Science.gov

Sample records for 4-t cms coil

  1. A multi-slot surface coil for MRI of dual-rat imaging at 4T

    SciTech Connect

    Solis, S.E.; Tomasi, D.; Solis, S.E.; Wang, R.; Tomasi, D.; Rodriguez, A.O.

    2011-07-01

    A slotted surface coil inspired by the hole-and-slot cavity magnetron was developed for magnetic resonance imaging of obese rats at 4 T. Full-wave analysis of the magnetic field was carried out at 170 MHz for both the slotted and circular-shaped coils. The noise figure values of two coils were investigated via the numerical calculation of the quality factors. Fat simulated phantoms to mimic overweight rats were included in the analysis with weights ranging from 300 to 900 g. The noise figures were 1.2 dB for the slotted coil and 2.4 dB for the circular coil when loaded with 600 g of simulated phantom. A slotted surface coil with eight circular slots and a circular coil with similar dimensions were built and operated in the transceiver mode, and their performances were experimentally compared. The imaging tests in phantoms demonstrated that the slotted surface coil has a deeper RF-sensitivity and better field uniformity than the single-loop RF-coil. High quality images of two overweight Zucker rats were acquired simultaneously with the slotted surface coil using standard spin-echo pulse sequences. Experimental results showed that the slotted surface coil outperformed the circular coil for imaging considerably overweight rats. Thus, the slotted surface coil can be a good tool for MRI experiments in rats on a human whole-body 4 T scanner.

  2. A multi-slot surface coil for MRI of dual-rat imaging at 4 T

    NASA Astrophysics Data System (ADS)

    Solis, S. E.; Wang, R.; Tomasi, D.; Rodriguez, A. O.

    2011-06-01

    A slotted surface coil inspired by the hole-and-slot cavity magnetron was developed for magnetic resonance imaging of obese rats at 4 T. Full-wave analysis of the magnetic field was carried out at 170 MHz for both the slotted and circular-shaped coils. The noise figure values of two coils were investigated via the numerical calculation of the quality factors. Fat simulated phantoms to mimic overweight rats were included in the analysis with weights ranging from 300 to 900 g. The noise figures were 1.2 dB for the slotted coil and 2.4 dB for the circular coil when loaded with 600 g of simulated phantom. A slotted surface coil with eight circular slots and a circular coil with similar dimensions were built and operated in the transceiver mode, and their performances were experimentally compared. The imaging tests in phantoms demonstrated that the slotted surface coil has a deeper RF-sensitivity and better field uniformity than the single-loop RF-coil. High quality images of two overweight Zucker rats were acquired simultaneously with the slotted surface coil using standard spin-echo pulse sequences. Experimental results showed that the slotted surface coil outperformed the circular coil for imaging considerably overweight rats. Thus, the slotted surface coil can be a good tool for MRI experiments in rats on a human whole-body 4 T scanner.

  3. Transceive surface coil array for MRI of the human prostate at 4T.

    PubMed

    Pinkerton, Robert G; Near, James P; Barberi, Enzo A; Menon, Ravi S; Bartha, Robert

    2007-02-01

    A novel torso transceive surface coil array for prostate magnetic resonance imaging (MRI) and spectroscopy (MRS) at 4T is presented. It is shown that with the use of a conformal transceive surface coil array with 50 Omega transmitter amplifiers and receiver preamplifiers, one can perform whole-volume torso imaging while maintaining the high signal-to-noise ratio (SNR) inherent to surface coil designs. Recent theoretical considerations have shown that by focusing the infringing radiofrequency (RF) electromagnetic field, one can achieve increased penetration and signal homogeneity compared to a conventional circularly polarized driving scheme. A variation of this driving scheme particular to the proposed coil design resulted in a twofold increase in SNR in the prostate compared to that achieved with a conventional circularly polarized driving scheme. The novel transceive surface coil array presented is capable of full-volume imaging of the human torso at 4T while maintaining signal penetration in the deep region of the prostate gland. PMID:17260367

  4. 4 T Actively detuneable double-tuned 1H/31P head volume coil and four-channel 31P phased array for human brain spectroscopy.

    PubMed

    Avdievich, N I; Hetherington, H P

    2007-06-01

    Typically 31P in vivo magnetic resonance spectroscopic studies are limited by SNR considerations. Although phased arrays can improve the SNR; to date 31P phased arrays for high-field systems have not been combined with 31P volume transmit coils. Additionally, to provide anatomical reference for the 31P studies, without removal of the coil or patient from the magnet, double-tuning (31P/1H) of the volume coil is required. In this work we describe a series of methods for active detuning and decoupling enabling use of phased arrays with double-tuned volume coils. To demonstrate these principles we have built and characterized an actively detuneable 31P/1H TEM volume transmit/four-channel 31P phased array for 4 T magnetic resonance spectroscopic imaging (MRSI) of the human brain. The coil can be used either in volume-transmit/array-receive mode or in TEM transmit/receive mode with the array detuned. Threefold SNR improvement was obtained at the periphery of the brain using the phased array as compared to the volume coil. PMID:17379554

  5. First in vivo potassium-39 (³⁹K) MRI at 9.4 T using conventional copper radio frequency surface coil cooled to 77 K.

    PubMed

    Elabyad, Ibrahim A; Kalayciyan, Raffi; Shanbhag, Nagesh C; Schad, Lothar R

    2014-02-01

    Potassium-39 ((39)K) magnetic resonance imaging (MRI) is a noninvasive technique which could potentially allow for detecting intracellular physiological variations in common human pathologies such as stroke and cancer. However, the low signal-to-noise ratio (SNR) achieved in (39)K-MR images hampered data acquisition with sufficiently high spatial and temporal resolution in animal models so far. Full wave electromagnetic (EM) simulations were performed for a single-loop copper (Cu) radio frequency (RF) surface resonator with a diameter of 30 mm optimized for rat brain imaging at room temperature (RT) and at liquid nitrogen (LN2) with a temperature of 77 K. A novel cryogenic Cu RF surface resonator with home-built LN2 nonmagnetic G10 fiberglass cryostat system for small animal scanner at 9.4 T was designed, built and tested in phantom and in in vivo MR measurements. Aerogel was used for thermal insulation in the developed LN2 cryostat. In this paper, we present the first in vivo (39)K-MR images at 9.4 T for both healthy and stroke-induced rats using the developed cryogenic coil at 77 K. In good agreement with EM-simulations and bench-top measurements, the developed cryogenic coil improved the SNR by factor of 2.7 ± 0.2 in both phantom and in in vivo MR imaging compared with the same coil at RT. PMID:24448595

  6. 35.4 T field generated using a layer-wound superconducting coil made of (RE)Ba2Cu3O7-x (RE = rare earth) coated conductor

    NASA Astrophysics Data System (ADS)

    Trociewitz, Ulf P.; Dalban-Canassy, Matthieu; Hannion, Muriel; Hilton, David K.; Jaroszynski, Jan; Noyes, Patrick; Viouchkov, Youri; Weijers, Hubertus W.; Larbalestier, David C.

    2011-11-01

    To explore the limits of layer wound (RE)Ba2Cu3O7-x (REBCO, RE = rare earth) coils in a high magnetic field environment >30 T, a series of small insert coils have been built and characterized in background fields. One of the coils repeatedly reached 35.4 T using a single ˜100 m length of REBCO tape wet wound with epoxy and nested in a 31 T background magnet. The coil was quenched safely several times without degradation. Contributing to the success of this coil was the introduction of a thin polyester film that surrounded the conductor. This approach introduces a weak circumferential plane in the coil pack that prevents conductor delamination that has caused degradation of several epoxy impregnated coils previously made by this and other groups.

  7. Analysis of eddy current distributions in the CMS magnet yoke during the solenoid discharge

    SciTech Connect

    Klyukhin, V.I.; Campi, D.; Cure, B.; Gaddi, A.; Gerwig, H.; Grillet, J.P.; Herve, A.; Loveless, R.; Smith, R.P.; /Fermilab

    2005-01-01

    Flux loops have been installed on selected segments of the magnetic flux return yoke of the 4 T superconducting coil of the Compact Muon Solenoid (CMS) detector under construction at CERN. Voltages induced in the loops during discharge of the solenoid will be sampled on-line during the entire discharge and integrated off-line to provide a measurement of the initial magnetic flux density in steel at the maximum field to an accuracy of a few percent. Although the discharge of the solenoid is rather slow (190 s time constant), the influence of eddy currents induced in the yoke elements should be estimated. The calculation of eddy currents is performed with Vector Fields program ELEKTRA. The results of calculations are reported.

  8. 9.4T Human MRI: Preliminary Results

    PubMed Central

    Vaughan, Thomas; DelaBarre, Lance; Snyder, Carl; Tian, Jinfeng; Akgun, Can; Shrivastava, Devashish; Liu, Wanzahn; Olson, Chris; Adriany, Gregor; Strupp, John; Andersen, Peter; Gopinath, Anand; van de Moortele, Pierre-Francois; Garwood, Michael; Ugurbil, Kamil

    2014-01-01

    This work reports the preliminary results of the first human images at the new high-field benchmark of 9.4T. A 65-cm-diameter bore magnet was used together with an asymmetric 40-cm-diameter head gradient and shim set. A multichannel transmission line (transverse electromagnetic (TEM)) head coil was driven by a programmable parallel transceiver to control the relative phase and magnitude of each channel independently. These new RF field control methods facilitated compensation for RF artifacts attributed to destructive interference patterns, in order to achieve homogeneous 9.4T head images or localize anatomic targets. Prior to FDA investigational device exemptions (IDEs) and internal review board (IRB)-approved human studies, preliminary RF safety studies were performed on porcine models. These data are reported together with exit interview results from the first 44 human volunteers. Although several points for improvement are discussed, the preliminary results demonstrate the feasibility of safe and successful human imaging at 9.4T. PMID:17075852

  9. α/β coiled coils

    PubMed Central

    Hartmann, Marcus D; Mendler, Claudia T; Bassler, Jens; Karamichali, Ioanna; Ridderbusch, Oswin; Lupas, Andrei N; Hernandez Alvarez, Birte

    2016-01-01

    Coiled coils are the best-understood protein fold, as their backbone structure can uniquely be described by parametric equations. This level of understanding has allowed their manipulation in unprecedented detail. They do not seem a likely source of surprises, yet we describe here the unexpected formation of a new type of fiber by the simple insertion of two or six residues into the underlying heptad repeat of a parallel, trimeric coiled coil. These insertions strain the supercoil to the breaking point, causing the local formation of short β-strands, which move the path of the chain by 120° around the trimer axis. The result is an α/β coiled coil, which retains only one backbone hydrogen bond per repeat unit from the parent coiled coil. Our results show that a substantially novel backbone structure is possible within the allowed regions of the Ramachandran space with only minor mutations to a known fold. DOI: http://dx.doi.org/10.7554/eLife.11861.001 PMID:26771248

  10. Optimization of CMS HCAL parameters using hanging file test data

    SciTech Connect

    Green, D.

    1994-06-01

    There are 2 basic choices for the magnetic solenoid coil location in large collider experiments. One can place the coil inside the calorimeter radius as in CDF, DO, ATLAS, and SDC. Alternatively, one can place the coil outside the calorimetry as in SLD, ZEUS, and CMS. There are clearly definite advantages to both schemes since different collaborations have chosen different topologies. In this note we examine the consequences of the second choice, which places no significant material in front of the EM compartment, but severely limits the total depth of hadronic calorimetry (HCAL) available before the appearance of inert material (the coil).

  11. Memory CD4 T cells in influenza.

    PubMed

    Zens, Kyra D; Farber, Donna L

    2015-01-01

    Influenza A virus is a significant cause of morbidity and mortality worldwide, particularly among young children and the elderly. Current vaccines induce neutralizing antibody responses directed toward highly variable viral surface proteins, resulting in limited heterosubtypic protection to new viral serotypes. By contrast, memory CD4 T cells recognize conserved viral proteins and are cross-reactive to multiple influenza strains. In humans, virus-specific memory CD4 T cells were found to be the protective correlate in human influenza challenge studies, suggesting their key role in protective immunity. In mouse models, memory CD4 T cells can mediate protective responses to secondary influenza infection independent of B cells or CD8 T cells, and can influence innate immune responses. Importantly, a newly defined, tissue-resident CD4 memory population has been demonstrated to be retained in lung tissue and promote optimal protective responses to an influenza infection. Here, we review the current state of results regarding the generation of memory CD4 T cells following primary influenza infection, mechanisms for their enhanced efficacy in protection from secondary challenge including their phenotype, localization, and function in the context of both mouse models and human infection. We also discuss the generation of memory CD4 T cells in response to influenza vaccines and its future implications for vaccinology. PMID:25005927

  12. The CMS Reconstruction Software

    NASA Astrophysics Data System (ADS)

    Lange, David J.; CMS Collaboration

    2011-12-01

    We report on the status and plans for the event reconstruction software of the CMS experiment. The CMS reconstruction algorithms are the basis for a wide range of data analysis approaches currently under study by the CMS collaboration using the first high-energy run of the LHC. These algorithms have been primarily developed and validated using simulated data samples, and are now being commissioned with LHC proton-proton collision data samples. The CMS reconstruction is now operated routinely on all events triggered by the CMS detector, both in a close to real-time prompt reconstruction processing and in frequent passes over the full recorded CMS data set. We discuss the overall software design, development cycle, computational requirements and performance, recent operational performance, and planned improvements of the CMS reconstruction software.

  13. Pulse Coil Tester

    NASA Technical Reports Server (NTRS)

    Simon, Richard A.

    1988-01-01

    Set of relays tested easily and repeatedly. Pulse coil tester causes coil under test to generate transient voltage; waveform indicates condition of coil. Tester accommodates assembly of up to four coils at a time.

  14. Noise properties of a NMR transceiver coil array.

    PubMed

    Pinkerton, Robert G; Barberi, Enzo A; Menon, Ravi S

    2004-11-01

    The use of multiple radiofrequency (RF) surface coil elements has applications in both fast parallel imaging and conventional imaging techniques. Through implementation of a simple magnetic decoupling network, 50 Omega matching can be achieved in both the transmitter and receiver chains, enabling the use of conventional RF power amplifiers and preamplifiers for transceive applications. Unlike phased array coil arrangements using low impedance preamplifiers for decoupling, the noise correlation between 50 Omega coils decoupled with discrete components has not been characterized. We have measured the dependence of coil quality factor (Q-factor) and noise correlation on coil separation and shown these quantities to be consistent with theoretical arguments, at least at 4 T (170 MHz). Our results suggest that a coil system for transmission and reception of NMR signals with 50 Omega coils can be built to take advantage of all the benefits of conventional array coils and with the added advantages of using conventional amplifiers. PMID:15504694

  15. Molecular basis of coiled-coil formation.

    PubMed

    Steinmetz, Michel O; Jelesarov, Ilian; Matousek, William M; Honnappa, Srinivas; Jahnke, Wolfgang; Missimer, John H; Frank, Sabine; Alexandrescu, Andrei T; Kammerer, Richard A

    2007-04-24

    Coiled coils have attracted considerable interest as design templates in a wide range of applications. Successful coiled-coil design strategies therefore require a detailed understanding of coiled-coil folding. One common feature shared by coiled coils is the presence of a short autonomous helical folding unit, termed "trigger sequence," that is indispensable for folding. Detailed knowledge of trigger sequences at the molecular level is thus key to a general understanding of coiled-coil formation. Using a multidisciplinary approach, we identify and characterize here the molecular determinants that specify the helical conformation of the monomeric early folding intermediate of the GCN4 coiled coil. We demonstrate that a network of hydrogen-bonding and electrostatic interactions stabilize the trigger-sequence helix. This network is rearranged in the final dimeric coiled-coil structure, and its destabilization significantly slows down GCN4 leucine zipper folding. Our findings provide a general explanation for the molecular mechanism of coiled-coil formation. PMID:17438295

  16. CMS Analysis School Model

    NASA Astrophysics Data System (ADS)

    Malik, S.; Shipsey, I.; Cavanaugh, R.; Bloom, K.; Chan, Kai-Feng; D'Hondt, J.; Klima, B.; Narain, M.; Palla, F.; Rolandi, G.; Schörner-Sadenius, T.

    2014-06-01

    To impart hands-on training in physics analysis, CMS experiment initiated the concept of CMS Data Analysis School (CMSDAS). It was born over three years ago at the LPC (LHC Physics Centre), Fermilab and is based on earlier workshops held at the LPC and CLEO Experiment. As CMS transitioned from construction to the data taking mode, the nature of earlier training also evolved to include more of analysis tools, software tutorials and physics analysis. This effort epitomized as CMSDAS has proven to be a key for the new and young physicists to jump start and contribute to the physics goals of CMS by looking for new physics with the collision data. With over 400 physicists trained in six CMSDAS around the globe, CMS is trying to engage the collaboration in its discovery potential and maximize physics output. As a bigger goal, CMS is striving to nurture and increase engagement of the myriad talents, in the development of physics, service, upgrade, education of those new to CMS and the career development of younger members. An extension of the concept to the dedicated software and hardware schools is also planned, keeping in mind the ensuing upgrade phase.

  17. CMS Analysis School Model

    SciTech Connect

    Malik, S.; Shipsey, I.; Cavanaugh, R.; Bloom, K.; Chan, Kai-Feng; D'Hondt, J.; Klima, B.; Narain, M.; Palla, F.; Rolandi, G.; Schörner-Sadenius, T.

    2014-01-01

    To impart hands-on training in physics analysis, CMS experiment initiated the concept of CMS Data Analysis School (CMSDAS). It was born over three years ago at the LPC (LHC Physics Centre), Fermilab and is based on earlier workshops held at the LPC and CLEO Experiment. As CMS transitioned from construction to the data taking mode, the nature of earlier training also evolved to include more of analysis tools, software tutorials and physics analysis. This effort epitomized as CMSDAS has proven to be a key for the new and young physicists to jump start and contribute to the physics goals of CMS by looking for new physics with the collision data. With over 400 physicists trained in six CMSDAS around the globe, CMS is trying to engage the collaboration in its discovery potential and maximize physics output. As a bigger goal, CMS is striving to nurture and increase engagement of the myriad talents, in the development of physics, service, upgrade, education of those new to CMS and the career development of younger members. An extension of the concept to the dedicated software and hardware schools is also planned, keeping in mind the ensuing upgrade phase.

  18. CMS tracker visualization tools

    NASA Astrophysics Data System (ADS)

    Mennea, M. S.; Osborne, I.; Regano, A.; Zito, G.

    2005-08-01

    This document will review the design considerations, implementations and performance of the CMS Tracker Visualization tools. In view of the great complexity of this sub-detector (more than 50 millions channels organized in 16540 modules each one of these being a complete detector), the standard CMS visualization tools (IGUANA and IGUANACMS) that provide basic 3D capabilities and integration within CMS framework, respectively, have been complemented with additional 2D graphics objects. Based on the experience acquired using this software to debug and understand both hardware and software during the construction phase, we propose possible future improvements to cope with online monitoring and event analysis during data taking.

  19. CMS Space Monitoring

    SciTech Connect

    Ratnikova, N.; Huang, C.-H.; Sanchez-Hernandez, A.; Wildish, T.; Zhang, X.

    2014-01-01

    During the first LHC run, CMS stored about one hundred petabytes of data. Storage accounting and monitoring help to meet the challenges of storage management, such as efficient space utilization, fair share between users and groups and resource planning. We present a newly developed CMS space monitoring system based on the storage metadata dumps produced at the sites. The information extracted from the storage dumps is aggregated and uploaded to a central database. A web based data service is provided to retrieve the information for a given time interval and a range of sites, so it can be further aggregated and presented in the desired format. The system has been designed based on the analysis of CMS monitoring requirements and experiences of the other LHC experiments. In this paper, we demonstrate how the existing software components of the CMS data placement system, PhEDEx, have been re-used, dramatically reducing the development effort.

  20. CMS investigates outlier payments.

    PubMed

    Brock, Thomas H

    2003-02-01

    CMS is increasing its scrutiny of hospital billing practices in the wake of excessive claims for outlier payments by some healthcare organizations. Hospitals should review their billing practices to ensure that they are using a charge schedule that complies with Medicare regulations Hospitals also should conduct ongoing reviews of their outlier cases to ensure that their charge structures are appropriate and their outlier services are medically necessary. Hospitals can expect CMS to implement changes to the outlier regulations. PMID:12602315

  1. CMS Geometry Through 2020

    NASA Astrophysics Data System (ADS)

    Osborne, I.; Brownson, E.; Eulisse, G.; Jones, C. D.; Lange, D. J.; Sexton-Kennedy, E.

    2014-06-01

    CMS faces real challenges with upgrade of the CMS detector through 2020 and beyond. One of the challenges, from the software point of view, is managing upgrade simulations with the same software release as the 2013 scenario. We present the CMS geometry description software model, its integration with the CMS event setup and core software. The CMS geometry configuration and selection is implemented in Python. The tools collect the Python configuration fragments into a script used in CMS workflow. This flexible and automated geometry configuration allows choosing either transient or persistent version of the same scenario and specific version of the same scenario. We describe how the geometries are integrated and validated, and how we define and handle different geometry scenarios in simulation and reconstruction. We discuss how to transparently manage multiple incompatible geometries in the same software release. Several examples are shown based on current implementation assuring consistent choice of scenario conditions. The consequences and implications for multiple/different code algorithms are discussed.

  2. Coil Welding Aid

    NASA Technical Reports Server (NTRS)

    Wiesenbach, W. T.; Clark, M. C.

    1983-01-01

    Positioner holds coil inside cylinder during tack welding. Welding aid spaces turns of coil inside cylinder and applies contact pressure while coil is tack-welded to cylinder. Device facilitates fabrication of heat exchangers and other structures by eliminating hand-positioning and clamping of individual coil turns.

  3. Starfire poloidal coil systems

    SciTech Connect

    Evans, K. Jr.; Kim, S.H.; Turner, L.R.; Wang, S.T.

    1980-01-01

    The poloidal coils for STARFIRE consists of three systems: (1) equilibrium field (EF) coils; (2) ohmic heating (OH) coils; and (3) correction field (CF) coils. The EF coils are superconducting and lie outside the toroidal field (TF) coils. These coils provide the bulk of the equilibrium field necessary to keep the plasma positioned in the vacuum chamber with the desired cross sectional shape and pressure and current distributions. Having these coils outside of the TF coils requires that they have a larger stored energy and larger currents but eases the assembly, maintenance, and reliability of the coils. The STARFIRE OH system is relatively small compared to tokamaks in which the current is entirely ohmically driven. It is designed to provide sufficient flux in the early startup to raise the plasma current to the point (1 to 2 MA) where the rf current drive can take over.

  4. 26 CFR 1.846-4T - Effective dates (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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  5. 32 CFR 1630.46 - Class 4-T: Treaty alien.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 6 2013-07-01 2013-07-01 false Class 4-T: Treaty alien. 1630.46 Section 1630.46 National Defense Other Regulations Relating to National Defense SELECTIVE SERVICE SYSTEM CLASSIFICATION RULES § 1630.46 Class 4-T: Treaty alien. In Class 4-T shall be placed any registrant who is an alien...

  6. 32 CFR 1630.46 - Class 4-T: Treaty alien.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 6 2011-07-01 2011-07-01 false Class 4-T: Treaty alien. 1630.46 Section 1630.46 National Defense Other Regulations Relating to National Defense SELECTIVE SERVICE SYSTEM CLASSIFICATION RULES § 1630.46 Class 4-T: Treaty alien. In Class 4-T shall be placed any registrant who is an alien...

  7. 32 CFR 1630.46 - Class 4-T: Treaty alien.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 6 2012-07-01 2012-07-01 false Class 4-T: Treaty alien. 1630.46 Section 1630.46 National Defense Other Regulations Relating to National Defense SELECTIVE SERVICE SYSTEM CLASSIFICATION RULES § 1630.46 Class 4-T: Treaty alien. In Class 4-T shall be placed any registrant who is an alien...

  8. 32 CFR 1630.46 - Class 4-T: Treaty alien.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Class 4-T: Treaty alien. 1630.46 Section 1630.46 National Defense Other Regulations Relating to National Defense SELECTIVE SERVICE SYSTEM CLASSIFICATION RULES § 1630.46 Class 4-T: Treaty alien. In Class 4-T shall be placed any registrant who is an alien...

  9. 32 CFR 1630.46 - Class 4-T: Treaty alien.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 6 2014-07-01 2014-07-01 false Class 4-T: Treaty alien. 1630.46 Section 1630.46 National Defense Other Regulations Relating to National Defense SELECTIVE SERVICE SYSTEM CLASSIFICATION RULES § 1630.46 Class 4-T: Treaty alien. In Class 4-T shall be placed any registrant who is an alien...

  10. Quench protection design of a 9.4 T whole-body MRI superconducting magnet

    NASA Astrophysics Data System (ADS)

    Chen, Shunzhong; Li, Yi; Dai, Yinming; Lei, Yuanzhong; Yan, Luguang

    2014-02-01

    A 9.4 T MRI superconducting magnet with a 800 mm clear warm bore in diameter is designed and fabricated for bioscience research. The superconducting magnet consisting of five coaxial solenoid coils is fabricated with NbTi Wire-in-Channel (WIC) conductor where the ratios of copper to non-copper are from 5 to 10. The four compensation solenoid coils are with rectangular NbTi/Cu strand wires. The magnet will be operated in a relative low nominal current of 224.5 A with a high level of stored energy, about 138 MJ. A protection method with the cold diodes and resistors in series across the subdivided sections and active trigger heater to accelerate quench is adopted to avoid the damage of the magnet. In the paper, the quench simulation results of currents, voltages and hot-spot temperatures based on the protection scheme are analyzed in details.

  11. CMS analysis operations

    NASA Astrophysics Data System (ADS)

    Andreeva, J.; Calloni, M.; Colling, D.; Fanzago, F.; D'Hondt, J.; Klem, J.; Maier, G.; Letts, J.; Maes, J.; Padhi, S.; Sarkar, S.; Spiga, D.; Van Mulders, P.; Villella, I.

    2010-04-01

    During normal data taking CMS expects to support potentially as many as 2000 analysis users. Since the beginning of 2008 there have been more than 800 individuals who submitted a remote analysis job to the CMS computing infrastructure. The bulk of these users will be supported at the over 40 CMS Tier-2 centres. Supporting a globally distributed community of users on a globally distributed set of computing clusters is a task that requires reconsidering the normal methods of user support for Analysis Operations. In 2008 CMS formed an Analysis Support Task Force in preparation for large-scale physics analysis activities. The charge of the task force was to evaluate the available support tools, the user support techniques, and the direct feedback of users with the goal of improving the success rate and user experience when utilizing the distributed computing environment. The task force determined the tools needed to assess and reduce the number of non-zero exit code applications submitted through the grid interfaces and worked with the CMS experiment dashboard developers to obtain the necessary information to quickly and proactively identify issues with user jobs and data sets hosted at various sites. Results of the analysis group surveys were compiled. Reference platforms for testing and debugging problems were established in various geographic regions. The task force also assessed the resources needed to make the transition to a permanent Analysis Operations task. In this presentation the results of the task force will be discussed as well as the CMS Analysis Operations plans for the start of data taking.

  12. The CMS pixel system

    NASA Astrophysics Data System (ADS)

    Bortoletto, Daniela; CMS Collaboration

    2007-09-01

    The CMS hybrid pixel detector is located at the core of the CMS tracker and will contribute significantly to track and vertex reconstruction. The detector is subdivided into a three-layer barrel, and two end-cap disks on either side of the interaction region. The system operating in the 25-ns beam crossing time of the LHC must be radiation hard, low mass, and robust. The construction of the barrel modules and the forward disks has started after extensive R&D. The status of the project is reported.

  13. Automating the CMS DAQ

    SciTech Connect

    Bauer, G.; et al.

    2014-01-01

    We present the automation mechanisms that have been added to the Data Acquisition and Run Control systems of the Compact Muon Solenoid (CMS) experiment during Run 1 of the LHC, ranging from the automation of routine tasks to automatic error recovery and context-sensitive guidance to the operator. These mechanisms helped CMS to maintain a data taking efficiency above 90% and to even improve it to 95% towards the end of Run 1, despite an increase in the occurrence of single-event upsets in sub-detector electronics at high LHC luminosity.

  14. Protective link for superconducting coil

    DOEpatents

    Umans, Stephen D.

    2009-12-08

    A superconducting coil system includes a superconducting coil and a protective link of superconducting material coupled to the superconducting coil. A rotating machine includes first and second coils and a protective link of superconducting material. The second coil is operable to rotate with respect to the first coil. One of the first and second coils is a superconducting coil. The protective link is coupled to the superconducting coil.

  15. The CMS Electromagnetic Calorimeter

    SciTech Connect

    Paramatti, Riccardo

    2005-10-12

    The electromagnetic calorimeter of the CMS experiment at LHC will consist of about 76000 Lead Tungstate crystals. Its main purpose is the very precise energy measurement of electrons and photons produced at 14 TeV centre-of-mass energy. A review of its performances and its construction status is given. Then the calibration strategy is described in details.

  16. Immune responses to coiled coil supramolecular biomaterials

    PubMed Central

    Rudra, Jai S.; Tripathi, Pulak; Hildeman, David A.; Jung, Jangwook P.; Collier, Joel H.

    2010-01-01

    Self-assembly has been increasingly utilized in recent years to create peptide-based biomaterials for 3D cell culture, tissue engineering, and regenerative medicine, but the molecular determinants of these materials' immunogenicity have remained largely unexplored. In this study, a set of molecules that self-assembled through coiled coil oligomerization was designed and synthesized, and immune responses against them were investigated in mice. Experimental groups spanned a range of oligomerization behaviors and included a peptide from the coiled coil region of mouse fibrin that did not form supramolecular structures, an engineered version of this peptide that formed coiled coil bundles, and a peptide-PEG-peptide triblock bioconjugate that formed coiled coil multimers and supramolecular aggregates. In mice, the native peptide and engineered peptide did not produce any detectable antibody response, and none of the materials elicited detectable peptide-specific T cell responses, as evidenced by the absence of IL-2 and interferon-gamma in cultures of peptide-challenged splenocytes or draining lymph node cells. However, specific antibody responses were elevated in mice injected with the multimerizing peptide-PEG-peptide. Minimal changes in secondary structure were observed between the engineered peptide and the triblock peptide-PEG-peptide, making it possible that the triblock's multimerization was responsible for this antibody response. PMID:20708258

  17. Precise mapping of the magnetic field in the CMS barrel yoke using cosmic rays

    SciTech Connect

    Chatrchyan, S.; et al.,

    2010-03-01

    The CMS detector is designed around a large 4 T superconducting solenoid, enclosed in a 12000-tonne steel return yoke. A detailed map of the magnetic field is required for the accurate simulation and reconstruction of physics events in the CMS detector, not only in the inner tracking region inside the solenoid but also in the large and complex structure of the steel yoke, which is instrumented with muon chambers. Using a large sample of cosmic muon events collected by CMS in 2008, the field in the steel of the barrel yoke has been determined with a precision of 3 to 8% depending on the location.

  18. Kinking the coiled coil--negatively charged residues at the coiled-coil interface.

    PubMed

    Straussman, Ravid; Ben-Ya'acov, Ami; Woolfson, Derek N; Ravid, Shoshana

    2007-03-01

    The coiled coil is one of the most common protein-structure motifs. It is believed to be adopted by 3-5% of all amino acids in proteins. It comprises two or more alpha-helical chains wrapped around one another. The sequences of most coiled coils are characterized by a seven-residue (heptad) repeat, denoted (abcdefg)(n). Residues at the a and d positions define the helical interface (core) and are usually hydrophobic, though about 20% are polar or charged. We show that parallel coiled-coils have a unique pattern of their negatively charged residues at the core positions: aspartic acid is excluded from these positions while glutamic acid is not. In contrast the antiparallel structures are more permissive in their amino acid usage. We show further, and for the first time, that incorporation of Asp but not Glu into the a positions of a parallel coiled coil creates a flexible hinge and that the maximal hinge angle is being directly related to the number of incorporated mutations. These new computational and experimental observations will be of use in improving protein-structure predictions, and as rules to guide rational design of novel coiled-coil motifs and coiled coil-based materials. PMID:17207815

  19. NCSX Trim Coil Design

    SciTech Connect

    M. Kalish, A. Brooks, J. Rushinski, R. Upcavage

    2009-05-29

    The National Compact Stellarator Experiment (NCSX) was being constructed at the Princeton Plasma Physics Laboratory in partnership with Oak Ridge National Laboratory before work was stopped in 2008. The objective of this experiment was to develop the stellarator concept and evaluate it's potential as a model for future fusion power plants. Stellarator design requires very precisely positioned Modular Coils of complex shape to form 3D plasmas. In the design of NCSX, Trim Coils were required to compensate for both the positioning of the coils during assembly and the fabrication tolerances of the Modular Coils. Use of the Trim Coils allowed for larger tolerances increasing ease of assembly and decreasing overall cost. A set of Trim coils was developed to suppress the toroidal flux in island regions due to misalignment, magnetic materials, and eddy currents. The requirement imposed upon the design forced the toroidal flux in island regions below 10% of the total toroidal flux in the plasma. An analysis was first performed to evaluate candidate Trim Coil configurations iterating both the size, number, and position of the coils. The design was optimized considering both performance and cost while staying within the tight restraints presented by the space limited geometry. The final design of the Trim Coils incorporated a 48 Coil top bottom symmetric set. Fabrication costs were minimized by having only two coil types and using a planar conventional design with off the shelf commercial conductor. The Trim Coil design incorporated supports made from simple structural shapes assembled together in a way which allowed for adjustment as well as accommodation for the tolerance build up on the mating surfaces. This paper will summarize the analysis that led to the optimization of the Trim Coils set, the trim coil mechanical design, thermal and stress analysis, and the design of the supporting Trim Coil structure.

  20. Electromagnetic pump stator coil

    DOEpatents

    Fanning, Alan W.; Dahl, Leslie R.

    1996-01-01

    An electrical stator coil for an electromagnetic pump includes a continuous conductor strip having first and second terminals at opposite ends thereof and an intermediate section disposed therebetween. The strip is configured in first and second coil halves, with the first coil half including a plurality of windings extending from the first terminal to the intermediate section, and the second coil half including a plurality of windings extending from the second terminal to the intermediate section. The first and second coil halves are disposed coaxially, and the first and second terminals are disposed radially inwardly therefrom with the intermediate section being disposed radially outwardly therefrom.

  1. Electromagnetic pump stator coil

    DOEpatents

    Fanning, A.W.; Dahl, L.R.

    1996-06-25

    An electrical stator coil for an electromagnetic pump includes a continuous conductor strip having first and second terminals at opposite ends thereof and an intermediate section disposed therebetween. The strip is configured in first and second coil halves, with the first coil half including a plurality of windings extending from the first terminal to the intermediate section, and the second coil half including a plurality of windings extending from the second terminal to the intermediate section. The first and second coil halves are disposed coaxially, and the first and second terminals are disposed radially inwardly therefrom with the intermediate section being disposed radially outwardly therefrom. 9 figs.

  2. The CMS muon detector

    NASA Astrophysics Data System (ADS)

    Giacomelli, P.

    2002-02-01

    The muon detection system of the Compact Muon Solenoid experiment is described. It consists of three different detector technologies: drift tubes in the barrel region, cathode strip chambers in the endcap region and resistive plate chambers in both barrel and endcap regions. The CMS muon detection system ensures excellent muon detection and efficient triggering in the pseudorapidity range 0< η<2.4. The most recent developments and some results from the R&D program will also be discussed.

  3. CMS electromagnetic calorimeter readout

    SciTech Connect

    Denes, P.; Wixted, R.

    1997-12-31

    The CMS Electromagnetic Calorimeter will consist of 109,008 crystals of Lead Tungstate (PbWO{sub 4}) arranged in a barrel (92880 crystals) and 2 endcaps (8064 crystals each). The crystals will be 25 radiation lengths long and cut in tapered shapes to make a hermetic calorimeter. The scintillation light from the crystals is captured by a photodetector, amplified and digitized. The properties of PbWO4, which is a new crystal still very much under development.

  4. Higgs Results from CMS

    NASA Astrophysics Data System (ADS)

    Bornheim, Adolf

    2014-03-01

    The Nobel Prize in physics 2013 has been awarded to François Englert and Peter W. Higgs for the theoretical discovery of a mechanism that contributes to our understanding of the origin of mass of subatomic particles which plays a crucial role in our understanding of electro-weak symmetry breaking. I will review the experimental results manifesting the discovery of the so called Higgs boson from the perspective of the Compact Muon Solenoid (CMS) collaboration. The review is based on the final results from the proton-proton collision data at 7 TeV and 8 TeV center-of-mass energy, collected in 2011 and 2012 in the initial run of the Large Hadron Collider (LHC) at the European Organization for Nuclear Research (CERN). Results on the properties of the new particle with a mass around 125 GeV, all in agreement with the expectations for the Standard Model (SM) Higgs boson, are highlighted. Latest results on the couplings between the Higgs and fermionic fields, in particular the final results of searches for a Higgs boson decaying into a b-quark or a tau-lepton pair, are presented. Non-SM Higgs searches are briefly summarized. Future perspectives for Higgs physics with CMS at LHC for the next data taking period starting in 2015 and beyond are discussed. CMS Collaboration.

  5. Biplanar Radiofrequency Coil Design

    NASA Astrophysics Data System (ADS)

    Roberts, D. A.; Insko, E. K.; Bolinger, L.; Leigh, J. S.

    A novel geometry for radiofrequency coil design is described. In this geometry, longitudinal wires of the coil lie on two parallel planes. The currents in the wires of one plane run in the direction opposite to those of the other plane. An analytic solution is provided for the field produced by infinite surface currents running in the biplanar geometry. For the case of discrete wires, computer-generated field maps imply that the homogeneity and sensitivity of the biplanar design are superior to those of a saddle coil, but worse than those obtained in an equivalent discrete cosine or birdcage coil design. Optimization of this coil design was performed using computer simulations. The measured B1 map of an optimized, single-tuned biplanar coil compares favorably to that of an equivalent discrete cosine coil, demonstrating excellent homogeneity in the central region of the coil. A 30 × 24 × 40 cm biplanar coil has been coupled to a 1.5 T imaging system. Images of the human abdomen generated with this coil demonstrate a high degree of homogeneity across nearly all of the sensitive region of the coil.

  6. Radiation hard avalanche photodiodes for CMS ECAL

    NASA Astrophysics Data System (ADS)

    Grahl, J.; Kronquist, I.; Rusack, R.; Singovski, A.; Kuznetsov, A.; Musienko, Y.; Reucroft, S.; Swain, J.; Deiters, K.; Ingram, Q.; Renker, D.; Sakhelashvili, T.

    2003-05-01

    The photo detectors of the CMS electromagnetic calorimeter have to operate in a rather hostile environment, in a strong magnetic field of 4 T and under unprecedented radiation levels. Avalanche Photo Diodes (APDs) have been chosen to detect the scintillation light of the 62,000 lead tungstate crystals in the barrel part of the calorimeter. After a 6 year long R&D work Hamamatsu Photonics produces APDs with a structure that is basically radiation hard. Only a few percent of the delivered APDs are weak due to defects at the surface caused by dust particles in the production process. Since a reliability of 99.9% is required, a method to detect weak APDs before they are built into the detector had to be developed. The described screening method is a combination of 60Co irradiations and annealing under bias of all APDs and irradiations with hadrons on a sampling basis.

  7. Allergen-Specific CD4(+) T Cells in Human Asthma.

    PubMed

    Ling, Morris F; Luster, Andrew D

    2016-03-01

    In allergic asthma, aeroallergen exposure of sensitized individuals mobilizes robust innate and adaptive airway immune responses, stimulating eosinophilic airway inflammation and the activation and infiltration of allergen-specific CD4(+) T cells into the airways. Allergen-specific CD4(+) T cells are thought to be central players in the asthmatic response as they specifically recognize the allergen and initiate and orchestrate the asthmatic inflammatory response. In this article, we briefly review the role of allergen-specific CD4(+) T cells in the pathogenesis of human allergic airway inflammation in allergic individuals, discuss the use of allergen-major histocompatibility complex class II tetramers to characterize allergen-specific CD4(+) T cells, and highlight current gaps in knowledge and directions for future research pertaining to the role of allergen-specific CD4(+) T cells in human asthma. PMID:27027948

  8. Coil bobbin for stable superconducting coils

    SciTech Connect

    Kashima, T.; Yamanaka, A.; Nishijima, S.; Okada, T.

    1996-12-31

    The coil bobbin for a.c. coils have been prepared with the high strength polyethylene fiber (DF) reinforced plastics (DFRP) or with hybrid composites reinforced by DF and glass fiber (GF). The coils with the bobbin were found to be markedly stable. The DF has a large negative thermal expansion coefficient and hence the circumferential thermal strain of bobbin can be designed by changing the ratio of DF to GF layer thickness (DF/GF). It was found that the thermal expansion coefficient in the circumferential direction of the outer surface changed from negative to positive with increasing DF/GF and became nearly zero at a DF/GF of approximately 5.1 kA rms class a.c. coils having a bobbin with a negative thermal expansion coefficient or small thermal contraction in the circumferential direction were fabricated and were confirmed to show higher quench current than that with a GFRP bobbin.

  9. Impact of sepsis on CD4 T cell immunity

    PubMed Central

    Cabrera-Perez, Javier; Condotta, Stephanie A.; Badovinac, Vladimir P.; Griffith, Thomas S.

    2014-01-01

    Sepsis remains the primary cause of death from infection in hospital patients, despite improvements in antibiotics and intensive-care practices. Patients who survive severe sepsis can display suppressed immune function, often manifested as an increased susceptibility to (and mortality from) nosocomial infections. Not only is there a significant reduction in the number of various immune cell populations during sepsis, but there is also decreased function in the remaining lymphocytes. Within the immune system, CD4 T cells are important players in the proper development of numerous cellular and humoral immune responses. Despite sufficient clinical evidence of CD4 T cell loss in septic patients of all ages, the impact of sepsis on CD4 T cell responses is not well understood. Recent findings suggest that CD4 T cell impairment is a multipronged problem that results from initial sepsis-induced cell loss. However, the subsequent lymphopenia-induced numerical recovery of the CD4 T cell compartment leads to intrinsic alterations in phenotype and effector function, reduced repertoire diversity, changes in the composition of naive antigen-specific CD4 T cell pools, and changes in the representation of different CD4 T cell subpopulations (e.g., increases in Treg frequency). This review focuses on sepsis-induced alterations within the CD4 T cell compartment that influence the ability of the immune system to control secondary heterologous infections. The understanding of how sepsis affects CD4 T cells through their numerical loss and recovery, as well as function, is important in the development of future treatments designed to restore CD4 T cells to their presepsis state. PMID:24791959

  10. The Muon Detector of Cms

    NASA Astrophysics Data System (ADS)

    Jiang, Chunhua

    2005-04-01

    Muons are an unmistakable signature of most of the LHC physics is designed to explore. The ability to trigger on and reconstruct muons at highest luminorsities is central to the concept of CMS. CMS is characterized by simplicity of design, with one magnet whose solenoideal field facilitates precision racking in the central barrel region and triggering on muons through their bending in the tharnverse and side views. The CMS muon system has three purpose: muon identification, muon trigger and nuon momentum measurement.

  11. Using fullscreen CMS at CERN

    SciTech Connect

    White, B.

    1991-05-01

    Fullscreen CMS is an optional console environment introduced in Release 5 of CMS which maintains the context of a VM session across invocations of full screen commands like XEDIT, FILELIST or MAIL. In addition it allows limited scrolling and windowing capabilities. This write-up provides CERNVM users who are interested in Fullscreen CMS with an overview of the concepts and operations which are involved. In that it is an optional environment, this write-up does not constitute an endorsement of Fullscreen CMS.

  12. Superconducting magnetic coil

    DOEpatents

    Aized, Dawood; Schwall, Robert E.

    1999-06-22

    A superconducting magnetic coil includes a plurality of sections positioned axially along the longitudinal axis of the coil, each section being formed of an anisotropic high temperature superconductor material wound about a longitudinal axis of the coil and having an associated critical current value that is dependent on the orientation of the magnetic field of the coil. The cross section of the superconductor, or the type of superconductor material, at sections along the axial and radial axes of the coil are changed to provide an increased critical current at those regions where the magnetic field is oriented more perpendicularly to the conductor plane, to thereby increase the critical current at these regions and to maintain an overall higher critical current of the coil.

  13. Superconducting magnetic coil

    DOEpatents

    Aized, D.; Schwall, R.E.

    1999-06-22

    A superconducting magnetic coil includes a plurality of sections positioned axially along the longitudinal axis of the coil, each section being formed of an anisotropic high temperature superconductor material wound about a longitudinal axis of the coil and having an associated critical current value that is dependent on the orientation of the magnetic field of the coil. The cross section of the superconductor, or the type of superconductor material, at sections along the axial and radial axes of the coil are changed to provide an increased critical current at those regions where the magnetic field is oriented more perpendicularly to the conductor plane, to thereby increase the critical current at these regions and to maintain an overall higher critical current of the coil. 15 figs.

  14. Superconducting magnetic coil

    DOEpatents

    Aized, Dawood; Schwall, Robert E.

    1996-06-11

    A superconducting magnetic coil includes a plurality of sections positioned axially along the longitudinal axis of the coil, each section being formed of an anisotropic high temperature superconductor material wound about a longitudinal axis of the coil and having an associated critical current value that is dependent on the orientation of the magnetic field of the coil. The cross section of the superconductor, or the type of superconductor material, at sections along the axial and radial axes of the coil are changed to provide an increased critical current at those regions where the magnetic field is oriented more perpendicularly to the conductor plane, to thereby increase the critical current at these regions and to maintain an overall higher critical current of the coil.

  15. MINIMARS choke coil design

    SciTech Connect

    Gurol, H.; Parmer, J.E.

    1986-01-01

    The choke coil is one of the most advanced of all the magnets in the MINIMARS tandem mirror reactor. Recent developments have enabled the high-field choke coil to be much more compact and consume less power than past designs. There are three main technology areas that have had the greatest impact on the choke coil design: (1) superfluid helium (He-II) at 1.8 K; (2) Nb/sub 3/Sn superconductor; and (3) high-strength alloys for conductor reinforcement. The purpose of this paper is to discuss the 24-T MINIMARS choke coil configuration. It is a hybrid design consisting of a superconducting (S/C) background coil and a normal (N/C) insert coil.

  16. CMS Frailty Adjustment Model

    PubMed Central

    Kautter, John; Pope, Gregory C.

    2004-01-01

    The authors document the development of the CMS frailty adjustment model, a Medicare payment approach that adjusts payments to a Medicare managed care organization (MCO) according to the functional impairment of its community-residing enrollees. Beginning in 2004, this approach is being applied to certain organizations, such as Program of All-Inclusive Care for the Elderly (PACE), that specialize in providing care to the community-residing frail elderly. In the future, frailty adjustment could be extended to more Medicare managed care organizations. PMID:25372243

  17. Coil system for plasmoid thruster

    NASA Technical Reports Server (NTRS)

    Eskridge, Richard H. (Inventor); Lee, Michael H. (Inventor); Martin, Adam K. (Inventor); Fimognari, Peter J. (Inventor)

    2010-01-01

    A coil system for a plasmoid thruster includes a bias coil, a drive coil and field coils. The bias and drive coils are interleaved with one another as they are helically wound about a conical region. A first field coil defines a first passage at one end of the conical region, and is connected in series with the bias coil. A second field coil defines a second passage at an opposing end of the conical region, and is connected in series with the bias coil.

  18. Opportunistic Resource Usage in CMS

    SciTech Connect

    Kreuzer, Peter; Hufnagel, Dirk; Dykstra, D.; Gutsche, O.; Tadel, M.; Sfiligoi, I.; Letts, J.; Wuerthwein, F.; McCrea, A.; Bockelman, B.; Fajardo, E.; Linares, L.; Wagner, R.; Konstantinov, P.; Blumenfeld, B.; Bradley, D.

    2014-01-01

    CMS is using a tiered setup of dedicated computing resources provided by sites distributed over the world and organized in WLCG. These sites pledge resources to CMS and are preparing them especially for CMS to run the experiment's applications. But there are more resources available opportunistically both on the GRID and in local university and research clusters which can be used for CMS applications. We will present CMS' strategy to use opportunistic resources and prepare them dynamically to run CMS applications. CMS is able to run its applications on resources that can be reached through the GRID, through EC2 compliant cloud interfaces. Even resources that can be used through ssh login nodes can be harnessed. All of these usage modes are integrated transparently into the GlideIn WMS submission infrastructure, which is the basis of CMS' opportunistic resource usage strategy. Technologies like Parrot to mount the software distribution via CVMFS and xrootd for access to data and simulation samples via the WAN are used and will be described. We will summarize the experience with opportunistic resource usage and give an outlook for the restart of LHC data taking in 2015.

  19. Opportunistic Resource Usage in CMS

    NASA Astrophysics Data System (ADS)

    Kreuzer, Peter; Hufnagel, Dirk; Dykstra, D.; Gutsche, O.; Tadel, M.; Sfiligoi, I.; Letts, J.; Wuerthwein, F.; McCrea, A.; Bockelman, B.; Fajardo, E.; Linares, L.; Wagner, R.; Konstantinov, P.; Blumenfeld, B.; Bradley, D.; Cms Collaboration

    2014-06-01

    CMS is using a tiered setup of dedicated computing resources provided by sites distributed over the world and organized in WLCG. These sites pledge resources to CMS and are preparing them especially for CMS to run the experiment's applications. But there are more resources available opportunistically both on the GRID and in local university and research clusters which can be used for CMS applications. We will present CMS' strategy to use opportunistic resources and prepare them dynamically to run CMS applications. CMS is able to run its applications on resources that can be reached through the GRID, through EC2 compliant cloud interfaces. Even resources that can be used through ssh login nodes can be harnessed. All of these usage modes are integrated transparently into the GlideIn WMS submission infrastructure, which is the basis of CMS' opportunistic resource usage strategy. Technologies like Parrot to mount the software distribution via CVMFS and xrootd for access to data and simulation samples via the WAN are used and will be described. We will summarize the experience with opportunistic resource usage and give an outlook for the restart of LHC data taking in 2015.

  20. Super radiation hard vacuum phototriodes for the CMS endcap ECAL

    NASA Astrophysics Data System (ADS)

    Gusev, Yu. I.; Kovalev, A. I.; Levchenko, L. A.; Lukianov, V. N.; Moroz, F. V.; Mamaeva, G. A.; Seliverstov, D. M.; Trautman, V. Yu.; Yakorev, D. O.

    2004-12-01

    The energy resolution σ/E of the electromagnetic calorimeter (ECAL) in the energy range of 50-500 GeV is defined mainly by two terms: stochastic α/√E and constant C. The photoreadout of the CMS Endcap ECAL consists of vacuum phototriodes (VPT), which are broadening a signal from np photoelectrons characterized by the excess noise factor F=np(σ/E)2. The technical specification of the CMS ECAL requires the value of F to be smaller than 4 in the CMS LHC environment during 10 years of detector operation. In this paper we present results of the VPT performance study in a magnetic field up to 4 T, in a gamma radiation field of 0-50 kGy and in a neutron fluence of 7×1015 n/cm2. The standard phototriodes FEU-188 with faceplates from UV glass used in CMS ECAL as well as VPTs with super radiation hard cerium-doped glasses were investigated at the 60Co gamma facility, a neutron generator and a nuclear reactor in the Petersburg Nuclear Physics Institute (PNPI). The dependence of the VPT gain and the excess noise factor in magnetic fields on the fine-mesh plane orientation has also been studied.

  1. CMS computing model evolution

    NASA Astrophysics Data System (ADS)

    Grandi, C.; Bonacorsi, D.; Colling, D.; Fisk, I.; Girone, M.

    2014-06-01

    The CMS Computing Model was developed and documented in 2004. Since then the model has evolved to be more flexible and to take advantage of new techniques, but many of the original concepts remain and are in active use. In this presentation we will discuss the changes planned for the restart of the LHC program in 2015. We will discuss the changes planning in the use and definition of the computing tiers that were defined with the MONARC project. We will present how we intend to use new services and infrastructure to provide more efficient and transparent access to the data. We will discuss the computing plans to make better use of the computing capacity by scheduling more of the processor nodes, making better use of the disk storage, and more intelligent use of the networking.

  2. Functional and Phenotypic Plasticity of CD4+ T Cell Subsets

    PubMed Central

    Caza, Tiffany; Landas, Steve

    2015-01-01

    The remarkable plasticity of CD4+ T cells allows individuals to respond to environmental stimuli in a context-dependent manner. A balance of CD4+ T cell subsets is critical to mount responses against pathogen challenges to prevent inappropriate activation, to maintain tolerance, and to participate in antitumor immune responses. Specification of subsets is a process beginning in intrathymic development and continuing within the circulation. It is highly flexible to adapt to differences in nutrient availability and the tissue microenvironment. CD4+ T cell subsets have significant cross talk, with the ability to “dedifferentiate” given appropriate environmental signals. This ability is dependent on the metabolic status of the cell, with mTOR acting as the rheostat. Autoimmune and antitumor immune responses are regulated by the balance between regulatory T cells and Th17 cells. When a homeostatic balance of subsets is not maintained, immunopathology can result. CD4+ T cells carry complex roles within tumor microenvironments, with context-dependent immune responses influenced by oncogenic drivers and the presence of inflammation. Here, we examine the signals involved in CD4+ T cell specification towards each subset, interconnectedness of cytokine networks, impact of mTOR signaling, and cellular metabolism in lineage specification and provide a supplement describing techniques to study these processes. PMID:26583116

  3. Human brain imaging at 9.4 T using a tunable patch antenna for transmission.

    PubMed

    Hoffmann, Jens; Shajan, G; Budde, Juliane; Scheffler, Klaus; Pohmann, Rolf

    2013-05-01

    For human brain imaging at ultrahigh fields, the traveling wave concept can provide a more uniform B1+ field over a larger field of view with improved patient comfort compared to conventional volume coils. It suffers, however, from limited transmit efficiency and receive sensitivity and is not readily applicable in systems where the radiofrequency shield is too narrow to allow for unattenuated wave propagation. Here, the near field of a capacitively adjustable patch antenna for excitation is combined with a receive-only array at 9.4 T. The antenna is designed in compact size and placed in close proximity to the subject to improve the transmit efficiency in narrow bores. Experimental and numerical comparisons to conventional microstrip arrays reveal improved B1+ homogeneity and longitudinal coverage, but at the cost of elevated local specific absorption rate. High-resolution functional and anatomical images demonstrate the use of this setup for in vivo human brain imaging at 9.4 T. PMID:22706783

  4. In vivo magnetic resonance microscopy of Drosophilae at 9.4 T.

    PubMed

    Même, Sandra; Joudiou, Nicolas; Szeremeta, Frédéric; Mispelter, Joël; Louat, Fanny; Decoville, Martine; Locker, Daniel; Beloeil, Jean-Claude

    2013-01-01

    In preclinical research, genetic studies have made considerable progress as a result of the development of transgenic animal models of human diseases. Consequently, there is now a need for higher resolution MRI to provide finer details for studies of small animals (rats, mice) or very small animals (insects). One way to address this issue is to work with high-magnetic-field spectrometers (dedicated to small animal imaging) with strong magnetic field gradients. It is also necessary to develop a complete methodology (transmit/receive coil, pulse sequence, fixing system, air supply, anesthesia capabilities, etc.). In this study, we developed noninvasive protocols, both in vitro and in vivo (from coil construction to image generation), for drosophila MRI at 9.4 T. The 10 10 80-μm resolution makes it possible to visualize whole drosophila (head, thorax, abdomen) and internal organs (ovaries, longitudinal and transverse muscles, bowel, proboscis, antennae and optical lobes). We also provide some results obtained with a Drosophila model of muscle degeneration. This opens the way for new applications of structural genetic modification studies using MRI of drosophila. PMID:22898691

  5. The design and test of a new volume coil for high field imaging.

    PubMed

    Wen, H; Chesnick, A S; Balaban, R S

    1994-10-01

    A major problem in the development of high field (> 100 MHz) large volume (> 6000 cm3) MR coils is the interaction of the coil with the subject as well as the radiation loss to the environment. To reduce subject perturbation of the coil resonance modes, a volume coil that uses an array of freely rotating resonant elements radially mounted between two concentric cylinders was designed for operation at 170 MHz. Substantial electromagnetic energy is stored in the resonant elements outside the sample region without compromising the efficiency of the overall coil. This stored energy reduces the effect of the subject on the circuit and maintains a high Q, facilitating the tuning and matching of the coil. The unloaded Q of the coil is 680; when loaded with a head, it was 129. The ratio of 5.3 of the unloaded to loaded Q supports the notion that the efficiency of the coil was maintained in comparison with previous designs. The power requirement and signal-to-noise performance are significantly improved. The coil is tuned by a mechanism that imparts the same degree of rotation on all of the elements simultaneously, varying their degree of mutual coupling and preserving the overall coil symmetry. A thin radiofrequency shield is an integral part of the coil to reduce the radiation effect, which is a significant loss mechanism at high fields. MR images were collected at 4T using this coil design with high sensitivity and B1 homogeneity. PMID:7997115

  6. Open coil traction system.

    PubMed

    Vibhute, Pavankumar Janardan

    2012-01-01

    Sliding mechanics have become a popular method for space closure, with the development of preadjusted edgewise appliances. Furthermore, various space closing auxiliaries have been developed and extensively evaluated for their clinical efficiency. Their effectiveness is enhanced with optimum force magnitude and low load deflection rate/force decay. With the advent of nickel-titanium (Ni-Ti) springs in orthodontics, load deflection rates have been markedly reduced. To use Ni-Ti springs, clinicians have to depend upon prefabricated closed coil springs. The open coil traction system, or open coil retraction spring, is developed utilizing Ni-Ti open coil springs for orthodontic space closure. This article describes the fabrication and clinical application of the open coil traction system, which has a number of advantages. It sustains a low load deflection rate with optimum force magnitude, and its design is adjustable for a desired length and force level. It is fail-safe for both activation and deactivation (ie, it cannot be overactivated, and the decompression limit of the open coil is controlled by the operator). The open coil traction system can be offset from the mucosa to help reduce soft tissue impingement. PMID:22567645

  7. Commercial applications for COIL

    NASA Astrophysics Data System (ADS)

    Solomon, Wayne C.; Carroll, David L.; King, D. M.; Fockler, L. A.; Stromberg, D. S.; Sexauer, M.; Milmoe, A.; Sentman, Lee H.

    2000-01-01

    The chemical oxygen-iodine laser (COIL) is a high power, fiber deliverable tool, which can be used for a number of different industrial applications. COIL is of particular interest because of its short fiber deliverable wavelength, high scaleable continuous wave power, and excellent material interaction properties. In past research the University of Illinois at Urbana-Champaign identified and decommissioning and decontamination (DD) of nuclear facilities as a primary focus for COIL technology. DD will be a major challenge in the coming decades. The use of a robotically driven fiber delivered cutting/ablation tool in contaminated areas promises to lower risks to workers for the DD mission. Further, the high cutting speed of COIL will significantly reduce the time required to cut contaminated equipment, reducing costs. The high power of COIL will permit the dismantling of thick stacks of piping and equipment as well as reactor vessels. COIL is very promising for the removal of material from contaminated surfaces, perhaps to depths thicker than an inch. Laser cutting and ablation minimizes dust and fumes, which reduces the required number of high efficiency particulate accumulator filters, thus reducing costly waste disposal. Other potential industrial applications for COIL are shipbuilding, automotive manufacturing, heavy machinery manufacturing, tasks requiring underwater cutting or welding, and there appear to be very promising applications for high powers lasers in the oil industry.

  8. Transcriptional Regulatory Networks for CD4 T Cell Differentiation

    PubMed Central

    Zhu, Jinfang

    2015-01-01

    CD4+ T cells play a central role in controlling the adaptive immune response by secreting cytokines to activate target cells. Naïve CD4+ T cells differentiate into at least four subsets, Th1, Th2, Th17, and inducible regulatory T cells, each with unique functions for pathogen elimination. The differentiation of these subsets is induced in response to cytokine stimulation, which is translated into Stat activation, followed by induction of master regulator transcription factors. In addition to these factors, multiple other transcription factors, both subset specific and shared, are also involved in promoting subset differentiation. This review will focus on the network of transcription factors that control CD4+ T cell differentiation. PMID:24839135

  9. Recent CMS results on diffraction

    NASA Astrophysics Data System (ADS)

    Benoît, Roland

    2015-03-01

    Recent CMS results on diffraction are presented. These include the measurements of the soft diffractive cross sections, of the forward rapidity gap cross section, of the diffractive dijet cross section, the measurement of a large rapidity gap in W and Z boson events and the measurement of the pseudorapidity distribution of charged particles in a single diffractive enhanced sample. This last measurement is the first common result of the CMS and TOTEM collaborations. Some prospects of common CMS-TOTEM data taking are also discussed.

  10. Correction coil cable

    DOEpatents

    Wang, S.T.

    1994-11-01

    A wire cable assembly adapted for the winding of electrical coils is taught. A primary intended use is for use in particle tube assemblies for the Superconducting Super Collider. The correction coil cables have wires collected in wire array with a center rib sandwiched therebetween to form a core assembly. The core assembly is surrounded by an assembly housing having an inner spiral wrap and a counter wound outer spiral wrap. An alternate embodiment of the invention is rolled into a keystoned shape to improve radial alignment of the correction coil cable on a particle tube in a particle tube assembly. 7 figs.

  11. Coil spring venting arrangement

    DOEpatents

    McCugh, R.M.

    1975-10-21

    A simple venting device for trapped gas pockets in hydraulic systems is inserted through a small access passages, operated remotely, and removed completely. The device comprises a small diameter, closely wound coil spring which is pushed through a guide temporarily inserted in the access passage. The guide has a central passageway which directs the coil spring radially upward into the pocket, so that, with the guide properly positioned for depth and properly oriented, the coil spring can be pushed up into the top of the pocket to vent it. By positioning a seal around the free end of the guide, the spring and guide are removed and the passage is sealed.

  12. ELECTRICAL COIL STRUCTURE

    DOEpatents

    Baker, W.R.; Hartwig, A.

