et al. 2009). This physically based spatially distributed rainfall runoff model is dedicated to flash flood prediction. The study aims at finding a methodology for flash flood prediction at ungauged locations in the Cévennes-Vivarais region in particular. The regionalization method is based on multiple calibrations on gauged catchments in order to extract model structures (model + parameter values) for each catchment. Several mathematical methods (multiple regressions, transfer functions, krigging…) will then be tested to calculate a regional parameter set. The study also investigates the usability of additional hydrologic indices at different time scales to constrain model predictions from parameters obtained using these indices, and this independently of the model considered. These hydrologic indices gather information on hydrograph shape or catchment dynamic for instance. Results explaining global catchments behaviour are expected that way. The spatial-temporal variability of storms is also described through indices and linked with

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

Science.gov (United States)

Golubovskaya, Vita; Wu, Lijun

2016-03-15

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

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

Directory of Open Access Journals (Sweden)

Vita Golubovskaya

2016-03-01

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

Flashing light in microalgae biotechnology.

Science.gov (United States)

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.

An unusual characteristic “flower-like” pattern: flash suppressor burns

OpenAIRE

Gurcan, Altun

2012-01-01

The case on contact shots from firearms with a flash suppressor is rare. When a rifle fitted with a flash suppressor is fired, the emerging soot-laden gas in the barrel escapes from the slits of the flash suppressor. If the shot is contact or near contact, the flash suppressor will produce a characteristic “flower-like” pattern of seared, blackened zones around the entrance. This paper presents the injury pattern of the flash suppressor in a 29-year-old man who committed suicide with a G3 aut...

An unusual characteristic “flower-like” pattern: flash suppressor burns

Science.gov (United States)

Gurcan, Altun

2012-01-01

The case on contact shots from firearms with a flash suppressor is rare. When a rifle fitted with a flash suppressor is fired, the emerging soot-laden gas in the barrel escapes from the slits of the flash suppressor. If the shot is contact or near contact, the flash suppressor will produce a characteristic “flower-like” pattern of seared, blackened zones around the entrance. This paper presents the injury pattern of the flash suppressor in a 29-year-old man who committed suicide with a G3 automatic infantry rifle. PMID:23935280

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

Science.gov (United States)

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

2013-11-13

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

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

Science.gov (United States)

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

2013-08-26

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

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

KAUST Repository

Pearce, Roger

2013-05-01

We present techniques to process large scale-free graphs in distributed memory. Our aim is to scale to trillions of edges, and our research is targeted at leadership class supercomputers and clusters with local non-volatile memory, e.g., NAND Flash. We apply an edge list partitioning technique, designed to accommodate high-degree vertices (hubs) that create scaling challenges when processing scale-free graphs. In addition to partitioning hubs, we use ghost vertices to represent the hubs to reduce communication hotspots. We present a scaling study with three important graph algorithms: Breadth-First Search (BFS), K-Core decomposition, and Triangle Counting. We also demonstrate scalability on BG/P Intrepid by comparing to best known Graph500 results. We show results on two clusters with local NVRAM storage that are capable of traversing trillion-edge scale-free graphs. By leveraging node-local NAND Flash, our approach can process thirty-two times larger datasets with only a 39% performance degradation in Traversed Edges Per Second (TEPS). © 2013 IEEE.