    1962-09-25

    A compactly wound electrical coil is designed for carrying intense pulsed currents such as are characteristic of controlled thermonuclear reaction devices. A flat strip of conductor is tightly wound in a spiral with a matching flat strip of insulator. To provide for a high fluid coolant flow through the coil with minimum pumping pressure, a surface of the conductor is scored with parallel transverse grooves which form short longitudinal coolant pasaages when the conductor is wound in the spiral configuration. Owing to this construction, the coil is extremely resistant to thermal and magnetic shock from sudden high currents. (AEC)

  13. Magnetic microhelix coil structures.

    PubMed

    Smith, Elliot J; Makarov, Denys; Sanchez, Samuel; Fomin, Vladimir M; Schmidt, Oliver G

    2011-08-26

    Together with the well-known ferro- and antiferromagnetic ordering, nature has created a variety of complex helical magnetic configurations. Here, we design and investigate three-dimensional microhelix coil structures that are radial-, corkscrew-, and hollow-bar-magnetized. The magnetization configurations of the differently magnetized coils are experimentally revealed by probing their specific dynamic response to an external magnetic field. Helix coils offer an opportunity to realize microscale geometries of the magnetic toroidal moment, observed so far only in bulk multiferroic materials. PMID:21929266

  14. Magnetic Microhelix Coil Structures

    NASA Astrophysics Data System (ADS)

    Smith, Elliot J.; Makarov, Denys; Sanchez, Samuel; Fomin, Vladimir M.; Schmidt, Oliver G.

    2011-08-01

    Together with the well-known ferro- and antiferromagnetic ordering, nature has created a variety of complex helical magnetic configurations. Here, we design and investigate three-dimensional microhelix coil structures that are radial-, corkscrew-, and hollow-bar-magnetized. The magnetization configurations of the differently magnetized coils are experimentally revealed by probing their specific dynamic response to an external magnetic field. Helix coils offer an opportunity to realize microscale geometries of the magnetic toroidal moment, observed so far only in bulk multiferroic materials.

  15. FIRE_AX_CMS_SOLAR_WK

    Atmospheric Science Data Center

    2015-11-24

    FIRE_AX_CMS_SOLAR_WK Project Title:  FIRE II ASTEX Discipline:  ... Order: Earthdata Search Parameters:  Solar Irradiance Order Data:  Search and Order: Earthdata Search Readme Files:  Readme CMS_SOLAR_WK CMS_SOLAR_WK Info 1 CMS_SOLAR_WK Info 2 ...

  16. Disruption of Bcr-Abl Coiled Coil Oligomerization by Design*

    PubMed Central

    Dixon, Andrew S.; Pendley, Scott S.; Bruno, Benjamin J.; Woessner, David W.; Shimpi, Adrian A.; Cheatham, Thomas E.; Lim, Carol S.

    2011-01-01

    Oligomerization is an important regulatory mechanism for many proteins, including oncoproteins and other pathogenic proteins. The oncoprotein Bcr-Abl relies on oligomerization via its coiled coil domain for its kinase activity, suggesting that a designed coiled coil domain with enhanced binding to Bcr-Abl and reduced self-oligomerization would be therapeutically useful. Key mutations in the coiled coil domain of Bcr-Abl were identified that reduce homo-oligomerization through intermolecular charge-charge repulsion yet increase interaction with the Bcr-Abl coiled coil through additional salt bridges, resulting in an enhanced ability to disrupt the oligomeric state of Bcr-Abl. The mutations were modeled computationally to optimize the design. Assays performed in vitro confirmed the validity and functionality of the optimal mutations, which were found to exhibit reduced homo-oligomerization and increased binding to the Bcr-Abl coiled coil domain. Introduction of the mutant coiled coil into K562 cells resulted in decreased phosphorylation of Bcr-Abl, reduced cell proliferation, and increased caspase-3/7 activity and DNA segmentation. Importantly, the mutant coiled coil domain was more efficacious than the wild type in all experiments performed. The improved inhibition of Bcr-Abl through oligomeric disruption resulting from this modified coiled coil domain represents a viable alternative to small molecule inhibitors for therapeutic intervention. PMID:21659527

  17. Theory of myelin coiling.

    PubMed

    Huang, J-R

    2006-04-01

    A new model is proposed to explain coiling of myelins composed of fluid bilayers. This model allows the constituent bilayer cylinders of a myelin to be non-coaxial and the bilayer lateral tension to vary from bilayer to bilayer. The calculations show that a myelin would bend or coil to lower its free energy when the bilayer lateral tension is sufficiently large. From a mechanical point of view, the proposed coiling mechanism is analogous to the classical Euler buckling of a thin elastic rod under axial compression. The analysis of a simple two-bilayer case suggests that a bilayer lateral tension of about 1 dyne/cm can easily induce coiling of myelins of typical lipid bilayers. This model signifies the importance of bilayer lateral tension in determining the morphology of myelinic structures. PMID:16465468

  18. Borehole induction coil transmitter

    DOEpatents

    Holladay, Gale; Wilt, Michael J.

    2002-01-01

    A borehole induction coil transmitter which is a part of a cross-borehole electromagnetic field system that is used for underground imaging applications. The transmitter consists of four major parts: 1) a wound ferrite or mu-metal core, 2) an array of tuning capacitors, 3) a current driver circuit board, and 4) a flux monitor. The core is wound with several hundred turns of wire and connected in series with the capacitor array, to produce a tuned coil. This tuned coil uses internal circuitry to generate sinusoidal signals that are transmitted through the earth to a receiver coil in another borehole. The transmitter can operate at frequencies from 1-200 kHz and supplies sufficient power to permit the field system to operate in boreholes separated by up to 400 meters.

  19. The CMS central hadron calorimeter

    SciTech Connect

    Freeman, J.

    1998-11-01

    The CMS central hadron calorimeter is a brass absorber/scintillator sampling structure. We describe details of the mechanical and optical structure. We also discuss calibration techniques, and finally the anticipated construction schedule. {copyright} {ital 1998 American Institute of Physics.}

  20. Heavy quark physics in CMS

    NASA Astrophysics Data System (ADS)

    Fedi, G.; CMS Collaboration

    2016-07-01

    The most recent results which concern the heavy quark hadrons done in the CMS experiment are reported. The searching area spans over the heavy quark spectroscopy, production cross sections, beauty meson decay properties, rare decays, and CP violation.

  1. CMS multicore scheduling strategy

    SciTech Connect

    Perez-Calero Yzquierdo, Antonio; Hernandez, Jose; Holzman, Burt; Majewski, Krista; McCrea, Alison

    2014-01-01

    In the next years, processor architectures based on much larger numbers of cores will be most likely the model to continue 'Moore's Law' style throughput gains. This not only results in many more jobs in parallel running the LHC Run 1 era monolithic applications, but also the memory requirements of these processes push the workernode architectures to the limit. One solution is parallelizing the application itself, through forking and memory sharing or through threaded frameworks. CMS is following all of these approaches and has a comprehensive strategy to schedule multicore jobs on the GRID based on the glideinWMS submission infrastructure. The main component of the scheduling strategy, a pilot-based model with dynamic partitioning of resources that allows the transition to multicore or whole-node scheduling without disallowing the use of single-core jobs, is described. This contribution also presents the experiences made with the proposed multicore scheduling schema and gives an outlook of further developments working towards the restart of the LHC in 2015.

  2. CMS multicore scheduling strategy

    NASA Astrophysics Data System (ADS)

    Pérez-Calero Yzquierdo, Antonio; Hernández, Jose; Holzman, Burt; Majewski, Krista; McCrea, Alison; Cms Collaboration

    2014-06-01

    In the next years, processor architectures based on much larger numbers of cores will be most likely the model to continue "Moore's Law" style throughput gains. This not only results in many more jobs in parallel running the LHC Run 1 era monolithic applications, but also the memory requirements of these processes push the workernode architectures to the limit. One solution is parallelizing the application itself, through forking and memory sharing or through threaded frameworks. CMS is following all of these approaches and has a comprehensive strategy to schedule multicore jobs on the GRID based on the glideinWMS submission infrastructure. The main component of the scheduling strategy, a pilot-based model with dynamic partitioning of resources that allows the transition to multicore or whole-node scheduling without disallowing the use of single-core jobs, is described. This contribution also presents the experiences made with the proposed multicore scheduling schema and gives an outlook of further developments working towards the restart of the LHC in 2015.

  3. The CMS dataset bookkeeping service

    SciTech Connect

    Afaq, Anzar,; Dolgert, Andrew; Guo, Yuyi; Jones, Chris; Kosyakov, Sergey; Kuznetsov, Valentin; Lueking, Lee; Riley, Dan; Sekhri, Vijay; /Fermilab

    2007-10-01

    The CMS Dataset Bookkeeping Service (DBS) has been developed to catalog all CMS event data from Monte Carlo and Detector sources. It provides the ability to identify MC or trigger source, track data provenance, construct datasets for analysis, and discover interesting data. CMS requires processing and analysis activities at various service levels and the DBS system provides support for localized processing or private analysis, as well as global access for CMS users at large. Catalog entries can be moved among the various service levels with a simple set of migration tools, thus forming a loose federation of databases. DBS is available to CMS users via a Python API, Command Line, and a Discovery web page interfaces. The system is built as a multi-tier web application with Java servlets running under Tomcat, with connections via JDBC to Oracle or MySQL database backends. Clients connect to the service through HTTP or HTTPS with authentication provided by GRID certificates and authorization through VOMS. DBS is an integral part of the overall CMS Data Management and Workflow Management systems.

  4. NCSX Toroidal Field Coil Design

    SciTech Connect

    Kalish, M.; Rushinski, J.; Myatt, L.; Brooks, A.; Dahlgren, F.; Chrzanowski, J.; Reiersen, W.; Freudenberg, K.

    2005-10-07

    The National Compact Stellarator Experiment (NCSX) is an experimental device whose design and construction is underway at the Department of Energy's Princeton Plasma Physics Laboratory (PPPL). The primary coil systems for the NCSX device consist of the twisted plasma-shaping Modular Coils, the Poloidal Field Coils, and the Toroidal Field (TF) Coils. The TF Coils are D-shaped coils wound from hollow copper conductor, and vacuum impregnated with a glass-epoxy resin system. There are 18 identical, equally spaced TF coils providing 1/R field at the plasma. They operate within a cryostat, and are cooled by LN2, nominally, to 80K. Wedge shaped castings are assembled to the inboard face of these coils, so that inward radial loads are reacted via the nesting of each of the coils against their adjacent partners. This paper outlines the TF Coil design methodology, reviews the analysis results, and summarizes how the design and analysis support the design requirements.

  5. Hierarchical Cascades of Instability Govern the Mechanics of Coiled Coils: Helix Unfolding Precedes Coil Unzipping

    PubMed Central

    Hamed, Elham; Keten, Sinan

    2014-01-01

    Coiled coils are a fundamental emergent motif in proteins found in structural biomaterials, consisting of α-helical secondary structures wrapped in a supercoil. A fundamental question regarding the thermal and mechanical stability of coiled coils in extreme environments is the sequence of events leading to the disassembly of individual oligomers from the universal coiled-coil motifs. To shed light on this phenomenon, here we report atomistic simulations of a trimeric coiled coil in an explicit water solvent and investigate the mechanisms underlying helix unfolding and coil unzipping in the assembly. We employ advanced sampling techniques involving steered molecular dynamics and metadynamics simulations to obtain the free-energy landscapes of single-strand unfolding and unzipping in a three-stranded assembly. Our comparative analysis of the free-energy landscapes of instability pathways shows that coil unzipping is a sequential process involving multiple intermediates. At each intermediate state, one heptad repeat of the coiled coil first unfolds and then unzips due to the loss of contacts with the hydrophobic core. This observation suggests that helix unfolding facilitates the initiation of coiled-coil disassembly, which is confirmed by our 2D metadynamics simulations showing that unzipping of one strand requires less energy in the unfolded state compared with the folded state. Our results explain recent experimental findings and lay the groundwork for studying the hierarchical molecular mechanisms that underpin the thermomechanical stability/instability of coiled coils and similar protein assemblies. PMID:25028889

  6. Adolescents' perceptions toward the internet: a 4-T framework.

    PubMed

    Tsai, Chin-Chung

    2004-08-01

    This study could be viewed as one of the initial attempts to probe adolescents' general perceptions toward the Internet. Through interviewing 40 adolescents in Taiwan, this study found the following 4-T categories for interpreting their perceptions toward the Internet, which included Technology, Tool, Toy, and Travel. Most adolescents perceived the Internet as a tool, implying that these adolescents, in general, held pragmatic views about the Internet. This paper further proposes a framework to elaborate the 4-T categories. The framework consists of the following two axes: one axis probably shows the ontology of the Internet, ranging from a "product" to a "process," whereas the other axis indicates the perceived feature of the Internet, varying from "functional" to "technical." It is finally suggested to carefully investigate the effects of people's Internet perceptions on their behaviors, as well as psychological and cognitive activities in Internet-related environments. PMID:15331033

  7. Heterogeneity of Human CD4(+) T Cells Against Microbes.

    PubMed

    Sallusto, Federica

    2016-05-20

    CD4(+) T helper (Th) cells play a central role in the adaptive immune response by providing help to B cells and cytotoxic T cells and by releasing different types of cytokines in tissues to mediate protection against a wide range of pathogenic microorganisms. These functions are performed by different types of Th cells endowed with distinct migratory capacities and effector functions. Here we discuss how studies of the human T cell response to microbes have advanced our understanding of Th cell functional heterogeneity, in particular with the discovery of a distinct Th1 subset involved in the response to Mycobacteria and the characterization of two types of Th17 cells specific for extracellular bacteria or fungi. We also review new approaches to dissect at the clonal level the human CD4(+) T cell response induced by pathogens or vaccines that have revealed an unexpected degree of intraclonal diversification and propose a progressive and selective model of CD4(+) T cell differentiation. PMID:27168241

  8. AAFreqCoil: a new classifier to distinguish parallel dimeric and trimeric coiled coils.

    PubMed

    Wang, Xiaofeng; Zhou, Yuan; Yan, Renxiang

    2015-07-01

    Coiled coils are characteristic rope-like protein structures, constituted by one or more heptad repeats. Native coiled-coil structures play important roles in various biological processes, while the designed ones are widely employed in medicine and industry. To date, two major oligomeric states (i.e. dimeric and trimeric states) of a coiled-coil structure have been observed, plausibly exerting different biological functions. Therefore, exploration of the relationship between heptad repeat sequences and coiled coil structures is highly important. In this paper, we develop a new method named AAFreqCoil to classify parallel dimeric and trimeric coiled coils. Our method demonstrated its competitive performance when benchmarked based on 10-fold cross validation and jackknife cross validation. Meanwhile, the rules that can explicitly explain the prediction results of the test coiled coil can be extracted from the AAFreqCoil model for a better explanation of user predictions. A web server and stand-alone program implementing the AAFreqCoil algorithm are freely available at . PMID:25918905

  9. Correction coil cable

    DOEpatents

    Wang, Sou-Tien

    1994-11-01

    A wire cable assembly (10, 310) adapted for the winding of electrical coils is taught. A primary intended use is for use in particle tube assemblies (532) for the superconducting super collider. The correction coil cables (10, 310) have wires (14, 314) collected in wire arrays (12, 312) with a center rib (16, 316) sandwiched therebetween to form a core assembly (18, 318 ). The core assembly (18, 318) is surrounded by an assembly housing (20, 320) having an inner spiral wrap (22, 322) and a counter wound outer spiral wrap (24, 324). An alternate embodiment (410) of the invention is rolled into a keystoned shape to improve radial alignment of the correction coil cable (410) on a particle tube (733) in a particle tube assembly (732).

  10. Coiling of Elastic Ropes

    NASA Astrophysics Data System (ADS)

    Habibi, M.; Ribe, N. M.; Bonn, Daniel

    2007-10-01

    A rope falling onto a solid surface typically forms a series of regular coils. Here, we study this phenomenon using laboratory experiments (with cotton threads and softened spaghetti) and an asymptotic “slender-rope” numerical model. The excellent agreement between the two with no adjustable parameters allows us to determine a complete phase diagram for elastic coiling comprising three basic regimes involving different force balances (elastic, gravitational, and inertial) together with resonant “whirling string” and “whirling shaft” eigenmodes in the inertial regime.

  11. A novel protein with anti-metastasis activity on 4T1 carcinoma from medicinal fungus Cordyceps militaris.

    PubMed

    Yang, Qing; Yin, Yalin; Yu, Guojun; Jin, Yanxia; Ye, Xiangdong; Shrestha, Alok; Liu, Wei; Yu, Wenhui; Sun, Hui

    2015-09-01

    Cordyceps militaris is a famous fungus used in traditional Chinese medicine for nearly one thousand years. And its fruiting body is known to possess anticancer and immunomodulatory activities. This study describes the isolation, characterization, and test of antitumor activity of a C. militaris protein, called here as "C. militaris immunoregulatory protein" (CMIP). CMIP was purified through a three-step chromatographic procedure. The MS analyses showed that CMIP corresponded to an uncharacterized protein (CCM_01955) in the C. militaris transcriptional database. Circular dichroism of CMIP revealed the composition of 35.5% β-sheet, 18.5% α-helix, 17.0% turn and 29.0% random coil. No significant cytotoxicity of CMIP was observed on HeLa, HepG2 and 4T1 tumor cells. However, CMIP demonstrated anti-metastasis activity on a mouse model of 4T1 breast cancer lung metastasis. It reduced the number of tumor nodules in the lung of tumor-bearing mice and prolonged their survival time. Furthermore, proliferation of the 4T1 cells was inhibited by macrophage-CMIP conditioned media. And the mRNA levels of cytokines TNF-α, IL-1β and IL-6 were increased significantly in peritoneal macrophages treated by CMIP. These results reveal the antitumor potential of CMIP, thus reinforcing the importance of biochemical prospecting of C. militaris. PMID:26136144

  12. Highly resolved in vivo 1H NMR spectroscopy of the mouse brain at 9.4 T.

    PubMed

    Tkác, Ivan; Henry, Pierre-Gilles; Andersen, Peter; Keene, C Dirk; Low, Walter C; Gruetter, Rolf

    2004-09-01

    An efficient shim system and an optimized localization sequence were used to measure in vivo 1H NMR spectra from cerebral cortex, hippocampus, striatum, and cerebellum of C57BL/6 mice at 9.4 T. The combination of automatic first- and second-order shimming (FASTMAP) with strong custom-designed second-order shim coils (shim strength up to 0.04 mT/cm2) was crucial to achieve high spectral resolution (water line width of 11-14 Hz). Requirements for second-order shim strengths to compensate field inhomogeneities in the mouse brain at 9.4 T were assessed. The achieved spectral quality (resolution, S/N, water suppression, localization performance) allowed reliable quantification of 16 brain metabolites (LCModel analysis) from 5-10-microL brain volumes. Significant regional differences (up to 2-fold, P < 0.05) were found for all quantified metabolites but Asp, Glc, and Gln. In contrast, 1H NMR spectra measured from the striatum of C57BL/6, CBA, and CBA/BL6 mice revealed only small (<13%, P < 0.05) interstrain differences in Gln, Glu, Ins, Lac, NAAG, and PE. It is concluded that 1H NMR spectroscopy at 9.4 T can provide precise biochemical information from distinct regions of the mouse brain noninvasively that can be used for monitoring of disease progression and treatment as well as phenotyping in transgenic mice models. PMID:15334565

  13. Inductively-overcoupled coil design for high resolution magnetic resonance imaging

    PubMed Central

    Bilgen, Mehmet

    2006-01-01

    Background Maintaining the quality of magnetic resonance images acquired with the current implantable coil technology is challenging in longitudinal studies. To overcome this challenge, the principle of 'inductive overcoupling' is introduced as a method to tune and match a dual coil system. This system consists of an imaging coil built with fixed electrical elements and a matching coil equipped with tuning and matching capabilities. Overcoupling here refers to the condition beyond which the peak of the current in the imaging coil splits. Methods The combined coils are coupled inductively to operate like a transformer. Each coil circuit is electrically represented by equivalent lumped-elements. A theoretical analysis is given to identify the frequency response characteristics of the currents in each coil. The predictions from this analysis are translated into experiments and applied to locally image rat spinal cord at 9.4 T using an implantable coil as the imaging coil and an external volume coil as the matching coil. Results The theoretical analysis indicated that strong coupling between the coils divides the resonance peaks on the response curves of the currents. Once these newly generated peaks were tuned and matched to the desired frequency and impedance of operation, in vivo images were acquired from the rat spinal cord at high quality and high resolution. Conclusion After proper implementation, inductive overcoupling provides a unique opportunity for tuning and matching the coil system, and allows reliable and repeatable acquisitions of magnetic resonance data. This feature is likely to be useful in experimental studies, such as those aimed at longitudinally imaging the rat following spinal cord injury. PMID:16401343

  14. Imprinted Clay Coil Vessels

    ERIC Educational Resources Information Center

    Lohr, Tresa Rae

    2006-01-01

    The author teaches clay vessel construction in the fifth grade, and it is amazing what can be accomplished in one forty-five minute period when the expectations are clarified in the initial lesson. The author introduces clay coil vessels with a discussion of the sources of clay and how clay relates to fifth-grade science curriculum concepts such…

  15. Improved Coil for Hydrogen Dissociators

    NASA Technical Reports Server (NTRS)

    Vessot, R.

    1984-01-01

    Flat coil has rigid printed circuit substrate. New coil structure minimizes RF electric field near glass walls of plasma vessel; therefore reduces direct electron bombardment of glass. Design lends itself well to high production and standardized dimensions.

  16. Pulse Test of Coil Insulation

    NASA Technical Reports Server (NTRS)

    Kroy, Ralph E.

    1987-01-01

    Waveform of back-electromotive force reveals defects. Simple pulse test reveals defects in inductor coils. Devised for use on servovalve solenoid coils on Space Shuttle, test also applicable to transformer windings, chokes, relays, and the like.

  17. Magnetic Coil Design and Analysis

    NASA Astrophysics Data System (ADS)

    Bulatowicz, Michael

    2012-06-01

    Modified magnetic field coil geometries as described in U.S. Patent Applications US20100194506 and US20110247414 can produce substantially greater magnetic field homogeneity as compared to the traditional realized versions of idealized magnetic coil geometries such as spherical or Helmholtz. The new coil geometries will be described in detail and will be compared and contrasted to realized versions of idealized geometries, including discussion of errors not typically accounted for in traditional coil design and analysis.

  18. Status of the CMS Detector

    NASA Astrophysics Data System (ADS)

    Focardi, Ettore

    The Compact Muon Solenoid (CMS) detector is one of the two largest and most powerful particle physics detectors ever built. CMS is installed in P5 at CERN's Large Hadron Collider (LHC) and as of early 2011 has completed nearly a year of operation in which it recorded products of interactions produced in protonproton collisions at a center of mass energy of 7 TeV. The proton-proton run 2010 lasted 7 months and was followed by Pb-Pb ion collisions in November. During the first few months of 2011 the LHC has delivered higher luminosity. The LHC machine is performing extremely well, allowing CMS to record enough data to perform a large number of studies of the Standard Model (SM) of particle physics in this new energy domain for the first time and to search for evidence of new physics in regions of phase space that have never before been entered. The CMS detector components, the operational experience and the performance with colliding beams will be described.

  19. The CMS DBS query language

    NASA Astrophysics Data System (ADS)

    Kuznetsov, Valentin; Riley, Daniel; Afaq, Anzar; Sekhri, Vijay; Guo, Yuyi; Lueking, Lee

    2010-04-01

    The CMS experiment has implemented a flexible and powerful system enabling users to find data within the CMS physics data catalog. The Dataset Bookkeeping Service (DBS) comprises a database and the services used to store and access metadata related to CMS physics data. To this, we have added a generalized query system in addition to the existing web and programmatic interfaces to the DBS. This query system is based on a query language that hides the complexity of the underlying database structure by discovering the join conditions between database tables. This provides a way of querying the system that is simple and straightforward for CMS data managers and physicists to use without requiring knowledge of the database tables or keys. The DBS Query Language uses the ANTLR tool to build the input query parser and tokenizer, followed by a query builder that uses a graph representation of the DBS schema to construct the SQL query sent to underlying database. We will describe the design of the query system, provide details of the language components and overview of how this component fits into the overall data discovery system architecture.

  20. The CMS central hadron calorimeter

    SciTech Connect

    Freeman, J.; E892 Collaboration

    1996-12-31

    The CMS central hadron calorimeter is a copper absorber/ scintillator sampling structure. We describe design choices that led us to this concept, details of the mechanical and optical structure, and test beam results. We discuss calibration techniques, and finally the anticipated construction schedule.

  1. Wet Winding Improves Coil Encapsulation

    NASA Technical Reports Server (NTRS)

    Hill, A. J.

    1987-01-01

    Wet-winding process encapsulates electrical coils more uniformily than conventional processes. Process requires no vacuum pump and adapts easily to existing winding machines. Encapsulant applied to each layer of wire as soon as added to coil. Wet-winding process eliminates voids, giving more uniformly encapsulated coil.

  2. Design of printed circuit coils

    NASA Technical Reports Server (NTRS)

    Higgins, W. T.

    1969-01-01

    Spiral-like coil is printed with several extra turns which increase the realizable coil inductance. Included are shorting connections which not only short the extra turns, but also short out several turns of the main body. Coil tuning is accomplished by removing the shorts until the desired inductance is obtained.

  3. Functional aortic stiffness: role of CD4+ T lymphocytes

    PubMed Central

    Majeed, Beenish A.; Eberson, Lance S.; Tawinwung, Supannikar; Larmonier, Nicolas; Secomb, Timothy W.; Larson, Douglas F.

    2015-01-01

    The immune system is suggested to be essential in vascular remodeling and stiffening. To study the dependence upon lymphocytes in vascular stiffening, we compared an angiotensin II-model of vascular stiffening in normal C57BL/6J mice with lymphocyte-deficient RAG 1−/− mice and additionally characterized the component of vascular stiffness due to vasoconstriction vs. vascular remodeling. Chronic angiotensin II increased aortic pulse wave velocity, effective wall stiffness, and effective Young's modulus in C57BL/6J mice by three-fold but caused no change in the RAG 1−/− mice. These functional measurements were supported by aortic morphometric analysis. Adoptive transfer of CD4+ T helper lymphocytes restored the angiotensin II-mediated aortic stiffening in the RAG 1−/− mice. In order to account for the hydraulic vs. material effects of angiotensin II on pulse wave velocity, subcutaneous osmotic pumps were removed after 21 days of angiotensin II-infusion in the WT mice to achieve normotensive values. The pulse wave velocity (PWV) decreased from three- to two-fold above baseline values up to 7 days following pump removal. This study supports the pivotal role of the CD4+ T-lymphocytes in angiotensin II-mediated vascular stiffening and that angiotensin II-mediated aortic stiffening is due to the additive effect of active vascular smooth muscle vasoconstriction and vascular remodeling. PMID:26379554

  4. Coiled-coil networking shapes cell molecular machinery

    PubMed Central

    Wang, Yongqiang; Zhang, Xinlei; Zhang, Hong; Lu, Yi; Huang, Haolong; Dong, Xiaoxi; Chen, Jinan; Dong, Jiuhong; Yang, Xiao; Hang, Haiying; Jiang, Taijiao

    2012-01-01

    The highly abundant α-helical coiled-coil motif not only mediates crucial protein–protein interactions in the cell but is also an attractive scaffold in synthetic biology and material science and a potential target for disease intervention. Therefore a systematic understanding of the coiled-coil interactions (CCIs) at the organismal level would help unravel the full spectrum of the biological function of this interaction motif and facilitate its application in therapeutics. We report the first identified genome-wide CCI network in Saccharomyces cerevisiae, which consists of 3495 pair-wise interactions among 598 predicted coiled-coil regions. Computational analysis revealed that the CCI network is specifically and functionally organized and extensively involved in the organization of cell machinery. We further show that CCIs play a critical role in the assembly of the kinetochore, and disruption of the CCI network leads to defects in kinetochore assembly and cell division. The CCI network identified in this study is a valuable resource for systematic characterization of coiled coils in the shaping and regulation of a host of cellular machineries and provides a basis for the utilization of coiled coils as domain-based probes for network perturbation and pharmacological applications. PMID:22875988

  5. Plasticity of human CD4 T cell subsets.

    PubMed

    Geginat, Jens; Paroni, Moira; Maglie, Stefano; Alfen, Johanna Sophie; Kastirr, Ilko; Gruarin, Paola; De Simone, Marco; Pagani, Massimiliano; Abrignani, Sergio

    2014-01-01

    Human beings are exposed to a variety of different pathogens, which induce tailored immune responses and consequently generate highly diverse populations of pathogen-specific T cells. CD4(+) T cells have a central role in adaptive immunity, since they provide essential help for both cytotoxic T cell- and antibody-mediated responses. In addition, CD4(+) regulatory T cells are required to maintain self-tolerance and to inhibit immune responses that could damage the host. Initially, two subsets of CD4(+) helper T cells were identified that secrete characteristic effector cytokines and mediate responses against different types of pathogens, i.e., IFN-γ secreting Th1 cells that fight intracellular pathogens, and IL-4 producing Th2 cells that target extracellular parasites. It is now well established that this dichotomy is insufficient to describe the complexity of CD4(+) T cell differentiation, and in particular the human CD4 compartment contains a myriad of T cell subsets with characteristic capacities to produce cytokines and to home to involved tissues. Moreover, it has become increasingly clear that these T cell subsets are not all terminally differentiated cells, but that the majority is plastic and that in particular central memory T cells can acquire different properties and functions in secondary immune responses. In addition, there is compelling evidence that helper T cells can acquire regulatory functions upon chronic stimulation in inflamed tissues. The plasticity of antigen-experienced human T cell subsets is highly relevant for translational medicine, since it opens new perspectives for immune-modulatory therapies for chronic infections, autoimmune diseases, and cancer. PMID:25566245

  6. Plasticity of Human CD4 T Cell Subsets

    PubMed Central

    Geginat, Jens; Paroni, Moira; Maglie, Stefano; Alfen, Johanna Sophie; Kastirr, Ilko; Gruarin, Paola; De Simone, Marco; Pagani, Massimiliano; Abrignani, Sergio

    2014-01-01

    Human beings are exposed to a variety of different pathogens, which induce tailored immune responses and consequently generate highly diverse populations of pathogen-specific T cells. CD4+ T cells have a central role in adaptive immunity, since they provide essential help for both cytotoxic T cell- and antibody-mediated responses. In addition, CD4+ regulatory T cells are required to maintain self-tolerance and to inhibit immune responses that could damage the host. Initially, two subsets of CD4+ helper T cells were identified that secrete characteristic effector cytokines and mediate responses against different types of pathogens, i.e., IFN-γ secreting Th1 cells that fight intracellular pathogens, and IL-4 producing Th2 cells that target extracellular parasites. It is now well established that this dichotomy is insufficient to describe the complexity of CD4+ T cell differentiation, and in particular the human CD4 compartment contains a myriad of T cell subsets with characteristic capacities to produce cytokines and to home to involved tissues. Moreover, it has become increasingly clear that these T cell subsets are not all terminally differentiated cells, but that the majority is plastic and that in particular central memory T cells can acquire different properties and functions in secondary immune responses. In addition, there is compelling evidence that helper T cells can acquire regulatory functions upon chronic stimulation in inflamed tissues. The plasticity of antigen-experienced human T cell subsets is highly relevant for translational medicine, since it opens new perspectives for immune-modulatory therapies for chronic infections, autoimmune diseases, and cancer. PMID:25566245

  7. Virtual data in CMS production

    SciTech Connect

    Arbree, A. et al.

    2004-08-26

    Initial applications of the GriPhyN Chimera Virtual Data System have been performed within the context of CMS Production of Monte Carlo Simulated Data. The GriPhyN Chimera system consists of four primary components: (1) a Virtual Data Language, which is used to describe virtual data products, (2) a Virtual Data Catalog, which is used to store virtual data entries, (3) an Abstract Planner, which resolves all dependencies of a particular virtual data product and forms a location and existence independent plan, (4) a Concrete Planner, which maps an abstract, logical plan onto concrete, physical grid resources accounting for staging in/out files and publishing results to a replica location service. A CMS Workflow Planner, MCRunJob, is used to generate virtual data products using the Virtual Data Language. Subsequently, a prototype workflow manager, known as WorkRunner, is used to schedule the instantiation of virtual data products across a grid.

  8. The CMS high level trigger

    NASA Astrophysics Data System (ADS)

    Gori, Valentina

    2014-05-01

    The CMS experiment has been designed with a 2-level trigger system: the Level 1 Trigger, implemented on custom-designed electronics, and the High Level Trigger (HLT), a streamlined version of the CMS offline reconstruction software running on a computer farm. A software trigger system requires a tradeoff between the complexity of the algorithms running on the available computing power, the sustainable output rate, and the selection efficiency. Here we will present the performance of the main triggers used during the 2012 data taking, ranging from simpler single-object selections to more complex algorithms combining different objects, and applying analysis-level reconstruction and selection. We will discuss the optimisation of the triggers and the specific techniques to cope with the increasing LHC pile-up, reducing its impact on the physics performance.

  9. The CMS High Level Trigger

    NASA Astrophysics Data System (ADS)

    Trocino, Daniele

    2014-06-01

    The CMS experiment has been designed with a two-level trigger system: the Level-1 Trigger, implemented in custom-designed electronics, and the High-Level Trigger (HLT), a streamlined version of the CMS offline reconstruction software running on a computer farm. A software trigger system requires a tradeoff between the complexity of the algorithms running with the available computing power, the sustainable output rate, and the selection efficiency. We present the performance of the main triggers used during the 2012 data taking, ranging from simple single-object selections to more complex algorithms combining different objects, and applying analysis-level reconstruction and selection. We discuss the optimisation of the trigger and the specific techniques to cope with the increasing LHC pile-up, reducing its impact on the physics performance.

  10. The CMS pixel luminosity telescope

    NASA Astrophysics Data System (ADS)

    Kornmayer, A.

    2016-07-01

    The Pixel Luminosity Telescope (PLT) is a new complement to the CMS detector for the LHC Run II data taking period. It consists of eight 3-layer telescopes based on silicon pixel detectors that are placed around the beam pipe on each end of CMS viewing the interaction point at small angle. A fast 3-fold coincidence of the pixel planes in each telescope will provide a bunch-by-bunch measurement of the luminosity. Particle tracking allows collision products to be distinguished from beam background, provides a self-alignment of the detectors, and a continuous in-time monitoring of the efficiency of each telescope plane. The PLT is an independent luminometer, essential to enhance the robustness on the measurement of the delivered luminosity and to reduce its systematic uncertainties. This will allow to determine production cross-sections, and hence couplings, with high precision and to set more stringent limits on new particle production.

  11. The CMS integration grid testbed

    SciTech Connect

    Graham, Gregory E.

    2004-08-26

    The CMS Integration Grid Testbed (IGT) comprises USCMS Tier-1 and Tier-2 hardware at the following sites: the California Institute of Technology, Fermi National Accelerator Laboratory, the University of California at San Diego, and the University of Florida at Gainesville. The IGT runs jobs using the Globus Toolkit with a DAGMan and Condor-G front end. The virtual organization (VO) is managed using VO management scripts from the European Data Grid (EDG). Gridwide monitoring is accomplished using local tools such as Ganglia interfaced into the Globus Metadata Directory Service (MDS) and the agent based Mona Lisa. Domain specific software is packaged and installed using the Distribution After Release (DAR) tool of CMS, while middleware under the auspices of the Virtual Data Toolkit (VDT) is distributed using Pacman. During a continuous two month span in Fall of 2002, over 1 million official CMS GEANT based Monte Carlo events were generated and returned to CERN for analysis while being demonstrated at SC2002. In this paper, we describe the process that led to one of the world's first continuously available, functioning grids.

  12. Upgrade of the CMS tracker

    NASA Astrophysics Data System (ADS)

    Tricomi, A.

    2014-03-01

    The LHC machine is planning an upgrade program which will smoothly bring the luminosity up to or above 5 × 1034 cm-2s-1 sometimes after 2020, to possibly reach an integrated luminosity of 3000 fb-1 at the end of that decade. The foreseen increases of both the instantaneous and the integrated luminosity by the LHC during the next ten years will necessitate a stepwise upgrade of the CMS tracking detector. During the extended end-of-year shutdown 2016-2017 the pixel detector will be exchanged with a new one. The so-called Phase1 Pixel foresees one additional barrel layer and one additional end-cap disk, a new readout chip, reduction of material, and the installation of more efficient cooling and powering systems. In the so-called Phase2, when LHC will reach the High Luminosity (HL-LHC) phase, CMS will need a completely new Tracker detector, in order to fully exploit the high-demanding operating conditions and the delivered luminosity. The new Tracker should have also trigger capabilities. To achieve such goals, R&D activities are ongoing to explore options and develop solutions that would allow including tracking information at Level-1. The design choices for the CMS pixel and outer tracker upgrades are discussed along with some highlights of the R&D activities.

  13. Distributed data transfers in CMS

    NASA Astrophysics Data System (ADS)

    Magini, Nicolo; Ratnikova, Natalia; Rossman, Paul; Sánchez-Hernández, Alberto; Wildish, Tony

    2011-12-01

    The multi-tiered computing infrastructure of the CMS experiment at the LHC depends on the reliable and fast transfer of data between the different CMS computing sites. Data have to be transferred from the Tier-0 to the Tier-l sites for archival in a timely manner to avoid overflowing disk buffers at CERN. Data have to be transferred in bursts to all Tier-2 level sites for analysis as well as synchronized between the different Tier-l sites. The data transfer system is the key ingredient which enables the optimal usage of all distributed resources. The operation of the transfer system consists of monitoring and debugging of transfer issues to guarantee a timely delivery of data to all corners of the CMS computing infrastructure. Further task of transfer operation is to guarantee the consistency of the data at all sites, both on disk and on tape. Procedures to verify the consistency and to debug and repair problems will be discussed.

  14. The Automotive Ignition Coil

    NASA Technical Reports Server (NTRS)

    Darnell, T H

    1932-01-01

    This report gives the results of a series of measurements on the secondary voltage induced in an ignition coil of typical construction under a variety of operating conditions. These results show that the theoretical predictions hitherto made as to the behavior of this type of apparatus are in satisfactory agreement with the observed facts. The large mass of data obtained is here published both for the use of other investigators who may wish to compare them with other theoretical predictions and for the use of automotive engineers who will here find definite experimental results showing the effect of secondary capacity and resistance on the crest voltage produced by ignition apparatus.

  15. Designing with null flux coils

    SciTech Connect

    Davey, K.R.

    1997-09-01

    Null flux were suggested by Danby and Powell in the late 1960`s as a useful means for realizing induced lift with little drag. As an array of alternating magnets is translated past a set of null flux coils, the currents induced in these coils act to vertically center the magnets on those coils. At present, one Japanese MAGLEV system company and two American-based companies are employing either null flux or flux eliminating coils in their design for high speed magnetically levitated transportation. The principle question addressed in paper is: what is the proper choice of coil length to magnet length in a null flux system? A generic analysis in the time and frequency domain is laid out with the intent of showing the optimal design specification in terms of coil parameters.

  16. Distinct Translational Control in CD4+ T Cell Subsets

    PubMed Central

    Yurchenko, Ekaterina; Zheng, Lei; Gandin, Valentina; Topisirovic, Ivan; Li, Shui; Wagner, Carston R.; Sonenberg, Nahum; Piccirillo, Ciriaco A.

    2013-01-01

    Regulatory T cells expressing the transcription factor Foxp3 play indispensable roles for the induction and maintenance of immunological self-tolerance and immune homeostasis. Genome-wide mRNA expression studies have defined canonical signatures of T cell subsets. Changes in steady-state mRNA levels, however, often do not reflect those of corresponding proteins due to post-transcriptional mechanisms including mRNA translation. Here, we unveil a unique translational signature, contrasting CD4+Foxp3+ regulatory T (TFoxp3+) and CD4+Foxp3− non-regulatory T (TFoxp3−) cells, which imprints subset-specific protein expression. We further show that translation of eukaryotic translation initiation factor 4E (eIF4E) is induced during T cell activation and, in turn, regulates translation of cell cycle related mRNAs and proliferation in both TFoxp3− and TFoxp3+ cells. Unexpectedly, eIF4E also affects Foxp3 expression and thereby lineage identity. Thus, mRNA–specific translational control directs both common and distinct cellular processes in CD4+ T cell subsets. PMID:23658533

  17. Enabling opportunistic resources for CMS Computing Operations

    NASA Astrophysics Data System (ADS)

    Hufnagel, D.; CMS Collaboration

    2015-12-01

    With the increased pressure on computing brought by the higher energy and luminosity from the LHC in Run 2, CMS Computing Operations expects to require the ability to utilize opportunistic resources resources not owned by, or a priori configured for CMS to meet peak demands. In addition to our dedicated resources we look to add computing resources from non CMS grids, cloud resources, and national supercomputing centers. CMS uses the HTCondor/glideinWMS job submission infrastructure for all its batch processing, so such resources will need to be transparently integrated into its glideinWMS pool. Bosco and parrot wrappers are used to enable access and bring the CMS environment into these non CMS resources. Here we describe our strategy to supplement our native capabilities with opportunistic resources and our experience so far using them.

  18. CMS Centres Worldwide - a New Collaborative Infrastructure

    NASA Astrophysics Data System (ADS)

    Taylor, Lucas

    2011-12-01

    The CMS Experiment at the LHC has established a network of more than fifty inter-connected "CMS Centres" at CERN and in institutes in the Americas, Asia, Australasia, and Europe. These facilities are used by people doing CMS detector and computing grid operations, remote shifts, data quality monitoring and analysis, as well as education and outreach. We present the computing, software, and collaborative tools and videoconferencing systems. These include permanently running "telepresence" video links (hardware-based H.323, EVO and Vidyo), Webcasts, and generic Web tools such as CMS-TV for broadcasting live monitoring and outreach information. Being Web-based and experiment-independent, these systems could easily be extended to other organizations. We describe the experiences of using CMS Centres Worldwide in the CMS data-taking operations as well as for major media events with several hundred TV channels, radio stations, and many more press journalists simultaneously around the world.

  19. CMS Full Simulation for Run-2

    NASA Astrophysics Data System (ADS)

    Hildreth, M.; Ivanchenko, V. N.; Lange, D. J.; Kortelainen, M. J.

    2015-12-01

    During LHC shutdown between run-1 and run-2 intensive developments were carried out to improve performance of CMS simulation. For physics improvements migration from Geant4 9.4p03 to Geant4 10.0p02 has been performed. CPU performance has been improved by introduction of the Russian roulette method inside CMS calorimeters, optimization of CMS simulation sub-libraries, and usage of statics build of the simulation executable. As a result of these efforts, CMS simulation has been speeded up by about factor two. In this work we provide description of updates for different software components of CMS simulation. Development of a multi-threaded (MT) simulation approach for CMS will be also discuss.

  20. Readiness of CMS Simulation Towards LHC Startup

    SciTech Connect

    Banerjee, Sunanda; /Fermilab

    2007-11-01

    CMS experiment has used detector simulation software in its conceptual as well as technical design. With the detector construction near its completion, the role of simulation has changed toward understanding collision data to be collected by CMS in near future. CMS simulation software is becoming a data driven, realistic and accurate Monte Carlo program. The software architecture is described with some detail of the framework as well as detector specific components. Performance issues are discussed as well.

  1. The CMS Journey to LHC Physics

    ScienceCinema

    None

    2011-10-06

    An overview of the design, the construction and physics of CMS will be given. A history of construction, encompassing the R&D; and challenges faced over the last decade and a half, will be recalled using selected examples. CMS is currently in the final stages of installation and commissioning is gathering pace. After a short status report of where CMS stands today some of the expected (great) physics to come will be outlined. * Tea & coffee will be served at 16:00.

  2. The CMS Journey to LHC Physics

    SciTech Connect

    2011-02-09

    An overview of the design, the construction and physics of CMS will be given. A history of construction, encompassing the R&D; and challenges faced over the last decade and a half, will be recalled using selected examples. CMS is currently in the final stages of installation and commissioning is gathering pace. After a short status report of where CMS stands today some of the expected (great) physics to come will be outlined. * Tea & coffee will be served at 16:00.

  3. Design of a conduction-cooled 4 T superconducting racetrack for a multi-field coupling measurement system

    NASA Astrophysics Data System (ADS)

    Chen, Yu-Quan; Ma, Li-Zhen; Wu, Wei; Guan, Ming-Zhi; Wu, Bei-Min; Mei, En-Ming; Xin, Can-Jie

    2015-12-01

    A conduction-cooled superconducting magnet producing a transverse field of 4 T has been designed for a new generation multi-field coupling measurement system, which will be used to study the mechanical behavior of superconducting samples at cryogenic temperatures and intense magnetic fields. A compact cryostat with a two-stage GM cryocooler is designed and manufactured for the superconducting magnet. The magnet is composed of a pair of flat racetrack coils wound by NbTi/Cu superconducting composite wires, a copper and stainless steel combinational former and two Bi2Sr2CaCu2Oy superconducting current leads. The two coils are connected in series and can be powered with a single power supply. In order to support the high stress and attain uniform thermal distribution in the superconducting magnet, a detailed finite element (FE) analysis has been performed. The results indicate that in the operating status the designed magnet system can sufficiently bear the electromagnetic forces and has a uniform temperature distribution. Supported by National Natural Science Foundation of China (11327802, 11302225), China Postdoctoral Science Foundation (2014M560820) and National Scholarship Foundation of China (201404910172)

  4. Triple Halo Coil: Development and Comparison with Other TMS Coils

    NASA Astrophysics Data System (ADS)

    Rastogi, Priyam; Hadimani, Ravi; Jiles, David

    Transcranial Magnetic Stimulation (TMS) is a non-invasive stimulation technique that can be used for the treatment of various neurological disorders such as Parkinson's Disease, PTSD, TBI and anxiety by regulating synaptic activity. TMS is FDA approved for the treatment of major depressive disorder. There is a critical need to develop deep TMS coils that can stimulate deeper regions of the brain without excessively stimulating the cortex in order to provide an alternative to surgical methods. We have developed a novel multi-coil configuration called ``Triple Halo Coil'' (THC) that can stimulate deep brain regions. Investigation of induced electric and magnetic field in these regions have been achieved by computer modelling. Comparison of the results due to THC configuration have been conducted with other TMS coils such as ``Halo Coil'', circular coil and ``Figure of Eight'' coil. There was an improvement of more than 15 times in the strength of magnetic field, induced by THC configuration at 10 cm below the vertex of the head when compared with the ``Figure of Eight'' coil alone. Carver Charitable Trust.

  5. Micropatterning of costimulatory ligands enhances CD4+ T cell function

    PubMed Central

    Shen, Keyue; Thomas, V. Kaye; Dustin, Michael L.; Kam, Lance C.

    2008-01-01

    Spatial organization of signaling complexes is a defining characteristic of the immunological synapse (IS), but its impact on cell communication is unclear. In T cell–APC pairs, more IL-2 is produced when CD28 clusters are segregated from central supramolecular activation cluster (cSMAC)-localized CD3 and into the IS periphery. However, it is not clear in these cellular experiments whether the increased IL-2 is driven by the pattern itself or by upstream events that precipitate the patterns. In this article, we recapitulate key features of physiological synapses using planar costimulation arrays containing antibodies against CD3 and CD28, surrounded by ICAM-1, created by combining multiple rounds of microcontact printing on a single surface. Naïve T cells traverse these arrays, stopping at features of anti-CD3 antibodies and forming a stable synapse. We directly demonstrate that presenting anti-CD28 in the cell periphery, surrounding an anti-CD3 feature, enhances IL-2 secretion by naïve CD4+ T cells compared with having these signals combined in the center of the IS. This increased cytokine production correlates with NF-κB translocation and requires PKB/Akt signaling. The ability to arbitrarily and independently control the locations of anti-CD3 and anti-CD28 offered the opportunity to examine patterns not precisely attainable in cell–cell interfaces. With these patterns, we show that the peripheral presentation of CD28 has a larger impact on IL-2 secretion than CD3 colocalization/segregation. PMID:18505845

  6. 26 CFR 1.475(a)-4T - Valuation safe harbor (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 6 2012-04-01 2012-04-01 false Valuation safe harbor (temporary). 1.475(a)-4T Section 1.475(a)-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Inventories § 1.475(a)-4T Valuation safe harbor (temporary). (a) through (d)(4) introductory text...

  7. 26 CFR 1.905-4T - Notification of foreign tax redetermination (temporary).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 9 2014-04-01 2014-04-01 false Notification of foreign tax redetermination (temporary). 1.905-4T Section 1.905-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Income from Sources Without the United States § 1.905-4T Notification of foreign...

  8. 26 CFR 1.905-4T - Notification of foreign tax redetermination (temporary).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 9 2013-04-01 2013-04-01 false Notification of foreign tax redetermination (temporary). 1.905-4T Section 1.905-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Income from Sources Without the United States § 1.905-4T Notification of foreign...

  9. 26 CFR 1.905-4T - Notification of foreign tax redetermination (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 9 2012-04-01 2012-04-01 false Notification of foreign tax redetermination (temporary). 1.905-4T Section 1.905-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Income from Sources Without the United States § 1.905-4T Notification of foreign...

  10. 26 CFR 1.905-4T - Notification of foreign tax redetermination (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 9 2010-04-01 2010-04-01 false Notification of foreign tax redetermination (temporary). 1.905-4T Section 1.905-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Income from Sources Without the United States § 1.905-4T Notification of foreign...

  11. 26 CFR 1.6038D-4T - Information required to be reported (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 13 2012-04-01 2012-04-01 false Information required to be reported (temporary). 1.6038D-4T Section 1.6038D-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Information Returns § 1.6038D-4T Information required to be reported (temporary)....

  12. A Parallel Coiled-Coil Tetramer with Offset Helices

    SciTech Connect

    Liu,J.; Deng, Y.; Zheng, Q.; Cheng, C.; Kallenbach, N.; Lu, M.

    2006-01-01

    Specific helix-helix interactions are fundamental in assembling the native state of proteins and in protein-protein interfaces. Coiled coils afford a unique model system for elucidating principles of molecular recognition between {alpha} helices. The coiled-coil fold is specified by a characteristic seven amino acid repeat containing hydrophobic residues at the first (a) and fourth (d) positions. Nonpolar side chains spaced three and four residues apart are referred to as the 3-4 hydrophobic repeat. The presence of apolar amino acids at the e or g positions (corresponding to a 3-3-1 hydrophobic repeat) can provide new possibilities for close-packing of {alpha}-helices that includes examples such as the lac repressor tetramerization domain. Here we demonstrate that an unprecedented coiled-coil interface results from replacement of three charged residues at the e positions in the dimeric GCN4 leucine zipper by nonpolar valine side chains. Equilibrium circular dichroism and analytical ultracentrifugation studies indicate that the valine-containing mutant forms a discrete {alpha}-helical tetramer with a significantly higher stability than the parent leucine-zipper molecule. The 1.35 {angstrom} resolution crystal structure of the tetramer reveals a parallel four-stranded coiled coil with a three-residue interhelical offset. The local packing geometry of the three hydrophobic positions in the tetramer conformation is completely different from that seen in classical tetrameric structures yet bears resemblance to that in three-stranded coiled coils. These studies demonstrate that distinct van der Waals interactions beyond the a and d side chains can generate a diverse set of helix-helix interfaces and three-dimensional supercoil structures.

  13. Replaceable Sleeve Protects Welder Coil

    NASA Technical Reports Server (NTRS)

    Baker, W. L.; Simpson, C., E.

    1983-01-01

    New replaceable carbon insert for deflection coil in electron-beam welder promises to decrease maintenance costs. Inserts made from materials other than carbon (not yet tried) are less expensive, thus reducing costs even further. With carbon insert, deflection coils last longer and are easier to maintain.

  14. Magnet Coil Shorted Turn Detector

    SciTech Connect

    Dinkel, J.A.; Biggs, J.E.

    1994-03-01

    The Magnet Coil Shorted Turn Detector has been developed to facilitate the location of shorted turns in magnet coils. Finding these shorted turns is necessary to determine failure modes that are a necessary step in developing future production techniques. Up to this point, coils with shorted turns had the insulation burned off without the fault having been located. This disassembly process destroyed any chance of being able to find the fault. In order to maintain a flux balance in a coupled system such as a magnet coil, the current in a shorted turn must be opposed to the incident current. If the direction of the current in each conductor can be measured relative to the incident current, then the exact location of the short can be determined. In this device, an AC voltage is applied to the magnet under test. A small hand held B-dot pickup coil monitors the magnetic field produced by current in the individual magnet conductors. The relative phase of this pickup coil voltage is compared to a reference signal derived from the input current to detect a current reversal as the B-dot pickup coil is swept over the conductors of the coil under test. This technique however, is limited to only those conductors that are accessible to the hand held probe.

  15. The CMS tracker control system

    NASA Astrophysics Data System (ADS)

    Dierlamm, A.; Dirkes, G. H.; Fahrer, M.; Frey, M.; Hartmann, F.; Masetti, L.; Militaru, O.; Shah, S. Y.; Stringer, R.; Tsirou, A.

    2008-07-01

    The Tracker Control System (TCS) is a distributed control software to operate about 2000 power supplies for the silicon modules of the CMS Tracker and monitor its environmental sensors. TCS must thus be able to handle about 104 power supply parameters, about 103 environmental probes from the Programmable Logic Controllers of the Tracker Safety System (TSS), about 105 parameters read via DAQ from the DCUs in all front end hybrids and from CCUs in all control groups. TCS is built on top of an industrial SCADA program (PVSS) extended with a framework developed at CERN (JCOP) and used by all LHC experiments. The logical partitioning of the detector is reflected in the hierarchical structure of the TCS, where commands move down to the individual hardware devices, while states are reported up to the root which is interfaced to the broader CMS control system. The system computes and continuously monitors the mean and maximum values of critical parameters and updates the percentage of currently operating hardware. Automatic procedures switch off selected parts of the detector using detailed granularity and avoiding widespread TSS intervention.

  16. 42 CFR 422.510 - Termination of contract by CMS.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... (CONTINUED) MEDICARE PROGRAM MEDICARE ADVANTAGE PROGRAM Application Procedures and Contracts for Medicare Advantage Organizations § 422.510 Termination of contract by CMS. (a) Termination by CMS. CMS may at...

  17. The Coil Method in Contemporary Ceramics

    ERIC Educational Resources Information Center

    Nigrosh, Leon I.

    1976-01-01

    For centuries coil building has been the primary method of making pottery the world over. Many classrooms still reflect this preference for symmetrical coil building. Describes coil building and what forms can be made from it. (Author/RK)

  18. Coiled-coil intermediate filament stutter instability and molecular unfolding.

    PubMed

    Arslan, Melis; Qin, Zhao; Buehler, Markus J

    2011-05-01

    Intermediate filaments (IFs) are the key components of cytoskeleton in eukaryotic cells and are critical for cell mechanics. The building block of IFs is a coiled-coil alpha-helical dimer, consisting of several domains that include linkers and other structural discontinuities. One of the discontinuities in the dimer's coiled-coil region is the so-called 'stutter' region. The stutter is a region where a variation of the amino acid sequence pattern from other parts of the alpha-helical domains of the protein is found. It was suggested in earlier works that due to this sequence variation, the perfect coiled-coil arrangement ceases to exist. Here, we show using explicit water molecular dynamics and well-tempered metadynamics that for the coil2 domain of vimentin IFs the stutter is more stable in a non-alpha-helical, unfolded state. This causes a local structural disturbance in the alpha helix, which has a global effect on the nanomechanics of the structure. Our analysis suggests that the stutter features an enhanced tendency to unfolding even under the absence of external forces, implying a much greater structural instability than previously assumed. As a result it features a smaller local bending stiffness than other segments and presents a seed for the initiation of molecular bending and unfolding at large deformation. PMID:21516532

  19. The diverse use of clouds by CMS

    DOE PAGESBeta

    Andronis, Anastasios; Bauer, Daniela; Chaze, Olivier; Colling, David; Dobson, Marc; Fayer, Simon; Girone, Maria; Grandi, Claudio; Huffman, Adam; Hufnagel, Dirk; et al

    2015-01-01

    The resources CMS is using are increasingly being offered as clouds. In Run 2 of the LHC the majority of CMS CERN resources, both in Meyrin and at the Wigner Computing Centre, will be presented as cloud resources on which CMS will have to build its own infrastructure. This infrastructure will need to run all of the CMS workflows including: Tier 0, production and user analysis. In addition, the CMS High Level Trigger will provide a compute resource comparable in scale to the total offered by the CMS Tier 1 sites, when it is not running as part of themore » trigger system. During these periods a cloud infrastructure will be overlaid on this resource, making it accessible for general CMS use. Finally, CMS is starting to utilise cloud resources being offered by individual institutes and is gaining experience to facilitate the use of opportunistically available cloud resources. Lastly, we present a snap shot of this infrastructure and its operation at the time of the CHEP2015 conference.« less

  20. The diverse use of clouds by CMS

    SciTech Connect

    Andronis, Anastasios; Bauer, Daniela; Chaze, Olivier; Colling, David; Dobson, Marc; Fayer, Simon; Girone, Maria; Grandi, Claudio; Huffman, Adam; Hufnagel, Dirk; Khan, Farrukh Aftab; Lahiff, Andrew; McCrae, Alison; Rand, Duncan; Sgaravatto, Massimo; Tiradani, Anthony; Zhang, Xiaomei

    2015-01-01

    The resources CMS is using are increasingly being offered as clouds. In Run 2 of the LHC the majority of CMS CERN resources, both in Meyrin and at the Wigner Computing Centre, will be presented as cloud resources on which CMS will have to build its own infrastructure. This infrastructure will need to run all of the CMS workflows including: Tier 0, production and user analysis. In addition, the CMS High Level Trigger will provide a compute resource comparable in scale to the total offered by the CMS Tier 1 sites, when it is not running as part of the trigger system. During these periods a cloud infrastructure will be overlaid on this resource, making it accessible for general CMS use. Finally, CMS is starting to utilise cloud resources being offered by individual institutes and is gaining experience to facilitate the use of opportunistically available cloud resources. Lastly, we present a snap shot of this infrastructure and its operation at the time of the CHEP2015 conference.

  1. The Diverse use of Clouds by CMS

    NASA Astrophysics Data System (ADS)

    Andronis, Anastasios; Bauer, Daniela; Chaze, Olivier; Colling, David; Dobson, Marc; Fayer, Simon; Girone, Maria; Grandi, Claudio; Huffman, Adam; Hufnagel, Dirk; Aftab Khan, Farrukh; Lahiff, Andrew; McCrae, Alison; Rand, Duncan; Sgaravatto, Massimo; Tiradani, Anthony; Zhang, Xiaomei

    2015-12-01

    The resources CMS is using are increasingly being offered as clouds. In Run 2 of the LHC the majority of CMS CERN resources, both in Meyrin and at the Wigner Computing Centre, will be presented as cloud resources on which CMS will have to build its own infrastructure. This infrastructure will need to run all of the CMS workflows including: Tier 0, production and user analysis. In addition, the CMS High Level Trigger will provide a compute resource comparable in scale to the total offered by the CMS Tier 1 sites, when it is not running as part of the trigger system. During these periods a cloud infrastructure will be overlaid on this resource, making it accessible for general CMS use. Finally, CMS is starting to utilise cloud resources being offered by individual institutes and is gaining experience to facilitate the use of opportunistically available cloud resources. We present a snap shot of this infrastructure and its operation at the time of the CHEP2015 conference.

  2. CMS: The Midwife of Instruction and Learning.

    ERIC Educational Resources Information Center

    Maxwell, Valerie

    1989-01-01

    Gifted students may exhibit a deficit in ability to follow a sequence of verbal instructions, termed Cognition of SeMantic Systems (CMS). Three types of low-CMS students are described, and counseling strategies are outlined. Achievement of academic success and emotional health calls for teachers to build students' self-esteem and be patient. (JDD)

  3. The Diverse use of Clouds by CMS

    SciTech Connect

    Andronis, Anastasios; Bauer, Daniela; Chaze, Olivier; Colling, David; Dobson, Marc; Fayer, Simon; Girone, Maria; Grandi, Claudio; Huffman, Adam; Hufnagel, Dirk; Khan, Farrukh Aftab; Lahiff, Andrew; McCrae, Alison; Rand, Duncan; Sgaravatto, Massimo; Tiradani, Anthony; Zhang, Xiaomei

    2015-12-23

    The resources CMS is using are increasingly being offered as clouds. In Run 2 of the LHC the majority of CMS CERN resources, both in Meyrin and at the Wigner Computing Centre, will be presented as cloud resources on which CMS will have to build its own infrastructure. This infrastructure will need to run all of the CMS workflows including: Tier 0, production and user analysis. In addition, the CMS High Level Trigger will provide a compute resource comparable in scale to the total offered by the CMS Tier 1 sites, when it is not running as part of the trigger system. During these periods a cloud infrastructure will be overlaid on this resource, making it accessible for general CMS use. Finally, CMS is starting to utilise cloud resources being offered by individual institutes and is gaining experience to facilitate the use of opportunistically available cloud resources.We present a snap shot of this infrastructure and its operation at the time of the CHEP2015 conference.

  4. Forward Physics Results from ATLAS and CMS

    NASA Astrophysics Data System (ADS)

    Sen, Sercan

    2013-12-01

    We present recent forward and diffractive physics results from ATLAS and CMS experiments. Mainly, the physics results on diffraction, underlying event at forward rapidity and forward jets measurements are discussed. Also, using the combined CMS and TOTEM detectors, we show the first event candidate for central jets production with two leading protons detected in the TOTEM Roman Pot stations.

  5. Final Technical Report CMS fast optical calorimetry

    SciTech Connect

    Winn, David R.

    2012-07-12

    This is the final report of CMS FAST OPTICAL CALORIMETRY, a grant to Fairfield University for development, construction, installation and operation of the forward calorimeter on CMS, and for upgrades of the forward and endcap calorimeters for higher luminosity and radiation damage amelioration.

  6. The Status of the Cms Experiment

    NASA Astrophysics Data System (ADS)

    Green, Dan

    The CMS experiment was completely assembled in the fall of 2008 after a decade of design, construction and installation. During the last two years, cosmic ray data were taken on a regular basis. These data have enabled CMS to align the detector components, both spatially and temporally. Initial use of muons has also established the relative alignment of the CMS tracking and muon systems. In addition, the CMS calorimetry has been crosschecked with test beam data, thus providing an initial energy calibration of CMS calorimetry to about 5%. The CMS magnet has been powered and field mapped. The trigger and data acquisition systems have been installed and run at full speed. The tiered data analysis system has been exercised at full design bandwidth for Tier0, Tier1 and Tier2 sites. Monte Carlo simulation of the CMS detector has been constructed at a detailed geometric level and has been tuned to test beam and other production data to provide a realistic model of the CMS detector prior to first collisions.

  7. Optimized quadrature surface coil designs

    PubMed Central

    Kumar, Ananda; Bottomley, Paul A.

    2008-01-01

    Background Quadrature surface MRI/MRS detectors comprised of circular loop and figure-8 or butterfly-shaped coils offer improved signal-to-noise-ratios (SNR) compared to single surface coils, and reduced power and specific absorption rates (SAR) when used for MRI excitation. While the radius of the optimum loop coil for performing MRI at depth d in a sample is known, the optimum geometry for figure-8 and butterfly coils is not. Materials and methods The geometries of figure-8 and square butterfly detector coils that deliver the optimum SNR are determined numerically by the electromagnetic method of moments. Figure-8 and loop detectors are then combined to create SNR-optimized quadrature detectors whose theoretical and experimental SNR performance are compared with a novel quadrature detector comprised of a strip and a loop, and with two overlapped loops optimized for the same depth at 3 T. The quadrature detection efficiency and local SAR during transmission for the three quadrature configurations are analyzed and compared. Results The SNR-optimized figure-8 detector has loop radius r8 ∼ 0.6d, so r8/r0 ∼ 1.3 in an optimized quadrature detector at 3 T. The optimized butterfly coil has side length ∼ d and crossover angle of ≥ 150° at the center. Conclusions These new design rules for figure-8 and butterfly coils optimize their performance as linear and quadrature detectors. PMID:18057975

  8. Improved Sensing Coils for SQUIDs

    NASA Technical Reports Server (NTRS)

    Penanen, Konstantin; Hahn, Inseob; Eom, Byeong Ho

    2007-01-01

    An improvement in the design and fabrication of sensing coils of superconducting quantum interference device (SQUID) magnetometers has been proposed to increase sensitivity. It has been estimated that, in some cases, it would be possible to increase sensitivity by about half or to reduce measurement time correspondingly. The pertinent aspects of the problems of design and fabrication can be summarized as follows: In general, to increase the sensitivity of a SQUID magnetometer, it is necessary to maximize the magnetic flux enclosed by the sensing coil while minimizing the self-inductance of this coil. It is often beneficial to fabricate the coil from a thicker wire to reduce its self-inductance. Moreover, to optimize the design of the coil with respect to sensitivity, it may be necessary to shape the wire to other than a commonly available circular or square cross-section. On the other hand, it is not practical to use thicker superconducting wire for the entire superconducting circuit, especially if the design of a specific device requires a persistent-current loop enclosing a remotely placed SQUID sensor. It may be possible to bond a thicker sensing-coil wire to thinner superconducting wires leading to a SQUID sensor, but it could be difficult to ensure reliable superconducting connections, especially if the bonded wires are made of different materials. The main idea is to mold the sensing coil in place, to more nearly optimum cross sectional shape, instead of making the coil by winding standard pre-fabricated wire. For this purpose, a thin superconducting wire loop that is an essential part of the SQUID magnetometer would be encapsulated in a form that would serve as a mold. A low-melting-temperature superconducting metal (e.g., indium, tin, or a lead/tin alloy) would be melted into the form, which would be sized and shaped to impart the required cross section to the coil thus formed.

  9. Coiling of a viscous filament

    NASA Astrophysics Data System (ADS)

    Samuel, A. D. T.; Ryu, W. S.; Mahadevan, L.

    1997-11-01

    A classic demonstration of fluid buckling is a daily occurence at the breakfast table, where a continuous stream of viscous fluid (honey) is often poured onto a flat surface (toast) from a sufficient height. The thin fluid filament quickly settles into a steady state; near the surface it bends into a helical shape while simultaneously rotating about the vertical and is laid out in a regular coil. This behavior is reminiscent of the coiling of a falling flexible rope. We derive a simple scaling law that predicts the coiling frequency in terms of the filament radius and the flow rate. We also verify this scaling law with the results of experiments.

  10. Laminated magnet field coil sheath

    DOEpatents

    Skaritka, John R.

    1987-12-01

    a method for manufacturing a magnet cable trim coil in a sheath assembly for use in a cryogenic particle accelerator. A precisely positioned pattern of trim coil turns is bonded to a flexible substrate sheath that is capable of withstanding cryogenic operating conditions. In the method of the invention the flexible sheath, with the trim coil pattern precisely positioned thereon, is accurately positioned at a precise location relative to a bore tube assembly of an accelerator and is then bonded to the bore tube with a tape suitable for cryogenic application. The resultant assembly can be readily handled and installed within an iron magnet yoke assembly of a suitable cryogenic particle accelerator.

  11. Laminated magnet field coil sheath

    DOEpatents

    Skaritka, J.R.

    1987-05-15

    A method for manufacturing a magnetic cable trim coil in a sheath assembly for use in a cryogenic particle accelerator. A precisely positioned pattern of trim coil turns is bonded to a flexible substrate sheath that is capable of withstanding cryogenic operating conditions. In the method of the invention the flexible substrate sheath, with the trim coil pattern precisely location relative to a bore tube assembly of an accelerator and is then bonded to the bore tube with a tape suitable for cryogenic application. The resultant assembly can be readily handled and installed within an iron magnet yoke assembly of a suitable cryogenic particle accelerator. 1 fig.

  12. The CMS Data Management System

    NASA Astrophysics Data System (ADS)

    Giffels, M.; Guo, Y.; Kuznetsov, V.; Magini, N.; Wildish, T.

    2014-06-01

    The data management elements in CMS are scalable, modular, and designed to work together. The main components are PhEDEx, the data transfer and location system; the Data Booking Service (DBS), a metadata catalog; and the Data Aggregation Service (DAS), designed to aggregate views and provide them to users and services. Tens of thousands of samples have been cataloged and petabytes of data have been moved since the run began. The modular system has allowed the optimal use of appropriate underlying technologies. In this contribution we will discuss the use of both Oracle and NoSQL databases to implement the data management elements as well as the individual architectures chosen. We will discuss how the data management system functioned during the first run, and what improvements are planned in preparation for 2015.

  13. Development of a pulsed cable test facility for superconducting ohmic heating coils

    SciTech Connect

    Kim, S.H.; Smith, R.P.; Kustom, R.L.; Praeg, W.F.; Krieger, C.I.

    1980-01-01

    This paper describes a Pulsed Cable Test Facility (PCTF) under development at Argonne National Laboratory (ANL). Its essential part is a pulsed superconducting split coil. The inner and outer diameters of the coil will be 45.1 cm and 88.3 cm, respectively, with an adjustable gap between the two halves of the coil. At a peak current of 11 kA, the coil will store an energy of 3.5 MJ and produce a magnetic field of 6.4 T. Using a 7 MW pulsed (2.9 MW rms) power supply, the PCTF coil will produce field change of 6 T/s. With the addition of a solid state switch to the system, dB/dt values of up to 24 T/s can be obtained. Pancake coils, wound with developmental cables, will be placed in the adjustable gap of the PCTF coil and be tested at up to 50 kA furnished by a separate power supply. The PCTF cryogenic facilities include a non-metallic cryostat and a helium liquefier.

  14. ASTROMAG coil cooling study

    NASA Technical Reports Server (NTRS)

    Maytal, Ben-Zion; Vansciver, Steven W.

    1990-01-01

    ASTROMAG is a planned particle astrophysics magnetic facility. Basically it is a large magnetic spectrometer outside the Earth's atmosphere for an extended period of time in orbit on a space station. A definition team summarized its scientific objectives assumably related to fundamental questions of astrophysics, cosmology, and elementary particle physics. Since magnetic induction of about 7 Tesla is desired, it is planned to be a superconducting magnet cooled to liquid helium 2 temperatures. The general structure of ASTROMAG is based on: (1) two superconducting magnetic coils, (2) dewar of liquid helium 2 to provide cooling capability for the magnets; (3) instrumentation, matter-anti matter spectrometer (MAS) and cosmic ray isotope spectrometer (CRIS); and (4) interfaces to the shuttle and space station. Many configurations of the superconducting magnets and the dewar were proposed and evaluated, since those are the heart of the ASTROMAG. Baseline of the magnet configuration and cryostat as presented in the phase A study and the one kept in mind while doing the present study are presented. ASTROMAG's development schedule reflects the plan of launching to the space station in 1995.

  15. Growth factor identity is encoded by discrete coiled coil rotamers in the EGFR juxtamembrane region

    PubMed Central

    Doerner, Amy; Scheck, Rebecca; Schepartz, Alanna

    2015-01-01

    Summary Binding of the growth factor TGF-α to the EGFR extracellular domain is encoded through the formation of a unique anti-parallel coiled coil within the juxtamembrane segment. This new coiled coil is an ‘inside-out’ version of the coiled coil formed in the presence of EGF. A third, intermediary coiled coil interface is formed in the juxtamembrane segment when EGFR is stimulated with betacellulin. The seven growth factors that activate EGFR in mammalian systems (EGF, TGF-α, epigen, epiregulin, betacellulin, heparin-binding EGF, and amphiregulin) fall into distinct categories in which the structure of the coiled coil induced within the juxtamembrane segment correlates with cell state. The observation that coiled coil state tracks with the downstream signaling profiles for each ligand provides evidence for growth factor functional selectivity by EGFR. Encoding growth factor identity in alternative coiled coil rotamers provides a simple and elegant method for communicating chemical information across the plasma membrane. PMID:26091170

  16. High-resolution structures of a heterochiral coiled coil

    PubMed Central

    Mortenson, David E.; Steinkruger, Jay D.; Kreitler, Dale F.; Perroni, Dominic V.; Sorenson, Gregory P.; Huang, Lijun; Mittal, Ritesh; Yun, Hyun Gi; Travis, Benjamin R.; Mahanthappa, Mahesh K.; Forest, Katrina T.; Gellman, Samuel H.

    2015-01-01

    Interactions between polypeptide chains containing amino acid residues with opposite absolute configurations have long been a source of interest and speculation, but there is very little structural information for such heterochiral associations. The need to address this lacuna has grown in recent years because of increasing interest in the use of peptides generated from d amino acids (d peptides) as specific ligands for natural proteins, e.g., to inhibit deleterious protein–protein interactions. Coiled–coil interactions, between or among α-helices, represent the most common tertiary and quaternary packing motif in proteins. Heterochiral coiled–coil interactions were predicted over 50 years ago by Crick, and limited experimental data obtained in solution suggest that such interactions can indeed occur. To address the dearth of atomic-level structural characterization of heterochiral helix pairings, we report two independent crystal structures that elucidate coiled-coil packing between l- and d-peptide helices. Both structures resulted from racemic crystallization of a peptide corresponding to the transmembrane segment of the influenza M2 protein. Networks of canonical knobs-into-holes side-chain packing interactions are observed at each helical interface. However, the underlying patterns for these heterochiral coiled coils seem to deviate from the heptad sequence repeat that is characteristic of most homochiral analogs, with an apparent preference for a hendecad repeat pattern. PMID:26460035

  17. Delayed migration of embolized coil with large renal stone formation: a rare presentation.

    PubMed

    Kumar, Santosh; Jayant, Kumar; Singh, Shrawan K; Parmar, Kalpesh M; Devana, Sudheer K; Choudhari, Gautam R; Mittal, Ankur

    2014-01-01

    Delayed bleeding following percutaneous nephrolithotomy (PCNL) usually occurs due to development of the pseudoaneurysm which can be successfully managed with coil embolization. However very few cases of such complications have been reported in the literature. Here we are reporting a case of delayed post-PCNL bleeding that occurred in a 53-year-old diabetic patient operated on for renal stone. Computed tomography scan revealed a presence of the pseudoaneurysm in the segmental branch of right renal artery, which was successfully managed with coiling. Patient remained asymptomatic for the next 9 years after which he again presented with similar complaints. X-ray KUB was done which revealed a 2.7 cms renal pelvic calculus with the migrated coil in its center and a left upper ureteric calculus. His routine haemogram, coagulogram, serum electrolytes, and liver function tests, renal function tests, vitamin D3, and PTH (parathyroid hormone) were within normal limits. He underwent left laparoscopic ureterolithotomy and right percutaneous nephrolithotomy (PCNL). Intraoperatively the migrated stainless steel embolization coil was seen engulfed all around by the multiple stones in the right renal pelvis. Postoperative period was uneventful. Later he was followed in the outpatient department and was doing well. To conclude, this is the only case report of development of a large calculus around a migrated embolization coil which was successfully managed with PCNL. PCNL offers better stone clearance in cases of stones being formed over foreign bodies like fragmented double J stents, fragmented nephrostomies, or migrated embolization coil. PMID:25610700

  18. Delayed Migration of Embolized Coil with Large Renal Stone Formation: A Rare Presentation

    PubMed Central

    Jayant, Kumar; Singh, Shrawan K.; Parmar, Kalpesh M.; Devana, Sudheer K.; Choudhari, Gautam R.; Mittal, Ankur

    2014-01-01

    Delayed bleeding following percutaneous nephrolithotomy (PCNL) usually occurs due to development of the pseudoaneurysm which can be successfully managed with coil embolization. However very few cases of such complications have been reported in the literature. Here we are reporting a case of delayed post-PCNL bleeding that occurred in a 53-year-old diabetic patient operated on for renal stone. Computed tomography scan revealed a presence of the pseudoaneurysm in the segmental branch of right renal artery, which was successfully managed with coiling. Patient remained asymptomatic for the next 9 years after which he again presented with similar complaints. X-ray KUB was done which revealed a 2.7 cms renal pelvic calculus with the migrated coil in its center and a left upper ureteric calculus. His routine haemogram, coagulogram, serum electrolytes, and liver function tests, renal function tests, vitamin D3, and PTH (parathyroid hormone) were within normal limits. He underwent left laparoscopic ureterolithotomy and right percutaneous nephrolithotomy (PCNL). Intraoperatively the migrated stainless steel embolization coil was seen engulfed all around by the multiple stones in the right renal pelvis. Postoperative period was uneventful. Later he was followed in the outpatient department and was doing well. To conclude, this is the only case report of development of a large calculus around a migrated embolization coil which was successfully managed with PCNL. PCNL offers better stone clearance in cases of stones being formed over foreign bodies like fragmented double J stents, fragmented nephrostomies, or migrated embolization coil. PMID:25610700

  19. The Majority of HIV Type 1 DNA in Circulating CD4+ T Lymphocytes Is Present in Non-Gut-Homing Resting Memory CD4+ T Cells

    PubMed Central

    Xu, Yin; Bailey, Michelle; Seddiki, Nabila; Suzuki, Kazuo; Murray, John M.; Gao, Yuan; Yan, Celine; Cooper, David A.; Kelleher, Anthony D.; Koelsch, Kersten K.; Zaunders, John

    2013-01-01

    Abstract Memory CD4+ T lymphocytes in peripheral blood that express integrins α4ß7 preferentially recirculate through gut-associated lymphoid tissue (GALT), a proposed site of significant HIV-1 replication. Tregs and activated CD4+ T cells in GALT could also be particularly susceptible to infection. We therefore hypothesized that infection of these subsets of memory CD4+ T cells may contribute disproportionately to the HIV-1 reservoir. A cross-sectional study of CD4+ T cell subsets of memory CD45RO+ cells in peripheral blood mononuclear cells (PBMCs) was conducted using leukapheresis from eight subjects with untreated chronic HIV-1 infection. Real-time polymerase chain reaction (PCR) was used to quantify total and integrated HIV-1 DNA levels from memory CD4+ T cells sorted into integrin β7+ vs. β7−, CD25+CD127low Treg vs. CD127high, and activated CD38+ vs. CD38−. More than 80% of total HIV-1 DNA was found to reside in the integrin β7-negative non-gut-homing subset of CD45RO+ memory CD4+ T cells. Less than 10% was found in highly purified Tregs or CD38+ activated memory cells. Similarly, integrated HIV-1 DNA copies were found to be more abundant in resting non-gut-homing memory CD4+ T cells (76%) than in their activated counterparts (23%). Our investigations showed that the majority of both total and integrated HIV-1 DNA was found within non-gut-homing resting CD4+ T cells. PMID:23971972

  20. CMS centres worldwide: A new collaborative infrastructure

    SciTech Connect

    Taylor, Lucas; Gottschalk, Erik; /Fermilab

    2010-01-01

    The CMS Experiment at the LHC is establishing a global network of inter-connected 'CMS Centres' for controls, operations and monitoring. These support: (1) CMS data quality monitoring, detector calibrations, and analysis; and (2) computing operations for the processing, storage and distribution of CMS data. We describe the infrastructure, computing, software, and communications systems required to create an effective and affordable CMS Centre. We present our highly successful operations experiences with the major CMS Centres at CERN, Fermilab, and DESY during the LHC first beam data-taking and cosmic ray commissioning work. The status of the various centres already operating or under construction in Asia, Europe, Russia, South America, and the USA is also described. We emphasise the collaborative communications aspects. For example, virtual co-location of experts in CMS Centres Worldwide is achieved using high-quality permanently-running 'telepresence' video links. Generic Web-based tools have been developed and deployed for monitoring, control, display management and outreach.

  1. Adjustable Induction-Heating Coil

    NASA Technical Reports Server (NTRS)

    Ellis, Rod; Bartolotta, Paul

    1990-01-01

    Improved design for induction-heating work coil facilitates optimization of heating in different metal specimens. Three segments adjusted independently to obtain desired distribution of temperature. Reduces time needed to achieve required temperature profiles.

  2. Zero-angle helical coil

    NASA Technical Reports Server (NTRS)

    Troendle, J. A.

    1976-01-01

    Device is constructed of bimetallic stock material formed into segments of small diameters and fastened together by metal strips. Coil is useful in various types of actuators, such as temperature controls.

  3. Bystander CD4+ T lymphocytes survive in HIV-infected human lymphoid tissue

    NASA Technical Reports Server (NTRS)

    Grivel, Jean-Charles; Biancotto, Angelique; Ito, Yoshinori; Lima, Rosangela G.; Margolis, Leonid B.

    2003-01-01

    HIV infection is associated with depletion of CD4(+) T cells. The mechanisms of this phenomenon remain to be understood. In particular, it remains controversial whether and to what extent uninfected ("bystander") CD4(+) T cells die in HIV-infected individuals. We address this question using a system of human lymphoid tissue ex vivo. Tissue blocks were inoculated with HIV-1. After productive infection was established, they were treated with the reverse transcriptase inhibitor nevirapine to protect from infection those CD4(+) T cells that had not yet been infected. These CD4(+) T cells residing in HIV-infected tissue are by definition bystanders. Our results demonstrate that after nevirapine application the number of bystander CD4(+) T cells is conserved. Thus, in the context of HIV-infected human lymphoid tissue, productive HIV infection kills infected cells but is not sufficient to cause the death of a significant number of uninfected CD4(+) T cells.

  4. Vaccine-Elicited CD4 T Cells Induce Immunopathology Following Chronic LCMV Infection

    PubMed Central

    Penaloza-MacMaster, Pablo; Barber, Daniel L.; Wherry, E. John; Provine, Nicholas M.; Teigler, Jeffrey E.; Parenteau, Lily; Blackmore, Stephen; Borducchi, Erica N.; Larocca, Rafael A.; Yates, Kathleen B.; Shen, Hao; Haining, W. Nicholas; Sommerstein, Rami; Pinschewer, Daniel D.; Ahmed, Rafi; Barouch, Dan. H.

    2015-01-01

    CD4 T cells promote innate and adaptive immune responses, but how vaccine-elicited CD4 T cells contribute to immune protection remains unclear. Here we evaluated whether induction of virus-specific CD4 T cells by vaccination would protect mice against infection with chronic lymphocytic choriomeningitis virus (LCMV). Immunization with vaccines that selectively induced CD4 T cell responses resulted in catastrophic inflammation and mortality following challenge with a persistent strain of LCMV. Immunopathology required antigen-specific CD4 T cells and was associated with a cytokine storm, generalized inflammation, and multi-organ system failure. Virus-specific CD8 T cells or antibodies abrogated the pathology. These data demonstrate that vaccine-elicited CD4 T cells in the absence of effective antiviral immune responses can trigger lethal immunopathology. PMID:25593185

  5. The CMS Masterclass and Particle Physics Outreach

    NASA Astrophysics Data System (ADS)

    Cecire, Kenneth; Bardeen, Marjorie; McCauley, Thomas

    2014-04-01

    The CMS Masterclass enables high school students to analyse authentic CMS data. Students can draw conclusions on key ratios and particle masses by combining their analyses. In particular, they can use the ratio of W+ to W- candidates to probe the structure of the proton, they can find the mass of the Z boson, and they can identify additional particles including, tentatively, the Higgs boson. In the United States, masterclasses are part of QuarkNet, a long-term program that enables students and teachers to use cosmic ray and particle physics data for learning with an emphasis on data from CMS.

  6. The CMS Masterclass and Particle Physics Outreach

    SciTech Connect

    Cecire, Kenneth; Bardeen, Marjorie; McCauley, Thomas

    2014-01-01

    The CMS Masterclass enables high school students to analyse authentic CMS data. Students can draw conclusions on key ratios and particle masses by combining their analyses. In particular, they can use the ratio of W^+ to W^- candidates to probe the structure of the proton, they can find the mass of the Z boson, and they can identify additional particles including, tentatively, the Higgs boson. In the United States, masterclasses are part of QuarkNet, a long-term program that enables students and teachers to use cosmic ray and particle physics data for learning with an emphasis on data from CMS.

  7. Dynamics of liquid rope coiling

    NASA Astrophysics Data System (ADS)

    Habibi, Mehdi; Maleki, Maniya; Golestanian, Ramin; Ribe, Neil M.; Bonn, Daniel

    2006-12-01

    We present a combined experimental and numerical investigation of the coiling of a liquid “rope” falling on a solid surface, focusing on three little-explored aspects of the phenomenon: The time dependence of “inertio-gravitational” coiling, the systematic dependence of the radii of the coil and the rope on the experimental parameters, and the “secondary buckling” of the columnar structure generated by high-frequency coiling. Inertio-gravitational coiling is characterized by oscillations between states with different frequencies, and we present experimental observations of four distinct branches of such states in the frequency-fall height space. The transitions between coexisting states have no characteristic period, may take place with or without a change in the sense of rotation, and usually (but not always) occur via an intermediate “figure of eight” state. We present extensive laboratory measurements of the radii of the coil and of the rope within it, and show that they agree well with the predictions of a “slender-rope” numerical model. Finally, we use dimensional analysis to reveal a systematic variation of the critical column height for secondary buckling as a function of (dimensionless) flow rate and surface tension parameters.

  8. TNF-α blockade induces IL-10 expression in human CD4+ T cells

    NASA Astrophysics Data System (ADS)

    Evans, Hayley G.; Roostalu, Urmas; Walter, Gina J.; Gullick, Nicola J.; Frederiksen, Klaus S.; Roberts, Ceri A.; Sumner, Jonathan; Baeten, Dominique L.; Gerwien, Jens G.; Cope, Andrew P.; Geissmann, Frederic; Kirkham, Bruce W.; Taams, Leonie S.

    2014-02-01

    IL-17+ CD4+ T (Th17) cells contribute to the pathogenesis of several human inflammatory diseases. Here we demonstrate that TNF inhibitor (TNFi) drugs induce the anti-inflammatory cytokine IL-10 in CD4+ T cells including IL-17+ CD4+ T cells. TNFi-mediated induction of IL-10 in IL-17+ CD4+ T cells is Treg-/Foxp3-independent, requires IL-10 and is overcome by IL-1β. TNFi-exposed IL-17+ CD4+ T cells are molecularly and functionally distinct, with a unique gene signature characterized by expression of IL10 and IKZF3 (encoding Aiolos). We show that Aiolos binds conserved regions in the IL10 locus in IL-17+ CD4+ T cells. Furthermore, IKZF3 and IL10 expression levels correlate in primary CD4+ T cells and Aiolos overexpression is sufficient to drive IL10 in these cells. Our data demonstrate that TNF-α blockade induces IL-10 in CD4+ T cells including Th17 cells and suggest a role for the transcription factor Aiolos in the regulation of IL-10 in CD4+ T cells.

  9. ESTABLISHING MEAN CD4+ T CELL VALUES AMONG HEALTHY JAVANESE ADULTS IN INDONESIA.

    PubMed

    Prasetyo, Afiono Agung; Zaini, Khilyat Ulin Nur

    2015-07-01

    The objective of this study was to establish mean CD4+ T cell values among healthy Javanese adults in Indonesia. Two hundred forty-one healthy adults (119 women and 122 men), aged 18-65 years, were enrolled in the study. CD4+ T cells were analyzed by immunophenotyping. The mean absolute CD4+ T cell count was 753.3 ± 270.3 cells/µl (median = 725.0 cells/µl) and the mean CD4+ T cell percentage was 32.6 ± 7.7%, (median = 31.0%). Women had a slightly higher mean absolute CD4+ T cell count and CD4+ T cell percentage (779.1 ± 271.0 cells/ µl; 33.4 ± 8.2%) than men (728.2 ± 268.3 cells/µl; 31.8 ± 7.1%), but the differences were not statistically significant (p = 0.126, p = 0.216, respectively). The mean absolute CD4+ T cell varied significantly by age group (p = 0.002). Sixty-one point seven percent of men studied (37/60) had a CD4+ T cell count less than 500 cells/µl (OR 1.8; 95% CI = 1.001-3.300). Absolute CD4+ T cell counts among Javanese Indonesians varied significantly by age. PMID:26867386

  10. Nylon screws make inexpensive coil forms

    NASA Technical Reports Server (NTRS)

    Aucoin, G.; Rosenthal, C.

    1978-01-01

    Standard nylon screws act as coil form copper wire laid down in spiral thread. Completed coil may be bonded to printed-circuit board. However, it is impossible to tune coil by adjusting spacing between windings, technique sometimes used with air-core coils.

  11. Retrieval of Distally Migrated Coils with Detachable Intracranial Stent during Coil Embolization of Cerebral Aneurysm

    PubMed Central

    Singh, Devendra Pal; Huang, Lijin; Lee, Won Joo

    2016-01-01

    Migration of coils during endovascular procedures is a rare, but well-known complication. We are reporting two cases of successfully retrieving migrated coil using detachable intracranial stent. In both of our cases there was distal migration of coil during the intracranial aneurysm coiling procedure. The Solitaire® AB stent (Covidien, Irvine, CA, USA) was used to retrieve those coils. The stent was passed distal to the migrated coil using standard technique. It was then partially deployed and gradually withdrawn along with the entangled coil. Coil retrieval using the fully retrievable intracranial stent is a very simple, safe and easily available alternative for retrieval of distally migrated coil. PMID:27114967

  12. 42 CFR 405.800 - Appeals of CMS or a CMS contractor.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 2 2014-10-01 2014-10-01 false Appeals of CMS or a CMS contractor. 405.800 Section 405.800 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM FEDERAL HEALTH INSURANCE FOR THE AGED AND DISABLED Appeals Under the Medicare Part B Program § 405.800 Appeals of CMS or a...

  13. Small animal simultaneous PET/MRI: initial experiences in a 9.4 T microMRI.

    PubMed

    Maramraju, Sri Harsha; Smith, S David; Junnarkar, Sachin S; Schulz, Daniela; Stoll, Sean; Ravindranath, Bosky; Purschke, Martin L; Rescia, Sergio; Southekal, Sudeepti; Pratte, Jean-François; Vaska, Paul; Woody, Craig L; Schlyer, David J

    2011-04-21

    We developed a non-magnetic positron-emission tomography (PET) device based on the rat conscious animal PET that operates in a small-animal magnetic resonance imaging (MRI) scanner, thereby enabling us to carry out simultaneous PET/MRI studies. The PET detector comprises 12 detector blocks, each being a 4 × 8 array of lutetium oxyorthosilicate crystals (2.22 × 2.22 × 5 mm(3)) coupled to a matching non-magnetic avalanche photodiode array. The detector blocks, housed in a plastic case, form a 38 mm inner diameter ring with an 18 mm axial extent. Custom-built MRI coils fit inside the positron-emission tomography (PET) device, operating in transceiver mode. The PET insert is integrated with a Bruker 9.4 T 210 mm clear-bore diameter MRI scanner. We acquired simultaneous PET/MR images of phantoms, of in vivo rat brain, and of cardiac-gated mouse heart using [(11)C]raclopride and 2-deoxy-2-[(18)F]fluoro-D-glucose PET radiotracers. There was minor interference between the PET electronics and the MRI during simultaneous operation, and small effects on the signal-to-noise ratio in the MR images in the presence of the PET, but no noticeable visual artifacts. Gradient echo and high-duty-cycle spin echo radio frequency (RF) pulses resulted in a 7% and a 28% loss in PET counts, respectively, due to high PET counts during the RF pulses that had to be gated out. The calibration of the activity concentration of PET data during MR pulsing is reproducible within less than 6%. Our initial results demonstrate the feasibility of performing simultaneous PET and MRI studies in adult rats and mice using the same PET insert in a small-bore 9.4 T MRI. PMID:21441651

  14. Small animal simultaneous PET/MRI: initial experiences in a 9.4T microMRI

    SciTech Connect

    Maramraju, S.H.; Schlyer, D.; Maramraju, S.H.; Smith, S.D.; Junnarkar, S.S.; Schulz, D.; Stoll, S.; Ravindranath, B.; Purschke, M.L.; Rescia, S.; Southekal, S.; Pratte, J.-F.; Vaska, P.; Woody, C.L.; Schlyer, D.J.

    2011-03-25

    We developed a non-magnetic positron-emission tomography (PET) device based on the rat conscious animal PET that operates in a small-animal magnetic resonance imaging (MRI) scanner, thereby enabling us to carry out simultaneous PET/MRI studies. The PET detector comprises 12 detector blocks, each being a 4 x 8 array of lutetium oxyorthosilicate crystals (2.22 x 2.22 x 5 mm{sup 3}) coupled to a matching non-magnetic avalanche photodiode array. The detector blocks, housed in a plastic case, form a 38 mm inner diameter ring with an 18 mm axial extent. Custom-built MRI coils fit inside the positron-emission tomography (PET) device, operating in transceiver mode. The PET insert is integrated with a Bruker 9.4 T 210 mm clear-bore diameter MRI scanner. We acquired simultaneous PET/MR images of phantoms, of in vivo rat brain, and of cardiac-gated mouse heart using [{sup 11}C]raclopride and 2-deoxy-2-[{sup 18}F]fluoro-d-glucose PET radiotracers. There was minor interference between the PET electronics and the MRI during simultaneous operation, and small effects on the signal-to-noise ratio in the MR images in the presence of the PET, but no noticeable visual artifacts. Gradient echo and high-duty-cycle spin echo radio frequency (RF) pulses resulted in a 7% and a 28% loss in PET counts, respectively, due to high PET counts during the RF pulses that had to be gated out. The calibration of the activity concentration of PET data during MR pulsing is reproducible within less than 6%. Our initial results demonstrate the feasibility of performing simultaneous PET and MRI studies in adult rats and mice using the same PET insert in a small-bore 9.4 T MRI.

  15. Small animal simultaneous PET/MRI: initial experiences in a 9.4 T microMRI

    NASA Astrophysics Data System (ADS)

    Harsha Maramraju, Sri; Smith, S. David; Junnarkar, Sachin S.; Schulz, Daniela; Stoll, Sean; Ravindranath, Bosky; Purschke, Martin L.; Rescia, Sergio; Southekal, Sudeepti; Pratte, Jean-François; Vaska, Paul; Woody, Craig L.; Schlyer, David J.

    2011-04-01

    We developed a non-magnetic positron-emission tomography (PET) device based on the rat conscious animal PET that operates in a small-animal magnetic resonance imaging (MRI) scanner, thereby enabling us to carry out simultaneous PET/MRI studies. The PET detector comprises 12 detector blocks, each being a 4 × 8 array of lutetium oxyorthosilicate crystals (2.22 × 2.22 × 5 mm3) coupled to a matching non-magnetic avalanche photodiode array. The detector blocks, housed in a plastic case, form a 38 mm inner diameter ring with an 18 mm axial extent. Custom-built MRI coils fit inside the positron-emission tomography (PET) device, operating in transceiver mode. The PET insert is integrated with a Bruker 9.4 T 210 mm clear-bore diameter MRI scanner. We acquired simultaneous PET/MR images of phantoms, of in vivo rat brain, and of cardiac-gated mouse heart using [11C]raclopride and 2-deoxy-2-[18F]fluoro-d-glucose PET radiotracers. There was minor interference between the PET electronics and the MRI during simultaneous operation, and small effects on the signal-to-noise ratio in the MR images in the presence of the PET, but no noticeable visual artifacts. Gradient echo and high-duty-cycle spin echo radio frequency (RF) pulses resulted in a 7% and a 28% loss in PET counts, respectively, due to high PET counts during the RF pulses that had to be gated out. The calibration of the activity concentration of PET data during MR pulsing is reproducible within less than 6%. Our initial results demonstrate the feasibility of performing simultaneous PET and MRI studies in adult rats and mice using the same PET insert in a small-bore 9.4 T MRI.

  16. JET divertor coils, manufacture, assembly and testing

    NASA Astrophysics Data System (ADS)

    Dolgetta, N.; Bertolini, E.; D'Urzo, C.; Last, J. R.; Laurenti, A.; Presle, P.; Sannazzaro, G.; Tait, J.; Tesini, A.

    1994-07-01

    Four coils have been built and installed in the JET vacuum vessel to produce divertor plasmas. The coils are copper with glass epoxy insulation and are enclosed in vacuum tight Inconel cases. At the coil contractor's factory, the coil parts were manufactured and process techniques qualified. In the JET vacuum vessel the conductor bars were brazed to form the coils, which were inserted in the casings and impregnated and cured with epoxy resin.

  17. 23 CFR 500.109 - CMS.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... future demand management strategies and operational improvements that will maintain the functional... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION TRANSPORTATION INFRASTRUCTURE MANAGEMENT MANAGEMENT AND MONITORING SYSTEMS Management Systems § 500.109 CMS. (a) For purposes of this part, congestion means the level...

  18. The CMS central hadron calorimeter: Update

    SciTech Connect

    Freeman, J.

    1998-06-01

    The CMS central hadron calorimeter is a brass absorber/ scintillator sampling structure. We describe details of the mechanical and optical structure. We also discuss calibration techniques, and finally the anticipated construction schedule.

  19. File level provenance tracking in CMS

    SciTech Connect

    Jones, C.D.; Kowalkowski, J.; Paterno, M.; Sexton-Kennedy, L.; Tanenbaum, W.; Riley, D.S.; /Cornell U., LEPP

    2009-05-01

    The CMS off-line framework stores provenance information within CMS's standard ROOT event data files. The provenance information is used to track how each data product was constructed, including what other data products were read to do the construction. We will present how the framework gathers the provenance information, the efforts necessary to minimize the space used to store the provenance in the file and the tools that will be available to use the provenance.

  20. The CD4(+) T cell methylome contributes to a distinct CD4(+) T cell transcriptional signature in Mycobacterium bovis-infected cattle.

    PubMed

    Doherty, Rachael; Whiston, Ronan; Cormican, Paul; Finlay, Emma K; Couldrey, Christine; Brady, Colm; O'Farrelly, Cliona; Meade, Kieran G

    2016-01-01

    We hypothesised that epigenetic regulation of CD4(+) T lymphocytes contributes to a shift toward a dysfunctional T cell phenotype which may impact on their ability to clear mycobacterial infection. Combined RNA-seq transcriptomic profiling and Reduced Representation Bisulfite Sequencing identified 193 significantly differentially expressed genes and 760 differentially methylated regions (DMRs), between CD4(+) T cells from M. bovis infected and healthy cattle. 196 DMRs were located within 10 kb of annotated genes, including GATA3 and RORC, both of which encode transcription factors that promote TH2 and TH17 T helper cell subsets respectively. Gene-specific DNA methylation and gene expression levels for the TNFRSF4 and Interferon-γ genes were significantly negatively correlated suggesting a regulatory relationship. Pathway analysis of DMRs identified enrichment of genes involved in the anti-proliferative TGF-β signaling pathway and TGFB1 expression was significantly increased in peripheral blood leukocytes from TB-infected cattle. This first analysis of the bovine CD4(+) T cell methylome suggests that DNA methylation directly contributes to a distinct gene expression signature in CD4(+) T cells from cattle infected with M. bovis. Specific methylation changes proximal to key inflammatory gene loci may be critical to the emergence of a non-protective CD4(+) T cell response during mycobacterial infection in cattle. PMID:27507428

  1. The CD4+ T cell methylome contributes to a distinct CD4+ T cell transcriptional signature in Mycobacterium bovis-infected cattle

    PubMed Central

    Doherty, Rachael; Whiston, Ronan; Cormican, Paul; Finlay, Emma K.; Couldrey, Christine; Brady, Colm; O’Farrelly, Cliona; Meade, Kieran G.

    2016-01-01

    We hypothesised that epigenetic regulation of CD4+ T lymphocytes contributes to a shift toward a dysfunctional T cell phenotype which may impact on their ability to clear mycobacterial infection. Combined RNA-seq transcriptomic profiling and Reduced Representation Bisulfite Sequencing identified 193 significantly differentially expressed genes and 760 differentially methylated regions (DMRs), between CD4+ T cells from M. bovis infected and healthy cattle. 196 DMRs were located within 10 kb of annotated genes, including GATA3 and RORC, both of which encode transcription factors that promote TH2 and TH17 T helper cell subsets respectively. Gene-specific DNA methylation and gene expression levels for the TNFRSF4 and Interferon-γ genes were significantly negatively correlated suggesting a regulatory relationship. Pathway analysis of DMRs identified enrichment of genes involved in the anti-proliferative TGF-β signaling pathway and TGFB1 expression was significantly increased in peripheral blood leukocytes from TB-infected cattle. This first analysis of the bovine CD4+ T cell methylome suggests that DNA methylation directly contributes to a distinct gene expression signature in CD4+ T cells from cattle infected with M. bovis. Specific methylation changes proximal to key inflammatory gene loci may be critical to the emergence of a non-protective CD4+ T cell response during mycobacterial infection in cattle. PMID:27507428

  2. Virtual data in CMS analysis

    SciTech Connect

    A. Arbree et al.

    2003-10-01

    The use of virtual data for enhancing the collaboration between large groups of scientists is explored in several ways: by defining ''virtual'' parameter spaces which can be searched and shared in an organized way by a collaboration of scientists in the course of their analysis; by providing a mechanism to log the provenance of results and the ability to trace them back to the various stages in the analysis of real or simulated data; by creating ''check points'' in the course of an analysis to permit collaborators to explore their own analysis branches by refining selections, improving the signal to background ratio, varying the estimation of parameters, etc.; by facilitating the audit of an analysis and the reproduction of its results by a different group, or in a peer review context. We describe a prototype for the analysis of data from the CMS experiment based on the virtual data system Chimera and the object-oriented data analysis framework ROOT. The Chimera system is used to chain together several steps in the analysis process including the Monte Carlo generation of data, the simulation of detector response, the reconstruction of physics objects and their subsequent analysis, histogramming and visualization using the ROOT framework.

  3. The CMS Condition Database System

    NASA Astrophysics Data System (ADS)

    Di Guida, S.; Govi, G.; Ojeda, M.; Pfeiffer, A.; Sipos, R.

    2015-12-01

    The Condition Database plays a key role in the CMS computing infrastructure. The complexity of the detector and the variety of the sub-systems involved are setting tight requirements for handling the Conditions. In the last two years the collaboration has put a substantial effort in the re-design of the Condition Database system, with the aim at improving the scalability and the operability for the data taking starting in 2015. The re-design has focused on simplifying the architecture, using the lessons learned during the operation of the Run I data-taking period (20092013). In the new system the relational features of the database schema are mainly exploited to handle the metadata (Tag and Interval of Validity), allowing for a limited and controlled set of queries. The bulk condition data (Payloads) are stored as unstructured binary data, allowing the storage in a single table with a common layout for all of the condition data types. In this paper, we describe the full architecture of the system, including the services implemented for uploading payloads and the tools for browsing the database. Furthermore, the implementation choices for the core software will be discussed.

  4. Selective culling of high avidity antigen-specific CD4+ T cells after virulent Salmonella infection

    PubMed Central

    Ertelt, James M; Johanns, Tanner M; Mysz, Margaret A; Nanton, Minelva R; Rowe, Jared H; Aguilera, Marijo N; Way, Sing Sing

    2011-01-01

    Typhoid fever is a persistent infection caused by host-adapted Salmonella strains adept at circumventing immune-mediated host defences. Given the importance of T cells in protection, the culling of activated CD4+ T cells after primary infection has been proposed as a potential immune evasion strategy used by this pathogen. We demonstrate that the purging of activated antigen-specific CD4+ T cells after virulent Salmonella infection requires SPI-2 encoded virulence determinants, and is not restricted only to cells with specificity to Salmonella-expressed antigens, but extends to CD4+ T cells primed to expand by co-infection with recombinant Listeria monocytogenes. Unexpectedly, however, the loss of activated CD4+ T cells during Salmonella infection demonstrated using a monoclonal population of adoptively transferred CD4+ T cells was not reproduced among the endogenous repertoire of antigen-specific CD4+ T cells identified with MHC class II tetramer. Analysis of T-cell receptor variable segment usage revealed the selective loss and reciprocal enrichment of defined CD4+ T-cell subsets after Salmonella co-infection that is associated with the purging of antigen-specific cells with the highest intensity of tetramer staining. Hence, virulent Salmonella triggers the selective culling of high avidity activated CD4+ T-cell subsets, which re-shapes the repertoire of antigen-specific T cells that persist later after infection. PMID:22044420

  5. 26 CFR 1.6041-4T - Foreign-related items and other exceptions (temporary).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 13 2014-04-01 2014-04-01 false Foreign-related items and other exceptions (temporary). 1.6041-4T Section 1.6041-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... chapter 3 of the Internal Revenue Code (Code), under § 1.1461-1(b) and (c) and, for purposes of chapter...

  6. 26 CFR 1.7874-4T - Disregard of certain stock related to the acquisition (temporary).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 13 2014-04-01 2014-04-01 false Disregard of certain stock related to the acquisition (temporary). 1.7874-4T Section 1.7874-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial...

  7. Polyfunctional CD4 T cells in the response to bovine tuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    CD4 T cells are crucial in immunity to tuberculosis (TB). Polyfunctional CD4 T cells simultaneously produce interferon-gamma (IFN-gamma), Interleukin-2 (IL-2) and Tumor necrosis factor-alpha (TNF-alpha) and play relevant roles in several chronic infections, including human TB and HIV. However, the a...

  8. Polyfunctional cytokine responses by central memory CD4+T cells in response to bovine tuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    CD4 T cells are crucial in immunity to tuberculosis (TB). Polyfunctional CD4 T cells simultaneously produce interferon-gamma (IFN-gamma), interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) and play relevant roles in several chronic infections, including human TB and HIV. Mycobacterium ...

  9. Polyfunctional cytokine responses by central memory CD4*T cells in response to bovine tuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    CD4 T cells are crucial in immunity to tuberculosis (TB). Polyfunctional CD4 T cells simultaneously produce interferon-gamma (IFN-gamma), interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) and play relevant roles in several chronic infections, including human TB. Mycobacterium bovis in...

  10. Tropomyosin lysine reactivities and relationship to coiled-coil structure.

    PubMed

    Hitchcock-DeGregori, S E; Lewis, S F; Chou, T M

    1985-06-18

    We have carried out a detailed analysis of tropomyosin structure using lysines as specific probes for the protein surface in regions of the molecule that have not been investigated by other methods. We have measured the relative reactivities of lysines in rabbit skeletal muscle alpha, alpha-tropomyosin with acetic anhydride using a competitive labeling procedure. We have identified 37 of 39 lysines and find that they range 20-fold in reactivity. The observed reactivities are related to the coiled-coil model of the tropomyosin molecule [Crick, F.H.C. (1953) Acta Crystallogr. 6, 689-697; McLachlan, A.D., Stewart, M., & Smillie, L.B. (1975) J. Mol. Biol. 98, 281-291] and other available chemical and physical information about the structure. In most cases, the observed lysine reactivities can be explained by allowable interactions with neighboring amino acid side chains on the same or facing alpha-helix. However, we found no correlation between reactivity and helical position of a given lysine. For example, lysines in the outer helical positions included lysines of low as well as high reactivity, indicating that they vary widely in their accessibility to solvent and that the coiled coil is heterogeneous along its length. Furthermore, the middle of the molecule (residues 126-182) that is susceptible to proteolysis and known to be the least stable region of the protein also contains some of the least and most reactive lysines. We have discussed the implications of our results on our understanding the structures of tropomyosin and other coiled-coil proteins as well as globular proteins containing helical regions. PMID:3927977

  11. Designed coiled coils promote folding of a recombinant bacterial collagen.

    PubMed

    Yoshizumi, Ayumi; Fletcher, Jordan M; Yu, Zhuoxin; Persikov, Anton V; Bartlett, Gail J; Boyle, Aimee L; Vincent, Thomas L; Woolfson, Derek N; Brodsky, Barbara

    2011-05-20

    Collagen triple helices fold slowly and inefficiently, often requiring adjacent globular domains to assist this process. In the Streptococcus pyogenes collagen-like protein Scl2, a V domain predicted to be largely α-helical, occurs N-terminal to the collagen triple helix (CL). Here, we replace this natural trimerization domain with a de novo designed, hyperstable, parallel, three-stranded, α-helical coiled coil (CC), either at the N terminus (CC-CL) or the C terminus (CL-CC) of the collagen domain. CD spectra of the constructs are consistent with additivity of independently and fully folded CC and CL domains, and the proteins retain their distinctive thermal stabilities, CL at ∼37 °C and CC at >90 °C. Heating the hybrid proteins to 50 °C unfolds CL, leaving CC intact, and upon cooling, the rate of CL refolding is somewhat faster for CL-CC than for CC-CL. A construct with coiled coils on both ends, CC-CL-CC, retains the ∼37 °C thermal stability for CL but shows less triple helix at low temperature and less denaturation at 50 °C. Most strikingly however, in CC-CL-CC, the CL refolds slower than in either CC-CL or CL-CC by almost two orders of magnitude. We propose that a single CC promotes folding of the CL domain via nucleation and in-register growth from one end, whereas initiation and growth from both ends in CC-CL-CC results in mismatched registers that frustrate folding. Bioinformatics analysis of natural collagens lends support to this because, where present, there is generally only one coiled-coil domain close to the triple helix, and it is nearly always N-terminal to the collagen repeat. PMID:21454493

  12. Pathogenic CD4 T cells in type 1 diabetes recognize epitopes formed by peptide fusion.

    PubMed

    Delong, Thomas; Wiles, Timothy A; Baker, Rocky L; Bradley, Brenda; Barbour, Gene; Reisdorph, Richard; Armstrong, Michael; Powell, Roger L; Reisdorph, Nichole; Kumar, Nitesh; Elso, Colleen M; DeNicola, Megan; Bottino, Rita; Powers, Alvin C; Harlan, David M; Kent, Sally C; Mannering, Stuart I; Haskins, Kathryn

    2016-02-12

    T cell-mediated destruction of insulin-producing β cells in the pancreas causes type 1 diabetes (T1D). CD4 T cell responses play a central role in β cell destruction, but the identity of the epitopes recognized by pathogenic CD4 T cells remains unknown. We found that diabetes-inducing CD4 T cell clones isolated from nonobese diabetic mice recognize epitopes formed by covalent cross-linking of proinsulin peptides to other peptides present in β cell secretory granules. These hybrid insulin peptides (HIPs) are antigenic for CD4 T cells and can be detected by mass spectrometry in β cells. CD4 T cells from the residual pancreatic islets of two organ donors who had T1D also recognize HIPs. Autoreactive T cells targeting hybrid peptides may explain how immune tolerance is broken in T1D. PMID:26912858

  13. Development and Function of Protective and Pathologic Memory CD4 T Cells

    PubMed Central

    Jaigirdar, Shafqat Ahrar; MacLeod, Megan K. L.

    2015-01-01

    Immunological memory is one of the defining features of the adaptive immune system. As key orchestrators and mediators of immunity, CD4 T cells are central to the vast majority of adaptive immune responses. Generated following an immune response, memory CD4 T cells retain pertinent information about their activation environment enabling them to make rapid effector responses upon reactivation. These responses can either benefit the host by hastening the control of pathogens or cause damaging immunopathology. Here, we will discuss the diversity of the memory CD4 T cell pool, the signals that influence the transition of activated T cells into that pool, and highlight how activation requirements differ between naïve and memory CD4 T cells. A greater understanding of these factors has the potential to aid the design of more effective vaccines and to improve regulation of pathologic CD4 T cells, such as in the context of autoimmunity and allergy. PMID:26441961

  14. Dissecting How CD4 T Cells Are Lost During HIV Infection.

    PubMed

    Doitsh, Gilad; Greene, Warner C

    2016-03-01

    Although the replicative life cycle of HIV within CD4 T cells is understood in molecular detail, less is known about how this human retrovirus promotes the loss of CD4 T lymphocytes. It is this cell death process that drives clinical progression to acquired immune deficiency syndrome (AIDS). Recent studies have highlighted how abortive infection of resting and thus nonpermissive CD4 T cells in lymphoid tissues triggers a lethal innate immune response against the incomplete DNA products generated by inefficient viral reverse transcription in these cells. Sensing of these DNA fragments results in pyroptosis, a highly inflammatory form of programmed cell death, that potentially further perpetuates chronic inflammation and immune activation. As discussed here, these studies cast CD4 T cell death during HIV infection in a different light. Further, they identify drug targets that may be exploited to both block CD4 T cell demise and the chronic inflammatory response generated during pyroptosis. PMID:26962940

  15. The Interplay Between Monocytes/Macrophages and CD4+ T Cell Subsets in Rheumatoid Arthritis

    PubMed Central

    Roberts, Ceri A.; Dickinson, Abigail K.; Taams, Leonie S.

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by inflammation of the synovial lining (synovitis). The inflammation in the RA joint is associated with and driven by immune cell infiltration, synovial hyperproliferation, and excessive production of proinflammatory mediators, such as tumor necrosis factor α (TNFα), interferon γ (IFNγ), interleukin (IL)-1β, IL-6, and IL-17, eventually resulting in damage to the cartilage and underlying bone. The RA joint harbors a wide range of immune cell types, including monocytes, macrophages, and CD4+ T cells (both proinflammatory and regulatory). The interplay between CD14+ myeloid cells and CD4+ T cells can significantly influence CD4+ T cell function, and conversely, effector vs. regulatory CD4+ T cell subsets can exert profound effects on monocyte/macrophage function. In this review, we will discuss how the interplay between CD4+ T cells and monocytes/macrophages may contribute to the immunopathology of RA. PMID:26635790

  16. CD4+ T cell-dependent and CD4+ T cell-independent cytokine-chemokine network changes in the immune responses of HIV-infected individuals.

    PubMed

    Arnold, Kelly B; Szeto, Gregory L; Alter, Galit; Irvine, Darrell J; Lauffenburger, Douglas A

    2015-10-20

    A vital defect in the immune systems of HIV-infected individuals is the loss of CD4(+) T cells, resulting in impaired immune responses. We hypothesized that there were CD4(+) T cell-dependent and CD4(+) T cell-independent alterations in the immune responses of HIV-1(+) individuals. To test this, we analyzed the secretion of cytokines and chemokines from stimulated peripheral blood mononuclear cell (PBMC) populations from HIV(+) donors, healthy donors, and healthy donors with CD4(+) T cells experimentally depleted. Multivariate analyses of 16 cytokines and chemokines at 6 and 72 hours after three stimuli (antibody-coated beads to stimulate T cells and R848 or lipopolysaccharide to stimulate innate immune cells) enabled integrative analysis of secreted profiles. Two major effects in HIV(+) PBMCs were not reproduced upon depletion of CD4(+) T cells in healthy PBMCs: (i) HIV(+) PBMCs maintained T cell-associated secreted profiles after T cell stimulation; (ii) HIV(+) PBMCs showed impaired interferon-γ (IFN-γ) secretion early after innate stimulation. These changes arose from hyperactive T cells and debilitated natural killer (NK) cell, respectively. Modeling and experiments showed that early IFN-γ secretion predicted later differences in secreted profiles in vitro. This effect was recapitulated in healthy PBMCs by blocking the IFN-γ receptor. Thus, we identified a critical deficiency in NK cell responses of HIV-infected individuals, independent of CD4(+) T cell depletion, which directs secreted profiles. Our findings illustrate a broad approach for identifying key disease-associated nodes in a multicellular, multivariate signaling network. PMID:26486173

  17. Gut Mucosal FOXP3+ Regulatory CD4+ T Cells and Nonregulatory CD4+ T Cells Are Differentially Affected by Simian Immunodeficiency Virus Infection in Rhesus Macaques▿

    PubMed Central

    Allers, Kristina; Loddenkemper, Christoph; Hofmann, Jörg; Unbehaun, Anett; Kunkel, Désirée; Moos, Verena; Kaup, Franz-Josef; Stahl-Hennig, Christiane; Sauermann, Ulrike; Epple, Hans-Jörg; Schneider, Thomas

    2010-01-01

    The gastrointestinal tract represents a major site for human and simian immunodeficiency virus (HIV and SIV) replication and CD4+ T-cell depletion. Despite severe depletion of mucosal CD4+ T cells, FOXP3+ regulatory CD4+ T cells (Treg) are highly increased in the gut mucosa of chronically HIV-infected individuals and may contribute to HIV pathogenesis, either by their immunosuppressive function or as a significant target cell population for virus production. Little is known about the susceptibility of mucosal Treg to viral infection and the longitudinal effect of HIV/SIV infection on Treg dynamics. In this study, we determined the level of SIV infection in Treg and nonregulatory CD4+ T cells (non-Treg) isolated from the colon of SIV-infected rhesus macaques. The dynamics of mucosal Treg and alterations in the mucosal CD4+ T-cell pool were examined longitudinally. Our findings indicate that mucosal Treg were less susceptible to productive SIV infection than non-Treg and thus were selectively spared from SIV-mediated cell death. In addition to improved survival, local expansion of Treg by SIV-induced proliferation of the mucosal CD4+ T-cell pool facilitated the accumulation of mucosal Treg during the course of infection. High frequency of mucosal Treg in chronic SIV infection was strongly related to a reduction of perforin-expressing cells. In conclusion, this study suggests that mucosal Treg are less affected by productive SIV infection than non-Treg and therefore spared from depletion. Although SIV production is limited in mucosal Treg, Treg accumulation may indirectly contribute to viral persistence by suppressing antiviral immune responses. PMID:20071575

  18. Eomesodermin Expression in CD4+ T Cells Restricts Peripheral Foxp3 Induction.

    PubMed

    Lupar, Ekaterina; Brack, Maria; Garnier, Laure; Laffont, Sophie; Rauch, Katharina S; Schachtrup, Kristina; Arnold, Sebastian J; Guéry, Jean-Charles; Izcue, Ana

    2015-11-15

    CD4(+) T cells polarize into effector Th subsets characterized by signature transcription factors and cytokines. Although T-bet drives Th1 responses and represses the alternative Th2, Th17, and Foxp3(+) regulatory T cell fates, the role of the T-bet-related transcription factor eomesodermin (Eomes) in CD4(+) T cells is less well understood. In this study, we analyze the expression and effects of Eomes in mouse CD4(+) T lymphocytes. We find that Eomes is readily expressed in activated CD4(+) Th1 T cells in vivo. Eomes(+) CD4(+) T cells accumulated in old mice, under lymphopenic conditions in a T cell transfer model of colitis, and upon oral Ag administration. However, despite its expression, genetic deletion of Eomes in CD4(+) T cells did not impact on IFN-γ production nor increase Th2 or Th17 responses. In contrast, Eomes deficiency favored the accumulation of Foxp3(+) cells in old mice, after in vivo differentiation of Eomes-deficient naive CD4(+) T cells, and in response to oral Ag in a cell-intrinsic way. Enforced Eomes expression during in vitro regulatory T cell induction also reduced Foxp3 transcription. Likewise, bystander Eomes-deficient CD4(+) T cells were more efficient at protecting from experimental autoimmune encephalitis compared with wild-type CD4(+) T cells. This enhanced capacity of Eomes-deficient CD4(+) T cells to inhibit EAE in trans was associated with an enhanced frequency of Foxp3(+) cells. Our data identify a novel role for Eomes in CD4(+) T cells and indicate that Eomes expression may act by limiting Foxp3 induction, which may contribute to the association of EOMES to susceptibility to multiple sclerosis. PMID:26453746

  19. Transient voltage oscillations in coils

    SciTech Connect

    Chowdhuri, P.

    1985-01-01

    Magnet coils may be excited into internal voltage oscillations by transient voltages. Such oscillations may electrically stress the magnet's dielectric components to many times its normal stress. This may precipitate a dielectric failure, and the attendant prolonged loss of service and costly repair work. Therefore, it is important to know the natural frequencies of oscillations of a magnet during the design stage, and to determine whether the expected switching transient voltages can excite the magnet into high-voltage internal oscillations. The series capacitance of a winding significantly affects its natural frequencies. However, the series capacitance is difficult to calculate, because it may comprise complex capacitance network, consisting of intra- and inter-coil turn-to-turn capacitances of the coil sections. A method of calculating the series capacitance of a winding is proposed. This method is rigorous but simple to execute. The time-varying transient voltages along the winding are also calculated.

  20. Higgs in bosonic channels (CMS)

    NASA Astrophysics Data System (ADS)

    Gori, Valentina

    2015-05-01

    The main Higgs boson decays into bosonic channels will be considered, presenting and discussing results from the latest reprocessing of data collected by the CMS experiment at the LHC, using the full dataset recorded at centre-of-mass energies of 7 and 8 TeV. For this purpose, results from the final Run-I papers for the H → ZZ → 4ℓ, H → γγ and H → WW analyses are presented, focusing on the Higgs boson properties, like the mass, the signal strenght, the couplings to fermions and vector bosons, the spin and parity properties. Furthermore, the Higgs boson width measurement exploiting the on-shell versus the off-shell cross section (in the H → ZZ → 4ℓ and H → ZZ → 2ℓ2ν decay channels) will be shown. All the investigated properties result to be fully consistent with the SM predictions: the signal strength and the signal strength modifiers are consistent with unity in all the bosonic channels considered; the hypothesis of a scalar particle is strongly favored, against the pseudoscalar or the vector/pseudovector or the spin-2 boson hypotheses (all excluded at 99% CL or higher in the H → ZZ → 4ℓ channel). The Higgs boson mass measurement from the combination of H → ZZ → 4ℓ and H → γγ channels gives a value mH = 125.03+0.26-0.27 (stat.) +0.13-0.15 (syst.). An upper limit ΓH < 22 MeV can be put on the Higgs boson width thanks to the new indirect method.

  1. The structure of the GemC1 coiled coil and its interaction with the Geminin family of coiled-coil proteins

    SciTech Connect

    Caillat, Christophe; Fish, Alexander; Pefani, Dafni-Eleftheria; Taraviras, Stavros; Lygerou, Zoi; Perrakis, Anastassis

    2015-10-31

    The GemC1 coiled-coil structure has subtle differences compared with its homologues Geminin and Idas. Co-expression experiments in cells and biophysical stability analysis of the Geminin-family coiled coils suggest that the GemC1 coiled coil alone is unstable. GemC1, together with Idas and Geminin, an important regulator of DNA-replication licensing and differentiation decisions, constitute a superfamily sharing a homologous central coiled-coil domain. To better understand this family of proteins, the crystal structure of a GemC1 coiled-coil domain variant engineered for better solubility was determined to 2.2 Å resolution. GemC1 shows a less typical coiled coil compared with the Geminin homodimer and the Geminin–Idas heterodimer structures. It is also shown that both in vitro and in cells GemC1 interacts with Geminin through its coiled-coil domain, forming a heterodimer that is more stable that the GemC1 homodimer. Comparative analysis of the thermal stability of all of the possible superfamily complexes, using circular dichroism to follow the unfolding of the entire helix of the coiled coil, or intrinsic tryptophan fluorescence of a unique conserved N-terminal tryptophan, shows that the unfolding of the coiled coil is likely to take place from the C-terminus towards the N-terminus. It is also shown that homodimers show a single-state unfolding, while heterodimers show a two-state unfolding, suggesting that the dimer first falls apart and the helices then unfold according to the stability of each protein. The findings argue that Geminin-family members form homodimers and heterodimers between them, and this ability is likely to be important for modulating their function in cycling and differentiating cells.

  2. Electromagnetic Gun With Commutated Coils

    NASA Technical Reports Server (NTRS)

    Elliott, David G.

    1991-01-01

    Proposed electromagnetic gun includes electromagnet coil, turns of which commutated in sequence along barrel. Electrical current fed to two armatures by brushes sliding on bus bars in barrel. Interaction between armature currents and magnetic field from coil produces force accelerating armature, which in turn, pushes on projectile. Commutation scheme chosen so magnetic field approximately coincides and moves with cylindrical region defined by armatures. Scheme has disadvantage of complexity, but in return, enables designer to increase driving magnetic field without increasing armature current. Attainable muzzle velocity increased substantially.

  3. SAMHD1 restricts HIV-1 infection in resting CD4+ T cells

    PubMed Central

    Baldauf, Hanna-Mari; Pan, Xiaoyu; Erikson, Elina; Schmidt, Sarah; Daddacha, Waaqo; Burggraf, Manja; Schenkova, Kristina; Ambiel, Ina; Wabnitz, Guido; Gramberg, Thomas; Panitz, Sylvia; Flory, Egbert; Landau, Nathaniel R; Sertel, Serkan; Rutsch, Frank; Lasitschka, Felix; Kim, Baek; König, Renate; Fackler, Oliver T; Keppler, Oliver T

    2013-01-01

    Unlike activated CD4+ T cells, resting CD4+ T cells are highly resistant to productive HIV-1 infection1–8. Early after HIV-1 entry, a major block limits reverse transcription of incoming viral genomes. Here we show that the deoxynucleoside triphosphate triphosphohydrolase SAMHD1 prevents reverse transcription of HIV-1 RNA in resting CD4+ T cells. SAMHD1 is abundantly expressed in resting CD4+ T cells circulating in peripheral blood and residing in lymphoid organs. The early restriction to infection in unstimulated CD4+ T cells is overcome by HIV-1 or HIV-2 virions into which viral Vpx is artificially or naturally packaged, respectively, or by addition of exogenous deoxynucleosides. Vpx-mediated proteasomal degradation of SAMHD1 and elevation of intracellular deoxynucleotide pools precede successful infection by Vpx-carrying HIV. Resting CD4+ T cells from healthy donors following SAMHD1 silencing or from a patient with Aicardi-Goutières syndrome homozygous for a nonsense mutation in SAMHD1 were permissive for HIV-1 infection. Thus, SAMHD1 imposes an effective restriction to HIV-1 infection in the large pool of noncycling CD4+ T cells in vivo. Bypassing SAMHD1 was insufficient for the release of viral progeny, implicating other barriers at later stages of HIV replication. Together, these findings may unveil new ways to interfere with the immune evasion and T cell immunopathology of pandemic HIV-1. PMID:22972397

  4. Itk Signals Promote Neuroinflammation by Regulating CD4+ T-Cell Activation and Trafficking

    PubMed Central

    Kannan, Arun K.; Kim, Do-Geun

    2015-01-01

    Here we demonstrate that interleukin-2-inducible T-cell kinase (Itk) signaling in cluster of differentiation 4-positive (CD4+) T cells promotes experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). We show that Itk−/− mice exhibit reduced disease severity, and transfer of Itk−/− CD4+ T cells into T cell-deficient recipients results in lower disease severity. We observed a significant reduction of CD4+ T cells in the CNS of Itk−/− mice or recipients of Itk−/− CD4+ T cells during EAE, which is consistent with attenuated disease. Itk−/− CD4+ T cells exhibit defective response to myelin antigen stimulation attributable to displacement of filamentous actin from the CD4+ coreceptor. This results in inadequate transmigration of Itk−/− CD4+ T cells into the CNS and across brain endothelial barriers in vitro. Finally, Itk−/− CD4+ T cells show significant reduction in production of T-helper 1 (Th1) and Th17 cytokines and exhibit skewed T effector/T regulatory cell ratios. These results indicate that signaling by Itk promotes autoimmunity and CNS inflammation, suggesting that it may be a viable target for treatment of MS. PMID:25568116

  5. Mannose-Capped Lipoarabinomannan from Mycobacterium tuberculosis Induces CD4+ T Cell Anergy via GRAIL.

    PubMed

    Sande, Obondo J; Karim, Ahmad F; Li, Qing; Ding, Xuedong; Harding, Clifford V; Rojas, Roxana E; Boom, W Henry

    2016-01-15

    Mycobacterium tuberculosis cell wall glycolipid, lipoarabinomannan, can inhibit CD4(+) T cell activation by downregulating the phosphorylation of key proximal TCR signaling molecules: Lck, CD3ζ, ZAP70, and LAT. Inhibition of proximal TCR signaling can result in T cell anergy, in which T cells are inactivated following an Ag encounter, yet remain viable and hyporesponsive. We tested whether mannose-capped lipoarabinomannan (LAM)-induced inhibition of CD4(+) T cell activation resulted in CD4(+) T cell anergy. The presence of LAM during primary stimulation of P25 TCR-transgenic murine CD4(+) T cells with M. tuberculosis Ag85B peptide resulted in decreased proliferation and IL-2 production. P25 TCR-transgenic CD4(+) T cells primed in the presence of LAM also exhibited decreased response upon restimulation with Ag85B. The T cell anergic state persisted after the removal of LAM. Hyporesponsiveness to restimulation was not due to apoptosis, generation of Foxp3-positive regulatory T cells, or inhibitory cytokines. Acquisition of the anergic phenotype correlated with upregulation of gene related to anergy in lymphocytes (GRAIL) protein in CD4(+) T cells. Inhibition of human CD4(+) T cell activation by LAM also was associated with increased GRAIL expression. Small interfering RNA-mediated knockdown of GRAIL before LAM treatment abrogated LAM-induced hyporesponsiveness. In addition, exogenous IL-2 reversed defective proliferation by downregulating GRAIL expression. These results demonstrate that LAM upregulates GRAIL to induce anergy in Ag-reactive CD4(+) T cells. Induction of CD4(+) T cell anergy by LAM may represent one mechanism by which M. tuberculosis evades T cell recognition. PMID:26667170

  6. Hydrogen peroxide-dependent 4-t-butylphenol hydroxylation by tyrosinase--a new catalytic activity.

    PubMed

    Jiménez, M; García-Carmona, F

    1996-09-13

    The aim of this work was to study the hydroxylation by tyrosinase of 4-t-butylphenol to 4-t-butylcatechol, in the presence of hydrogen peroxide. This hydroxylation reaction does not take place without the addition of hydrogen peroxide. Some properties of this new hydroxylating activity have been analysed. The kinetic parameters of mushroom tyrosinase for hydrogen peroxide (K(m) = 4.9 mM, V(m) = 48.1 microM/min) and 4-t-butylphenol (K(m) = 16 microM/min, V(m) = 6.7 microM/min) were evaluated. A lag period appeared, which was similar to the characteristic lag of monophenolase activity at the expense of molecular oxygen. The length of the lag phase decreased with increasing hydrogen peroxide concentrations but was longer with higher 4-t-butylphenol concentrations. The pH optimum for this hydroxylating activity was close to 5.5. The lag also varied with pH, reaching its highest value at pH 4.8. The lag was shortened by the addition of increasing amounts of 4-t-butylcatechol, and was abolished at 24.5 microM of 4-t-butylcatechol. 4-t-Butylphenol was oxidized by mushroom tyrosinase in the presence of 24.5 microM 4-t-butylcatechol and in the absence of hydrogen peroxide although the enzymatic activity tailed off. The presence of hydrogen peroxide is necessary to maintain a constant steady-state rate of 4-t-butylphenol oxidation by tyrosinase. PMID:8841378

  7. [Two Cases of Ruptured Cerebral Aneurysm Complicated with Delayed Coil Protrusion after Coil Embolization].

    PubMed

    Furukawa, Takashi; Ogata, Atsushi; Ebashi, Ryo; Takase, Yukinori; Masuoka, Jun; Kawashima, Masatou; Abe, Tatsuya

    2016-07-01

    We report two cases of delayed coil protrusion after coil embolization for ruptured cerebral aneurysms. Case 1:An 82-year-old woman with a subarachnoid hemorrhage due to a ruptured small anterior communicating artery aneurysm underwent successful coil embolization. Eighteen days after the procedure, coil protrusion from the aneurysm into the right anterior cerebral artery was observed without any symptoms. Further coil protrusion did not develop after 28 days. Case 2:A 78-year-old woman with a subarachnoid hemorrhage due to a ruptured small left middle cerebral artery aneurysm underwent successful coil embolization. Twenty days after the procedure, coil protrusion from the aneurysm into the left middle cerebral artery was observed, with a transient ischemic attack. Further coil protrusion did not develop. Both patients recovered with antithrombotic treatment. Even though delayed coil protrusion after coil embolization is rare, it should be recognized as a long-term complication of coil embolization for cerebral aneurysms. PMID:27384117

  8. The CMS Beam Halo Monitor electronics

    NASA Astrophysics Data System (ADS)

    Tosi, N.; Dabrowski, A. E.; Fabbri, F.; Grassi, T.; Hughes, E.; Mans, J.; Montanari, A.; Orfanelli, S.; Rusack, R.; Torromeo, G.; Stickland, D. P.; Stifter, K.

    2016-02-01

    The CMS Beam Halo Monitor has been successfully installed in the CMS cavern in LHC Long Shutdown 1 for measuring the machine induced background for LHC Run II. The system is based on 40 detector units composed of synthetic quartz Cherenkov radiators coupled to fast photomultiplier tubes (PMTs). The readout electronics chain uses many components developed for the Phase 1 upgrade to the CMS Hadronic Calorimeter electronics, with dedicated firmware and readout adapted to the beam monitoring requirements. The PMT signal is digitized by a charge integrating ASIC (QIE10), providing both the signal rise time, with few nanosecond resolution, and the charge integrated over one bunch crossing. The backend electronics uses microTCA technology and receives data via a high-speed 5 Gbps asynchronous link. It records histograms with sub-bunch crossing timing resolution and is read out via IPbus using the newly designed CMS data acquisition for non-event based data. The data is processed in real time and published to CMS and the LHC, providing online feedback on the beam quality. A dedicated calibration monitoring system has been designed to generate short triggered pulses of light to monitor the efficiency of the system. The electronics has been in operation since the first LHC beams of Run II and has served as the first demonstration of the new QIE10, Microsemi Igloo2 FPGA and high-speed 5 Gbps link with LHC data.

  9. Finite element coiled cochlea model

    NASA Astrophysics Data System (ADS)

    Isailovic, Velibor; Nikolic, Milica; Milosevic, Zarko; Saveljic, Igor; Nikolic, Dalibor; Radovic, Milos; Filipović, Nenad

    2015-12-01

    Cochlea is important part of the hearing system, and thanks to special structure converts external sound waves into neural impulses which go to the brain. Shape of the cochlea is like snail, so geometry of the cochlea model is complex. The simplified cochlea coiled model was developed using finite element method inside SIFEM FP7 project. Software application is created on the way that user can prescribe set of the parameters for spiral cochlea, as well as material properties and boundary conditions to the model. Several mathematical models were tested. The acoustic wave equation for describing fluid in the cochlea chambers - scala vestibuli and scala timpani, and Newtonian dynamics for describing vibrations of the basilar membrane are used. The mechanical behavior of the coiled cochlea was analyzed and the third chamber, scala media, was not modeled because it does not have a significant impact on the mechanical vibrations of the basilar membrane. The obtained results are in good agreement with experimental measurements. Future work is needed for more realistic geometry model. Coiled model of the cochlea was created and results are compared with initial simplified coiled model of the cochlea.

  10. Wedding ring shaped excitation coil

    DOEpatents

    MacLennan, Donald A.; Tsai, Peter

    2001-01-01

    A high frequency inductively coupled electrodeless lamp includes an excitation coil with an effective electrical length which is less than one half wavelength of a driving frequency applied thereto, preferably much less. The driving frequency may be greater than 100 MHz and is preferably as high as 915 MHz. Preferably, the excitation coil is configured as a non-helical, semi-cylindrical conductive surface having less than one turn, in the general shape of a wedding ring. At high frequencies, the current in the coil forms two loops which are spaced apart and parallel to each other. Configured appropriately, the coil approximates a Helmholtz configuration. The lamp preferably utilizes an bulb encased in a reflective ceramic cup with a pre-formed aperture defined therethrough. The ceramic cup may include structural features to aid in alignment and/or a flanged face to aid in thermal management. The lamp head is preferably an integrated lamp head comprising a metal matrix composite surrounding an insulating ceramic with the excitation integrally formed on the ceramic. A novel solid-state oscillator preferably provides RF power to the lamp. The oscillator is a single active element device capable of providing over 70 watts of power at over 70% efficiency.

  11. Coupled Coils, Magnets and Lenz's Law

    ERIC Educational Resources Information Center

    Thompson, Frank

    2010-01-01

    Great scientists in the past have experimented with coils and magnets. Here we have a variation where coupling occurs between two coils and the oscillatory motion of two magnets to give somewhat surprising results. (Contains 6 figures and 1 footnote.)

  12. Radiation experience with the CMS pixel detector

    NASA Astrophysics Data System (ADS)

    Veszpremi, V.

    2015-04-01

    The CMS pixel detector is the innermost component of the CMS tracker occupying the region around the centre of CMS, where the LHC beams are crossed, between 4.3 cm and 30 cm in radius and 46.5 cm along the beam axis. It operates in a high-occupancy and high-radiation environment created by particle collisions. Studies of radiation damage effects to the sensors were performed throughout the first running period of the LHC . Leakage current, depletion voltage, pixel readout thresholds, and hit finding efficiencies were monitored as functions of the increasing particle fluence. The methods and results of these measurements will be described together with their implications to detector operation as well as to performance parameters in offline hit reconstruction.

  13. Calorimeter Simulation with Hadrons in CMS

    SciTech Connect

    Piperov, Stefan; /Sofiya, Inst. Nucl. Res. /Fermilab

    2008-11-01

    CMS is using Geant4 to simulate the detector setup for the forthcoming data from the LHC. Validation of physics processes inside Geant4 is a major concern in view of getting a proper description of jets and missing energy for signal and background events. This is done by carrying out an extensive studies with test beam using the prototypes or real detector modules of the CMS calorimeter. These data are matched with Geant4 predictions using the same framework that is used for the entire CMS detector. Tuning of the Geant4 models is carried out and steps to be used in reproducing detector signals are defined in view of measurements of energy response, energy resolution, transverse and longitudinal shower profiles for a variety of hadron beams over a broad energy spectrum between 2 to 300 GeV/c. The tuned Monte Carlo predictions match many of these measurements within systematic uncertainties.

  14. Commissioning of the Cms Tracker Outer Barrel

    NASA Astrophysics Data System (ADS)

    Bloch, Christoph

    2006-04-01

    Fully equipped final substructures of the CMS Tracker are installed in a dedicated mechanical support, the Cosmic Rack, providing a geometry suitable for tracking cosmic muons, and equipped with a dedicated trigger that allows the selection of tracks synchronous with the fast readout electronics. Data collected at room temperature and at the tracker operating temperature of -10°C can be used to test reconstruction and alignment algorithms for the tracker, as well as to perform a detailed qualification of the geometry and the functionality of the structures at different temperatures. The CMS Monte Carlo simulation has been adapted to the geometry of the cosmic rack, and the comparison with the data will provide a valuable test to improve the tracker simulation in CMS.

  15. The Physics of the CMS Experiment

    SciTech Connect

    Sanabria, J. C.

    2007-10-26

    The Large Hadron Collider (LHC) at CERN will start running 2008 producing proton-proton collisions with a center-of-mass energy of 14 TeV. Four large experiments will operate together with this accelerator: ALICE, ATLAS, CMS and LHCb. The main scientific goal of this project is to understand in detail the mechanism for electro-weak symmetry breaking and to search for physics beyond the standard model of particles. ATLAS and CMS are general purpose detectors designed for search and discovery of new physics, and optimized to search for Higgs and signals of supersymmetric matter (SUSY). In this paper the main features of the CMS detector will be presented and its potential for Higgs and SUSY discoveries will be discussed.

  16. Plans for Jet Energy Corrections at CMS

    NASA Astrophysics Data System (ADS)

    Mishra, Kalanand

    2009-05-01

    We present a plan for Jet Energy Corrections at CMS. Jet corrections at CMS will come initially from simulation tuned on test beam data, directly from collision data when available, and ultimately from a simulation tuned on collision data. The corrections will be factorized into a fixed sequence of sub-corrections associated with different detector and physics effects. The following three factors are minimum requirements for most analysis: offset corrections for pile-up and noise; correction for the response of the calorimeter as a function of jet pseudorapidity relative to the barrel; correction for the absolute response as a function of transverse momentum in the barrel. The required correction gives a jet Lorentz vector equivalent to the sum of particles in the jet cone emanating from a QCD hard collision. We discuss the status of these corrections, the planned data-driven techniques for their derivation, and their anticipated evolution with the stages of the CMS experiment.

  17. Fireworks: A physics event display for CMS

    SciTech Connect

    Kovalskyi, D.; Tadel, M.; Mrak-Tadel, A.; Bellenot, B.; Kuznetsov, V.; Jones, C.D.; Bauerdick, L. Case, M.; Mulmenstadt, J.; Yagil, A.; /UC, San Diego

    2010-01-01

    Fireworks is a CMS event display which is specialized for the physics studies case. This specialization allows us to use a stylized rather than 3D-accurate representation when appropriate. Data handling is greatly simplified by using only reconstructed information and ideal geometry. Fireworks provides an easy-to-use interface which allows a physicist to concentrate only on the data in which he is interested. Data is presented via graphical and textual views. Fireworks is built using the Eve subsystem of the CERN ROOT project and CMS's FWLite project. The FWLite project was part of CMS's recent code redesign which separates data classes into libraries separate from algorithms producing the data and uses ROOT directly for C++ object storage, thereby allowing the data classes to be used directly in ROOT.

  18. Power Studies for the CMS Pixel Tracker

    SciTech Connect

    Todri, A.; Turqueti, M.; Rivera, R.; Kwan, S.; /Fermilab

    2009-01-01

    The Electronic Systems Engineering Department of the Computing Division at the Fermi National Accelerator Laboratory is carrying out R&D investigations for the upgrade of the power distribution system of the Compact Muon Solenoid (CMS) Pixel Tracker at the Large Hadron Collider (LHC). Among the goals of this effort is that of analyzing the feasibility of alternative powering schemes for the forward tracker, including DC to DC voltage conversion techniques using commercially available and custom switching regulator circuits. Tests of these approaches are performed using the PSI46 pixel readout chip currently in use at the CMS Tracker. Performance measures of the detector electronics will include pixel noise and threshold dispersion results. Issues related to susceptibility to switching noise will be studied and presented. In this paper, we describe the current power distribution network of the CMS Tracker, study the implications of the proposed upgrade with DC-DC converters powering scheme and perform noise susceptibility analysis.

  19. Power distribution studies for CMS forward tracker

    SciTech Connect

    Todri, A.; Turqueti, M.; Rivera, R.; Kwan, S.

    2009-01-01

    The Electronic Systems Engineering Department of the Computing Division at the Fermi National Accelerator Laboratory is carrying out R&D investigations for the upgrade of the power distribution system of the Compact Muon Solenoid (CMS) Pixel Tracker at the Large Hadron Collider (LHC). Among the goals of this effort is that of analyzing the feasibility of alternative powering schemes for the forward tracker, including DC to DC voltage conversion techniques using commercially available and custom switching regulator circuits. Tests of these approaches are performed using the PSI46 pixel readout chip currently in use at the CMS Tracker. Performance measures of the detector electronics will include pixel noise and threshold dispersion results. Issues related to susceptibility to switching noise will be studied and presented. In this paper, we describe the current power distribution network of the CMS Tracker, study the implications of the proposed upgrade with DC-DC converters powering scheme and perform noise susceptibility analysis.

  20. Remote Operations for LHC and CMS

    SciTech Connect

    Gottschalk, E.E.; /Fermilab

    2007-04-01

    Commissioning the Large Hadron Collider (LHC) and its experiments will be a vital part of the worldwide high energy physics program beginning in 2007. A remote operations center has been built at Fermilab to contribute to commissioning and operations of the LHC and the Compact Muon Solenoid (CMS) experiment, and to develop new capabilities for real-time data analysis and monitoring for LHC, CMS, and grid computing. Remote operations will also be essential to a future International Linear Collider with its multiple, internationally distributed control rooms. In this paper we present an overview of Fermilab's LHC@FNAL remote operations center for LHC and CMS, describe what led up to the development of the center, and describe noteworthy features of the center.

  1. Human CD141+ DCs induce CD4+ T cells to produce type 2 cytokines1

    PubMed Central

    Yu, Chun I; Becker, Christian; Metang, Patrick; Marches, Florentina; Wang, Yuanyuan; Toshiyuki, Hori; Banchereau, Jacques; Merad, Miriam; Palucka, Karolina

    2014-01-01

    Dendritic cells (DCs) play the central role in the priming of naïve T cells and the differentiation of unique effector T cells. Here, using lung tissues and blood from both humans and humanized mice, we analyzed the response of human CD1c+ and CD141+ DC subsets to live-attenuated influenza virus (LAIV). Specifically, we analyzed the type of CD4+ T cell immunity elicited by LAIV-exposed DCs. Both DC subsets induce proliferation of allogeneic naïve CD4+ T cells with capacity to secrete IFN-γ. However, CD141+ DCs are uniquely able to induce the differentiation of IL-4 and IL-13 producing CD4+ T cells. CD141+ DCs induce IL-4 and IL-13 secreting CD4+ T cells through OX40L. Thus, CD141+ DCs demonstrate remarkable plasticity in guiding adaptive immune responses. PMID:25246496

  2. Radiative recombination kinetics in electroluminescent spin cast pristine α-4T

    NASA Astrophysics Data System (ADS)

    Ben Hamed, Zied; Kouki, Fayçal; Bouchriha, Habib; Mejatty, Mohamed

    2016-09-01

    Many experimental studies have established the substantial impact of the sound structure of the organic thin films on optoelectronic device performances. This study is a collection of experimental and theoretical investigation of the radiative recombination kinetics in an organic light emitting diode based on spin cast α-4T. The structural properties of the organic thin films (α-4T) deposited by the spin coating technique are discussed. The electrical characterization of the diode-like samples (ITO/α-4T/Al) have revealed a very low effective mobility of charge carriers in the spin cast α-4Tand the radiative recombination current was extracted. The luminescence-current characterization of the diode-like samples (ITO/α-4T/Al) was investigated and modeled.

  3. Interleukin-7 is required for CD4(+) T cell activation and autoimmune neuroinflammation.

    PubMed

    Lawson, Brian R; Gonzalez-Quintial, Rosana; Eleftheriadis, Theodoros; Farrar, Michael A; Miller, Stephen D; Sauer, Karsten; McGavern, Dorian B; Kono, Dwight H; Baccala, Roberto; Theofilopoulos, Argyrios N

    2015-12-01

    IL-7 is known to be vital for T cell homeostasis but has previously been presumed to be dispensable for TCR-induced activation. Here, we show that IL-7 is critical for the initial activation of CD4(+) T cells in that it provides some of the necessary early signaling components, such as activated STAT5 and Akt. Accordingly, short-term in vivo IL-7Rα blockade inhibited the activation and expansion of autoantigen-specific CD4(+) T cells and, when used to treat experimental autoimmune encephalomyelitis (EAE), prevented and ameliorated disease. Our studies demonstrate that IL-7 signaling is a prerequisite for optimal CD4(+) T cell activation and that IL-7R antagonism may be effective in treating CD4(+) T cell-mediated neuroinflammation and other autoimmune inflammatory conditions. PMID:26319414

  4. Clonally expanded CD4+ T cells can produce infectious HIV-1 in vivo.

    PubMed

    Simonetti, Francesco R; Sobolewski, Michele D; Fyne, Elizabeth; Shao, Wei; Spindler, Jonathan; Hattori, Junko; Anderson, Elizabeth M; Watters, Sarah A; Hill, Shawn; Wu, Xiaolin; Wells, David; Su, Li; Luke, Brian T; Halvas, Elias K; Besson, Guillaume; Penrose, Kerri J; Yang, Zhiming; Kwan, Richard W; Van Waes, Carter; Uldrick, Thomas; Citrin, Deborah E; Kovacs, Joseph; Polis, Michael A; Rehm, Catherine A; Gorelick, Robert; Piatak, Michael; Keele, Brandon F; Kearney, Mary F; Coffin, John M; Hughes, Stephen H; Mellors, John W; Maldarelli, Frank

    2016-02-16

    Reservoirs of infectious HIV-1 persist despite years of combination antiretroviral therapy and make curing HIV-1 infections a major challenge. Most of the proviral DNA resides in CD4(+)T cells. Some of these CD4(+)T cells are clonally expanded; most of the proviruses are defective. It is not known if any of the clonally expanded cells carry replication-competent proviruses. We report that a highly expanded CD4(+) T-cell clone contains an intact provirus. The highly expanded clone produced infectious virus that was detected as persistent plasma viremia during cART in an HIV-1-infected patient who had squamous cell cancer. Cells containing the intact provirus were widely distributed and significantly enriched in cancer metastases. These results show that clonally expanded CD4(+)T cells can be a reservoir of infectious HIV-1. PMID:26858442

  5. Clonally expanded CD4+ T cells can produce infectious HIV-1 in vivo

    PubMed Central

    Simonetti, Francesco R.; Sobolewski, Michele D.; Fyne, Elizabeth; Shao, Wei; Spindler, Jonathan; Hattori, Junko; Anderson, Elizabeth M.; Watters, Sarah A.; Hill, Shawn; Wu, Xiaolin; Wells, David; Su, Li; Luke, Brian T.; Halvas, Elias K.; Besson, Guillaume; Penrose, Kerri J.; Yang, Zhiming; Kwan, Richard W.; Van Waes, Carter; Uldrick, Thomas; Citrin, Deborah E.; Kovacs, Joseph; Polis, Michael A.; Rehm, Catherine A.; Gorelick, Robert; Piatak, Michael; Keele, Brandon F.; Kearney, Mary F.; Coffin, John M.; Hughes, Stephen H.; Mellors, John W.; Maldarelli, Frank

    2016-01-01

    Reservoirs of infectious HIV-1 persist despite years of combination antiretroviral therapy and make curing HIV-1 infections a major challenge. Most of the proviral DNA resides in CD4+T cells. Some of these CD4+T cells are clonally expanded; most of the proviruses are defective. It is not known if any of the clonally expanded cells carry replication-competent proviruses. We report that a highly expanded CD4+ T-cell clone contains an intact provirus. The highly expanded clone produced infectious virus that was detected as persistent plasma viremia during cART in an HIV-1–infected patient who had squamous cell cancer. Cells containing the intact provirus were widely distributed and significantly enriched in cancer metastases. These results show that clonally expanded CD4+T cells can be a reservoir of infectious HIV-1. PMID:26858442

  6. CD4 T Cell Responses in Latent and Chronic Viral Infections

    PubMed Central

    Walton, Senta; Mandaric, Sanja; Oxenius, Annette

    2013-01-01

    The spectrum of tasks which is fulfilled by CD4 T cells in the setting of viral infections is large, ranging from support of CD8 T cells and humoral immunity to exertion of direct antiviral effector functions. While our knowledge about the differentiation pathways, plasticity, and memory of CD4 T cell responses upon acute infections or immunizations has significantly increased during the past years, much less is still known about CD4 T cell differentiation and their beneficial or pathological functions during persistent viral infections. In this review we summarize current knowledge about the differentiation, direct or indirect antiviral effector functions, and the regulation of virus-specific CD4 T cells in the setting of persistent latent or active chronic viral infections with a particular emphasis on herpes virus infections for the former and chronic lymphocytic choriomeningitis virus infection for the latter. PMID:23717308

  7. Bow-shaped toroidal field coils

    SciTech Connect

    Bonanos, P.

    1981-05-01

    Design features of Bow-Shaped Toroidal Field Coils are described and compared with circular and D shaped coils. The results indicate that bow coils can produce higher field strengths, store more energy and be made demountable. The design offers the potential for the production of ultrahigh toroidal fields. Included are representative coil shapes and their engineering properties, a suggested structural design and an analysis of a specific case.

  8. Multi-Canted Coils, Tubes, and Structures

    NASA Technical Reports Server (NTRS)

    Jaster, Mark L. (Inventor)

    2015-01-01

    Coil, tube, and other structures configured with a plurality of individual coils, internal structures, legs or extensions with each having multiple cants per coil, internal structure, leg or extension, and wherein the cants formed therein allow for a load-deflection force when each is compressed. In addition, any horizontal or moment forces are substantially reduced and/or eliminated when a downward vertical force is applied, as minimal or no torsion is created in the individual coils, legs or extensions.

  9. Design and modelling of a SMES coil

    NASA Astrophysics Data System (ADS)

    Yuan, Weijia; Campbell, A. M.; Coombs, T. A.

    2010-06-01

    The design of a Superconducting Magnetic Energy Storage (SMES) coil wound by coated conductors has been presented. Based on an existing model for coated conductor pancake coils, this paper analysed the magnetic field and current density distribution of the coil at two different operation temperatures, 77K and 22K. A comparison table of the critical currents and AC losses at these two temperatures has been presented. Several steps to improve the transport current of the coil have been suggested as well.

  10. Rotor assembly including superconducting magnetic coil

    DOEpatents

    Snitchler, Gregory L.; Gamble, Bruce B.; Voccio, John P.

    2003-01-01

    Superconducting coils and methods of manufacture include a superconductor tape wound concentrically about and disposed along an axis of the coil to define an opening having a dimension which gradually decreases, in the direction along the axis, from a first end to a second end of the coil. Each turn of the superconductor tape has a broad surface maintained substantially parallel to the axis of the coil.

  11. The CMS CERN Analysis Facility (CAF)

    NASA Astrophysics Data System (ADS)

    Buchmüller, O.; Bonacorsi, D.; Fanzago, F.; Gowdy, S.; Kreuzer, P.; Malgeri, L.; Mankel, R.; Metson, S.; Panzer-Steindel, B.; Afonso Sanches, J.; Schwickerath, U.; Spiga, D.; Teodoro, D.; Többicke, Rainer

    2010-04-01

    The CMS CERN Analysis Facility (CAF) was primarily designed to host a large variety of latency-critical workflows. These break down into alignment and calibration, detector commissioning and diagnosis, and high-interest physics analysis requiring fast-turnaround. In addition to the low latency requirement on the batch farm, another mandatory condition is the efficient access to the RAW detector data stored at the CERN Tier-0 facility. The CMS CAF also foresees resources for interactive login by a large number of CMS collaborators located at CERN, as an entry point for their day-by-day analysis. These resources will run on a separate partition in order to protect the high-priority use-cases described above. While the CMS CAF represents only a modest fraction of the overall CMS resources on the WLCG GRID, an appropriately sized user-support service needs to be provided. We will describe the building, commissioning and operation of the CMS CAF during the year 2008. The facility was heavily and routinely used by almost 250 users during multiple commissioning and data challenge periods. It reached a CPU capacity of 1.4MSI2K and a disk capacity at the Peta byte scale. In particular, we will focus on the performances in terms of networking, disk access and job efficiency and extrapolate prospects for the upcoming LHC first year data taking. We will also present the experience gained and the limitations observed in operating such a large facility, in which well controlled workflows are combined with more chaotic type analysis by a large number of physicists.

  12. Nuclear Retention of Multiply Spliced HIV-1 RNA in Resting CD4+ T Cells

    PubMed Central

    Lassen, Kara G; Ramyar, Kasra X; Bailey, Justin R; Zhou, Yan; Siliciano, Robert F

    2006-01-01

    HIV-1 latency in resting CD4+ T cells represents a major barrier to virus eradication in patients on highly active antiretroviral therapy (HAART). We describe here a novel post-transcriptional block in HIV-1 gene expression in resting CD4+ T cells from patients on HAART. This block involves the aberrant localization of multiply spliced (MS) HIV-1 RNAs encoding the critical positive regulators Tat and Rev. Although these RNAs had no previously described export defect, we show that they exhibit strict nuclear localization in resting CD4+ T cells from patients on HAART. Overexpression of the transcriptional activator Tat from non-HIV vectors allowed virus production in these cells. Thus, the nuclear retention of MS HIV-1 RNA interrupts a positive feedback loop and contributes to the non-productive nature of infection of resting CD4+ T cells. To define the mechanism of nuclear retention, proteomic analysis was used to identify proteins that bind MS HIV-1 RNA. Polypyrimidine tract binding protein (PTB) was identified as an HIV-1 RNA-binding protein differentially expressed in resting and activated CD4+ T cells. Overexpression of PTB in resting CD4+ T cells from patients on HAART allowed cytoplasmic accumulation of HIV-1 RNAs. PTB overexpression also induced virus production by resting CD4+ T cells. Virus culture experiments showed that overexpression of PTB in resting CD4+ T cells from patients on HAART allowed release of replication-competent virus, while preserving a resting cellular phenotype. Whether through effects on RNA export or another mechanism, the ability of PTB to reverse latency without inducing cellular activation is a result with therapeutic implications. PMID:16839202

  13. Gut Microbial Membership Modulates CD4 T Cell Reconstitution and Function after Sepsis.

    PubMed

    Cabrera-Perez, Javier; Babcock, Jeffrey C; Dileepan, Thamotharampillai; Murphy, Katherine A; Kucaba, Tamara A; Badovinac, Vladimir P; Griffith, Thomas S

    2016-09-01

    Transient lymphopenia is one hallmark of sepsis, and emergent data indicate the CD4 T cell compartment in sepsis survivors is numerically and functionally altered (when examined at the Ag-specific level) compared with nonseptic control subjects. Previous data from our laboratory demonstrated Ag-independent, lymphopenia-induced homeostatic proliferation to be a contributing mechanism by which CD4 T cells numerically recover in sepsis survivors. However, we reasoned it is also formally possible that some CD4 T cells respond directly to Ag expressed by gut-resident microbes released during polymicrobial sepsis. The effect of gut microbiome leakage on CD4 T cells is currently unknown. In this study, we explored the number and function of endogenous CD4 T cells specific for segmented filamentous bacterium (SFB) after cecal ligation and puncture (CLP)-induced sepsis using mice that either contained or lacked SFB as a normal gut-resident microbe. Interestingly, SFB-specific CD4 T cells underwent Ag-driven proliferation in CLP-treated SFB(+), but not in SFB(-), mice. Moreover, CLP-treated SFB(+) mice showed resistance to secondary lethal infection with recombinant SFB Ag-expressing virulent Listeria (but not wild-type virulent Listeria), suggesting the CLP-induced polymicrobial sepsis primed for a protective response by the SFB-specific CD4 T cells. Thus, our data demonstrate that the numerical recovery and functional responsiveness of Ag-specific CD4 T cells in sepsis survivors is, in part, modulated by the intestinal barrier's health discreetly defined by individual bacterial populations of the host's microbiome. PMID:27448587

  14. Split Coil Forms for Rotary Transformers

    NASA Technical Reports Server (NTRS)

    Mclyman, C. W. T.

    1982-01-01

    Split cores for rotor and stator windings of rotary transformer mounted around their respective coils (which are in bobbins) and cemented together. This arrangement simplifies winding of stator coil to go in a slot in inner diameter of stator coil. One practical application of rotary transformers fabricated according to this technique is for centrifuges, in which conventional sliprings are of uncertain reliability.

  15. Inductively coupled wireless RF coil arrays.

    PubMed

    Bulumulla, S B; Fiveland, E; Park, K J; Foo, T K; Hardy, C J

    2015-04-01

    As the number of coils increases in multi-channel MRI receiver-coil arrays, RF cables and connectors become increasingly bulky and heavy, degrading patient comfort and slowing workflow. Inductive coupling of signals provides an attractive "wireless" approach, with the potential to reduce coil weight and cost while simplifying patient setup. In this work, multi-channel inductively coupled anterior arrays were developed and characterized for 1.5T imaging. These comprised MR receiver coils inductively (or "wirelessly") linked to secondary or "sniffer" coils whose outputs were transmitted via preamps to the MR system cabinet. The induced currents in the imaging coils were blocked by passive diode circuits during RF transmit. The imaging arrays were totally passive, obviating the need to deliver power to the coils, and providing lightweight, untethered signal reception with easily positioned coils. Single-shot fast spin echo images were acquired from 5 volunteers using a 7-element inductively coupled coil array and a conventionally cabled 7-element coil array of identical geometry, with the inductively-coupled array showing a relative signal-to-noise ratio of 0.86 +/- 0.07. The concept was extended to a larger 9-element coil array to demonstrate the effect of coil element size on signal transfer and RF-transmit blocking. PMID:25523607

  16. Experience with the CMS Event Data Model

    SciTech Connect

    Elmer, P.; Hegner, B.; Sexton-Kennedy, L.; /Fermilab

    2009-06-01

    The re-engineered CMS EDM was presented at CHEP in 2006. Since that time we have gained a lot of operational experience with the chosen model. We will present some of our findings, and attempt to evaluate how well it is meeting its goals. We will discuss some of the new features that have been added since 2006 as well as some of the problems that have been addressed. Also discussed is the level of adoption throughout CMS, which spans the trigger farm up to the final physics analysis. Future plans, in particular dealing with schema evolution and scaling, will be discussed briefly.

  17. Pathogenic CD4 T cells in type 1 diabetes recognize epitopes formed by peptide fusion

    PubMed Central

    Delong, Thomas; Wiles, Timothy A.; Baker, Rocky L.; Bradley, Brenda; Barbour, Gene; Reisdorph, Richard; Kumar, Nitesh; Elso, Colleen M.; Armstrong, Michael; Powell, Roger L.; Reisdorph, Nichole; DeNicola, Megan; Bottino, Rita; Powers, Alvin C.; Harlan, David M.; Kent, Sally C.; Mannering, Stuart I.; Haskins, Kathryn

    2016-01-01

    Type 1 diabetes (T1D) is caused by T cell mediated destruction of the insulin-producing β cells. CD4 T cell responses play a central role in β-cell destruction but the identity of the epitopes recognized by pathogenic CD4 T cells remains unknown. To address this we used a panel of diabetes triggering CD4 T cell clones isolated from non-obese diabetic (NOD) mice. Here we show that these pathogenic CD4 T cells target peptide ligands that are formed by covalent crosslinking of proinsulin peptides to other peptides present in β-cell secretory granules. These hybrid insulin peptides (HIPs) are highly antigenic for CD4 T cells and can be detected by mass spectrometry in β-cells. CD4 T cells from the residual pancreatic islets of two organ donors who had T1D also recognize HIPs. The discovery that autoreactive T cells target hybrid peptides may explain how immune tolerance is broken in T1D. PMID:26912858

  18. SAMHD1 restricts HIV-1 reverse transcription in quiescent CD4+ T-cells

    PubMed Central

    2012-01-01

    Background Quiescent CD4+ T lymphocytes are highly refractory to HIV-1 infection due to a block at reverse transcription. Results Examination of SAMHD1 expression in peripheral blood lymphocytes shows that SAMHD1 is expressed in both CD4+ and CD8+ T cells at levels comparable to those found in myeloid cells. Treatment of CD4+ T cells with Virus-Like Particles (VLP) containing Vpx results in the loss of SAMHD1 expression that correlates with an increased permissiveness to HIV-1 infection and accumulation of reverse transcribed viral DNA without promoting transcription from the viral LTR. Importantly, CD4+ T-cells from patients with Aicardi-Goutières Syndrome harboring mutation in the SAMHD1 gene display an increased susceptibility to HIV-1 infection that is not further enhanced by VLP-Vpx-treatment. Conclusion Here, we identified SAMHD1 as the restriction factor preventing efficient viral DNA synthesis in non-cycling resting CD4+ T-cells. These results highlight the crucial role of SAMHD1 in mediating restriction of HIV-1 infection in quiescent CD4+ T-cells and could impact our understanding of HIV-1 mediated CD4+ T-cell depletion and establishment of the viral reservoir, two of the HIV/AIDS hallmarks. PMID:23092122

  19. Use of MHC class II tetramers to investigate CD4+ T cell responses: problems and solutions.

    PubMed

    Cecconi, Virginia; Moro, Monica; Del Mare, Sara; Dellabona, Paolo; Casorati, Giulia

    2008-11-01

    MHC-class I tetramers technology enabled the characterization of peptide-specific T cells at the single cell level in a variety of studies. Several laboratories have also developed MHC-class II multimers to characterize Ag-specific CD4+ T cells. However, the generation and use of MHC-class II multimers seems more problematic than that of MHC-I multimers. We have generated HLA-DR*1101 tetramers in a versatile empty form, which can be loaded after purification with peptides of interest. We discuss the impact of critical biological and structural parameters for the optimal staining of Ag-specific CD4+ T cells using HLA-DR*1101 tetramers, such as: (i) activation state of CD4+ T cells; (ii) membrane trafficking in the target CD4+ T cells; (iii) binding characteristics of the loaded CD4 epitope. Our data indicate that reorganization of TCR on the plasma membrane upon CD4+ T cell activation, as well as an homogenous binding frame of the CD4 epitopes to the soluble HLA-DR monomer, are critical for a stable TCR/MHC-class II tetramer interaction. These factors, together with the low frequencies and affinities of specific CD4+ T cells, explain the need for in vitro expansion or ex vivo enrichment of specific T cells for the optimal visualization with MHC-class II tetramers. PMID:18612991

  20. Predictor for the effect of amino acid composition on CD4+ T cell epitopes preprocessing.

    PubMed

    Hoze, Ehud; Tsaban, Lea; Maman, Yaakov; Louzoun, Yoram

    2013-05-31

    Predictive tools for all levels of CD8+ T cell epitopes processing have reached a maturation level. Good prediction algorithms have been developed for proteasomal cleavage, TAP and MHC class I peptide binding. The same cannot be said of CD4+ T cell epitopes. While multiple algorithms of varying accuracy have been proposed for MHC class II peptide binding, the preprocessing of CD4+ T cell epitopes is still lacking a good prediction algorithm. CD4+ T cell epitopes generation includes several stages, not all which are well-defined. We here group these stages to produce a generic preprocessing stage predictor for the cleavage processes preceding the presentation of epitopes to CD4+ T cell. The predictor is learnt using a combination of in vitro cleavage experiments and observed naturally processed MHC class II binding peptides. The properties of the predictor highlight the effect of different factors on CD4+ T cell epitopes preprocessing. The most important factor emerging from the predictor is the secondary structure of the cleaved region in the protein. The effect of the secondary structure is expected since CD4+ T cell epitopes are not denatured before cleavage. A website developed based on this predictor is available at: http://peptibase.cs.biu.ac.il/PepCleave_cd4/. PMID:23481624

  1. Methodologies for the Analysis of HCV-Specific CD4+ T Cells

    PubMed Central

    Lokhande, Megha U.; Thimme, Robert; Klenerman, Paul; Semmo, Nasser

    2015-01-01

    Virus-specific CD4+ T cells play a major role in viral infections, such as hepatitis C virus (HCV). Viral clearance is associated with vigorous and multi-specific CD4+ T-cell responses, while chronic infection has been shown to be associated with weak or absent T-cell responses. Most of these studies have used functional assays to analyze virus-specific CD4+ T-cell responses; however, these and other detection methods have various limitations. Therefore, the important question of whether virus-specific CD4+ T cells are completely absent or primarily impaired in specific effector functions during chronic infection, has yet to be analyzed in detail. A novel assay, in which virus-specific CD4+ T-cell frequencies can be determined by de novo CD154 (CD40 ligand) expression in response to viral antigens, can help to overcome some of the limitations of functional assays and restrictions of multimer-based methods. This and other current established methods for the detection of HCV-specific CD4+ T cells will be discussed in this review. PMID:25767470

  2. Impact of nicotine on the interplay between human periodontal ligament cells and CD4+ T cells.

    PubMed

    Ge, Xin; Liu, Ying-Feng; Wong, Yong; Wu, Li-Zheng; Tan, Ling; Liu, Fen; Wang, Xiao-Jing

    2016-09-01

    Periodontitis is a common infectious disease associated with destruction of periodontal ligaments and alveolar bones. CD4(+) T cell-mediated immune response is involved in the progression of periodontitis. Tobacco consumption increases the risk of periodontal disease. However, the impact of nicotine on the interaction between human periodontal ligament (PDL) cells and CD4(+) T cells remains unrevealed. Our study aims to investigate the effect of nicotine on PDL cells and the cocultured CD4(+) T cells. The PDL cell cultures were established by explants from healthy individuals, exposed to nicotine or α-bungarotoxin (α-BTX), and incubated solely or in combination with CD4(+) T cells. Afterwards, cell viability, secreted cytokines, and matrix metalloproteinases (MMPs) were evaluated. In monoculture of PDL cells, nicotine dramatically repressed cell viability and increased apoptosis. Meanwhile, α-BTX largely reversed the nicotine-induced apoptosis and increased viability of PDL cells. Compared with the monoculture, MMP-1, MMP-3, interleukin (IL)-1β, IL-6, IL-17, and IL-21 in supernatant of cocultures were markedly elevated after treatment with nicotine. Moreover, α-BTX significantly attenuated nicotine-triggered production of these components either in mono- or co-cultures. In addition, PDL cell-derived CXCL12 following nicotine treatment recruited CD4(+) T cells. Above all, nicotine deteriorated periodontitis partially by promoting PDL cell-CD4(+) T cell-mediated inflammatory response and matrix degradation. PMID:26553320

  3. Simian immunodeficiency virus selectively infects proliferating CD4+ T cells in neonatal rhesus macaques

    PubMed Central

    Wang, Xiaolei; Xu, Huanbin; Pahar, Bapi; Alvarez, Xavier; Green, Linda C.; Dufour, Jason; Moroney-Rasmussen, Terri; Lackner, Andrew A.

    2010-01-01

    Infants infected with HIV have a more severe course of disease and persistently higher viral loads than HIV-infected adults. However, the underlying pathogenesis of this exacerbation remains obscure. Here we compared the rate of CD4+ and CD8+ T-cell proliferation in intestinal and systemic lymphoid tissues of neonatal and adult rhesus macaques, and of normal and age-matched simian immunodeficiency virus (SIV)–infected neonates. The results demonstrate infant primates have much greater rates of CD4+ T-cell proliferation than adult macaques, and that these proliferating, recently “activated” CD4+ T cells are infected in intestinal and other lymphoid tissues of neonates, resulting in selective depletion of proliferating CD4+ T cells in acute infection. This depletion is accompanied by a marked increase in CD8+ T-cell activation and production, particularly in the intestinal tract. The data indicate intestinal CD4+ T cells of infant primates have a markedly accelerated rate of proliferation and maturation resulting in more rapid and sustained production of optimal target cells (activated memory CD4+ T cells), which may explain the sustained “peak” viremia characteristic of pediatric HIV infection. Eventual failure of CD4+ T-cell turnover in intestinal tissues may indicate a poorer prognosis for HIV-infected infants. PMID:20716768

  4. Expression of fas protein on CD4+T cells irradiated by low level He-Ne

    NASA Astrophysics Data System (ADS)

    Nie, Fan; Zhu, Jing; Zhang, Hui-Guo

    2005-07-01

    Objective: To investigate the influence on the Expression of Fas protein on CD4+ T cells irradiated by low level He-Ne laser in the cases of psoriasis. Methods:the expression of CD4+ T Fas protein was determined in the casee of psoriasis(n=5) pre and post-low level laser irradiation(30 min、60min and 120min)by flow cytometry as compared withthe control(n=5). Results:In the cases of psoriasis,the expression of CD4+T FAS protein 21.4+/-3.1% was increased significantly than that of control group 16.8+/-2.1% pre-irradiation, p<0.05in the control,there is no difference between pre and post- irradiation,p>0.05in the cases , the expression of CD4+T Fas protein wae positively corelated to the irradiation times, when the energy density arrived to 22.92J/cm2(60 minutes)and 45.84J/cm2(120minutes), the expression of CD4+ T Fas protein was increased significantly as compared with pre-irradiation,p<0.05.Conclusion: The expression of CD4+T Fas protein may be increased by low level He-Ne laser irradiation ,the uncontrolled status of apoptosis could be corrected.

  5. Microbial exposure alters HIV-1-induced mucosal CD4+ T cell death pathways Ex vivo

    PubMed Central

    2014-01-01

    Background Early HIV-1 infection causes massive CD4+ T cell death in the gut and translocation of bacteria into the circulation. However, the programmed cell death (PCD) pathways used by HIV-1 to kill CD4+ T cells in the gut, and the impact of microbial exposure on T cell loss, remain unclear. Understanding mucosal HIV-1 triggered PCD could be advanced by an ex vivo system involving lamina propria mononuclear cells (LPMCs). We therefore modeled the interactions of gut LPMCs, CCR5-tropic HIV-1 and a commensal gut bacterial species, Escherichia coli. In this Lamina Propria Aggregate Culture (LPAC) model, LPMCs were infected with HIV-1BaL by spinoculation and cultured in the presence or absence of heat killed E.coli. CD4+ T cell numbers derived from flow cytometry and viable cell counts were reported relative to mock infection. Viable cells were identified by viability dye exclusion (AqVi), and intracellular HIV-1 Gag p24 protein was used to identify infected cells. Annexin V and AqVi were used to identify apoptotic versus necrotic cells. Caspase-1 and Caspase-3 activities were blocked using specific inhibitors YVAD and DEVD, respectively. Results CD4+ T cell depletion following HIV-1 infection was reproducibly observed by 6 days post infection (dpi). Depletion at 6 dpi strongly correlated with infection frequency at 4 dpi, was significantly blocked by Efavirenz treatment, and was primarily driven by p24-negative cells that were predominantly necrotic. HIV-1 infection significantly induced CD4+ T-cell intrinsic Caspase-1 activity, whereas Caspase-1 inhibition, but not Caspase-3 inhibition, significantly blocked CD4+ T cell depletion. Exposure to E.coli enhanced HIV-1 infection and CD4+ T depletion, and significantly increased the number of apoptotic p24+ cells. Notably, CD4+ T cell depletion in the presence of E.coli was partially blocked by Caspase-3, but not by Caspase-1 inhibition. Conclusions In the LPAC model, HIV-1 induced Caspase-1 mediated pyroptosis in

  6. 26 CFR 51.4T - Information provided by the agencies (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... sales price (ASP) for each Healthcare Common Procedure Coding System (HCPCS) code for the sales year...IdentifiableDataFiles/03_PartBNationalSummaryDataFile.asp to obtain the number of allowed billing units per... respective NDCs) manufactured by a single entity, CMS will multiply the annual weighted ASP by the...

  7. 26 CFR 51.4T - Information provided by the agencies (temporary).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... sales price (ASP) for each Healthcare Common Procedure Coding System (HCPCS) code for the sales year...IdentifiableDataFiles/03_PartBNationalSummaryDataFile.asp to obtain the number of allowed billing units per... respective NDCs) manufactured by a single entity, CMS will multiply the annual weighted ASP by the...

  8. 26 CFR 51.4T - Information provided by the agencies (temporary).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... sales price (ASP) for each Healthcare Common Procedure Coding System (HCPCS) code for the sales year...IdentifiableDataFiles/03_PartBNationalSummaryDataFile.asp to obtain the number of allowed billing units per... respective NDCs) manufactured by a single entity, CMS will multiply the annual weighted ASP by the...

  9. Three-dimensional coil inductor

    DOEpatents

    Bernhardt, Anthony F.; Malba, Vincent

    2002-01-01

    A three-dimensional coil inductor is disclosed. The inductor includes a substrate; a set of lower electrically conductive traces positioned on the substrate; a core placed over the lower traces; a set of side electrically conductive traces laid on the core and the lower traces; and a set of upper electrically conductive traces attached to the side traces so as to form the inductor. Fabrication of the inductor includes the steps of forming a set of lower traces on a substrate; positioning a core over the lower traces; forming a set of side traces on the core; connecting the side traces to the lower traces; forming a set of upper traces on the core; and connecting the upper traces to the side traces so as to form a coil structure.

  10. Coil Embolization for Intracranial Aneurysms

    PubMed Central

    2006-01-01

    Executive Summary Objective To determine the effectiveness and cost-effectiveness of coil embolization compared with surgical clipping to treat intracranial aneurysms. The Technology Endovascular coil embolization is a percutaneous approach to treat an intracranial aneurysm from within the blood vessel without the need of a craniotomy. In this procedure, a microcatheter is inserted into the femoral artery near the groin and navigated to the site of the aneurysm. Small helical platinum coils are deployed through the microcatheter to fill the aneurysm, and prevent it from further expansion and rupture. Health Canada has approved numerous types of coils and coil delivery systems to treat intracranial aneurysms. The most favoured are controlled detachable coils. Coil embolization may be used with other adjunct endovascular devices such as stents and balloons. Background Intracranial Aneurysms Intracranial aneurysms are the dilation or ballooning of part of a blood vessel in the brain. Intracranial aneurysms range in size from small (<12 mm in diameter) to large (12–25 mm), and to giant (>25 mm). There are 3 main types of aneurysms. Fusiform aneurysms involve the entire circumference of the artery; saccular aneurysms have outpouchings; and dissecting aneurysms have tears in the arterial wall. Berry aneurysms are saccular aneurysms with well-defined necks. Intracranial aneurysms may occur in any blood vessel of the brain; however, they are most commonly found at the branch points of large arteries that form the circle of Willis at the base of the brain. In 85% to 95% of patients, they are found in the anterior circulation. Aneurysms in the posterior circulation are less frequent, and are more difficult to treat surgically due to inaccessibility. Most intracranial aneurysms are small and asymptomatic. Large aneurysms may have a mass effect, causing compression on the brain and cranial nerves and neurological deficits. When an intracranial aneurysm ruptures and bleeds

  11. Multi circular-cavity surface coil for magnetic resonance imaging of monkey's brain at 4 Tesla

    NASA Astrophysics Data System (ADS)

    Osorio, A. I.; Solis-Najera, S. E.; Vázquez, F.; Wang, R. L.; Tomasi, D.; Rodriguez, A. O.

    2014-11-01

    Animal models in medical research has been used to study humans diseases for several decades. The use of different imaging techniques together with different animal models offers a great advantage due to the possibility to study some human pathologies without the necessity of chirurgical intervention. The employ of magnetic resonance imaging for the acquisition of anatomical and functional images is an excellent tool because its noninvasive nature. Dedicated coils to perform magnetic resonance imaging experiments are obligatory due to the improvement on the signal-to-noise ratio and reduced specific absorption ratio. A specifically designed surface coil for magnetic resonance imaging of monkey's brain is proposed based on the multi circular-slot coil. Numerical simulations of the magnetic and electric fields were also performed using the Finite Integration Method to solve Maxwell's equations for this particular coil design and, to study the behavior of various vector magnetic field configurations and specific absorption ratio. Monkey's brain images were then acquired with a research-dedicated magnetic resonance imaging system at 4T, to evaluate the anatomical images with conventional imaging sequences. This coil showed good quality images of a monkey's brain and full compatibility with standard pulse sequences implemented in research-dedicated imager.

  12. 45 CFR 150.203 - Circumstances requiring CMS enforcement.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Determining Whether States Are Failing To Substantially Enforce HIPAA Requirements § 150.203 Circumstances requiring CMS enforcement. CMS enforces HIPAA requirements to the extent warranted (as determined by CMS) in... enacted legislation to enforce or that it is not otherwise enforcing HIPAA requirements. (b)...

  13. 45 CFR 150.203 - Circumstances requiring CMS enforcement.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Determining Whether States Are Failing To Substantially Enforce HIPAA Requirements § 150.203 Circumstances requiring CMS enforcement. CMS enforces HIPAA requirements to the extent warranted (as determined by CMS) in... enacted legislation to enforce or that it is not otherwise enforcing HIPAA requirements. (b)...

  14. 45 CFR 150.203 - Circumstances requiring CMS enforcement.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Determining Whether States Are Failing To Substantially Enforce HIPAA Requirements § 150.203 Circumstances requiring CMS enforcement. CMS enforces HIPAA requirements to the extent warranted (as determined by CMS) in... enacted legislation to enforce or that it is not otherwise enforcing HIPAA requirements. (b)...

  15. 42 CFR 426.517 - CMS' statement regarding new evidence.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false CMS' statement regarding new evidence. 426.517... DETERMINATIONS Review of an NCD § 426.517 CMS' statement regarding new evidence. (a) CMS may review any new... limited to new evidence: (1) Submitted with the initial complaint; (2) Submitted with an amended...

  16. Segmented Coil Fails In Steps

    NASA Technical Reports Server (NTRS)

    Stedman, Ronald S.

    1990-01-01

    Electromagnetic coil degrades in steps when faults occur, continues to operate at reduced level instead of failing catastrophically. Made in segments connected in series and separated by electrically insulating barriers. Fault does not damage adjacent components or create hazard. Used to control valves in such critical applications as cooling systems of power generators and chemical process equipment, where flammable liquids or gases handled. Also adapts to electrical control of motors.

  17. The CMS Remote Analysis Builder (CRAB)

    SciTech Connect

    Spiga, D.; Cinquilli, M.; Servoli, L.; Lacaprara, S.; Fanzago, F.; Dorigo, A.; Merlo, M.; Farina, F.; Fanfani, A.; Codispoti, G.; Bacchi, W.; /INFN, Bologna /Bologna U /CERN /INFN, CNAF /INFN, Trieste /Fermilab

    2008-01-22

    The CMS experiment will produce several Pbytes of data every year, to be distributed over many computing centers geographically distributed in different countries. Analysis of this data will be also performed in a distributed way, using grid infrastructure. CRAB (CMS Remote Analysis Builder) is a specific tool, designed and developed by the CMS collaboration, that allows a transparent access to distributed data to end physicist. Very limited knowledge of underlying technicalities are required to the user. CRAB interacts with the local user environment, the CMS Data Management services and with the Grid middleware. It is able to use WLCG, gLite and OSG middleware. CRAB has been in production and in routine use by end-users since Spring 2004. It has been extensively used in studies to prepare the Physics Technical Design Report (PTDR) and in the analysis of reconstructed event samples generated during the Computing Software and Analysis Challenge (CSA06). This involved generating thousands of jobs per day at peak rates. In this paper we discuss the current implementation of CRAB, the experience with using it in production and the plans to improve it in the immediate future.

  18. The Tracker of the CMS Experiment

    SciTech Connect

    Migliore, Ernesto

    2005-10-12

    With more than 200 m2 the Silicon Strip Tracker of the Compact Muon Solenoid (CMS) experiment will be the largest silicon detector ever built. In this contribution the main design considerations and the status of the construction, at about one and a half year after the begin of the production of the modules, are reviewed.

  19. CMS results on exclusive and diffractive production

    SciTech Connect

    Alves, Gilvan A.

    2015-04-10

    We present recent CMS measurements of diffractive and exclusive processes, using data collected at 7 TeV at the LHC. Measurements of soft single- and double-diffractive cross sections are presented, as well as measurements of photon-induced processes including studies of exclusive WW production via photon-photon exchange.

  20. Monte Carlo Production Management at CMS

    NASA Astrophysics Data System (ADS)

    Boudoul, G.; Franzoni, G.; Norkus, A.; Pol, A.; Srimanobhas, P.; Vlimant, J.-R.

    2015-12-01

    The analysis of the LHC data at the Compact Muon Solenoid (CMS) experiment requires the production of a large number of simulated events. During the RunI of LHC (20102012), CMS has produced over 12 Billion simulated events, organized in approximately sixty different campaigns each emulating specific detector conditions and LHC running conditions (pile up). In order to aggregate the information needed for the configuration and prioritization of the events production, assure the book-keeping of all the processing requests placed by the physics analysis groups, and to interface with the CMS production infrastructure, the web- based service Monte Carlo Management (McM) has been developed and put in production in 2013. McM is based on recent server infrastructure technology (CherryPy + AngularJS) and relies on a CouchDB database back-end. This contribution covers the one and half year of operational experience managing samples of simulated events for CMS, the evolution of its functionalities and the extension of its capability to monitor the status and advancement of the events production.

  1. 23 CFR 500.109 - CMS.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... provides accurate, up-to-date information on transportation system operations and performance and assesses... and local officials may vary by type of transportation facility, geographic location (metropolitan... SYSTEMS Management Systems § 500.109 CMS. (a) For purposes of this part, congestion means the level...

  2. 23 CFR 500.109 - CMS.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... provides accurate, up-to-date information on transportation system operations and performance and assesses... and local officials may vary by type of transportation facility, geographic location (metropolitan... SYSTEMS Management Systems § 500.109 CMS. (a) For purposes of this part, congestion means the level...

  3. 23 CFR 500.109 - CMS.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... provides accurate, up-to-date information on transportation system operations and performance and assesses... and local officials may vary by type of transportation facility, geographic location (metropolitan... SYSTEMS Management Systems § 500.109 CMS. (a) For purposes of this part, congestion means the level...

  4. 23 CFR 500.109 - CMS.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... provides accurate, up-to-date information on transportation system operations and performance and assesses... and local officials may vary by type of transportation facility, geographic location (metropolitan... SYSTEMS Management Systems § 500.109 CMS. (a) For purposes of this part, congestion means the level...

  5. WLCG scale testing during CMS data challenges

    NASA Astrophysics Data System (ADS)

    Gutsche, O.; Hajdu, C.

    2008-07-01

    The CMS computing model to process and analyze LHC collision data follows a data-location driven approach and is using the WLCG infrastructure to provide access to GRID resources. As a preparation for data taking, CMS tests its computing model during dedicated data challenges. An important part of the challenges is the test of the user analysis which poses a special challenge for the infrastructure with its random distributed access patterns. The CMS Remote Analysis Builder (CRAB) handles all interactions with the WLCG infrastructure transparently for the user. During the 2006 challenge, CMS set its goal to test the infrastructure at a scale of 50,000 user jobs per day using CRAB. Both direct submissions by individual users and automated submissions by robots were used to achieve this goal. A report will be given about the outcome of the user analysis part of the challenge using both the EGEE and OSG parts of the WLCG. In particular, the difference in submission between both GRID middlewares (resource broker vs. direct submission) will be discussed. In the end, an outlook for the 2007 data challenge is given.

  6. Commissioning of the CMS Forward Pixel Detector

    SciTech Connect

    Kumar, Ashish; /SUNY, Buffalo

    2008-12-01

    The Compact Muon Solenoid (CMS) experiment is scheduled for physics data taking in summer 2009 after the commissioning of high energy proton-proton collisions at Large Hadron Collider (LHC). At the core of the CMS all-silicon tracker is the silicon pixel detector, comprising three barrel layers and two pixel disks in the forward and backward regions, accounting for a total of 66 million channels. The pixel detector will provide high-resolution, 3D tracking points, essential for pattern recognition and precise vertexing, while being embedded in a hostile radiation environment. The end disks of the pixel detector, known as the Forward Pixel detector, has been assembled and tested at Fermilab, USA. It has 18 million pixel cells with dimension 100 x 150 {micro}m{sup 2}. The complete forward pixel detector was shipped to CERN in December 2007, where it underwent extensive system tests for commissioning prior to the installation. The pixel system was put in its final place inside the CMS following the installation and bake out of the LHC beam pipe in July 2008. It has been integrated with other sub-detectors in the readout since September 2008 and participated in the cosmic data taking. This report covers the strategy and results from commissioning of CMS forward pixel detector at CERN.

  7. Commissioning of CMS Endcap Muon System

    NASA Astrophysics Data System (ADS)

    Brownell, Elizabeth

    2009-05-01

    This talk is as an overview of the evolution and current state of commissioning work on the CMS endcap muon system. I intend to highlight the progress in operating the detector, some problems encountered and solutions developed, lessons learned in the process, points which still require action to be taken, and data taking results.

  8. 4T1 Murine Mammary Carcinoma Cells Enhance Macrophage-Mediated Innate Inflammatory Responses

    PubMed Central

    Madera, Laurence; Greenshields, Anna; Coombs, Melanie R. Power; Hoskin, David W.

    2015-01-01

    Tumor progression and the immune response are intricately linked. While it is known that cancers alter macrophage inflammatory responses to promote tumor progression, little is known regarding how cancers affect macrophage-dependent innate host defense. In this study, murine bone-marrow-derived macrophages (BMDM) were exposed to murine carcinoma-conditioned media prior to assessment of the macrophage inflammatory response. BMDMs exposed to 4T1 mammary carcinoma-conditioned medium demonstrated enhanced production of pro-inflammatory cytokines tumor necrosis factor α, interleukin-6, and CCL2 in response to lipopolysaccharide (LPS) while production of interleukin-10 remained unchanged. The increased LPS-induced production of pro-inflammatory cytokines was transient and correlated with enhanced cytokine production in response to other Toll-like receptor agonists, including peptidoglycan and flagellin. In addition, 4T1-conditioned BMDMs exhibited strengthened LPS-induced nitric oxide production and enhanced phagocytosis of Escherichia coli. 4T1-mediated augmentation of macrophage responses to LPS was partially dependent on the NFκB pathway, macrophage-colony stimulating factor, and actin polymerization, as well as the presence of 4T1-secreted extracellular vesicles. Furthermore, peritoneal macrophages obtained from 4T1 tumor-bearing mice displayed enhanced pro-inflammatory cytokine production in response to LPS. These results suggest that uptake of 4T1-secreted factors and actin-mediated ingestion of 4T1-secreted exosomes by macrophages cause a transient enhancement of innate inflammatory responses. Mammary carcinoma-mediated regulation of innate immunity may have significant implications for our understanding of host defense and cancer progression. PMID:26177198

  9. 4T1 Murine Mammary Carcinoma Cells Enhance Macrophage-Mediated Innate Inflammatory Responses.

    PubMed

    Madera, Laurence; Greenshields, Anna; Coombs, Melanie R Power; Hoskin, David W

    2015-01-01

    Tumor progression and the immune response are intricately linked. While it is known that cancers alter macrophage inflammatory responses to promote tumor progression, little is known regarding how cancers affect macrophage-dependent innate host defense. In this study, murine bone-marrow-derived macrophages (BMDM) were exposed to murine carcinoma-conditioned media prior to assessment of the macrophage inflammatory response. BMDMs exposed to 4T1 mammary carcinoma-conditioned medium demonstrated enhanced production of pro-inflammatory cytokines tumor necrosis factor α, interleukin-6, and CCL2 in response to lipopolysaccharide (LPS) while production of interleukin-10 remained unchanged. The increased LPS-induced production of pro-inflammatory cytokines was transient and correlated with enhanced cytokine production in response to other Toll-like receptor agonists, including peptidoglycan and flagellin. In addition, 4T1-conditioned BMDMs exhibited strengthened LPS-induced nitric oxide production and enhanced phagocytosis of Escherichia coli. 4T1-mediated augmentation of macrophage responses to LPS was partially dependent on the NFκB pathway, macrophage-colony stimulating factor, and actin polymerization, as well as the presence of 4T1-secreted extracellular vesicles. Furthermore, peritoneal macrophages obtained from 4T1 tumor-bearing mice displayed enhanced pro-inflammatory cytokine production in response to LPS. These results suggest that uptake of 4T1-secreted factors and actin-mediated ingestion of 4T1-secreted exosomes by macrophages cause a transient enhancement of innate inflammatory responses. Mammary carcinoma-mediated regulation of innate immunity may have significant implications for our understanding of host defense and cancer progression. PMID:26177198

  10. Equations determine coiled tubing collapse pressure

    SciTech Connect

    Avakov, V.; Taliaferro, W.

    1995-07-24

    A set of equations has been developed for calculating pipe collapse pressure for oval tubing such as coiled tubing. When coiled tubing is placed onto a reel, the tubing is forced into an oval shape and never again returns to perfect roundness because the coiling process exceeds the plasticity limits of the tubing. Straightening the tubing for the trip into the well does not restore roundness. The consequence of this physical property is that all coiled tubing collapse pressure calculations should be made considering oval tubing, not round tubing. Tubing collapse can occur when formation pressure against the coiled tubing exceeds the collapse resistance inherent in the coiled tubing. As coiled tubing becomes more oval in shape, it becomes more oval in shape, it becomes more susceptible to collapse from outside pressure.

  11. Coiled transmission line pulse generators

    DOEpatents

    McDonald, Kenneth Fox

    2010-11-09

    Methods and apparatus are provided for fabricating and constructing solid dielectric "Coiled Transmission Line" pulse generators in radial or axial coiled geometries. The pour and cure fabrication process enables a wide variety of geometries and form factors. The volume between the conductors is filled with liquid blends of monomers, polymers, oligomers, and/or cross-linkers and dielectric powders; and then cured to form high field strength and high dielectric constant solid dielectric transmission lines that intrinsically produce ideal rectangular high voltage pulses when charged and switched into matched impedance loads. Voltage levels may be increased by Marx and/or Blumlein principles incorporating spark gap or, preferentially, solid state switches (such as optically triggered thyristors) which produce reliable, high repetition rate operation. Moreover, these Marxed pulse generators can be DC charged and do not require additional pulse forming circuitry, pulse forming lines, transformers, or an a high voltage spark gap output switch. The apparatus accommodates a wide range of voltages, impedances, pulse durations, pulse repetition rates, and duty cycles. The resulting mobile or flight platform friendly cylindrical geometric configuration is much more compact, light-weight, and robust than conventional linear geometries, or pulse generators constructed from conventional components. Installing additional circuitry may accommodate optional pulse shape improvements. The Coiled Transmission Lines can also be connected in parallel to decrease the impedance, or in series to increase the pulse length.

  12. A thermodynamic model for the helix-coil transition coupled to dimerization of short coiled-coil peptides.

    PubMed Central

    Qian, H

    1994-01-01

    A simple thermodynamic formalism is presented to model the conformational transition between a random-coil monomeric peptide and a coiled-coil helical dimer. The coiled-coil helical dimer is the structure of a class of proteins also called leucine zipper, which has been studied intensively in recent years. Our model, which is appropriate particularly for short peptides, is an alternative to the theory developed by Skolnick and Holtzer. Using the present formalism, we discuss the multi-equilibriatory nature of this transition and provide an explanation for the apparent two-state behavior of coiled-coil formation when the helix-coil transition is coupled to dimerization. It is found that such coupling between multi-equilibria and a true two-state transition can simplify the data analysis, but care must be taken in using the overall association constant to determine helix propensities (w) of single residues. Successful use of the two-state model does not imply that the helix-coil transition is all-or-none. The all-or-none assumption can provide good numerical estimates when w is around unity (0.35 < or = w < or = 1.35), but when w is small (w < 0.01), similar estimations can lead to large errors. The theory of the helix-coil transition in denaturation experiments is also discussed. PMID:7919005

  13. Modular Coils with Low Hydrogen Content Especially for MRI of Dry Solids

    PubMed Central

    Fischer, Elmar; Gröbner, Jens; Göpper, Michael; Eisenbeiss, Anne-Katrin; Flügge, Tabea; Hennig, Jürgen; von Elverfeldt, Dominik; Hövener, Jan-Bernd

    2015-01-01

    Introduction Recent advances have enabled fast magnetic resonance imaging (MRI) of solid materials. This development has opened up new applications for MRI, but, at the same time, uncovered new challenges. Previously, MRI-invisible materials like the housing of MRI detection coils are now readily depicted and either cause artifacts or lead to a decreased image resolution. In this contribution, we present versatile, multi-nuclear single and dual-tune MRI coils that stand out by (1) a low hydrogen content for high-resolution MRI of dry solids without artifacts; (2) a modular approach with exchangeable inductors of variable volumes to optimally enclose the given object; (3) low cost and low manufacturing effort that is associated with the modular approach; (4) accurate sample placement in the coil outside of the bore, and (5) a wide, single- or dual-tune frequency range that covers several nuclei and enables multinuclear MRI without moving the sample. Materials and Methods The inductors of the coils were constructed from self-supporting copper sheets to avoid all plastic materials within or around the resonator. The components that were mounted at a distance from the inductor, including the circuit board, coaxial cable and holder were manufactured from polytetrafluoroethylene. Results and Conclusion Residual hydrogen signal was sufficiently well suppressed to allow 1H-MRI of dry solids with a minimum field of view that was smaller than the sensitive volume of the coil. The SNR was found to be comparable but somewhat lower with respect to commercial, proton-rich quadrature coils, and higher with respect to a linearly-polarized commercial coil. The potential of the setup presented was exemplified by 1H / 23Na high-resolution zero echo time (ZTE) MRI of a model solution and a dried human molar at 9.4 T. A full 3D image dataset of the tooth was obtained, rich in contrast and similar to the resolution of standard cone-beam computed tomography. PMID:26496192

  14. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection

    NASA Astrophysics Data System (ADS)

    Doitsh, Gilad; Galloway, Nicole L. K.; Geng, Xin; Yang, Zhiyuan; Monroe, Kathryn M.; Zepeda, Orlando; Hunt, Peter W.; Hatano, Hiroyu; Sowinski, Stefanie; Muñoz-Arias, Isa; Greene, Warner C.

    2014-01-01

    The pathway causing CD4 T-cell death in HIV-infected hosts remains poorly understood although apoptosis has been proposed as a key mechanism. We now show that caspase-3-mediated apoptosis accounts for the death of only a small fraction of CD4 T cells corresponding to those that are both activated and productively infected. The remaining over 95% of quiescent lymphoid CD4 T cells die by caspase-1-mediated pyroptosis triggered by abortive viral infection. Pyroptosis corresponds to an intensely inflammatory form of programmed cell death in which cytoplasmic contents and pro-inflammatory cytokines, including IL-1β, are released. This death pathway thus links the two signature events in HIV infection--CD4 T-cell depletion and chronic inflammation--and creates a pathogenic vicious cycle in which dying CD4 T cells release inflammatory signals that attract more cells to die. This cycle can be broken by caspase 1 inhibitors shown to be safe in humans, raising the possibility of a new class of `anti-AIDS' therapeutics targeting the host rather than the virus.

  15. IL-21-producer CD4+ T cell kinetics during primary simian immunodeficiency virus infection.

    PubMed

    Shi, Shoi; Seki, Sayuri; Matano, Tetsuro; Yamamoto, Hiroyuki

    2013-01-01

    IL-21 signaling is important for T cell and B cell-mediated clearance of chronic viral infections. While non-cognate follicular helper CD4+ T cells (TFH) are indicated to be pivotal in providing IL-21-mediated help to activated B cells within germinal centers, how this signaling may be disrupted in early AIDS virus infection is not clear. In this study, we assessed the lineage and kinetics of peripheral blood IL-21-producing CD4+ T cells in primary simian immunodeficiency virus (SIV) infection of rhesus macaques. After SIV challenge, antigen-nonspecific IL-21 production was observed in Th1, Th2 and Th17 cells with Th1 dominance. While IL-21+ Th2 and IL-21+ Th17 showed variable kinetics, an increase in total IL-21+ CD4+ T cells and IL-21+ Th1 from week 3 to week 8 was observed, preceding plasma SIV-specific IgG development from week 5 to week 12. SIV Gag-specific IL-21+ CD4+ T cells detectable at week 2 were decreased in frequencies at week 5. Results imply that kinetics of IL-21+ CD4+ T cells comprised of multiple lineages, potentially targeted by SIV with a bias of existing frequencies during their precursor stage, associate with availability of cooperative B-cell help provided through a proportionate precursor pool developing into TFH and subsequent anti-SIV antibody responses. PMID:23791954

  16. Role of miRNAs in CD4 T cell plasticity during inflammation and tolerance.

    PubMed

    Sethi, Apoorva; Kulkarni, Neeraja; Sonar, Sandip; Lal, Girdhari

    2013-01-01

    Gene expression is tightly regulated in a tuneable, cell-specific and time-dependent manner. Recent advancement in epigenetics and non-coding RNA (ncRNA) revolutionized the concept of gene regulation. In order to regulate the transcription, ncRNA can promptly response to the extracellular signals as compared to transcription factors present in the cells. microRNAs (miRNAs) are ncRNA (~22 bp) encoded in the genome, and present as intergenic or oriented antisense to neighboring genes. The strategic location of miRNA in coding genes helps in the coupled regulation of its expression with host genes. miRNA together with complex machinery called RNA-induced silencing complex (RISC) interacts with target mRNA and degrade the mRNA or inhibits the translation. CD4 T cells play an important role in the generation and maintenance of inflammation and tolerance. Cytokines and chemokines present in the inflamed microenvironment controls the differentiation and function of various subsets of CD4 T cells [Th1, Th2, Th17, and regulatory CD4 T cells (Tregs)]. Recent studies suggest that miRNAs play an important role in the development and function of all subsets of CD4 T cells. In current review, we focused on how various miRNAs are regulated by cell's extrinsic and intrinsic signaling, and how miRNAs affect the transdifferentiation of subsets of CD4 T cell and controls their plasticity during inflammation and tolerance. PMID:23386861

  17. Temporal requirements for B cells in the establishment of CD4 T cell memory.

    PubMed

    Mollo, Sarah B; Zajac, Allan J; Harrington, Laurie E

    2013-12-15

    CD4 T cell memory generation is shaped by a number of factors, including the strength and duration of TCR signaling, as well as the priming environment, all of which can be modified by B cells. Studies using B cell-deficient mice indicate B cells play a critical role in generating effector and memory CD4 T cells; however, when and how B cells are acting to promote these responses has not yet been ascertained. In this study, we use anti-CD20 Ab depletion of B cells at different times following Listeria monocytogenes infection to show that B cells are necessary for the induction of optimal CD4 T cell memory, but not for the transition and maintenance of this population. Importantly, the prerequisite of B cells early postinfection is partially dependent on their expression of MHC class II. B cells are not only required during the priming phase, but also necessary for the initiation of robust secondary responses by memory CD4 T cells. Interestingly, the requirement during the recall response is independent of B cell Ag presentation. Overall, these studies demonstrate the temporally and functionally distinct roles for B cells in regulating CD4 T cell responses. PMID:24218454

  18. Human CD4+ T-Cells: A Role for Low-Affinity Fc Receptors

    PubMed Central

    Chauhan, Anil K.

    2016-01-01

    Both lymphoid and myeloid cells express Fc receptors (FcRs). Low-affinity FcRs engage circulating immune complexes, which results in the cellular activation and pro-inflammatory cytokine production. FcRs participate in the internalization, transport, and/or recycling of antibodies and antigens. Cytosolic FcRs also route these proteins to proteasomes and antigen-presentation pathways. Non-activated CD4+ T-cells do not express FcRs. Once activated, naive CD4+ T-cells express FcγRIIIa, which, upon IC ligation, provide a costimulatory signal for the differentiation of these cells into effector cell population. FcγRIIIa present on CD4+ T-cell membrane could internalize nucleic acid-containing ICs and elicit a cross-talk with toll-like receptors. FcγRIIIa common γ-chain forms a heterodimer with the ζ-chain of T-cell receptor complex, suggesting a synergistic role for these receptors. This review first summarizes our current understanding of FcRs on CD4+ T-cells. Thereafter, I will attempt to correlate the findings from the recent literature on FcRs and propose a role for these receptors in modulating adaptive immune responses via TLR signaling, nucleic acid sensing, and epigenetic changes in CD4+ T-cells. PMID:27313579

  19. Role of miRNAs in CD4 T cell plasticity during inflammation and tolerance

    PubMed Central

    Sethi, Apoorva; Kulkarni, Neeraja; Sonar, Sandip; Lal, Girdhari

    2013-01-01

    Gene expression is tightly regulated in a tuneable, cell-specific and time-dependent manner. Recent advancement in epigenetics and non-coding RNA (ncRNA) revolutionized the concept of gene regulation. In order to regulate the transcription, ncRNA can promptly response to the extracellular signals as compared to transcription factors present in the cells. microRNAs (miRNAs) are ncRNA (~22 bp) encoded in the genome, and present as intergenic or oriented antisense to neighboring genes. The strategic location of miRNA in coding genes helps in the coupled regulation of its expression with host genes. miRNA together with complex machinery called RNA-induced silencing complex (RISC) interacts with target mRNA and degrade the mRNA or inhibits the translation. CD4 T cells play an important role in the generation and maintenance of inflammation and tolerance. Cytokines and chemokines present in the inflamed microenvironment controls the differentiation and function of various subsets of CD4 T cells [Th1, Th2, Th17, and regulatory CD4 T cells (Tregs)]. Recent studies suggest that miRNAs play an important role in the development and function of all subsets of CD4 T cells. In current review, we focused on how various miRNAs are regulated by cell's extrinsic and intrinsic signaling, and how miRNAs affect the transdifferentiation of subsets of CD4 T cell and controls their plasticity during inflammation and tolerance. PMID:23386861

  20. Access of protective antiviral antibody to neuronal tissues requires CD4 T-cell help.

    PubMed

    Iijima, Norifumi; Iwasaki, Akiko

    2016-05-26

    Circulating antibodies can access most tissues to mediate surveillance and elimination of invading pathogens. Immunoprivileged tissues such as the brain and the peripheral nervous system are shielded from plasma proteins by the blood-brain barrier and blood-nerve barrier, respectively. Yet, circulating antibodies must somehow gain access to these tissues to mediate their antimicrobial functions. Here we examine the mechanism by which antibodies gain access to neuronal tissues to control infection. Using a mouse model of genital herpes infection, we demonstrate that both antibodies and CD4 T cells are required to protect the host after immunization at a distal site. We show that memory CD4 T cells migrate to the dorsal root ganglia and spinal cord in response to infection with herpes simplex virus type 2. Once inside these neuronal tissues, CD4 T cells secrete interferon-γ and mediate local increase in vascular permeability, enabling antibody access for viral control. A similar requirement for CD4 T cells for antibody access to the brain is observed after intranasal challenge with vesicular stomatitis virus. Our results reveal a previously unappreciated role of CD4 T cells in mobilizing antibodies to the peripheral sites of infection where they help to limit viral spread. PMID:27225131

  1. Exogenous and endogenous hyaluronic acid reduces HIV infection of CD4+ T cells

    PubMed Central

    Li, Peilin; Fujimoto, Katsuya; Bourguingnon, Lilly; Yukl, Steven; Deeks, Steven; Wong, Joseph K

    2014-01-01

    Preventing mucosal transmission of HIV is critical to halting the HIV epidemic. Novel approaches to preventing mucosal transmission are needed. Hyaluronic acid (HA) is a major extracellular component of mucosa and the primary ligand for the cell surface receptor CD44. CD44 enhances HIV infection of CD4+ T cells, but the role of HA in this process is not clear. To study this, virions were generated with CD44 (HIVCD44) or without CD44 (HIVmock). Exogenous HA reduced HIV infection of unstimulated CD4+ T cells in a CD44-dependent manner. Conversely, hyaluronidase-mediated reduction of endogenous HA on the cell surface enhanced HIV binding to and infection of unstimulated CD4+ T cells. Exogenous HA treatment reduced activation of protein kinase C alpha via CD44 on CD4+ T cells during infection with HIVCD44. These results reveal new roles for HA during the interaction of HIV with CD4+ T cells that may be relevant to mucosal HIV transmission and could be exploitable as a future strategy to prevent HIV infection. PMID:24957217

  2. A comparison of coupling efficiencies for a Stix coil and an m equals 1 coil

    NASA Technical Reports Server (NTRS)

    Sigman, D. R.

    1972-01-01

    This theoretical and experimental study compares the ion-cyclotron wave generating characteristics of a Stix coil (which generates waves with azimuthal mode number m = 0) with those of a coil which produces primarily m = + or -1 ion-cyclotron modes. The theoretical work of J.E. Hipp, which predicted very good coupling for the m = 1 coil, was extended to determine the scaling laws for plasma column radius and coil wavelength. Experimentally, an m = 1 coil and an m = 0 coil were used to generate ion-cyclotron waves on a beam generated plasma column with electron density = 10 to the 12th power/cu cm. Coupling resonances with peak efficiencies of approximately 40 to 50 percent were measured for both coils in low power (approximately 10k W) experiments. For equal power transfer to the plasma, the m = 0 coil voltage was more than a factor of two greater than that for the m = 1 coil.

  3. A Mechanical Coil Insertion System for Endovascular Coil Embolization of Intracranial Aneurysms

    PubMed Central

    Haraguchi, K.; Miyachi, S.; Matsubara, N.; Nagano, Y.; Yamada, H.; Marui, N.; Sano, A.; Fujimoto, H.; Izumi, T.; Yamanouchi, T.; Asai, T.; Wakabayashi, T.

    2013-01-01

    Summary Like other fields of medicine, robotics and mechanization might be introduced into endovascular coil embolization of intracranial aneurysms for effective treatment. We have already reported that coil insertion force could be smaller and more stable when the coil delivery wire is driven mechanically at a constant speed. Another background is the difficulty in synchronizing operators' minds and hands when two operators control the microcatheter and the coil respectively. We have therefore developed a mechanical coil insertion system enabling a single operator to insert coils at a fixed speed while controlling the microcatheter. Using our new system, the operator manipulated the microcatheter with both hands and drove the coil using foot switches simultaneously. A delivery wire force sensor previously reported was used concurrently, allowing the operator to detect excessive stress on the wire. In vitro coil embolization was performed using three methods: simple mechanical advance of the coil; simple mechanical advance of the coil with microcatheter control; and driving (forward and backward) of the coil using foot switches in addition to microcatheter control. The system worked without any problems, and did not interfere with any procedures. In experimental coil embolization, delivery wire control using the foot switches as well as microcatheter manipulation helped to achieve successful insertion of coils. This system could offer the possibility of developing safer and more efficient coil embolization. Although we aim at total mechanization and automation of procedures in the future, microcatheter manipulation and synchronized delivery wire control are still indispensable using this system. PMID:23693038

  4. A mechanical coil insertion system for endovascular coil embolization of intracranial aneurysms.

    PubMed

    Haraguchi, K; Miyachi, S; Matsubara, N; Nagano, Y; Yamada, H; Marui, N; Sano, A; Fujimoto, H; Izumi, T; Yamanouchi, T; Asai, T; Wakabayashi, T

    2013-06-01

    Like other fields of medicine, robotics and mechanization might be introduced into endovascular coil embolization of intracranial aneurysms for effective treatment. We have already reported that coil insertion force could be smaller and more stable when the coil delivery wire is driven mechanically at a constant speed. Another background is the difficulty in synchronizing operators' minds and hands when two operators control the microcatheter and the coil respectively. We have therefore developed a mechanical coil insertion system enabling a single operator to insert coils at a fixed speed while controlling the microcatheter. Using our new system, the operator manipulated the microcatheter with both hands and drove the coil using foot switches simultaneously. A delivery wire force sensor previously reported was used concurrently, allowing the operator to detect excessive stress on the wire. In vitro coil embolization was performed using three methods: simple mechanical advance of the coil; simple mechanical advance of the coil with microcatheter control; and driving (forward and backward) of the coil using foot switches in addition to microcatheter control. The system worked without any problems, and did not interfere with any procedures. In experimental coil embolization, delivery wire control using the foot switches as well as microcatheter manipulation helped to achieve successful insertion of coils. This system could offer the possibility of developing safer and more efficient coil embolization. Although we aim at total mechanization and automation of procedures in the future, microcatheter manipulation and synchronized delivery wire control are still indispensable using this system. PMID:23693038

  5. CMS dashboard for monitoring of the user analysis activities

    NASA Astrophysics Data System (ADS)

    Karavakis, Edward; Andreeva, Julia; Maier, Gerhild; Khan, Akram

    2012-12-01

    The CMS Virtual Organisation (VO) uses various fully distributed job submission methods and execution backends. The CMS jobs are processed on several middleware platforms such as the gLite, the ARC and the OSG. Up to 200,000 CMS jobs are submitted daily to the Worldwide LHC Computing Grid (WLCG) infrastructure and this number is steadily growing. These mentioned factors increase the complexity of the monitoring of the user analysis activities within the CMS VO. Reliable monitoring is an aspect of particular importance; it is a vital factor for the overall improvement of the quality of the CMS VO infrastructure.

  6. CD4+ T cell anergy prevents autoimmunity and generates regulatory T cell precursors

    PubMed Central

    Kalekar, Lokesh A.; Schmiel, Shirdi E.; Nandiwada, Sarada L.; Lam, Wing Y.; Barsness, Laura O.; Zhang, Na; Stritesky, Gretta L.; Malhotra, Deepali; Pauken, Kristen E.; Linehan, Jonathan L.; O’Sullivan, M. Gerard; Fife, Brian T.; Hogquist, Kristin A.; Jenkins, Marc K.; Mueller, Daniel L.

    2015-01-01

    The role that anergy, an acquired state of T cell functional unresponsiveness, plays in natural peripheral tolerance remains unclear. In this study, we demonstrate that anergy is selectively induced in fetal antigen-specific maternal CD4+ T cells during pregnancy. A naturally occurring subpopulation of anergic polyclonal CD4+ T cells, enriched in self antigen-specific T cell receptors, is also observed in healthy hosts. Neuropilin-1 expression in anergic conventional CD4+ T cells is associated with thymic regulatory T cell (Treg cell)-related gene hypomethylation, and this correlates with their capacity to differentiate into Foxp3+ Treg cells that suppress immunopathology. Thus, our data suggest that not only is anergy induction important in preventing autoimmunity, but it also generates the precursors for peripheral Treg cell differentiation. PMID:26829766

  7. IL-33 enhances retinoic acid signaling on CD4+ T cells.

    PubMed

    Gajardo, Tania; Pérez, Francisco; Terraza, Claudia; Campos-Mora, Mauricio; Noelle, Randolph J; Pino-Lagos, Karina

    2016-09-01

    Several molecules have been described as CD4+ T cells differentiation modulators and among them retinoic acid (RA) and more recently, IL-33, have been studied. Due to the similarities in T helper cell skewing properties between RA and IL-33, we asked whether IL-33 intersects, directly or indirectly, the RA signaling pathway. Total CD4+ T cells from DR5-luciferase mice were activated in the presence of RA with or without IL-33, and RA signaling was visualized using ex vivo imaging. Our results demonstrate that IL-33 itself is able to trigger RA signaling on CD4+ T cells, which is highly increased when IL-33 is added in conjunction with RA. This study presents IL-33 as a potential player that may synergize with RA in controlling T cell differentiation, and suggests that IL-33 may be an attractive target in controlling T cell differentiation in vivo. PMID:27322964

  8. IL-10-producing CD4+ T cells negatively regulate fucosylation of epithelial cells in the gut

    PubMed Central

    Goto, Yoshiyuki; Lamichhane, Aayam; Kamioka, Mariko; Sato, Shintaro; Honda, Kenya; Kunisawa, Jun; Kiyono, Hiroshi

    2015-01-01

    Fucosylated glycans on the surface of epithelial cells (ECs) regulate intestinal homeostasis by serving as attachment receptors and a nutrient source for some species of bacteria. We show here that epithelial fucosylation in the ileum is negatively regulated by IL-10-producing CD4+ T cells. The number of fucosylated ECs was increased in the ileum of mice lacking T cells, especially those expressing αβ T cell receptor (TCR), CD4, and IL-10. No such effect was observed in mice lacking B cells. Adoptive transfer of αβTCR+ CD4+ T cells from normal mice, but not IL-10-deficient mice, normalized fucosylation of ECs. These findings suggest that IL-10-producing CD4+ T cells contribute to the maintenance of the function of ECs by regulating their fucosylation. PMID:26522513

  9. The ion channel TRPV1 regulates the activation and proinflammatory properties of CD4+ T cells

    PubMed Central

    Bertin, Samuel; Aoki-Nonaka, Yukari; de Jong, Petrus Rudolf; Stanwood, Shawna R.; Srikanth, Sonal; Lee, Jihyung; To, Keith; Abramson, Lior; Yu, Timothy; Han, Tiffany; Touma, Ranim; Li, Xiangli; González-Navajas, José M.; Herdman, Scott; Corr, Maripat; Fu, Guo; Dong, Hui; Gwack, Yousang; Franco, Alessandra; Jefferies, Wilfred A.; Raz, Eyal

    2016-01-01

    TRPV1 is a Ca2+-permeable channel mostly studied as a pain receptor in sensory neurons. However, its role in other cell types is poorly understood. Here, we demonstrate that TRPV1 is functionally expressed in CD4+ T cells where it acts as a non-store-operated Ca2+ channel and contributes to T cell receptor (TCR)-induced Ca2+ influx, TCR signaling and T cell activation. In models of T cell-mediated colitis, TRPV1 promotes colitogenic T cell responses and intestinal inflammation. Furthermore, genetic and pharmacological inhibition of TRPV1 in human CD4+ T cells recapitulates the phenotype of murine Trpv1−/− CD4+ T cells. These findings suggest that TRPV1 inhibition could represent a new therapeutic strategy to restrain proinflammatory T cell responses. PMID:25282159

  10. Optimized Geometry for Superconducting Sensing Coils

    NASA Technical Reports Server (NTRS)

    Eom, Byeong Ho; Pananen, Konstantin; Hahn, Inseob

    2008-01-01

    An optimized geometry has been proposed for superconducting sensing coils that are used in conjunction with superconducting quantum interference devices (SQUIDs) in magnetic resonance imaging (MRI), magnetoencephalography (MEG), and related applications in which magnetic fields of small dipoles are detected. In designing a coil of this type, as in designing other sensing coils, one seeks to maximize the sensitivity of the detector of which the coil is a part, subject to geometric constraints arising from the proximity of other required equipment. In MRI or MEG, the main benefit of maximizing the sensitivity would be to enable minimization of measurement time. In general, to maximize the sensitivity of a detector based on a sensing coil coupled with a SQUID sensor, it is necessary to maximize the magnetic flux enclosed by the sensing coil while minimizing the self-inductance of this coil. Simply making the coil larger may increase its self-inductance and does not necessarily increase sensitivity because it also effectively increases the distance from the sample that contains the source of the signal that one seeks to detect. Additional constraints on the size and shape of the coil and on the distance from the sample arise from the fact that the sample is at room temperature but the coil and the SQUID sensor must be enclosed within a cryogenic shield to maintain superconductivity.

  11. Heterologous vaccination against human tuberculosis modulates antigen-specific CD4+ T-cell function.

    PubMed

    Dintwe, One B; Day, Cheryl L; Smit, Erica; Nemes, Elisa; Gray, Clive; Tameris, Michele; McShane, Helen; Mahomed, Hassan; Hanekom, Willem A; Scriba, Thomas J

    2013-09-01

    Heterologous prime-boost strategies hold promise for vaccination against tuberculosis. However, the T-cell characteristics required for protection are not known. We proposed that boost vaccines should induce long-lived functional and phenotypic changes to T cells primed by Bacille Calmette Guerin (BCG) and/or natural exposure to mycobacteria. We characterized changes among specific CD4(+) T cells after vaccination with the MVA85A vaccine in adults, adolescents, and children. CD4(+) T cells identified with Ag85A peptide-bearing HLA class II tetramers were characterized by flow cytometry. We also measured proliferative potential and cytokine expression of Ag85A-specific CD4(+) T cells. During the effector phase, MVA85A-induced specific CD4(+) T cells coexpressed IFN-γ and IL-2, skin homing integrins, and the activation marker CD38. This was followed by contraction and a transition to predominantly IL-2-expressing, CD45RA(-) CCR7(+) CD27(+) or CD45RA(+) CCR7(+) CD27(+) specific CD4(+) T cells. These surface phenotypes were similar to Ag85A-specific T cells prior to MVA85A. However, functional differences were observed postvaccination: specific proliferative capacity was markedly higher after 6-12 months than before vaccination. Our data suggest that MVA85A vaccination may modulate Ag85A-specific CD4(+) T-cell function, resulting in greater recall potential. Importantly, surface phenotypes commonly used as proxies for memory T-cell function did not associate with functional effects of vaccination. PMID:23737382

  12. Increased Mucosal CD4+ T Cell Activation in Rhesus Macaques following Vaccination with an Adenoviral Vector

    PubMed Central

    Bukh, Irene; Calcedo, Roberto; Roy, Soumitra; Carnathan, Diane G.; Grant, Rebecca; Qin, Qiuyue; Boyd, Surina; Ratcliffe, Sarah J.; Veeder, Christin L.; Bellamy, Scarlett L.; Betts, Michael R.

    2014-01-01

    ABSTRACT The possibility that vaccination with adenovirus (AdV) vectors increased mucosal T cell activation remains a central hypothesis to explain the potential enhancement of HIV acquisition within the Step trial. Modeling this within rhesus macaques is complicated because human adenoviruses, including human adenovirus type 5 (HAdV-5), are not endogenous to macaques. Here, we tested whether vaccination with a rhesus macaque-derived adenoviral vector (simian adenovirus 7 [SAdV-7]) enhances mucosal T cell activation within rhesus macaques. Following intramuscular SAdV-7 vaccination, we observed a pronounced increase in SAdV-7-specific CD4+ T cell responses in peripheral blood and, more dramatically, in rectal mucosa tissue. Vaccination also induced a significant increase in the frequency of activated memory CD4+ T cells in SAdV-7- and HAdV-5-vaccinated animals in the rectal mucosa but not in peripheral blood. These fluctuations within the rectal mucosa were also associated with a pronounced decrease in the relative frequency of naive resting CD4+ T cells. Together, these results indicate that peripheral vaccination with an AdV vector can increase the activation of mucosal CD4+ T cells, potentially providing an experimental model to further evaluate the role of host-vector interactions in increased HIV acquisition after AdV vector vaccination. IMPORTANCE The possibility that vaccination with a human adenovirus 5 vector increased mucosal T cell activation remains a central hypothesis to explain the potential enhancement of human immunodeficiency virus (HIV) acquisition within the Step trial. In this study, we tested whether vaccination with a rhesus macaque-derived adenoviral vector in rhesus macaques enhances mucosal CD4+ T cell activation, the main cell target of simian immunodeficiency virus (SIV)/HIV. The results showed that vaccination with an adenoviral vector indeed increases activation of mucosal CD4+ T cells and potentially increases susceptibility to SIV

  13. DNA methylation analysis of CD4+ T cells in patients with psoriasis.

    PubMed

    Park, Geon Tae; Han, Jihye; Park, Sin-Gi; Kim, Sangsoo; Kim, Tae-Yoon

    2014-04-01

    Psoriasis is a chronic inflammatory skin disease that is characterized by aberrant cross-talk between keratinocytes and immune cells such as CD4+ T cells, resulting in keratinocyte hyperproliferation in the epidermis. DNA methylation, one of several epigenetic mechanisms, plays an important role in gene expression without changing the DNA sequence. Several studies have suggested the involvement of epigenetic regulation in skin lesions from patients with psoriasis. In this study, we investigated the genome-wide DNA methylation status of CD4+ T cells in patients with psoriasis compared with healthy subjects using methylated DNA immunoprecipitation sequencing (MeDIP-Seq). The results of MeDIP-Seq showed that the global methylation values of CD4+ T cells are higher in patients with psoriasis than in healthy controls, particularly in the promoter regions. Among the most hypermethylated genes in the promoter regions, we selected the genes whose expression is significantly reduced in the CD4+ T cells of psoriasis patients. Studies using the methylation inhibitor 5-azacytidine in vitro methylation assays have shown that the differential expression levels were associated with the methylation status of each gene. Bisulfite sequencing of the transcription start region of phosphatidic acid phosphatase type 2 domain containing 3 (PPAPDC3), one of the selected genes, showed hypermethylation in the CD4+ T cells of psoriasis patients. These results suggested that the methylation status, which is identified by MeDIP-Seq of the genes, was correlated with the mRNA expression level of the genes. Collectively, the DNA methylation status in CD4+ T cells might be associated with the pathogenesis of psoriasis. PMID:24323136

  14. Natural CD4+ T-Cell Responses against Indoleamine 2,3-Dioxygenase

    PubMed Central

    Munir, Shamaila; Larsen, Stine Kiaer; Iversen, Trine Zeeberg; Donia, Marco; Klausen, Tobias Wirenfeldt; Svane, Inge Marie; Straten, Per thor; Andersen, Mads Hald

    2012-01-01

    Background The enzyme indoleamine 2,3-dioxygenase (IDO) contributes to immune tolerance in a variety of settings. In cancer IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it endorses the establishment of peripheral immune tolerance to tumor antigens. Recently, we described cytotoxic CD8+ T-cell reactivity towards IDO-derived peptides. Methods and Findings In the present study, we show that CD4+ helper T cells additionally spontaneously recognize IDO. Hence, we scrutinized the vicinity of the previously described HLA-A*0201-restricted IDO-epitope for CD4+ T-cell epitopes. We demonstrated the presence of naturally occurring IDO-specific CD4+ T cells in cancer patients and to a lesser extent in healthy donors by cytokine release ELISPOT. IDO-reactive CD4+ T cells released IFN-γ, TNF-α, as well as IL-17. We confirm HLA class II-restriction by the addition of HLA class II specific blocking antibodies. In addition, we detected a trend between class I- and class II-restricted IDO responses and detected an association between IDO-specific CD4+ T cells and CD8+ CMV-responses. Finally, we could detect IL-10 releasing IDO-reactive CD4+ T cells. Conclusion IDO is spontaneously recognized by HLA class II-restricted, CD4+ T cells in cancer patients and in healthy individuals. IDO-specific T cells may participate in immune-regulatory networks where the activation of pro-inflammatory IDO-specific CD4+ responses may well overcome or delay the immune suppressive actions of the IDO-protein, which are otherwise a consequence of the early expression of IDO in maturing antigen presenting cells. In contrast, IDO-specific regulatory T cells may enhance IDO-mediated immune suppression. PMID:22539948

  15. Immunodominant HIV-1 Cd4+ T Cell Epitopes in Chronic Untreated Clade C HIV-1 Infection

    PubMed Central

    Ramduth, Danni; Day, Cheryl L.; Thobakgale, Christina F.; Mkhwanazi, Nompumelelo P.; de Pierres, Chantal; Reddy, Sharon; van der Stok, Mary; Mncube, Zenele; Nair, Kriebashne; Moodley, Eshia S.; Kaufmann, Daniel E.; Streeck, Hendrik; Coovadia, Hoosen M.; Kiepiela, Photini; Goulder, Philip J. R.; Walker, Bruce D.

    2009-01-01

    Background A dominance of Gag-specific CD8+ T cell responses is significantly associated with a lower viral load in individuals with chronic, untreated clade C human immunodeficiency virus type 1 (HIV-1) infection. This association has not been investigated in terms of Gag-specific CD4+ T cell responses, nor have clade C HIV-1–specific CD4+ T cell epitopes, likely a vital component of an effective global HIV-1 vaccine, been identified. Methodology/Principal Findings Intracellular cytokine staining was conducted on 373 subjects with chronic, untreated clade C infection to assess interferon-gamma (IFN-γ) responses by CD4+ T cells to pooled Gag peptides and to determine their association with viral load and CD4 count. Gag-specific IFN-γ–producing CD4+ T cell responses were detected in 261/373 (70%) subjects, with the Gag responders having a significantly lower viral load and higher CD4 count than those with no detectable Gag response (p<0.0001 for both parameters). To identify individual peptides targeted by HIV-1–specific CD4+ T cells, separate ELISPOT screening was conducted on CD8-depleted PBMCs from 32 chronically infected untreated subjects, using pools of overlapping peptides that spanned the entire HIV-1 clade C consensus sequence, and reconfirmed by flow cytometry to be CD4+ mediated. The ELISPOT screening identified 33 CD4+ peptides targeted by 18/32 patients (56%), with 27 of the 33 peptides located in the Gag region. Although the breadth of the CD4+ responses correlated inversely with viral load (p = 0.015), the magnitude of the response was not significantly associated with viral load. Conclusions/Significance These data indicate that in chronic untreated clade C HIV-1 infection, IFN-γ–secreting Gag-specific CD4+ T cell responses are immunodominant, directed at multiple distinct epitopes, and associated with viral control. PMID:19352428

  16. Coiled-coil protein composition of 22 proteomes – differences and common themes in subcellular infrastructure and traffic control

    PubMed Central

    Rose, Annkatrin; Schraegle, Shannon J; Stahlberg, Eric A; Meier, Iris

    2005-01-01

    Background Long alpha-helical coiled-coil proteins are involved in diverse organizational and regulatory processes in eukaryotic cells. They provide cables and networks in the cyto- and nucleoskeleton, molecular scaffolds that organize membrane systems and tissues, motors, levers, rotating arms, and possibly springs. Mutations in long coiled-coil proteins have been implemented in a growing number of human diseases. Using the coiled-coil prediction program MultiCoil, we have previously identified all long coiled-coil proteins from the model plant Arabidopsis thaliana and have established a searchable Arabidopsis coiled-coil protein database. Results Here, we have identified all proteins with long coiled-coil domains from 21 additional fully sequenced genomes. Because regions predicted to form coiled-coils interfere with sequence homology determination, we have developed a sequence comparison and clustering strategy based on masking predicted coiled-coil domains. Comparing and grouping all long coiled-coil proteins from 22 genomes, the kingdom-specificity of coiled-coil protein families was determined. At the same time, a number of proteins with unknown function could be grouped with already characterized proteins from other organisms. Conclusion MultiCoil predicts proteins with extended coiled-coil domains (more than 250 amino acids) to be largely absent from bacterial genomes, but present in archaea and eukaryotes. The structural maintenance of chromosomes proteins and their relatives are the only long coiled-coil protein family clearly conserved throughout all kingdoms, indicating their ancient nature. Motor proteins, membrane tethering and vesicle transport proteins are the dominant eukaryote-specific long coiled-coil proteins, suggesting that coiled-coil proteins have gained functions in the increasingly complex processes of subcellular infrastructure maintenance and trafficking control of the eukaryotic cell. PMID:16288662

  17. De Novo Design of Ln(III) Coiled Coils for Imaging Applications

    PubMed Central

    2014-01-01

    A new peptide sequence (MB1) has been designed which, in the presence of a trivalent lanthanide ion, has been programmed to self-assemble to form a three stranded metallo-coiled coil, Ln(III)(MB1)3. The binding site has been incorporated into the hydrophobic core using natural amino acids, restricting water access to the lanthanide. The resulting terbium coiled coil displays luminescent properties consistent with a lack of first coordination sphere water molecules. Despite this the gadolinium coiled coil, the first to be reported, displays promising magnetic resonance contrast capabilities. PMID:24405157

  18. RECENT TEST RESULTS OF THE FAST-PULSED 4 T COS DIPOLE GSI 001.

    SciTech Connect

    MORITZ, G.; KAUGERTS, J.; ESCALLIER, J.; GANETIS, G.; JAIN, A.; MARONE, A.; MURATORE, J.; THOMAS, R.; WANDERER, P.; ET AL.

    2005-05-26

    For the FAIR-project at GSI a model dipole was built at BNL with the nominal field of 4 T and a nominal ramp rate of 1 T/S. The magnet design was similar to the RHIC dipole, with some changes for loss reduction and better cooling. The magnet was already successfully tested in a vertical cryostat, with good training behavior. Cryogenic losses were measured and first results of field harmonics were published. However, for a better understanding of the cooling process, quench currents at several ramp rates were investigated. Detailed measurements of the field harmonics at 2 T/S between 0 and 4 T were performed.

  19. CD4+ T-cell subsets and host defense in the lung

    PubMed Central

    Kolls, Jay K.

    2012-01-01

    Summary CD4+ T-helper subsets are lineages of T cells that have effector function in the lung and control critical aspects of lung immunity. Depletion of these cells experimentally or by drugs or human immunodeficiency virus (HIV) infection in humans leads to the development of opportunistic infections as well as increased rates of bacteremia with certain bacterial pneumonias. Recently, it has been proposed that CD4+ T-cell subsets may also be excellent targets for mucosal vaccination to prevent pulmonary infections in susceptible hosts. Here we review recent findings that increase our understanding of T-cell subsets and their effector cytokines in the context of pulmonary infection. PMID:23405903

  20. Sequestration from Immune CD4^+ T Cells of Mycobacteria Growing in Human Macrophages

    NASA Astrophysics Data System (ADS)

    Pancholi, Preeti; Mirza, Asra; Bhardwaj, Nina; Steinman, Ralph M.

    1993-05-01

    CD4^+ helper T cells mediate resistance to tuberculosis, presumably by enhancing the antimicrobial activity of macrophages within which the Mycobacterium tuberculosis organism grows. A first step in resistance should be the presentation of mycobacterial antigens by macrophages to CD4^+ T cells. However, when the antigenic stimulus is limited to organisms growing in human monocytes, the organisms become sequestered from immune CD4^+ T cells. This block in presentation is selective for growing mycobacteria and not for other stimuli. Sequestration would allow replicating organisms to persist in infected individuals and may contribute to virulence.

  1. Occurrence of 4-tert-butylphenol (4-t-BP) biodegradation in an aquatic sample caused by the presence of Spirodela polyrrhiza and isolation of a 4-t-BP-utilizing bacterium.

    PubMed

    Ogata, Yuka; Toyama, Tadashi; Yu, Ning; Wang, Xuan; Sei, Kazunari; Ike, Michihiko

    2013-04-01

    Although 4-tert-butylphenol (4-t-BP) is a serious aquatic pollutant, its biodegradation in aquatic environments has not been well documented. In this study, 4-t-BP was obviously and repeatedly removed from water from four different environments in the presence of Spirodela polyrrhiza, giant duckweed, but 4-t-BP persisted in the environmental waters in the absence of S. polyrrhiza. Also, 4-t-BP was not removed from autoclaved pond water with sterilized S. polyrrhiza. These results suggest that the 4-t-BP removal from the environmental waters was caused by biodegradation stimulated by the presence of S. polyrrhiza rather than by uptake by the plant. Moreover, Sphingobium fuliginis OMI capable of utilizing 4-t-BP as a sole carbon and energy source was isolated from the S. polyrrhiza rhizosphere. Strain OMI degraded 4-t-BP via a meta-cleavage pathway, and also degraded a broad range of alkylphenols with linear or branched alkyl side chains containing two to nine carbon atoms. Root exudates of S. polyrrhiza stimulated 4-t-BP degradation and cell growth of strain OMI. Thus, the stimulating effects of S. polyrrhiza root exudates on 4-t-BP-degrading bacteria might have contributed to 4-t-BP removal in the environmental waters with S. polyrrhiza. These results demonstrate that the S. polyrrhiza-bacteria association may be applicable to the removal of highly persistent 4-t-BP from wastewaters or polluted aquatic environments. PMID:22777343

  2. The Golgin Family of Coiled-Coil Tethering Proteins

    PubMed Central

    Witkos, Tomasz M.; Lowe, Martin

    2016-01-01

    The golgins are a family of predominantly coiled-coil proteins that are localized to the Golgi apparatus. Golgins are present in all eukaryotes, suggesting an evolutionary conserved function. Golgins are anchored to the Golgi membrane by their carboxy terminus and are predicted to adopt an extended conformation that projects into the surrounding cytoplasm. This arrangement is ideal for the capture or tethering of nearby membranes or cytoskeletal elements. Golgin-mediated tethering is thought to be important for vesicular traffic at the Golgi apparatus, the maintenance of Golgi architecture, as well as the positioning of the Golgi apparatus within cells. In addition to acting as tethers, some golgins can also sequester various factors at the Golgi membrane, allowing for the spatiotemporal regulation of downstream cellular functions. Although it is now established that golgins are membrane and cytoskeleton tethers, the mechanisms underlying tethering remain poorly defined. Moreover, the importance of golgin-mediated tethering in a physiological context remains to be fully explored. This review will describe our current understanding of golgin function, highlighting recent progress that has been made, and goes on to discuss outstanding questions and potential avenues for future research with regard to this family of conserved Golgi-associated proteins. PMID:26793708

  3. Current COIL research in Samara

    NASA Astrophysics Data System (ADS)

    Nikolaev, Valeri D.

    1996-02-01

    Development of the high pressure singlet oxygen generator (SOG) is a very important aspect for chemical oxygen-iodine laser (COIL). Increasing of oxygen pressure up to 30 torr and more at conserving high O2(1(Delta) ) yield and maintaining BHP temperature at minus (10 divided by 20) degrees Celsius permits us to decrease ration [H2O]/[O2] to 5% and less. In this case COIL can operate successfully without a water vapor trap. With raising the total pressure Reynolds number increases too, diminishing boundary layers in supersonic nozzles and improving pressure recovery. The weight and dimensions of the SOG and laser become reduced for the same gas flow rate. For solving these problems the jet SOG has been suggested and developed in Lebedev Physical Institute, Samara Branch. The advantages of the jet SOG consist of the following: (1) Large and controlled specific surface of contact liquid-gas provides for high mass transfer efficiency. (2) High jets velocity guarantees fast basic hydrogen peroxide (BHP) surface renovation. (3) High gas velocity in the reaction zone diminishes O2(1(Delta) ) quenching. (4) Efficient gas-liquid heat exchange eliminates the gas heating and generation water vapor due O2(1(Delta) ) quenching. (5) Counterflowing design of the jet SOG produces the best conditions for self-cleaning gas flow of droplets in the reaction zone and gives the possibility of COIL operation without droplets separator. High pressure jet SOG has some features connected with intrachannel jet formation, free space jets reconstruction, interaction jets ensemble with counter moving gas flow and drag part of gas by jets, disintegrating jets, generation and separation of droplets, heat effects, surface renovation, impoverishment BHP surface by HO2- ions, moving solution film on the reaction zone walls, etc. In this communication our current understanding of the major processes in the jet SOG is set forth. The complex gas and hydrodynamic processes with heat and mass transfer

  4. Development of a new error field correction coil (C-coil) for DIII-D

    SciTech Connect

    Robinson, J.I.; Scoville, J.T.

    1995-12-01

    The C-coil recently installed on the DIII-D tokamak was developed to reduce the error fields created by imperfections in the location and geometry of the existing coils used to confine, heat, and shape the plasma. First results from C-coil experiments include stable operation in a 1.6 MA plasma with a density less than 1.0 {times} 10{sup 13} cm{sup {minus}3}, nearly a factor of three lower density than that achievable without the C-coil. The C-coil has also been used in magnetic braking of the plasma rotation and high energy particle confinement experiments. The C-coil system consists of six individual saddle coils, each 60{degree} wide toroidally, spanning the midplane of the vessel with a vertical height of 1.6 m. The coils are located at a major radius of 3.2 m, just outside of the toroidal field coils. The actual shape and geometry of each coil section varied somewhat from the nominal dimensions due to the large number of obstructions to the desired coil path around the already crowded tokamak. Each coil section consists of four turns of 750 MCM insulated copper cable banded with stainless steel straps within the web of a 3 in. x 3 in. stainless steel angle frame. The C-coil structure was designed to resist peak transient radial forces (up to 1,800 Nm) exerted on the coil by the toroidal and ploidal fields. The coil frames were supported from existing poloidal field coil case brackets, coil studs, and various other structures on the tokamak.

  5. Critical evaluation of in silico methods for prediction of coiled-coil domains in proteins.

    PubMed

    Li, Chen; Ching Han Chang, Catherine; Nagel, Jeremy; Porebski, Benjamin T; Hayashida, Morihiro; Akutsu, Tatsuya; Song, Jiangning; Buckle, Ashley M

    2016-03-01

    Coiled-coils refer to a bundle of helices coiled together like strands of a rope. It has been estimated that nearly 3% of protein-encoding regions of genes harbour coiled-coil domains (CCDs). Experimental studies have confirmed that CCDs play a fundamental role in subcellular infrastructure and controlling trafficking of eukaryotic cells. Given the importance of coiled-coils, multiple bioinformatics tools have been developed to facilitate the systematic and high-throughput prediction of CCDs in proteins. In this article, we review and compare 12 sequence-based bioinformatics approaches and tools for coiled-coil prediction. These approaches can be categorized into two classes: coiled-coil detection and coiled-coil oligomeric state prediction. We evaluated and compared these methods in terms of their input/output, algorithm, prediction performance, validation methods and software utility. All the independent testing data sets are available at http://lightning.med.monash.edu/coiledcoil/. In addition, we conducted a case study of nine human polyglutamine (PolyQ) disease-related proteins and predicted CCDs and oligomeric states using various predictors. Prediction results for CCDs were highly variable among different predictors. Only two peptides from two proteins were confirmed to be CCDs by majority voting. Both domains were predicted to form dimeric coiled-coils using oligomeric state prediction. We anticipate that this comprehensive analysis will be an insightful resource for structural biologists with limited prior experience in bioinformatics tools, and for bioinformaticians who are interested in designing novel approaches for coiled-coil and its oligomeric state prediction. PMID:26177815

  6. Crystal Structure of a Super Leucine Zipper an Extended Two-Stranded Super Long Coiled Coil

    SciTech Connect

    J Diao

    2011-12-31

    Coiled coil is a ubiquitous structural motif in proteins, with two to seven alpha helices coiled together like the strands of a rope, and coiled coil folding and assembly is not completely understood. A GCN4 leucine zipper mutant with four mutations of K3A, D7A, Y17W, and H18N has been designed, and the crystal structure has been determined at 1.6 {angstrom} resolution. The peptide monomer shows a helix trunk with short curved N- and C-termini. In the crystal, two monomers cross in 35{sup o} and form an X-shaped dimer, and each X-shaped dimer is welded into the next one through sticky hydrophobic ends, thus forming an extended two-stranded, parallel, super long coiled coil rather than a discrete, two-helix coiled coil of the wild-type GCN4 leucine zipper. Leucine residues appear at every seventh position in the super long coiled coil, suggesting that it is an extended super leucine zipper. Compared to the wild-type leucine zipper, the N-terminus of the mutant has a dramatic conformational change and the C-terminus has one more residue Glu 32 determined. The mutant X-shaped dimer has a large crossing angle of 35{sup o} instead of 18{sup o} in the wild-type dimer. The results show a novel assembly mode and oligomeric state of coiled coil, and demonstrate that mutations may affect folding and assembly of the overall coiled coil. Analysis of the formation mechanism of the super long coiled coil may help understand and design self-assembling protein fibers.

  7. Electromagnetic levitation coil fabrication technique for MSFC containerless processing facilities

    NASA Technical Reports Server (NTRS)

    Ethridge, E. C.; Theiss, J.; Curreri, P. A.; Abbaschian, G. J.

    1983-01-01

    A technique is described for more reproducible fabrication of electromagnetic levitation coils. A split mandrel was developed upon which the coil is wound. After fabrication the mandrel can be disassembled to remove it from the coil. Previously, a full day was required to fabricate a levitation coil and the success rate for a functional coil was only 50 percent. About eight coils may be completed in one day using the technique developed and 95 percent of them are good levitation coils.

  8. Muon Reconstruction and Identification in CMS

    SciTech Connect

    Everett, A.

    2010-02-10

    We present the design strategies and status of the CMS muon reconstruction and identification identification software. Muon reconstruction and identification is accomplished through a variety of complementary algorithms. The CMS muon reconstruction software is based on a Kalman filter technique and reconstructs muons in the standalone muon system, using information from all three types of muon detectors, and links the resulting muon tracks with tracks reconstructed in the silicon tracker. In addition, a muon identification algorithm has been developed which tries to identify muons with high efficiency while maintaining a low probability of misidentification. The muon identification algorithm is complementary by design to the muon reconstruction algorithm that starts track reconstruction in the muon detectors. The identification algorithm accepts reconstructed tracks from the inner tracker and attempts to quantify the muon compatibility for each track using associated calorimeter and muon detector hit information. The performance status is based on detailed detector simulations as well as initial studies using cosmic muon data.

  9. The structure of the GemC1 coiled coil and its interaction with the Geminin family of coiled-coil proteins

    PubMed Central

    Caillat, Christophe; Fish, Alexander; Pefani, Dafni-Eleftheria; Taraviras, Stavros; Lygerou, Zoi; Perrakis, Anastassis

    2015-01-01

    GemC1, together with Idas and Geminin, an important regulator of DNA-replication licensing and differentiation decisions, constitute a superfamily sharing a homologous central coiled-coil domain. To better understand this family of proteins, the crystal structure of a GemC1 coiled-coil domain variant engineered for better solubility was determined to 2.2 Å resolution. GemC1 shows a less typical coiled coil compared with the Geminin homodimer and the Geminin–Idas heterodimer structures. It is also shown that both in vitro and in cells GemC1 interacts with Geminin through its coiled-coil domain, forming a heterodimer that is more stable that the GemC1 homodimer. Comparative analysis of the thermal stability of all of the possible superfamily complexes, using circular dichroism to follow the unfolding of the entire helix of the coiled coil, or intrinsic tryptophan fluorescence of a unique conserved N-terminal tryptophan, shows that the unfolding of the coiled coil is likely to take place from the C-terminus towards the N-terminus. It is also shown that homodimers show a single-state unfolding, while heterodimers show a two-state unfolding, suggesting that the dimer first falls apart and the helices then unfold according to the stability of each protein. The findings argue that Geminin-family members form homodimers and heterodimers between them, and this ability is likely to be important for modulating their function in cycling and differentiating cells. PMID:26527144

  10. Observation of hard diffraction with CMS

    SciTech Connect

    Obertino, M. M.

    2009-03-23

    Diffraction with a hard scale can be observed in the first LHC data. We present studies of single diffractive W-boson production (pp{yields}Xp, with X including a W boson) and of {upsilon} photoproduction (pp{yields}{upsilon}p, with {upsilon}{yields}{mu}{sup +}{mu}{sup -}). The feasibility of observing these processes with the CMS detector using the first 100 pb{sup -1} of collected integrated luminosity for single interactions is discussed.

  11. Studies of vector boson production at CMS

    NASA Astrophysics Data System (ADS)

    Dordevic, Milos; CMS Collaboration

    2016-07-01

    The most recent diboson production and electroweak physics results from CMS are presented. This overview is focused on the precise measurement of WW , WZ , ZZ and γ γ production, as well as W or Z production in association with a photon. These results are interpreted in terms of constraints on anomalous triple gauge couplings, while the study of WW γ and WZ γ production is used to set limits on anomalous quartic gauge couplings. Selection of the latest electroweak results is also presented.

  12. New Forward and Diffractive Physics at CMS

    NASA Astrophysics Data System (ADS)

    Santoro, Alberto

    2011-04-01

    Forward and Diffractive Physics (FWP) in LHC is a new open window to understand this type of strong interactions. We will present a didactic description of the topics being developed at CMS. As we know there still is no new results to present for FWP. We are accumulating data to have soon new results. We will show a number of topics and the detectors properties to do the observation of several topologies. We expect to give an optimistic view of the area.

  13. High CD4+ T cell density is associated with poor prognosis in patients with non-muscle-invasive bladder cancer

    PubMed Central

    Zhang, Qinglei; Hao, Chongli; Cheng, Guangzhou; Wang, Lei; Wang, Xiang; Li, Chang; Qiu, Juhui; Ding, Kejia

    2015-01-01

    Purpose: The aim of this study was to investigate the clinical significance of CD4+ T cells in non-muscle-invasive bladder cancer (NMIBC) tissues in situ. Methods: Immunohistochemistry was used to examine the distribution of CD4+ T cells in 131 NMIBC tissues. Kaplan-Meier analysis and Cox proportional hazards regression models were applied to estimate overall survival (OS) and recurrence-free survival (RFS). Results: NMIBC patients were divided into two groups based on the median frequency of CD4+ T cells (median, 1/×400 high resolution). On univariate analysis, CD4+ T cell density was inversely associated with overall survival (P = 0.01). In those patients with high CD4+ T density, 5-year OS rates was only 77%, compared with 86% in those with low density, respectively. Although CD4+ T cell density showed no prognostic significance for RFS (P = 0.36), 5-year RFS rates of patients with high CD4+ T density (58%) was lower than those of patients with low CD4+ T density (65%, respectively). By multivariate analysis, tumor infiltrating CD4+ T cell density emerged as an independent prognostic factor for OS (HR, 2.75; P = 0.004). In addition, no association was found between CD4+ T cell density and any clinicopathological variables (P > 0.05). Conclusion: Our findings suggest that CD4+ T cells could potentially serve as a poor prognostic marker for patients with NMIBC. PMID:26617883

  14. Exhaustion of bacteria-specific CD4 T cells and microbial translocation in common variable immunodeficiency disorders.

    PubMed

    Perreau, Matthieu; Vigano, Selena; Bellanger, Florence; Pellaton, Céline; Buss, Guillaume; Comte, Denis; Roger, Thierry; Lacabaratz, Christine; Bart, Pierre-Alexandre; Levy, Yves; Pantaleo, Giuseppe

    2014-09-22

    In the present study, we have investigated the functional profile of CD4 T cells from patients with common variable immunodeficiency (CVID), including production of cytokines and proliferation in response to bacteria and virus-derived antigens. We show that the functional impairment of CD4 T cells, including the reduced capacity to proliferate and to produce IFN-γ and IL-2, was restricted to bacteria-specific and not virus-specific CD4 T cells. High levels of endotoxins were found in the plasma of patients with CVID, suggesting that CD4 T cell dysfunction might be caused by bacterial translocation. Of note, endotoxemia was associated with significantly higher expression of programmed death 1 (PD-1) on CD4 T cells. The blockade of the PD-1-PD-L1/2 axis in vitro restored CD4 T cell proliferation capacity, thus indicating that PD-1 signaling negatively regulates CD4 T cell functions. Finally, we showed that intravenous immunoglobulin G (IVIG) treatment significantly reduced endotoxemia and the percentage of PD-1(+) CD4 T cells, and restored bacteria-specific CD4 T cell cytokine production and proliferation. In conclusion, the present study demonstrates that the CD4 T cell exhaustion and functional impairment observed in CVID patients is associated with bacterial translocation and that IVIG treatment resolves bacterial translocation and restores CD4 T cell functions. PMID:25225461

  15. CMS High Level Trigger Timing Measurements

    NASA Astrophysics Data System (ADS)

    Richardson, Clint

    2015-12-01

    The two-level trigger system employed by CMS consists of the Level 1 (L1) Trigger, which is implemented using custom-built electronics, and the High Level Trigger (HLT), a farm of commercial CPUs running a streamlined version of the offline CMS reconstruction software. The operational L1 output rate of 100 kHz, together with the number of CPUs in the HLT farm, imposes a fundamental constraint on the amount of time available for the HLT to process events. Exceeding this limit impacts the experiment's ability to collect data efficiently. Hence, there is a critical need to characterize the performance of the HLT farm as well as the algorithms run prior to start up in order to ensure optimal data taking. Additional complications arise from the fact that the HLT farm consists of multiple generations of hardware and there can be subtleties in machine performance. We present our methods of measuring the timing performance of the CMS HLT, including the challenges of making such measurements. Results for the performance of various Intel Xeon architectures from 2009-2014 and different data taking scenarios are also presented.

  16. Operation of the CMS silicon strip tracker

    NASA Astrophysics Data System (ADS)

    Yuri, Gotra; CMS Collaboration

    2011-10-01

    The CMS Silicon Strip Tracker (SST), comprising 9.6 million readout channels from 15148 modules covering an area of about 200 m², needs to be precisely calibrated in order to correctly interpret and reconstruct the events recorded from the detector, ensuring that the SST performance fully meets the physics research program of the CMS experiment. Calibration constants may be derived from promptly reconstructed events as well as from pedestal runs gathered just before the acquisition of physics runs. These calibration procedures were exercised in summer and winter 2009, when the CMS detector was commissioned using cosmic muons and proton-proton collisions at a center-of-mass energies of 900 GeV and 2.36 TeV. During these data taking periods the performance of the SST was carefully studied: the noise of the detector, the data integrity, the signal-to-noise ratio, the hit reconstruction efficiency, the calibration workflows have been all checked for stability and for different conditions, at the module level. The calibration procedures and the detector performance results from recent physics runs are described.

  17. Registration of tufted-naked seed in upland cotton germplasm 9023n4t

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A naked-tufted mutant called 9023n4t (PI 667553) was developed from the cultivar SC 9023 (Gossypium hirsutum L.) through chemical mutagenesis. This germplasm was developed by the Department of Plant and Soil Science, Texas Tech University and released in April, 2013. This mutant is quite unique sinc...

  18. Identification of beryllium-dependent peptides recognized by CD4+ T cells in chronic beryllium disease

    PubMed Central

    Falta, Michael T.; Mack, Douglas G.; Tinega, Alex N.; Crawford, Frances; Giulianotti, Marc; Santos, Radleigh; Clayton, Gina M.; Wang, Yuxiao; Zhang, Xuewu; Maier, Lisa A.; Marrack, Philippa; Kappler, John W.

    2013-01-01

    Chronic beryllium disease (CBD) is a granulomatous disorder characterized by an influx of beryllium (Be)-specific CD4+ T cells into the lung. The vast majority of these T cells recognize Be in an HLA-DP–restricted manner, and peptide is required for T cell recognition. However, the peptides that stimulate Be-specific T cells are unknown. Using positional scanning libraries and fibroblasts expressing HLA-DP2, the most prevalent HLA-DP molecule linked to disease, we identified mimotopes and endogenous self-peptides that bind to MHCII and Be, forming a complex recognized by pathogenic CD4+ T cells in CBD. These peptides possess aspartic and glutamic acid residues at p4 and p7, respectively, that surround the putative Be-binding site and cooperate with HLA-DP2 in Be coordination. Endogenous plexin A peptides and proteins, which share the core motif and are expressed in lung, also stimulate these TCRs. Be-loaded HLA-DP2–mimotope and HLA-DP2–plexin A4 tetramers detected high frequencies of CD4+ T cells specific for these ligands in all HLA-DP2+ CBD patients tested. Thus, our findings identify the first ligand for a CD4+ T cell involved in metal-induced hypersensitivity and suggest a unique role of these peptides in metal ion coordination and the generation of a common antigen specificity in CBD. PMID:23797096

  19. Preferential loss of IL-2-secreting CD4+ T helper cells in chronic HCV infection.

    PubMed

    Semmo, Nasser; Day, Cheryl L; Ward, Scott M; Lucas, Michaela; Harcourt, Gillian; Loughry, Andrew; Klenerman, Paul

    2005-05-01

    Hepatitis C virus (HCV) becomes persistent in the majority of infected individuals. In doing so, the virus evades host adaptive immune responses, although the mechanisms responsible in this evasion are not clear. Several groups have demonstrated weak or absent HCV-specific CD4+ T cell responses during chronic HCV infection using proliferation assays and, more recently, class II tetramers. However, the functional status of HCV-specific CD4+ T cells in resolved and persistent infection is poorly understood. Using interferon gamma (IFN-gamma) and interleukin 2 (IL-2) enzyme-linked immunospot assays, we analyzed cytokine secretion patterns in chronically infected patients and compared them with those with resolved infection. In the spontaneous resolver group, strong IL-2 secretion in relation to IFN-gamma secretion was observed. However, in the persistently infected group, a consistent and significant loss of IL-2-secreting cells, compared with IFN-gamma-secreting cells, was identified. In vitro addition of IL-2 had a substantial effect in restoring CD4+ T cell activity. In conclusion, failure of IL-2 secretion, as opposed to physical deletion or complete functional unresponsiveness, appears to be an important determinant of the status of CD4+ T cell populations in chronic HCV infection. Loss of IL-2 secretory capacity may lead to disruption of IFN-gamma and proliferative function in vivo-a status that characterizes the cellular immune response in both CD4+ and CD8+ compartments in chronic disease. PMID:15841456

  20. 26 CFR 1.125-4T - Permitted election changes (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Permitted election changes (temporary). 1.125-4T... Permitted election changes (temporary). (a) Election changes. A cafeteria plan may permit an employee to revoke an election during a period of coverage and to make a new election only as provided in...

  1. 26 CFR 1.125-4T - Permitted election changes (temporary).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 2 2013-04-01 2013-04-01 false Permitted election changes (temporary). 1.125-4T... Permitted election changes (temporary). (a) Election changes. A cafeteria plan may permit an employee to revoke an election during a period of coverage and to make a new election only as provided in...

  2. 26 CFR 1.125-4T - Permitted election changes (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 2 2011-04-01 2011-04-01 false Permitted election changes (temporary). 1.125-4T... Permitted election changes (temporary). (a) Election changes. A cafeteria plan may permit an employee to revoke an election during a period of coverage and to make a new election only as provided in...

  3. 26 CFR 1.125-4T - Permitted election changes (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 2 2012-04-01 2012-04-01 false Permitted election changes (temporary). 1.125-4T... Permitted election changes (temporary). (a) Election changes. A cafeteria plan may permit an employee to revoke an election during a period of coverage and to make a new election only as provided in...

  4. 26 CFR 1.883-4T - Qualified shareholder stock ownership test (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Foreign Corporations § 1.883-4T Qualified shareholder stock...; and (3) Any other relevant information specified by the Form 1120-F, “U.S. Income Tax Return of a... Service (see § 601.601(d)(2) of this chapter)....

  5. Spontaneous Proliferation of H2M-/- CD4 T Cells Results in Unusual Acute Hepatocellular Necrosis

    PubMed Central

    Do, Jeong-su; Baldwin, William M.; Min, Booki

    2014-01-01

    Naïve CD4 T cells are triggered to undergo spontaneous proliferation, a proliferative response induced in response to homeostatic stimulation, when exposed to severe lymphopenic environments. They spontaneously acquire proinflammatory effector phenotypes, playing a major role in inducing chronic inflammation in the intestine that is believed to be induced by T cell recognition of commensal antigens. While the antigens inducing the T cell responses and inflammation are being extensively investigated, the role of clonality of T cells involved in this process remains poorly understood. In this study, we utilized naïve CD4 T cells isolated from B6 H2M−/− mice, in which MHCII molecules are complexed with a single CLIP molecule, and examined spontaneous proliferation and intestinal inflammation of CD4 T cells expressing limited T cell receptor repertoire diversity. We found that H2M−/− CD4 T cells undergo robust spontaneous proliferation, differentiate into IFNγ-producing Th1 type effector cells, and, most unexpectedly, induce severe acute hepatocellular necrosis. T cell interaction with MHCII molecule on cells of hematopoietic origin was essential to induce the pathology. Interestingly, B cells are fully capable of preventing necrotic inflammation via IL-10-independent and B7-H1-dependent mechanism. This could be a useful animal model to examine T cell-mediated liver inflammation and B cell-mediated immune regulation. PMID:25313460

  6. 26 CFR 1.468A-4T - Treatment of nuclear decommissioning fund (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 6 2010-04-01 2010-04-01 false Treatment of nuclear decommissioning fund...-4T Treatment of nuclear decommissioning fund (temporary). (a) In general. A nuclear decommissioning... income earned by the assets of the nuclear decommissioning fund. (b) Modified gross income. For...

  7. The differentiation and protective function of cytolytic CD4 T cells in influenza infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    CD4 T cells that recognize peptide antigen in the context of Class II MHC can differentiate into various subsets that are characterized by their helper functions. However, increasing evidence indicates that CD4 cells with direct cytolytic activity play a role in chronic, as well as, acute infections...

  8. Polyfunctional CD4 T cells in the response to bovine tuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polyfunctional CD4 T cells simultaneously produce interferon-gamma (IFN-gamma), interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) and play relevant roles in several chronic infections, including human TB and HIV. However, the assessment of this response in bovine infections was not fe...

  9. The Control of the Specificity of CD4 T Cell Responses: Thresholds, Breakpoints, and Ceilings

    PubMed Central

    Sant, Andrea J.; Chaves, Francisco A.; Leddon, Scott A.; Tung, Jacqueline

    2013-01-01

    It has been known for over 25 years that CD4 T cell responses are restricted to a finite number of peptide epitopes within pathogens or protein vaccines. These selected peptide epitopes are termed “immunodominant.” Other peptides within the antigen that can bind to host MHC molecules and recruit CD4 T cells as single peptides are termed “cryptic” because they fail to induce responses when expressed in complex proteins or when in competition with other peptides during the immune response. In the last decade, our laboratory has evaluated the mechanisms that underlie the preferential specificity of CD4 T cells and have discovered that both intracellular events within antigen presenting cells, particular selective DM editing, and intercellular regulatory pathways, involving IFN-γ, indoleamine 2,3-dioxygenase, and regulatory T cells, play a role in selecting the final peptide specificity of CD4 T cells. In this review, we summarize our findings, discuss the implications of this work on responses to pathogens and vaccines and speculate on the logic of these regulatory events. PMID:24167504

  10. 26 CFR 1.509(a)-4T - Supporting organizations (temporary).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) of this chapter (with “supporting organization” being substituted for “foundation” or “private foundation” and “August 17, 2006” being substituted for “December 31, 1969”); and (ii) Exempt-use assets...) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Private Foundations § 1.509(a)-4T...

  11. 26 CFR 1.509(a)-4T - Supporting organizations (temporary).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) of this chapter (with “supporting organization” being substituted for “foundation” or “private foundation” and “August 17, 2006” being substituted for “December 31, 1969”); and (ii) Exempt-use assets... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Private Foundations § 1.509(a)-4T...

  12. The BMP Pathway Participates in Human Naive CD4+ T Cell Activation and Homeostasis

    PubMed Central

    Martínez, Víctor G.; Sacedón, Rosa; Hidalgo, Laura; Valencia, Jaris; Fernández-Sevilla, Lidia M.; Hernández-López, Carmen

    2015-01-01

    Bone Morphogenetic Proteins (BMPs) form a group of secreted factors that belongs to the TGF-β superfamily. Among different roles in a number of immune cell types, BMPs are known to regulate T cell development within the thymus, although the role of BMP signaling in human mature T cells remains elusive. In this study, we demonstrate that canonical BMP signaling is necessary during two critical events that regulate the size and function of human naive CD4+ T cell population: activation and homeostasis. Upon stimulation via TCR, naive CD4+ T cells upregulate the expression of BMP ligands triggering canonical BMP signaling in CD25+ cells. Blockade of BMP signaling severely impairs CD4+ T cell proliferation after activation mainly through regulation of IL-2, since the addition of this cytokine recuperates normal T cell expansion after inhibition of BMP signaling. Similarly, activation of canonical BMP pathway is required for both the maintenance of cell survival and the homeostatic proliferation induced by IL-7, a key factor for T cell homeostasis. Moreover, upregulation of two critical receptors for T cell homeostasis, CXCR4 and CCR9, triggered by IL-7 is also abrogated in the absence of BMP signaling. Collectively, we describe important roles of the canonical BMP signaling in human naive CD4+ T cell activation and homeostasis that could be valuable for clinical application. PMID:26110906

  13. Measurement of CD8 and CD4 T Cell Responses in Mouse Lungs

    PubMed Central

    Fett, Craig; Zhao, Jincun; Perlman, Stanley

    2016-01-01

    Study of the adaptive immune response to a viral challenge in an animal model often includes analysis of the T cell response. Here we discuss in detail the methods that are used to characterize the CD8 and CD4 T cell response following viral challenge in the lung.

  14. Alternatively expressed genes identified in the CD4+ T cells of allograft rejection mice.

    PubMed

    Xu, Jia; Wang, Dan; Zhang, Chao; Song, Jing; Liang, Ting; Jin, Weirong; Kim, Yeong C; Wang, San Ming; Hou, Guihua

    2011-01-01

    Allograft rejection is a leading cause for the failure of allotransplantation. CD4(+) T cells play critical roles in this process. The identification of genes that alternatively expressed in CD4(+) T cells during allograft rejection will provide critical information for studying the mechanism of allograft rejection, finding specific gene markers for monitoring, predicting allograft rejection, and opening new ways to regulate and prevent allograft rejection. Here, we established allograft and isograft transplantation models by adoptively transferring wild-type BALB/c mouse CD4(+) T cells into severe combined immunodeficient (SCID) mice with a C57BL/6 or BALB/c mouse skin graft. Using the whole transcriptome sequencing-based serial analysis of gene expression (SAGE) technology, we identified 97 increasingly and 88 decreasingly expressed genes that may play important roles in allograft rejection and tolerance. Functional classification of these genes shows that apoptosis, transcription regulation, cell growth and maintenance, and signal transduction are among the frequently changed functional groups. This study provides a genome-wide view for the candidate genes of CD4(+) T cells related to allotransplantation, and this report is a good resource for further microarray studies and for identifying the specific markers that are associated with clinical organ transplantations. PMID:21294963

  15. HIV-1 gp120 induces NFAT nuclear translocation in resting CD4+ T-cells

    SciTech Connect

    Cicala, Claudia . E-mail: ccicala@nih.gov; Arthos, James; Censoplano, Nina; Cruz, Catherine; Chung, Eva; Martinelli, Elena; Lempicki, Richard A.; Natarajan, Ven; VanRyk, Donald; Daucher, Marybeth; Fauci, Anthony S.

    2006-02-05

    The replication of human immunodeficiency virus (HIV) in CD4+ T-cells is strongly dependent upon the state of activation of infected cells. Infection of sub-optimally activated cells is believed to play a critical role in both the transmission of virus and the persistence of CD4+ T-cell reservoirs. There is accumulating evidence that HIV can modulate signal-transduction pathways in a manner that may facilitate replication in such cells. We previously demonstrated that HIV gp120 induces virus replication in resting CD4+ T cells isolated from HIV-infected individuals. Here, we show that in resting CD4+ T-cells, gp120 activates NFATs and induces their translocation into the nucleus. The HIV LTR encodes NFAT recognition sites, and NFATs may play a critical role in promoting viral replication in sub-optimally activated cells. These observations provide insight into a potential mechanism by which HIV is able to establish infection in resting cells, which may have implications for both transmission of HIV and the persistence of viral reservoirs.

  16. Aire-Overexpressing Dendritic Cells Induce Peripheral CD4+ T Cell Tolerance

    PubMed Central

    Li, Dongbei; Li, Haijun; Fu, Haiying; Niu, Kunwei; Guo, Yantong; Guo, Chuan; Sun, Jitong; Li, Yi; Yang, Wei

    2015-01-01

    Autoimmune regulator (Aire) can promote the ectopic expression of peripheral tissue-restricted antigens (TRAs) in thymic medullary epithelial cells (mTECs), which leads to the deletion of autoreactive T cells and consequently prevents autoimmune diseases. However, the functions of Aire in the periphery, such as in dendritic cells (DCs), remain unclear. This study’s aim was to investigate the effect of Aire-overexpressing DCs (Aire cells) on the functions of CD4+ T cells and the treatment of type 1 diabetes (T1D). We demonstrated that Aire cells upregulated the mRNA levels of the tolerance-related molecules CD73, Lag3, and FR4 and the apoptosis of CD4+ T cells in STZ-T1D mouse-derived splenocytes. Furthermore, following insulin stimulation, Aire cells decreased the number of CD4+ IFN-γ+ T cells in both STZ-T1D and WT mouse-derived splenocytes and reduced the expression levels of TCR signaling molecules (Ca2+ and p-ERK) in CD4+ T cells. We observed that Aire cells-induced CD4+ T cells could delay the development of T1D. In summary, Aire-expressing DCs inhibited TCR signaling pathways and decreased the quantity of CD4+IFN-γ+ autoreactive T cells. These data suggest a mechanism for Aire in the maintenance of peripheral immune tolerance and provide a potential method to control autoimmunity by targeting Aire. PMID:26729097

  17. High avidity autoreactive CD4+ T cells induce host CTL, overcome Tregs and mediate tumor destruction

    PubMed Central

    Brandmaier, Andrew G.; Leitner, Wolfgang W.; Ha, Sung P.; Sidney, John; Restifo, Nicholas P.; Touloukian, Christopher E.

    2009-01-01

    Despite progress made over the past 25 years, existing immunotherapies have limited clinical effectiveness in patients with cancer. Immune tolerance consistently blunts the generated immune response, and the largely solitary focus on CD8+ T cell immunity has proven ineffective in the absence of CD4+ T cell help. To address these twin-tier deficiencies, we developed a translational model of melanoma immunotherapy focused on the exploitation of high avidity CD4+ T cells that become generated in germline antigen deficient mice. We had previously identified a TRP-1 specific HLA-DRB1*0401-restricted epitope. Using this epitope in conjunction with a newly described TRP-1 germline-knockout, we demonstrate that endogenous TRP-1 expression alters the functionality of the auto-reactive T cell repertoire. More importantly, we show, by using MHC-mismatched combinations, that CD4+ T cells derived from the self-antigen deficient host indirectly triggers the eradication of established B16 lung metastases. We demonstrate that the treatment effect is mediated entirely by endogenous CD8+ T cells and is not affected by the depletion of host Tregs. These findings suggest that high avidity CD4+ T cells can overcome endogenous conditions and mediate their anti-tumor effects exclusively through the elicitation of CD8+ T cell immunity. PMID:19561540

  18. ADAR1 Facilitates HIV-1 Replication in Primary CD4+ T Cells

    PubMed Central

    van Hamme, John L.; Jansen, Machiel H.; van Dort, Karel A.; Vanderver, Adeline; Rice, Gillian I.; Crow, Yanick J.; Kootstra, Neeltje A.; Kuijpers, Taco W.

    2015-01-01

    Unlike resting CD4+ T cells, activated CD4+T cells are highly susceptible to infection of human immunodeficiency virus 1 (HIV-1). HIV-1 infects T cells and macrophages without activating the nucleic acid sensors and the anti-viral type I interferon response. Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA editing enzyme that displays antiviral activity against several RNA viruses. Mutations in ADAR1 cause the autoimmune disorder Aicardi-Goutieères syndrome (AGS). This disease is characterized by an inappropriate activation of the interferon-stimulated gene response. Here we show that HIV-1 replication, in ADAR1-deficient CD4+T lymphocytes from AGS patients, is blocked at the level of protein translation. Furthermore, viral protein synthesis block is accompanied by an activation of interferon-stimulated genes. RNA silencing of ADAR1 in Jurkat cells also inhibited HIV-1 protein synthesis. Our data support that HIV-1 requires ADAR1 for efficient replication in human CD4+T cells. PMID:26629815

  19. Transient response of coaxial pulse coils

    NASA Astrophysics Data System (ADS)

    Clifton, S.; Mongeau, P.

    1984-03-01

    Of central importance in designing coaxial launcher systems is understanding the mechanical response and structural limits of the magnetic pulse coils. In normal operation the driving frequency can vary from static conditions through the lowest natural modes to well beyond the highest frequencies. By using a lumped parameter model the transient behavior of a magnetic pulse coil can be readily characterized. In an effort to understand the failure mechanism of coaxial pulse coils the results of this model are compared to the experimental performance of several thin build coils.

  20. A precise technique for manufacturing correction coil

    SciTech Connect

    Schieber, L.

    1992-11-01

    An automated method of manufacturing correction coils has been developed which provides a precise embodiment of the coil design. Numerically controlled machines have been developed to accurately position coil windings on the beam tube. Two types of machines have been built. One machine bonds the wire to a substrate which is wrapped around the beam tube after it is completed while the second machine bonds the wire directly to the beam tube. Both machines use the Multiwire{reg_sign} technique of bonding the wire to the substrate utilizing an ultrasonic stylus. These machines are being used to manufacture coils for both the SSC and RHIC.

  1. A precise technique for manufacturing correction coil

    SciTech Connect

    Schieber, L.

    1992-01-01

    An automated method of manufacturing correction coils has been developed which provides a precise embodiment of the coil design. Numerically controlled machines have been developed to accurately position coil windings on the beam tube. Two types of machines have been built. One machine bonds the wire to a substrate which is wrapped around the beam tube after it is completed while the second machine bonds the wire directly to the beam tube. Both machines use the Multiwire[reg sign] technique of bonding the wire to the substrate utilizing an ultrasonic stylus. These machines are being used to manufacture coils for both the SSC and RHIC.

  2. Defect-Free Carbon Nanotube Coils.

    PubMed

    Shadmi, Nitzan; Kremen, Anna; Frenkel, Yiftach; Lapin, Zachary J; Machado, Leonardo D; Legoas, Sergio B; Bitton, Ora; Rechav, Katya; Popovitz-Biro, Ronit; Galvão, Douglas S; Jorio, Ado; Novotny, Lukas; Kalisky, Beena; Joselevich, Ernesto

    2016-04-13

    Carbon nanotubes are promising building blocks for various nanoelectronic components. A highly desirable geometry for such applications is a coil. However, coiled nanotube structures reported so far were inherently defective or had no free ends accessible for contacting. Here we demonstrate the spontaneous self-coiling of single-wall carbon nanotubes into defect-free coils of up to more than 70 turns with identical diameter and chirality, and free ends. We characterize the structure, formation mechanism, and electrical properties of these coils by different microscopies, molecular dynamics simulations, Raman spectroscopy, and electrical and magnetic measurements. The coils are highly conductive, as expected for defect-free carbon nanotubes, but adjacent nanotube segments in the coil are more highly coupled than in regular bundles of single-wall carbon nanotubes, owing to their perfect crystal momentum matching, which enables tunneling between the turns. Although this behavior does not yet enable the performance of these nanotube coils as inductive devices, it does point a clear path for their realization. Hence, this study represents a major step toward the production of many different nanotube coil devices, including inductors, electromagnets, transformers, and dynamos. PMID:26708150

  3. Helical axis stellarator with noninterlocking planar coils

    DOEpatents

    Reiman, Allan; Boozer, Allen H.

    1987-01-01

    A helical axis stellarator using only noninterlocking planar, non-circular coils, generates magnetic fields having a magnetic well and large rotational transform with resultant large equilibrium beta.

  4. Self-correction coil: Operation mechanism of self-correction coil

    NASA Astrophysics Data System (ADS)

    Hosoyama, K.

    1983-06-01

    The operation mechanism of self-correction coil is extended with a simple model. For the ideal self-correction coil case, The self-inductance L of the self-correction coil is calculated. This calculation method is extended to a non-ideal self-correction coil case. For measure of completeness of self-correction coil is measured by the ratio of induced magnetic field by the self-correction coil and error field. Examples are L, M and N calculated for two cases; one is a single block approximation of self-correction coil winding and the other is a two block approximation case. By choosing the adequate angles of self-correction coil winding, one can get about 98% efficiency for single block approximation case and 99.8% for two block approximation case.

  5. Transport Vesicle Tethering at the Trans Golgi Network: Coiled Coil Proteins in Action

    PubMed Central

    Cheung, Pak-yan P.; Pfeffer, Suzanne R.

    2016-01-01

    The Golgi complex is decorated with so-called Golgin proteins that share a common feature: a large proportion of their amino acid sequences are predicted to form coiled-coil structures. The possible presence of extensive coiled coils implies that these proteins are highly elongated molecules that can extend a significant distance from the Golgi surface. This property would help them to capture or trap inbound transport vesicles and to tether Golgi mini-stacks together. This review will summarize our current understanding of coiled coil tethers that are needed for the receipt of transport vesicles at the trans Golgi network (TGN). How do long tethering proteins actually catch vesicles? Golgi-associated, coiled coil tethers contain numerous binding sites for small GTPases, SNARE proteins, and vesicle coat proteins. How are these interactions coordinated and are any or all of them important for the tethering process? Progress toward understanding these questions and remaining, unresolved mysteries will be discussed. PMID:27014693

  6. pH sensitive coiled coils: a strategy for enhanced liposomal drug delivery.

    PubMed

    Reja, Rahi M; Khan, Mohsina; Singh, Sumeet K; Misra, Rajkumar; Shiras, Anjali; Gopi, Hosahudya N

    2016-03-01

    Stimuli responsive controlled release from liposome based vesicles is a promising strategy for the site specific delivery of drugs. Herein, we report the design of pH sensitive coiled coils and their incorporation into the liposome as triggers for the controlled release of encapsulated drugs. The designed coiled coil peptides with the incorporation of environment sensitive fluorescent amino acids were found to be stable at physiological pH and unstructured while changing the pH of the environment to either acidic or basic. This pH dependent conformational switch of the coiled-coil polypeptides was exploited as triggers for the enhanced release of the encapsulated drug molecules from liposomes. The SEM, DLS and TEM analysis revealed the uniform morphology of the peptide liposome hybrid vesicles. Further, the drug encapsulated liposome internalization experiments with cancer cells revealed the enhanced release and accumulation of drugs in the acidic lysosomal compartments in comparison with liposomes without coiled coils. PMID:26876788

  7. Novel Insights into the Regulatory Architecture of CD4+ T Cells in Rheumatoid Arthritis

    PubMed Central

    Aterido, Adrià; Palacio, Carlos; Marsal, Sara; Ávila, Gabriela; Julià, Antonio

    2014-01-01

    Rheumatoid arthritis (RA) is the most frequent autoimmune chronic inflammatory disease of the joints and it is characterized by the inflammation of the synovial membrane and the subsequent destruction of the joints. In RA, CD4+ T cells are the main drivers of disease initiation and the perpetuation of the damaging inflammatory process. To date, however, the genetic regulatory mechanisms of CD4+ T cells associated with RA etiology are poorly understood. The genome-wide analysis of expression quantitative trait loci (eQTL) in disease-relevant cell types is a recent genomic integration approach that is providing significant insights into the genetic regulatory mechanisms of many human pathologies. The objective of the present study was to analyze, for the first time, the genome-wide genetic regulatory mechanisms associated with the gene expression of CD4+ T cells in RA. Whole genome gene expression profiling of CD4+ T cells and the genome-wide genotyping (598,258 SNPs) of 29 RA patients with an active disease were performed. In order to avoid the excessive burden of multiple testing associated with genome-wide trans-eQTL analysis, we developed and implemented a novel systems genetics approach. Finally, we compared the genomic regulation pattern of CD4+ T cells in RA with the genomic regulation observed in reference lymphoblastoid cell lines (LCLs). We identified a genome-wide significant cis-eQTL associated with the expression of FAM66C gene (P = 6.51e−9). Using our new systems genetics approach we identified six statistically significant trans-eQTLs associated with the expression of KIAA0101 (P<7.4e−8) and BIRC5 (P = 5.35e−8) genes. Finally, comparing the genomic regulation profiles between RA CD4+ T cells and control LCLs we found 20 genes showing differential regulatory patterns between both cell types. The present genome-wide eQTL analysis has identified new genetic regulatory elements that are key to the activity of CD4+ T cells in RA. PMID:24959711

  8. Compact stellarators with modular coils

    PubMed Central

    Garabedian, P. R.

    2000-01-01

    Compact stellarator designs with modular coils and only two or three field periods are now available; these designs have both good stability and quasiaxial symmetry providing adequate transport for a magnetic fusion reactor. If the bootstrap current assumes theoretically predicted values a three field period configuration is optimal, but if that net current turns out to be lower, a device with two periods and just 12 modular coils might be better. There are also attractive designs with quasihelical symmetry and four or five periods whose properties depend less on the bootstrap current. Good performance requires that there be a satisfactory magnetic well in the vacuum field, which is a property lacking in a stellarator-tokamak hybrid that has been proposed for a proof of principle experiment. In this paper, we present an analysis of stability for these configurations that is based on a mountain pass theorem asserting that, if two solutions of the problem of magnetohydrodynamic equilibrium can be found, then there has to be an unstable solution. We compare results of our theory of equilibrium, stability, and transport with recently announced measurements from the large LHD experiment in Japan. PMID:10899993

  9. Intraoral approach for imaging teeth using the transverse B1 field components of an occlusally oriented loop coil

    PubMed Central

    Idiyatullin, Djaudat; Corum, Curtis A.; Nixdorf, Donald R.; Garwood, Michael

    2013-01-01

    Purpose The signal-to-noise ratio and resolution are two competing parameters for dental MRI and are highly dependent on the radiofrequency (RF) coil configuration and performance. The purpose of this work is to describe an intraoral approach for imaging teeth with the RF coil plane oriented orthogonally to the Zeeman field to use the transverse components of the B1 field for transmitting and receiving the NMR signal. Methods A single loop coil with shape and size fitted to the average adult maxillary arch was built and tested with a phantom and human subjects in vivo on a whole-body 4T MRI scanner. Supporting Biot-Savart law simulations were performed with Matlab. Results In the occlusion position (in bite plane between the upper and lower teeth), the sensitive volume of the coil encompasses the most important dental structures, the teeth and their supporting structures, while uninteresting tissues containing much higher proton density (cheeks, lips, and tongue) are outside the sensitive volume. The presented images and simulated data show the advantages of using a coil in the orthogonal orientation for dental applications. Conclusion The transverse components of the B1 field of a surface coil can effectively be used for imaging of teeth and associated structures. PMID:23900995

  10. High-field actively detuneable transverse electromagnetic (TEM) coil with low-bias voltage for high-power RF transmission.

    PubMed

    Avdievich, Nikolai I; Bradshaw, Ken; Kuznetsov, Andrey M; Hetherington, Hoby P

    2007-06-01

    The design and construction of a 4T (170 MHz) transverse electromagnetic (TEM) actively detuneable quadrature head coil is described. Conventional schemes for active detuning require high negative bias voltages (>300 V) to prevent leakage of RF pulses with amplitudes of 1-2 kW. To extend the power handling capacity and avoid the use of high DC bias voltages, we developed an alternate method of detuning the volume coil. In this method the PIN diodes in the detuning circuits are shorted when the RF volume coil is tuned, and negatively biased with -12 V when the coil is detuned. To preserve the high Q(U)/Q(L) ratio of the TEM coil, we modified the method of Nabetani and Watkins (Proceedings of the 13th Annual Meeting of ISMRM, Kyoto, Japan, 2004, abstract 1574) by utilizing a high-impedance (approximately 200 Omega), lumped-element, quarter-wavelength transformer. A Q(U) of 500 was achieved for the detuneable TEM, such that incorporation of the detuning network had minimal effect (<1 dB) on the performance of the coil in vivo. PMID:17534919

  11. A Non-perturbing Probe of Coiled Coil Formation Based on Electron Transfer Mediated Fluorescence Quenching.

    PubMed

    Watson, Matthew D; Peran, Ivan; Raleigh, Daniel P

    2016-07-01

    Coiled coils are abundant in nature, occurring in ∼3% of proteins across sequenced genomes, and are found in proteins ranging from transcription factors to structural proteins. The motif continues to be an important model system for understanding protein-protein interactions and is finding increased use in bioinspired materials and synthetic biology. Knowledge of the thermodynamics of self-assembly, particularly the dissociation constant KD, is essential for the application of designed coiled coils and for understanding the in vivo specificity of natural coiled coils. Standard methods for measuring KD typically rely on concentration dependent circular dichroism (CD). Fluorescence methods are an attractive alternative; however Trp is rarely found in an interior position of a coiled coil, and appending unnatural fluorophores can perturb the system. We demonstrate a simple, non-perturbing method to monitor coiled coil formation using p-cyanophenylalanine (FCN) and selenomethionine (MSe), the Se analogue of Met. FCN fluorescence can be selectively excited and is effectively quenched by electron transfer with MSe. Both FCN and MSe represent minimally perturbing substitutions in coiled coils. MSe quenching of FCN fluorescence is shown to offer a non-perturbing method for following coiled coil formation and for accurately determining dissociation constants. The method is validated using a designed heterodimeric coiled coil. The KD deduced by fluorescence monitored titration is in excellent agreement with the value deduced from concentration dependent CD measurements to within the uncertainty of the measurement. However, the fluorescence approach requires less protein, is less time-consuming, can be applied to lower concentrations and could be applied to high throughput screens. PMID:27258904

  12. Oligoclonal CD4+ T Cells Promote Host Memory Immune Responses to Zwitterionic Polysaccharide of Streptococcus pneumoniae▿

    PubMed Central

    Groneck, Laura; Schrama, David; Fabri, Mario; Stephen, Tom Li; Harms, Fabian; Meemboor, Sonja; Hafke, Helena; Bessler, Martina; Becker, Jürgen C.; Kalka-Moll, Wiltrud M.

    2009-01-01

    Zwitterionic polysaccharides of the normal flora bacteria represent a novel class of antigens in that they correct systemic CD4+ T-cell deficiencies and direct lymphoid organogenesis during colonization of the host. Presentation of these polysaccharides to CD4+ T cells depends on major histocompatibility complex class II- and DM-dependent retrograde transport from lysosomes to the cell surface. Yet the phenotype and clonality of the immune response to the polysaccharide in the mature host immune system have not been studied. Using the zwitterionic capsular polysaccharide Sp1 of Streptococcus pneumoniae, a transient member of the bacterial flora, in an experimental mouse model of cellular immunity, we demonstrated the accumulation of TH1- and TH17-polarized CD4+ CD44high CD62low CD25− memory T cells. Subcutaneous immunization with Sp1 resulted in an increase of serum immunoglobulin G (IgG), predominantly of the IgG1 subclass, and suggested the presence of a humoral memory response to the polysaccharide. CD4+ T cells stimulated with polysaccharide in vitro and in vivo showed a nonrestricted pattern for the T-cell receptor (TCR) β-chain variable region, as demonstrated by semiquantitative reverse transcription-PCR and flow cytometry. Clonotype mapping of in vivo and in vitro polysaccharide-activated CD4+ T cells revealed clonotypic TCR transcripts. Taken together, the data show the induction of clonal expansion of CD4+ T cells by polysaccharides of commensal bacteria. Cellular and humoral memory host responses imply the ability of these polysaccharides to mediate the expansion of T cells via recognition within the CDR3 region of the TCR. PMID:19546196

  13. The Immune-Metabolic Basis of Effector Memory CD4+ T Cell Function under Hypoxic Conditions.

    PubMed

    Dimeloe, Sarah; Mehling, Matthias; Frick, Corina; Loeliger, Jordan; Bantug, Glenn R; Sauder, Ursula; Fischer, Marco; Belle, Réka; Develioglu, Leyla; Tay, Savaş; Langenkamp, Anja; Hess, Christoph

    2016-01-01

    Effector memory (EM) CD4(+) T cells recirculate between normoxic blood and hypoxic tissues to screen for cognate Ag. How mitochondria of these cells, shuttling between normoxia and hypoxia, maintain bioenergetic efficiency and stably uphold antiapoptotic features is unknown. In this study, we found that human EM CD4(+) T cells had greater spare respiratory capacity (SRC) than did naive counterparts, which was immediately accessed under hypoxia. Consequently, hypoxic EM cells maintained ATP levels, survived and migrated better than did hypoxic naive cells, and hypoxia did not impair their capacity to produce IFN-γ. EM CD4(+) T cells also had more abundant cytosolic GAPDH and increased glycolytic reserve. In contrast to SRC, glycolytic reserve was not tapped under hypoxic conditions, and, under hypoxia, glucose metabolism contributed similarly to ATP production in naive and EM cells. However, both under normoxic and hypoxic conditions, glucose was critical for EM CD4(+) T cell survival. Mechanistically, in the absence of glycolysis, mitochondrial membrane potential (ΔΨm) of EM cells declined and intrinsic apoptosis was triggered. Restoring pyruvate levels, the end product of glycolysis, preserved ΔΨm and prevented apoptosis. Furthermore, reconstitution of reactive oxygen species (ROS), whose production depends on ΔΨm, also rescued viability, whereas scavenging mitochondrial ROS exacerbated apoptosis. Rapid access of SRC in hypoxia, linked with built-in, oxygen-resistant glycolytic reserve that functionally insulates ΔΨm and mitochondrial ROS production from oxygen tension changes, provides an immune-metabolic basis supporting survival, migration, and function of EM CD4(+) T cells in normoxic and hypoxic conditions. PMID:26621861

  14. Vitamin D Actions on CD4+ T Cells in Autoimmune Disease

    PubMed Central

    Hayes, Colleen Elizabeth; Hubler, Shane L.; Moore, Jerott R.; Barta, Lauren E.; Praska, Corinne E.; Nashold, Faye E.

    2015-01-01

    This review summarizes and integrates research on vitamin D and CD4+ T-lymphocyte biology to develop new mechanistic insights into the molecular etiology of autoimmune disease. A deep understanding of molecular mechanisms relevant to gene–environment interactions is needed to deliver etiology-based autoimmune disease prevention and treatment strategies. Evidence linking sunlight, vitamin D, and the risk of multiple sclerosis and type 1 diabetes is summarized to develop the thesis that vitamin D is the environmental factor that most strongly influences autoimmune disease development. Evidence for CD4+ T-cell involvement in autoimmune disease pathogenesis and for paracrine calcitriol signaling to CD4+ T lymphocytes is summarized to support the thesis that calcitriol is sunlight’s main protective signal transducer in autoimmune disease risk. Animal modeling and human mechanistic data are summarized to support the view that vitamin D probably influences thymic negative selection, effector Th1 and Th17 pathogenesis and responsiveness to extrinsic cell death signals, FoxP3+CD4+ T-regulatory cell and CD4+ T-regulatory cell type 1 (Tr1) cell functions, and a Th1–Tr1 switch. The proposed Th1–Tr1 switch appears to bridge two stable, self-reinforcing immune states, pro- and anti-inflammatory, each with a characteristic gene regulatory network. The bi-stable switch would enable T cells to integrate signals from pathogens, hormones, cell–cell interactions, and soluble mediators and respond in a biologically appropriate manner. Finally, unanswered questions and potentially informative future research directions are highlighted to speed delivery of etiology-based strategies to reduce autoimmune disease. PMID:25852682

  15. Vitamin D Actions on CD4(+) T Cells in Autoimmune Disease.

    PubMed

    Hayes, Colleen Elizabeth; Hubler, Shane L; Moore, Jerott R; Barta, Lauren E; Praska, Corinne E; Nashold, Faye E

    2015-01-01

    This review summarizes and integrates research on vitamin D and CD4(+) T-lymphocyte biology to develop new mechanistic insights into the molecular etiology of autoimmune disease. A deep understanding of molecular mechanisms relevant to gene-environment interactions is needed to deliver etiology-based autoimmune disease prevention and treatment strategies. Evidence linking sunlight, vitamin D, and the risk of multiple sclerosis and type 1 diabetes is summarized to develop the thesis that vitamin D is the environmental factor that most strongly influences autoimmune disease development. Evidence for CD4(+) T-cell involvement in autoimmune disease pathogenesis and for paracrine calcitriol signaling to CD4(+) T lymphocytes is summarized to support the thesis that calcitriol is sunlight's main protective signal transducer in autoimmune disease risk. Animal modeling and human mechanistic data are summarized to support the view that vitamin D probably influences thymic negative selection, effector Th1 and Th17 pathogenesis and responsiveness to extrinsic cell death signals, FoxP3(+)CD4(+) T-regulatory cell and CD4(+) T-regulatory cell type 1 (Tr1) cell functions, and a Th1-Tr1 switch. The proposed Th1-Tr1 switch appears to bridge two stable, self-reinforcing immune states, pro- and anti-inflammatory, each with a characteristic gene regulatory network. The bi-stable switch would enable T cells to integrate signals from pathogens, hormones, cell-cell interactions, and soluble mediators and respond in a biologically appropriate manner. Finally, unanswered questions and potentially informative future research directions are highlighted to speed delivery of etiology-based strategies to reduce autoimmune disease. PMID:25852682

  16. German contributions to the CMS computing infrastructure

    NASA Astrophysics Data System (ADS)

    Scheurer, A.; German CMS Community

    2010-04-01

    The CMS computing model anticipates various hierarchically linked tier centres to counter the challenges provided by the enormous amounts of data which will be collected by the CMS detector at the Large Hadron Collider, LHC, at CERN. During the past years, various computing exercises were performed to test the readiness of the computing infrastructure, the Grid middleware and the experiment's software for the startup of the LHC which took place in September 2008. In Germany, several tier sites are set up to allow for an efficient and reliable way to simulate possible physics processes as well as to reprocess, analyse and interpret the numerous stored collision events of the experiment. It will be shown that the German computing sites played an important role during the experiment's preparation phase and during data-taking of CMS and, therefore, scientific groups in Germany will be ready to compete for discoveries in this new era of particle physics. This presentation focuses on the German Tier-1 centre GridKa, located at Forschungszentrum Karlsruhe, the German CMS Tier-2 federation DESY/RWTH with installations at the University of Aachen and the research centre DESY. In addition, various local computing resources in Aachen, Hamburg and Karlsruhe are briefly introduced as well. It will be shown that an excellent cooperation between the different German institutions and physicists led to well established computing sites which cover all parts of the CMS computing model. Therefore, the following topics are discussed and the achieved goals and the gained knowledge are depicted: data management and distribution among the different tier sites, Grid-based Monte Carlo production at the Tier-2 as well as Grid-based and locally submitted inhomogeneous user analyses at the Tier-3s. Another important task is to ensure a proper and reliable operation 24 hours a day, especially during the time of data-taking. For this purpose, the meta-monitoring tool "HappyFace", which was

  17. Structural Characteristics of the Redox-sensing Coiled Coil in the Voltage-gated H+ Channel*

    PubMed Central

    Fujiwara, Yuichiro; Takeshita, Kohei; Nakagawa, Atsushi; Okamura, Yasushi

    2013-01-01

    Oxidation is an important biochemical defense mechanism, but it also elicits toxicity; therefore, oxidation must be under strict control. In phagocytotic events in neutrophils, the voltage-gated H+ (Hv) channel is a key regulator of the production of reactive oxygen species against invading bacteria. The cytoplasmic domain of the Hv channel forms a dimeric coiled coil underpinning a dimerized functional unit. Importantly, in the alignment of the coiled-coil core, a conserved cysteine residue forms a potential intersubunit disulfide bond. In this study, we solved the crystal structures of the coiled-coil domain in reduced, oxidized, and mutated (Cys → Ser) states. The crystal structures indicate that a pair of Cys residues forms an intersubunit disulfide bond dependent on the redox conditions. CD spectroscopy revealed that the disulfide bond increases the thermal stability of the coiled-coil protein. We also reveal that two thiol modifier molecules are able to bind to Cys in a redox-dependent manner without disruption of the dimeric coiled-coil assembly. Thus, the biochemical properties of the cytoplasmic coiled-coil domain in the Hv channel depend on the redox condition, which may play a role in redox sensing in the phagosome. PMID:23667254

  18. Accommodation of structural rearrangements in the huntingtin-interacting protein 1 coiled-coil domain

    SciTech Connect

    Wilbur, Jeremy D.; Hwang, Peter K.; Brodsky, Frances M.; Fletterick, Robert J.

    2010-03-01

    Variable packing interaction related to the conformational flexibility within the huntingtin-interacting protein 1 coiled coil domain. Huntingtin-interacting protein 1 (HIP1) is an important link between the actin cytoskeleton and clathrin-mediated endocytosis machinery. HIP1 has also been implicated in the pathogenesis of Huntington’s disease. The binding of HIP1 to actin is regulated through an interaction with clathrin light chain. Clathrin light chain binds to a flexible coiled-coil domain in HIP1 and induces a compact state that is refractory to actin binding. To understand the mechanism of this conformational regulation, a high-resolution crystal structure of a stable fragment from the HIP1 coiled-coil domain was determined. The flexibility of the HIP1 coiled-coil region was evident from its variation from a previously determined structure of a similar region. A hydrogen-bond network and changes in coiled-coil monomer interaction suggest that the HIP1 coiled-coil domain is uniquely suited to allow conformational flexibility.

  19. Natural templates for coiled-coil biomaterials from praying mantis egg cases.

    PubMed

    Walker, Andrew A; Weisman, Sarah; Kameda, Tsunenori; Sutherland, Tara D

    2012-12-10

    Whereas there is growing interest in producing biomaterials containing coiled-coils, relatively few studies have made use of naturally occurring fibrous proteins. In this study, we have characterized fibrous proteins used by mother praying mantises to produce an extensive covering for their eggs called an ootheca and demonstrate the production of artificial ootheca using recombinantly produced proteins. Examination of natural oothecae by infrared spectroscopy and solid-state nuclear magnetic resonance revealed the material to consist of proteins organized predominately as coiled-coils. Two structural proteins, Mantis Fibroin 1 and Mantis Fibroin 2, were identified in ootheca from each of three species. Between species, the primary sequences of both proteins had diverged considerably, but other features were tightly conserved, including low molecular weight, high abundance of Ala, Glu, Lys, and Ser, and a triblock-like architecture with extensive central coiled-coil domain. Mantis fibroin hydrophobic cores had an unusual composition containing high levels of alanine and aromatic residues. Recombinantly produced mantis fibroins folded into coiled-coils in solution and could be fabricated into solid materials with high coiled-coil content. The structural features of mantis fibroins and their straightforward recombinant production make them promising templates for the production of coiled-coil biomimetics materials. PMID:23137042

  20. A comparative study of flat coil and coil sensor for landslide detection

    NASA Astrophysics Data System (ADS)

    Sanjaya, Edi; Muslimin, Ahmad Novi; Djamal, Mitra; Suprijadi, Handayani, Gunawan; Ramli

    2016-03-01

    The landslide is one of the most costly catastrophic events in terms of human lives and infrastructure damage, thus an early warning monitoring for landslides becomes more and more important. Currently existing monitoring systems for early warning are available in terms of monolithic systems. This is a very cost-intensive way, considering installation as well as operational and personal expenses. We have been developing a landslide detection system based on flat coil and coil sensor. The flat coil element being developed is an inductive proximity sensor for detection mass of soil movement. The simple method of flat coil manufactures and low cost, is an attraction that is still inspired to develop flat coil sensors. Meanwhile, although it has a drawback in terms of their size, the coil sensor is still required in many fields due to their sensitivity and robustness. The simple method of coil manufacture and the materials are commonly available and low cost, is an attraction that is still inspired to develop induction coil sensors. A comparative study of alternative configuration of sensor based on flat coil elements and a coil in application to landslide detection has been discussed in this paper. The purpose of this comparison is to show the ideal conditions and the challenges for each sensor. Furthermore, a comparison between flat coil and coil sensor is presented.

  1. THz-waves channeling in a monolithic saddle-coil for Dynamic Nuclear Polarization enhanced NMR.

    PubMed

    Macor, A; de Rijk, E; Annino, G; Alberti, S; Ansermet, J-Ph

    2011-10-01

    A saddle coil manufactured by electric discharge machining (EDM) from a solid piece of copper has recently been realized at EPFL for Dynamic Nuclear Polarization enhanced Nuclear Magnetic Resonance experiments (DNP-NMR) at 9.4 T. The corresponding electromagnetic behavior of radio-frequency (400 MHz) and THz (263 GHz) waves were studied by numerical simulation in various measurement configurations. Moreover, we present an experimental method by which the results of the THz-wave numerical modeling are validated. On the basis of the good agreement between numerical and experimental results, we conducted by numerical simulation a systematic analysis on the influence of the coil geometry and of the sample properties on the THz-wave field, which is crucial in view of the optimization of DNP-NMR in solids. PMID:21903436

  2. THz-waves channeling in a monolithic saddle-coil for Dynamic Nuclear Polarization enhanced NMR

    NASA Astrophysics Data System (ADS)

    Macor, A.; de Rijk, E.; Annino, G.; Alberti, S.; Ansermet, J.-Ph.

    2011-10-01

    A saddle coil manufactured by electric discharge machining (EDM) from a solid piece of copper has recently been realized at EPFL for Dynamic Nuclear Polarization enhanced Nuclear Magnetic Resonance experiments (DNP-NMR) at 9.4 T. The corresponding electromagnetic behavior of radio-frequency (400 MHz) and THz (263 GHz) waves were studied by numerical simulation in various measurement configurations. Moreover, we present an experimental method by which the results of the THz-wave numerical modeling are validated. On the basis of the good agreement between numerical and experimental results, we conducted by numerical simulation a systematic analysis on the influence of the coil geometry and of the sample properties on the THz-wave field, which is crucial in view of the optimization of DNP-NMR in solids.

  3. Designed Coiled-Coil Peptides Inhibit the Type Three Secretion System of Enteropathogenic Escherichia coli

    PubMed Central

    Larzábal, Mariano; Mercado, Elsa C.; Vilte, Daniel A.; Salazar-González, Hector; Cataldi, Angel; Navarro-Garcia, Fernando

    2010-01-01

    Background Enteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli (EHEC) are two categories of E. coli strains associated with human disease. A major virulence factor of both pathotypes is the expression of a type three secretion system (TTSS), responsible for their ability to adhere to gut mucosa causing a characteristic attaching and effacing lesion (A/E). The TTSS translocates effector proteins directly into the host cell that subvert mammalian cell biochemistry. Methods/Principal Findings We examined synthetic peptides designed to inhibit the TTSS. CoilA and CoilB peptides, both representing coiled-coil regions of the translocator protein EspA, and CoilD peptide, corresponding to a coiled–coil region of the needle protein EscF, were effective in inhibiting the TTSS dependent hemolysis of red blood cells by the EPEC E2348/69 strain. CoilA and CoilB peptides also reduced the formation of actin pedestals by the same strain in HEp-2 cells and impaired the TTSS-mediated protein translocation into the epithelial cell. Interestingly, CoilA and CoilB were able to block EspA assembly, destabilizing the TTSS and thereby Tir translocation. This blockage of EspA polymerization by CoilA or CoilB peptides, also inhibited the correct delivery of EspB and EspD as detected by immunoblotting. Interestingly, electron microscopy of bacteria incubated with the CoilA peptide showed a reduction of the length of EspA filaments. Conclusions Our data indicate that coiled-coil peptides can prevent the assembly and thus the functionality of the TTSS apparatus and suggest that these peptides could provide an attractive tool to block EPEC and EHEC pathogenesis. PMID:20140230

  4. Undulator Long Coil Measurement System Tests

    SciTech Connect

    Wolf, Zachary; Levashov, Yurii; /SLAC

    2010-11-24

    The first and second field integrals in the LCLS undulators must be below a specified limit. To accurately measure the field integrals, a long coil system is used. This note describes a set of tests which were used to check the performance of the long coil system. A long coil system was constructed to measure the first and second field integrals of the LCLS undulators. The long coil measurements of the background fields were compared to field integrals obtained by sampling the background fields and numerically calculating the integrals. This test showed that the long coil has the sensitivity required to measure at the levels specified for the field integrals. Tests were also performed by making long coil measurements of short magnets of known strength placed at various positions The long coil measurements agreed with the known field integrals obtained by independent measurements and calculation. Our tests showed that the long coil measurements are a valid way to determine whether the LCLS undulator field integrals are below the specified limits.

  5. Magnetic Fields at the Center of Coils

    ERIC Educational Resources Information Center

    Binder, Philippe; Hui, Kaleonui; Goldman, Jesse

    2014-01-01

    In this note we synthesize and extend expressions for the magnetic field at the center of very short and very long current-carrying coils. Elementary physics textbooks present the following equation for the magnetic field inside a very long current-carrying coil (solenoid): B[subscript sol] = µ[subscript 0] (N/L) I, (1) where I is the current, N…

  6. Precise Fabrication of Electromagnetic-Levitation Coils

    NASA Technical Reports Server (NTRS)

    Ethridge, E.; Curreri, P.; Theiss, J.; Abbaschian, G.

    1985-01-01

    Winding copper tubing on jig ensures reproducible performance. Sequence of steps insures consistent fabrication of levitation-and-melting coils. New method enables technician to produce eight coils per day, 95 percent of them acceptable. Method employs precise step-by-step procedure on specially designed wrapping and winding jig.

  7. Novel transcranial magnetic stimulation coil for mice

    NASA Astrophysics Data System (ADS)

    March, Stephen; Stark, Spencer; Crowther, Lawrence; Hadimani, Ravi; Jiles, David

    2014-03-01

    Transcranial magnetic stimulation (TMS) shows potential for non-invasive treatment of various neurological disorders. Significant work has been performed on the design of coils used for TMS on human subjects but few reports have been made on the design of coils for use on the brains of animals such as mice. This work is needed as TMS studies utilizing mice can allow rapid preclinical development of TMS for human disorders but the coil designs developed for use on humans are inadequate for optimal stimulation of the much smaller mouse brain. A novel TMS coil has been developed with the goal of inducing strong and focused electric fields for the stimulation of small animals such as mice. Calculations of induced electric fields were performed utilizing an MRI derived inhomogeneous model of an adult male mouse. Mechanical and thermal analysis of this new TMS helmet-coil design have also been performed at anticipated TMS operating conditions to ensure mechanical stability of the new coil and establish expected linear attraction and rotational force values. Calculated temperature increases for typical stimulation periods indicate the helmet-coil system is capable of operating within established medical standards. A prototype of the coil has been fabricated and characterization results are presented.

  8. Optimal Coil Orientation for Transcranial Magnetic Stimulation

    PubMed Central

    Richter, Lars; Neumann, Gunnar; Oung, Stephen; Schweikard, Achim; Trillenberg, Peter

    2013-01-01

    We study the impact of coil orientation on the motor threshold (MT) and present an optimal coil orientation for stimulation of the foot. The result can be compared to results of models that predict this orientation from electrodynamic properties of the media in the skull and from orientations of cells, respectively. We used a robotized TMS system for precise coil placement and recorded motor-evoked potentials with surface electrodes on the abductor hallucis muscle of the right foot in 8 healthy control subjects. First, we performed a hot-spot search in standard (lateral) orientation and then rotated the coil in steps of 10° or 20°. At each step we estimated the MT. For navigated stimulation and for correlation with the underlying anatomy a structural MRI scan was obtained. Optimal coil orientation was 33.1±18.3° anteriorly in relation to the standard lateral orientation. In this orientation the threshold was 54±18% in units of maximum stimulator output. There was a significant difference of 8.0±5.9% between the MTs at optimal and at standard orientation. The optimal coil orientations were significantly correlated with the direction perpendicular to the postcentral gyrus (). Robotized TMS facilitates sufficiently precise coil positioning and orientation to study even small variations of the MT with coil orientation. The deviations from standard orientation are more closely matched by models based on field propagation in media than by models based on orientations of pyramidal cells. PMID:23593200

  9. Completion of the Polo model coil

    SciTech Connect

    Bourquard, A.; Plat, X.; Bonnet, P.; Semal, D.; Personeni, G.; Bernaudat, M.; Hacquard, A.; Salvador, R.; Dombrowski, D.

    1996-07-01

    A superconducting poloidal field model coil as needed for tokamaks has been constructed by GEC Alsthom within the Polo project in effective collaboration with Forschungszentrum Karlsruhe, Institut fuer Technische Physik, Germany. The manufacturing procedures for the coil and its terminals are described.

  10. Operator coil monitoring Acceptance Test Procedure

    SciTech Connect

    Erhart, M.F.

    1995-05-16

    The readiness of the Data Acquisition and Control System (DACS) to provide monitoring and control of the Programmable Logic Controller (PLC) abort coils from the Master and RSS stations will be systematically tested during performance of this procedure. It should be noted that these are not physical abort coils but software coils controlled by the software`s ladder logic. The readiness of the DACS to properly interface with the ENRAF wire level gauge installed in the SY-101 storage tank will also be tested. During this test, a verification of all abort coil indications will be conducted at the DACS Development Facility in the 306E Building by injecting an input signal for each DACS sensor that has an associated abort coil until the abort coil actuates, and then ensuring that the status of the abort coil indicated at the Master and RSS stations is correct. Each abort coil will also be tested to ensure that the ``ENABLE`` and ``DISABLE`` controls from the Master and RSS stations function correctly, and only with the use of proper passwords.

  11. Operator coil monitoring acceptance test procedure

    SciTech Connect

    Erhart, M.F.

    1995-06-05

    The readiness of the Data Acquisition and Control System (DACS) to provide monitoring and control of the Programmable Logic Controller (PLC) abort coils from the Master and RSS stations will be systematically tested during performance of this procedure. It should be noted that these are not physical abort coils but software coils controlled by the software`s ladder logic. The readiness of the DACS to properly interface with the ENRAF wire level gauge installed in the SY101 storage tank will also be tested. During this test, a verification of all abort coil indications will be conducted at the DACS Development Facility in the 306E Building by injecting an input signal for each DACS sensor that has an associated abort coil until the abort coil actuates, and then ensuring that the status of the abort coil indicated at the Master and RSS stations correct. Each abort coil will also be tested to ensure that the ``ENABLE`` and ``DISABLE`` controls from the Master and RSS stations function correctly, and only with the use of proper passwords.

  12. Helical axis stellarator with noninterlocking planar coils

    DOEpatents

    Reiman, A.; Boozer, A.H.

    1984-03-06

    The present invention generates stellarator fields having favorable properties (magnetic well and large rotational transform) by a simple coil system consisting only of unlinked planar non-circular coils. At large rotational transform toroidal effects on magnetic well and rotational transform are small and can be ignored. We do so herein, specializing in straight helical systems.

  13. Rod-Coil Block Polyimide Copolymers

    NASA Technical Reports Server (NTRS)

    Meador, Mary Ann B. (Inventor); Kinder, James D. (Inventor)

    2005-01-01

    This invention is a series of rod-coil block polyimide copolymers that are easy to fabricate into mechanically resilient films with acceptable ionic or protonic conductivity at a variety of temperatures. The copolymers consist of short-rigid polyimide rod segments alternating with polyether coil segments. The rods and coil segments can be linear, branched or mixtures of linear and branched segments. The highly incompatible rods and coil segments phase separate, providing nanoscale channels for ion conduction. The polyimide segments provide dimensional and mechanical stability and can be functionalized in a number of ways to provide specialized functions for a given application. These rod-coil black polyimide copolymers are particularly useful in the preparation of ion conductive membranes for use in the manufacture of fuel cells and lithium based polymer batteries.

  14. MIT 12 Tesla Coil test results

    NASA Astrophysics Data System (ADS)

    Steeves, M. M.; Hoenig, M. O.

    1985-07-01

    Test results from the MIT 12 Tesla Coil experiment are presented. The coil was tested in the High Field Test Facility (HFTF) of the Lawrence Livermore National Laboratory in October 1984 and January 1985. The experiment measured the performance of an Internally Cooled, Cabled Superconductor (ICCS) of practical size, intended for use in magnetic fusion experiments. The MIT coil carried 15 kA at 11 T for 5 min with no sign of instability. A half turn length in a 10 T field was able to absorb a heat load in 4 msec of more than 200 mJ sub cm of cable volume while carrying a current of 12 kA. The MIT coil successfully met the performance requirements of the Department of Energy's 12 Tesla Coil Program.

  15. Recent advances in helix-coil theory.

    PubMed

    Doig, Andrew J

    2002-12-10

    Peptide helices in solution form a complex mixture of all helix, all coil or, most frequently, central helices with frayed coil ends. In order to interpret experiments on helical peptides and make theoretical predictions on helices, it is therefore essential to use a helix-coil theory that takes account of this equilibrium. The original Zimm-Bragg and Lifson-Roig helix-coil theories have been greatly extended in the last 10 years to include additional interactions. These include preferences for the N-cap, N1, N2, N3 and C-cap positions, capping motifs, helix dipoles, side chain interactions and 3(10)-helix formation. These have been applied to determine energies for these preferences from experimental data and to predict the helix contents of peptides. This review discusses these newly recognised structural features of helices and how they have been included in helix-coil models. PMID:12488008

  16. NMR local coil with adjustable spacing

    SciTech Connect

    Dembinski, G.T.

    1988-03-22

    A local coil assembly for use in NMR imaging is described which comprises: a base; a first local coil module mounted to the base and extending upward therefrom; sockets disposed in the base, each at a different distance from the first local coil module; a second local coil module having a connector therein which mates with each of the sockets to enable the second local coil module to be connected to the base at any one of the sockets; and a set of reactive components. The values of the respective reactive components are selected such that the second local oil module may be connected to any of the sockets without any substantial change in the resonant frequency of the assembly.

  17. Intra-coil interactions in split gradient coils in a hybrid MRI-LINAC system

    NASA Astrophysics Data System (ADS)

    Tang, Fangfang; Freschi, Fabio; Sanchez Lopez, Hector; Repetto, Maurizio; Liu, Feng; Crozier, Stuart

    2016-04-01

    An MRI-LINAC system combines a magnetic resonance imaging (MRI) system with a medical linear accelerator (LINAC) to provide image-guided radiotherapy for targeting tumors in real-time. In an MRI-LINAC system, a set of split gradient coils is employed to produce orthogonal gradient fields for spatial signal encoding. Owing to this unconventional gradient configuration, eddy currents induced by switching gradient coils on and off may be of particular concern. It is expected that strong intra-coil interactions in the set will be present due to the constrained return paths, leading to potential degradation of the gradient field linearity and image distortion. In this study, a series of gradient coils with different track widths have been designed and analyzed to investigate the electromagnetic interactions between coils in a split gradient set. A driving current, with frequencies from 100 Hz to 10 kHz, was applied to study the inductive coupling effects with respect to conductor geometry and operating frequency. It was found that the eddy currents induced in the un-energized coils (hereby-referred to as passive coils) positively correlated with track width and frequency. The magnetic field induced by the eddy currents in the passive coils with wide tracks was several times larger than that induced by eddy currents in the cold shield of cryostat. The power loss in the passive coils increased with the track width. Therefore, intra-coil interactions should be included in the coil design and analysis process.

  18. A study on geometry effect of transmission coil for micro size magnetic induction coil

    NASA Astrophysics Data System (ADS)

    Lee, Kyung Hwa; Jun, Byoung Ok; Kim, Seunguk; Lee, Gwang Jun; Ryu, Mingyu; Choi, Ji-Woong; Jang, Jae Eun

    2016-05-01

    The effects of transmission (Tx) coil structure have been studied for micro-size magnetic induction coil. The size of the receiving (Rx) coil should be shrunk to the micrometer level for the various new applications such as micro-robot and wireless body implanted devices. In case of the macro-scale magnetic induction coil, the power transmission efficiency is generally considered to be higher as the inductance of the transmission coil became larger; however, the large size difference between macro-size Tx coil and micro-size Rx coil can decrease the power transmission efficiency due to the difference of resonance frequency. Here, we study a correlation of the power transmission with the size and distance between the macro-size Tx and micro-size Rx coils using magnetic induction technique. The maximum power efficiency was 0.28/0.23/0.13/0.12% at the distance of 0.3/1/3/5 cm between Rx and Tx coil. In addition, more efficient wireless power transferring method is suggested with a floating coil for the body implantable devices. The voltage output increased up to 5.4 mV than the original one Tx coil system. The results demonstrated the foundational wireless power transferring system with enhanced power efficiency.

  19. Intra-coil interactions in split gradient coils in a hybrid MRI-LINAC system.

    PubMed

    Tang, Fangfang; Freschi, Fabio; Sanchez Lopez, Hector; Repetto, Maurizio; Liu, Feng; Crozier, Stuart

    2016-04-01

    An MRI-LINAC system combines a magnetic resonance imaging (MRI) system with a medical linear accelerator (LINAC) to provide image-guided radiotherapy for targeting tumors in real-time. In an MRI-LINAC system, a set of split gradient coils is employed to produce orthogonal gradient fields for spatial signal encoding. Owing to this unconventional gradient configuration, eddy currents induced by switching gradient coils on and off may be of particular concern. It is expected that strong intra-coil interactions in the set will be present due to the constrained return paths, leading to potential degradation of the gradient field linearity and image distortion. In this study, a series of gradient coils with different track widths have been designed and analyzed to investigate the electromagnetic interactions between coils in a split gradient set. A driving current, with frequencies from 100Hz to 10kHz, was applied to study the inductive coupling effects with respect to conductor geometry and operating frequency. It was found that the eddy currents induced in the un-energized coils (hereby-referred to as passive coils) positively correlated with track width and frequency. The magnetic field induced by the eddy currents in the passive coils with wide tracks was several times larger than that induced by eddy currents in the cold shield of cryostat. The power loss in the passive coils increased with the track width. Therefore, intra-coil interactions should be included in the coil design and analysis process. PMID:26852418

  20. CMS Jet and Missing $E_T$ Commissioning

    SciTech Connect

    Elvira, V.Daniel; /Fermilab

    2009-01-01

    We describe how jets and E{sub T} are defined, reconstructed, and calibrated in CMS, as well as how the CMS detector performs in measuring these physics objects. Performance results are derived from the CMS simulation application, based on Geant4, and also from noise and cosmic commissioning data taken before the first collision event was recorded by CMS in November 2009. A jet and E{sub T} startup plan is in place which includes a data quality monitoring and prompt analysis task force to identify and fix problems as they arise.

  1. Using the CMS threaded framework in a production environment

    SciTech Connect

    Jones, C. D.; Contreras, L.; Gartung, P.; Hufnagel, D.; Sexton-Kennedy, L.

    2015-12-23

    During 2014, the CMS Offline and Computing Organization completed the necessary changes to use the CMS threaded framework in the full production environment. We will briefly discuss the design of the CMS Threaded Framework, in particular how the design affects scaling performance. We will then cover the effort involved in getting both the CMSSW application software and the workflow management system ready for using multiple threads for production. Finally, we will present metrics on the performance of the application and workflow system as well as the difficulties which were uncovered. As a result, we will end with CMS' plans for using the threaded framework to do production for LHC Run 2.

  2. Grid Interoperation with ARC middleware for the CMS experiment

    NASA Astrophysics Data System (ADS)

    Edelmann, Erik; Field, Laurence; Frey, Jaime; Grønager, Michael; Happonen, Kalle; Johansson, Daniel; Kleist, Josva; Klem, Jukka; Koivumäki, Jesper; Lindén, Tomas; Pirinen, Antti; Qing, Di

    2010-04-01

    The Compact Muon Solenoid (CMS) is one of the general purpose experiments at the CERN Large Hadron Collider (LHC). CMS computing relies on different grid infrastructures to provide computational and storage resources. The major grid middleware stacks used for CMS computing are gLite, Open Science Grid (OSG) and ARC (Advanced Resource Connector). Helsinki Institute of Physics (HIP) hosts one of the Tier-2 centers for CMS computing. CMS Tier-2 centers operate software systems for data transfers (PhEDEx), Monte Carlo production (ProdAgent) and data analysis (CRAB). In order to provide the Tier-2 services for CMS, HIP uses tools and components from both ARC and gLite grid middleware stacks. Interoperation between grid systems is a challenging problem and HIP uses two different solutions to provide the needed services. The first solution is based on gLite-ARC grid level interoperability. This allows to use ARC resources in CMS without modifying the CMS application software. The second solution is based on developing specific ARC plugins in CMS software.

  3. Using the CMS Threaded Framework In A Production Environment

    NASA Astrophysics Data System (ADS)

    Jones, C. D.; Contreras, L.; Gartung, P.; Hufnagel, D.; Sexton-Kennedy, L.

    2015-12-01

    During 2014, the CMS Offline and Computing Organization completed the necessary changes to use the CMS threaded framework in the full production environment. We will briefly discuss the design of the CMS Threaded Framework, in particular how the design affects scaling performance. We will then cover the effort involved in getting both the CMSSW application software and the workflow management system ready for using multiple threads for production. Finally, we will present metrics on the performance of the application and workflow system as well as the difficulties which were uncovered. We will end with CMS' plans for using the threaded framework to do production for LHC Run 2.

  4. CD4+ T Cell Depletion in Human Immunodeficiency Virus (HIV) Infection: Role of Apoptosis

    PubMed Central

    Février, Michèle; Dorgham, Karim; Rebollo, Angelita

    2011-01-01

    Human immunodeficiency virus (HIV) infection is principally a mucosal disease and the gastrointestinal (GI) tract is the major site of HIV replication. Loss of CD4+ T cells and systemic immune hyperactivation are the hallmarks of HIV infection. The end of acute infection is associated with the emergence of specific CD4+ and CD8+ T cell responses and the establishment of a chronic phase of infection. Abnormal levels of immune activation and inflammation persist despite a low steady state level of viremia. Although the causes of persistent immune hyperactivation remain incompletely characterized, physiological alterations of gastrointestinal tract probably play a major role. Failure to restore Th17 cells in gut-associated lymphoid tissues (GALT) might impair the recovery of the gut mucosal barrier. This review discusses recent advances on understanding the contribution of CD4+ T cell depletion to HIV pathogenesis. PMID:21994747

  5. Interest of Tumor-Specific CD4 T Helper 1 Cells for Therapeutic Anticancer Vaccine

    PubMed Central

    Galaine, Jeanne; Borg, Christophe; Godet, Yann; Adotévi, Olivier

    2015-01-01

    Nowadays, immunotherapy represents one promising approach for cancer treatment. Recently, spectacular results of cancer immunotherapy clinical trials have confirmed the crucial role of immune system in cancer regression. Therapeutic cancer vaccine represents one widely used immunotherapy strategy to stimulate tumor specific T cell responses but clinical impact remains disappointing in targeting CD8 T cells. Although CD8 T cells have been initially considered to be the main protagonists, it is now clear that CD4 T cells also play a critical role in antitumor response. In this article, we discuss the role of tumor antigen-specific CD4 T cell responses and how we can target these cells to improve cancer vaccines. PMID:26350591

  6. CD4+ T-cell survival in the GI tract requires dectin-1 during fungal infection

    PubMed Central

    Drummond, R A; Dambuza, I M; Vautier, S; Taylor, J A; Reid, D M; Bain, C C; Underhill, D M; Masopust, D; Kaplan, D H; Brown, G D

    2016-01-01

    Dectin-1 is an innate antifungal C-type lectin receptor necessary for protective antifungal immunity. We recently discovered that Dectin-1 is involved in controlling fungal infections of the gastrointestinal (GI) tract, but how this C-type lectin receptor mediates these activities is unknown. Here, we show that Dectin-1 is essential for driving fungal-specific CD4+ T-cell responses in the GI tract. Loss of Dectin-1 resulted in abrogated dendritic cell responses in the mesenteric lymph nodes (mLNs) and defective T-cell co-stimulation, causing substantial increases in CD4+ T-cell apoptosis and reductions in the cellularity of GI-associated lymphoid tissues. CD8+ T-cell responses were unaffected by Dectin-1 deficiency. These functions of Dectin-1 have significant implications for our understanding of intestinal immunity and susceptibility to fungal infections. PMID:26349660

  7. Novel autoantigens for diabetogenic CD4 T cells in autoimmune diabetes

    PubMed Central

    Delong, Thomas; Baker, Rocky L; He, Jing; Haskins, Kathryn

    2013-01-01

    Autoreactive CD4 T cells play a central role in the development of type 1 diabetes. The BDC-panel of diabetogenic T cell clones was originally isolated from non-obese diabetic (NOD) mice and has been used to study the role of autoreactive CD4 T cells and T cell autoantigens in the development of diabetes. Recent studies by our group have led to the identification of two new target antigens for clones of this panel. This review describes the proteomic strategy used for antigen identification, the antigens identified, and the potential contribution of post-translational modification to autoantigen generation. In addition, we compare peptide epitopes for the T cell clones and discuss their potential applications in investigating the role of T cell autoantigens in the pathogenesis and regulation of disease. PMID:22971988

  8. Ubiquitin Ligases and Deubiquitinating Enzymes in CD4+ T Cell Effector Fate Choice and Function.

    PubMed

    Layman, Awo A K; Oliver, Paula M

    2016-05-15

    The human body is exposed to potentially pathogenic microorganisms at barrier sites such as the skin, lungs, and gastrointestinal tract. To mount an effective response against these pathogens, the immune system must recruit the right cells with effector responses that are appropriate for the task at hand. Several types of CD4(+) T cells can be recruited, including Th cells (Th1, Th2, and Th17), T follicular helper cells, and regulatory T cells. These cells help to maintain normal immune homeostasis in the face of constantly changing microbes in the environment. Because these cells differentiate from a common progenitor, the composition of their intracellular milieu of proteins changes to appropriately guide their effector function. One underappreciated process that impacts the levels and functions of effector fate-determining factors is ubiquitylation. This review details our current understanding of how ubiquitylation regulates CD4(+) T cell effector identity and function. PMID:27183634

  9. CD4+ T Cell Priming as Biomarker to Study Immune Response to Preventive Vaccines

    PubMed Central

    Ciabattini, Annalisa; Pettini, Elena; Medaglini, Donata

    2013-01-01

    T cell priming is a critical event in the initiation of the immune response to vaccination since it deeply influences both the magnitude and the quality of the immune response induced. CD4+ T cell priming, required for the induction of high-affinity antibodies and immune memory, represents a key target for improving and modulating vaccine immunogenicity. A major challenge in the study of in vivo T cell priming is due to the low frequency of antigen-specific T cells. This review discusses the current knowledge on antigen-specific CD4+ T cell priming in the context of vaccination, as well as the most advanced tools for the characterization of the in vivo T cell priming and the opportunities offered by the application of systems biology. PMID:24363656

  10. New insights into CD4(+) T cell abnormalities in systemic sclerosis.

    PubMed

    Liu, Mengguo; Wu, Wenyu; Sun, Xinfen; Yang, Ji; Xu, Jinhua; Fu, Wenwen; Li, Ming

    2016-04-01

    Systemic sclerosis (SSc) is an autoimmune connective tissue disease that is characterized by vasculopathy and excessive deposition of extracellular matrix, which causes fibrosis of the skin and internal organs and eventually leads to multiorgan dysfunction. Studies have shown that CD4(+) T cell activation is a key factor in the pathogenesis of scleroderma because activated T cells can release various cytokines, resulting in inflammation, microvascular damage and fibrosis. T helper cell 17 (Th17) and regulatory T (Treg) cell activities are a hallmark SSc, as Th17-type cytokines can induce both inflammation and fibrosis. More recently, several studies have reported new T cell subsets, including Th9 and Th22 cells, along with their respective cytokines in the peripheral blood, serum and skin lesions of individuals with SSc. Herein, we review recent data on various CD4(+) T helper cell subsets in SSc, and discuss potential roles of these cells in promoting inflammation and fibrosis. PMID:26724976

  11. Performance improvement of a high-temperature superconducting coil by separating and grading the coil edge

    NASA Astrophysics Data System (ADS)

    Ishiguri, Shinichi; Funamoto, Taisuke

    2011-06-01

    In this paper, we establish a model to analyze the transport current performance of a high-temperature superconducting (HTS) coil, considering the dependencies of critical current and n-value of an HTS tape on magnetic field and magnetic field angles. This analysis shows that relatively large electric fields appear at the coil’s edges, preventing improvement in the transport current performance of the coil. To solve this problem, in this paper, we propose a graded coil in which several coil edges of different heights are separated and graded. Analysis of its performance shows that the coil’s critical current increases, thus confirming that there exists an optimum coil cross section at which the stored energy and central magnetic field improve 2.1 times and 45%, respectively, compared with a typical rectangular coil that employs the same total length of the HTS tape. It is recommended that these results of the coil should be applied to SMES.

  12. Blockade of the Programmed Death-1 Pathway Restores Sarcoidosis CD4+ T-Cell Proliferative Capacity

    PubMed Central

    Braun, Nicole A.; Celada, Lindsay J.; Herazo-Maya, Jose D.; Abraham, Susamma; Shaginurova, Guzel; Sevin, Carla M.; Grutters, Jan; Culver, Daniel A.; Dworski, Ryszard; Sheller, James; Massion, Pierre P.; Polosukhin, Vasiliy V.; Johnson, Joyce E.; Kaminski, Naftali; Wilkes, David S.; Oswald-Richter, Kyra A.

    2014-01-01

    Rationale: Effective therapeutic interventions for chronic, idiopathic lung diseases remain elusive. Normalized T-cell function is an important contributor to spontaneous resolution of pulmonary sarcoidosis. Up-regulation of inhibitor receptors, such as programmed death-1 (PD-1) and its ligand, PD-L1, are important inhibitors of T-cell function. Objectives: To determine the effects of PD-1 pathway blockade on sarcoidosis CD4+ T-cell proliferative capacity. Methods: Gene expression profiles of sarcoidosis and healthy control peripheral blood mononuclear cells were analyzed at baseline and follow-up. Flow cytometry was used to measure ex vivo expression of PD-1 and PD-L1 on systemic and bronchoalveolar lavage–derived cells of subjects with sarcoidosis and control subjects, as well as the effects of PD-1 pathway blockade on cellular proliferation after T-cell receptor stimulation. Immunohistochemistry analysis for PD-1/PD-L1 expression was conducted on sarcoidosis, malignant, and healthy control lung specimens. Measurements and Main Results: Microarray analysis demonstrates longitudinal increase in PDCD1 gene expression in sarcoidosis peripheral blood mononuclear cells. Immunohistochemistry analysis revealed increased PD-L1 expression within sarcoidosis granulomas and lung malignancy, but this was absent in healthy lungs. Increased numbers of sarcoidosis PD-1+ CD4+ T cells are present systemically, compared with healthy control subjects (P < 0.0001). Lymphocytes with reduced proliferative capacity exhibited increased proliferation with PD-1 pathway blockade. Longitudinal analysis of subjects with sarcoidosis revealed reduced PD-1+ CD4+ T cells with spontaneous clinical resolution but not with disease progression. Conclusions: Analogous to the effects in other chronic lung diseases, these findings demonstrate that the PD-1 pathway is an important contributor to sarcoidosis CD4+ T-cell proliferative capacity and clinical outcome. Blockade of the PD-1 pathway may be a

  13. CD4+ T Cells Promote Antibody Production but Not Sustained Affinity Maturation during Borrelia burgdorferi Infection

    PubMed Central

    Elsner, Rebecca A.; Hastey, Christine J.

    2014-01-01

    CD4 T cells are crucial for enhancing B cell-mediated immunity, supporting the induction of high-affinity, class-switched antibody responses, long-lived plasma cells, and memory B cells. Previous studies showed that the immune response to Borrelia burgdorferi appears to lack robust T-dependent B cell responses, as neither long-lived plasma cells nor memory B cells form for months after infection, and nonswitched IgM antibodies are produced continuously during this chronic disease. These data prompted us to evaluate the induction and functionality of B. burgdorferi infection-induced CD4 TFH cells. We report that CD4 T cells were effectively primed and TFH cells induced after B. burgdorferi infection. These CD4 T cells contributed to the control of B. burgdorferi burden and supported the induction of B. burgdorferi-specific IgG responses. However, while affinity maturation of antibodies against a prototypic T-dependent B. burgdorferi protein, Arthritis-related protein (Arp), were initiated, these increases were reversed later, coinciding with the previously observed involution of germinal centers. The cessation of affinity maturation was not due to the appearance of inhibitory or exhausted CD4 T cells or a strong induction of regulatory T cells. In vitro T-B cocultures demonstrated that T cells isolated from B. burgdorferi-infected but not B. burgdorferi-immunized mice supported the rapid differentiation of B cells into antibody-secreting plasma cells rather than continued proliferation, mirroring the induction of rapid short-lived instead of long-lived T-dependent antibody responses in vivo. The data further suggest that B. burgdorferi infection drives the humoral response away from protective, high-affinity, and long-lived antibody responses and toward the rapid induction of strongly induced, short-lived antibodies of limited efficacy. PMID:25312948

  14. Tolerance induction in memory CD4 T cells requires two rounds of antigen-specific activation.

    PubMed

    David, Alexandria; Crawford, Frances; Garside, Paul; Kappler, John W; Marrack, Philippa; MacLeod, Megan

    2014-05-27

    A major goal for immunotherapy is to tolerize the immune cells that coordinate tissue damage in autoimmune and alloantigen responses. CD4 T cells play a central role in many of these conditions and improved antigen-specific regulation or removal of these cells could revolutionize current treatments. A confounding factor is that little is known about whether and how tolerance is induced in memory CD4 T cells. We used MHC class II tetramers to track and analyze a population of endogenous antigen-specific memory CD4 T cells exposed to soluble peptide in the absence of adjuvant. We found that such memory T cells proliferated and reentered the memory pool apparently unperturbed by the incomplete activation signals provided by the peptide. Upon further restimulation in vivo, CD4 memory T cells that had been previously exposed to peptide proliferated, provided help to primary responding B cells, and migrated to inflamed sites. However, these reactivated memory cells failed to survive. The reduction in T-cell number was marked by low expression of the antiapoptotic molecule B cell lymphoma 2 (Bcl2) and increased expression of activated caspase molecules. Consequently, these cells failed to sustain a delayed-type hypersensitivity response. Moreover, following two separate exposures to soluble antigen, no T-cell recall response and no helper activity for B cells could be detected. These results suggest that the induction of tolerance in memory CD4 T cells is possible but that deletion and permanent removal of the antigen-specific T cells requires reactivation following exposure to the tolerogenic antigen. PMID:24821788

  15. 26 CFR 1.905-4T - Notification of foreign tax redetermination (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... or after November 7, 2007, see 26 CFR 1.905-4T and 1.905-5T (as contained in 26 CFR part 1, revised... satisfied the notification requirements described in § 1.905-3T and this section (as contained in 26 CFR.... The average exchange rate for 2008 was $1:1n. X claimed a foreign tax credit of $150 ($100 (100m at...

  16. Azithromycin suppresses CD4+ T-cell activation by direct modulation of mTOR activity

    PubMed Central

    Ratzinger, F.; Haslacher, H.; Poeppl, W.; Hoermann, G.; Kovarik, J. J.; Jutz, S.; Steinberger, P.; Burgmann, H.; Pickl, W. F.; Schmetterer, K. G.

    2014-01-01

    Advanced macrolides, such as azithromycin (AZM) or clarithromycin (CLM), are antibiotics with immunomodulatory properties. Here we have sought to evaluate their in vitro influence on the activation of CD4+ T-cells. Isolated CD4+ T-cells were stimulated with agonistic anti-CD3/anti-CD28 monoclonal antibodies in the presence of 0.6 mg/L, 2.5 mg/L, 10 mg/L or 40 mg/L AZM or CLM. Cell proliferation, cytokine level in supernatants and cell viability was assessed. Intracellular signaling pathways were evaluated using reporter cell lines, FACS analysis, immunoblotting and in vitro kinase assays. AZM inhibited cell proliferation rate and cytokine secretion of CD4+ T-cells in a dose-dependent manner. Similarly, high concentrations of CLM (40 mg/L) also suppressed these T-cell functions. Analysis of molecular signaling pathways revealed that exposure to AZM reduced the phosphorylation of the S6 ribosomal protein, a downstream target of mTOR. This effect was also observed at 40 mg/L CLM. In vitro kinase studies using recombinant mTOR showed that AZM inhibited mTOR activity. In contrast to rapamycin, this inhibition was independent of FKBP12. We show for the first time that AZM and to a lesser extent CLM act as immunosuppressive agents on CD4+ T-cells by inhibiting mTOR activity. Our results might have implications for the clinical use of macrolides. PMID:25500904

  17. Identification of two regulatory elements controlling Fucosyltransferase 7 transcription in murine CD4+ T cells.

    PubMed

    Pink, Matthias; Ratsch, Boris A; Mardahl, Maibritt; Schröter, Micha F; Engelbert, Dirk; Triebus, Julia; Hamann, Alf; Syrbe, Uta

    2014-11-01

    Fucosyltransferase VII encoded by the gene Fut7 is essential in CD4(+) T cells for the generation of E- and P-selectin ligands (E- and P-lig) which facilitate recruitment of lymphocytes into inflamed tissues and into the skin. This study aimed to identify regulatory elements controlling the inducible Fut7 expression in CD4(+) T cells that occurs upon activation and differentiation of naive T cells into effector cells. Comparative analysis of the histone modification pattern in non-hematopoetic cells and CD4(+) T cell subsets revealed a differential histone modification pattern within the Fut7 locus including a conserved non-coding sequence (CNS) identified by cross-species conservation comparison suggesting that regulatory elements are confined to this region. Cloning of the CNS located about 500 bp upstream of the Fut7 locus, into a luciferase reporter vector elicited reporter activity after transfection of the αβ-WT T cell line, but not after transfection of primary murine CD4(+) Th1 cells. As quantification of different Fut7 transcripts revealed a predominance of transcripts lacking the first exons in primary Th1 cells we searched for an alternative promoter. Cloning of an intragenic region spanning a 1kb region upstream of exon 4 into an enhancer-containing vector indeed elicited promoter activity. Interestingly, also the CNS enhanced activity of this intragenic minimal promoter in reporter assays in primary Th1 cells suggesting that both elements interact in primary CD4(+) T cells to induce Fut7 transcription. PMID:24915132

  18. Interferon-alpha stimulates production of interleukin-10 in activated CD4+ T cells and monocytes.

    PubMed

    Aman, M J; Tretter, T; Eisenbeis, I; Bug, G; Decker, T; Aulitzky, W E; Tilg, H; Huber, C; Peschel, C

    1996-06-01

    In the present study, we investigated the effect of interferon-alpha (IFN-alpha) on the expression of interleukin-10 (IL-10) mRNA and protein synthesis in human monocytes and CD4+ T cells. In mononuclear cells, IFN-alpha induced expression of IL-10 mRNA and further enhanced lipopolysaccharide (LPS)-stimulated IL-10 expression. In purified monocytes, a strong expression of IL-10 mRNA induced by LPS was not further enhanced by IFN-alpha. In highly purified CD4+ T cells, IFN-alpha upregulated IL-10 mRNA upon activation with phytohemagglutinin and phorbol myristate acetate. In purified monocytes, an effect of IFN-alpha on IL-10 protein synthesis was dependent on costimulation with LPS. Maximal stimulation of IL-10 protein by IFN-alpha was seen after prolonged incubation periods of 48 to 96 hours, whereas IFN-gamma reduced IL-10 production in the early incubation period. Similar effects of IFN-alpha were observed in CD4+ T cells activated with CD3 and CD28 monoclonal antibodies. Addition of IFN-alpha caused an increase of IL-10 in culture supernatants of activated T-helper cells of more than 100% after 96 hours of incubation. In contrast, other cytokines, including IFN-gamma and IL-4, had no influence on IL-10 secretion stimulated by CD3 and CD28 in CD4+ T cells. In serum samples of IFN-alpha-treated individuals, we failed to detect an influence of cytokine treatment on IL-10 serum levels, confirming the requirement of additional activating signals for IFN-alpha-mediated effects on IL-10 synthesis. In conclusion, IFN-alpha enhances the late induction of IL-10, which physiologically occurs upon stimulation of monocytes and T cells. Biologically, this effect might enhance the negative-feedback mechanism ascribed to IL-10, which limits inflammatory reactions. PMID:8639843

  19. E4BP4 overexpression: a protective mechanism in CD4+ T cells from SLE patients.

    PubMed

    Zhao, Ming; Liu, Qian; Liang, Gongping; Wang, Litao; Luo, Shuangyan; Tang, Qian; Zhao, Hongjun; Su, Yuwen; Yung, Susan; Chan, Tak Mao; Lu, Qianjin

    2013-03-01

    Systemic lupus erythematosus (SLE) is a prototype autoimmune disease characterized by various immunological abnormalities, including dysregulated activation of T and B lymphocytes, which trigger autoantibody production and immune-complex deposition. E4BP4, also known as NFIL3, has emerged as a major transcription factor that regulates the development and function of immune cells in a number of lineages. E4BP4 has been shown to regulate cytokines expression, and its synthesis is in turn controlled by various cytokines. To date, the roles of E4BP4 in immune dysregulation and autoimmune disorders are unclear. In this study, we demonstrated that E4BP4 expression is increased in CD4(+) T cells isolated from patients with active systemic lupus erythematosus (SLE), especially in patients treated with glucocorticoid (GC). Increased expression of E4BP4 inhibited the activation and self-reactivity of T cells stimulated by anti-CD3/CD28 antibodies. In contrast, the self-reactivity was enhanced in CD4(+) T cells from SLE patients following E4BP4 gene silencing and the production of autoantibody was increased in autologous B cells. We further demonstrated that E4BP4 directly regulated CD40L expression by binding to the promoter region and altering histone acetylation and methylation of the CD40L loci. Taken together, our data provide evidence that E4BP4 can inhibit CD40L expression through epigenetic modifications in the promoter region of CD40L, thus negatively regulating self-reactivity of SLE CD4(+) T cells. Furthermore, our data demonstrate that overexpression of E4BP4 initiates a protective mechanism in SLE CD4(+) T cells, which may be a promising target in the therapy for SLE. PMID:23340290

  20. CD4+ T cell responses to self- and mutated p53 determinants during tumorigenesis in mice.

    PubMed

    Fedoseyeva, E V; Boisgérault, F; Anosova, N G; Wollish, W S; Arlotta, P; Jensen, P E; Ono, S J; Benichou, G

    2000-06-01

    We analyzed CD4+ T helper responses to wild-type (wt) and mutated (mut) p53 protein in normal and tumor-bearing mice. In normal mice, we observed that although some self-p53 determinants induced negative selection of p53-reactive CD4+ T cells, other p53 determinants (cryptic) were immunogenic. Next, BALB/c mice were inoculated with J774 syngeneic tumor cell line expressing mut p53. BALB/c tumor-bearing mice mounted potent CD4+ T cell responses to two formerly cryptic peptides on self-p53. This response was characterized by massive production of IL-5, a Th2-type lymphokine. Interestingly, we found that T cell response was induced by different p53 peptides depending upon the stage of cancer. Mut p53 gene was shown to contain a single mutation resulting in the substitution of a tyrosine by a histidine at position 231 of the protein. Two peptides corresponding to wt and mutated sequences of this region were synthesized. Both peptides bound to the MHC class II-presenting molecule (Ed) with similar affinities. However, only mut p53.225-239 induced T cell responses in normal BALB/c mice, a result strongly suggesting that high-affinity wt p53.225-239 autoreactive T cells had been eliminated in these mice. Surprisingly, CD4+ T cell responses to both mut and wt p53.225-239 peptides were recorded in J774 tumor-bearing mice, a phenomenon attributed to the recruitment of low-avidity p53.225-239 self-reactive T cells. PMID:10820239

  1. Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria.

    PubMed

    Hepworth, Matthew R; Monticelli, Laurel A; Fung, Thomas C; Ziegler, Carly G K; Grunberg, Stephanie; Sinha, Rohini; Mantegazza, Adriana R; Ma, Hak-Ling; Crawford, Alison; Angelosanto, Jill M; Wherry, E John; Koni, Pandelakis A; Bushman, Frederic D; Elson, Charles O; Eberl, Gérard; Artis, David; Sonnenberg, Gregory F

    2013-06-01

    Innate lymphoid cells (ILCs) are a recently characterized family of immune cells that have critical roles in cytokine-mediated regulation of intestinal epithelial cell barrier integrity. Alterations in ILC responses are associated with multiple chronic human diseases, including inflammatory bowel disease, implicating a role for ILCs in disease pathogenesis. Owing to an inability to target ILCs selectively, experimental studies assessing ILC function have predominantly used mice lacking adaptive immune cells. However, in lymphocyte-sufficient hosts ILCs are vastly outnumbered by CD4(+) T cells, which express similar profiles of effector cytokines. Therefore, the function of ILCs in the presence of adaptive immunity and their potential to influence adaptive immune cell responses remain unknown. To test this, we used genetic or antibody-mediated depletion strategies to target murine ILCs in the presence of an adaptive immune system. We show that loss of retinoic-acid-receptor-related orphan receptor-γt-positive (RORγt(+)) ILCs was associated with dysregulated adaptive immune cell responses against commensal bacteria and low-grade systemic inflammation. Remarkably, ILC-mediated regulation of adaptive immune cells occurred independently of interleukin (IL)-17A, IL-22 or IL-23. Genome-wide transcriptional profiling and functional analyses revealed that RORγt(+) ILCs express major histocompatibility complex class II (MHCII) and can process and present antigen. However, rather than inducing T-cell proliferation, ILCs acted to limit commensal bacteria-specific CD4(+) T-cell responses. Consistent with this, selective deletion of MHCII in murine RORγt(+) ILCs resulted in dysregulated commensal bacteria-dependent CD4(+) T-cell responses that promoted spontaneous intestinal inflammation. These data identify that ILCs maintain intestinal homeostasis through MHCII-dependent interactions with CD4(+) T cells that limit pathological adaptive immune cell responses to commensal

  2. Analysis of Virus-Specific CD4+ T Cells during Long-Term Gammaherpesvirus Infection

    PubMed Central

    Flaño, Emilio; Woodland, David L.; Blackman, Marcia A.; Doherty, Peter C.

    2001-01-01

    Major histocompatibility complex class II-mediated antigen presentation after intranasal infection with murine gammaherpesvirus 68 differs in mediastinal lymph nodes and spleen. Evidence that virus-specific CD4+ T cells were being stimulated was found as late as 6 to 8 months after infection, and cells specific for the viral gp15067–83 and ORF11168–180 peptides were maintained as a fairly stable proportion of the total response. PMID:11462049

  3. Memory CD4 T cells emerge from effector T-cell progenitors.

    PubMed

    Harrington, Laurie E; Janowski, Karen M; Oliver, James R; Zajac, Allan J; Weaver, Casey T

    2008-03-20

    A hallmark of adaptive immunity is the generation of memory T cells that confer long-lived, antigen-specific protection against repeat challenges by pathogens. Understanding the mechanisms by which memory T cells arise is important for rational vaccination strategies and improved therapeutic interventions for chronic infections and autoimmune disorders. The large clonal expansion of CD8 T cells in response to some infections has made the development of CD8 T-cell memory more amenable to study, giving rise to a model of memory cell differentiation in which a fraction of fully competent effector T cells transition into long-lived memory T cells. Delineation of CD4 T-cell memory development has proved more difficult as a result of limitations on tracking the smaller populations of CD4 effector T cells generated during a pathogenic challenge, complicating efforts to determine whether CD4 memory T cells are direct descendants of effector T cells or whether they develop by alternative pathways. Here, using two complementary cytokine reporter mouse models to identify interferon (IFN)-gamma-positive effector T cells and track their fate, we show that the lineage relationship between effector and memory CD4 T cells resembles that for CD8 T cells responding to the same pathogen. We find that, in parallel with effector CD8 T cells, IFN-gamma-positive effector CD4 T cells give rise to long-lived memory T cells capable of anamnestic responses to antigenic rechallenge. PMID:18322463

  4. Secretion of N- and O-linked Glycoproteins from 4T1 Murine Mammary Carcinoma Cells

    PubMed Central

    Phang, Wai-Mei; Tan, Aik-Aun; Gopinath, Subash C.B.; Hashim, Onn H.; Kiew, Lik Voon; Chen, Yeng

    2016-01-01

    Breast cancer is one of the most common cancers that affect women globally and accounts for ~23% of all cancers diagnosed in women. Breast cancer is also one of the leading causes of death primarily due to late stage diagnoses and a lack of effective treatments. Therefore, discovering protein expression biomarkers is mandatory for early detection and thus, critical for successful therapy. Two-dimensional electrophoresis (2D-E) coupled with lectin-based analysis followed by mass spectrometry were applied to identify potential biomarkers in the secretions of a murine mammary carcinoma cell line. Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. PMID:27226773

  5. Expanding Roles for CD4 T Cells and Their Subpopulations in Tumor Immunity and Therapy

    PubMed Central

    Dobrzanski, Mark J.

    2013-01-01

    The importance of CD4 T cells in orchestrating the immune system and their role in inducing effective T cell-mediated therapies for the treatment of patients with select established malignancies are undisputable. Through a complex and balanced array of direct and indirect mechanisms of cellular activation and regulation, this functionally diverse family of lymphocytes can potentially promote tumor eradication, long-term tumor immunity, and aid in establishing and/or rebalancing immune cell homeostasis through interaction with other immune cell populations within the highly dynamic tumor environment. However, recent studies have uncovered additional functions and roles for CD4 T cells, some of which are independent of other lymphocytes, that can not only influence and contribute to tumor immunity but paradoxically promote tumor growth and progression. Here, we review the recent advances in our understanding of the various CD4 T cell lineages and their signature cytokines in disease progression and/or regression. We discuss their direct and indirect mechanistic interplay among themselves and with other responding cells of the antitumor response, their potential roles and abilities for “plasticity” and memory cell generation within the hostile tumor environment, and their potentials in cancer treatment and immunotherapy. PMID:23533029

  6. NAFLD causes selective CD4(+) T lymphocyte loss and promotes hepatocarcinogenesis.

    PubMed

    Ma, Chi; Kesarwala, Aparna H; Eggert, Tobias; Medina-Echeverz, José; Kleiner, David E; Jin, Ping; Stroncek, David F; Terabe, Masaki; Kapoor, Veena; ElGindi, Mei; Han, Miaojun; Thornton, Angela M; Zhang, Haibo; Egger, Michèle; Luo, Ji; Felsher, Dean W; McVicar, Daniel W; Weber, Achim; Heikenwalder, Mathias; Greten, Tim F

    2016-03-10

    Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death. Non-alcoholic fatty liver disease (NAFLD) affects a large proportion of the US population and is considered to be a metabolic predisposition to liver cancer. However, the role of adaptive immune responses in NAFLD-promoted HCC is largely unknown. Here we show, in mouse models and human samples, that dysregulation of lipid metabolism in NAFLD causes a selective loss of intrahepatic CD4(+) but not CD8(+) T lymphocytes, leading to accelerated hepatocarcinogenesis. We also demonstrate that CD4(+) T lymphocytes have greater mitochondrial mass than CD8(+) T lymphocytes and generate higher levels of mitochondrially derived reactive oxygen species (ROS). Disruption of mitochondrial function by linoleic acid, a fatty acid accumulated in NAFLD, causes more oxidative damage than other free fatty acids such as palmitic acid, and mediates selective loss of intrahepatic CD4(+) T lymphocytes. In vivo blockade of ROS reversed NAFLD-induced hepatic CD4(+) T lymphocyte decrease and delayed NAFLD-promoted HCC. Our results provide an unexpected link between lipid dysregulation and impaired anti-tumour surveillance. PMID:26934227

  7. Endogenous antigen processing drives the primary CD4+ T cell response to influenza

    PubMed Central

    Miller, Michael A.; Ganesan, Asha Purnima V.; Luckashenak, Nancy; Mendonca, Mark; Eisenlohr, Laurence C.

    2015-01-01

    By convention, CD4+ T lymphocytes recognize foreign and self peptides derived from internalized antigens in combination with MHC class II molecules. Alternative pathways of epitope production have been identified but their contributions to host defense have not been established. We show here in a mouse infection model that the CD4+ T cell response to influenza, critical for durable protection from the virus, is driven principally by unconventional processing of antigen synthesized within the infected antigen-presenting cell, not by classical processing of endocytosed virions or material from infected cells. Investigation of the cellular components involved, including the H2-M molecular chaperone, the proteasome, and gamma-interferon inducible lysosomal thiol reductase revealed considerable heterogeneity in the generation of individual epitopes, an arrangement that ensures peptide diversity and broad CD4+ T cell engagement. These results could fundamentally revise strategies for rational vaccine design and may lead to key insights into the induction of autoimmune and anti-tumor responses. PMID:26413780

  8. Quantitative and qualitative characterization of expanded CD4+ T cell clones in rheumatoid arthritis patients

    PubMed Central

    Ishigaki, Kazuyoshi; Shoda, Hirofumi; Kochi, Yuta; Yasui, Tetsuro; Kadono, Yuho; Tanaka, Sakae; Fujio, Keishi; Yamamoto, Kazuhiko

    2015-01-01

    Rheumatoid arthritis (RA) is an autoimmune destructive arthritis associated with CD4+ T cell-mediated immunity. Although expanded CD4+ T cell clones (ECs) has already been confirmed, the detailed characteristics of ECs have not been elucidated in RA. Using combination of a single-cell analysis and next-generation sequencing (NGS) in TCR repertoire analysis, we here revealed the detailed nature of ECs by examining peripheral blood (PB) from 5 RA patients and synovium from 1 RA patient. When we intensively investigated the single-cell transcriptome of the most expanded clones in memory CD4+ T cells (memory-mECs) in RA-PB, senescence-related transcripts were up-regulated, indicating circulating ECs were constantly stimulated. Tracking of the transcriptome shift within the same memory-mECs between PB and the synovium revealed the augmentations in senescence-related gene expression and the up-regulation of synovium-homing chemokine receptors in the synovium. Our in-depth characterization of ECs in RA successfully demonstrated the presence of the specific immunological selection pressure, which determines the phenotype of ECs. Moreover, transcriptome tracking added novel aspects to the underlying sequential immune processes. Our approach may provide new insights into the pathophysiology of RA. PMID:26245356

  9. Excess Lymphangiogenesis Cooperatively Induced by Macrophages and CD4(+) T Cells Drives the Pathogenesis of Lymphedema.

    PubMed

    Ogata, Fusa; Fujiu, Katsuhito; Matsumoto, Sahohime; Nakayama, Yukiteru; Shibata, Munehiko; Oike, Yuichi; Koshima, Isao; Watabe, Tetsuro; Nagai, Ryozo; Manabe, Ichiro

    2016-03-01

    Lymphedema is a debilitating progressive condition that severely restricts quality of life and is frequently observed after cancer surgery. The mechanism underlying lymphedema development remains poorly understood, and no effective pharmacological means to prevent or alleviate the ailment is currently available. Using a mouse model of lymphedema, we show here that excessive generation of immature lymphatic vessels is essential for initial edema development and that this early process is also important for later development of lymphedema pathology. We found that CD4(+) T cells interact with macrophages to promote lymphangiogenesis, and that both lymphangiogenesis and edema were greatly reduced in macrophage-depleted mice, lymphocyte-deficient Rag2(?/?) mice or CD4(+) T-cell-deficient mice. Mechanistically, T helper type 1 and T helper type 17 cells activate lesional macrophages to produce vascular endothelial growth factor-C, which promotes lymphangiogenesis, and inhibition of this mechanism suppressed not only early lymphangiogenesis, but also later development of lymphedema. Finally, we show that atorvastatin suppresses excessive lymphangiogenesis and lymphedema by inhibiting T helper type 1 and T helper type 17 cell activation. These results demonstrate that the interaction between CD4(+) T cells and macrophages is a potential therapeutic target for prevention of lymphedema after surgery. PMID:27015456

  10. Secretion of N- and O-linked Glycoproteins from 4T1 Murine Mammary Carcinoma Cells.

    PubMed

    Phang, Wai-Mei; Tan, Aik-Aun; Gopinath, Subash C B; Hashim, Onn H; Kiew, Lik Voon; Chen, Yeng

    2016-01-01

    Breast cancer is one of the most common cancers that affect women globally and accounts for ~23% of all cancers diagnosed in women. Breast cancer is also one of the leading causes of death primarily due to late stage diagnoses and a lack of effective treatments. Therefore, discovering protein expression biomarkers is mandatory for early detection and thus, critical for successful therapy. Two-dimensional electrophoresis (2D-E) coupled with lectin-based analysis followed by mass spectrometry were applied to identify potential biomarkers in the secretions of a murine mammary carcinoma cell line. Comparisons of the protein profiles of the murine 4T1 mammary carcinoma cell line and a normal murine MM3MG mammary cell line indicated that cadherin-1 (CDH), collagenase 3 (MMP-13), Viral envelope protein G7e (VEP), Gag protein (GAG) and Hypothetical protein LOC433182 (LOC) were uniquely expressed by the 4T1 cells, and pigment epithelium-derived factor (PEDF) was exclusively secreted by the MM3MG cells. Further analysis by a lectin-based study revealed that aberrant O-glycosylated CDH, N-glycosylated MMP-13 and LOC were present in the 4T1 medium. These differentially expressed N- and O-linked glycoprotein candidates, which were identified by combining lectin-based analysis with 2D-E, could serve as potential diagnostic and prognostic markers for breast cancer. PMID:27226773

  11. Adenoviral transduction of naive CD4 T cells to study Treg differentiation.

    PubMed

    Warth, Sebastian C; Heissmeyer, Vigo

    2013-01-01

    Regulatory T cells (Tregs) are essential to provide immune tolerance to self as well as to certain foreign antigens. Tregs can be generated from naive CD4 T cells in vitro with TCR- and co-stimulation in the presence of TGFβ and IL-2. This bears enormous potential for future therapies, however, the molecules and signaling pathways that control differentiation are largely unknown. Primary T cells can be manipulated through ectopic gene expression, but common methods fail to target the most important naive state of the T cell prior to primary antigen recognition. Here, we provide a protocol to express ectopic genes in naive CD4 T cells in vitro before inducing Treg differentiation. It applies transduction with the replication-deficient adenovirus and explains its generation and production. The adenovirus can take up large inserts (up to 7 kb) and can be equipped with promoters to achieve high and transient overexpression in T cells. It effectively transduces naive mouse T cells if they express a transgenic Coxsackie adenovirus receptor (CAR). Importantly, after infection the T cells remain naive (CD44(low), CD62L(high)) and resting (CD25(-), CD69(-)) and can be activated and differentiated into Tregs similar to non-infected cells. Thus, this method enables manipulation of CD4 T cell differentiation from its very beginning. It ensures that ectopic gene expression is already in place when early signaling events of the initial TCR stimulation induces cellular changes that eventually lead into Treg differentiation. PMID:23979424

  12. Transcription regulates HIF-1α expression in CD4(+) T cells.

    PubMed

    Bollinger, Thomas; Bollinger, Annalena; Gies, Sydney; Feldhoff, Lea; Solbach, Werner; Rupp, Jan

    2016-01-01

    The transcription factor hypoxia inducible factor-1α (HIF-1α) mediates the metabolic adaptation of cells to hypoxia and T-helper cell fate. However, HIF-1α regulation in CD4(+) T cells (T cells) remains elusive. Here we observed that depletion of oxygen (O2⩽2%) alone was not sufficient to induce HIF-1α expression in T cells. However, when hypoxic T cells were stimulated, HIF-1α was expressed and this was dependent on nuclear factor-κB- and nuclear factor of activated T cell (NFAT)-mediated transcriptional upregulation of Hif-1α mRNA. HIF-1α upregulation could be blocked by drugs inhibiting NF-κB, NFAT or mammalian target of rapamycin precluding CD4(+) T-cell stimulation or translation in T cells, as well as by blocking transcription. CD3, CD28, phorbol-12-myristat-13-acetat (PMA) or ionomycin-stimulated T cells did not express HIF-1α under normoxic conditions. In conclusion, regulation of HIF-1α expression in CD4(+) T cells in hypoxia gravely relies on its transcriptional upregulation and subsequent enhanced protein stabilization. PMID:26150319

  13. NK cell regulation of CD4 T cell-mediated graft-versus-host disease.

    PubMed

    Noval Rivas, Magali; Hazzan, Marc; Weatherly, Kathleen; Gaudray, Florence; Salmon, Isabelle; Braun, Michel Y

    2010-06-15

    CD3-negative NK cells are granular lymphocytes capable of producing inflammatory cytokines and killing malignant, infected, or stressed cells. We have recently observed a new role for NK cells in the control of the proliferation of CD4 T cells under persistent antigenic stimulation. Monoclonal anti-male CD4 T cells transferred into Rag2-/- male recipients did not expand or were rapidly eliminated. Remarkably, T cells transferred into NK cell-deficient Rag2-/- Il-2Rgammac-/- male hosts expanded extensively and mediated tissue lesions usually observed in chronic graft-versus-host disease (GVHD). T cell failure to proliferate and to induce chronic GVHD was the result of NK cell activity, because depletion of the recipient's NK1.1+ cells by Ab treatment induced T cell expansion and chronic GVHD. T cells under chronic Ag stimulation upregulated ligands of the activating receptor NKG2D, and regulatory activity of NK cells was inhibited by the injection of Abs directed to NKG2D. On the contrary, blocking NKG2A inhibitory receptors did not increase NK cell regulatory activity. Finally, we show that NK regulation of T cell expansion did not involve perforin-mediated lytic activity of NK cells, but depended on T cell surface expression of a functional Fas molecule. These results highlight the potential role played by NK cells in controlling the Ag-specific CD4+ T cells responsible for chronic GVHD. PMID:20488796

  14. Role of acid sphingomyelinase bioactivity in human CD4+ T-cell activation and immune responses

    PubMed Central

    Bai, A; Kokkotou, E; Zheng, Y; Robson, S C

    2015-01-01

    Acid sphingomyelinase (ASM), a lipid hydrolase enzyme, has the potential to modulate various cellular activation responses via the generation of ceramide and by interaction with cellular receptors. We have hypothesized that ASM modulates CD4+ T-cell receptor activation and impacts immune responses. We first observed interactions of ASM with the intracellular domains of both CD3 and CD28. ASM further mediates T-cell proliferation after anti-CD3/CD28 antibody stimulation and alters CD4+ T-cell activation signals by generating ceramide. We noted that various pharmacological inhibitors of ASM or knockdown of ASM using small hairpin RNA inhibit CD3/CD28-mediated CD4+ T-cell proliferation and activation. Furthermore, such blockade of ASM bioactivity by biochemical inhibitors and/or molecular-targeted knockdown of ASM broadly abrogate T-helper cell responses. In conclusion, we detail immune, pivotal roles of ASM in adaptive immune T-cell responses, and propose that these pathways might provide novel targets for the therapy of autoimmune and inflammatory diseases. PMID:26203857

  15. Coordinated Changes in DNA Methylation in Antigen-Specific Memory CD4 T Cells

    PubMed Central

    Ogoshi, Katsumi; Sasaki, Atsushi; Abe, Jun; Qu, Wei; Nakatani, Yoichiro; Ahsan, Budrul; Oshima, Kenshiro; Shand, Francis H. W.; Ametani, Akio; Suzuki, Yutaka; Kaneko, Shuichi; Wada, Takashi; Hattori, Masahira; Sugano, Sumio; Morishita, Shinichi; Matsushima, Kouji

    2013-01-01

    Memory CD4+ T cells are central regulators of both humoral and cellular immune responses. T cell differentiation results in specific changes in chromatin structure and DNA methylation of cytokine genes. Although the methylation status of a limited number of gene loci in T cells has been examined, the genome-wide DNA methylation status of memory CD4+ T cells remains unexplored. To further elucidate the molecular signature of memory T cells, we conducted methylome and transcriptome analyses of memory CD4+ T cells generated using T cells from TCR-transgenic mice. The resulting genome-wide DNA methylation profile revealed 1144 differentially methylated regions (DMRs) across the murine genome during the process of T cell differentiation, 552 of which were associated with gene loci. Interestingly, the majority of these DMRs were located in introns. These DMRs included genes such as CXCR6, Tbox21, Chsy1, and Cish, which are associated with cytokine production, homing to bone marrow, and immune responses. Methylation changes in memory T cells exposed to specific Ag appeared to regulate enhancer activity rather than promoter activity of immunologically relevant genes. In addition, methylation profiles differed between memory T cell subsets, demonstrating a link between T cell methylation status and T cell differentiation. By comparing DMRs between naive and Ag-specific memory T cells, this study provides new insights into the functional status of memory T cells. PMID:23509353

  16. 26 CFR 1.103(n)-4T - Elective carryforward of unused private activity bond limit (temporary).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... carryforward for any one or more projects described in A-5 of this § 1.103(n)-4T (carryforward projects). Q-2... titled “Carryforward election under section 103(n)”. (ii) The statement required by (i) of this A-2 shall... bond limit (temporary). 1.103(n)-4T Section 1.103(n)-4T Internal Revenue INTERNAL REVENUE...

  17. 26 CFR 1.103(n)-4T - Elective carryforward of unused private activity bond limit (temporary).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... carryforward for any one or more projects described in A-5 of this § 1.103(n)-4T (carryforward projects). Q-2... titled “Carryforward election under section 103(n)”. (ii) The statement required by (i) of this A-2 shall... bond limit (temporary). 1.103(n)-4T Section 1.103(n)-4T Internal Revenue INTERNAL REVENUE...

  18. Laser monitoring for the CMS ECAL

    NASA Astrophysics Data System (ADS)

    Rogan, Christopher; CMS ECAL Group

    2010-11-01

    The Compact Muon Solenoid (CMS) detector at the LHC is equipped with a high precision lead tungstate crystal electromagnetic calorimeter (ECAL). To ensure the stability of the calorimetric response at the level of a few per mille, every channel of the detector is monitored with a laser system. This system enables corrections for fluctuations in the detector response with high precision, in particular the expected radiation induced changes in the crystal transparency. We describe the implementation of the laser monitoring system and report results from tests on the fully equipped supermodules of the ECAL. Specifically, we discuss results concerning the dynamics of crystal transparency change from dedicated irradiation studies in test beams.

  19. The CMS High-Level Trigger

    SciTech Connect

    Covarelli, R.

    2009-12-17

    At the startup of the LHC, the CMS data acquisition is expected to be able to sustain an event readout rate of up to 100 kHz from the Level-1 trigger. These events will be read into a large processor farm which will run the 'High-Level Trigger'(HLT) selection algorithms and will output a rate of about 150 Hz for permanent data storage. In this report HLT performances are shown for selections based on muons, electrons, photons, jets, missing transverse energy, {tau} leptons and b quarks: expected efficiencies, background rates and CPU time consumption are reported as well as relaxation criteria foreseen for a LHC startup instantaneous luminosity.

  20. SUSY Search Strategies at Atlas and CMS

    SciTech Connect

    Autermann, Christian

    2008-11-23

    Supersymmetry is regarded as the most promising candidate for physics beyond the Standard Model. Various search strategies for SUSY are conducted at the Atlas and CMS experiments. In the early data inclusive searches, with different lepton multiplicities, are most sensitive and will be discussed here. The reach of both experiments is interpreted within the mSUGRA model.The LHC has started operation and the experiments are expected to collect of the order of 100 pb{sup -1} integrated luminosity within the first year.

  1. The upgrade of the CMS Global Trigger

    NASA Astrophysics Data System (ADS)

    Wittmann, J.; Arnold, B.; Bergauer, H.; Jeitler, M.; Matsushita, T.; Rabady, D.; Rahbaran, B.; Wulz, C.-E.

    2016-02-01

    The Global Trigger is the final step of the CMS Level-1 Trigger. Previously implemented in VME, it has been redesigned and completely rebuilt in MicroTCA technology, using the Virtex-7 FPGA chip family. It will allow to implement trigger algorithms close to the final physics selection. The new system is presented, together with performance tests undertaken in parallel operation with the legacy system during the initial months of Run II of the LHC at a beam energy of 13 TeV.

  2. The evolution of CMS software performance studies

    NASA Astrophysics Data System (ADS)

    Kortelainen, M. J.; Elmer, P.; Eulisse, G.; Innocente, V.; Jones, C. D.; Tuura, L.

    2011-12-01

    CMS has had an ongoing and dedicated effort to optimize software performance for several years. Initially this effort focused primarily on the cleanup of many issues coming from basic C++ errors, namely reducing dynamic memory churn, unnecessary copies/temporaries and tools to routinely monitor these things. Over the past 1.5 years, however, the transition to 64bit, newer versions of the gcc compiler, newer tools and the enabling of techniques like vectorization have made possible more sophisticated improvements to the software performance. This presentation will cover this evolution and describe the current avenues being pursued for software performance, as well as the corresponding gains.

  3. CMS OnlineWeb-Based Monitoring

    NASA Astrophysics Data System (ADS)

    Badgett, William; Chakaberia, Irakli; Lopez-Perez, Juan Antonio; Maeshima, Kaori; Maruyama, Sho; Soha, Aron; Sulmanas, Balys; Wan, Zongru

    For large international High Energy Physics experiments, modern web technologies make the online monitoring of detector status, data acquisition status, trigger rates, luminosity, etc., accessible for the collaborators anywhere and anytime. This helps the collaborating experts monitor the status of the experiment, identify the problems and improve data taking efficiency. We present the online Web-Based Monitoring project of the CMS experiment at the LHC at CERN.The data sources are relational databasesandvarious messaging systems. The projectprovidesavast amountof in-depth information including real-time data, historical trends and correlations in a user-friendly way.

  4. Searching for extra-dimensions at CMS

    NASA Astrophysics Data System (ADS)

    Benucci, Leonardo

    2009-06-01

    A possible solution to the hierarchy problem is the presence of extra space dimensions beyond the three ones which are known from our everyday experience. The phenomenological ADD model of large extra-dimensions predicts a ETmiss +jet signature. Randall-Sundrum-type extra-dimensions predict di-lepton and di-jet resonances. This contribution addresses an overview of experimental issues and discovery potential for these new particles at the LHC, focusing on perspectives with the CMS detector during early data taking.

  5. HIV-1 Antibody Neutralization Breadth Is Associated with Enhanced HIV-Specific CD4+ T Cell Responses

    PubMed Central

    Soghoian, Damien Z.; Lindqvist, Madelene; Ghebremichael, Musie; Donaghey, Faith; Carrington, Mary; Seaman, Michael S.; Kaufmann, Daniel E.; Walker, Bruce D.

    2015-01-01

    ABSTRACT Antigen-specific CD4+ T helper cell responses have long been recognized to be a critical component of effective vaccine immunity. CD4+ T cells are necessary to generate and maintain humoral immune responses by providing help to antigen-specific B cells for the production of antibodies. In HIV infection, CD4+ T cells are thought to be necessary for the induction of Env-specific broadly neutralizing antibodies. However, few studies have investigated the role of HIV-specific CD4+ T cells in association with HIV neutralizing antibody activity in vaccination or natural infection settings. Here, we conducted a comprehensive analysis of HIV-specific CD4+ T cell responses in a cohort of 34 untreated HIV-infected controllers matched for viral load, with and without neutralizing antibody breadth to a panel of viral strains. Our results show that the breadth and magnitude of Gag-specific CD4+ T cell responses were significantly higher in individuals with neutralizing antibodies than in those without neutralizing antibodies. The breadth of Gag-specific CD4+ T cell responses was positively correlated with the breadth of neutralizing antibody activity. Furthermore, the breadth and magnitude of gp41-specific, but not gp120-specific, CD4+ T cell responses were significantly elevated in individuals with neutralizing antibodies. Together, these data suggest that robust Gag-specific CD4+ T cells and, to a lesser extent, gp41-specific CD4+ T cells may provide important intermolecular help to Env-specific B cells that promote the generation or maintenance of Env-specific neutralizing antibodies. IMPORTANCE One of the earliest discoveries related to CD4+ T cell function was their provision of help to B cells in the development of antibody responses. Yet little is known about the role of CD4+ T helper responses in the setting of HIV infection, and no studies to date have evaluated the impact of HIV-specific CD4+ T cells on the generation of antibodies that can neutralize

  6. Design and performance of the alignment system for the CMS muon endcaps

    SciTech Connect

    Hohlmann, Marcus; Baksay, Gyongyi; Browngold, Max; Dehmelt, Klaus; Guragain, Samir; Andreev, Valery; Yang, Xiaofeng; Bellinger, James; Carlsmith, Duncan; Feyzi, Farshid; Loveless, Richard J.; /Florida Inst. Tech. /UCLA /Wisconsin U., Madison /UC, Davis /Fermilab /St. Petersburg, INP /UC, Riverside

    2006-12-01

    The alignment system for the CMS Muon Endcap detector employs several hundred sensors such as optical 1-D CCD sensors illuminated by lasers and analog distance- and tilt-sensors to monitor the positions of one sixth of 468 large Cathode Strip Chambers. The chambers mounted on the endcap yoke disks undergo substantial deformation on the order of centimeters when the 4T field is switched on and off. The Muon Endcap alignment system is required to monitor chamber positions with 75-200 {micro}m accuracy in the R? plane, {approx}400 {micro}m in the radial direction, and {approx}1 mm in the z-direction along the beam axis. The complete alignment hardware for one of the two endcaps has been installed at CERN. A major system test was performed when the 4T solenoid magnet was ramped up to full field for the first time in August 2006. We present the overall system design and first results on disk deformations, which indicate that the measurements agree with expectations.

  7. Autophagy Restricts HIV-1 Infection by Selectively Degrading Tat in CD4+ T Lymphocytes

    PubMed Central

    Sagnier, Sophie; Daussy, Coralie F.; Borel, Sophie; Robert-Hebmann, Véronique; Faure, Mathias; Blanchet, Fabien P.; Beaumelle, Bruno; Biard-Piechaczyk, Martine

    2014-01-01

    ABSTRACT Autophagy is a ubiquitous mechanism involved in the lysosomal-mediated degradation of cellular components when they are engulfed in vacuoles called autophagosomes. Autophagy is also recognized as an important regulator of the innate and adaptive immune responses against numerous pathogens, which have, therefore, developed strategies to block or use the autophagy machinery to their own benefit. Upon human immunodeficiency virus type 1 (HIV-1) infection, viral envelope (Env) glycoproteins induce autophagy-dependent apoptosis of uninfected bystander CD4+ T lymphocytes, a mechanism likely contributing to the loss of CD4+ T cells. In contrast, in productively infected CD4+ T cells, HIV-1 is able to block Env-induced autophagy in order to avoid its antiviral effect. To date, nothing is known about how autophagy restricts HIV-1 infection in CD4+ T lymphocytes. Here, we report that autophagy selectively degrades the HIV-1 transactivator Tat, a protein essential for viral transcription and virion production. We demonstrated that this selective autophagy-mediated degradation of Tat relies on its ubiquitin-independent interaction with the p62/SQSTM1 adaptor. Taken together, our results provide evidence that the anti-HIV effect of autophagy is specifically due to the degradation of the viral transactivator Tat but that this process is rapidly counteracted by the virus to favor its replication and spread. IMPORTANCE Autophagy is recognized as one of the most ancient and conserved mechanisms of cellular defense against invading pathogens. Cross talk between HIV-1 and autophagy has been demonstrated depending on the virally challenged cell type, and HIV-1 has evolved strategies to block this process to replicate efficiently. However, the mechanisms by which autophagy restricts HIV-1 infection remain to be elucidated. Here, we report that the HIV-1 transactivator Tat, a protein essential for viral replication, is specifically degraded by autophagy in CD4+ T lymphocytes

  8. Optimization of RMP Coils for ELM Control

    NASA Astrophysics Data System (ADS)

    Dutta, Someswar; Evans, T. E.; Orlov, D. M.

    2015-11-01

    Advanced DIII-D RMP coils with improved capabilities are studied using a vacuum island overlap width (VIOW) criterion. Changes in characteristics of the RMP field produced by different geometrical parameters using both ex-vessel (C- and O-) and in-vessel (I- and CP-) coils are discussed. By reducing the poloidal span of each coil, the spacing between them and varying the geometric angle between the coils and the plasma, the resonant field can be adjusted to optimize the edge VIOW criterion while minimizing core resonances. Three separate phase scans using a combination of the as built I-coils and proposed CP-coils are compared for three different equilibria. Two of these equilibria have different edge safety factors and the third one has a different gap between plasma and wall than the standard equilibrium scenario of DIII D. The scan results show that the VIOW correlation criterion is well satisfied in all three cases, resulting in a new way to optimize the RMP coils for the future reactors in order to achieve the ELM suppression criterion over a significantly wider range of fusion plasma operating scenarios. Work supported by the U.S. DOE under DE-FG02-05ER54809 and DE-FC02-04ER54698.

  9. ENGINEERING OF THE AGS SNAKE COIL ASSEMBLY.

    SciTech Connect

    ANERELLA,M.GUPTA,R.KOVACH,P.MARONE,A.PLATE,S.POWER,K.SCHMALZLE,J.WILLEN,E.

    2003-05-12

    A 30% Snake superconducting magnet is proposed to maintain polarization in the AGS proton beam, the magnetic design of which is described elsewhere. The required helical coils for this magnet push the limits of the technology developed for the RHIC Snake coils. First, fields must be provided with differing pitch along the length of the magnet. To accomplish this, a new 3-D CAD system (''Pro/Engineer'' from PTC), which uses parametric techniques to enable fast iterations, has been employed. Revised magnetic field calculations are then based on the output of the mechanical model. Changes are made in turn to the model on the basis of those field calculations. To ensure that accuracy is maintained, the final solid model is imported directly into the CNC machine programming software, rather than by the use of graphics translating software. Next, due to the large coil size and magnetic field, there was concern whether the structure could contain the coil forces. A finite element analysis was performed, using the 3-D model, to ensure that the stresses and deflections were acceptable. Finally, a method was developed using ultrasonic energy to improve conductor placement during coil winding, in an effort to minimize electrical shorts due to conductor misplacement, a problem that occurred in the RHIC helical coil program. Each of these activities represents a significant improvement in technology over that which was used previously for the RHIC snake coils.

  10. Switching transients in a superconducting coil

    SciTech Connect

    Owen, E.W.; Shimer, D.W.

    1983-11-18

    A study is made of the transients caused by the fast dump of large superconducting coils. Theoretical analysis, computer simulation, and actual measurements are used. Theoretical analysis can only be applied to the simplest of models. In the computer simulations two models are used, one in which the coil is divided into ten segments and another in which a single coil is employed. The circuit breaker that interrupts the current to the power supply, causing a fast dump, is represented by a time and current dependent conductance. Actual measurements are limited to measurements made incidental to performance tests on the MFTF Yin-yang coils. It is found that the breaker opening time is the critical factor in determining the size and shape of the transient. Instantaneous opening of the breaker causes a lightly damped transient with large amplitude voltages to ground. Increasing the opening time causes the transient to become a monopulse of decreasing amplitude. The voltages at the external terminals are determined by the parameters of the external circuit. For fast opening times the frequency depends on the dump resistor inductance, the circuit capacitance, and the amplitude on the coil current. For slower openings the dump resistor inductance and the current determine the amplitude of the voltage to ground at the terminals. Voltages to ground are less in the interior of the coil, where transients related to the parameters of the coil itself are observed.

  11. Microsensor coils for miniature fiber optic gyroscopes

    NASA Astrophysics Data System (ADS)

    Ruffin, Paul B.; Baeder, Janet S.

    2004-10-01

    Depolarized Interferometric Fiber Optic Gyroscopes (D-IFOGs) that are constructed with inexpensive single mode (SM) fiber have provided an opportunity for developers to meet Army emerging missions goals for affordable, small volume, reliable inertial guidance systems for use in small missiles, munitions, and future micro-unmanned autonomous vehicles. However, there remain several vital issues associated with substantially reducing the diameter of the sensor coil. Optical fiber that is precision-wound onto a micro coil experiences increased stress due to small radius bending, fiber distortions at crossover sites, and increased interlayer pressures as a result of multiple layers of fiber wound under tension. Tension and small radius bending stresses can have a detrimental effect on the performance of D-IFOGs. Therefore, other scenarios for the application of SM fiber to a micro-sensor coil must be considered. One scheme involves taking advantage of the bending-induced birefringence and employing the low cost SM fiber as a polarization-maintaining (PM) fiber. The mechanics of how a substantial reduction in the coil radius produces PM fiber properties in SM fiber is investigated under this research effort. Conventional and specialty SM fibers are characterized to identify optimal fibers for the development of micro-sensor coils. The results from extinction ratio measurements on the SM fibers and micro-sensor coils are presented in this paper. The significant cross coupling suggests that scattering centers are present in very small radius bending. Also, measurements show that optical loss is significant in micro IFOG coils.

  12. CMS distributed data analysis with CRAB3

    SciTech Connect

    Mascheroni, M.; Balcas, J.; Belforte, S.; Bockelman, B. P.; Hernandez, J. M.; Ciangottini, D.; Konstantinov, P. B.; Silva, J. M. D.; Ali, M. A. B. M.; Melo, A. M.; Riahi, H.; Tanasijczuk, A. J.; Yusli, M. N. B.; Wolf, M.; Woodard, A. E.; Vaandering, E.

    2015-12-23

    The CMS Remote Analysis Builder (CRAB) is a distributed workflow management tool which facilitates analysis tasks by isolating users from the technical details of the Grid infrastructure. Throughout LHC Run 1, CRAB has been successfully employed by an average of 350 distinct users each week executing about 200,000 jobs per day.CRAB has been significantly upgraded in order to face the new challenges posed by LHC Run 2. Components of the new system include 1) a lightweight client, 2) a central primary server which communicates with the clients through a REST interface, 3) secondary servers which manage user analysis tasks and submit jobs to the CMS resource provisioning system, and 4) a central service to asynchronously move user data from temporary storage in the execution site to the desired storage location. Furthermore, the new system improves the robustness, scalability and sustainability of the service.Here we provide an overview of the new system, operation, and user support, report on its current status, and identify lessons learned from the commissioning phase and production roll-out.

  13. Performance of the CMS High Level Trigger

    NASA Astrophysics Data System (ADS)

    Perrotta, Andrea

    2015-12-01

    The CMS experiment has been designed with a 2-level trigger system. The first level is implemented using custom-designed electronics. The second level is the so-called High Level Trigger (HLT), a streamlined version of the CMS offline reconstruction software running on a computer farm. For Run II of the Large Hadron Collider, the increases in center-of-mass energy and luminosity will raise the event rate to a level challenging for the HLT algorithms. The increase in the number of interactions per bunch crossing, on average 25 in 2012, and expected to be around 40 in Run II, will be an additional complication. We present here the expected performance of the main triggers that will be used during the 2015 data taking campaign, paying particular attention to the new approaches that have been developed to cope with the challenges of the new run. This includes improvements in HLT electron and photon reconstruction as well as better performing muon triggers. We will also present the performance of the improved tracking and vertexing algorithms, discussing their impact on the b-tagging performance as well as on the jet and missing energy reconstruction.

  14. CMS distributed data analysis with CRAB3

    DOE PAGESBeta

    Mascheroni, M.; Balcas, J.; Belforte, S.; Bockelman, B. P.; Hernandez, J. M.; Ciangottini, D.; Konstantinov, P. B.; Silva, J. M. D.; Ali, M. A. B. M.; Melo, A. M.; et al

    2015-12-23

    The CMS Remote Analysis Builder (CRAB) is a distributed workflow management tool which facilitates analysis tasks by isolating users from the technical details of the Grid infrastructure. Throughout LHC Run 1, CRAB has been successfully employed by an average of 350 distinct users each week executing about 200,000 jobs per day.CRAB has been significantly upgraded in order to face the new challenges posed by LHC Run 2. Components of the new system include 1) a lightweight client, 2) a central primary server which communicates with the clients through a REST interface, 3) secondary servers which manage user analysis tasks andmore » submit jobs to the CMS resource provisioning system, and 4) a central service to asynchronously move user data from temporary storage in the execution site to the desired storage location. Furthermore, the new system improves the robustness, scalability and sustainability of the service.Here we provide an overview of the new system, operation, and user support, report on its current status, and identify lessons learned from the commissioning phase and production roll-out.« less

  15. Status of the CMS Detector Control System

    NASA Astrophysics Data System (ADS)

    Bauer, Gerry; Behrens, Ulf; Bowen, Matthew; Branson, James; Bukowiec, Sebastian; Cittolin, Sergio; Coarasa, Jose Antonio; Deldicque, Christian; Dobson, Marc; Dupont, Aymeric; Erhan, Samim; Flossdorf, Alexander; Gigi, Dominique; Glege, Frank; Gomez-Reino, Robert; Hartl, Christian; Hegeman, Jeroen; Holzner, Andre; Hwong, Yi Ling; Masetti, Lorenzo; Meijers, Frans; Meschi, Emilio; Mommsen, Remigius K.; O'Dell, Vivian; Orsini, Luciano; Paus, Christoph; Petrucci, Andrea; Pieri, Marco; Polese, Giovanni; Racz, Attila; Raginel, Olivier; Sakulin, Hannes; Sani, Matteo; Schwick, Christoph; Shpakov, Dennis; Simon, Michal; Cristian Spataru, Andrei; Sumorok, Konstanty

    2012-12-01

    The Compact Muon Solenoid (CMS) is a CERN multi-purpose experiment that exploits the physics of the Large Hadron Collider (LHC). The Detector Control System (DCS) is responsible for ensuring the safe, correct and efficient operation of the experiment, and has contributed to the recording of high quality physics data. The DCS is programmed to automatically react to the LHC operational mode. CMS sub-detectors’ bias voltages are set depending on the machine mode and particle beam conditions. An operator provided with a small set of screens supervises the system status summarized from the approximately 6M monitored parameters. Using the experience of nearly two years of operation with beam the DCS automation software has been enhanced to increase the system efficiency by minimizing the time required by sub-detectors to prepare for physics data taking. From the infrastructure point of view the DCS will be subject to extensive modifications in 2012. The current rack mounted control PCs will be replaced by a redundant pair of DELL Blade systems. These blade servers are a high-density modular solution that incorporates servers and networking into a single chassis that provides shared power, cooling and management. This infrastructure modification associated with the migration to blade servers will challenge the DCS software and hardware factorization capabilities. The on-going studies for this migration together with the latest modifications are discussed in the paper.

  16. CMS distributed data analysis with CRAB3

    NASA Astrophysics Data System (ADS)

    Mascheroni, M.; Balcas, J.; Belforte, S.; Bockelman, B. P.; Hernandez, J. M.; Ciangottini, D.; Konstantinov, P. B.; Silva, J. M. D.; Ali, M. A. B. M.; Melo, A. M.; Riahi, H.; Tanasijczuk, A. J.; Yusli, M. N. B.; Wolf, M.; Woodard, A. E.; Vaandering, E.

    2015-12-01

    The CMS Remote Analysis Builder (CRAB) is a distributed workflow management tool which facilitates analysis tasks by isolating users from the technical details of the Grid infrastructure. Throughout LHC Run 1, CRAB has been successfully employed by an average of 350 distinct users each week executing about 200,000 jobs per day. CRAB has been significantly upgraded in order to face the new challenges posed by LHC Run 2. Components of the new system include 1) a lightweight client, 2) a central primary server which communicates with the clients through a REST interface, 3) secondary servers which manage user analysis tasks and submit jobs to the CMS resource provisioning system, and 4) a central service to asynchronously move user data from temporary storage in the execution site to the desired storage location. The new system improves the robustness, scalability and sustainability of the service. Here we provide an overview of the new system, operation, and user support, report on its current status, and identify lessons learned from the commissioning phase and production roll-out.

  17. Status of the CMS pixel project

    SciTech Connect

    Uplegger, Lorenzo; /Fermilab

    2008-01-01

    The Compact Muon Solenoid Experiment (CMS) will start taking data at the Large Hadron Collider (LHC) in 2008. The closest detector to the interaction point is the silicon pixel detector which is the heart of the tracking system. It consists of three barrel layers and two pixel disks on each side of the interaction point for a total of 66 million channels. Its proximity to the interaction point means there will be very large particle fluences and therefore a radiation-tolerant design is necessary. The pixel detector will be crucial to achieve a good vertex resolution and will play a key role in pattern recognition and track reconstruction. The results from test beam runs prove that the expected performances can be achieved. The detector is currently being assembled and will be ready for insertion into CMS in early 2008. During the assembly phase, a thorough electronic test is being done to check the functionality of each channel to guarantee the performance required to achieve the physics goals. This report will present the final detector design, the status of the production as well as results from test beam runs to validate the expected performance.

  18. Phase reconstruction from multiple coil data using a virtual reference coil

    PubMed Central

    Parker, Dennis L.; Payne, Allison; Todd, Nick; Hadley, J. Rock

    2013-01-01

    Purpose This paper develops a method to obtain optimal estimates of absolute magnetization phase from multiple-coil MRI data. Methods The element-specific phases of a multi-element receiver coil array are accounted for by using the phase of a real or virtual reference coil that is sensitive over the entire imaged volume. The virtual-reference coil is generated as a weighted combination of measurements from all receiver coils. The phase-corrected multiple coil complex images are combined using the inverse covariance matrix. These methods are tested on images of an agar phantom, an in vivo breast, and an anesthetized rabbit obtained using combinations of four, nine, and three receiver channels, respectively. Results The four- and three- channel acquisitions require formation of a virtual-reference receiver coil while one channel of the nine-channel receive array has a sensitivity profile covering the entire imaged volume. Referencing to a real or virtual coil gives receiver phases that are essentially identical except for the individual receiver channel noise. The resulting combined images, which account for receiver channel noise covariance, show the expected reduction in phase variance. Conclusions The proposed virtual reference coil method determines a phase distribution for each coil from which an optimal phase map can be obtained. PMID:24006172

  19. Crystal Structure of the Central Coiled-Coil Domain from Human Liprin-[beta]2

    SciTech Connect

    Stafford, Ryan L.; Tang, Ming-Yun; Sawaya, Michael R.; Phillips, Martin L.; Bowie, James U.

    2012-02-07

    Liprins are a conserved family of scaffolding proteins important for the proper regulation and development of neuronal synapses. Humans have four liprin-{alpha}s and two liprin-{beta}s which all contain long coiled-coil domains followed by three tandem SAM domains. Complex interactions between the coiled-coil and SAM domains are thought to create liprin scaffolds, but the structural and biochemical properties of these domains remain largely uncharacterized. In this study we find that the human liprin-{beta}2 coiled-coil forms an extended dimer. Several protease-resistant subdomains within the liprin-{beta}1 and liprin-{beta}2 coiled-coils were also identified. A 2.0 {angstrom} crystal structure of the central, protease-resistant core of the liprin-{beta}2 coiled-coil reveals a parallel helix orientation. These studies represent an initial step toward determining the overall architecture of liprin scaffolds and understanding the molecular basis for their synaptic functions.

  20. Crystal Structure of a Coiled-Coil Domain from Human ROCK I

    PubMed Central

    Tu, Daqi; Li, Yiqun; Song, Hyun Kyu; Toms, Angela V.; Gould, Christopher J.; Ficarro, Scott B.; Marto, Jarrod A.; Goode, Bruce L.; Eck, Michael J.

    2011-01-01

    The small GTPase Rho and one of its targets, Rho-associated kinase (ROCK), participate in a variety of actin-based cellular processes including smooth muscle contraction, cell migration, and stress fiber formation. The ROCK protein consists of an N-terminal kinase domain, a central coiled-coil domain containing a Rho binding site, and a C-terminal pleckstrin homology domain. Here we present the crystal structure of a large section of the central coiled-coil domain of human ROCK I (amino acids 535–700). The structure forms a parallel α-helical coiled-coil dimer that is structurally similar to tropomyosin, an actin filament binding protein. There is an unusual discontinuity in the coiled-coil; three charged residues (E613, R617 and D620) are positioned at what is normally the hydrophobic core of coiled-coil packing. We speculate that this conserved irregularity could function as a hinge that allows ROCK to adopt its autoinhibited conformation. PMID:21445309

  1. A Synthetic Coiled-Coil Interactome Provides Heterospecific Modules for Molecular Engineering

    SciTech Connect

    Reinke, Aaron W.; Grant, Robert A.; Keating, Amy E.

    2010-06-21

    The versatile coiled-coil protein motif is widely used to induce and control macromolecular interactions in biology and materials science. Yet the types of interaction patterns that can be constructed using known coiled coils are limited. Here we greatly expand the coiled-coil toolkit by measuring the complete pairwise interactions of 48 synthetic coiled coils and 7 human bZIP coiled coils using peptide microarrays. The resulting 55-member protein 'interactome' includes 27 pairs of interacting peptides that preferentially heteroassociate. The 27 pairs can be used in combinations to assemble sets of 3 to 6 proteins that compose networks of varying topologies. Of special interest are heterospecific peptide pairs that participate in mutually orthogonal interactions. Such pairs provide the opportunity to dimerize two separate molecular systems without undesired crosstalk. Solution and structural characterization of two such sets of orthogonal heterodimers provide details of their interaction geometries. The orthogonal pair, along with the many other network motifs discovered in our screen, provide new capabilities for synthetic biology and other applications.

  2. Vaccine-Induced CD107a+ CD4+ T Cells Are Resistant to Depletion following AIDS Virus Infection

    PubMed Central

    Terahara, Kazutaka; Ishii, Hiroshi; Nomura, Takushi; Takahashi, Naofumi; Takeda, Akiko; Shiino, Teiichiro; Tsunetsugu-Yokota, Yasuko

    2014-01-01

    ABSTRACT CD4+ T-cell responses are crucial for effective antibody and CD8+ T-cell induction following virus infection. However, virus-specific CD4+ T cells can be preferential targets for human immunodeficiency virus (HIV) infection. HIV-specific CD4+ T-cell induction by vaccination may thus result in enhancement of virus replication following infection. In the present study, we show that vaccine-elicited CD4+ T cells expressing CD107a are relatively resistant to depletion in a macaque AIDS model. Comparison of virus-specific CD107a, macrophage inflammatory protein-1β, gamma interferon, tumor necrosis factor alpha, and interleukin-2 responses in CD4+ T cells of vaccinated macaques prechallenge and 1 week postchallenge showed a significant reduction in the CD107a− but not the CD107a+ subset after virus exposure. Those vaccinees that failed to control viremia showed a more marked reduction and exhibited significantly higher viral loads at week 1 than unvaccinated animals. Our results indicate that vaccine-induced CD107a− CD4+ T cells are depleted following virus infection, suggesting a rationale for avoiding virus-specific CD107a− CD4+ T-cell induction in HIV vaccine design. IMPORTANCE Induction of effective antibody and/or CD8+ T-cell responses is a principal vaccine strategy against human immunodeficiency virus (HIV) infection. CD4+ T-cell responses are crucial for effective antibody and CD8+ T-cell induction. However, virus-specific CD4+ T cells can be preferential targets for HIV infection. Here, we show that vaccine-induced virus-specific CD107a− CD4+ T cells are largely depleted following infection in a macaque AIDS model. While CD4+ T-cell responses are important in viral control, our results indicate that virus-specific CD107a− CD4+ T-cell induction by vaccination may not lead to efficient CD4+ T-cell responses following infection but rather be detrimental and accelerate viral replication in the acute phase. This suggests that HIV vaccine design

  3. Comparison of Coil and Kiil Dialysers

    PubMed Central

    Down, P. F.; Farrand, D. E.; Wood, S. E.; Lee, H. A.

    1970-01-01

    To assess the comparative efficiency, safety, and cost of maintenance dialysis, the treatment of 13 patients with a Kiil dialyser (representing 1,477 hospital and 735 home dialyses) was compared with that of 11 patients using a coil dialyser (898 hospital and 396 home dialyses). Kiil and coil dialysers proved equally satisfactory from a medical standpoint and equally acceptable to the patients. The capital costs of home dialysis were considerably reduced without any threat to safety or efficiency. The running costs of coil dialysers approximate to those of Kiil dialysers. ImagesFig. 3 PMID:4320676

  4. Coiled Fiber Pulsed Laser Simulator

    Energy Science and Technology Software Center (ESTSC)

    2009-01-29

    This suite of codes simulates the transient output pulse from an optically-pumped coiled fiber amplifier. The input pulse is assumed to have a Gaussian time dependence and a spatial dependence that may be Gaussian or an eigenmode of the straight of bent fiber computed using bend10 or bend20. Only one field component is used (semivectorial approximation). The fully-spatially-dependent fiber gain profile is specified is subroutines "inversion" and "interp_inversion" and is presently read from a datamore » file, although other means of specifying fiber gain could be reallized through modification of these subroutines. The input pulse is propagated through the fiber, including the following physical effects: spatial and temporal gain saturation, self-focusing, bend losses, and confinement from a user-defined fiber index profile. The user can follow the propagation progress with 3D graphics that show an intensity profile via user-modifiable cutting planes through the time space axes. A restart capability is also included. Approximate solutions in the frequency domain may be obtained much faster using the auxilliary codes bendbpm10 (full vector), bendbpm20 (semivectoral), and bendbpm21 (semivectoral with gain sheet spproximation for gain and self-focusing). These codes all include bend loss and spatial (but not temporal) gain saturation.« less

  5. Helical coil thermal hydraulic model

    NASA Astrophysics Data System (ADS)

    Caramello, M.; Bertani, C.; De Salve, M.; Panella, B.

    2014-11-01

    A model has been developed in Matlab environment for the thermal hydraulic analysis of helical coil and shell steam generators. The model considers the internal flow inside one helix and its associated control volume of water on the external side, both characterized by their inlet thermodynamic conditions and the characteristic geometry data. The model evaluates the behaviour of the thermal-hydraulic parameters of the two fluids, such as temperature, pressure, heat transfer coefficients, flow quality, void fraction and heat flux. The evaluation of the heat transfer coefficients as well as the pressure drops has been performed by means of the most validated literature correlations. The model has been applied to one of the steam generators of the IRIS modular reactor and a comparison has been performed with the RELAP5/Mod.3.3 code applied to an inclined straight pipe that has the same length and the same elevation change between inlet and outlet of the real helix. The predictions of the developed model and RELAP5/Mod.3.3 code are in fairly good agreement before the dryout region, while the dryout front inside the helical pipes is predicted at a lower distance from inlet by the model.

  6. Coiled Fiber Pulsed Laser Simulator

    SciTech Connect

    Hadley, G. Ronald

    2009-01-29

    This suite of codes simulates the transient output pulse from an optically-pumped coiled fiber amplifier. The input pulse is assumed to have a Gaussian time dependence and a spatial dependence that may be Gaussian or an eigenmode of the straight of bent fiber computed using bend10 or bend20. Only one field component is used (semivectorial approximation). The fully-spatially-dependent fiber gain profile is specified is subroutines "inversion" and "interp_inversion" and is presently read from a data file, although other means of specifying fiber gain could be reallized through modification of these subroutines. The input pulse is propagated through the fiber, including the following physical effects: spatial and temporal gain saturation, self-focusing, bend losses, and confinement from a user-defined fiber index profile. The user can follow the propagation progress with 3D graphics that show an intensity profile via user-modifiable cutting planes through the time space axes. A restart capability is also included. Approximate solutions in the frequency domain may be obtained much faster using the auxilliary codes bendbpm10 (full vector), bendbpm20 (semivectoral), and bendbpm21 (semivectoral with gain sheet spproximation for gain and self-focusing). These codes all include bend loss and spatial (but not temporal) gain saturation.

  7. Higgs Boson Search at LHC (and LHC/CMS status)

    SciTech Connect

    Korytov, Andrey

    2008-11-23

    Presented are the results of the most recent studies by the CMS and ATLAS collaborations on the expected sensitivity of their detectors to observing a Higgs boson at LHC. The overview is preceded with a brief summary of the LHC and the CMS Experiment status.

  8. Prospects for SUSY searches in CMS and ATLAS

    SciTech Connect

    Jong, Paul de

    2008-11-23

    We discuss how the CMS and ATLAS experiments are preparing for the analysis of first LHC data with emphasis on the search for supersymmetry. We will show the importance of the understanding of detector, trigger, reconstruction and backgrounds, and we will present realistic estimates of the reach of CMS and ATLAS.

  9. Proteomic Analysis of Male-Fertility Restoration in CMS Onion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The production of hybrid-onion seed is dependent on cytoplasmic-genic male sterility (CMS) systems. For the most commonly used CMS, male-sterile (S) cytoplasm interacts with a dominant allele at one nuclear male-fertility restoration locus (Ms) to condition male fertility. We are using proteomics ...

  10. Proteomic analyses of male-fertility restoration in CMS onion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The production of hybrid-onion seed is dependent on cytoplasmic-genic male sterility (CMS) systems. For the most commonly used CMS, male-sterile (S) cytoplasm interacts with a dominant allele at one nuclear male-fertility restoration locus (Ms) to condition male fertility. We are using a proteomics ...

  11. 42 CFR 405.1834 - CMS reviewing official procedure.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false CMS reviewing official procedure. 405.1834 Section 405.1834 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM FEDERAL HEALTH INSURANCE FOR THE AGED AND DISABLED Provider Reimbursement Determinations and Appeals § 405.1834 CMS...

  12. 42 CFR 422.2264 - Guidelines for CMS review.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 3 2014-10-01 2014-10-01 false Guidelines for CMS review. 422.2264 Section 422.2264 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 422.2264 Guidelines for CMS review. In reviewing marketing material or election forms under §...

  13. 42 CFR 423.2264 - Guidelines for CMS review.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 3 2012-10-01 2012-10-01 false Guidelines for CMS review. 423.2264 Section 423.2264 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Requirements § 423.2264 Guidelines for CMS review. In reviewing marketing material or enrollment forms...

  14. 42 CFR 423.2264 - Guidelines for CMS review.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 3 2014-10-01 2014-10-01 false Guidelines for CMS review. 423.2264 Section 423.2264 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Requirements § 423.2264 Guidelines for CMS review. In reviewing marketing material or enrollment forms...

  15. 42 CFR 422.2264 - Guidelines for CMS review.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 3 2012-10-01 2012-10-01 false Guidelines for CMS review. 422.2264 Section 422.2264 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 422.2264 Guidelines for CMS review. In reviewing marketing material or election forms under §...

  16. 42 CFR 411.379 - When CMS accepts a request.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 2 2013-10-01 2013-10-01 false When CMS accepts a request. 411.379 Section 411.379 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE... receiving a request for an advisory opinion, CMS promptly makes an initial determination of whether...

  17. 42 CFR 411.379 - When CMS accepts a request.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 2 2014-10-01 2014-10-01 false When CMS accepts a request. 411.379 Section 411.379 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE... receiving a request for an advisory opinion, CMS promptly makes an initial determination of whether...

  18. 42 CFR 411.379 - When CMS accepts a request.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false When CMS accepts a request. 411.379 Section 411.379 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE... receiving a request for an advisory opinion, CMS promptly makes an initial determination of whether...

  19. 42 CFR 411.379 - When CMS accepts a request.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false When CMS accepts a request. 411.379 Section 411.379 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE... receiving a request for an advisory opinion, CMS promptly makes an initial determination of whether...

  20. 42 CFR 411.379 - When CMS accepts a request.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 2 2012-10-01 2012-10-01 false When CMS accepts a request. 411.379 Section 411.379 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE... receiving a request for an advisory opinion, CMS promptly makes an initial determination of whether...

  1. 42 CFR 422.210 - Assurances to CMS.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Assurances to CMS. 422.210 Section 422.210 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM MEDICARE ADVANTAGE PROGRAM Relationships With Providers § 422.210 Assurances to CMS....

  2. 26 CFR 1.6664-4T - Reasonable cause and good faith exception to section 6662 penalties.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Reasonable cause and good faith exception to section 6662 penalties. 1.6664-4T Section 1.6664-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Additions to the Tax,...

  3. Green tea epigallocatechin-3-gallate modulates differentiation of naive CD4+ T cells into specific lineage effector cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    CD4+ T helper (Th) subsets Th1, Th9, and Th17 cells are implicated in inducing autoimmunity whereas regulatory T cells (Treg) have a protective effect. We previously showed that epigallocatechin-3-gallate (EGCG) attenuated experimental autoimmune encephalomyelitis (EAE) and altered CD4+ T cell subpo...

  4. 26 CFR 1.79-4T - Questions and answers relating to the nondiscrimination requirements for group-term life...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... nondiscrimination requirements for group-term life insurance (temporary). 1.79-4T Section 1.79-4T Internal Revenue... nondiscrimination requirements for group-term life insurance (temporary). Q-1: When does section 79, as amended by..., however, several exceptions to this effective date where there is coverage under a group-term...

  5. 26 CFR 1.79-4T - Questions and answers relating to the nondiscrimination requirements for group-term life...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... nondiscrimination requirements for group-term life insurance (temporary). 1.79-4T Section 1.79-4T Internal Revenue... nondiscrimination requirements for group-term life insurance (temporary). Q-1: When does section 79, as amended by..., however, several exceptions to this effective date where there is coverage under a group-term...

  6. 26 CFR 1.79-4T - Questions and answers relating to the nondiscrimination requirements for group-term life...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... nondiscrimination requirements for group-term life insurance (temporary). 1.79-4T Section 1.79-4T Internal Revenue... nondiscrimination requirements for group-term life insurance (temporary). Q-1: When does section 79, as amended by..., however, several exceptions to this effective date where there is coverage under a group-term...

  7. 26 CFR 1.79-4T - Questions and answers relating to the nondiscrimination requirements for group-term life...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... nondiscrimination requirements for group-term life insurance (temporary). 1.79-4T Section 1.79-4T Internal Revenue... nondiscrimination requirements for group-term life insurance (temporary). Q-1: When does section 79, as amended by..., however, several exceptions to this effective date where there is coverage under a group-term...

  8. 26 CFR 1.79-4T - Questions and answers relating to the nondiscrimination requirements for group-term life...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... nondiscrimination requirements for group-term life insurance (temporary). 1.79-4T Section 1.79-4T Internal Revenue... nondiscrimination requirements for group-term life insurance (temporary). Q-1: When does section 79, as amended by..., however, several exceptions to this effective date where there is coverage under a group-term...

  9. Elevated expression of T-bet in mycobacterial antigen-specific CD4(+) T cells from patients with tuberculosis.

    PubMed

    Yang, Bingfen; Zhai, Fei; Jiang, Jing; Wang, Xinjing; Cao, Zhihong; Cheng, Xiaoxing

    2015-01-01

    T-bet is a T-box transcriptional factor that controls the differentiation and effector functions of CD4 T cells. In this study, we studied the role of T-bet in regulating CD4(+) T cell immunity against tuberculosis (TB). T-bet expression in Mycobacterium tuberculosis antigen-specific CD4(+) T cells was significantly higher in patients with active TB than in individuals with latent TB infection (p<0.0001). Comparison of T-bet expression in TCM and TEM subsets showed that CD4(+)T-bet(+)M. tuberculosis antigen-specific CD4(+) T cells had significantly lower frequency of TCM (p=0.003) and higher frequency of TEM (p=0.003) than CD4(+)T-bet(-) cells. The expression of PD-1 in antigen-specific CD4(+) T cells was significantly higher in patients with TB than in individuals with latent TB infection (p=0.006). CD4(+)CD154(+)T-bet(+) T cells had significantly higher expression of PD-1 than CD4(+)CD154(+)T-bet(-) T cells (p=0.0028). It is concluded that T-bet expression might be associated with differentiation into effector memory cells and PD-1 expression in mycobacterial antigen-specific CD4(+) T cells. PMID:26302932

  10. Genome Sequence of Anaerobacillus macyae JMM-4T (DSM 16346), the First Genomic Information of the Newly Established Genus Anaerobacillus

    PubMed Central

    Wang, Jie-ping; Liu, Guo-hong; Ge, Ci-bin; Chen, Qian-qian; Zhu, Yu-jing; Chen, Zheng

    2015-01-01

    Anaerobacillus macyae JMM-4T (DSM 16346) is a Gram-positive, spore-forming, strictly anaerobic, and arsenate-respiring bacterium. Here, we report the 4.26-Mb genome sequence of A. macyae JMM-4T, which is the first genome information of the newly established genus Anaerobacillus. PMID:26272580

  11. Genome Sequence of Anaerobacillus macyae JMM-4T (DSM 16346), the First Genomic Information of the Newly Established Genus Anaerobacillus.

    PubMed

    Wang, Jie-Ping; Liu, Bo; Liu, Guo-Hong; Ge, Ci-Bin; Chen, Qian-Qian; Zhu, Yu-Jing; Chen, Zheng

    2015-01-01

    Anaerobacillus macyae JMM-4(T) (DSM 16346) is a Gram-positive, spore-forming, strictly anaerobic, and arsenate-respiring bacterium. Here, we report the 4.26-Mb genome sequence of A. macyae JMM-4(T), which is the first genome information of the newly established genus Anaerobacillus. PMID:26272580

  12. CD4+ T cells from MHC II-dependent thymocyte–thymocyte interaction provide efficient help for B cells

    PubMed Central

    Kim, Eun Ji; Choi, Bomi; Moon, Hana; Lee, You Jeong; Jeon, Yoon Kyeong; Park, Seong Hoe; Kim, Tae Jin; Jung, Kyeong Cheon

    2011-01-01

    Recently, a novel CD4+ T-cell developmental pathway was reported that generates thymocyte–thymocyte (T–T) CD4+ T cells. We established a mouse system (CIITAtgCIITApIV−/−) where thymic positive selection occurred only by major histocompatibility complex (MHC) class II+ thymocytes. T–T CD4+ T cells selected via MHC class II-dependent T–T interaction are comprised of PLZF-negative and innate PLZF-positive populations. Until recently, the functional role of the PLZF-negative population was unclear. In this study, we demonstrate that naïve T–T CD4+ T cells provide B-cell help to a level comparable with that of naïve conventional CD4+ T cells. Considering the absence of PLZF expression in naïve T–T CD4+ T cells, these results suggest that PLZF-negative naïve T–T CD4+ T cells are functionally equivalent to conventional naïve CD4+ T cells in terms of B-cell help. PMID:21358747

  13. 26 CFR 1.103(n)-4T - Elective carryforward of unused private activity bond limit (temporary).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... unused private activity bond limit in order to provide a sports facility described in section 103(b)(4)(B... carry forward its unused private activity bond limit in order to issue an exempt small issue of... bond limit (temporary). 1.103(n)-4T Section 1.103(n)-4T Internal Revenue INTERNAL REVENUE...

  14. 26 CFR 1.103(n)-4T - Elective carryforward of unused private activity bond limit (temporary).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... unused private activity bond limit in order to provide a sports facility described in section 103(b)(4)(B... carry forward its unused private activity bond limit in order to issue an exempt small issue of... bond limit (temporary). 1.103(n)-4T Section 1.103(n)-4T Internal Revenue INTERNAL REVENUE...

  15. 26 CFR 1.103(n)-4T - Elective carryforward of unused private activity bond limit (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... unused private activity bond limit in order to provide a sports facility described in section 103(b)(4)(B... carry forward its unused private activity bond limit in order to issue an exempt small issue of... bond limit (temporary). 1.103(n)-4T Section 1.103(n)-4T Internal Revenue INTERNAL REVENUE...

  16. Relationships between LDH-A, Lactate and Metastases in 4T1 Breast Tumors

    PubMed Central

    Rizwan, Asif; Serganova, Inna; Khanin, Raya; Karabeber, Hazem; Ni, Xiaohui; Thakur, Sunitha; Zakian, Kristen L.; Blasberg, Ronald; Koutcher, Jason A.

    2013-01-01

    Purpose To investigate the relationship between LDH-A expression, lactate concentration, cell metabolism and metastases in murine 4T1 breast tumors. Experimental Design Inhibition of LDH-A expression and protein levels were achieved in a metastatic breast cancer cell line (4T1) using shRNA technology. The relationship between tumor LDH-A protein levels and lactate concentration (measured by magnetic resonance spectroscopic imaging-MRSI) and metastases was assessed. Results LDH-A knockdown cells (KD9) showed a significant reduction in LDH-A protein and LDH activity, less acid production, decreased transwell migration and invasion, lower proliferation, reduced glucose utilization and glycolysis and increase in oxygen consumption, ROS and cellular ATP levels, compared to control (NC) cells cultured in 25 mM glucose. In vivo studies showed lower lactate levels in KD9, KD5, KD317 tumors than in NC or 4T1 wild-type tumors (p<0.01), and a linear relationship between tumor LDH-A protein expression and lactate concentration. Metastases were delayed and primary tumor growth rate decreased. Conclusions We show for the first time that LDH-A knockdown inhibited the formation of metastases, and was accompanied by in vivo changes in tumor cell metabolism. Lactate MRSI can be used as a surrogate to monitor targeted inhibition of LDH-A in a pre-clinical setting and provides a non-invasive imaging strategy to monitor LDH-A targeted therapy. This imaging strategy can be translated to the clinic to identify and monitor patients who are at high risk of developing metastatic disease. PMID:23833310

  17. Specific CD4+ T-Cell Reactivity and Cytokine Release in Different Clinical Presentations of Leptospirosis.

    PubMed

    Volz, Magdalena Sarah; Moos, Verena; Allers, Kristina; Luge, Enno; Mayer-Scholl, Anne; Nöckler, Karsten; Loddenkemper, Christoph; Jansen, Andreas; Schneider, Thomas

    2015-12-01

    Clinical manifestations of leptospirosis are highly variable: from asymptomatic to severe and potentially fatal. The outcome of the disease is usually determined in the immunological phase, beginning in the second week of symptoms. The underlying mechanisms, predictive factors, and individual immune responses that contribute to clinical variations are not well understood. The aim of this study was to determine the specifics of CD4(+) T-cell reactivity and cytokine release after stimulation with leptospiral antigens in patients with leptospirosis of different disease severities (patients with mild and severe symptoms) and in control subjects (with and without proven exposure to Leptospira). Whole-blood specimens were stimulated with Leptospira antigens in vitro. Subsequently, intracellular staining of cytokines was performed, and flow cytometry was used to assess the expression of CD40 ligand (CD40L) and the production of gamma interferon (IFN-γ), interleukin-10 (IL-10), IL-2, and tumor necrosis factor alpha (TNF-α) by CD4(+) T cells. The production of inflammatory cytokines such as TNF-α by CD4(+) T cells after stimulation with leptospiral antigens was highest in patients with severe disease. In contrast, the ratio of IL-10 production to TNF-α production was higher in exposed subjects than in patients with mild and severe disease. Levels of proinflammatory cytokines such as TNF-α may be useful markers of the severity of the immunological phase of leptospirosis. IL-10 production by T cells after antigen-specific stimulation may indicate a more successful downregulation of the inflammatory response and may contribute to an asymptomatic course of the disease. PMID:26491036

  18. CD4(+) T-Cell-Independent Secondary Immune Responses to Pneumocystis Pneumonia.

    PubMed

    de la Rua, Nicholas M; Samuelson, Derrick R; Charles, Tysheena P; Welsh, David A; Shellito, Judd E

    2016-01-01

    Pneumocystis pneumonia is a major cause of morbidity and mortality among immunocompromised patients, especially in the context of HIV/AIDS. In the murine model of Pneumocystis pneumonia, CD4(+) T-cells are required for clearance of a primary infection of Pneumocystis, but not the memory recall response. We hypothesized that the memory recall response in the absence of CD4(+) T-cells is mediated by a robust memory humoral response, CD8(+) T-cells, and IgG-mediated phagocytosis by alveolar macrophages. To investigate the role of CD8(+) T-cells and alveolar macrophages in the immune memory response to Pneumocystis, mice previously challenged with Pneumocystis were depleted of CD8(+) T-cells or alveolar macrophages prior to re-infection. Mice depleted of CD4(+) T-cells prior to secondary challenge cleared Pneumocystis infection within 48 h identical to immunocompetent mice during a secondary memory recall response. However, loss of CD8(+) T-cells or macrophages prior to the memory recall response significantly impaired Pneumocystis clearance. Specifically, mice depleted of CD8(+) T-cells or alveolar macrophages had significantly higher fungal burden in the lungs. Furthermore, loss of alveolar macrophages significantly skewed the lung CD8(+) T-cell response toward a terminally differentiated effector memory population and increased the percentage of IFN-γ(+) CD8(+) T-cells. Finally, Pneumocystis-infected animals produced significantly more bone marrow plasma cells and Pneumocystis-specific IgG significantly increased macrophage-mediated killing of Pneumocystis in vitro. These data suggest that secondary immune memory responses to Pneumocystis are mediated, in part, by CD8(+) T-cells, alveolar macrophages, and the production of Pneumocystis-specific IgG. PMID:27242785

  19. CD4+ T-Cell-Independent Secondary Immune Responses to Pneumocystis Pneumonia

    PubMed Central

    de la Rua, Nicholas M.; Samuelson, Derrick R.; Charles, Tysheena P.; Welsh, David A.; Shellito, Judd E.

    2016-01-01

    Pneumocystis pneumonia is a major cause of morbidity and mortality among immunocompromised patients, especially in the context of HIV/AIDS. In the murine model of Pneumocystis pneumonia, CD4+ T-cells are required for clearance of a primary infection of Pneumocystis, but not the memory recall response. We hypothesized that the memory recall response in the absence of CD4+ T-cells is mediated by a robust memory humoral response, CD8+ T-cells, and IgG-mediated phagocytosis by alveolar macrophages. To investigate the role of CD8+ T-cells and alveolar macrophages in the immune memory response to Pneumocystis, mice previously challenged with Pneumocystis were depleted of CD8+ T-cells or alveolar macrophages prior to re-infection. Mice depleted of CD4+ T-cells prior to secondary challenge cleared Pneumocystis infection within 48 h identical to immunocompetent mice during a secondary memory recall response. However, loss of CD8+ T-cells or macrophages prior to the memory recall response significantly impaired Pneumocystis clearance. Specifically, mice depleted of CD8+ T-cells or alveolar macrophages had significantly higher fungal burden in the lungs. Furthermore, loss of alveolar macrophages significantly skewed the lung CD8+ T-cell response toward a terminally differentiated effector memory population and increased the percentage of IFN-γ+ CD8+ T-cells. Finally, Pneumocystis-infected animals produced significantly more bone marrow plasma cells and Pneumocystis-specific IgG significantly increased macrophage-mediated killing of Pneumocystis in vitro. These data suggest that secondary immune memory responses to Pneumocystis are mediated, in part, by CD8+ T-cells, alveolar macrophages, and the production of Pneumocystis-specific IgG. PMID:27242785

  20. Communication between Human Dendritic Cell Subsets in Tuberculosis: Requirements for Naive CD4+ T Cell Stimulation

    PubMed Central

    Lozza, Laura; Farinacci, Maura; Bechtle, Marina; Stäber, Manuela; Zedler, Ulrike; Baiocchini, Andrea; del Nonno, Franca; Kaufmann, Stefan H. E.

    2014-01-01

    Human primary dendritic cells (DCs) are heterogeneous by phenotype, function, and tissue localization and distinct from inflammatory monocyte-derived DCs. Current information regarding the susceptibility and functional role of primary human DC subsets to Mycobacterium tuberculosis (Mtb) infection is limited. Here, we dissect the response of different primary DC subsets to Mtb infection. Myeloid CD11c+ cells and pDCs (C-type lectin 4C+ cells) were located in human lymph nodes (LNs) of tuberculosis (TB) patients by histochemistry. Rare CD141hi DCs (C-type lectin 9A+ cells) were also identified. Infection with live Mtb revealed a higher responsiveness of myeloid CD1c+ DCs compared to CD141hi DCs and pDCs. CD1c+ DCs produced interleukin (IL)-6, tumor necrosis factor α, and IL-1β but not IL-12p70, a cytokine important for Th1 activation and host defenses against Mtb. Yet, CD1c+ DCs were able to activate autologous naïve CD4+ T cells. By combining cell purification with fluorescence-activated cell sorting and gene expression profiling on rare cell populations, we detected in responding CD4+ T cells, genes related to effector-cytolytic functions and transcription factors associated with Th1, Th17, and Treg polarization, suggesting multifunctional properties in our experimental conditions. Finally, immunohistologic analyses revealed contact between CD11c+ cells and pDCs in LNs of TB patients and in vitro data suggest that cooperation between Mtb-infected CD1c+ DCs and pDCs favors stimulation of CD4+ T cells. PMID:25071784

  1. Reviving function in CD4+ T cells adapted to persistent systemic antigen.

    PubMed

    Noval Rivas, Magali; Weatherly, Kathleen; Hazzan, Marc; Vokaer, Benoit; Dremier, Sarah; Gaudray, Florence; Goldman, Michel; Salmon, Isabelle; Braun, Michel Y

    2009-10-01

    In bone marrow-transplanted patients, chronic graft-versus-host disease is a complication that results from the persistent stimulation of recipient minor histocompatibility Ag (mHA)-specific T cells contained within the graft. In this study, we developed a mouse model where persistent stimulation of donor T cells by recipient's mHA led to multiorgan T cell infiltration. Exposure to systemic mHA, however, deeply modified T cell function and chronically stimulated T cells developed a long-lasting state of unresponsiveness, or immune adaptation, characterized by their inability to mediate organ immune damages in vivo. However, analysis of the gene expression profile of adapted CD4+ T cells revealed the specific coexpression of genes known to promote differentiation and function of Th1 effector cells as well as genes coding for proteins that control T cell activity, such as cell surface-negative costimulatory molecules and regulatory cytokines. Strikingly, blockade of negative costimulation abolished T cell adaptation and stimulated strong IFN-gamma production and severe multiorgan wasting disease. Negative costimulation was also shown to control lethal LPS-induced toxic shock in mice with adapted T cells, as well as the capacity of adapted T cells to reject skin graft. Our results demonstrate that negative costimulation is the molecular mechanism used by CD4+ T cells to adapt their activity in response to persistent antigenic stimulation. The effector function of CD4+ T cells that have adapted to chronic Ag presentation can be activated by stimuli strong enough to overcome regulatory signals delivered to the T cells by negative costimulation. PMID:19734216

  2. Influence of phthiocerol dimycocerosate on CD4(+) T cell priming and persistence during Mycobacterium tuberculosis infection.

    PubMed

    Pinto, Rachel; Nambiar, Jonathan K; Leotta, Lisa; Counoupas, Claudio; Britton, Warwick J; Triccas, James A

    2016-07-01

    The characterisation of mycobacterial factors that influence or modulate the host immune response may aid the development of more efficacious TB vaccines. We have previously reported that Mycobacterium tuberculosis deficient in export of Phthiocerol Dimycocerosates (DIM) (MT103(ΔdrrC)) is more attenuated than wild type M. tuberculosis and provides sustained protective immunity compared to the existing BCG vaccine. Here we sought to define the correlates of immunity associated with DIM deficiency by assessing the impact of MT103(ΔdrrC) delivery on antigen presenting cell (APC) function and the generation of CD4(+) T cell antigen-specific immunity. MT103(ΔdrrC) was a potent activator of bone marrow derived dendritic cells, inducing significantly greater expression of CD86 and IL-12p40 compared to BCG or the MT103 parental strain. This translated to an increased ability to initiate early in vivo priming of antigen-specific CD4(+) T cells compared to BCG with enhanced release of IFN-γ and TNF upon antigen-restimulation. The heightened immunity induced by MT103(ΔdrrC) correlated with greater persistence within the spleen compared to BCG, however both MT103(ΔdrrC) and BCG were undetectable in the lung at 70 days post-vaccination. In immunodeficient RAG (-/-) mice, MT103(ΔdrrC) was less virulent than the parental MT103 strain, yet MT103(ΔdrrC) infected mice succumbed more rapidly compared to BCG-infected animals. These results suggest that DIM translocation plays a role in APC stimulation and CD4(+) T cell activation during M. tuberculosis infection and highlights the potential of DIM-deficient strains as novel TB vaccine candidates. PMID:27450001

  3. CD4+ T-cell epitope prediction using antigen processing constraints.

    PubMed

    Mettu, Ramgopal R; Charles, Tysheena; Landry, Samuel J

    2016-05-01

    T-cell CD4+ epitopes are important targets of immunity against infectious diseases and cancer. State-of-the-art methods for MHC class II epitope prediction rely on supervised learning methods in which an implicit or explicit model of sequence specificity is constructed using a training set of peptides with experimentally tested MHC class II binding affinity. In this paper we present a novel method for CD4+ T-cell eptitope prediction based on modeling antigen-processing constraints. Previous work indicates that dominant CD4+ T-cell epitopes tend to occur adjacent to sites of initial proteolytic cleavage. Given an antigen with known three-dimensional structure, our algorithm first aggregates four types of conformational stability data in order to construct a profile of stability that allows us to identify regions of the protein that are most accessible to proteolysis. Using this profile, we then construct a profile of epitope likelihood based on the pattern of transitions from unstable to stable regions. We validate our method using 35 datasets of experimentally measured CD4+ T cell responses of mice bearing I-Ab or HLA-DR4 alleles as well as of human subjects. Overall, our results show that antigen processing constraints provide a significant source of predictive power. For epitope prediction in single-allele systems, our approach can be combined with sequence-based methods, or used in instances where little or no training data is available. In multiple-allele systems, sequence-based methods can only be used if the allele distribution of a population is known. In contrast, our approach does not make use of MHC binding prediction, and is thus agnostic to MHC class II genotypes. PMID:26891811

  4. Helenalin suppresses essential immune functions of activated CD4+ T cells by multiple mechanisms.

    PubMed

    Berges, Carsten; Fuchs, Dominik; Opelz, Gerhard; Daniel, Volker; Naujokat, Cord

    2009-09-01

    Helenalin is a naturally occuring sesquiterpene lactone extracted from Arnica montana and Arnica chamissonis ssp. foliosa. Helenalin and its derivatives are known for anti-cancer and anti-inflammatory effects via inhibiting NF-kappaB and telomerase activity and impairing protein and DNA synthesis, suggesting that helenalin is a potential candidate for the treatment of deregulated and unwanted T cell-mediated immune responses. Here we show that helenalin induces apoptosis in activated CD4+ T cells by triggering the mitochondrial pathway of apoptosis. Induction of apoptosis is accompanied by rapid stabilization of p53, nuclear localization of p53 and AIF, and an increase in ROS production that results in loss of mitochondrial membrane potential (DeltaPsim). Activated CD4+ T cells which survive exposure to helenalin undergo inhibition of proliferation by induction of G2/M cell cycle arrest. Cell cycle arrest is accompanied by the accumulation of cell cycle regulator proteins p21(WAF/CIP1), p2(KIP1) and cyclin D2, whereas abundance of cyclin A and B(1) is decreased. Cell surface expression of the activation-associated receptors CD25, CD27, CD28, CD120b as well as production of IL-2 are impaired. Transcriptional activation of genes encoding for CD25, IL-2 and IFN-gamma is mediated by transcription factors of the NFAT family, and we demonstrate that helenalin suppresses nuclear translocation of NFATc2 in activated CD4+ T cells. Thus, helenalin can be defined as a new immunosuppressive compound suited for the treatment of deregulated and unwanted T cell-mediated immune responses. PMID:19656571

  5. Specific CD4+ T-Cell Reactivity and Cytokine Release in Different Clinical Presentations of Leptospirosis

    PubMed Central

    Moos, Verena; Allers, Kristina; Luge, Enno; Mayer-Scholl, Anne; Nöckler, Karsten; Loddenkemper, Christoph; Jansen, Andreas; Schneider, Thomas

    2015-01-01

    Clinical manifestations of leptospirosis are highly variable: from asymptomatic to severe and potentially fatal. The outcome of the disease is usually determined in the immunological phase, beginning in the second week of symptoms. The underlying mechanisms, predictive factors, and individual immune responses that contribute to clinical variations are not well understood. The aim of this study was to determine the specifics of CD4+ T-cell reactivity and cytokine release after stimulation with leptospiral antigens in patients with leptospirosis of different disease severities (patients with mild and severe symptoms) and in control subjects (with and without proven exposure to Leptospira). Whole-blood specimens were stimulated with Leptospira antigens in vitro. Subsequently, intracellular staining of cytokines was performed, and flow cytometry was used to assess the expression of CD40 ligand (CD40L) and the production of gamma interferon (IFN-γ), interleukin-10 (IL-10), IL-2, and tumor necrosis factor alpha (TNF-α) by CD4+ T cells. The production of inflammatory cytokines such as TNF-α by CD4+ T cells after stimulation with leptospiral antigens was highest in patients with severe disease. In contrast, the ratio of IL-10 production to TNF-α production was higher in exposed subjects than in patients with mild and severe disease. Levels of proinflammatory cytokines such as TNF-α may be useful markers of the severity of the immunological phase of leptospirosis. IL-10 production by T cells after antigen-specific stimulation may indicate a more successful downregulation of the inflammatory response and may contribute to an asymptomatic course of the disease. PMID:26491036

  6. Helminth-conditioned dendritic cells prime CD4+ T cells to IL-4 production in vivo.

    PubMed

    Connor, Lisa M; Tang, Shiau-Choot; Camberis, Mali; Le Gros, Graham; Ronchese, Franca

    2014-09-15

    Dendritic cells (DC) are critical for the initiation of immune responses; however, their role in priming IL-4-producing Th2 cells in vivo is not fully understood. We used a model of intradermal injection with fluorescent-labeled, nonviable larvae from the helminth parasite nonviable Nippostrongylus brasiliensis L3 larvae (Nb), a strong inducer of Th2 responses, together with IL-4-GFP reporter mice that enable a sensitive detection of IL-4 production to examine the contribution of DC to the priming of IL-4-producing CD4(+) T cells in vivo. We found that parasite material is taken up by two distinct DC populations in draining lymph nodes: a mostly CD11c(int)MHC class II (MHCII)(hi)CD11b(+)Ly6C(-) dermal DC population and a CD11c(hi)MHCII(int)CD11b(+)Ly6C(+) monocyte-derived DC population. After Nb treatment, these two DC populations appeared in the draining lymph nodes in comparable numbers and with similar kinetics; however, treatment with pertussis toxin blocked the migration of dermal DC and the priming of IL-4-producing T cells, but only partially affected monocyte-derived DC numbers. In line with this observation, transfer of OVA-loaded CD11c(int)MHCII(hi) DC from Nb-treated mice into naive hosts could sensitize OVA-specific CD4(+) T cells to IL-4 production, whereas transfer of CD11c(int)MHCII(hi) DC from naive mice, or CD11c(hi)MHCII(int) DC from Nb-treated or naive mice, induced CD4(+) T cell expansion but no IL-4 production. Phenotypic analysis of Nb-loaded CD11c(int)MHCII(hi) DC revealed expression of programmed death ligand 2, CD301b, IFN regulatory factor 4, and moderate upregulation of OX40 ligand. However, thymic stromal lymphopoietin and OX40 ligand were not required for Th2 priming. Thus, our data suggest that appropriate stimuli can induce DC to express the unique signals sufficient to direct CD4(+) T cells to Th2 differentiation. PMID:25108019

  7. Imagable 4T1 model for the study of late stage breast cancer

    PubMed Central

    Tao, Kai; Fang, Min; Alroy, Joseph; Sahagian, G Gary

    2008-01-01

    Background The 4T1 mouse mammary tumor cell line is one of only a few breast cancer models with the capacity to metastasize efficiently to sites affected in human breast cancer. Here we describe two 4T1 cell lines modified to facilitate analysis of tumor growth and metastasis and evaluation of gene function in vivo. New information regarding the involvement of innate and acquired immunity in metastasis and other characteristics of the model relevant to its use in the study of late stage breast cancer are reported. Methods The lines were engineered for stable expression of firefly luciferase to allow tracking and quantitation of the cells in vivo. Biophotonic imaging was used to characterize growth and metastasis of the lines in vivo and an improved gene expression approach was used to characterize the basis for the metastatic phenotype that was observed. Results Growth of cells at the primary site was biphasic with metastasis detected during the second growth phase 5–6 weeks after introduction of the cells. Regression of growth, which occurred in weeks 3–4, was associated with extensive necrosis and infiltration of leukocytes. Biphasic tumor growth did not occur in BALB/c SCID mice indicating involvement of an acquired immune response in the effect. Hematopoiesis in spleen and liver and elevated levels of circulating leukocytes were observed at week 2 and increased progressively until death at week 6–8. Gene expression analysis revealed an association of several secreted factors including colony stimulatory factors, cytokines and chemokines, acute phase proteins, angiogenesis factors and ECM modifying proteins with the 4T1 metastatic phenotype. Signaling pathways likely to be responsible for production of these factors were also identified. Conclusion The production of factors that stimulate angiogenesis and ECM modification and induce hematopoiesis, recruitment and activation of leukocytes suggest that 4T1 tumor cells play a more direct role than previously

  8. Progressive Multifocal Leukoencephalopathy Localized in the Cerebellum and Brainstem Associated with Idiopathic CD4(+) T Lymphocytopenia.

    PubMed

    Aotsuka, Yuya; Uzawa, Akiyuki; Nishimura, Kazutaka; Kojima, Kazuho; Yamaguchi, Mika; Makino, Takahiro; Nakamichi, Kazuo; Saijo, Masayuki; Kuwabara, Satoshi

    2016-01-01

    Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease that favors the cerebrum and typically occurs in immunosuppressed patients. We herein report the case of a 66-year-old man with PML, idiopathic CD4(+) T lymphocytopenia (ICL), and chronic renal failure. Cranial magnetic resonance imaging (MRI) showed a crescent-shaped lesion in the left cerebellum, brainstem, and middle cerebellar peduncle. Although the patient did not present with HIV infection, collagen diseases, or tumors, JC virus DNA was detected in the cerebrospinal fluid. Clinicians should consider PML and ICL in the differential diagnosis if the patient develops progressive ataxia and a crescent-shaped cerebellar lesion on MRI. PMID:27301521

  9. CD4+ T cells provide protection against acute lethal encephalitis caused by Venezuelan equine encephalitis virus

    PubMed Central

    Yun, Nadezhda E.; Peng, Bi-Hung; Bertke, Andrea S.; Borisevich, Viktoriya; Smith, Jennifer K.; Smith, Jeanon N.; Poussard, Allison L.; Salazar, Milagros; Judy, Barbara M.; Zacks, Michele A.; Estes, D. Mark; Paessler, Slobodan

    2009-01-01

    Studying the mechanisms of host survival resulting from viral encephalitis is critical to the development of vaccines. Here we have shown in several independent studies that high-dose treatment with neutralizing antibody prior to intranasal infection with Venezuelan equine encephalitis virus had an antiviral effect in the visceral organs and prolonged survival time of infected mice, even in the absence of alpha beta T cells. Nevertheless, the antibody treatment did not prevent the development of lethal encephalitis. In contrary, the adoptive transfer of primed CD4+ T cells is necessary to prevent lethal encephalitis in mice lacking alpha beta T cell receptor. PMID:19446933

  10. Computational Analysis of the Model Describing HIV Infection of CD4+T Cells

    PubMed Central

    Atangana, Abdon

    2014-01-01

    An analysis of the model underpinning the description of the spread of HIV infection of CD4+T cells is examined in detail in this work. Investigations of the disease free and endemic equilibrium are done using the method of Jacobian matrix. An iteration technique, namely, the homotopy decomposition method (HDM), is implemented to give an approximate solution of nonlinear ordinary differential equation systems. The technique is described and illustrated with numerical examples. The approximated solution obtained via HDM is compared with those obtained via other methods to prove the trustworthiness of HDM. Moreover, the lessening and simplicity in calculations furnish HDM with a broader applicability. PMID:25136605

  11. Advances in hybrid MR-PET at 3 T and 9.4 T in humans

    NASA Astrophysics Data System (ADS)

    Jon Shah, N.; Mauler, Jörg; Neuner, Irene; Oros-Peusquens, Ana-Maria; Romanzetti, Sandro; Vahedipour, Kaveh; Felder, Jörg; Celik, Avdo; Iida, Hidehiro; Langen, Karl-Josef; Herzog, Hans

    2013-02-01

    Hybrid MR-PET data acquisition in simultaneous mode confers a number of advantages at 3 T and 9.4 T. From an MR perspective, the potential for ultra-high resolution structural imaging is discussed and example images of the cerebellum with an isotropic resolution of 320 μm are presented. Further, metabolic imaging is discussed and high-resolution images of the sodium distribution are demonstrated. Examples of tumour imaging on a 3 T MR-PET system are included and discussed.

  12. Data Driven Model Development for the Supersonic Semispan Transport (S(sup 4)T)

    NASA Technical Reports Server (NTRS)

    Kukreja, Sunil L.

    2011-01-01

    We investigate two common approaches to model development for robust control synthesis in the aerospace community; namely, reduced order aeroservoelastic modelling based on structural finite-element and computational fluid dynamics based aerodynamic models and a data-driven system identification procedure. It is shown via analysis of experimental Super- Sonic SemiSpan Transport (S4T) wind-tunnel data using a system identification approach it is possible to estimate a model at a fixed Mach, which is parsimonious and robust across varying dynamic pressures.

  13. Quantitation of Replication-Competent HIV-1 in Populations of Resting CD4+ T Cells

    PubMed Central

    Soriano-Sarabia, Natalia; Bateson, Rosalie E.; Dahl, Noelle P.; Crooks, Amanda M.; Kuruc, JoAnn D.; Margolis, David M.

    2014-01-01

    ABSTRACT Central memory (TCM) CD4+ T cells are the principal reservoir of latent HIV-1 infection that persists despite durable, successful antiretroviral therapy (ART). In a study that measured HIV DNA in 17 patients and replication-competent HIV in 4 patients, pools of resting and activated transitional memory (TTM) CD4+ T cells were found to be a reservoir for HIV infection. As defective viruses account for the majority of integrated HIV DNA and do not reflect the actual frequency of latent, replication-competent proviral infection, we assessed the specific contribution of resting TTM cells to latent HIV infection. We measured the frequency of replication-competent HIV in purified resting memory cell subpopulations by a limiting-dilution, quantitative viral outgrowth assay (QVOA). HIV was routinely detected within the resting central memory compartment but was infrequently detected within the resting TTM compartment. These observations suggest that prolonged ART may limit persistent latent infection in the TTM compartment. Our results confirm the importance of latent infection within the TCM compartment and again focus attention on these cells as the most important latent viral reservoir. While proliferation may drive expansion of detectable viral genomes in cells, the frequency of replication-competent HIV must be carefully assessed. Latent infection appears to wane within the transitional memory compartment in patients who have sustained successful viral suppression via ART or were treated very early in infection. IMPORTANCE Antiretroviral therapy (ART) has led to a significant decrease in morbidity and mortality among HIV-infected patients. However, HIV integrates into the genome of CD4+ T cells, generating pools of long-lived cells that are reservoirs of latent HIV. Two main subsets of CD4+ T cells, central memory and transitional memory cells, were reported to be major reservoirs of HIV infection. However, this study primarily measured the HIV DNA content

  14. Electrical wire insulation and electromagnetic coil

    DOEpatents

    Bich, George J.; Gupta, Tapan K.

    1984-01-01

    An electromagnetic coil for high temperature and high radiation application in which glass is used to insulate the electrical wire. A process for applying the insulation to the wire is disclosed which results in improved insulation properties.

  15. Screen-printed flexible MRI receive coils

    NASA Astrophysics Data System (ADS)

    Corea, Joseph R.; Flynn, Anita M.; Lechêne, Balthazar; Scott, Greig; Reed, Galen D.; Shin, Peter J.; Lustig, Michael; Arias, Ana C.

    2016-03-01

    Magnetic resonance imaging is an inherently signal-to-noise-starved technique that limits the spatial resolution, diagnostic image quality and results in typically long acquisition times that are prone to motion artefacts. This limitation is exacerbated when receive coils have poor fit due to lack of flexibility or need for padding for patient comfort. Here, we report a new approach that uses printing for fabricating receive coils. Our approach enables highly flexible, extremely lightweight conforming devices. We show that these devices exhibit similar to higher signal-to-noise ratio than conventional ones, in clinical scenarios when coils could be displaced more than 18 mm away from the body. In addition, we provide detailed material properties and components performance analysis. Prototype arrays are incorporated within infant blankets for in vivo studies. This work presents the first fully functional, printed coils for 1.5- and 3-T clinical scanners.

  16. Coiling Temperature Control in Hot Strip Mill

    NASA Astrophysics Data System (ADS)

    Imanari, Hiroyuki; Fujiyama, Hiroaki

    Coiling temperature is one of the most significant factors in products of hot strip mill to determine material properties such as strength, toughness of steel, so it is very important to achieve accurate coiling temperature control (CTC). Usually there are a few pyrometers on the run out table in hot strip mill, therefore temperature model and its adapting system have large influences on the accuracy of CTC. Also unscheduled change of rolling speed has a bad effect to keep coiling temperature as its target. Newly developed CTC system is able to get very accurate coiling temperature against uncertain factors and disturbances by adopting easily identified temperature model, learning method and dynamic set up function. The features of the CTC system are discussed with actual data, and the effectiveness of the system is shown by actual control results.

  17. Electrical Wire Insulation and Electromagnetic Coil

    SciTech Connect

    Bich, G. J.; Gupta, T. K.

    1984-01-31

    An electromagnetic coil for high temperature and high radiation application in which glass is used to insulate the electrical wire. A process for applying the insulation to the wire is disclosed which results in improved insulation properties.

  18. Screen-printed flexible MRI receive coils.

    PubMed

    Corea, Joseph R; Flynn, Anita M; Lechêne, Balthazar; Scott, Greig; Reed, Galen D; Shin, Peter J; Lustig, Michael; Arias, Ana C

    2016-01-01

    Magnetic resonance imaging is an inherently signal-to-noise-starved technique that limits the spatial resolution, diagnostic image quality and results in typically long acquisition times that are prone to motion artefacts. This limitation is exacerbated when receive coils have poor fit due to lack of flexibility or need for padding for patient comfort. Here, we report a new approach that uses printing for fabricating receive coils. Our approach enables highly flexible, extremely lightweight conforming devices. We show that these devices exhibit similar to higher signal-to-noise ratio than conventional ones, in clinical scenarios when coils could be displaced more than 18 mm away from the body. In addition, we provide detailed material properties and components performance analysis. Prototype arrays are incorporated within infant blankets for in vivo studies. This work presents the first fully functional, printed coils for 1.5- and 3-T clinical scanners. PMID:26961073

  19. Magnetic propulsion of a magnetic device using three square-Helmholtz coils and a square-Maxwell coil.

    PubMed

    Ha, Yong H; Han, Byung H; Lee, Soo Y

    2010-02-01

    We introduce a square coil system for remote magnetic navigation of a magnetic device without any physical movements of the coils. We used three square-Helmholtz coils and a square-Maxwell coil for magnetic propulsion of a small magnet along the desired path. All the square coils are mountable on a cubic frame that has an opening to accommodate a living subject. The square-Helmholtz coils control the magnetic propulsion direction by generating uniform magnetic field along the desired direction while the square-Maxwell coil controls the propulsion force by generating magnetic gradient field. We performed magnetic propulsion experiments with a down-scaled coil set and a three-channel coil driver. Experimental results demonstrate that we can use the square coil set for magnetic navigation of a magnetic device without any physical movements of the coils. PMID:20054666

  20. Passive energy dump for superconducting coil protection

    DOEpatents

    Luton, J.N. Jr.

    1973-01-16

    The patent describes a passive resistance type energy dump for the protection of the coils of a superconducting magnet. Insertion heaters are immersed in a rigid container filled with a fusible alloy. The energy dump is connected across the coils of the superconducting magnet wherein individual heater elements are connected singly to the windings or otherwise according to the energy dumping requirements upon transition of the magnet to a normal state.